Influence of sunflower seed oil or baby lotion on the skin barrier function of newborns: A pilot study

Summary

Background

Skin care influences skin barrier function during the first postnatal weeks. Although the use of natural oils in preterms has been investigated, there are currently no data comparing the effect of sunflower oil to an emollient on barrier development in healthy term newborns.

Methods

In a prospective, randomized clinical study, 50 healthy full-term newborns aged ≤72 h were randomly assigned to two groups: group baby lotion (L, n=22) and sunflower seed oil (SSO, n=24). The skin barrier function was evaluated in three anatomical areas (front, abdomen, and thigh) by noninvasive assessment of transepidermal water loss (TEWL), stratum corneum hydration (SCH), sebum, and skin pH at inclusion and after five weeks.

Results

In both groups, skin pH decreased and SCH increased statistically significantly in all measured areas at W5 compared to baseline. TEWL decreased statistically significantly on the forearm in both groups, on the upper leg in group L, and on the abdomen in group SSO.

Conclusions

Both skin care regimes did not harm skin barrier function adaptation in healthy term neonates during the first five weeks of life.

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Successful management of synchronous recurrent breast carcinoma with chronic myelogenous leukemia: a case report

Survival is increasing after early breast cancer revealing frequent relapses and possibility of developing secondary malignancies. The concomitant occurrence of these two events is exceptionally disastrous and...

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Chromosomal abnormalities and molecular landscape of metastasizing mucinous salivary adenocarcinoma

Publication date: March 2017
Source:Oral Oncology, Volume 66
Author(s): Alex Panaccione, Yi Zhang, Yanfang Mi, Yoshitsugu Mitani, Guo Yan, Manju L. Prasad, W. Hayes McDonald, Adel K. El-Naggar, Wendell G. Yarbrough, Sergey V. Ivanov
BackgroundMucinous adenocarcinoma of the salivary gland (MAC) is a lethal cancer with unknown molecular etiology and a high propensity to lymph node metastasis. Mostly due to its orphan status, MAC remains one of the least explored cancers that lacks cell lines and mouse models that could help translational and pre-clinical studies. Surgery with or without radiation remains the only treatment modality but poor overall survival (10-year, 44%) underscores the urgent need for mechanism-based therapies.MethodsWe developed the first patient-derived xenograft (PDX) model for pre-clinical MAC studies and a cell line that produces aggressively growing tumors after subcutaneous injection into nude mice. We performed cytogenetic, exome, and proteomic profiling of MAC to identify driving mutations, therapeutic targets, and pathways involved in aggressive cancers based on TCGA database mining and GEO analysis.ResultsWe identified in MAC KRAS (G13D) and TP53 (R213X) mutations that have been previously reported as drivers in a variety of highly aggressive cancers. Somatic mutations were also found in KDM6A, KMT2D, and other genes frequently mutated in colorectal and other cancers: FAT1, NBEA, RELN, RLP1B, and ZFHX3. Proteomic analysis of MAC implied epigenetic up-regulation of a genetic program involved in proliferation and cancer stem cell maintenance.ConclusionGenomic and proteomic analyses provided the first insight into potential molecular drivers of MAC metastases pointing at common mechanisms of CSC propagation in aggressive cancers. The in vitro/in vivo models that we created should aid in the development and validation of new treatment strategies against MAC.

Graphical abstract

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The importance of extranodal extension in metastatic head and neck squamous cell carcinoma, in the light of the new AJCC cancer staging system

Publication date: Available online 9 January 2017
Source:Oral Oncology
Author(s): Claudio Luchini, Nicola Veronese




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Trends in the epidemiology of head and neck cancer in London

Background

Head and neck cancers [HNCs] are biologically heterogeneous tumours. The objectives of this study were to describe trends in incidence of HNCs amongst London residents by sex, age, anatomical site, deprivation and ethnicity.

Methods

Annual age-standardised incidence rates [ASRs] were calculated on HNC registration data, overall and for specific cancer sites, by sex and morphology (1985–2010) and area-based socio-economic deprivation score (2006–2010). Age-standardised incidence rate ratios [IRRs] for the main ethnic groups were calculated by cancer site, using White males and females as the reference groups (1998–2009).

Results

The ASR of HNC in males increased by 40% from 17.3 [95% CI: 15.8–18.6] to 24.2 [95% CI: 22.5–25.8] per 100 000 and in females by 87% from 7.0 [95% CI: 6.2–7.8] to 13.1 [95% CI: 11.9–14.2] per 100 000. Seventy-three per cent of cases spanned four cancer sites: larynx, thyroid, oral and oropharynx. Larynx was most common (23%), and had the highest male: female ratio (6 : 1); ASRs decreased significantly over time, most notably in males [P < 0.001]. Oral cavity was the second most common (21%), with a male: female ratio of 2 : 1, and increasing ASRs in both sexes [P < 0.001]. The majority of cases were male (64%) and from deprived areas (59%). Deprivation was associated with a significantly higher incidence for larynx (males), oropharynx (males and females) and oral cavity (females) [P < 0.05]. The age-specific rate for middle-aged adults (45–64 years) was high for oropharyngeal cancer. The incidence of thyroid cancers increased significantly in both sexes [P < 0.001], and this was the only site more common in females. One in five cases with known ethnicity was from a non-White group (20%). Compared with their White counterparts, Bangladeshi females had a higher incidence of oral, laryngeal and thyroid cancers; Chinese males and females had a higher incidence of nasopharyngeal cancer; and Pakistani and Indian females and Indian males also had higher incidence of oral cancer.

Conclusions

HNCs are increasing in London males and females with significant variation by cancer site over time; oral and oropharyngeal cancers show the most significant rise, with implications for public health action and service provision.

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Outcomes of intensity-modulated radiotherapy as primary treatment for oropharyngeal squamous cell carcinoma – a European singleinstitution analysis

Objectives

To analyse survival and toxicity outcomes in patients treated with primary intensity-modulated radiotherapy (IMRT) for oropharyngeal squamous cell carcinoma (OPSCC) in the era of routine human papilloma virus (HPV) testing.

Design

Single-institution case series.

Setting

Tertiary Head and Neck Cancer Unit.

Participants

A total of 186 patients received IMRT (+/− chemotherapy) for radical primary treatment of OPSCC between March 2010 and December 2013. HPV status was available for 88% of cases. Median radiation dose was 65 Gy in 30 daily fractions. 90% of stage III/IV patients received concurrent chemotherapy or cetuximab.

Main Outcome Measures

Overall, disease-free and disease-specific survival; rates of late xerostomia and dysphagia.

Results

A total of 177 patients completed treatment (Stage I/II: 23; Stage III/IV: 154), with median follow-up of 26 months. Estimated 3-year overall survival (OS), disease-free survival (DFS) and disease-specific survival (DSS) rates were 77.2% (70.5–83.9), 72.3% (65.4–79.2) and 80.2% (74.1–86.3). Estimated 3-year OS, DFS and DSS for HPV-positive patients were 90.9% (85.2–96.6), 87.9% (81.4–94.4) and 91.8% (86.3–97.3). A previously identified risk stratification method was validated, showing improved OS for low-risk over high-risk patients (HR 0.09, P < 0.001). The 2-year feeding tube retention rate was 6%, and 2-year grade ≥2 xerostomia rate was 38% (23% if mean contralateral parotid dose <24 Gy).

Conclusions

Outcomes with IMRT are favourable, particularly in the HPV-positive patient group. This data further supports the use of a previously described prognostication model that can be used to select patients for escalation/de-escalation clinical trials.

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Development and Evaluation of the LittlEARS® Early Speech Production Questionnaire – LEESPQ

Publication date: Available online 9 January 2017
Source:International Journal of Pediatric Otorhinolaryngology
Author(s): Bianka Wachtlin, Joanna Brachmaier, Edda Amann, Vanessa Hoffmann, Annerose Keilmann
ObjectiveUniversal Newborn Hearing Screening programs, now instituted throughout the German-speaking countries, allow hearing loss to be detected and treated much earlier than ever before. With this earlier detection, arises the need for tools fit for assessing the very early speech and language production development of today's younger (0-18 month old) children. We have created the LittlEARS® Early Speech Production Questionnaire, with the aim of meeting this need.Methods600 questionnaires of the pilot version of the LittlEARS® Early Speech Production Questionnaire were distributed to parents via pediatricians' practices, day care centers, and personal contact. The completed questionnaires were statistically analyzed to determine their reliability, predictive accuracy, internal consistency, and to what extent gender or unilingualism influenced a child's score. Further, a norm curve was generated to plot the children's increased expected speech production ability with age.ResultsAnalysis of the data from the 352/600 returned questionnaires revealed that scores on LittlEARS® Early Speech Production Questionnaire correlate positively with a child's age, with older children scoring higher than do younger children. Further, the questionnaire has a high measuring reliability, high predictability, high unidemensionality of scale, and is not significantly gender or uni-/multilingually biased. A norm curve for expected development with age was created.ConclusionsThe LittlEARS® Early Speech Production Questionnaire (LEESPQ) is a valid tool for assessing the most important milestones in very early development of speech and language production of German language children with normal hearing aged 0-18 months old. The questionnaire is a potentially useful tool for long-term infant screening and follow-up testing and for children with normal hearing and those who would benefit from or use hearing devices.



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Impact of environmental volatile organic compounds on otitis media in children: Correlation between exposure and urinary metabolites

Publication date: February 2017
Source:International Journal of Pediatric Otorhinolaryngology, Volume 93
Author(s): So Young Kim, Bu-Soon Son, Hee-jin Park, Seung Ha Oh, Jun Ho Lee, Myung-Hwan Suh, Moo Kyun Park
IntroductionVolatile organic compounds (VOCs) induce inflammatory responses. Tobacco smoke contains numerous VOCs and is a risk factor for otitis media effusion (OME); however, no previous studies have investigated the association between VOCs and OME.ObjectivesWe used urinary metabolites and exposure to environmental risk factors to investigate the association between VOC and polycyclic aromatic hydrocarbon exposure and recurrent OME in children.MethodsChildren with recurrent OME who visited the Otorhinolaryngology Department of Seoul National University Hospital between November 2014 and June 2015 were prospectively enrolled in the study. Recurrent OME was defined as more than two OME episodes over a 6-month period lasting longer than 2 months. The control group consisted of children without OME in the last year. Demographic information, including age, sex, and previous medical history was obtained, and endoscopic examinations of the tympanic membrane were performed. Urinary concentrations of 1-hydroxypyrene, 2-naphthol, hippuric acid, trans, trans-muconic acid (t,t-MA), mandelic acid, phenyl glyoxylic acid, and methyl hippuric acid were analyzed using high-performance liquid chromatography/tandem mass spectroscopy. Environmental factors assessed included house type, age, renovations, the presence of furniture <6 months old, proximity to a road, and exposure to passive smoking.ResultsWe enrolled 11 children with OME and 39 controls. Age and sex did not differ between groups. Exposure to passive smoking was significantly more common in the OME group than in the controls (P < 0.001). Urinary concentrations of t.t.-MA were significantly higher in the OME group (126.33 μg/g cr) than in controls (52.661 μg/g cr; P = 0.003). Other metabolites including 1-hydroxypyrene, 2-naphthol, hippuric acid, mandelic acid, phenyl glyoxylic acid, and methyl hippuric acid did not demonstrated significant relation with the OME.ConclusionsLevels of t,t-MA, a biomarker of benzene exposure, were significantly higher in the OME group than in controls. Passive smoking was significantly more common in the OME group. Our findings suggest that high t,t-MA levels which were probably originated from passive smoking and other pollutants could be indicative OME in children.



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Acute care revisits after adenotonsillectomy in a pediatric Medicaid population in Ohio

Publication date: Available online 9 January 2017
Source:International Journal of Pediatric Otorhinolaryngology
Author(s): Dmitry Tumin, Hina Walia, Vidya T. Raman, Joseph D. Tobias
IntroductionGuidelines for inpatient admission after pediatric tonsillectomy have been proposed to improve the safety of this procedure. This study examined the association between performing adenotonsillectomy in an inpatient setting and acute care revisits within 30 days among children enrolled in a Medicaid Accountable Care Organization in Ohio.MethodsThe Affordable Care Organization's claims database was queried for adenotonsillectomies performed in children ages 0–18 years in 2008–2014. Procedures associated with an inpatient facility stay were classified as inpatient adenotonsillectomies. The primary outcome was emergency department visit or inpatient re-admission within 30 days. Secondary outcomes were revisits within 7 days and >7 days post-discharge. Logistic regression was used to test for association between inpatient procedure and need for revisits.ResultsAdenotonsillectomies in 8835 girls and 7773 boys (age 6.8 ± 3.8 years) were analyzed, of which 842 (5%) were inpatient procedures. Revisits were required in 2511 (15%) cases and were primarily visits to the emergency department. In multivariable analysis, inpatient and outpatient procedures had comparable need for 30-day revisits (OR = 0.85; 95% CI: 0.69, 1.05; p = 0.124). In sub-analyses, inpatient adenotonsillectomy was associated with lower odds of early (≤7 days post-discharge; OR = 0.76; 95% CI: 0.58, 0.99; p = 0.045) but not later (>7 days) revisits.ConclusionsIn a pediatric Medicaid population, inpatient adenotonsillectomy was not associated with greater odds of acute care revisits, compared to outpatient procedures. Appropriate risk stratification of children undergoing adenotonsillectomy can reduce the need for early acute care revisits by scheduling high-risk patients for prolonged observation.



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Visual Speech Alters the Discrimination and Identification of Non-Intact Auditory Speech in Children with Hearing Loss

Publication date: Available online 9 January 2017
Source:International Journal of Pediatric Otorhinolaryngology
Author(s): Susan Jerger, Markus F. Damian, Rachel P. McAlpine, Hervé Abdi
ObjectivesUnderstanding spoken language is an audiovisual event that depends critically on the ability to discriminate and identify phonemes yet we have little evidence about the role of early auditory experience and visual speech on the development of these fundamental perceptual skills. Objectives of this research were to determine 1) how visual speech influences phoneme discrimination and identification; 2) whether visual speech influences these two processes in a like manner, such that discrimination predicts identification; and 3) how the degree of hearing loss affects this relationship. Such evidence is crucial for developing effective intervention strategies to mitigate the effects of hearing loss on language development.MethodsParticipants were 58 children with early-onset sensorineural hearing loss (CHL, 53% girls, M = 9;4 yrs) and 58 children with normal hearing (CNH, 53% girls, M = 9;4 yrs). Test items were consonant-vowel (CV) syllables and nonwords with intact visual speech coupled to non-intact auditory speech (excised onsets) as, for example, an intact consonant/rhyme in the visual track (Baa or Baz) coupled to non-intact onset/rhyme in the auditory track (/–B/aa or /–B/az). The items started with an easy-to-speechread /B/ or difficult-to-speechread /G/ onset and were presented in the auditory (static face) vs. audiovisual (dynamic face) modes. We assessed discrimination for intact vs. non-intact different pairs (e.g., Baa:/–B/aa). We predicted that visual speech would cause the non-intact onset to be perceived as intact and would therefore generate more same—as opposed to different—responses in the audiovisual than auditory mode. We assessed identification by repetition of nonwords with non-intact onsets (e.g., /–B/az). We predicted that visual speech would cause the non-intact onset to be perceived as intact and would therefore generate more Baz—as opposed to az— responses in the audiovisual than auditory mode.ResultsPerformance in the audiovisual mode showed more same responses for the intact vs. non-intact different pairs (e.g., Baa:/–B/aa) and more intact onset responses for nonword repetition (Baz for /–B/az). Thus visual speech altered both discrimination and identification in the CHL—to a large extent for the /B/ onsets but only minimally for the /G/ onsets. The CHL identified the stimuli similarly to the CNH but did not discriminate the stimuli similarly. A bias-free measure of the children's discrimination skills (i.e., d́ analysis) revealed that the CHL had greater difficulty discriminating intact from non-intact speech in both modes. As the degree of HL worsened, the ability to discriminate the intact vs. non-intact onsets in the auditory mode worsened. Discrimination ability in CHL significantly predicted their identification of the onsets—even after variation due to the other variables was controlled.ConclusionsThese results clearly established that visual speech can fill in non-intact auditory speech, and this effect, in turn, made the non-intact onsets more difficult to discriminate from intact speech and more likely to be perceived as intact. Such results 1) demonstrate the value of visual speech at multiple levels of linguistic processing and 2) support intervention programs that view visual speech as a powerful asset for developing spoken language in CHL.



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External airway splint to treat tracheomalacia following laryngotracheal reconstruction

Publication date: Available online 9 January 2017
Source:International Journal of Pediatric Otorhinolaryngology
Author(s): Wayne D. Hsueh, Lee P. Smith
This observation reports the use of an external airway splint to treat tracheomalacia in a pediatric patient. The patient underwent a double stage laryngotracheal reconstruction however was unable to be decannulated due to severe tracheomalacia. Our purpose is to further support the use of external splinting in the treatment of tracheomalacia in a unique case involving isolated nighttime airway obstruction following laryngotracheal reconstruction.



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Clearance of recalcitrant warts in a patient with idiopathic immune deficiency following administration of the quadrivalent human papillomavirus vaccine

Summary

Human papillomavirus (HPV)-induced cutaneous warts are potentially serious and debilitating. In immunosuppressed patients, these warts may be resistant to standard therapies. We report a case of a young patient with a primary immune deficiency whose recalcitrant cutaneous warts regressed completely following administration of a quadrivalent HPV vaccine.

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Unusual skin changes on the neck

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Looking forward to new targeted treatments for chronic spontaneous urticaria

The introduction of omalizumab to the management of chronic spontaneous urticaria (CSU) has markedly improved the therapeutic possibilities for both, patients and physicians dealing with this disabling disease...

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Can we use lower volume of local anesthetic for infraclavicular brachial plexus nerve block under ultrasound guidance in children?

To determine if the infraclavicular brachial plexus block can be applied with lower volume of local anesthetic.

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The importance of extranodal extension in metastatic head and neck squamous cell carcinoma, in the light of the new AJCC cancer staging system

We have read with great interest the manuscript by Mermod et al. [1], in which the prognostic role of extranodal extension (ENE) of lymph node metastasis in head and neck squamous cell carcinoma (SCC) has been investigated through a meta-analytic approach. The main results, shown by Mermod et al., indicate a negative impact of ENE on loco-regional recurrence and distant metastasis in head and neck SCC, as well as an absence of such negative impact of ENE in HPV-positive oropharyngeal SCC. These results confirm the negative prognostic role of ENE in head and neck SCC, but also point out a biological peculiarity of this prognostic moderator, since its role is not significant in influencing the prognosis in case of HPV-positive cancers.

http://ift.tt/2jn15jC

Classification of orbital exenteration and reconstruction

Orbital exenteration (OE) is considered to be a mutilating surgical procedure reserved for relentlessly progressive neoplastic disorders or extensive facial trauma with unfavourable eye involvement. Malignant tumours, accounting for the majority of ablative orbital surgeries, may be caused by primary orbital tumours or secondarily by neoplasias from the surrounding skin, the maxillary sinus or intracranial malignomas. Orbital exenteration following trauma is mostly caused by penetrating globe defects or extended infections with the danger of intracranial effects.

http://ift.tt/2iXGci0

In vitro evaluation of wound healing and antimicrobial potential of ozone therapy

Although ozone therapy is extensively applied when wound repair and antimicrobial effect are necessary, little is known about cellular mechanisms regarding this process. Thus, this study aimed to evaluate ozone cytotoxicity in fibroblasts (L929) and keratinocytes (HaCat) cell lines, its effects on cell migration and its antimicrobial activity. Cells were treated with ozonated phosphate-buffered saline (8, 4, 2, 1, 0.5 and 0.25 μg/mL ozone), chlorhexidine 0.2% or buffered-solution, and cell viability was determined through MTT assay.

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Role of microbiological culture and polymerase chain reaction (PCR) of Actinomyces in Medication-related Osteonecrosis of the jaw (MRONJ)

We hypothesized that local infection plays a critical role in the pathogenesis of medication-related osteonecrosis of the jaw (MRONJ). Recent developments in molecular methods have revolutionized new approaches for the rapid detection of microorganisms including those difficult to culture. The aim of our study is to identify the bacterial profiles in MRONJ by microbiological culture and polymerase chain reactions (PCR). A retrospective analysis was performed on MRONJ patients from 2008 to 2014. The bacterial profile from MRONJ bone samples was determined using microbiological culture and PCR.

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No correlation between two-dimensional measurements and three-dimensional configuration of the pharyngeal upper airway space in cone-beam computed tomography

The aim of this study was to evaluate both the 2-dimensional (2D) and 3-dimensional (3D) configuration of the pharyngeal airway space (PAS) in healthy 239 patients using cone-beam computed tomography (CBCT). In particular, we investigated the correlation between the 2D and 3D measurements in view of the potential impact on diagnosis of upper airway obstruction.The pharyngeal airway of each patient was studied at five levels: the level of the posterior nasal spine (PNS), the level of half-height of the PNS and the tip of the soft palate, the level of the tip of the soft palate, the level of the anterior-inferior point of the second vertebra, and at least the level of the top of the epiglottis.

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Quantifying the effect of corrective surgery for trigonocephaly: A non-invasive, non-ionizing method using three-dimensional handheld scanning and statistical shape modelling

Trigonocephaly in patients with metopic synostosis is corrected by fronto-orbital remodeling (FOR). The aim of this study was to quantitatively assess aesthetic outcomes of FOR by capturing 3D forehead scans of metopic patients pre- and post-operatively and comparing them with controls. Ten single-suture metopic patients undergoing FOR and 15 age-matched non-craniosynostotic controls were recruited at Great Ormond Street Hospital for Children (UK). Scans were acquired with a three-dimensional (3D) handheld camera and post-processed combining 3D imaging software.

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Sleep Surgery Tool: A Medical Checklist to Review Prior to Operating

The objective of this study was to systematically review the international literature for studies providing a preoperative checklist for medical disorders to be evaluated or treated before performing sleep surgery. If no checklist exists, then the identified studies would be used to develop a checklist de novo.

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How to use an metered-dose inhaler with closed-mouth technique

The Chronic Obstructive Pulmonary Disease Foundation demonstrates how to properly use a metered-dose inhaler with a closed-mouth technique.

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Endoscopic excision of a giant pleomorphic adenoma of the nasal septum

Publication date: Available online 9 January 2017
Source:Egyptian Journal of Ear, Nose, Throat and Allied Sciences
Author(s): Ramaprabah Kandiah, Pathma Letchumanan, Harvinder Singh, Baharudin Abdullah
Pleomorphic adenoma of nasal cavity is very rare. Approximately 80% is found in the nasal septum while the remaining 20% is found in the lateral nasal wall. Histologically, pleomorphic adenoma of the nasal cavity differs from the tumor arising from the major salivary glands. It contains more cellularity and epithelial components than the stromal elements. The treatment is total excision with long term follow up as there is potential risk of recurrence and malignancy. Endonasal endoscopic excision has lesser morbidity with better prognosis. In this case report, we highlighted the successful endoscopic excision of an extensive posteriorly located pleomorphic adenoma.



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MCPIP1/Regnase-1 Restricts IL-17A- and IL-17C-Dependent Skin Inflammation [INNATE IMMUNITY AND INFLAMMATION]

The IL-17 family cytokines IL-17A and IL-17C drive the pathogenesis of psoriatic skin inflammation, and anti–IL-17A Abs were recently approved to treat human psoriasis. Little is known about mechanisms that restrain IL-17 cytokine-mediated signaling, particularly IL-17C. In this article, we show that the endoribonuclease MCP-1–induced protein 1 (MCPIP1; also known as regnase-1) is markedly upregulated in human psoriatic skin lesions. Similarly, MCPIP1 was overexpressed in the imiquimod (IMQ)-driven mouse model of cutaneous inflammation. Mice with an MCPIP1 deficiency (Zc3h12a^+/–) displayed no baseline skin inflammation, but they showed exacerbated pathology following IMQ treatment. Pathology in Zc3h12a^+/– mice was associated with elevated expression of IL-17A– and IL-17C–dependent genes, as well as with increased accumulation of neutrophils in skin. However, IL-17A and IL-17C expression was unaltered, suggesting that the increased inflammation in Zc3h12a^+/– mice was due to enhanced downstream IL-17R signaling. Radiation chimeras demonstrated that MCPIP1 in nonhematopoietic cells is responsible for controlling skin pathology. Moreover, Zc3h12a^+/–Il17ra^–/– mice given IMQ showed almost no disease. To identify which IL-17RA ligand was essential, Zc3h12a^+/–Il17a^–/– and Zc3h12a^+/–Il17c^–/– mice were given IMQ; these mice had reduced but not fully abrogated pathology, indicating that MCPIP1 inhibits IL-17A and IL-17C signaling. Confirming this hypothesis, Zc3h12a^–/– keratinocytes showed increased responsiveness to IL-17A and IL-17C stimulation. Thus, MCPIP1 is a potent negative regulator of psoriatic skin inflammation through IL-17A and IL-17C. Moreover, to our knowledge, MCPIP1 is the first described negative regulator of IL-17C signaling.

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MARCH1 E3 Ubiquitin Ligase Dampens the Innate Inflammatory Response by Modulating Monocyte Functions in Mice [INNATE IMMUNITY AND INFLAMMATION]

Ubiquitination was recently identified as a central process in the pathogenesis and development of numerous inflammatory diseases, such as obesity, atherosclerosis, and asthma. Treatment with proteasomal inhibitors led to severe side effects because ubiquitination is heavily involved in a plethora of cellular functions. Thus, new players regulating ubiquitination processes must be identified to improve therapies for inflammatory diseases. In addition to their role in adaptive immunity, endosomal MHC class II (MHCII) molecules were shown to modulate innate immune responses by fine tuning the TLR4 signaling pathway. However, the role of MHCII ubiquitination by membrane associated ring-CH-type finger 1 (MARCH1) E3 ubiquitin ligase in this process remains to be assessed. In this article, we demonstrate that MARCH1 is a key inhibitor of innate inflammation in response to bacterial endotoxins. The higher mortality of March1^–/– mice challenged with a lethal dose of LPS was associated with significantly stronger systemic production of proinflammatory cytokines and splenic NK cell activation; however, we did not find evidence that MARCH1 modulates LPS or IL-10 signaling pathways. Instead, the mechanism by which MARCH1 protects against endotoxic shock rests on its capacity to promote the transition of monocytes from Ly6C^Hi to Ly6C^+/–. Moreover, in competitive bone marrow chimeras, March1^–/– monocytes and polymorphonuclear neutrophils outcompeted wild-type cells with regard to bone marrow egress and homing to peripheral organs. We conclude that MARCH1 exerts MHCII-independent effects that regulate the innate arm of immunity. Thus, MARCH1 might represent a potential new target for emerging therapies based on ubiquitination reactions in inflammatory diseases.

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A Novel Function of F-Box Protein FBXO17 in Negative Regulation of Type I IFN Signaling by Recruiting PP2A for IFN Regulatory Factor 3 Deactivation [INNATE IMMUNITY AND INFLAMMATION]

The F-box proteins were originally identified as the key component of SKP1-Cullin1-F-box E3 ligase complexes that control the stability of their specific downstream substrates essential for cell growth and survival. However, the involvement of these proteins in type I IFN (IFN-I) signaling during innate immunity has not been investigated. In this study we report that the F-box protein FBXO17 negatively regulates IFN-I signaling triggered by double-strand DNA, RNA, or viral infection. We found that FBXO17 specifically interacts with IFN regulatory factor 3 (IRF3) and decreases its dimerization and nuclear translocation. The decrease of IRF3 dimerization and nuclear translocation is due to the recruitment of protein phosphatase 2 (PP2A) mediated by FBXO17, resulting in IRF3 dephosphorylation. Interestingly, PP2A recruitment does not require the F-box domain but instead the F-box associated region of the protein; thus, the recruitment is independent of the canonical function of the SKP1-Cullin1-F-box family of E3 ligase. Together, our studies identify a previously unreported role of FBXO17 in regulating IFN-I signaling and further demonstrate a novel mechanism for IRF3 deactivation by F-box protein-mediated recruitment of PP2A.

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Allergen-Induced CD4+ T Cell Cytokine Production within Airway Mucosal Dendritic Cell-T Cell Clusters Drives the Local Recruitment of Myeloid Effector Cells [MUCOSAL IMMUNOLOGY]

Allergic asthma develops in the mucosal tissue of small bronchi. At these sites, local cytokine production by Th2/Th17 cells is believed to be critical for the development of tissue eosinophilia/neutrophilia. Using the mouse trachea as a relevant model of human small airways, we performed advanced in vivo dynamic and in situ static imaging to visualize individual cytokine-producing T cells in the airway mucosa and to define their immediate cellular environment. Upon allergen sensitization, newly recruited CD4⁺ T cells formed discrete Ag-driven clusters with dendritic cells (DCs). Within T cell–DC clusters, a small fraction of CD4⁺ T cells produced IL-13 or IL-17 following prolonged Ag-specific interactions with DCs. As a result of local Th2 cytokine signaling, eosinophils were recruited into these clusters. Neutrophils also infiltrated these clusters in a T cell–dependent manner, but their mucosal distribution was more diffuse. Our findings reveal the focal nature of allergen-driven responses in the airways and define multiple steps with potential for interference with the progression of asthmatic pathology.

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Intracellular Activation of Complement 3 Is Responsible for Intestinal Tissue Damage during Mesenteric Ischemia [INNATE IMMUNITY AND INFLAMMATION]

Intestinal ischemia followed by reperfusion leads to local and remote organ injury attributed to inflammatory response during the reperfusion phase. The extent to which ischemia contributes to ischemia/reperfusion injury has not been thoroughly studied. After careful evaluation of intestinal tissue following 30 min of ischemia, we noticed significant local mucosal injury in wild-type mice. This injury was drastically reduced in C3-deficient mice, suggesting C3 involvement. Depletion of circulating complement with cobra venom factor eliminated, as expected, injury recorded at the end of the reperfusion phase but failed to eliminate injury that occurred during the ischemic phase. Immunohistochemical studies showed that tissue damage during ischemia was associated with increased expression of C3/C3 fragments primarily in the intestinal epithelial cells, suggesting local involvement of complement. In vitro studies using Caco2 intestinal epithelial cells showed that in the presence of LPS or exposure to hypoxic conditions the cells produce higher C3 mRNA as well as C3a fragment. Caco2 cells were also noted to produce cathepsins B and L, and inhibition of cathepsins suppressed the release of C3a. Finally, we found that mice treated with a cathepsin inhibitor and cathepsin B–deficient mice suffer limited intestinal injury during the ischemic phase. To our knowledge, our findings demonstrate for the first time that significant intestinal injury occurs during ischemia prior to reperfusion and that this is due to activation of C3 within the intestinal epithelial cells in a cathepsin-dependent manner. Modulation of cathepsin activity may prevent injury of organs exposed to ischemia.

http://ift.tt/2ixozTa

Divergent Functions of TLR2 on Hematopoietic and Nonhematopoietic Cells during Chronic Mycobacterium tuberculosis Infection [INFECTIOUS DISEASE AND HOST RESPONSE]

We have reported that TLR2 is crucial for host resistance against chronic Mycobacterium tuberculosis infection; however, which cell types are key players in this response remain unknown. This led us to decipher the relative contribution of TLR2 on nonhematopoietic and hematopoietic cells in resistance against chronic M. tuberculosis infection in mice infected with M. tuberculosis Erdman. Consistent with our previous report, at 8 wk of infection, TLR2 knockout (TLR2KO)->TLR2KO bone marrow chimeric mice exhibited increased bacterial burden, disorganized accumulation of lymphocytes and mononuclear cells, and extensive pulmonary immunopathology compared with wild-type (WT)->WT chimeric mice. Bacterial burden and pulmonary immunopathology of chimeric mice lacking TLR2 in the hematopoietic compartment (TLR2KO->WT) was comparable to TLR2KO mice. In contrast, chimeric mice deficient in TLR2 in the nonhematopoietic compartment (WT->TLR2KO) exhibited a marked attenuation in granulomatous inflammation compared with WT mice. Although the latter mice did not exhibit improved pulmonary bacterial control, significant reductions in bacterial burden in the draining lymph nodes, spleen, and liver were observed. These findings establish that the TLR2-mediated hematopoietic response promotes stable control of pulmonary bacterial burden and granuloma integrity, whereas TLR2 signaling on nonhematopoietic cells may partly facilitate granulomatous inflammation and bacterial dissemination.

http://ift.tt/2ibP8Q6

TGF-{beta} Controls the Formation of Kidney-Resident T Cells via Promoting Effector T Cell Extravasation [INFECTIOUS DISEASE AND HOST RESPONSE]

Tissue-resident memory T (T_RM) cells, a population of noncirculating memory T cells, are one of the essential components of immunological memory in both mouse and human. Although CD69⁺CD103⁺ T_RM cells represent a major T_RM cell population in barrier tissues including the mucosal surface and the skin, CD69⁺CD103^– T_RM cells dominate most nonbarrier tissues, such as the kidney. TGF-β is required for the differentiation of CD69⁺CD103⁺ T_RM cells in barrier tissues. However, the developmental control of CD69⁺CD103^– T_RM cells in nonbarrier tissues remains largely unknown and the involvement of TGF-β signaling is less clear. In this study we demonstrated that TGF-β promoted the formation of kidney-resident T cells via enhancing the tissue entry of effector T cells. Mechanistically, TGF-β enhanced E- and P-selectin and inflammatory chemokine-mediated extravasation of effector T cells. Thus TGF-β controls the first developmental checkpoint of T_RM cell differentiation in nonbarrier tissues.

http://ift.tt/2jmBpna

Correction: Regulation of Adenosine Deaminase on Induced Mouse Experimental Autoimmune Uveitis [CORRECTIONS]

http://ift.tt/2jmzv62

Correction: Hepatitis C Virus Sensing by Human Trophoblasts Induces Innate Immune Responses and Recruitment of Maternal NK Cells: Potential Implications for Limiting Vertical Transmission [CORRECTIONS]

http://ift.tt/2ic30tn

Correction: Breakpoint Cluster Region-Mediated Inflammation Is Dependent on Casein Kinase II [CORRECTIONS]

http://ift.tt/2jmoOjN

Combined Single-Cell Measurement of Cytokine mRNA and Protein Identifies T Cells with Persistent Effector Function [NOVEL IMMUNOLOGICAL METHODS]

Effective T cell responses entail the coproduction of IFN-, TNF-α, and IL-2. Cytokine production is determined by transcriptional and posttranscriptional events. However, increased transcript levels do not always translate into protein production, and therefore simultaneous transcripts and protein measurement are essential for the appropriate analysis of T cell responses. In this study, we optimized flow cytometry–based fluorescence in situ hybridization (Flow-FISH) for IFN- to multicolor flow cytometry that allows for single-cell measurement of mRNA and protein levels. This high-throughput analysis detected Ag-specific human T cells of low frequency. We also employed Flow-FISH for single-tube analysis of IFN- transcript and protein profile to simultaneously study the responsiveness of different T cell subsets, that is, naive, effector, and memory T cells. Importantly, the simultaneous transcript and protein analysis of IFN- and of TNF-α and IL-2 revealed that T cell responses consist of two types: one subtype loses mRNA expression during activation, whereas the other maintains high transcript levels throughout stimulation. High cytokine transcript levels correlated with increased protein production. Intriguingly, this mRNA^hi-expressing T cell population also produced higher levels of other cytokines, indicating that Flow-FISH helps identify the best cytokine producers during T cell activation. We conclude that Flow-FISH is a rapid, sensitive, and cost-effective method to determine the quality of T cell responses induced by, for instance, T cell vaccines.

http://ift.tt/2ibTK8y

IL-23 Inhibits Melanoma Development by Augmenting DNA Repair and Modulating T Cell Subpopulations [TUMOR IMMUNOLOGY]

In animal models, IL-12 and IL-23 participate in the development of malignant neoplasms of keratinocytes. However, the role of these cytokines in pigmented lesion development and their progression to melanoma has received little attention. IL-12p35, IL-23p19, and IL-12/IL-23p40 knockout mice on a C3H/HeN background, subjected to a melanomagenesis protocol, demonstrated profound differences in susceptibility to nevus initiation, transformation, tumorigenicity, and metastatic potential. IL-23 was found to be essential for melanocyte homeostasis, whereas IL-12 supported nevus development. A direct action of IL-23 on primary melanocytes, shown to be IL-23R⁺, demonstrated that DNA repair of damaged melanocytes requires IL-23. Furthermore, IL-23 modulated the cutaneous microenvironment by limiting regulatory T cells and IFN- and inhibiting IL-10 production. Neutralizing Ab to IFN-, but not IL-17, inhibited nevus development (p < 0.01).

http://ift.tt/2jmyYRD

Epigenetic Networks Regulate the Transcriptional Program in Memory and Terminally Differentiated CD8+ T Cells [SYSTEMS IMMUNOLOGY]

Epigenetic mechanisms play a critical role during differentiation of T cells by contributing to the formation of stable and heritable transcriptional patterns. To better understand the mechanisms of memory maintenance in CD8⁺ T cells, we performed genome-wide analysis of DNA methylation, histone marking (acetylated lysine 9 in histone H3 and trimethylated lysine 9 in histone), and gene-expression profiles in naive, effector memory (EM), and terminally differentiated EM (TEMRA) cells. Our results indicate that DNA demethylation and histone acetylation are coordinated to generate the transcriptional program associated with memory cells. Conversely, EM and TEMRA cells share a very similar epigenetic landscape. Nonetheless, the TEMRA transcriptional program predicts an innate immunity phenotype associated with genes never reported in these cells, including several mediators of NK cell activation (VAV3 and LYN) and a large array of NK receptors (e.g., KIR2DL3, KIR2DL4, KIR2DL1, KIR3DL1, KIR2DS5). In addition, we identified up to 161 genes that encode transcriptional regulators, some of unknown function in CD8⁺ T cells, and that were differentially expressed in the course of differentiation. Overall, these results provide new insights into the regulatory networks involved in memory CD8⁺ T cell maintenance and T cell terminal differentiation.

http://ift.tt/2ibSmTE

Establishing High Dimensional Immune Signatures from Peripheral Blood via Mass Cytometry in a Discovery Cohort of Stage IV Melanoma Patients [SYSTEMS IMMUNOLOGY]

The identification of blood-borne biomarkers correlating with melanoma patient survival remains elusive. Novel techniques such as mass cytometry could help to identify melanoma biomarkers, allowing simultaneous detection of up to 100 parameters. However, the evaluation of multiparametric data generated via time-of-flight mass cytometry requires novel analytical techniques because the application of conventional gating strategies currently used in polychromatic flow cytometry is not feasible. In this study, we have employed 38-channel time-of-flight mass cytometry analysis to generate comprehensive immune cell signatures using matrix boolean analysis in a cohort of 28 stage IV melanoma patients and 17 controls. Clusters of parameters were constructed from the abundance of cellular phenotypes significantly different between patients and controls. This approach identified patient-specific combinatorial immune signatures consisting of high-resolution subsets of the T cell, NK cell, B cell, and myeloid compartments. An association with superior survival was characterized by a balanced distribution of myeloid-derived suppressor cell-like and APC-like myeloid phenotypes and differentiated NK cells. The results of this study in a discovery cohort of melanoma patients suggest that multifactorial immune signatures have the potential to allow more accurate prediction of individual patient outcome. Further investigation of the identified immune signatures in a validation cohort is now warranted.

http://ift.tt/2jmwFOh

Clr-a: A Novel Immune-Related C-Type Lectin-like Molecule Exclusively Expressed by Mouse Gut Epithelium [MUCOSAL IMMUNOLOGY]

The mouse gut epithelium represents a constitutively challenged environment keeping intestinal commensal microbiota at bay and defending against invading enteric pathogens. The complex immunoregulatory network of the epithelial barrier surveillance also involves NK gene complex (NKC)–encoded C-type lectin-like molecules such as NKG2D and Nkrp1 receptors. To our knowledge, in this study, we report the first characterization of the orphan C-type lectin-like molecule Clr-a encoded by the Clec2e gene in the mouse NKC. Screening of a panel of mouse tissues revealed that Clec2e transcripts are restricted to the gastrointestinal tract. Using Clr-a–specific mAb, we characterize Clr-a as a disulfide-linked homodimeric cell surface glycoprotein. Of note, a substantial fraction of Clr-a molecules are retained intracellularly, and analyses of Clr-a/Clr-f hybrids attribute intracellular retention to both the stalk region and parts of the cytoplasmic domain. Combining quantitative PCR analyses with immunofluorescence studies revealed exclusive expression of Clr-a by intestinal epithelial cells and crypt cells throughout the gut. Challenge with polyinosinic-polycytidylic acid results in a rapid and strong downregulation of intestinal Clr-a expression in contrast to the upregulation of Clr-f, a close relative of Clr-a, that also is specifically expressed by the intestinal epithelium and acts as a ligand of the inhibitory Nkrp1g receptor. Collectively, we characterize expression of the mouse NKC-encoded glycoprotein Clr-a as strictly associated with mouse intestinal epithelium. Downregulation upon polyinosinic-polycytidylic acid challenge and expression by crypt cells clearly distinguish Clr-a from the likewise intestinal epithelium-restricted Clr-f, pointing to a nonredundant function of these highly related C-type lectin-like molecules in the context of intestinal immunosurveillance.

http://ift.tt/2ic0vaM

{gamma}{delta} T Cells Coexpressing Gut Homing {alpha}4{beta}7 and {alpha}E Integrins Define a Novel Subset Promoting Intestinal Inflammation [MUCOSAL IMMUNOLOGY]

T lymphocytes, dominant T cell subsets in the intestine, mediate both regulatory and pathogenic roles, yet the mechanisms underlying such opposing effects remain unclear. In this study, we identified a unique T cell subset that coexpresses high levels of gut-homing integrins, CD103 and α4β7. They were exclusively found in the mesenteric lymph node after T cell–mediated colitis induction, and their appearance preceded the inflammation. Adoptive transfer of the CD103⁺α4β7^high subsets enhanced Th1/Th17 T cell generation and accumulation in the intestine, and the disease severity. The level of generation correlated with the disease severity. Moreover, these cells were also found to be elevated in a spontaneous mouse model of ileitis. Based on the procolitogenic function, we referred to this subset as "inflammatory" T cells. Targeting inflammatory T cells may open a novel strategy to treat inflammatory diseases where T cells play a pathogenic role including inflammatory bowel disease.

http://ift.tt/2jmxqXO

Shedding New Light on the Process of "Licensing" for Pathogenicity by Th Lymphocytes [AUTOIMMUNITY]

Th cells sensitized against autoantigens acquire pathogenicity following two sequential events, namely activation by their target Ag and a process named "licensing." In this study, we analyzed these processes in a transgenic mouse system in which TCR-transgenic Th cells specific to hen egg lysozyme (HEL) are adoptively transferred to recipients and induce inflammation in eyes expressing HEL. Our data show that the notion that the lung is the organ where "licensing" for pathogenicity takes place is based on biased data collected with cells injected i.v., a route in which most transferred cells enter via the lung. Thus, we found that when donor cells were activated in vitro and injected intraperitoneally, or were activated in vivo, they migrated simultaneously to the lung, spleen, and other tested organs. In all, tested organs donor cells undergo "licensing" for pathogenicity, consisting of vigorous increase in number and changes in expression levels of inflammation-related genes, monitored by both flow cytometry and microarray analysis. After reaching peak numbers, around day 3, the "licensed" donor cells migrate to the circulation and initiate inflammation in the HEL-expressing recipient eyes. Importantly, the kinetics of increase in number and of changes in gene expression by the donor cells were similar in lung, spleen, and other tested organs of the recipient mice. Furthermore, the total numbers of donor cells in the spleen at their peaks were 10- to 100-fold larger in the spleen than in the lung, contradicting the notion that the lung is the organ where "licensing" takes place.

http://ift.tt/2ibXtTE

Neutrophil Resolvin E1 Receptor Expression and Function in Type 2 Diabetes [IMMUNE REGULATION]

Unresolved inflammation is key in linking metabolic dysregulation and the immune system in type 2 diabetes. Successful regulation of acute inflammation requires biosynthesis of specialized proresolving lipid mediators, such as E-series resolvin (RvE) 1, and activation of cognate G protein–coupled receptors. RvE1 binds to leukotriene B4 (BLT-1) on neutrophils and to ERV-1/ChemR23 on monocyte/macrophages. We show novel actions of RvE1 and expression patterns of neutrophil receptors in type 2 diabetes. Neutrophils from healthy subjects express functional BLT-1, low levels of minimally functional ERV-1, and inversed coexpression when compared to neutrophils from type 2 diabetes subjects. Stimulation with TNF-α or LPS increased the expression of ERV-1 by healthy and diabetic neutrophils. RvE1 counteracted LPS and TNF-α induction of ERV-1 overexpression and endogenous diabetic overexpression, activating phagocytosis and resolution signals. Functional ERV-1 was determined by phosphorylation of the signaling protein ribosomal S6. Receptor-antagonism experiments revealed that the increase in phosphorylation of ribosomal S6 was mediated by BLT-1 in healthy subject neutrophils and by ERV-1 in diabetes. Metabololipidomics reveal a proinflammatory profile in diabetic serum. Cell phagocytosis is impaired in type 2 diabetes and requires RvE1 for activation. The dose of RvE1 required to activate resolution signals in type 2 diabetic neutrophils was significantly higher than in healthy controls. RvE1 rescues the dysregulation seen on neutrophil receptor profile and, following a therapeutic dosage, activates phagocytosis and resolution signals in type 2 diabetes. These findings reveal the importance of resolution receptors in health, disease, and dysregulation of inflammation in type 2 diabetes.

http://ift.tt/2jmrv4W

Cutting Edge: Helminth Coinfection Blocks Effector Differentiation of CD8 T Cells through Alternate Host Th2- and IL-10-Mediated Responses [CUTTING EDGE]

Concurrent helminth infection potently inhibits T cell immunity; however, whether helminthes prevent T cell priming or skew clonal recruitment and effector differentiation is not known. Using coinfection with two natural mouse pathogens, Heligsomosoides polygyrus and Toxoplasma gondii, to investigate the negative impact of helminthes on the CD8 T cell response, we demonstrate helminth-induced suppression of IL-12–dependent differentiation of killer-like receptor G1⁺ effector CD8 T cells and IFN- production. Nevertheless, reversal of helminth suppression of the innate IL-12 response of CD8α⁺ dendritic cells, which occurred in STAT6-deficient mice, was not sufficient to normalize CD8 T cell differentiation. Instead, a combined deficiency in IL-4 and IL-10 was required to reverse the negative effects of helminth coinfection on the CD8 T cell response. Monoclonal T. gondii–specific CD8 T cells adoptively transferred into coinfected mice recapitulated the spectrum of helminth-induced effects on the polyclonal CD8 T response, indicating the lack of requirement for clonal skewing.

http://ift.tt/2ibQSZB

TLR10 Is a B Cell Intrinsic Suppressor of Adaptive Immune Responses [IMMUNE REGULATION]

Toll-like receptors play a central role in the initiation of adaptive immune responses with several TLR agonists acting as known B cell mitogens. Despite thousands of publications on TLRs, the function of TLR10 remains unknown. We have found that Ab-mediated engagement of TLR10 on primary human B cells suppresses B cell proliferation, cytokine production, and signal transduction. When challenged with either a T independent or T dependent Ag, TLR10 transgenic mice exhibit diminished Ab responses. Adoptive transfer of splenic B cells into B cell–deficient mice revealed that the suppressive effects on Ag-specific humoral immune responses are entirely B cell intrinsic. Our results demonstrate that TLR10 has a functional role within the B cell lineage that is distinct from that of other TLR family members and may provide a potential therapeutic target for diseases characterized by dysregulated B cell activity.

http://ift.tt/2jmGWdc

Cutting Edge: Murine Mast Cells Rapidly Modulate Metabolic Pathways Essential for Distinct Effector Functions [CUTTING EDGE]

There is growing appreciation that cellular metabolic and bioenergetic pathways do not play merely passive roles in activated leukocytes. Rather, metabolism has important roles in controlling cellular activation, differentiation, survival, and effector function. Much of this work has been performed in T cells; however, there is still very little information regarding mast cell metabolic reprogramming and its effect on cellular function. Mast cells perform important barrier functions and help control type 2 immune responses. In this study we show that murine bone marrow–derived mast cells rapidly alter their metabolism in response to stimulation through the FcRI. We also demonstrate that specific metabolic pathways appear to be differentially required for the control of mast cell function. Manipulation of metabolic pathways may represent a novel point for the manipulation of mast cell activation.

http://ift.tt/2ic0aF3

The Systemic Lupus Erythematosus-Associated Single Nucleotide Polymorphism rs1143678 in Integrin {alpha}M Cytoplasmic Tail Generates a 14-3-3{zeta} Binding Site That Is Proinflammatory [MOLECULAR AND STRUCTURAL IMMUNOLOGY]

The leukocyte integrin α_Mβ₂ (CR3 or Mac-1) has both proinflammatory and immune regulatory functions. Genome-wide association studies have identified several ITGAM (α_M subunit) single nucleotide polymorphisms that are associated with systemic lupus erythematosus. The single nucleotide polymorphism rs1143678 substitutes Pro¹¹⁴⁶ for Ser in the integrin α_M cytoplasmic tail. A detailed functional characterization of this substitution is lacking. Using transfected human cell lines, reconstituted mouse bone marrow neutrophils, and bone marrow–derived macrophages (BMDMs), we showed that P1146S (PS) substitution promoted integrin α_Mβ₂–mediated adhesion, spreading, and migration of cells on iC3b and fibrinogen. In the presence of LPS together with iC3b or fibrinogen, the expression levels of IL-6 and TNF-α in integrin α_M(PS)β₂ BMDMs were significantly higher than those of integrin α_M(wild-type)β₂ BMDMs, and they showed faster kinetics of Erk1/2 activation through the src family kinase(s)–Syk signaling pathway. Integrin α_M(PS)β₂ BMDMs also exhibited higher levels of active RhoA and phagocytic activity. Mechanistically, P1146S substitution in the α_M cytoplasmic tail generates a noncanonical 14-3-3 binding site that modulates integrin α_M(PS)β₂ outside-in signaling.

http://ift.tt/2jmxpDh

Role of CCL7 in Type I Hypersensitivity Reactions in Murine Experimental Allergic Conjunctivitis [ALLERGY AND OTHER HYPERSENSITIVITIES]

Molecules that are necessary for ocular hypersensitivity reactions include the receptors CCR1 and CCR3; CCL7 is a ligand for these receptors. Therefore, we explored the role of CCL7 in mast cell activity and motility in vitro and investigated the requirement for CCL7 in a murine model of IgE-mediated allergic conjunctivitis. For mast cells treated with IgE and Ag, the presence of CCL7 synergistically enhanced degranulation and calcium influx. CCL7 also induced chemotaxis in mast cells. CCL7-deficient bone marrow–derived mast cells showed decreased degranulation following IgE and Ag treatment compared with wild-type bone marrow–derived mast cells, but there was no difference in degranulation when cells were activated via an IgE-independent pathway. In vivo, CCL7 was upregulated in conjunctival tissue during an OVA-induced allergic response. Notably, the early-phase clinical symptoms in the conjunctiva after OVA challenge were significantly higher in OVA-sensitized wild-type mice than in control challenged wild-type mice; the increase was suppressed in CCL7-deficient mice. In the OVA-induced allergic response, the numbers of conjunctival mast cells were lower in CCL7-deficient mice than in wild-type mice. Our results demonstrate that CCL7 is required for maximal OVA-induced ocular anaphylaxis, mast cell recruitment in vivo, and maximal FcRI-mediated mast cell activation in vitro. A better understanding of the role of CCL7 in mediating ocular hypersensitivity reactions will provide insights into mast cell function and novel treatments for allergic ocular diseases.

http://ift.tt/2ibZgID

Dimethyl Fumarate Treatment Mediates an Anti-Inflammatory Shift in B Cell Subsets of Patients with Multiple Sclerosis [CLINICAL AND HUMAN IMMUNOLOGY]

The therapeutic mode of action of dimethyl fumarate (DMF), approved for treating patients with relapsing-remitting multiple sclerosis, is not fully understood. Recently, we and others demonstrated that Ab-independent functions of distinct B cell subsets are important in mediating multiple sclerosis (MS) relapsing disease activity. Our objective was to test whether and how DMF influences both the phenotype and functional responses of disease-implicated B cell subsets in patients with MS. High-quality PBMC were obtained from relapsing-remitting MS patients prior to and serially after initiation of DMF treatment. Multiparametric flow cytometry was used to monitor the phenotype and functional response-profiles of distinct B cell subsets. Total B cell counts decreased following DMF treatment, largely reflecting losses of circulating mature/differentiated (but not of immature transitional) B cells. Within the mature B cell pool, DMF had a greater impact on memory than naive B cells. In keeping with these in vivo effects, DMF treatment in vitro remarkably diminished mature (but not transitional B cell) survival, mediated by inducing apoptotic cell death. Although DMF treatment (both in vivo and in vitro) minimally impacted B cell IL-10 expression, it strongly reduced B cell expression of GM-CSF, IL-6, and TNF-α, resulting in a significant anti-inflammatory shift of B cell response profiles. The DMF-mediated decrease in B cell proinflammatory cytokine responses was further associated with reduced phosphorylation of STAT5/6 and NF-B in surviving B cells. Together, these data implicate novel mechanisms by which DMF may modulate MS disease activity through shifting the balance between pro- and anti-inflammatory B cell responses.

http://ift.tt/2jmBdnW

Endogenous Nur77 Is a Specific Indicator of Antigen Receptor Signaling in Human T and B Cells [ANTIGEN RECOGNITION AND RESPONSES]

Distinguishing true Ag-stimulated lymphocytes from bystanders activated by the inflammatory milieu has been difficult. Nur77 is an immediate early gene whose expression is rapidly upregulated by TCR signaling in murine T cells and human thymocytes. Nur77-GFP transgenes serve as specific TCR and BCR signaling reporters in murine transgenic models. In this study, we demonstrate that endogenous Nur77 protein expression can serve as a reporter of TCR and BCR specific signaling in human PBMCs. Nur77 protein amounts were assessed by immunofluorescence and flow cytometry in T and B cells isolated from human PBMCs obtained from healthy donors that had been stimulated by their respective Ag receptors. We demonstrate that endogenous Nur77 is a more specific reporter of Ag-specific signaling events than the commonly used CD69 activation marker in both human T and B cells. This is reflective of the disparity in signaling pathways that regulate the expression of Nur77 and CD69. Assessing endogenous Nur77 protein expression has great potential to identify Ag-activated lymphocytes in human disease.

http://ift.tt/2ic7ksH

Correlation of Radiological and Endoscopic Findings in Patients Presenting with Dysphagia

Abstract

Dysphagia is a common symptom with diverse etiology in otolaryngology. In the present study clinicopathological, radiological and endoscopic evaluation of patients was done in a tertiary care hospital in patients presenting with dysphagia. A prospective nonrandomized observational study was carried out on total of 80 cases having dysphagia during March 2015 to August 2016. In the present study, out of 80 patients, youngest case was a three years old child while oldest case was an 85 years old female. The mean age was 48.3 ± 20.3 years. The majority of cases were in age group 41–59 years (35%). Male to female ratio was 2.33:1. The mean duration of illness was 15.44 weeks. 15% of patients had absolute dysphagia. For detecting the lesion, Barium swallow study (BSS) showed a total sensitivity of 49.05% (n = 53), Computerised Tomography (CT) showed a total sensitivity of 85.70% (n = 49), plain skiagram neck & chest showed a total sensitivity of 88.88% (n = 9) and endoscopy was the most sensitive test overall as it showed a total sensitivity of 98.75% (n = 80). No complications were reported with either rigid or flexible endoscopy. Dysphagia is a common presenting complaint in otolaryngology with cases coming directly or being referred from other specialities. Males are more commonly affected than females and incidence of malignancy increases with age. Endoscopy can become the first screening test in dysphagia due to its high sensitivity and low risk of complications, with radiological tests being done in an adjunct manner.

http://ift.tt/2i9diaq

Human Fibrin Sealant: Effective Hemostasis in Otolaryngologic Surgeries

Abstract

In otolaryngologic surgeries, achieving hemostasis is of paramount importance for reducing associated morbidities. Topical hemostatic agents have been studied mainly in endonasal operations. Its use in other surgeries has been minimally reported. In this "real world data" study, we retrospectively evaluated the surgeries between June 2014 and December 2014, where topical hemostatic agent—Evicel^® (Ethicon BioSurgery, US) was used to achieve hemostasis. All the patients were followed till 15 day post operation. The data on Evicel^® preparation time, intraoperative blood loss, hemostasis time, length of hospital stay, blood transfusion given, and complications were evaluated. The quality of life was assessed by using discomfort score and it was statistically analyzed for patients underwent surgery for chronic rhinosinusitis and chronic otitis media. The surgical clinical data of 103 patients (63 males and 40 females) were considered for the analysis. In all patients, hemostasis was achieved in less than 1 min. The intraoperative blood loss was between 23 and 99 ml for all surgeries. No postoperative bleeding was reported and blood transfusion was not required for any patients. The hospital stay was 1–2 days. In endonasal surgeries, nasal packing was not required in 36.9% of patients. The discomfort score was statistically improved in patients underwent surgery for chronic rhinosinusits and chronic otitis media (p < 0.001). No complications were reported till day 15 postoperatively. Evicel^®, a topical human fibrin sealant found to be effective in achieving hemostasis and for better clinical outcome in various otolaryngologic surgical procedures.

http://ift.tt/2i6mrpc

Drugs in Anaesthesia and Intensive Care, 5th Ed.

No abstract available

http://ift.tt/2j161y0

Fresh-Frozen Plasma: Ordering Patterns and Utilization in the Operating Rooms of a Tertiary Referral Hospital.

BACKGROUND: Blood product transfusion is the most commonly performed hospital procedure. Intraoperative blood product utilization varies between institutions and anesthesiologists. In the United States in 2011, nearly 4 million plasma units were transfused. METHODS: A retrospective analysis of intraoperative plasma ordering patterns and utilization (thawing and transfusing) was performed at a tertiary, academic hospital between January 2015 and March 2016. RESULTS: Over 15 months, 46,002 operative procedures were performed. In 1540 of them, plasma was thawed or transfused: 8297 plasma units were thawed and 3306 of those units were transfused. These 3306 plasma units were transfused in 749 cases with a median of 2 plasma units (interquartile range, 2-4) transfused. The percentage of average monthly procedures with plasma thawed and none transfused was 51.3% (confidence interval, 49.0%-53.6%). The cardiac surgery service requested the greatest number of plasma units to be thawed (2143) but only transfused 712 (33.2%) of them. Of all plasma units not transfused, 45% were generated by procedures with 1 to 4 units of plasma thawed; 95.7% of these units were thawed as even integers (ie, 2, 4). CONCLUSIONS: For operative procedures, far more plasma was thawed than was transfused and this practice occurred across surgical specialties and anesthesiologists. Considering the plasma that was not transfused, 45% occurred in procedures with 4 or fewer units of plasma requested suggesting these low-volume requests were a primary source of potential waste. Further studies are needed to examine associations between plasma utilization and clinical outcomes. (C) 2017 International Anesthesia Research Society

http://ift.tt/2iW9XO0

Economic Evaluation of Pharmacologic Pre- and Postconditioning With Sevoflurane Compared With Total Intravenous Anesthesia in Liver Surgery: A Cost Analysis.

BACKGROUND: Pharmacologic pre- and postconditioning with sevoflurane compared with total IV anesthesia in patients undergoing liver surgery reduced complication rates as shown in 2 recent randomized controlled trials. However, the potential health economic consequences of these different anesthesia regimens have not yet been assessed. METHODS: An expostcost analysis of these 2 trials in 129 patients treated between 2006 and 2010 was performed. We analyzed direct medical costs for in-hospital stay and compared pharmacologic pre- and postconditioning with sevoflurane (intervention) with total IV anesthesia (control) from the perspective of a Swiss university hospital. Year 2015 costs, converted to US dollars, were derived from hospital cost accounting data and compared with a multivariable regression analysis adjusting for relevant covariables. Costs with negative prefix indicate savings and costs with positive prefix represent higher spending in our analysis. RESULTS: Treatment-related costs per patient showed a nonsignificant change by -12,697 US dollars (95% confidence interval [CI], 10,956 to -36,352; P = .29) with preconditioning and by -6139 US dollars (95% CI, 6723 to -19,000; P = .35) with postconditioning compared with the control group. Results were robust in our sensitivity analysis. For both procedures (control and intervention) together, major complications led to a significant increase in costs by 86,018 US dollars (95% CI, 13,839-158,198; P = .02) per patient compared with patients with no major complications. CONCLUSIONS: In this cost analysis, reduced in-hospital costs by pharmacologic conditioning with sevoflurane in patients undergoing liver surgery are suggested. This possible difference in costs compared with total IV anesthesia is the result of reduced complication rates with pharmacologic conditioning, because major complications have significant cost implications. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. (C) 2017 International Anesthesia Research Society

http://ift.tt/2j1d3Tj

Duke's Anesthesia Secrets, 5th Edition.

No abstract available

http://ift.tt/2iWayz6

Anesthesia for Ambulatory Pediatric Surgery in Sub-Saharan Africa: A Pilot Study in Burkina Faso.

BACKGROUND: Long surgical wait times and limited hospital capacity are common obstacles to surgical care in many countries in Sub-Saharan Africa (SSA). Introducing ambulatory surgery might contribute to a solution to these problems. The purpose of this study was to evaluate the safety and feasibility of introducing ambulatory surgery into a pediatric hospital in SSA. METHODS: This is a cross-sectional descriptive study that took place over 6 months. It includes all patients assigned to undergo ambulatory surgery in the Pediatric University Hospital in Ouagadougou, Burkina Faso. Eligibility criteria for the ambulatory surgery program included >1 year of age, American Society of Anesthesiologists (ASA) 1 status, surgery with a low risk of bleeding, lasting

http://ift.tt/2j12nUM

Intravenous Ketamine Infusions for Neuropathic Pain Management: A Promising Therapy in Need of Optimization.

Intravenous ketamine infusions have been used extensively to treat often-intractable neuropathic pain conditions. Because there are many widely divergent ketamine infusion protocols described in the literature, the variation in these protocols presents a challenge for direct comparison of one protocol with another and in discerning an optimal protocol. Careful examination of the published literature suggests that ketamine infusions can be useful to treat neuropathic pain and that certain characteristics of ketamine infusions may be associated with better clinical outcomes. Increased duration of relief from neuropathic pain is associated with (1) higher total infused doses of ketamine; (2) prolonged infusion durations, although the rate of infusion does not appear to be a factor; and (3) coadministration of adjunct medications such as midazolam and/or clonidine that mitigate some of the unpleasant psychomimetic side effects. However, there are few studies designed to optimize ketamine infusion protocols by defining what an effective infusion protocol entails with regard to a respective neuropathic pain condition. Therefore, despite common clinical practice, the current state of the literature leaves the use of ketamine infusions without meaningful guidance from high-quality comparative evidence. The objectives of this topical review are to (1) analyze the available clinical evidence related to ketamine infusion protocols and (2) call for clinical studies to identify optimal ketamine infusion protocols tailored for individual neuropathic pain conditions. The Oxford Center for Evidence-Based Medicine classification for levels of evidence was used to stratify the grades of clinical recommendation for each infusion variable studied. (C) 2017 International Anesthesia Research Society

http://ift.tt/2iW5yeb

Pain and the Conscious Brain.

No abstract available

http://ift.tt/2j1jCFp

Impact of Systemic Vascular Resistance on the Accuracy of the Pulsioflex Device.

BACKGROUND: The accuracy of currently available devices using pulse contour analysis without external calibration for cardiac index (CI) estimation is negatively impacted by hyperdynamic states, low systemic vascular resistance (SVR), and abrupt changes in SVR. The aim of this study was to evaluate the accuracy of a new device, the Pulsioflex (Pulsion Medical System), in patients undergoing liver transplantation. METHODS: Thirty consecutive patients scheduled for liver transplantation were included. CI was monitored using pulmonary arterial catheter (CI-PAC) and Pulsioflex (CI-Pulsio). Simultaneous CI measurements were made intraoperatively at 9 different stages of the procedure. RESULTS: Two hundred seventy pairs of measurements were analyzed. The median CI-Pulsio values (3.3; interquartile range, 2.8-3.8 L[middle dot]min-1[middle dot]m2) were significantly different from the median CI-PAC (4.1; interquartile range, 3.1-5.0 L[middle dot]min-1[middle dot]m2; P

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Dural Puncture Epidural Technique Improves Labor Analgesia Quality With Fewer Side Effects Compared With Epidural and Combined Spinal Epidural Techniques: A Randomized Clinical Trial.

BACKGROUND: The dural puncture epidural (DPE) technique is a modification of the combined spinal epidural (CSE) technique, where a dural perforation is created from a spinal needle but intrathecal medication administration is withheld. The DPE technique has been shown to improve caudal spread of analgesia compared with epidural (EPL) technique without the side effects observed with the CSE technique. We hypothesized that the onset of labor analgesia would follow this order: CSE > DPE > EPL techniques. METHODS: A total of 120 parturients in early labor were randomly assigned to EPL, DPE, or CSE groups. Initial dosing for EPL and DPE consisted of epidural 20 mL of 0.125% bupivacaine plus fentanyl 2 [mu]g/mL over 5 minutes, and for CSE, intrathecal 0.25% bupivacaine 1.7 mg and fentanyl 17 [mu]g. Upon block completion, a blinded coinvestigator assessed the outcomes. Two blinded obstetricians retrospectively interpreted uterine contractions and fetal heart rate tracings 1 hour before and after the neuraxial technique. The primary outcome was time to numeric pain rating scale (NPRS)

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Preoperative Evaluation.

No abstract available

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Factors Associated With Risk of Neurologic Complications After Peripheral Nerve Blocks: A Systematic Review.

The onset of neurologic complications after regional anesthesia is a complex process and may result from an interaction of host, agent, and environmental risk factors. The purpose of this systematic review was examine the qualitative evidence relating to various risk factors implicated in neurologic dysfunction after peripheral nerve block (PNB). The MEDLINE, OVID, and EMBASE databases were primary sources for literature. Cochrane, LILACS, DARE, IndMed, ERIC, NHS, and HTA via Centre for Reviews and Dissemination (CRD; York University) databases were searched for additional unique results. Randomized controlled studies, case-control studies, cohort studies, retrospective reviews, and case reports/case series reporting neurologic outcomes after PNB were included. Relevant, good-quality systematic reviews were also eligible. Human and animal studies evaluating factors important for neurologic outcomes were assessed separately. Information on study design, outcomes, and quality was extracted and reviewed independently by the 2 review authors. An overall rating of the quality of evidence was assigned using GRADE (Grading of Recommendations Assessment, Development and Evaluation) criteria. Relevant full-text articles were separated based on type (prospective, retrospective, and nonhuman studies). Strengths of association were defined as high, moderate, inconclusive, or inadequate based on study quality and direction of association. The evidence from 77 human studies was reviewed to assess various host, agent, and environmental factors that have been implicated as possible risks. Most of the available evidence regarding the injurious effects of the 3 cardinal agents of mechanical insult, pressure, and neurotoxicity was extracted from animal studies (42 studies). Among the risk factors investigated in humans, block type had a strong association with neurologic outcome. Intraneural injection, which seems to occur commonly with PNBs, showed an inconsistent direction of association. Measures meant to increase precision and ostensibly reduce the occurrence of complications such as currently available guidance techniques showed little effect on the incidence of neurologic complications. Recovery from neurologic injury appears to be worse in patients with pre-existing risk factors. Categorization and definition of neurologic complication varied among studies, making synthesis of evidence difficult. Also, a significant portion of the evidence surrounding neurologic injury associated with PNB comes from animal or laboratory studies, the results of which are difficult to translate to clinical scenarios. Of the human studies, few had an a priori design to test associations between a specific risk factor exposure and resultant neurologic sequelae. A few risk factor associations were identified in human studies, but overall quality of evidence was low. Much of the evidence for risk factors comes from animal models and case reports. The final neurologic outcome seems to represent the complex interaction of the host, agent, and the environment. (C) 2017 International Anesthesia Research Society

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Time- and Dose-Dependent Effects of Desflurane in Sensitized Airways.

BACKGROUND: Although the bronchodilatory actions of volatile anesthetics, such as halothane, isoflurane, and sevoflurane, have been well documented in previous studies, the properties of desflurane remain controversial. The aim of this study was to investigate the effects of desflurane at different concentrations and durations in an ovalbumin-sensitized guinea pig model of airway hyper-responsiveness. METHODS: Ovalbumin-sensitized animals (n = 176) were randomly assigned to 5 groups according to the minimum alveolar concentration (MAC) of desflurane they received: 0.0, 0.5, 1.0, 1.5, and 2.0 MAC. Total lung resistance in vivo, airway smooth muscle tension in vitro, and intracellular cyclic adenosine monophosphate (AMP) levels were measured to evaluate the effects of desflurane. RESULTS: In 5 sensitized groups, total lung resistance increased from baseline to peak at approximately 8 minutes and then decreased slowly until about 17 minutes with extended administration of desflurane. Desflurane dose-dependently increased total lung resistance with or without incremental doses of acetylcholine and reduced muscle tension with increasing concentrations of carbacholine. Cyclic AMP levels were increased by desflurane: at the 60-minute time point, cyclic AMP concentrations (means +/- SD) with 0.5 MAC (1.96 +/- 0.40) and 1.0 MAC (2.11 +/- 0.50) desflurane were higher than those at the 8-minute time point (1.11 +/- 0.23 and 1.32 +/- 0.32). CONCLUSIONS: Desflurane exerted time- and dose-dependent effects and could be used at 0.5 and 1.0 MAC concentrations without significant bronchoconstriction in ovalbumin-sensitized guinea pigs. Cyclic AMP-mediated airway smooth muscle relaxation might be one mechanism by which desflurane induces bronchodilation. (C) 2017 International Anesthesia Research Society

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Surveying the Literature: Synopsis of Recent Key Publications.

No abstract available

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Anesthesia management of cesarean section in parturient with anti- N -methyl- d -aspartate receptor encephalitis: a case report

Abstract

A 24-year-old woman at 29 weeks' gestation, and with psychiatric symptoms, was admitted to hospital and diagnosed as having anti-N-methyl-d-aspartate receptor encephalitis. After 4 weeks of immunotherapy with little effect, an emergency cesarean section was performed at 33⁺⁴ weeks gestation under general anesthesia. The parturient was intubated after rapid sequence induction with etomidate, remifentanil and succinylcholine. Anesthesia was maintained with sevoflurane and remifentanil. Except for low weight, the infant was normal at birth. The surgery went uneventfully and teratoma or other masses were not found. The parturient was sent to ICU for further treatment without extubation after surgery. She was extubated on the 6th day after surgery and was transferred to the general ward of the neurology department to control her seizures. After the seizures were controlled, she was discharged home on the 80th postoperative day and her neurological symptoms had slowly improved half a year later. This case report presents the anesthetic considerations in patients with anti-NMDAR encephalitis undergoing cesarean section.

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Impact of acute changes in perfusion index and blood pressure on the accuracy of non-invasive continuous hemoglobin concentration measurements during induction of anesthesia

Abstract

Purpose

Several factors affect the accuracy of non-invasive continuous hemoglobin concentration (SpHb) measurements. We had previously shown an increase in the perfusion index (PI) following induction of anesthesia which was associated with an increase in the difference between SpHb and total hemoglobin (tHb) (SpHb–tHb). We hypothesized that blunting the increase in PI by maintaining blood pressure during induction of anesthesia would improve the agreement between SpHb and tHb measurements.

Methods

Twenty-nine adult patients were enrolled. Patients were randomly assigned by use of sequentially numbered, opaque sealed envelopes to a control (group C) or a phenylephrine group (group P). Anesthesia was induced and maintained with propofol, remifentanil, and ketamine. In group P, phenylephrine was infused at 0.5 µg/kg/min during induction of anesthesia. SpHb and PI were monitored with a Radical-7 Pulse CO-Oximeter. tHb and hematocrit were measured with the ABL800 blood gas analyzer.

Results

Following induction of anesthesia, PI increased significantly in both groups (p < 0.001 and p < 0.05 in groups C and P, respectively). However, the increase in PI was significantly smaller in group P than in group C (2.6 ± 1.3 vs 0.8 ± 1.4%, p < 0.001). Similarly, the change in SpHb–tHb was significantly smaller in group P than in group C (0.40 ± 0.78 vs 0.97 ± 0.70 g/dl, p < 0.05). Changes in SpHb–tHb are correlated with changes in PI (r = 0.46, p < 0.05).

Conclusions

The findings suggest that blunting the increase in PI by maintaining arterial pressure during induction of anesthesia improves the agreement between SpHb and tHb values.

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Similarities between parasternal intercostal nerve block and subpectoral interfascial plane block

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Single Nucleotide Polymorphisms in Adiponectin Gene Are Not Directly Associated with Increased Risk of Obstructive Sleep Apnea Syndrome in a Chinese Han Population

Purpose: This study aims to test the possible correlation between single nucleotide polymorphisms (SNPs) in the adiponectin gene and increased risk of obstructive sleep apnea syndrome (OSAS) in a Chinese Han population. Materials and Methods: A total of 266 subjects were enrolled into the study to detect 9 SNPs in the adiponectin gene. Multivariate unconditional logistic regression analysis, adjusted for gender and age, was used to estimate the associations of these SNPs with OSAS risk. Results: No evidence of a direct association was observed between these SNPs and the risk of OSAS in the Chinese Han population. However, the stratified analysis also revealed a remarkable genotype difference for SNP rs6773957 between cases and controls in the overweight subgroup (p p Conclusion: The current research demonstrated that the SNPs in the adiponectin gene did not represent susceptibility loci for OSAS in Chinese Han individuals overall. However, variants of rs6773957 have an association with OSAS in overweight individuals. In addition, polymorphisms of rs12495941, rs182052, and rs16861205 are associated with the severity of OSAS.
ORL 2016;78:308-319

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Sensation loss after superficial parotidectomy: A prospective controlled multicenter trial

ABSTRACT

Background

The purpose of this study was to evaluate the occurrence of hypoesthesia after superficial parotidectomy depending on preservation of posterior branch of the great auricular nerve (GAN).

Methods

This prospective, controlled, double blind, multicenter trial included 130 patients. The posterior branch was preserved in 93 patients (GAN group), and ligated in 33 patients (non-GAN group). In 4 patients, GAN status was unknown. Included patients underwent sensory testing (TouchTest) and subjective evaluation at 6, 12, and 24 months after surgery.

Results

Better improvement of sensation was present in the GAN group. After 12 months, 59% of the patients in the GAN-group showed positive test results in the lobule, versus 24% of the non-GAN group (p = .013). Additionally, after 24 months, 71% of the patients in the GAN-group showed a positive test in the antitragus, versus 31% in the non-GAN group (p = .045). Hypoesthesia equally limited quality of life in both groups (all p > .05).

Conclusion

Preservation of the posterior branch of the GAN led to significantly better improvement of sensation in the lobule and antitragus, and should be recommended during parotidectomy. © 2017 Wiley Periodicals, Inc. Head Neck, 2017

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Single innervated segmented vastus lateralis for midfacial reanimation during radical parotidectomy

Abstract

Background

Innervated free muscle transfer using the gracilis muscle or temporalis myoplasty has been successfully utilized for facial reanimation in chronic facial palsy. These techniques are less suited to immediate facial reconstruction in the setting of radical parotidectomy, in which the complexity of the defect, patient age, postoperative radiotherapy, and limited life expectancy pose particular challenges.

Methods

We present a novel description of the use of a chimeric anterolateral thigh (ALT) flap and innervated vastus lateralis to achieve midface static suspension and dynamic reanimation in the setting of radical parotidectomy.

Results

The technique is described in detail along with a video demonstrating the early and medium-term results in an example case.

Conclusion

Although outcomes using the vastus lateralis free flap for midface reanimation need to be objectively determined, the flap adds the potential of dynamic midface movement in patients undergoing radical parotidectomy who would otherwise not be afforded this opportunity. © 2017 Wiley Periodicals, Inc. Head Neck, 2017

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Feasibility of using the retroauricular approach without endoscopic or robotic assistance for excision of benign neck masses

ABSTRACT

Background

The purpose of this study was to present our evaluation of the feasibility of using a retroauricular approach for excision of benign upper neck mass lesions without assistance of an endoscopic or robotic system.

Methods

We enrolled 23 patients with benign neck mass lesions of the parotid gland, submandibular gland, and the level II/III region who underwent surgery via a retroauricular approach.

Results

In 22 of 23 patients (95.7%), parotidectomies, submandibular gland resections, and mass excisions were successfully completed under direct vision, without endoscopic or robotic assistance. Mean operation time, drainage amount, and drainage duration were 99.1 minutes, 44.3 mL, and 2.9 days, respectively. For a total of 23 patients, the mean visual analog scale score for subjective satisfaction with the incision scar was 8.9. No serious or permanent complications occurred.

Conclusion

Excision using a retroauricular approach under direct vision is technically feasible for many benign mass lesions of the parotid gland, submandibular gland, and levels II/III of the neck region. © 2017 Wiley Periodicals, Inc. Head Neck, 2017

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Prognostic value of the seventh AJCC/UICC TNM classification of intestinal-type ethmoid adenocarcinoma: Systematic review and risk prediction model

Abstract

Background

The purpose of this study was to propose a prognostic classification of intestinal-type adenocarcinoma (ITAC) based on literature search and prognostic modeling of cohort data.

Methods

We first conducted a literature search to assess the homogeneity of the reported estimates of 5-year survival and to identify the influence of T classification. We then pooled prospective data from 3 large French and Italian series to predict time to all-cause mortality. The sample was randomly split to derive and then to validate the proposed prognostic model.

Results

Literature analysis confirmed the heterogeneity in 5-year survival rates, partly explained in subsets of homogeneous T-values. The sample included 223 patients, randomly separated into a derivation (n = 141) and a validation set (n = 82). Invasion of the sphenoid lateral and/or posterior walls and dura/cerebral invasion were systematically associated with a poor survival.

Conclusion

The incorporation of the invasion of the sphenoid lateral or posterior walls should be considered for ITAC management and prognostication. © 2017 Wiley Periodicals, Inc. Head Neck, 2017

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Proteinase 3-antineutrophil cytoplasmic antibody-positive ulcerative colitis presenting with abducens neuropathy

A 72-year-old man with ulcerative colitis (UC) presented with complete left abducens nerve palsy. Although MRI showed no significant changes, cerebrospinal fluid analysis revealed pleocytosis and elevated protein and interleukin (IL)-6 levels. His serum proteinase 3-antineutrophil cytoplasmic antibody (PR3-ANCA) level was also elevated to 31.1 U/mL, but granulomatosis with polyangiitis was not observed. On the basis of the diagnosis of autoimmune cranial neuropathy, he was treated with steroid therapy. While tapering steroid therapy, his serum PR3-ANCA levels; cerebrospinal fluid findings, including IL-6 levels; and symptoms improved. Serum PR3-ANCA could be a useful parameter of neurological disorders associated with ANCA-positive UC.

http://ift.tt/2iw4RHe

Delivering patient-centred care in rural family practice: using the patient's concept of health to guide treatment

Through an examination of the life of an 83-year-old patient diagnosed clinically with secondary progressive multiple sclerosis (MS), general practice specialists, consultants and junior doctors will see the importance of assessing their patient's concept of health and how to use this understanding to target healthcare options within their healthcare system. This article highlights, in a resource limited context of rural family practice, the utility of a strong physician–patient relationship, recalls the definition of patient-centred care, and the role of judicious inaction in certain contexts. These lessons can be extrapolated for use in more resource rich or specialised settings such as academic hospitals throughout Europe.

http://ift.tt/2jv6A3A

Portomesenteric vein thrombosis after laparoscopic sleeve gastrectomy for morbid obesity

Portomesenteric vein thrombosis (PMVT) is a rare, life-threatening pathology associated with increased prevalence in laparoscopic sleeve gastrectomy (LSG) versus other gastric bypass procedures. Gaining popularity, LSG is becoming the first choice of patients and physicians alike due to its low complication profile compared to the gastric bypass procedure. We present the case of a 34-year-old woman who underwent an uncomplicated LSG for the treatment of morbid obesity, and presented on postoperative day 13 with PMVT. The patient underwent mechanical thrombectomy and thrombolytic therapy. After 2 days, patency was restored and the patient was discharged in stable condition. A high index of suspicion for PMVT should be considered in patients reporting diffuse abdominal pain after LSG. Owing to its lethality, upon confirmation of PMVT, therapy should begin immediately along with extended anticoagulation therapy on discharge.

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Secondary asplenia as a complication of severe Meningococcal Sepsis

We report the case of an 11-month-old infant who had a medical history of meningococcal septicaemia 6 months prior to this admission and presented to hospital with an episode of fever due to Streptococcus pneumoniae bacteraemia. During this second admission, an abdominal ultrasound scan revealed secondary asplenia.

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Bluish nodules of the breast in an adolescent girl

Description

A 15-year-old girl was referred due to skin lesions of the right breast, which had first been noticed shortly after birth and had enlarged slowly with the patient's growth but more rapidly in the past few years. Family history disclosed that the patient's father had similar lesions on the left shoulder. Physical examination revealed multiple bluish coalescent soft nodules on the right breast, which were slightly tender to palpation (figure 1). Histological examination demonstrated dilated irregular vascular channels surrounded by endothelial cells and one to several layers of uniform cuboidal cells with a pale or faintly eosinophilic cytoplasm (figure 2). These features were consistent with the diagnosis of glomuvenous malformation (GVM).

Figure 1

Clinical presentation. Multiple well-defined bluish to purple coalescent soft and slightly tender nodules on the right breast.

Figure 2

Histopathological findings. Dilated capillaries containing...

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Short-term treatment with oral amiodarone resulting in bilateral optic neuropathy and permanent blindness

A 66-year-old man was hospitalised due to worsening of his atrial fibrillation, and successfully underwent an electrocardioversion to restore sinus rhythm. He was discharged with a prescription of 600 mg amiodarone daily to retain the sinus rhythm prospectively. 3 weeks after discharge, he noticed that his vision became blurry with cloudy areas spreading throughout his field of view on both eyes simultaneously. The visual symptoms gradually worsened throughout the following 5 months, and the patient was hospitalised in the department of ophthalmology. At this point, his vision had dramatically decreased and visual acuity was measured to 0.05 (1.3 LogMAR) on both eyes. After a thorough medical examination, the patient was diagnosed with an amiodarone-induced toxic optic neuropathy. Regular follow-ups conducted throughout 7 years have shown that the patient's vision has stabilised, but remains limited to the ability of recognising hand motions on both eyes, thus characterising him as blind.

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Bilateral indwelling pleural catheter for hepatic hydrothorax

A 68-year-old man with alcoholic liver cirrhosis and portal hypertension was admitted due to ascites. Bilateral severe hepatic hydrothorax did not resolve despite sodium restriction, and diuretic treatment, requiring repeated thoracentesis for relief of dyspnoea. Curative options, as transjugular intrahepatic portosystemic shunt and liver transplantation were both contraindicated. An attempt of pleurodesis was ineffective. Bilateral insertion of tunnelled pleural catheter allowed symptom control and home discharge. After 6 months, bilateral stable pleurodesis has been achieved and patient is still free from dyspnoea.

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Postoperative Mycoplasma hominis brain abscess: keep it in mind!

A temporal lobe abscess was diagnosed in a 57-year-old man. A urethral catheter had been inserted 12 days earlier, just prior to clot evacuation of a subacute haematoma secondary to an arterio-venous malformation. Fever persisted despite debridement and treatment with meropenem and vancomycin. Gram stains of operative samples showed no bacteria. Extended cultures grew pinpoint colonies after 5 days. Meanwhile, sequencing of bacterial 16S rDNA from operative specimens had identified Mycoplasma hominis; the bacterial colonies were subsequently similarly identified. The patient responded promptly following addition of oral doxycycline 100 mg two times per day. There is a growing literature of similar cases. Transient bacteraemia, following urinary catheterisation, with seeding of existing sites of inflammation is the proposed explanation. Urethral carriage of M. hominis is 15% and catheterisation is a common procedure. Mycoplasma hominis maybe more common than appreciated, especially as the need for extended cultures makes a correct diagnosis less likely.

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Hypotension induced by the concomitant use of a calcium-channel blocker and clarithromycin

In the elderly, calcium-channel blockers are the first-line treatment for hypertension, and macrolides are commonly prescribed antibiotics. Here we report a 78-year-old man taking nifedipine, diltiazem and carvedilol who presented with persistent hypotension and bradycardia after clarithromycin was prescribed. He was diagnosed with drug-induced hypotension and treated with fluid resuscitation and vasoactive agents. His symptoms gradually improved. He was transferred out of the intensive care unit 3 days after hospitalisation. Combining calcium-channel blockers and clarithromycin can cause vasodilatory hypotension. The concomitant use of calcium-channel blockers and macrolide antibiotics increases the levels of calcium-channel blockers in the blood as they are metabolised by cytochrome P450 3A4 (CYP3A4), which is inhibited by macrolide antibiotics. Moreover, the addition of another calcium-channel blocker and a β blocker can lower cardiac output due to bradycardia and worsen hypotension. Therefore, it is important to consider drug interactions when the cause of hypotension is unknown.

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Prolonged indirect hyperbilirubinemia in a moderately preterm boy with Mediterranean glucose-6-phosphate dehydrogenase and glutathione S-transferase Mu 1 null mutations

A 33-week gestation boy with Mediterranean glucose-6-phosphate dehydrogenase (G6PD) and a glutathione S-transferase Mu 1 null mutations (GSTM1*0/*0) developed prolonged indirect hyperbilirubinemia (PIH). He had no laboratory evidence of haemolysis or infection, and no exposure to oxidising agents. He has two full-term older brothers who have no history of neonatal hyperbilirubinemia. One brother, who was exclusively breast fed, has only Mediterranean G6PD and the other has only GSTM1*0/*0. The three boys have no mutation in the uridine diphosphate glucuronosyltransferase 1A1 gene. This suggests that a combination of all or any two of prematurity, G6PD deficiency and GSTM1*0/*0 is a possible risk factor for PIH. However, this remains to be confirmed.

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Acute colonic pseudo-obstruction associated with abdominal paracentesis

A 61-year-old man presented with accumulation of ascites secondary to alcoholic liver disease. He had an ascitic drain sited and 24 hours later he developed acute colonic pseudo-obstruction (ACPO). This is a rare condition previously associated with major surgery and severe sepsis. The patient did well with conservative management, and avoided the need for endoscopic decompression or surgical intervention. We believe that this is the first report of ACPO secondary to abdominal paracentesis.

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Correlation of Radiological and Endoscopic Findings in Patients Presenting with Dysphagia

Abstract

Dysphagia is a common symptom with diverse etiology in otolaryngology. In the present study clinicopathological, radiological and endoscopic evaluation of patients was done in a tertiary care hospital in patients presenting with dysphagia. A prospective nonrandomized observational study was carried out on total of 80 cases having dysphagia during March 2015 to August 2016. In the present study, out of 80 patients, youngest case was a three years old child while oldest case was an 85 years old female. The mean age was 48.3 ± 20.3 years. The majority of cases were in age group 41–59 years (35%). Male to female ratio was 2.33:1. The mean duration of illness was 15.44 weeks. 15% of patients had absolute dysphagia. For detecting the lesion, Barium swallow study (BSS) showed a total sensitivity of 49.05% (n = 53), Computerised Tomography (CT) showed a total sensitivity of 85.70% (n = 49), plain skiagram neck & chest showed a total sensitivity of 88.88% (n = 9) and endoscopy was the most sensitive test overall as it showed a total sensitivity of 98.75% (n = 80). No complications were reported with either rigid or flexible endoscopy. Dysphagia is a common presenting complaint in otolaryngology with cases coming directly or being referred from other specialities. Males are more commonly affected than females and incidence of malignancy increases with age. Endoscopy can become the first screening test in dysphagia due to its high sensitivity and low risk of complications, with radiological tests being done in an adjunct manner.

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Human Fibrin Sealant: Effective Hemostasis in Otolaryngologic Surgeries

Abstract

In otolaryngologic surgeries, achieving hemostasis is of paramount importance for reducing associated morbidities. Topical hemostatic agents have been studied mainly in endonasal operations. Its use in other surgeries has been minimally reported. In this "real world data" study, we retrospectively evaluated the surgeries between June 2014 and December 2014, where topical hemostatic agent—Evicel^® (Ethicon BioSurgery, US) was used to achieve hemostasis. All the patients were followed till 15 day post operation. The data on Evicel^® preparation time, intraoperative blood loss, hemostasis time, length of hospital stay, blood transfusion given, and complications were evaluated. The quality of life was assessed by using discomfort score and it was statistically analyzed for patients underwent surgery for chronic rhinosinusitis and chronic otitis media. The surgical clinical data of 103 patients (63 males and 40 females) were considered for the analysis. In all patients, hemostasis was achieved in less than 1 min. The intraoperative blood loss was between 23 and 99 ml for all surgeries. No postoperative bleeding was reported and blood transfusion was not required for any patients. The hospital stay was 1–2 days. In endonasal surgeries, nasal packing was not required in 36.9% of patients. The discomfort score was statistically improved in patients underwent surgery for chronic rhinosinusits and chronic otitis media (p < 0.001). No complications were reported till day 15 postoperatively. Evicel^®, a topical human fibrin sealant found to be effective in achieving hemostasis and for better clinical outcome in various otolaryngologic surgical procedures.

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