Moderate to severe hidradenitis suppurativa patients do not have an altered bacterial composition in peripheral blood compared to healthy controls

Abstract

Background

Hidradenitis Suppurativa (HS) is a chronic inflammatory skin disease defined by recurrent nodules, tunnels and scarring involving the intertriginous skin. HS patients often report an array of systemic symptoms such as fatigue and malaise. The etiology of these symptoms remains unclear. Previously, various bacteria have been associated with mature HS lesions and bacteremia has been reported in HS patients using traditional culturing methods. Thus, we hypothesized that a low-grade bacteremia contributes to the symptomatology in HS patients.

Objective

To explore the potential presence of bacteraemia in HS patients and healthy controls.

Method

A case control study. Compositions of bacteria in the blood of 27 moderate to severe HS patients and 26 healthy controls were investigated using Next Generation 16S ribosomal RNA gene Sequencing (NGS) and routine anaerobic and aerobic blood culturing.

None of the participants received any antibiotics (systemic or topical therapy) within one month prior to the study. HS patients with a recent flare were randomly selected by consecutive recruitment of eligible patients from the Department of Dermatology, Zealand University Hospital, Denmark. Healthy controls were recruited from the University of Copenhagen as well as from the health care staff.

Results

The different bacterial compositions were investigated using NGS and traditional anaerobic and aerobic blood culturing. Our NGS analysis provided a previously unreported characterization of the bacterial composition in peripheral blood from HS patients and healthy controls. Overall, our data demonstrated that HS patients do not have a different bacterial composition in their peripheral blood than healthy controls.

Conclusion

The study suggests the self-reported symptoms in HS such as malaise and fatigue may not be linked to bacteremia.

This article is protected by copyright. All rights reserved.

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Killing two birds with one stone: response to pembrolizumab in a patient with metastatic melanoma and B-cell chronic lymphocytic leukemia

Abstract

Pembrolizumab, a humanized immunoglobulin G4 monoclonal antibody against PD-1, has demonstrated antitumor activity and a manageable safety profile in patients with different solid tumors and hematologic malignancies in multiple clinical trials (1-4). Although these data highlight the effectiveness of PD-1 pathway inhibition, some patients, even those with highly immunogenic tumors, such as melanoma, do not achieve objective response (1).

An increased association of B-cell chronic lymphocytic leukemia (B-CLL) and melanoma, possibly related to an underlying immunologic defect, has been previously reported (5). We still have limited data on the management of advanced stages of cancer duplicities.

This article is protected by copyright. All rights reserved.

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Loss-of-function mutations in filaggrin gene and malignant melanoma: a case control study

Abstract

Background

Loss-of-function mutations in filaggrin gene (FLG) have been suggested to increase the susceptibility of skin malignancies due to reduced levels of epidermal filaggrin and its degradation products, urocanic acid, which may be protective against ultraviolet irradiation.

Objective

We aimed to investigate the association between FLG mutation status and the occurrence of malignant melanoma (MM) in Danish adults.

Methods

The prevalence of FLG mutations in a sample of MM biopsies was compared with a FLG genotyped cohort from two general population studies. Pearson's chi-square and Fisher's exact tests were used to compare the two groups.

Results

A total of 867 MM biopsies and 9965 general population controls were genotyped, respectively. In the MM sample 2 (0.23%) individuals were homozygous and 80 (9.4%) heterozygous mutation carriers. In the general population controls the prevalence of FLG mutations was 18 (0.18%) and 835 (8.4%) for homozygous and heterozygous mutations, respectively. Fisher's exact test and Pearson's chi square test yielded non-significant p-values when the groups were compared.

Conclusion

FLG mutation was not associated with MM in the studied populations. This finding indicates that epidermal deficiency of filaggrin and its degradation products do not influence the risk of MM significantly.

This article is protected by copyright. All rights reserved.

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Cutaneous disseminated sporotrichosis: Clinical experience of 24 cases

Abstract

Sporotrichosis is a subcutaneous mycosis, caused by complex Sporothrix schenckii, It is the most common implantation mycoses in worldwide. It is a polymorphic disease, cutaneous-lymphatic is the most frequent (75-90%).^1-3 We report our 25 years' experience (1990-2015) in cutaneous disseminated sporotrichosis (CDS). We conducted, an open, retrospective and observational study.

This article is protected by copyright. All rights reserved.

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Melanoma and chronic exposure to contraceptives containing micro doses of ethinyl estradiol in young women: a retrospective study from the Research on Adverse Drug Events and Reports (RADAR) project comprising a large Midwestern U.S. patient population

Abstract

An association between the use of contraceptives containing exogenous estrogen compounds and subsequent diagnosis for malignant melanoma (MM) has been suspected for decades. This is, in part, due to the finding that estrogen stimulates melanogenesis¹ and the observation that the incidence of MM is greater in women vs. men before the age of 50, but lower than men after the age of 50², corresponding with the average age of menopause when estrogen levels dramatically decrease.

Prior studies assessing the relationship between the incidence of MM and exposure to exogenous estrogen provide conflicting results^3-6.

This article is protected by copyright. All rights reserved.

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Trichothiodystrophy, complementation group A complicated with squamous cell carcinoma

Abstract

There are three related, clinically defined disorders of DNA repair: xeroderma pigmentosum (XP), trichothiodystrophy (TTD) and Cockayne syndrome (CS).¹ Photosensitivity, neurological/developmental abnormalities, and skin cancer are important pathological features that can be used to distinguish between these three archetypes.^1,2 TTD is a rare, autosomal recessive disease characterized by brittle, sulfur-deficient hair and multisystem abnormalities.³

This article is protected by copyright. All rights reserved.

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Unusually high prevalence of classical Kaposi's sarcoma in Druze Muslims of Northern Israel

Abstract

Kaposi's sarcoma (KS) is a systemic disease that can present with cutaneous lesions with or without internal involvement. It is the most common vascular neoplasm. It can involve any skin surface, including the genitalia. ^1,2 KS limited to the external genitalia is rare in HIV sero-negative individuals. Kaposi sarcoma became known because of the correlation with AIDS-defining illnesses in the 1980s.³

This article is protected by copyright. All rights reserved.

http://ift.tt/2v0T66a

The effect of botulinum neurotoxin A in patients with plaque psoriasis – an exploratory trial

Abstract

A few case stories have described patients with psoriasis who suffered from nerve injury which resulted in clearance of psoriasis (1, 2). Recently three reports have addressed a positive effect of botulinum neurotoxin A (BoNT-A) injections in patients with psoriasis (3-5). BoNT-A inhibits neuropeptide releasement and inflammatory cytokines(6), thus the hypothesis was that blocking neuromodulator could lower neurogenic inflammation resulting in improvement of psoriasis.

This article is protected by copyright. All rights reserved.

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The clinical impact of bedside fiberoptic laryngoscopic recording on a tertiary consult service

Objectives/Hypothesis

Fiberoptic laryngoscopy is dependent on accurate descriptions of examination findings. Traditional recording methods can be impractical for inpatient consults. Therefore, we aim to determine the utility of a smartphone-coupled portable recording system with flexible laryngoscopy for transmitting information between resident and attending physicians in a real-time setting.

Study Design

Pilot prospective study in a tertiary academic hospital.

Methods

This is a prospective study of inpatient consultations in a tertiary referral hospital over a 3-month period from April 2015 to June 2015. Flexible laryngoscopy was performed by a resident physician, and mobile recordings were relayed to an attending physician. Concordance of laryngoscopy interpretations between resident and attending physicians as well as changes in management were documented.

Results

Seventy-nine fiberoptic examinations were recorded and compared. Each consult was categorized as follows: airway evaluation (AE) (43%, 34/79), voice evaluation (VE) (3.7%, 3/79), dysphagia (D) (24%, 19/79), and aerodigestive tract mass/pathology (ADM) (29.1%, 23/79). Nine examinations showed discordance between resident and attending interpretations. Inter-rater agreement was good, with a kappa value of 0.747 (95% confidence interval: 0.643-0.851). The frequency of discordant exams within each group was as follows: AE (15%, 5/34), VE (33%, 1/3), D (11%, 2/19), and ADM (4.3%, 1/23). In five patients, changes in laryngoscopy interpretation changed clinical management. Seven nondiscordant exams had a change in management after attending review. Of the 79 exams, only one required repeat flexible laryngoscopy by the attending physician.

Conclusions

Portable recording of flexible laryngoscopy is an effective tool for timely management of inpatient consultations.

Level of Evidence

4. Laryngoscope, 2017

http://ift.tt/2x7Ekrr

Semicircular canal dehiscence among idiopathic intracranial hypertension patients

Objectives/Hypothesis

The cause of superior semicircular canal dehiscence (SSCD) is unknown. Because of a demonstrated association with tegmental defects and obesity, some have suggested idiopathic intracranial hypertension (IIH) could contribute by eroding the bone over the canal and resulting in SSCD. However, an association between IIH and SSCD has not previously been evaluated. Our objective was to evaluate an association between IIH and SSCD.

Study Design

Retrospective cohort.

Methods

A retrospective study was performed of opening pressures for consecutive patients presenting at a lumbar puncture clinic between August 2012 and October 2015. Imaging for patients who also had thin-sectioned computed tomography (CT) imaging was reviewed for the presence of radiographic SSCD. Association between IIH and SSCD was evaluated using the Student t test and multivariate logistic regression.

Results

One hundred twenty-one patients had both a lumbar puncture performed and thin-sectioned CT imaging available, of which 24 patients (19.8%) met the criteria for IIH with an opening pressure >25 cm H₂O. The remaining 97 patients (80.2%) did not have elevated opening pressures and served as the control cohort. None of the 24 patients with IIH had radiographic SSCD, whereas eight of the 97 patients (8.2%) without IIH had radiographic SSCD. The average opening pressure in patients without radiographic SSCD was 20.2 cm H₂O compared to 19.3 cm H₂O in patients with radiographic SSCD (P = .521). In multivariate logistic regression controlling for age, body mass index, gender, and comorbidities (hypertension, diabetes, hyperlipidemia), opening pressure was not a significant predictor of radiographic SSCD.

Conclusions

The results of this retrospective pilot study do not suggest an association between IIH and SSCD.

Level of Evidence

3b Laryngoscope, 2017

http://ift.tt/2vUc2lX

In response to “in reference to is esophagoscopy necessary during panendoscopy?”

http://ift.tt/2x7NT9O

Sonographic differentiation between lymphatic and metastatic diseases in cervical lymphadenopathy

Objectives/Hypothesis

The spectrum of differential diagnosis in cervical lymphadenopathy is extremely broad. In lymphoma and inflammatory diseases, surgical approaches are restricted to diagnostic lymph extirpation, whereas metastatic outgrowth into regional lymph nodes usually requires neck dissection. Lymph node surgery has to manage the balancing act between sufficient radicality and preservation of functional structures. The current study, therefore, aimed to identify parameters to differentiate between lymph nodes of lymphatic and metastatic origin.

Study Design

Single-center, retrospective cohort study.

Methods

Clinical and sonographic parameters from all patients who underwent diagnostic cervical lymphadenectomy from 2010 to 2015 (N = 262) were included in this retrospective analysis. Parameters with significant differences between the two subgroups were utilized to create a clinical algorithm to distinguish between cervical lymphadenopathy of lymphatic and metastatic genesis.

Results

Statistically significant differences between the two subgroups could be shown for clinical (gender, age, nicotine/alcohol abuse, B symptoms, history of cutaneous melanoma, or lymphoma) and ultrasonographic parameters (string-of-beads confirmation, bilaterality, homogenous echostructure, localization in level I, long-to-short axis ratio, and hilar vascularity). The proposed algorithm yielded a sensitivity of 92.4% for metastatic disease.

Conclusions

The implemented algorithm based on ultrasonographic and clinical criteria contributes to one-step surgical approaches that guarantee a sufficient radicality with a minimum of functional loss.

Level of Evidence

4. Laryngoscope, 2017

http://ift.tt/2vTU3Md

Intraosseous mucoepidermoid carcinoma: Outcome review

Objective

Identify the effect of patient characteristics, disease traits, and treatment modality on patient outcomes in the rare disease process of intraosseous mucoepidermoid carcinoma.

Study Design

Retrospective review of institutional case records and literature.

Methods

This study includes one case report, a literature review of the MEDLINE database from 1950 through June 2017 using keywords "intraosseous" and "mucoepidermoid," and a query of the University of California, Los Angeles, Department of Pathology database for all documented cases of intraosseous mucoepidermoid carcinoma of the head and neck.

Results

Indicators of poorer prognosis were male gender (P = 0.0071) and higher histological grade (P = 0.0095). Lesion site, size, association with odontogenic cyst, and treatment type did not have a statistically significant correlation with patient outcomes. There also was no statistically significant correlation observed between treatment modality and recurrent or progressive disease when stratified by histological grade of the cancer.

Conclusion

This study identified male gender and high histological tumor grade as poor prognostic indicators; however, it did not reveal a statistically significant relationship between treatment modality and patient outcomes. Data regarding patient outcomes following treatment was limited due to loss to follow-up, suggesting that further investigation is required. Based on this review, decisions regarding treatment should be clinically guided and individually tailored to the patient's baseline health, disease severity, and the patient's treatment goals. A multi-disciplinary conference, as was utilized in the presented case report, may be the best approach to treatment planning for these patients at this time.

Level of Evidence

4. Laryngoscope, 2017

http://ift.tt/2x82Cl1

Gastrostomy in the era of minimally invasive head and neck cancer surgery

Objective

Minimally invasive transoral robotic surgery (TORS) is less likely to necessitate gastrostomy tube (GT) following resection of head and neck lesions versus conventional open procedures. However, the incidence of and indications for GT after TORS have not been reported in detail. This study defines the incidence of intra- and postoperative gastrostomy following robotic resection of advanced head and neck disease. It seeks to clarify the relevance of GT after TORS.

Study Design

Adult patients undergoing TORS and neck dissection from 2008 to 2014 were identified in the New York Statewide Planning and Research Cooperative System all-payer administrative database.

Methods

Demographic data and timing of GT in relation to surgery were recorded. Emergency department (ED) visits and inpatient readmissions were compared with multivariable logistic analysis.

Results

Of the 441 included patients, immediate, delayed, and total GT incidence within the first postoperative year was 9.5%, 11.6%, and 21.1%, respectively. Gastrostomy tube complications resulted in 4.5% of 30-day ED visits, 3.3% of 30-day readmissions, and 3.5% of 90-day readmissions. Thirty-nine percent of 90-day readmissions were linked to poor postoperative oral intake. Delayed GT status was associated with an increase in 30-day ED visits, and 30- or 90-day readmissions attributable to poor oral intake (P = 0.10, P < 0.0001, 0.002, respectively).

Conclusion

Even in the era of minimally invasive TORS, impaired oral intake is a significant postoperative burden to head and neck cancer patients with advanced disease. Attention to patient risk factors combined with a complicated hospital course may identify patients benefiting from early GT.

Level of Evidence

2c. Laryngoscope, 2017

http://ift.tt/2vTXHpj

A case-control evaluation of fungiform papillae density in burning mouth syndrome

Hypothesis

It has been hypothesized that high fungiform papillae density may be a risk factor for developing the taste and pain alterations characteristic of burning mouth syndrome.

Objective

Evaluate whether fungiform papillae density, taste sensitivity, and mechanical pain sensitivity differ between burning mouth syndrome cases and controls.

Study Design

This case-control study compared cases diagnosed with primary burning mouth syndrome with pain-free controls.

Methods

Participants (17 female cases and 23 female controls) rated the intensity of sucrose, sodium chloride, citric acid, and quinine applied separately to each side of the anterior tongue and sampled whole mouth. Mechanical pain sensitivity was assessed separately for each side of the tongue using weighted pins. Digital photographs of participants' tongues were used to count fungiform papillae.

Results

Burning mouth syndrome cases had increased whole mouth taste intensity. Cases also had increased sensitivity to quinine on the anterior tongue, as well as increased mechanical pain sensitivity on the anterior tongue. Fungiform papillae density did not differ significantly between cases and controls. Fungiform papillae density on the left and right sides of the tongue were correlated in controls; however, there was no left/right side correlation in cases.

Conclusion

Cases had increased pain and taste perception on the anterior tongue. The lack of correlation between left and right fungiform papillae density in cases may be an indication of asymmetrical lingual innervation in these patients.

Level of Evidence

3b. Laryngoscope, 2017

http://ift.tt/2x7EkaV

The effect of inferior turbinate surgery on ear symptoms

Objective

The aim of this placebo-controlled study was to evaluate the effect of various inferior turbinate surgery techniques on Eustachian tube dysfunction-related symptoms.

Study Design

Outcomes were evaluated using the Eustachian Tube Dysfunction Questionnaire (ETDQ-7) and tympanometry results.

Methods

A total of 72 consecutively blinded and randomized adult patients with enlarged inferior turbinates due to persistent year-round rhinitis underwent either a radiofrequency ablation, diode laser, microdebrider-assisted inferior turbinoplasty, or sham surgery procedure. Assessments were conducted prior to surgery and 3 months subsequent to the surgery.

Results

In the evaluation of all patients, radiofrequency ablation, microdebrider-assisted inferior turbinoplasty, and sham surgery procedures decreased the ETDQ-7 total score significantly. In a three-way analysis of covariance, there were no significant differences in the results between sham surgery and any of the active treatment procedures. Allergic sensitization, sex, and age also had no effect on the results. There were no significant changes in the pre- and postoperative amounts of abnormal tympanometry curves or in the pre- and postoperative tympanometric peak pressure values in the actively treated patients or in the sham surgery group.

Conclusion

The improvement of Eustachian tube dysfunction-related symptoms due to surgery of the anterior half of the inferior turbinate was found to be equal to placebo. The findings of this study do not support the use of reduction of the anterior half of the inferior turbinate as a sole procedure intended to treat the ear symptoms assessed by the ETDQ-7 questionnaire.

Level of Evidence

1b. Laryngoscope, 2017

http://ift.tt/2vU7Bav

Persistent respiratory effort after adenotonsillectomy in children with sleep-disordered breathing

Objectives

Adenotonsillectomy (AT) markedly improves but does not necessarily normalize polysomnographic findings in children with adenotonsillar hypertrophy and related sleep-disordered breathing (SDB). Adenotonsillectomy efficacy should be evaluated by follow-up polysomnography (PSG), but this method may underestimate persistent respiratory effort (RE). Mandibular movement (MMas) monitoring is an innovative measurement that readily identifies RE during upper airway obstruction. We hypothesized that MMas indices would decrease in parallel of PSG indices and that children with persistent RE more reliably could be identified with MMas.

Methods

Twenty-five children (3–12 years of age) with SDB were enrolled in this individual prospective-cohort study. Polysomnography was supplemented with a midsagittal movement magnetic sensor that measured MMas during each respiratory cycle before and > 3 months after AT.

Results

Adenotonsillectomy significantly improved PSG indices, except for RE-related arousals (RERA). Mandibular movement index changes after AT significantly were correlated with corresponding decreases in sleep apnea–hypopnea index (AHI) and O₂ desaturation index (ODI) (Spearman's rho = 0.978 and 0.922, respectively), whereas changes in MMas duration significantly were associated with both RERA duration (rho = 0.475, P = 0.017) and index (rho = 0.564, P = 0.003). Conditional multivariate analysis showed that both AHI and RERA significantly contributed to the variance of MMas index after AT (P = 0.0003 and 0.0005, respectively), whereas MMas duration consistently was related to the duration of RERA regardless of AT.

Conclusion

Adenotonsillectomy significantly reduced AHI. However, persistent RERA were apparent in a significant proportion of children, and this was reflected by the remaining abnormal MMas pattern. Follow-up of children after AT can be recommended and readily achieved by monitoring MMas to identify persistent RE.

Level of Evidence

4. Laryngoscope, 2017

http://ift.tt/2x7K5FD

What is the role of imaging in the evaluation of the patient presenting with unilateral facial paralysis?

http://ift.tt/2vTrtdQ

Is acupuncture an effective complementary tool within otolaryngological perioperative care?

http://ift.tt/2x7JILn

Effect of postoperative radiotherapy in pT1pN1cM0 and pT2p/cN0cM0 oropharyngeal squamous cell carcinoma

Objectives/Hypothesis

Consulting of patients with oropharyngeal carcinoma, classified as pT1pN1cM0 and pT2p/cN0cM0, about postoperative radiotherapy is a precarious task as data are lacking. The aim of this study was to evaluate the effects of postoperative radiotherapy for patients with intermediate-stage oropharyngeal carcinoma.

Study Design

Multicentric retrospective study.

Methods

This analysis was conducted at seven Austrian institutions and included data of patients treated between 2000 and 2012. A total of 81 patients with oropharyngeal squamous cell carcinoma were included, of whom 33 patients received postoperative radiotherapy. p16 status determined by immunohistochemistry was available in 68 patients.

Results

Median follow-up was 47.9 months. Postoperative radiotherapy showed no benefits in regard to overall survival (P = .701). In contrast, disease-free survival was significantly shortened in all patients without postoperative radiotherapy (P = .001). When dividing the cohort in dependence of p16, p16-positive patients did not benefit from postoperative radiotherapy regarding overall and disease-free survival (P = .934 and P = .102), whereas p16-negative patients showed improved disease-free survival after postoperative radiotherapy (P = .007). Multivariate analysis showed that outcome of postoperative radiotherapy is dependent on p16 status.

Conclusions

In terms of disease-free survival, patients with p16-negative tumors may benefit from postoperative radiotherapy, whereas survival of p16-positive patients is good regardless of additional treatment.

Level of Evidence

4 Laryngoscope, 2017

http://ift.tt/2x7WklA

Expiratory muscle strength training for radiation-associated aspiration after head and neck cancer: A case series

Objective/Hypothesis

Expiratory muscle strength training (EMST) is a simple, inexpensive, device-driven exercise therapy. Therapeutic potential of EMST was examined among head and neck cancer survivors with chronic radiation-associated aspiration.

Study Design

Retrospective case series.

Methods

Maximum expiratory pressures (MEPs) were examined among n = 64 radiation-associated aspirators (per penetration–aspiration scale score ≥ 6 on modified barium swallow). Pre–post EMST outcomes were examined in a nested subgroup of patients (n = 26) who enrolled in 8 weeks of EMST (25 repetitions, 5 days/week, 75% load). Nonparametric analyses examined effects of EMST on the primary endpoint MEPs. Secondary measures included swallowing safety (Dynamic Imaging Grade of Swallowing Toxicity [DIGEST]), perceived dysphagia (M.D. Anderson Dysphagia Inventory [MDADI]), and diet (performance status scale for head and neck cancer patients [PSSHN]).

Results

Compared to sex-matched published normative data, MEPs were reduced in 91% (58 of 64) of aspirators (mean ± standard deviation: 89 ± 37). Twenty-six patients enrolled in EMST and three patients withdrew. MEPs improved on average 57% (87 ± 29 to 137 ± 44 cm H₂O, P < 0.001) among 23 who completed EMST. Swallowing safety (per DIGEST) improved significantly (P = 0.03). Composite MDADI scores improved post-EMST (pre-EMST: 59.9 ± 17.1, post-EMST: 62.7 ± 13.9, P = 0.13). PSSHN diet scores did not significantly change.

Conclusion

MEPs were reduced in chronic radiation-associated aspirators relative to normative data, suggesting that expiratory strengthening could be a novel therapeutic target to improve airway protection in this population. Similar to findings in neurogenic populations, these data also suggest improved expiratory pressure-generating capabilities after EMST and translation to functional improvements in swallowing safety in chronic radiation-associated aspirators.

Level of Evidence

4. Laryngoscope, 2017

http://ift.tt/2vTsTVO

Volumetric analysis of olfactory neuroblastoma skull base laterality and implications on neck disease

Objective

To determine if the laterality of primary tumors in patients with olfactory neuroblastoma (ONB) influenced the pattern and development of neck disease.

Methods

Using a retrospective cohort study design from 1994 to 2015, the primary tumors of patients who either presented with or developed neck disease were volumetrically analyzed using iPlan software (version 3.0.0, BrainLAB, Feldkirchen, Germany) by two independent observers. Agreement of volume-derived sidedness was assessed with a kappa statistic, whereas agreement in volume-derived degree of tumor laterality was evaluated with an intraclass correlation coefficient. A one-sample t test was used to assess the difference in dominant percentage between the two observers.

Results

Sixty-one patients with histological diagnosis and treatment of ONB at our institution were identified. Twenty-four patients exhibited neck involvement, 13 of whom could be volumetrically analyzed. Tumors that were greater than 75% eccentric to one side all exhibited contralateral disease, whereas the majority of unilateral neck disease was associated with relatively midline masses. Within the entire cohort, ipsilateral level 2 lymph nodes displayed the highest involvement (83%, 20 of 24), followed by ipsilateral level 1 (54%, 13 of 24), contralateral level 2 (46%, 11 of 24), contralateral level 1 (21%, 5 of 24), and ipsilateral level 3 (21%, 5 of 24).

Conclusion

Ipsilateral neck involvement frequently was observed; however, the degree of ONB primary site laterality did not appear to have implications on the development of contralateral neck disease. Therefore, when considering elective therapy to the neck, ONB laterality should not be used to justify unilateral neck treatment.

Level of Evidence

4. Laryngoscope, 2017

http://ift.tt/2x85nTo

In response to letter to the editor to Does mutational analysis influence the management of differentiated thyroid cancers? - Molecular markers for thyroid nodules

http://ift.tt/2vU1GCy

Life-threatening intraoperative anaphylaxis as a result of chlorhexidine present in Instillagel

A 70-year-old man with left lower limb critical ischaemia was admitted to our vascular unit for a femoral-popliteal bypass. He had experienced a skin reaction to chlorhexidine 6 months previously during an angioplasty procedure. After intubation, once in the operating theatre, the patient had a urinary catheter inserted using Instillagel. Around 30 min later the patient had a full-blown anaphylactic reaction that required aggressive medical management and the abandoning of surgery. Postoperative allergy testing confirmed that the suspected primary trigger for the anaphylaxis was indeed chlorhexidine, which was present in Instillagel. The patient was also found to have allergies to atracurium and teicoplanin, which had been given on induction. This case report highlights the importance of recognising that Instillagel contains chlorhexidine, and that indeed intraurethral use during routine urinary catheterisation can be a cause of life-threatening anaphylaxis.

http://ift.tt/2wiVXHt

A typical presentation of a hepatocellular carcinoma in a middle-aged patient

Description

A 54-year-old man was admitted to our hospital due to experiencing a sudden, severe pain in the right shoulder after mild exercise. He had been losing weight over the previous month and had noticed a lump near his right shoulder. A chest X-ray showed a lytic lesion in the lateral half of his right collarbone (figure 1A) with a cortical break and the presence of a soft-tissue component. A chest CT scan showed the destruction of the bone and a 10x8x7 cm mass associated with the pathological fracture of the collarbone (figure 1B). The diagnostic workup was completed with an abdominal CT scan, which showed a large hepatic tumour, an alpha-fetoprotein blood test level of 1468 ng/mL (normal range <10 ng/mL) and a fine-needle aspiration cytology, which yielded the final diagnosis of disseminated disease of a hepatocellular carcinoma. Cells showed both TTF-1 and hepatocyte antigen positivity, whereas CK7,...

http://ift.tt/2vZhemW

Swiss S1 guideline for the treatment of rosacea

Abstract

Rosacea (in German sometimes called 'Kupferfinne', in French 'Couperose' and in Italian 'Copparosa') is a chronic and frequently relapsing inflammatory skin disease primarily affecting the central areas of the face. Its geographic prevalence varies from 1% to 22%. The differential diagnosis is wide, and the treatment is sometimes difficult and varies by stage of rosacea. For erythematous lesions and telangiectasia, intense pulsed light (IPL) therapy and lasers are popular treatment option. In addition, a vasoconstrictor agent, brimonidine, has recently been developed. For papulopustular rosacea, topical antibiotics, topical and systemic retinoids, as well as systemic antibiotics are used. A topical acaricidal agent, ivermectin, has undergone clinical development and is now on the market. In the later stages, hyperplasia of the sebaceous glands develops, resulting in phymatous growths such as the frequently observed bulbous nose or rhinophyma. Ablative laser treatments have largely replaced classical abrasive tools. Here, we reviewed the current evidence on the treatment of rosacea, provide a guideline (S1 level) and discuss the differential diagnosis of rosacea.

http://ift.tt/2x80EB8

Therapeutic Strategies of Clustered Regularly Interspaced Palindromic Repeats-Cas Systems for Different Viral Infections

Viral Immunology , Vol. 0, No. 0.


http://ift.tt/2ilhRnB

Immune mechanisms of respiratory viral infections in asthma

Hugo A Farne | Sebastian L Johnston

http://ift.tt/2xmRmAS

The nonspecific face of adaptive immunity

Eric Muraille | Stanislas Goriely

http://ift.tt/2wsn9DR

Protective immunity against tuberculosis: what does it look like and how do we find it?

Lu Huang | David G Russell

http://ift.tt/2xmQgEW

Different engagement of TLR2 and TLR4 in Porphyromonas gingivalis vs. ligature-induced periodontal bone loss

Abstract This study was conducted to investigate the roles of different Toll-like receptor (TLR) signaling in Porphyromonas gingivalis (P. gingivalis)-induced and ligature-induced experimental periodontal bone resorption in mice. Wild-type (WT), TLR2 knockout (KO), TLR4KO, and TLR2&4 KO mice with C57/BL6 background were divided into three groups: control, P. gingivalis infection, and ligation. Live P. gingivalis or silk ligatures were placed in the sulcus around maxillary second molars over a 2-week period. Images were captured by digital stereomicroscopy, and the bone resorption area was measured with ImageJ software. The protein expression level of gingival RANKL was measured by ELISA. The gingival mRNA levels of RANKL, IL-1β, TNF-α, and IL-10 were detected by RT-qPCR. The results showed that P. gingivalis induced significant periodontal bone resorption in WT mice and TLR2 KO mice but not in TLR4 KO mice or TLR2&4 KO mice. For all four types of mice, ligation induced significant bone loss compared with that in control groups, and this bone loss was significantly higher than that in the P. gingivalis infection group. RANKL protein expression was significantly increased in the ligation group compared with that in the control group for all four types of mice, and in the P. gingivalis infection group of WT, TLR2 KO, and TLR4 KO mice. Expression patterns of RANKL, IL-1β, TNF-α, and IL-10 mRNA were different in the P. gingivalis infection group and the ligation group in different types of mice. In summary, P. gingivalis-induced periodontal bone resorption is TLR4-dependent, whereas ligation-induced periodontal bone resorption is neither TLR2- nor TLR4-dependent.

http://ift.tt/2v8Mizc

Comparing depth-dependent curing radiant exposure and time of curing of regular and flow bulk-fill composites

Abstract The effect of restoration depth on the curing time of a conventional and two bulk-fill composite resins by measuring microhardness and the respective radiosity of the bottom surface of the specimen was investigated. 1-, 3- and 5-mm thick washers were filled with Surefil SDR Flow–U (SDR), Tetric EvoCeram Bulk Fill-IVA (TEC) or Esthet-X HD–B1 (EHD), and cured with Bluephase® G2 for 40s. Additional 1-mm washers were filled with SDR, TEC or EHD, placed above the light sensor of MARC®, stacked with pre-cured 1-, 3- or 5-mm washer of respective material, and cured for 2.5~60s to mimic 2-, 4- and 6-mm thick composite curing. The sensor measured the radiosity (EB) at the bottom of specimen stacks. Vickers hardness (VH) was measured immediately at 5 locations with triplicate specimens. Nonlinear regression of VH vs EB by VH=α[1-exp(-EB/β)] with all thickness shows that the values of α, maximum hardness, are 21.6±1.0 kg/mm2 for SDR, 38.3±0.6 kg/mm2 for TEC and 45.3±2.6 kg/mm2 for EHD, and the values of β, rate parameter, are 0.40±0.06 J/cm2 for SDR, 0.77±0.04 J/cm2 for TEC and 0.58±0.09 J/cm2 for EHD. The radiosity of the bottom surface was calculated when the bottom surface of each material attained 80% of α of each material. The curing times for each material are in agreement with manufacturer recommendation for thickness. It is possible to estimate time needed to cure composite resin of known depth adequately by the radiosity and microhardness of the bottom surface.

http://ift.tt/2wyJdMg

Ki-67 protein predicts survival in oral squamous carcinoma cells: an immunohistochemical study

Abstract The aim of this study was to identify the expression of Ki-67 and MCM3 in oral squamous cell carcinoma (OSCC) as well as to address the correlation with patient survival and clinical features. Samples were collected from 51 patients with OSCC who presented for follow-up. Immunohistochemical expression of Ki-67 and MCM3 in all groups was performed. The scoring system was previous published by Tsurutani in 2005. We used Kappa index to evaluate observers agreement degree. The associations between protein expression and clinical variables were examined for statistical significance using the chi-squared test. The overall survival rates were estimated by the Kaplan-Meier method and the relationship between protein expression and survival was compared using the log-rank test (p < 0.05). The overall survival time for a patient with positive immunostaining for Ki-67 is shorter than for a patient with negative immunostaining, (log-rank test, p = 0.00882). Patients with tumor size T3 and T4 showed a statistically significant relationship with Ki-67 immunoexpression (log-rank test, p = 0.0174). The relationship between Ki-67 expression and the relation between age, gender, smoking, tumor site, lymph node metastasis and disease stage was not significant. The examiners agreement degree by Kappa presented p value < 0.05. There was not a significant correlation when we evaluated MCM3 expression regarding clinical characteristics and survival rate. From these results, the present study suggests that positive Ki-67 expression found in OSCC patients may contribute to predict the survival in OSCC samples, as well as the relation between the protein and the tumor size.

http://ift.tt/2v8Qhfm

Characterization and coating stability evaluation of nickel-titanium orthodontic esthetic wires: an in vivo study

Abstract The objective of this study was to compare coating dimensions and surface characteristics of two different esthetic covered nickel-titanium orthodontic rectangular archwires, as-received from the manufacturer and after oral exposure. The study was designed for comparative purposes. Both archwires, as-received from the manufacturer, were observed using a stereomicroscope to measure coating thickness and inner metallic dimensions. The wires were also exposed to oral environment in 11 orthodontic active patients for 21 days. After removing the samples, stereomicroscopy images were captured, coating loss was measured and its percentage was calculated. Three segments of each wire (one as-received and two after oral exposure) were observed using scanning electron microscopy for a qualitative analysis of the labial surface of the wires. The Lilliefors test and independent t-test were applied to verify normality of data and statistical differences between wires, respectively. The significance level adopted was 0.05. The results showed that the differences between the wires while comparing inner height and thickness were statistically significant (p < 0.0001). In average, the most recently launched wire presented a coating thickness twice that of the control wire, which was also a statistically significant difference. The coating loss percentage was also statistically different (p = 0.0346) when the latest launched wire (13.27%) was compared to the control (29.63%). In conclusion, the coating of the most recent wire was thicker and more uniform, whereas the control had a thinner coating on the edges. After oral exposure, both tested wires presented coating loss, but the most recently launched wire exhibited better results.

http://ift.tt/2wysNDD

Risk factors for implant failure: a retrospective study in an educational institution using GEE analyses

Abstract This study aimed to evaluate dental implant outcomes and to identify risk factors associated with implant failure over 12 years via dental records of patients attending an educational institution. Dental records of 202 patients receiving 774 dental implants from 2002 to 2014 were analyzed by adopting a more reliable statistical method to evaluate risk factors with patients as the unit [generalized estimating equation (GEE)]. Information regarding patient age at implantation, sex, use of tobacco, and history of systemic diseases was collected. Information about implant location in the arch region and implant length, diameter, and placement in a grafted area was evaluated after 2 years under load. Systemic and local risk factors for early and late implant failure were studied. A total of 18 patients experienced 25 implant failures, resulting in an overall survival rate of 96.8% (2.84% and 0.38% early and late implant failures, respectively). The patient-based survival rate was 91.8%. GEE univariate and multivariate analyses revealed that a significant risk factor for implant failure was the maxillary implant (p = 0.006 and p = 0.014, respectively). Bone grafting appeared to be a risk factor for implant failure (p = 0.054). According to GEE analyses, maxillary implants had significantly worse outcomes in this population and were considered to be a risk factor for implant failure. Our results suggested that implants placed in a bone augmentation area had a tendency to fail.

http://ift.tt/2wyY8WQ

Longitudinal impact of clinical and socioenvironmental variables on oral health-related quality of life in adolescents

Abstract The aim of the present study was to investigate the impact of oral diseases, socioeconomic status, and family environmental factors on changes in the perception of oral health-related quality of life (OHRQoL) in adolescents. A prospective cohort study was conducted in Juiz de Fora, Minas Gerais, Brazil, with a sample of 286 twelve-year-old adolescents from public and private schools, selected by means of multistage random sampling. The adolescents were clinically examined for dental caries experience (number of decayed, missing, and filled teeth - DMFT index), presence of bleeding, and orthodontic treatment needs. They were asked to complete the Brazilian version of the Child Perceptions Questionnaire (CPQ11-14). In addition, parents answered a questionnaire about their socioeconomic status and family environmental characteristics. After 3 years, the adolescents were contacted again to participate in the research. Logistic regression models, with explanatory variables assessed both individually and jointly, were used to determine which independent variables impacted longitudinally on OHRQoL. The final result demonstrated that only DMFT explained part of the response variability in CPQ11-14 scores. In conclusion, caries experience was an important predictor of OHRQoL in adolescents followed up for 3 years.

http://ift.tt/2v95ZH1

Evaluation of the physicochemical properties of silicone- and epoxy resin-based root canal sealers

Abstract To assess the physicochemical properties of AH Plus, GuttaFlow 2, GuttaFlow BioSeal, and MM Seal, five samples of each root canal sealer were evaluated to determine their setting time (ST), dimensional change (DC), solubility (SL), flow (FL), and radiopacity (RD) according to American National Standards Institute/American Dental Association (ANSI/ADA) Specification 57. The distilled and deionized water obtained from the SL test were subjected to atomic absorption spectrometry to observe the presence of Ca2+, K+, and Na+ ions. Statistical analysis was performed by using one-way ANOVA and Tukey–Kramer tests (p < 0.05). The following results were obtained: ST (min) (AH Plus 463.6 ± 13.22; GuttaFlow 2 24.35 ± 2.78; GuttaFlow Bioseal 17.4 ± 0.55; MM Seal 47.60 ± 4.39), DC (%) (AH Plus 0.06 ± 0.12; GuttaFlow 2 −26.06 ± 1.24; GuttaFlow Bioseal 2.10 ± 1.47; MM Seal 8.47 ± 2.41), SL (%) (AH Plus 0.41 ± 0.21; GuttaFlow 2 5.13 ± 4.11; GuttaFlow Bioseal 3.03 ± 1.05; MM Seal 0.94 ± 0.17), FL (mm) (AH Plus 36.42 ± 0.40; GuttaFlow 2 36.44 ± 0.05; GuttaFlow Bioseal 35.4 ± 0.03; MM Seal 52.75 ± 0.60), and RD (mmAl) (AH Plus 7.52 ± 1.59; GuttaFlow 2 6.85 ± 0.14; GuttaFlow Bioseal 7.02 ± 0.18; MM Seal 3.32 ± 0.90). ST, DC, SL, FL, and RD showed statistical differences among the root canal sealers (p < 0.05). As AH Plus showed the lowest DC and SL values (p < 0.05), the findings indicate that this sample is the only sealer conforming to ANSI/ADA standards.

http://ift.tt/2wyHcQh

Large Subcapsular Splenic Hematoma with a Large Pancreatic Pseudocyst Was Successfully Treated with Splenic Arterial Embolization and Ultrasound-Guided Percutaneous Drainage of Pancreatic Pseudocyst

Subcapsular splenic hematoma is a rare complication of pancreatitis. The management for subcapsular splenic hematoma remains controversial. We herein report a case of a large subcapsular splenic hematoma with a large pancreatic pseudocyst, which was successfully treated with splenic arterial embolization and ultrasound- (US-) guided percutaneous drainage of pancreatic pseudocyst, for the first time. A 44-year-old male suffered from recurrent abdominal pain for more than two years. He had previous 3 episodes of pancreatitis. A subcapsular splenic hematoma (16.0 × 16.0 × 7.6 cm) with pancreatic pseudocyst (13.5 × 10.0 × 8.0 cm) was shown on abdominal computed tomography (CT). He underwent splenic arterial embolization to decrease the blood supply of the spleen and then ultrasound-guided percutaneous drainage of the large pancreatic pseudocyst. After 2 weeks, the repeated CT-Abdomen showed the disappearance of pancreatic pseudocyst and multiple areas of infarction on the spleen, while the splenic subcapsular hematoma had also significantly reduced. The patient was discharged after almost a month of his hospital admission with the drainage tube attached, and about 2 weeks later the drainage tube was removed upon CT scan confirmation of decrease in the volume of the subcapsular hematoma. Patient had no abdominal symptoms at the 1.5-year follow-up.

http://ift.tt/2x7bwzv

Epithelial TNF Receptor Signaling Promotes Mucosal Repair in Inflammatory Bowel Disease [MUCOSAL IMMUNOLOGY]

TNF plays an integral role in inflammatory bowel disease (IBD), as evidenced by the dramatic therapeutic responses in Crohn's disease (CD) patients induced by chimeric anti-TNF mAbs. However, treatment of CD patients with etanercept, a decoy receptor that binds soluble TNF, fails to improve disease. To explore this discrepancy, we investigated the role of TNF signaling in Wnt/β-catenin–mediated intestinal stem cell and progenitor cell expansion in CD patients, human cells, and preclinical mouse models. We hypothesized that TNF exerts beneficial effects on intestinal epithelial cell (IEC) responses to injury. In CD patients, intestinal stem cell and progenitor cell Wnt/β-catenin signaling correlates with inflammation status. TNF-deficient (Tnf^–/–) mice exhibited increased apoptosis, less IEC proliferation, and less Wnt signaling when stimulated with anti-CD3 mAb. Bone marrow (BM) chimera mice revealed that mucosal repair depended on TNF production by BM–derived cells and TNFR expression by radioresistant IECs. Wild-type->Tnfr1/2^–/– BM chimera mice with chronic dextran sodium sulfate colitis exhibited delayed ulcer healing, more mucosal inflammation, and impaired Wnt/β-catenin signaling, consistent with the hypothesis that epithelial TNFR signaling participates in mucosal healing. The direct effect of TNF on stem cells was demonstrated by studies of TNF-induced Wnt/β-catenin target gene expression in murine enteroids and colonoid cultures and TNF-induced β-catenin activation in nontransformed human NCM460 cells (TOPFlash) and mice (TOP-GAL). Together, these data support the hypothesis that TNF plays a beneficial role in enhancing Wnt/β-catenin signaling during ulcer healing in IBD. These novel findings will inform clinicians and therapeutic chemists alike as they strive to develop novel therapies for IBD patients.

http://ift.tt/2fZM0Ik

Immune Protection by a Cytomegalovirus Vaccine Vector Expressing a Single Low-Avidity Epitope [IMMUNOTHERAPY AND VACCINES]

Experimental CMV-based vaccine vectors expressing a single MHC class I–restricted high-avidity epitope provided strong, T cell–dependent protection against viruses or tumors. In this study we tested the low-avidity epitope KCSRNRQYL, and show that a mouse CMV (MCMV) vector provides complete immune control of recombinant vaccinia virus expressing the same epitope if KCSRNRQYL is expressed within the immediate-early MCMV gene ie2. The same epitope expressed within the early M45 gene provided no protection, although MCMV vectors expressing the high-avidity epitope SSIEFARL induced protective immunity irrespective of gene expression context. Immune protection was matched by Ag-induced, long-term expansion of effector memory CD8 T cells, regardless of epitope avidity. We explained this pattern by observing regularities in Ag competition, where responses to high-avidity epitopes outcompeted weaker ones expressed later in the replicative cycle of the virus. Conversely, robust and early expression of a low-avidity epitope compensated its weak intrinsic antigenicity, resulting in strong and sustained immunity and immune protection.

http://ift.tt/2fZ4etk

Lactation-Based Maternal Educational Immunity Crosses MHC Class I Barriers and Can Impart Th1 Immunity to Th2-Biased Recipients [IMMUNE SYSTEM DEVELOPMENT]

We have previously demonstrated lactational transfer of T cell–based immunity from dam to foster pup. In the short term, a significant part of transferred immunity is passive cellular immunity. However, as time progresses, this is replaced by what we have described as maternal educational immunity such that by young adulthood, all immune cells responding to a foster dam immunogen are the product of the foster pup's thymus. To reduce confounding factors, this original demonstration used congenic/syngeneic dam and foster pup pairs. In this study, we investigated lactational transfer of immunity to Mycobacterium tuberculosis in MHC class I–mismatched animals, as well as from Th1-biased dams to Th2-biased foster pups. Using immunized C57BL/6J dams, lactational transfer to nonimmunized BALB/cJ foster pups resulted in much greater immunity than direct immunization in 5-wk-old pups (ex vivo assay of pup splenocytes). At this age, 82% of immunogen-responding cells in the pup spleen were produced through maternal educational immunity. FVB/NJ nonimmunized foster recipients had a greater number of maternal cells in the spleen and thymus but a much larger percentage was Foxp3⁺, resulting in equivalent immunity to direct immunization. Depletion of maternal Foxp3⁺ cells from pup splenocytes illustrated a substantial role for lactationally transferred dam regulatory T cells in suppression of the ex vivo response in FVB/NJ, but not BALB/cJ, recipients. We conclude that lactational transfer of immunity can cross MHC class I barriers and that Th1 immunity can be imparted to Th2-biased offspring; in some instances, it can be greater than that achieved by direct immunization.

http://ift.tt/2imqMVZ

Correction: Macrophage Mitochondrial and Stress Response to Ingestion of Cryptococcus neoformans [CORRECTIONS]

http://ift.tt/2ilTNAY

Correction: A CD80-Biased CTLA4-Ig Fusion Protein with Superior In Vivo Efficacy by Simultaneous Engineering of Affinity, Selectivity, Stability, and FcRn Binding [CORRECTIONS]

http://ift.tt/2fZWBmB

Retraction: Hypoxia-Inducible Factor-1{alpha}-Dependent Protection from Intestinal Ischemia/Reperfusion Injury Involves Ecto-5'-Nucleotidase (CD73) and the A2B Adenosine Receptor [LETTERS OF RETRACTION]

http://ift.tt/2in5wzo

Versican-Derived Matrikines Regulate Batf3-Dendritic Cell Differentiation and Promote T Cell Infiltration in Colorectal Cancer [TUMOR IMMUNOLOGY]

Colorectal cancer originates within immunologically complex microenvironments. To date, the benefits of immunotherapy have been modest, except in neoantigen-laden mismatch repair–deficient tumors. Approaches to enhance tumor-infiltrating lymphocytes in the tumor bed may substantially augment clinical immunotherapy responses. In this article, we report that proteolysis of the tolerogenic matrix proteoglycan versican (VCAN) strongly correlated with CD8⁺ T cell infiltration in colorectal cancer, regardless of mismatch repair status. Tumors displaying active VCAN proteolysis and low total VCAN were associated with robust (10-fold) CD8⁺ T cell infiltration. Tumor-intrinsic WNT pathway activation was associated with CD8⁺ T cell exclusion and VCAN accumulation. In addition to regulating VCAN levels at the tumor site, VCAN proteolysis results in the generation of bioactive fragments with novel functions (VCAN-derived matrikines). Versikine, a VCAN-derived matrikine, enhanced the generation of CD103⁺CD11c^hiMHCII^hi conventional dendritic cells (cDCs) from Flt3L-mobilized primary bone marrow–derived progenitors, suggesting that VCAN proteolysis may promote differentiation of tumor-seeding DC precursors toward IRF8- and BATF3-expressing cDCs. Intratumoral BATF3-dependent DCs are critical determinants for T cell antitumor immunity, effector T cell trafficking to the tumor site, and response to immunotherapies. Our findings provide a rationale for testing VCAN proteolysis as a predictive and/or prognostic immune biomarker and VCAN-derived matrikines as novel immunotherapy agents.

http://ift.tt/2fZLXME

Modified Vaccinia Virus Ankara Vector Induces Specific Cellular and Humoral Responses in the Female Reproductive Tract, the Main HIV Portal of Entry [MUCOSAL IMMUNOLOGY]

The female reproductive tract (FRT) is one of the major mucosal invasion sites for HIV-1. This site has been neglected in previous HIV-1 vaccine studies. Immune responses in the FRT after systemic vaccination remain to be characterized. Using a modified vaccinia virus Ankara (MVA) as a vaccine model, we characterized specific immune responses in all compartments of the FRT of nonhuman primates after systemic vaccination. Memory T cells were preferentially found in the lower tract (vagina and cervix), whereas APCs and innate lymphoid cells were mainly located in the upper tract (uterus and fallopian tubes). This compartmentalization of immune cells in the FRT was supported by transcriptomic analyses and a correlation network. Polyfunctional MVA-specific CD8⁺ T cells were detected in the blood, lymph nodes, vagina, cervix, uterus, and fallopian tubes. Anti-MVA IgG and IgA were detected in cervicovaginal fluid after a second vaccine dose. Thus, systemic vaccination with an MVA vector elicits cellular and Ab responses in the FRT.

http://ift.tt/2ilsxTi

The Development of Steady-State Activation Hubs between Adult LTi ILC3s and Primed Macrophages in Small Intestine [MUCOSAL IMMUNOLOGY]

Group 3 innate lymphoid cells (ILC3s) are important for intestinal health, particularly in controlling inflammation in response to epithelial dysregulation, but their role during homeostasis remains less well understood. We generated IL-22 reporter mice to assess production of this key cytokine by ILC3s in the small intestine during development and under basal conditions. Although IL-22 is produced by a variety of lymphocyte populations, constitutively high IL-22 expression was limited to lymphoid-tissue inducer (LTi) cells residing in lymph node–like structures in the gut called solitary intestinal lymphoid tissues (SILT). Constitutive IL-22 expression was dependent on the microbiota and MyD88 signaling, appeared upon weaning, and was present across the spectrum of SILT, including in cryptopatches. Activated SILT LTi cells colocalized with a rare subpopulation of activated macrophages constitutively positive for IL-12/23 p40 and capable of activating neonatal LTi cells in response to TLR stimulus. Thus, weaning leads to the organization of innate immune activation hubs at SILT that mature and are continuously sustained by signals from the microbiota. This functional and anatomic organization constitutes a significant portion of the steady-state IL-23/IL-22 axis.

http://ift.tt/2fZLZEg

Impaired Transmigration of Myeloid-Derived Suppressor Cells across Human Sinusoidal Endothelium Is Associated with Decreased Expression of CD13 [IMMUNE REGULATION]

Human monocytic myeloid-derived suppressor cells (MO-MDSCs) within the hepatic compartment suppress inflammation and impair immune surveillance in liver cancer. It is currently not known whether recruitment of MO-MDSCs from blood via hepatic sinusoidal endothelium (HSEC) contributes to their enrichment within the hepatic compartment. We compared the transmigratory potential of MO-MDSCs and monocytes after adhesion to hepatic endothelial monolayers in flow-based assays that mimic in vivo shear stress in the sinusoids. Despite comparable binding to HSEC monolayers, proportionally fewer MO-MDSCs underwent transendothelial migration, indicating that the final steps of extravasation, where actin polymerization plays an important role, are impaired in MO-MDSCs. In this article, we found reduced levels of CD13 on MO-MDSCs, which has recently been reported to control cell motility in monocytes, alongside reduced VLA-4 expression, an integrin predominantly involved in adherence to the apical side of the endothelium. CD13 and VLA-4 blocking and activating Abs were used in flow-based adhesion assays, live-cell imaging of motility, and actin polymerization studies to confirm a role for CD13 in impaired MO-MDSC transmigration. These findings indicate that CD13 significantly contributes to tissue infiltration by MO-MDSCs and monocytes, thereby contributing to the pathogenesis of hepatic inflammation.

http://ift.tt/2imrfaH

IL-7 Restores T Lymphocyte Immunometabolic Failure in Septic Shock Patients through mTOR Activation [CLINICAL AND HUMAN IMMUNOLOGY]

T lymphocyte alterations are central to sepsis pathophysiology, whereas related mechanisms remain poorly understood. We hypothesized that metabolic alterations could play a role in sepsis-induced T lymphocyte dysfunction. Samples from septic shock patients were obtained at day 3 and compared with those from healthy donors. T cell metabolic status was evaluated in the basal condition and after T cell stimulation. We observed that basal metabolic content measured in lymphocytes by nuclear magnetic resonance spectroscopy was altered in septic patients. Basal ATP concentration, oxidative phosphorylation (OXPHOS), and glycolysis pathways in T cells were decreased as well. After stimulation, T lymphocytes from patients failed to induce glycolysis, OXPHOS, ATP production, GLUT1 expression, glucose entry, and proliferation to similar levels as controls. This was associated with significantly altered mTOR, but not Akt or HIF-1α, activation and only minor AMPKα phosphorylation dysfunction. IL-7 treatment improved mTOR activation, GLUT1 expression, and glucose entry in septic patients' T lymphocytes, leading to their enhanced proliferation. mTOR activation was central to this process, because rapamycin systematically inhibited the beneficial effect of recombinant human IL-7. We demonstrate the central role of immunometabolism and, in particular, mTOR alterations in the pathophysiology of sepsis-induced T cell alterations. Our results support the rationale for targeting metabolism in sepsis with recombinant human IL-7 as a treatment option.

http://ift.tt/2fZ30yt

Control of Regulatory T Cell Differentiation by the Transcription Factors Thpok and LRF [IMMUNE SYSTEM DEVELOPMENT]

The CD4⁺ lineage–specific transcription factor Thpok is required for intrathymic CD4⁺ T cell differentiation and, together with its homolog LRF, supports CD4⁺ T cell helper effector responses. However, it is not known whether these factors are needed for the regulatory T cell (Treg) arm of MHC class II responses. In this study, by inactivating in mice the genes encoding both factors in differentiated Tregs, we show that Thpok and LRF are redundantly required to maintain the size and functions of the postthymic Treg pool. They support IL-2–mediated gene expression and the functions of the Treg-specific factor Foxp3. Accordingly, Treg-specific disruption of Thpok and Lrf causes a lethal inflammatory syndrome similar to that resulting from Treg deficiency. Unlike in conventional T cells, Thpok and LRF functions in Tregs are not mediated by their repression of the transcription factor Runx3. Additionally, we found that Thpok is needed for the differentiation of thymic Treg precursors, an observation in line with the fact that Foxp3⁺ Tregs are CD4⁺ cells. Thus, a common Thpok-LRF node supports both helper and regulatory arms of MHC class II responses.

http://ift.tt/2g0ho9u

Induction of Regulatory T Cells and Its Regulation with Insulin-like Growth Factor/Insulin-like Growth Factor Binding Protein-4 by Human Mesenchymal Stem Cells [CLINICAL AND HUMAN IMMUNOLOGY]

Human mesenchymal stem cells (MSCs) are multipotent and exert anti-inflammatory effects, but the underlying mechanism remains to be elucidated. In the current study, we investigated the regulatory mechanism of regulatory T cell (Treg) induction through the growth factors released by human MSCs. Human naive CD4⁺ T cells were stimulated with anti-CD3/28 Abs and cocultured with human MSC culture supernatant for 48 h. The proliferation and cytokine production of CD4⁺ T cells and surface molecule expression on CD4⁺ T cells were evaluated. The proliferation of anti-CD3/28 Abs–stimulated CD4⁺ T cells was suppressed by the addition of human MSC culture supernatant; in addition, the production of IL-10 and IL-4 increased. The human MSC culture supernatant induced CD4⁺FOXP3⁺ Tregs that expressed CD25, CTLA-4, glucocorticoid-induced TNFR-related protein, insulin-like growth factor (IGF)-1R, and IGF-2R, showing antiproliferative activity against CD4⁺ T cells. In addition, the induction of Tregs by human MSC culture supernatant was enhanced by the addition of IGF and suppressed by the inhibition of IGF-1R. In contrast, a significant amount of IGF binding protein (IGFBP)-4, an inhibitor of IGF action, was detected in the human MSC culture supernatant. After neutralization of IGFBP-4 in the human MSC culture supernatant by anti–IGFBP-4 Ab, Treg numbers increased significantly. Thus, our results raise the possibility that human MSC actions also involve a negative-regulatory mechanism that suppresses Treg proliferation by releasing IGFBP-4. The results of this study suggest that regulation of IGF may be important for treatments using human MSCs.

http://ift.tt/2fZ2Yql

Adaptive from Innate: Human IFN-{gamma}+CD4+ T Cells Can Arise Directly from CXCL8-Producing Recent Thymic Emigrants in Babies and Adults [IMMUNE SYSTEM DEVELOPMENT]

We recently demonstrated that the major effector function of neonatal CD4⁺ T cells is to produce CXCL8, a prototypic cytokine of innate immune cells. In this article, we show that CXCL8 expression, prior to proliferation, is common in newly arising T cells (so-called "recent thymic emigrants") in adults, as well as in babies. This effector potential is acquired in the human thymus, prior to TCR signaling, but rather than describing end-stage differentiation, such cells, whether isolated from neonates or adults, can further differentiate into IFN-–producing CD4⁺ T cells. Thus, the temporal transition of host defense from innate to adaptive immunity is unexpectedly mirrored at the cellular level by the capacity of human innate-like CXCL8-producing CD4⁺ T cells to transition directly into Th1 cells.

http://ift.tt/2imren9

Neoantigen Expression in Steady-State Langerhans Cells Induces CTL Tolerance [IMMUNE REGULATION]

The skin hosts a variety of dendritic cells (DCs), which act as professional APC to control cutaneous immunity. Langerhans cells (LCs) are the only DC subset in the healthy epidermis. However, due to the complexity of the skin DC network, their relative contribution to either immune activation or immune tolerance is still not entirely understood. To specifically study the function of LCs in vivo, without altering the DC subset composition in the skin, we have generated transgenic mouse models for tamoxifen-inducible de novo expression of Ags in LCs but no other langerin⁺ DCs. Therefore, this system allows for LC-restricted Ag presentation to T cells. Presentation of nonsecreted OVA (GFPOVA) by steady-state LCs resulted in transient activation of endogenous CTL in transgenic mice. However, when these mice were challenged with OVA by gene gun immunization in the contraction phase of the primary CTL response they did not respond with a recall of CTL memory but, instead, with robust Ag-specific CTL tolerance. We found regulatory T cells (T_regs) enriched in the skin of tolerized mice, and depletion of T_regs or adoptive experiments revealed that T_regs were critically involved in CTL tolerance. By contrast, when OVA was presented by activated LCs, a recallable CTL memory response developed in transgenic mice. Thus, neoantigen presentation by epidermal LCs results in either robust CTL tolerance or CTL memory, and this decision-making depends on the activation state of the presenting LCs.

http://ift.tt/2ilnrGj

CXCL1 and CXCL2 Regulate NLRP3 Inflammasome Activation via G-Protein-Coupled Receptor CXCR2 [IMMUNE REGULATION]

Inflammation is an extensively concerted process that confers protection to the host encountering immune insult. The major inflammatory mediators include IL-1 family members, such as IL-1β, and the functional activation of such molecules is arbitrated by their regulated cleavage brought about by components of a multiprotein complex called inflammasome. In this context, NLR family pyrin domain containing 3 (NLRP3) inflammasome activation often acts as a rate-limiting step in regulating critical cell-fate decisions in various inflammatory scenarios. In this study, we identify the G-protein–coupled receptor CXCR2 (recognizing chemokines CXCL1 and CXCL2) as another arm feeding into the regulated activation of NLRP3 inflammasome in macrophages. We demonstrate that in vivo blocking of CXCL1 and CXCL2 can significantly reduce the Mycobacterium tuberculosis–induced bioactive IL-1β production. Further, CXCL1 could amplify the inflammasome activation in in vivo mouse models of carrageenan-induced inflammation in footpads and air pouches. The mechanistic insights revealed CXCR2-driven protein kinase C μ–dependent integrin-linked kinase to be essential for CXCL1-mediated activation of NLRP3 inflammasome. Blocking the activity of integrin-linked kinase or protein kinase C μ either by small interfering RNA–mediated knockdown or pharmacological inhibitor compromised inflammasome activation and subsequent production of bioactive IL-1β. Taken together, our study demonstrates CXCR2-driven activation of NLRP3 inflammasome in macrophages and indicates a potential host-directed therapeutic target to limit the damaging inflammation associated with overt production of proinflammatory IL-1β.

http://ift.tt/2fZ2W1H

sIgM-Fc{mu}R Interactions Regulate Early B Cell Activation and Plasma Cell Development after Influenza Virus Infection [IMMUNE REGULATION]

Previous studies with mice lacking secreted IgM (sIgM) due to a deletion of the μs splice region (μs^–/–) had shown sIgM involvement in normal B cell development and in support of maximal Ag-specific IgG responses. Because of the changes to B cell development, it remains unclear to which extent and how sIgM directly affects B cell responses. In this study, we aimed to explore the underlying mechanisms of sIgM-mediated IgG response regulation during influenza virus infection. Generating mice with normally developed μs-deficient B cells, we demonstrate that sIgM supports IgG responses by enhancing early Ag-specific B cell expansion, not by altering B cell development. Lack of FcμR expression on B cells, but not lack of Fcα/μR expression or complement activation, reduced antiviral IgG responses to the same extent as observed in μs^–/– mice. B cell–specific Fcmr^–/– mice lacked robust clonal expansion of influenza hemagglutinin-specific B cells early after infection and developed fewer spleen and bone marrow IgG plasma cells and memory B cells, compared with controls. However, germinal center responses appeared unaffected. Provision of sIgM rescued plasma cell development from μs^–/– but not Fcmr^–/– B cells, as demonstrated with mixed bone marrow chimeric mice. Taken together, the data suggest that sIgM interacts with FcμR on B cells to support early B cell activation and the development of long-lived humoral immunity.

http://ift.tt/2fZ2Xmh

The Small Rho GTPase TC10 Modulates B Cell Immune Responses [IMMUNE REGULATION]

Rho family GTPases regulate diverse cellular events, such as cell motility, polarity, and vesicle traffic. Although a wealth of data exists on the canonical Rho GTPases RhoA, Rac1, and Cdc42, several other family members remain poorly studied. In B cells, we recently demonstrated a critical role for Cdc42 in plasma cell differentiation. In this study, we focus on a close homolog of Cdc42, TC10 (also known as RhoQ), and investigate its physiological role in B cells. By generating a TC10-deficient mouse model, we show that despite reduced total B cell numbers, B cell development in these mice occurs normally through distinct developmental stages. Upon immunization, IgM levels were reduced and, upon viral infection, germinal center responses were defective in TC10-deficient mice. BCR signaling was mildly affected, whereas cell migration remained normal in TC10-deficient B cells. Furthermore, by generating a TC10/Cdc42 double knockout mouse model, we found that TC10 can compensate for the lack of Cdc42 in TLR-induced cell activation and proliferation, so the two proteins play partly redundant roles. Taken together, by combining in vivo and in vitro analysis using TC10-deficient mice, we define the poorly studied Rho GTPase TC10 as an immunomodulatory molecule playing a role in physiological B cell responses.

http://ift.tt/2fZ2TTz

ORMDL3 Facilitates the Survival of Splenic B Cells via an ATF6{alpha}-Endoplasmic Reticulum Stress-Beclin1 Autophagy Regulatory Pathway [IMMUNE REGULATION]

The genetic association of orosomucoid-like 3 (ORMDL3) with an array of immunoinflammatory disorders has been recently unraveled in multiple ethnic groups, and functional exploration has received attention of the particular relevance of this gene in endoplasmic reticulum stress, lipid metabolism, and inflammatory response. In this study, we demonstrated the upregulation of ORMDL3 in both patients with systemic lupus erythematosus and lupus mice compared with controls. By establishing ORMDL3 knockout mice (Ormdl3^–/–), we showed that silencing Ormdl3 in vivo significantly decreased the proportions of mature B lymphocytes and transitional 2B cells in spleen and B1a cells from abdominal cavity perfusion fluid, the secretion of IgG and IgM, and the expression of Baff. Additionally, knockdown of Ormdl3 augmented the apoptosis of total splenic cells and splenic CD19⁺ B cells but did not affect B cell proliferation and cell cycle. Subsequently, we in vitro and in vivo demonstrated that ORMDL3 potentially mediates the autophagy via the ATF 6–Beclin1 autophagy pathway, and it facilitates the survival of splenic B cells via promoting autophagy and suppressing apoptosis. Taken together, we uncovered a role of ORMDL3 in fine-tuning B cell development and survival, besides highlighting a potential mechanism by which ORMDL3 regulates autophagy via ATF6 pathway.

http://ift.tt/2ilnq5d

Zebrafish B Cell Development without a Pre-B Cell Stage, Revealed by CD79 Fluorescence Reporter Transgenes [IMMUNE SYSTEM DEVELOPMENT]

CD79a and CD79b proteins associate with Ig receptors as integral signaling components of the B cell Ag receptor complex. To study B cell development in zebrafish, we isolated orthologs of these genes and performed in situ hybridization, finding that their expression colocalized with IgH-μ in the kidney, which is the site of B cell development. CD79 transgenic lines were made by linking the promoter and upstream regulatory segments of CD79a and CD79b to enhanced GFP to identify B cells, as demonstrated by PCR analysis of IgH-μ expression in sorted cells. We crossed these CD79-GFP lines to a recombination activating gene (Rag)2:mCherry transgenic line to identify B cell development stages in kidney marrow. Initiation of CD79:GFP expression in Rag2:mCherry⁺ cells and the timing of Ig H and L chain expression revealed simultaneous expression of both IgH-μ– and IgL-–chains, without progressing through the stage of IgH-μ–chain alone. Rag2:mCherry⁺ cells without CD79:GFP showed the highest Rag1 and Rag2 mRNAs compared with CD79a and CD79b:GFP⁺ B cells, which showed strongly reduced Rag mRNAs. Thus, B cell development in zebrafish does not go through a Rag^hi CD79⁺IgH-μ⁺ pre–B cell stage, different from mammals. After the generation of CD79:GFP⁺ B cells, decreased CD79 expression occurred upon differentiation to Ig secretion, as detected by alteration from membrane to secreted IgH-μ exon usage, similar to in mammals. This confirmed a conserved role for CD79 in B cell development and differentiation, without the requirement of a pre–B cell stage in zebrafish.

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Radioanatomic study of the skull base and septum in Asians: implications for using the nasoseptal flap for anterior skull-base reconstruction

Background

The objective of this work was to assess the feasibility of using the nasoseptal flap (NSF) for covering the anterior skull-base defect in Asians, and to compare the results in whites.

Methods

A retrospective radioanatomic analysis was conducted in 100 Korean adult patients. Septal and skull-base dimensions were measured and the feasibility of the NSF in reconstructing a full anterior skull-base defect was evaluated. Scans of 49 white patients were analyzed for a comparative study.

Results

Among various septal dimensions, the length of the septum was significantly different in Koreans when compared to whites. Skull-base dimensions such as anterior skull-base length and width at the level of the anterior ethmoidal artery were different between the 2 ethnic groups. Individual differences between the anterior width of the hypothetical NSF and the anterior margin of the skull-base defect (2.8 ± 3.1 vs 6.4 ± 4.8) and the difference between the hypothetical NSF length and the length of the flap needed for full coverage of the defect were significantly smaller in Korean patients (7.2 ± 3.8 vs 13.1 ± 5.6), leading to a statistically higher chance of flap insufficiency. The insufficiency was more often found in female patients.

Conclusion

The risk of NSF insufficiency for covering the anterior skull-base defect in Koreans is higher relative to whites, and is accentuated in female patients. Efforts to increase the size of the NSF as well as efforts to avoid intraoperative shrinkage of the NSF should be considered to compensate for the relatively small NSF in Asians.

http://ift.tt/2v7ZeWb

A Study of CDX-3379 and Cetuximab and in Patients With Advanced Head and Neck Squamous Cell Carcinoma

Condition:   Advanced Head and Neck Squamous Cell Carcinoma
Intervention:   Drug: CDX-3379 and cetuximab
Sponsor:   Celldex Therapeutics
Not yet recruiting - verified August 2017

http://ift.tt/2whgxaR

Voice Guard Processing Evaluation in a Cohort of Subjects Implanted With the Neuro Cochlear Implant System

Condition:   Cochlear Implantation
Interventions:   Device: XDP sound processing strategy;   Device: Voice Guard sound processing strategy;   Device: Voice Track
Sponsor:   Oticon Medical
Not yet recruiting - verified August 2017

http://ift.tt/2vXBDZk

Monocenter, Open Label Clinical Investigation on the Treatment of Radiation Induced Dermatitis With Xonrid®

Condition:   Radiodermatitis, Quality of Life
Intervention:   Device: Xonrid® gel
Sponsor:   Helsinn Healthcare SA
Recruiting - verified August 2017

http://ift.tt/2whmJjq

Cyclin D1 Based TPF Induction Chemotherapy for Oral Squamous Cell Carcinoma Patients at Clinical N2 Stage

Conditions:   Mouth Neoplasms;   Carcinoma, Squamous Cell
Interventions:   Drug: TPF group;   Procedure: surgery group;   Radiation: Post-operative radiotherapy
Sponsor:   Shanghai Jiao Tong University School of Medicine
Recruiting - verified November 2015

http://ift.tt/2x6gr3z

GDF15 Based TPF Induction Chemotherapy for OSCC Patients

Conditions:   Mouth Neoplasms;   Carcinoma, Squamous Cell
Interventions:   Drug: TPF induction chemotherapy;   Procedure: surgery group;   Radiation: Post-operative radiotherapy
Sponsor:   Shanghai Jiao Tong University School of Medicine
Recruiting - verified November 2015

http://ift.tt/2vSSbn1

ADAR1 splicing mutation leading to dyschromatosis hereditaria in a Caucasian patient

Abstract

Dyschromatosis symmetrica hereditaria (DSH, OMIM 127400) is a rare autosomal dominant disorder characterized by hypo-and hyperpigmented macules on the dorsal aspects of hands and feet and freckle-like macules on the face(1). Histologically, there is an increase in epidermal melanin pigment in the hyperpigmented area and with normally structured melanosomes, together with an absence of melanin pigment in hypopigmented macules. The disease is known to be caused by mutations in the adenosine deaminase, RNA-specific (ADAR) gene (Miyamura et al., 2003).

This article is protected by copyright. All rights reserved.

http://ift.tt/2wgGZSa

Lipopolysaccharide suppresses IgE-mast cell mediated reactions

Abstract

Background

Clinical and experimental analyses have identified a central role for IgE/FcεRI/mast cells in promoting IgE-mediated anaphylaxis. Recent data from human studies suggest that bacterial infections can alter susceptibility to anaphylaxis.

Objective

We examined the effect of LPS exposure on the induction of IgE-mast cell-(MC) mediated reactions in mice.

Methods

C57BL/6 WT, TLR-4^-/- and IL10^-/- mice were exposed to LPS and serum cytokines (TNF and IL-10) were measured. Mice were subsequently treated with anti-IgE and the symptoms of passive IgE-mediated anaphylaxis, MC activation, Ca²⁺-mobilization and expression of FcεRI on peritoneal MCs were quantitated.

Results

We show that LPS exposure of C57BL/6 WT mice constrains IgE-MC mediated reactions. LPS-induced suppression of IgE-MC mediated responses was TLR-4-dependent and associated with increased systemic IL-10 levels, decreased surface expression of FcεRI on MCs and loss of sensitivity to IgE activation. Notably, LPS-induced desensitization of MCs was short-term with MC sensitivity to IgE reconstituted within 48 hours which was associated with recapitulation of FcεRI expression on the MCs. Mechanistic analyses revealed a requirement for IL-10 in LPS-mediated decrease in MC FcεRI surface expression.

Conclusions & Clinical Relevance

Collectively, these studies suggest that LPS-induced IL-10 promotes the down regulation of MC surface FcεRI expression and leads to desensitization of mice to IgE-mediated reactions. These studies indicate that targeting of the LPS-TLR-4-IL-10-pathway maybe used as a therapeutic approach to prevent adverse IgE-mediated reactions.

This article is protected by copyright. All rights reserved.

http://ift.tt/2xl6O09

Arterial thoracic outlet syndrome secondary to hypertrophy of the anterior scalene muscle

Abstract

Thoracic outlet syndrome (TOS) was first introduced in literature by Peet et al. in 1956. Since then is has been studied extensively and subcategorized into at least four closely related syndrome. Neurogenic TOS due to the compression of brachial plexus, arterial TOS in cases of compression of the subclavian artery, venous TOS in cases of compression of the subclavian vein, and non-specific type of TOS. Neurogenic TOS is by far the most common consisting of 95% of the cases, followed by venous and lastly arterial. Arterial TOS comprises ~1% of all TOS cases, they are caused largely by presence of cervical rib and/or anomalies of first rib. Here we describe arterial TOS caused by hypertrophy of the anterior scalene muscle in a 65-year-old male. Patient underwent successful open surgical repair with Dacron interposition graft. Postoperative course was unremarkable. Patient was discharged home on POD 2.

http://ift.tt/2wwQTie

Does omphalocele major undergo spontaneous closure?

Abstract

The early surgical management of omphalocele major in Africa predisposes neonates to surgical complications which are often worsened by the presence of associated anomalies. Conservative management using available escharotics results in early skin cover by secondary wound healing. This delays the need for fascial closure and avoids neonatal surgical risks thus improving survival. We present a case of omphalocele major that underwent spontaneous closure during conservative management with honey dressing without surgical intervention.

http://ift.tt/2wx6vlJ

Aggressive angiomyxoma of the perineum: a rare presentation in a male with 4 years follow up

Abstract

Angiomyxoma are rare myxoid cells tumours that occur predominantly in women in the fourth decade. They are classified as the less aggressive superficial and the deeper aggressive variety commonly called aggressive angimyxomas. We report a rare perineal aggressive angiomyxoma in a 79-year-old male presenting with a painless perineo-scrotal mass. Radiological investigations confirmed a lobulated well-defined mass separate from the testicles and histology following wide local excision confirmed aggressive angiomyxoma. He remains recurrence free at 4 years of surveillance which is the among longest reported follow-up for perineal angiomyxoma.

http://ift.tt/2wx6uOH

Septic abortion presenting as a right lower trapezius abscess secondary to Bacteroides fragilis bacteraemia

A 43-year-old Japanese woman was evaluated in the outpatient department for right shoulder pain and fever, which began 5 days earlier. MRI of the right shoulder revealed a high-intensity area deep in the right trapezius muscle. Aspiration revealed purulent fluid, and Gram staining of the fluid showed Gram-negative bacilli. The patient was also found to be profoundly anaemic and to have a positive urine pregnancy test. On admission, we initiated intravenous ampicillin–sulbactam and aztreonam. She underwent dilatation and curettage for septic abortion and surgical drainage of the right shoulder abscess. Bacteroides fragilis was isolated from the blood, uterine aspiration and abscess samples. On hospital day 4, a whole-body CT scan revealed no other abscesses, and ampicillin–sulbactam was continued for 28 days. The patient was discharged on hospital day 29. Gram staining is an important tool for evaluating infectious aetiologies.

http://ift.tt/2vicbMk

Herpes simplex transmission to chest and face through autoinoculation in an infant

A 4-month-old female infant presented with a vesicular lesion on her left hand present since 1 day. A few days prior to presentation, she had a similar lesion on the lower lip. Two days after presentation, she returned with new lesions on her thorax and upper eyelid. PCR of the vesicle was positive for herpes simplex virus type 1. The transmission to her chest and face probably resulted from autoinoculation, caused by rubbing of the hand on other parts of the body. Transmission of herpes simplex through skin-to-skin contact is a common route of infection in people engaging in contact sports. Antiviral therapy was started because of the extensiveness and expansion of lesions and risk of developing herpetic keratitis. The patient completely recovered. This case shows that in an otherwise healthy infant, multiple herpetic skin lesions were not due to disseminated infection, but through autoinoculation.

http://ift.tt/2uYFmZu

Novel use of rituximab in macrophage activation syndrome secondary to systemic lupus erythematosus

Macrophage activation syndrome (MAS) is a rare disease characterised by aberrant immune hyperactivation of T lymphocytes and macrophages driven by cytokine dysfunction. The HLH-2004 protocol is commonly used for the treatment of MAS, but significant toxicities are associated. We describe a case of MAS secondary to systemic lupus erythematosus in a young female that responded well to rituximab in lieu of etoposide. She continues to be in remission 1 year following the completion of rituximab infusion and is maintained on hydroxychloroquine. This case highlights the need for further research on the use of rituximab and other available biologics in the setting of MAS in order to help guide further alternative treatment decisions.

http://ift.tt/2vhtMEg

Parosteal lipoma mimicking a breast tumor

Description

Parosteal lipoma is a rare benign tumour that is composed mainly of mature adipose tissue, and is contiguous to the periosteum of the underlying bone.1 Most parosteal lipomas are asymptomatic, but some may present motor and/or sensory deficits.2

A woman was seen in our office complaining a left breast tumour. The woman first noticed the tumour several years ago and underwent breast cancer screening annually but was never required for further evaluation. The tumour was slowly growing, and was associated with pain when lying in a prone position. On physical examination, a soft tumour measuring 9 cm could be felt in the lower-inner quadrant of the left breast, and was firmly fixed to the chest wall. Mammogram showed a well-circumscribed, smooth, lipomatous mass containing a coral-like calcification (figure 1). Breast ultrasonogram showed a large lipomatous nodule near the caudal end of the...

http://ift.tt/2vhGra9

Ponticulus posticus of atlas vertebrae: an incidental finding in Malaysian orthodontic patients

Description

Ponticulus posticus is a normal anatomical variant of atlas vertebrae (C1) and resides in the posterior arch of atlas in relation to vertebral artery. It is an incidental finding visualised from lateral cephalograms taken for routine orthodontic treatment purpose. Ponticulus posticus in Latin means 'little posterior bridge'. Other synonyms for ponticulus are arcuate foramen, kimerle anomaly, retroarticular foramen and retocondylar foramen.1 An overall incidence of ponticulus posticus has been reported to be 16.7%. Literature reveals a higher incidence in females compared with males and this anomaly was age independent.2

This additional bone formation is formed by the calcification of posterior-atlanto occipital membrane. Radiographically, three variations are seen in this normal variant according to Miki et al: a complete form, partial form and calcified form of ponticulus posticus.1 The complete form is where the bony ring is fully formed, thus, resembling a foramen....

http://ift.tt/2vh9nz5

Near-toe amputation from prolonged compression stocking use

Description

A 73-year-old man was referred to the acute medical team by his general practitioner with a suspected diabetic footinfection. He had a background of type 2 diabetes mellitus, chronic venous insufficiency and ulcers, peripheral vascular disease and deep venous thromboses (DVT).

The patient revealed that he had not removed his compression stockings for 4 months. He had chronic venous changes bilaterally, a swollen, erythematous right leg and foul-smelling discharge from his right foot with a deep wound at the base of his fourth toe due to compression by the distal edge of the stocking, with partial amputation of this digit (figure 1).

Figure 1

Photograph of patient's right foot showing near amputation of fourth toe.

X-ray of his foot (figure 2) showed bone destruction of the right fourth toe in keeping with osteomyelitis. Venous Doppler scans showed acute and chronic...

http://ift.tt/2uYaKHL

Ectopic cerebellar tissue in the occipital bone: a case report

Ectopic cerebellar tissue located distantly from the normal cerebellum is very rare, and its pathophysiology remains to be elucidated.

http://ift.tt/2vRNqdb

Klippel–Trenaunay–Weber syndrome with atypical presentation of hypersplenism and nephrotic syndrome: a case report

Klippel–Trenaunay–Weber syndrome is a rare syndrome; unfortunately, very few studies of the connection between hypersplenism, nephrotic syndrome, and Klippel–Trenaunay–Weber syndrome have been published.

http://ift.tt/2x5yarT

A Rare Case of Cavitary Lesion of the Lung Caused by Mycoplasma pneumoniae in an Immunocompetent Patient

Mycoplasma pneumoniae is an atypical bacterium that most commonly causes upper respiratory tract infections, but it can also cause pneumonia, referred to as "walking pneumonia." Although cavitary lesions are present in a wide variety of infectious and noninfectious processes, those attributable to M. pneumoniae are extremely uncommon; thus, to date, epidemiological studies are lacking. Here, we present a rare case of a 20-year-old male, referred to us from a psychiatric facility for evaluation of a cough, who was found to have a cavitary lesion in the right upper lobe. An extensive workup for cavitary lesion was negative, but his mycoplasma IgM level was high. A computed tomography (CT) of the chest confirmed the presence of a cavitary lesion. After treatment with levofloxacin antibiotics, a follow-up CT showed complete resolution of the lesion. Our case is a rare presentation of mycoplasma pneumonia as a cavitary lesion in a patient without any known risk factors predisposing to mycoplasma infection. Early recognition and treatment with an appropriate antibiotic may lead to complete resolution of the cavitary lesion.

http://ift.tt/2fYoGL2

Percutaneous management of complex acquired aortic coarctation in an adult with tetralogy of Fallot and pulmonary atresia

Michael D Seckeler, Emily Lawson, Brent J Barber, Scott E Klewer

Annals of Pediatric Cardiology 2017 10(3):295-297

We present the case of a female adult with complex cyanotic congenital heart disease who had long-standing thoracic aortic obstruction due to scarring from earlier surgical procedures. She was symptomatic but felt to be too high risk for surgical intervention. With careful planning, she was able to undergo successful stenting of her aorta with subsequent clinical improvement. This case highlights some of the complexities of caring for adults with congenital heart disease and the importance of a thorough understanding of their anatomy and physiology and prior interventions before undertaking interventions.

http://ift.tt/2wh8VW6

Change of guard: Introducing the new editor of the Annals of Pediatric Cardiology, Dr. KS Iyer

Raman Krishna Kumar

Annals of Pediatric Cardiology 2017 10(3):223-223



http://ift.tt/2wgNoNb

Quantification of ventricular unloading by 3D echocardiography in single ventricle of left ventricular morphology following superior cavo-pulmonary anastomosis and Fontan completion – a feasibility study

Deepa Sasikumar, Bijulal Sasidharan, Baiju S Dharan, Arun Gopalakrishnan, Kavasseri M Krishnamoorthy, Sivasubramanian Sivasankaran

Annals of Pediatric Cardiology 2017 10(3):224-229

Background: Three-dimensional echocardiography. (3DE) is comparable to cardiac magnetic resonance imaging for estimating ventricular volume in congenital heart diseases. However, there are limited data on estimation of ventricular volumes by 3DE in univentricular heart and change in ventricular volumes after surgical creation of cavopulmonary connection. We sought to quantify the unloading of the single ventricle of left ventricular. (LV) morphology by 3DE after superior cavopulmonary anastomosis. (SCPA) or Fontan operation over a period of 3 months and thereby derive a preliminary 3DE data set on this patient subset. Patients and Methods: Eighteen patients with functional single ventricle of LV morphology, who underwent SCPA or completion of Fontan circulation, were included in the study. Volume of the ventricle was estimated by 3DE before surgery and after surgery. (in the early postoperative phase and 3 months after surgery), and indexed end-diastolic volume. (EDV), end.systolic volume. (ESV), and ejection fraction. (EF) were derived. Results: Twelve patients underwent SCPA and six patients underwent staged completion of Fontan circulation. Before surgery, EDV was similar in both groups. There was a significant fall in EDV immediately after SCPA (from 48.3 ± 14.9 ml/m2 to 39.5 ± 12.3 ml/m2). However, EDV increased at 3 months' follow-up to 41.3 ± 10.5 ml/m2. There was no significant fall in EDV immediately after Fontan operation (47.2 ± 10.1 ml/m2−46.6 ± 14.2 ml/m2), but EDV continued to fall at 3 months of follow-up (44.7 ± 10. ml/m2). There was no significant change in ESV in either group, but EF fell significantly after SCPA. Conclusions: We provide preliminary information on 3DE volume data of single ventricle of LV morphology and the pattern of unloading after SCPA and Fontan operation. Immediate significant volume unloading occurred after SCPA which tended to catch-up after 3 months, whereas continued fall in ventricular volume with time was noted after Fontan.

http://ift.tt/2vWX7FX

Hypoplastic left heart syndrome with coronary-cameral fistulas: Echocardiographic demonstration of coronary artery steal and successful interventional treatment

Arshid Mir, Mary Niu, Merick Yamada, Ed Overholt

Annals of Pediatric Cardiology 2017 10(3):306-309

We report a case of a patient with hypoplastic left heart syndrome with significant coronary-cameral fistulas and exertional symptoms from coronary steal. Symptoms resolved following successful coil occlusion of his left ventricle.

http://ift.tt/2wgIRu3

Speckle tracking evaluation of right ventricular functions in children with sickle cell disease

Osama Abd Rab Elrasol Tolba, Mohamed Ramadan El-Shanshory, Mohamed Abd Elaziz El-Gamasy, Walid Ahmed El-Shehaby

Annals of Pediatric Cardiology 2017 10(3):230-233

Background: Cardiac dysfunction is a risk factor for death in patients with sickle cell disease (SCD). Aim of the Work: Aim of the work is to evaluate the right ventricular systolic and diastolic functions by tissue Doppler and speckling tracking imaging in children with SCD. Subjects and Methods: Thirty children with SCD and thirty controls were subjected to clinical, laboratory evaluations, and echocardiographic study using GE Vivid 7 (GE Medical System, Horten, Norway with a 3.5-MHz multifrequency transducer) including; Two-dimensional and tissue Doppler echocardiographic study (lateral tricuspid valve annulus peak E' velocity, lateral tricuspid valve annulus peak A' velocity, E'/A' ratio, isovolumetric relaxation time, lateral tricuspid valve annulus S' and septal S' waves and peak longitudinal systolic strain [PLSS] and time to PLSS) were done in six right ventricular segments. Results: There was a significant decrease in right ventricular systolic and diastolic function in patients group when compared to controls. Conclusions: Children with SCD have impaired right ventricular systolic and diastolic functions when compared to healthy children with early evaluation of the systolic dysfunction by speckle tracking imaging technique.

http://ift.tt/2whc5sK

Flecainide toxicity in a preterm neonate with permanent junctional reciprocating tachycardia

Balaganesh Karmegaraj, Danish Menon, Mukund A Prabhu, Balu Vaidyanathan

Annals of Pediatric Cardiology 2017 10(3):288-292

We report a case of flecainide toxicity in a premature neonate with permanent junctional reciprocating tachycardia which was managed successfully by reversal of the sodium blockade with intravenous sodium bicarbonate and supportive care. This report highlights the importance of strict supervision and monitoring while administering antiarrhythmic drugs in neonates and prompt institution of appropriate remedial action for treatment when toxicity is suspected.

http://ift.tt/2wgIT59

Intraocular pressure in children after congenital heart surgery: A single-center study

Sunali Goyal, Paul H Phillips, Lamonda A Corder, Michael J Robertson, Xiomara Garcia, Michael L Schmitz, Punkaj Gupta

Annals of Pediatric Cardiology 2017 10(3):234-239

Background: The impact of varied cardiac physiologies on intraocular pressure (IOP) among children undergoing heart operations is unknown. Aim: The aim of this study was to determine the IOP among children with varying cardiovascular physiologies and varying hemodynamics after their heart operation. Setting and Design: This was a prospective, observational study. Materials and Methods: Patients ≤18 years undergoing congenital heart surgery were included in this study. IOP measurement was performed by Icare® tonometer between 3 and 14 days after heart operation. Statistical Analysis: Summary statistics were estimated for all demographic, anthropometric, and clinical data. Results: A total of 116 eyes from 58 children were included. The mean and standard deviation age was 28.4 (45.8) months. Single-ventricle anatomy was present in 26 patients (45%). Despite similar heart rate and blood pressure, the mean IOP among the patients with single-ventricle anatomy was significantly elevated as compared to patients with two-ventricle anatomy (18 mm Hg vs. 12 mm Hg, P < 0.001). There was no difference in IOP measurements based on the complexity of operation performed. We noted that patients undergoing surgical palliation with central shunt (21 mm Hg), Fontan operation (19 mm Hg), bidirectional Glenn operation (19 mm Hg), Norwood operation (19 mm Hg), or definitive repairs such as tetralogy of Fallot repair (17 mm Hg), and atrioventricular canal repair (19 mm Hg) were associated with the highest IOPs in the study cohort. Conclusions: This study demonstrates that IOPs vary with varying cardiovascular physiology after pediatric cardiac surgery.

http://ift.tt/2vWnyvn

Anomalous origin of the left brachiocephalic artery in the right aortic arch: Is there a method to the madness?

Mani Ram Krishna, Ganesh Kumar Gnanappa, Rachel Fitzpatrick, Julian Ayer, David Winlaw

Annals of Pediatric Cardiology 2017 10(3):301-303

The anomalous origin of the left brachiocephalic artery in a right sided aortic arch is a rare vascular ring which might lead to esophageal compression. The exact embryological origin of this anomaly is still widely debated. We present an infant who presented with esophageal compression symptoms and review the various hypotheses about the embryological origin of this anomaly.

http://ift.tt/2whc3B8

Initial experience with the 3.3 Fr Mongoose® pigtail catheter for aortic angiography during patent ductus arteriosus closure in small patients

Zachary Hena, Nicole J Sutton, Gregory J Gates, Benjamin H Taragin, Robert H Pass

Annals of Pediatric Cardiology 2017 10(3):240-244

Background: Smaller femoral arterial sheaths may be associated with fewer vascular complications. The 3.3 Fr Mongoose® Pediavascular pigtail catheter is a catheter that allows higher flow rates, potentially resulting in improved angiographic quality. We reviewed our experience with this small catheter during patent ductus arteriosus (PDA) closure. Materials and Methods: Review of patients ≤20 kg in whom the Mongoose® catheter was used during PDA closure from 12/13 to 4/15. Angiographic efficacy and procedural details were compared to ten 4 Fr catheter cases. Comparisons were performed using Mann–Whitney U-test; P < 0.05 was statistically significant. Results: Twelve (9 female) patients were catheterized with a 3.3 Fr Mongoose®. Median weight 10.5 kg (range 6.4–18.2), height 81 cm (range 37–111), and body surface area (BSA) 0.47 m2 (range 0.33–0.75) were similar to ten patients (3 females) in the 4 Fr control group (P = NS); median weight 9.9 kg (range 6–16.8), height 80 cm (range 64–102), and BSA 0.46 m2 (range 0.31–0.74). Angiographic quality was subjectively adequate with both with no difference in the median pixel density between the two techniques (3.3 Fr: 76.7 [range 33.5–90] and 4 Fr: [70; 38–102]; P = NS). Contrast used was similar between the groups (3.3 Fr: median 4.2 ml/kg and 4 Fr: 4.9 ml/kg; P = NS). Median radiation dose was similar in the two groups (3.3 Fr: 28.1 mGy [range 17.2–38] and 4 Fr: 38 mGy [range 20.4–58.5]; P = NS). All ducts were closed at latest follow-up ( P = NS). No complications were encountered. Conclusions: The 3.3 Fr Mongoose® allowed similar angiography to the 4 Fr pigtail catheter, allowing safe and effective transcatheter PDA closure in small children.

http://ift.tt/2wgL3Sn