Head and Neck Medicine by Alexandros G.Sfakianakis: 03/14/18

Τετάρτη 14 Μαρτίου 2018

Percutaneous Dilatational Tracheostomy Using Tube Exchanger

We describe a modified technique for percutaneous dilatational tracheostomy using a 15F tube exchanger or Eschmann catheter. A retrospective review of 1180 procedures using this modified technique demonstrated it to be effective with a failure rate of only 0.25% (3 patients). Moreover, it provides an additional safeguard with the ability to rapidly reintroduce the endotracheal tube into the trachea guided by the exchange catheter in the event of accidental extubation during the procedure. This technique needs no additional special devices or equipment (eg, a bronchoscope). However, a prospective study is needed to better define its complication rate. Accepted for publication January 22, 2018. Funding: None. The authors declare no conflicts of interest. Reprints will not be available from the authors. Address correspondence to Ohad Ronen, MD, Department of Otolaryngology, Head and Neck Surgery, Galilee Medical Center, POB 21, Nahariya 2210001, Israel. Address e-mail to ohadr@gmc.gov.il. © 2018 International Anesthesia Research Society

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Perioperative Cardiac Arrest: Focus on Local Anesthetic Systemic Toxicity (LAST) Erratum

No abstract available

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Burnout in American Anesthetists, Comparison With a French Cohort

No abstract available

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Intrathecal Drug Delivery Systems for Refractory Pancreatic Cancer Pain: Observational Follow-Up Study Over an 11-Year Period in a Comprehensive Cancer Center

BACKGROUND: Pancreatic cancer is the fourth leading cause of cancer-related death in Europe and the United States. Studies have demonstrated that patients with pancreatic cancer have a high prevalence of pain, with rates varying from 47% to 82%. Analgesia using intrathecal drug delivery systems (IDDS) has been poorly studied specifically in this population. METHODS: The IDDS for pancreatic cancer pain was a follow-up observational study designed to evaluate 11-year results of IDDS for refractory pancreatic cancer pain at the Institut de Cancérologie de L'Ouest, Paul Papin in France. Patients were followed from March 2006 to April 2017. Patients were selected for IDDS based on multidisciplinary meeting discussion. All IDDS-treated patients were prescribed a combined intrathecal analgesics regimen through a catheter placed according to painful metameric level. Postimplant assessment of pain was determined using a numerical rating scale (NRS). Patients were followed via day-hospital visits and telephone calls at least monthly until death. Pain scores were compared using the Wilcoxon signed rank test. Overall survival (OS) was estimated using the Kaplan–Meier method and compared between groups by log rank tests. RESULTS: Ninety-three patients received IDDS, and total therapy duration accounts for 10,300 IDDS days. Implanted patients suffered from severe pain before implantation (median presurgical NRS, 8 [interquartile range, 7–9]) despite a median 360 mg (260–600) oral morphine equivalent daily dose. Median OS in the whole cohort after intrathecal treatment start was 82 days (95% confidence interval, 59–95). Median OS after surgery for implantable pump was 91 days (83–111) and for external pump 27 days (20–49; P

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In Response

No abstract available

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Anesthesia for Percutaneous Pulmonary Valve Implantation: A Case Series

BACKGROUND: Twenty percent of patients born with congenital heart disease present with right ventricular outflow tract abnormalities. These patients require multiple surgical procedures in their lifetime. Transcatheter pulmonary valve replacement (TPVR) has become a viable alternative to conventional pulmonary valve and right ventricular outflow tract surgery in pediatric and adult populations. In this retrospective review, we analyze the perioperative management of adult patients who underwent TPVR in our center. METHODS: The study consisted of a chart review of patients who underwent TPVR at Toronto General Hospital between 2006 and 2015. Information about preoperative assessment, intraoperative anesthetic management, and intra- and postprocedural complications was collected. Two types of percutaneous valves have been used for a conduit or valve size between 16 and 28 mm. These procedures are done via the femoral, jugular, or subclavian vein under general anesthesia. RESULTS: Seventy-nine adults (17–68 years of age) who underwent elective TPVR procedures were included. General anesthesia was used in all cases. Defibrillation was necessary in 1 case, and bradycardia was spontaneously resolved in another 1. Eighty-five percent were successfully extubated at the end of the procedure. Five patients required intraoperative inotropic support. Three patients presented self-resolved hemoptysis. Mechanical ventilation for >24 hours was necessary in 3 cases, 2 of which also required concomitant inotropic support. Four failed deployments and 1 case of persistent conduit stenosis were reported. Three patients required reintubation. All patients were discharged home. CONCLUSIONS: Patients undergoing TPVR represent a complex and heterogeneous population. General anesthesia with endotracheal intubation is preferred. Setup for urgent lung isolation and cardiac defibrillation should be considered. Postoperative monitoring and intensive care setting are required. Anesthesiologists with cardiac anesthesia training are probably better suited to manage these patients. Accepted for publication January 22, 2018. Funding: None. The authors declare no conflicts of interest. Reprints will not be available from the authors. Address correspondence to Massimiliano Meineri, MD, Department of Anesthesia and Pain Management, Toronto General Hospital, 200 Elizabeth St, EN3-400, Toronto, ON M5G 2C4, Canada. Address e-mail to massimiliano.meineri@uhn.ca. © 2018 International Anesthesia Research Society

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Protective Effect of Punica granatum Extract in Head and Neck Cancer Patients Undergoing Radiotherapy

Abstract

In India, head and neck cancers account for 30–40% cancers of all sites. Due to lack of screening program, wide variation in the availability of infrastructures and expertise, patients present at an advanced stage. The main stay of management of the head and neck tumours is surgery and chemoradiation. Radiation dermatitis and mucositis is one of the most common side effect encountered during the radiotherapy. Aim of our study was to study protective role of pomegranate extract on radiation induced dermatitis and mucositis in head and neck cancer patients. It was a prospective, clinical, double blind, case control study. 60 patients (30 active and controls) undergoing radiotherapy for head and neck cancer were studied for 12 months. Patients in study group were given whole fruit pomegranate extract. Each capsule contained 300 mg of whole fruit extract, each capsule contains 40% polyphenols and 27% punicalagin. Each patient were given 2 capsules every day for a period of 6–7 weeks. The skin and mucosal changes was graded according to the acute radiation morbidity scoring criteria (RTOG) for skin and mucous membrane. The results were statistically significant. Pomegranate extract proved to be radioprotective. Our study is one of the first study in humans to demonstrate the effectiveness of pomegranate extract in preventing radiation dermatitis and mucositis.

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ILC2 frequency and activity are inhibited by glucocorticoid treatment via STAT pathway in patients with asthma

Abstract

Background

Group 2 innate lymphoid cells (ILC2s) were closely associated with asthma. However, there were no perspective studies about the effects of glucocorticoid on ILC2s in asthma patients. Our objective was to perform a perspective study and evaluate the ILC2 activity after glucocorticoid therapy in asthma patients.

Methods

The asthma and asthma with allergic rhinitis patients were treated with glucocorticoid for 3 months. The circulating ILC2 levels were evaluated. The effects of glucocorticoid on ILC2s and possible signaling pathways were investigated in vitro.

Results

The patients were well-controlled and the high ILC2 levels were significantly decreased at 1 and 3 months after treatment. Peripheral blood monocytes from allergic patients produced dramatic IL-5, IL-13 and IL-9 in response to IL-25, IL-33 plus IL-2, and glucocorticoid significantly decreased their levels. Moreover, ILC2s were identified to be the predominant source of IL-5, IL-13 and IL-9, and glucocorticoid treatment was able to reverse their high levels. STAT3, STAT5, STAT6, JAK3 and MEK signaling pathways were proved to be involved in regulating ILC2 activity under the glucocorticoid treatment.

Conclusions

The data suggested that glucocorticoid administration could be effective in treating asthma by regulating ILC2s via MEK/JAK-STAT signaling pathways. This provides a new understanding of glucocorticoid application in regards to allergic diseases.

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Electroretinogram evaluation for the treatment of proliferative diabetic retinopathy by short-pulse pattern scanning laser panretinal photocoagulation

Abstract

Panretinal photocoagulation (PRP) is a standard method for proliferative diabetic retinopathy (PDR) treatment. However, conventional PRP usually significantly damages the retinal structure and vision. Retinal pattern scanning laser (PASCAL) photocoagulation has emerged as a new technique with fewer complications for the treatment of retinal disorders. This study compares the therapeutic effects of short-pulse PASCAL to conventional single-spot PRP for PDR. Fifty-two PDR patients (104 eyes) were randomly assigned into a short-pulse PASCAL-PRP treatment (SP) group and a conventional PRP treatment (TP) group. The best corrected visual acuity (BCVA) and full-field flash electroretinogram (ERG) data were evaluated before and after the two treatments. The BCVA data between before and after the PRP treatments did not show any significant difference. After the PRP treatment, the b-wave amplitude (b-A) in the dark-adapted 3.0 ERG (p = 0.0005) and the amplitude in the light-adapted 3.0 flicker ERG (p = 0.009) were significantly higher in the SP group compared with that of the TP group. In addition, after the PRP treatment, the a-wave implicit time (a-T) of light-adapted 3.0 ERG prolonged significantly in the TP group compared to the SP group. Compared with the parameters before the treatments, the a-A and b-A under dark-adapted 3.0 ERG and the b-A under the light-adapted 3.0 ERG in both TP and SP groups after the treatments decreased significantly (p < 0.05). Short-pulse PASCAL-PRP significantly attenuated partial vision damage compared to conventional PRP, although it still caused limited retinal injury and mild reduction in retinal function. These findings suggest that short-pulse PASCAL-PRP is a promising technique for PDR treatment.

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2S protein Ara h 7.0201 has unique epitopes compared to other Ara h 7 isoforms and is comparable to 2S proteins Ara h 2 and 6 in basophil degranulation capacity

Abstract

Background

Screening for specific IgE against 2S albumin proteins Ara h 2 and 6 has good positive predictive value in diagnosing peanut allergy. From the third 2S member Ara h 7, three isoforms have been identified. Their allergenicity has not been elucidated.

Objective

This study investigated the allergenicity of Ara h 7 isoforms compared to Ara h 2 and 6.

Methods

Sensitization of 15 DBPCFC confirmed peanut allergic patients to recombinant Ara h 2.0201, 6.01 and isoforms of recombinant Ara h 7 was determined by IgE immunoblotting strips. A basophil activation test (BAT) was performed in nine patients to determine IgE-crosslinking capacities of the allergens. Sensitivity to the allergens was tested in five patients that were sensitized to at least one Ara h 7 isoform, by a concentration range in the BAT. 3D-prediction models and sequence alignments were used to visualize differences between isoforms and to predict allergenic epitope regions.

Results

Sensitization to Ara h 7.0201 was most frequent (80%) and showed to be equally potent as Ara h 2.0201 and 6.01 in inducing basophil degranulation. Sensitization to Ara h 7.0201 together with Ara h 2.0201 and/or 6.01 was observed, indicating the presence of unique epitopes compared to the other two isoforms. Differences between the three Ara h 7 isoforms were observed in C-terminal cysteine residues, pepsin and trypsin cleavage sites and three single amino acid substitutions.

Conclusion & clinical relevance

The majority of peanut-allergic patients are sensitized to isoform Ara h 7.0201, which is functionally as active as Ara h 2.0201 and 6.01. Unique epitopes are most likely located in the C-terminus or an allergenic loop region which is a known allergenic epitope region for Ara h 2.0201 and 6.01. Due to its unique epitopes and allergenicity, it is an interesting candidate to improve the diagnostic accuracy for peanut allergy.

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A Single Radioactive Iodine Treatment Has a Deleterious Effect on Ovarian Reserve in Women with Thyroid Cancer: Results of a Prospective Pilot Study

Thyroid, Ahead of Print.

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Vitamin D Status and Cardiovascular Risk in Obesity: Effect of Physical Activity in Nonvitamin D Supplemented Adolescents

Metabolic Syndrome and Related Disorders, Ahead of Print.

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Untangling Waist Circumference and Hip Circumference from Body Mass Index with a Body Shape Index, Hip Index, and Anthropometric Risk Indicator

Metabolic Syndrome and Related Disorders, Ahead of Print.

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Sexual Coercion and Women's Education: A Pilot Study

Violence and Gender, Ahead of Print.

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Addressing Onset and Desistance of Bullying Behavior: Surveying Perpetrators

Violence and Gender, Ahead of Print.

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Anti-Podocalyxin Monoclonal Antibody 47-mG2a Detects Lung Cancers by Immunohistochemistry

Monoclonal Antibodies in Immunodiagnosis and Immunotherapy, Ahead of Print.

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Myeloid derived-suppressor cells: their role in cancer and obesity

Suzanne Ostrand-Rosenberg

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Repair of a perforated sinus membrane with an autogenous periosteal graft: a study in 24 patients

We describe a technique for repairing a perforation of the sinus membrane with a periosteal graft. Of 117 patients who had augmentation of the sinus floor, the sinus membrane perforated in 24, and these were repaired with autogenous periosteal grafts. Patients were followed up daily for the first 10days and monthly for the next six months, and clinical and radiographic variables were recorded. Patients had to be free of complications such as wound dehiscence, sinus infections, exposure of the graft, local inflammation, or pain.

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Mucoepidermoid carcinoma of the parotid gland: A National Cancer Database study

To describe the demographics, tumor characteristics, and prognostic features of mucoepidermoid carcinoma of the parotid gland.

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Are surgeons overdosing patients with lidocaine?

Local anesthetics have long been used since the 1850s following the first pure extraction of cocaine from coca leaves. Cocaine was a potent anesthetic, however, it led to deaths and addictions for health care members and patients alike [1]. Other local anesthetics such as tetracaine, tropocaine, lidocaine, bupivacaine and more recently, ropivacaine, were synthesized to minimize the cocaine toxicity. These newer anesthetic agents included both ester and amide preparationswith varying degrees of cardiovascular and neurotoxicity [1].

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Molecular alterations of newly formed mandibular bone caused by zoledronate

Bone quality is defined by structural and material characteristics. Most studies on the mandible have focused on the analysis of structural characteristics, with insufficient investigation of material characteristics. This study tested whether zoledronate affects the material characteristics of newly formed mandibular bone. Thirty-six female Wistar rats were assigned to three groups: sham-ovariectomized rats (SHAM, n=12), ovariectomized rats (OVX, n=12), and ovariectomized rats treated with zoledronate (ZOL, n=12).

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Mixed facial reanimation technique to treat paralysis in medium-term cases

Recent facial paralyses, in which fibrillations of the mimetic muscles are still detectable by electromyography (EMG), allow facial reanimation based on giving new neural stimuli to musculature. However, if more time has elapsed, mimetic muscles can undergo irreversible atrophy, and providing a new neural stimulus is simply not effective. In these cases function is provided by transferring free flaps into the face or transposing masticatory muscles to reinstitute major movements, such as eyelid closure and smiling.

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Double-layer closure techniques after bone surgery of medication-related osteonecrosis of the jaw – a single center cohort study

Mucosal wound closure plays a key role after surgery of manifested medication-related osteonecrosis of the jaw (MRONJ). Additional soft tissue layers promise better vascularization and mechanical stability. The objectives of this study were to examine success rates of double-layer closure techniques in MRONJ patients, namely the mylohyoideus muscle flap (MMF) for the lower jaw and the pedicled buccal fat flap (BFF) for the upper jaw.

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Management of duct obstruction in transplanted submandibular glands

Submandibular gland (SMG) transplantation is a successful treatment approach for patients with severe dry eye. However, duct obstruction can occur post-transplant.

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Development of a patient-specific temporomandibular joint prosthesis according to the Groningen principle through a cadaver test series

Patients suffering from osteoarthritis, ankylosis (e.g. post-trauma or tumour) in the temporomandibular joint (TMJ) can present with symptoms such as severely restricted mouth opening, pain or other dynamic restrictions of the mandible. To alleviate the symptoms, a total joint prosthesis can be indicated, such as the Groningen TMJ prosthesis. This was developed as a stock device with a lowered centre of rotation for improved translational and opening capacity. This study aimed to improve the design of the prosthesis, and produce a workflow for a customized Groningen TMJ prosthesis, in order to make it more accurate and predictable.

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Effect of interleukin-1β on ghrelin receptor in periodontal cells

Abstract

Objectives

Periodontopathogens induce immunoinflammatory responses characterized by the release of inflammatory mediators, e.g., interleukin (IL)-1β, IL-6, and IL-8. Ghrelin (GHRL) is an appetite hormone which mediates its effect via the functional receptor GHS-R1a. This study was to examine the effect of an inflammatory insult on GHS-R1a in human periodontal cells.

Materials and methods

Periodontal ligament (PDL) cells and gingival fibroblasts (HGFs) were exposed to IL-1β in the presence and absence of GHRL. Cells were also pre-incubated with specific inhibitors of NF-κB or MEK1/MEK2 signaling. Gene expression of GHS-R1a and proinflammatory mediators was assessed by real-time PCR, GHS-R1 protein level by immunocytochemistry, and NF-κB nuclear translocation by immunofluorescence.

Results

IL-1β increased significantly the GHS-R1a expression in both cell types in a dose-dependent manner. The stimulatory effect of IL-1β involved the NF-κB and MAPK pathways. Exposure of cells to IL-1β also resulted in an increased production of GHS-R1 protein in both cell types. Furthermore, GHRL counteracted significantly the stimulatory actions of IL-1β on IL-6 and IL-8 in PDL cells.

Conclusions

This study demonstrates for the first time that IL-1β upregulates the functional ghrelin receptor in periodontal fibroblastic cells. Moreover, these results further support the assumption that the GHRL/GHS-R system exerts anti-inflammatory effects. Therefore, the upregulation of ghrelin receptor in periodontal cells in response to an inflammatory stimulus may represent a negative feedback mechanism to attenuate the initial inflammatory process in periodontal diseases.

Clinical relevance

The anti-inflammatory GHRL/GHS-R system may serve as a promising target for the prevention and therapy of periodontal diseases.

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Effects of nasal septum perforation repair on nasal airflow: An analysis using computational fluid dynamics on preoperative and postoperative three-dimensional models

Publication date: Available online 13 March 2018
Source:Auris Nasus Larynx
Author(s): Tsutomu Nomura, Munetaka Ushio, Kenji Kondo, Shigeru Kikuchi
ObjectiveThe purpose of this research is to examine the changes in nasal airflow dynamics before and after the nasal perforation repair.MethodsThree dimensional (3D) models of the nasal cavity before and after septal perforation repair was reconstructed using preoperative and postoperative computed tomography (CT) images of a patient. The numerical simulation was carried out using ANSYS CFX V15.0. Pre- and post-operative models were compared by their velocity, pressure (P), pressure gradient (PG), wall shear (WS), shear strain rate (SSR) and turbulence kinetic energy (TKE) in three plains.ResultsIn the post-operative state, the cross flows disappeared. In preoperative state, there were areas showing high PG, WS, SSR at the posterior border of the perforation, which exactly correspond to the area showing erosive mucosa on endoscopic inspection of the patient. In postoperative state, such high PG, WS and SSR areas disappeared. High TKEs also disappeared after surgery.ConclusionThe effects of septal perforation repair on airflow dynamics were evaluated using computer fluid dynamics (CFD). High WS, PG and SSR observed at the edge of the septal perforation may be related to the clinical symptom such as nasal bleeding and pain. TKE was considered to cause nasal symptom.

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Clinical features of nasal and sinonasal inverted papilloma associated with malignancy

Publication date: Available online 13 March 2018
Source:Auris Nasus Larynx
Author(s): Takuya Miyazaki, Yasuharu Haku, Akira Yoshizawa, Ken Iwanaga, Takashi Fujiwara, Masanobu Mizuta, Atsuhiro Yoshida, Shinichi Satou, Hisanobu Tamaki
ObjectiveNasal and sinonasal inverted papilloma (IP) are rare benign tumors and have the potential to exhibit malignancy in approximately 10% of cases. This study aimed to analyze the clinical features of IP associated with malignancy. Furthermore, we reviewed our therapeutic strategy and the clinical course of malignant IP.MethodsOverall, 70 patients with IP at our institution were retrospectively analyzed from April 2006 to December 2015; of these, six (9%) had associated malignancy. Data was collected on sex, age, presenting symptoms (nasal bleeding, rhinorrhea, facial or cheek pain, and nasal obstruction), bone destruction, and extent of disease on CT and MRI. Categorical data of patients with and without malignancy were compared using the chi-square test. A p value of <0.05 was considered statistically significant. Our therapeutic strategy for IP with malignancy, particularly the surgical procedure, i.e., the external incision or the endoscopic nasal approach, varied based on when the carcinoma was detected. In addition, we considered postoperative radiation therapy depending on histological examination.ResultsNasal bleeding (p<0.001), pain (p=0.040), bone destruction (p<0.001), and extent of disease (p=0.026) on CT and MRI findings were significantly associated with malignancy. Carcinoma was diagnosed preoperatively in two (33%) and postoperatively in four patients (67%). We operated five patients (one case was not treated because of end-stage pancreatic cancer). Two patients underwent endoscopic sinus surgery (ESS) alone, two ESS plus Denker's method, and one ESS plus anterior craniotomy. Three patients underwent surgery only, and two patients received postoperative radiotherapy. The median follow-up period was 69.3 months. One patient died of the disease and the remaining patients are alive without recurrence.ConclusionFor IP patients exhibiting these clinical findings preoperatively, we should suspect complication with malignancy and plan a treatment. Even if postoperative histology does not confirm malignancy, we should ensure careful observation because of metachronous malignant transformation or the possibility to overlook small malignant lesions. Our result suggests that our strategy for malignant IP could be a reasonable option.

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Mucoepidermoid carcinoma of the parotid gland: A National Cancer Database study

Publication date: Available online 14 March 2018
Source:American Journal of Otolaryngology
Author(s): Karthik Rajasekaran, Vanessa Stubbs, Jinbo Chen, Pratyusha Yalamanchi, Steven Cannady, Jason Brant, Jason Newman
ObjectiveTo describe the demographics, tumor characteristics, and prognostic features of mucoepidermoid carcinoma of the parotid gland.Materials and methodsA retrospective study of the National Cancer Database was reviewed for all mucoepidermoid carcinomas of the parotid gland between 2004 and 2012). Patient demographics and tumor characteristics were abstracted and analyzed. Univariate and multivariate Cox multivariate regression models were used to identify predictors of survival.ResultsA total of 4431 patients met inclusion criteria. Average age at diagnosis was 57 years (median 62, SD 19), with no overall sex preference (52% female), and majority white (78%). The 1-year overall survival was 92.9% (95% CI [92.1–93.6]) and 5-year overall survival was 75.2% (95% CI [73.8–76.7%]). Median overall survival was not reached at 5 years. Factors associated with decreased survival were increasing age, comorbidities, high tumor grade, advanced pathologic group stage, and positive surgical margins. Female sex was the only factor associated with improved survival. Controlling for either histopathologic grade or pathologic stage to determine how patient demographics and tumor characteristics affected overall survival yielded similar results. Of note, intermediate grade tumors, although not independently associated with worse survival, when seen in conjunction with tumors ≥T2 and/or ≥N2, a negative impact on overall survival was seen.ConclusionAlthough mucoepidermoid carcinoma of the parotid gland is the most common parotid gland malignancy, it is still a rare tumor with a lack of large population-based studies. Advanced stage and high-grade tumors are significant predictors of decreased survival. Females have improved survival compared to males.

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Decidual granulomatous reaction in a placenta from a preeclamptic pregnancy: a case report and review of the literature

Abstract

We report a case of decidual perivascular non-necrotizing granulomas in a placenta from a pregnancy complicated by severe preeclampsia with no evidence of infection. The mother was a 20-year-old primigravida with severe preeclampsia diagnosed in the third trimester with subsequent delivery of a healthy baby boy at 37 weeks 5 days gestation. Pathologic examination of the placenta showed scattered non-necrotizing granulomas in decidua, often adjacent to remodeled decidual arteries without fibrinoid necrosis. These were well-formed, non-necrotizing granulomas with scant lymphoid cuffs. Polarization microscopy did not show foreign material. There were no histopathologic or clinical findings suggestive of maternal-fetal infection or systemic vasculitis at the time of delivery, and the mother had no other reported conditions associated with granulomatous inflammation. Our case demonstrates that granulomatous reaction may be seen in the placenta from a pregnancy complicated by severe preeclampsia, although work-up for infection may be indicated.

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Airway pathological heterogeneity in asthma: Visualization of disease microclusters using topological data analysis

Publication date: Available online 14 March 2018
Source:Journal of Allergy and Clinical Immunology
Author(s): Salman Siddiqui, Aarti Shikotra, Matthew Richardson, Emma Doran, David Choy, Alex Bell, Cary D. Austin, Jeffrey Eastham-Anderson, Beverley Hargadon, Joseph R. Arron, Andrew Wardlaw, Christopher E. Brightling, Liam G. Heaney, Peter Bradding
BackgroundAsthma is a complex chronic disease underpinned by pathological changes within the airway wall. How variations in structural airway pathology and cellular inflammation contribute to the expression and severity of asthma are poorly understood.ObjectivesTherefore we evaluated pathological heterogeneity using topological data analysis (TDA) with the aim of visualizing disease clusters and microclusters.MethodsA discovery population of 202 adult patients (142 asthmatic patients and 60 healthy subjects) and an external replication population (59 patients with severe asthma) were evaluated. Pathology and gene expression were examined in bronchial biopsy samples. TDA was applied by using pathological variables alone to create pathology-driven visual networks.ResultsIn the discovery cohort TDA identified 4 groups/networks with multiple microclusters/regions of interest that were masked by group-level statistics. Specifically, TDA group 1 consisted of a high proportion of healthy subjects, with a microcluster representing a topological continuum connecting healthy subjects to patients with mild-to-moderate asthma. Three additional TDA groups with moderate-to-severe asthma (Airway Smooth Muscle^High, Reticular Basement Membrane^High, and Remodeling^Low groups) were identified and contained numerous microclusters with varying pathological and clinical features. Mutually exclusive TH2 and TH17 tissue gene expression signatures were identified in all pathological groups. Discovery and external replication applied to the severe asthma subgroup identified only highly similar "pathological data shapes" through analyses of persistent homology.ConclusionsWe have identified and replicated novel pathological phenotypes of asthma using TDA. Our methodology is applicable to other complex chronic diseases.

Graphical abstract

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Repair of a perforated sinus membrane with an autogenous periosteal graft: a study in 24 patients

Publication date: Available online 14 March 2018
Source:British Journal of Oral and Maxillofacial Surgery
Author(s): H.A.A.B. de Oliveira, R.P.F. de Moraes, P.H.J.O. Limirio, P. Dechichi
We describe a technique for repairing a perforation of the sinus membrane with a periosteal graft. Of 117 patients who had augmentation of the sinus floor, the sinus membrane perforated in 24, and these were repaired with autogenous periosteal grafts. Patients were followed up daily for the first 10days and monthly for the next six months, and clinical and radiographic variables were recorded. Patients had to be free of complications such as wound dehiscence, sinus infections, exposure of the graft, local inflammation, or pain. The radiographs showed correct osseointegration of all implants. Periosteal grafts are an effective alternative for repair of a perforation of the sinus membrane.

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Double-layer closure techniques after bone surgery of medication-related osteonecrosis of the jaw – a single center cohort study

Publication date: Available online 14 March 2018
Source:Journal of Cranio-Maxillofacial Surgery
Author(s): Oliver Ristow, Thomas Rückschloß, Jens Bodem, Moritz Berger, Eva Bodem, Steffen Kargus, Michael Engel, Jürgen Hoffmann, Christian Freudlsperger
IntroductionMucosal wound closure plays a key role after surgery of manifested medication-related osteonecrosis of the jaw (MRONJ). Additional soft tissue layers promise better vascularization and mechanical stability. The objectives of this study were to examine success rates of double-layer closure techniques in MRONJ patients, namely the mylohyoideus muscle flap (MMF) for the lower jaw and the pedicled buccal fat flap (BFF) for the upper jaw.Materials and MethodsWe designed and implemented a restrospective cohort study and enrolled a sample of patients diagnosed with MRONJ that were treated between 2015 and 2017 with either the MMF or the BFF after removal of the necrotic bone areal. Success was assessed as the maintenance of full mucosal coverage without signs of residual infection at (T0) four weeks (T1), four months (T2), and eight months (T3) after operation. The occurrence of side effects was evaluated.ResultsA total of 87 (MMF n=57; BFF n=30) patients with 104 MRONJ (MMF 68=; BFF n=36) lesions were included. At the time of the last follow-up, 88.0% (44 of 50) of patients in the MMF group and 93.1% (27 of 29) of patients in the BFF group showed mucosal integrity. No serious side effects were reported. Overall treatment of earlier lesions (stage I and II) showed a better outcome than more severe necrosis (stage III).ConclusionDouble-layer closure techniques after surgery in MRONJ patients provide a mechanically stable, well-vascularized covering of the bone defect and should be considered as an option in the standard protocol for all degrees of severity of the disease.

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Disseminated Asymptomatic Papules Over the Body

A woman in her 30s had a 15-year history of generalized asymptomatic papules on her arms, trunk, legs, neck, and face; examination revealed skin-colored to red-brown papules distributed over her trunk, extremities, neck, forehead, and periocular regions. What is your diagnosis?

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HLA-B*1301 and Dapsone-Induced Cutaneous Adverse Drug Reactions

This systematic review and meta-analysis examines case-control studies to assess the association between the HLA-B*1301 genotype and cutaneous adverse reactions in Asian patients treated with dapsone.

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JAMA Dermatology—The Year in Review, 2017

JAMA Dermatology continues to enhance our digital presence, which serves to inform physicians and the public about advances in treatment of skin conditions. The journal content is available online ahead of print, and we connect with our readers via the electronic table of contents and through social media. Each weekly online issue of the journal offers an article free to be downloaded for 1 week; thus, the public has free access to selected articles. Our reach extended to 3.4 million people in 2017 with full-text downloads. Our online presence is international, with more than 100 000 users in Canada, India, the United Kingdom, and the United States.

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Spinal Dysraphism Presenting as a Translucent Papule in a Man

This case report describes a man with spinal dysraphism presenting as a translucent papule.

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Light Therapies for Acne

This Clinical Evidence Synopsis summarizes a Cochrane review that assessed effectiveness of different light therapies for acne.

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Sun Protection Use and Sunburn Among US Adults

This cross-sectional study using National Health Interview Survey data examined the prevalence of sun protection use and sunburn and the association between sunburn and demographic characteristics and health behaviors in the US population.

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JAMA Dermatology Peer Reviewers in 2017

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Updated Guidelines on Hirsutism in Premenopausal Women

Endocrine Society has released an updated guideline on hirsutism in premenopausal women, cosponsored by the Androgen Excess and PCOS Society and European Society of Endocrinology.
Medscape Medical News

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In reference to Is multidisciplinary team care for head and neck cancer worth it? and Does a multidisciplinary approach to voice and swallowing disorders improve therapy adherence and outcome?

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Monroe’s Mark

For most of human history, beauty marks have not always considered to be beautiful. In Ancient Rome, the standard of beauty was fair and spotless skin. In medieval Europe, pigmented lesions were one of several cutaneous signs associated with "evil" or demonic connection, the so-called Devil's mark. The attitude toward beauty marks improved in the 18th century, when moles became popular among the royal courts of Europe. Artificial beauty marks, known as mouches, were created from silk, velvet, or taffeta and were worn by both men and women. After a several-centuries–long period of quiescence, however, the beauty mark reemerged in the 1950s in association with the era's greatest sex symbol, Marilyn Monroe. She quickly became known for the off-center mole above her left upper lip, and with it she appealed to generations of women for many years to come.

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Potential COIs in Dermatology Clinical Practice Guidelines

This Viewpoint discusses the importance of achieving balance between the practical and the ideal in clinical practice guideline development.

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Generalized Lichen Nitidus Following Anti–PD-1 Antibody Treatment

This case report describes the occurrence of generalized lichen nitidus following anti–PD-1 antibody treatment.

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US Food and Drug Administration Approach for Safe Medical Devices

With the increased awareness of skin conditions and demand for aesthetic treatments requiring the expertise of dermatologists, there has been a growth in the associated medical device industry. Dermatology medical devices include point-of-care diagnostics, ablative technologies, skin imaging devices, dermal fillers, lasers, and wound dressings. Many new devices in dermatology offer practitioners and patients additional options for a variety of conditions including diabetic wound care, skin lesion screening, and alopecia treatment.

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Trends in Melanoma Incidence Among Non-Hispanic Whites

This analysis examines data from 2 major databases on melanoma incidence trends among the non-Hispanic white population in the United States by 10-year age groups.

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Comorbidities in Autoimmune Skin Diseases

Alvan Feinstein, both a clinician and an epidemiologist, introduced the concept of comorbidity as a peculiar and important feature of chronic diseases almost 50 years ago. This concept may still require a more precise definition and a deeper understanding, but there is no doubt that better knowledge about comorbidities will always be conducive to improvements in clinical care, epidemiology, and health services planning and financing. Also, as noted by Tinetti and Fried nearly 15 years ago, awareness of existing comorbidities of a given chronic disease will facilitate "The End of the Disease Era," as they titled their article, and ultimately bring about the essential paradigm shift in clinical medicine from the "disease-oriented" model to a more "integrated individually tailored model" in which clinical decision making can be "focused primarily on the priorities and preferences of individual patients,"^(p181) and health conditions are recognized as a complex interplay of genetic, environmental, psychological, social, and other factors.

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Evaluating Industry Payments Among Dermatology Clinical Practice Guideline Authors

To the Editor The article by Checketts et al regarding industry payments among dermatology clinical practice guideline (CPG) authors was accompanied by an editorial by Katz highlighting some of the problems with the study's methodology. We have significant additional concerns regarding its conclusions.

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Dermatologic Device Approval by the US Food and Drug Administration

This cross-sectional database study characterizes the postapproval changes to Class III dermatologic devices and evaluates inconsistencies in the use of the premarket approval pathway.

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Sun Safety

This Patient Page provides information on sun protection and safety.

http://ift.tt/2FJ5xEQ

Association Between Pemphigus and Neurologic Diseases

This population-based cross-sectional study estimates the association between pemphigus and 4 neurologic conditions using one of the largest cohorts of patients with pemphigus.

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Rituximab as Single Long-term Maintenance Therapy in Difficult-to-Treat Pemphigus

This case-series study of 11 patients with severe, difficult-to-treat pemphigus examines whether rituximab alone can be used long-term as maintenance therapy for prevention of relapse.

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Comorbidity Development in Children With Psoriasis

This cohort study examines the risk ocomorbidities in children with and without psoriasis, after accounting for obesity.

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Rapid Repigmentation of Vitiligo-Affected Skin After Tofacitinib Plus UV-B

This case report describes 2 patients who experienced rapid repigmentation of vitiligo-affected skin after tofacitinib plus low-dose, narrowband UV-B therapy.

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Skin Microbiome and Gene Mutations in Adult Atopic Dermatitis

This case-control study examines skin and nasal microbiome diversity and composition in patients with atopic dermatitis.

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Congenital Syphilis and The Inheritance by Edvard Munch

This Notable Note provides an example of how an artistic work may unexpectedly provide information about the history of a disease.

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Follicular and Epidermal Cell Suspension for Vitiligo Treatment

This randomized clinical trial compares the effects of combined epidermal cell suspension and follicular cell suspension with those of epidermal cell suspension alone in treatment of vitiligo.

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Sir James Paget—Contributions of a Surgeon and Pathologist

Sir James Paget is remembered as one of the greatest English surgeons and fathers of pathology. After passing the College of Surgeon's Examination in 1836, he struggled to find a job practicing medicine and spent 7 years doing various odd jobs for minimal compensation.

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Efficacy and Safety of Guselkumab for Palmoplantar Pustulosis

This randomized clinical trial evaluates the safety and efficacy of guselkumab compared with placebo for the treatment of palmoplantar pustulosis.

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March 2018 Issue Highlights

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Opioid Prescribing Patterns and Complications in the Dermatology Medicare Population

This cross-sectional study characterizes the current status and potential complications of opioid prescribing practices among dermatologists for Medicare beneficiaries.

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Curious case of a calcified food bolus

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Abstract

Authors present an 80-year-old male attending with obstructive food bolus. Lateral soft tissue neck x-ray demonstrated a suspected calcified foreign body at the level of the larynx. Subsequent senior radiological input reported the findings as incidental calcification of carotid arteries. ENT surgeons should demonstrate increased awareness for potentially calcified soft tissues on interpreting such x-rays.

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Cost-effectiveness analysis of salvage therapies in locoregional previously irradiated head and neck cancer

Abstract

Background

The purpose of this study was to present our evaluation of the cost-effectiveness of salvage therapies for patients with recurrent head and neck cancer.

Methods

A Markov model was developed with 5 salvage treatment strategies: (1) platinum-based chemotherapy alone; (2) chemotherapy plus cetuximab; (3) stereotactic body radiotherapy (SBRT) alone; (4) SBRT plus cetuximab; and (5) intensity-modulated radiotherapy (IMRT) plus chemotherapy. Clinical parameters were obtained from comprehensive literature review and 2016 Medicare reimbursement. Strategies were compared using the incremental cost-effectiveness ratio (ICER), with effectiveness in quality-adjusted life years (QALYs), and evaluated with a willingness-to-pay (WTP) threshold of $100 000 per QALY gained.

Results

In the base case analysis, no treatment strategy was cost-effective at a WTP threshold. The most cost-effective therapy was SBRT alone with $150 866 per QALY gained. If median survival of SBRT alone was ≥11 months, SBRT was considered to be cost-effective.

Conclusion

None of the treatment strategies were cost-effective. However, SBRT-based reirradiation has potential to be cost-effective.

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Comprehensive approach to functional palatomaxillary reconstruction using regional and free tissue transfer: Report of reconstructive and prosthodontic outcomes of 140 patients

Abstract

Background

Palatomaxillary defects were historically restored with a prosthetic obturator; however, advances in local and free tissue transfer has provided a viable alternative for appropriately selected patients with palatomaxillary defects.

Methods

A retrospective chart review of patients who underwent palatomaxillary reconstruction by the lead author between 1998 and 2016 was conducted. Patients who were restored with a palatal obturator were excluded.

Results

One hundred forty patients were reconstructed with a total of 159 local, regional, and free flaps with a 96.7% success rate. Seventy-four patients (52.8%) underwent prosthodontic rehabilitation, with 183 implants placed and an 86% success rate.

Conclusion

Palatomaxillary reconstruction applying a systematic approach, using a multitude of techniques, is a safe and effective way to restore patients without compromising the ability to maintain surveillance. Prosthodontic rehabilitation can be achieved in a high percentage of patients using dental implants, leading to optimal aesthetic and functional results.

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Nasopharyngeal biopsy in adults presenting with serous otitis media: Cross-sectional study

Abstract

Background

The purpose of this study was to investigate the association between isolated serous otitis media (SOM) and/or conductive hearing loss (CHL) and nasopharyngeal carcinoma (NPC) in a low-to-intermediate endemic area.

Methods

Medical records of all adult patients (≥17 years) with SOM/CHL who underwent endoscopic-guided nasopharyngeal biopsy to exclude NPC during a 10-year period were reviewed. Statistical analyses were conducted to identify significant predictors for NPC.

Results

A total of 195 patients were included (121/195; 62.1% men), among whom 169 (86.7%) presented with isolated SOM/CHL. Overall, 12 patients were diagnosed with NPC (12/195; 6.2%), however, only 1 patient (1/169; 0.6%) had isolated SOM/CHL. Coexisting clinical manifestations and suspicious nasopharyngeal findings on fiber-optic nasopharyngoscopy were found to be significant predictors for NPC on univariate and multivariate analyses (P < .05).

Conclusion

Patients with isolated SOM/CHL and without coexisting clinical manifestations or suspicious findings on nasopharyngoscopy may avoid a routine nasopharyngeal biopsy.

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Postoperative mechanical bowel obstruction after pharyngolaryngectomy for hypopharyngeal cancer: Retrospective analysis using a Japanese inpatient database

Abstract

Background

Data have been limited on donor-site mechanical bowel obstruction after pharyngolaryngectomy with free jejunum graft reconstruction.

Methods

Using a nationwide Japanese inpatient database, we extracted data on patients who underwent pharyngolaryngectomy for hypopharyngeal cancer between July 2007 and March 2014. A Cox proportional hazard model was used to determine the association between background characteristics and the occurrence of mechanical bowel obstruction.

Results

Among the 3320 eligible patients from 332 hospitals, 108 patients (3.3%) developed mechanical bowel obstruction after a median 88 (interquartile range 26-217) postoperative days. Multivariable Cox regression analysis revealed that older age (≥60 years old) was independently associated with an increased risk of mechanical bowel obstruction, whereas sex, body mass index [BMI], smoking status, comorbidity at admission, blood transfusion, history of surgery, and hospital type were not.

Conclusion

In pharyngolaryngectomy, careful attention should be paid to the risk of abdominal complications and, thus, to the graft choice, especially in elderly patients.

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Smoking, environmental tobacco smoke and occupational irritants increase the risk of chronic rhinitis

Allergic and non-allergic rhinitis cause a lot of symptoms in everyday life. To decrease the burden more information of the preventable risk factors is needed. We assessed prevalence and risk factors for chron...

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Oral Manifestation of Lymphomatoid Granulomatosis

Abstract

Lymphomatoid granulomatosis (LYG) is a rare B-cell lymphoproliferative disorder driven by Esptein–Barr virus (EBV) that most commonly affects the lungs, although extra pulmonary sites like the central nervous system, skin, liver and kidney can also be involved. It is microscopically characterized by an angiocentric and angiodestructive growth pattern, predominantly composed by small T-cells, although a smaller population of atypical large B-cells is considered the true neoplastic component. Oral cavity involvement of LYG has rarely been described and the diagnosis of this neoplasm is very difficult. The aim of this report is to present a rare case of LYG affecting an 86-year-old female patient that was diagnosed due to an extensive, ulcerated and painful oral lesion affecting the hard palate. Detailed microscopic evaluation together with a large immunohistochemical study were necessary to achieve the correct diagnosis of LYG.

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Low-Grade Malignant Fibrous Histiocytoma Originating From the Medial Rectus Muscle

Purpose: Fibrous histiocytomas (FHs) involving the orbit are uncommon. To our knowledge, here the authors report the first patient with an orbital low-grade malignant FH originating from the medial rectus muscle. Methods: A clinical report relating clinical features as well as imaging and histopathologic findings is presented. Results: A 26-year-old female presented with a left eye proptosis that had been present for 4 months. A small left exotropia was observed and ocular motility evaluation revealed a −3 adduction and −1 abduction of the left eye. B-mode ultrasonic scans demonstrated a 2.5 × 2.0 cm mass with medium internal echo and a clear boundary located in the nasal region of the left orbit. Magnetic resonance imaging (MRI) showed a 2.8 × 2.0 cm oval extraconal orbital mass, with isointensity on T1-weighted MRI and hyperintensity on T2-weighted MRI. An anterior orbitotomy was performed and the tumor was completely removed. The mass originated from the medial rectus muscle. Histopathologic evaluation confirmed a low-grade malignant FH. After surgery, the left exotropia was no longer present. Ocular motility revealed a −1 adduction and −1 abduction of the left eye. No recurrence was evident at 1 year after surgery. Conclusions: This rare patient demonstrates that FH may originate from the medial rectus muscle. With careful surgical dissection, a near normal function of the involved muscle can be restored. Address correspondence and reprint requests to Jianhua Yan, MD, PhD, Zhongshan Ophthalmic Center, Sun Yat-sen University, 54 Xianlie Nan Road, Guangzhou 510060, China; E-mail: yanjh2011@126.com Received 18 November, 2017 Accepted 27 January, 2018 This work was supported by the Nature Science Foundation of China (Grant No. 81670885), the Science and Technology Program of Guangdong Province, China (Grant No. 2013B020400003), and the Science and Technology Program of Guangzhou, China (Grant No. 15570001). The author reports no conflicts of interest. © 2018 by Mutaz B. Habal, MD.

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Review of “Overlapping Surgeries Are Not Associated With Worse Patient Outcomes: Retrospective Multivariate Analysis of 14,872 Neurosurgical Cases Performed at a Single Institution” by Bohl MA in Neurosurg [published online September 27, 2017] doi: 10.1093/neuros/nyx472

No abstract available

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Relations Between Hyoid-Related Cephalometric Measurements and Severity of Obstructive Sleep Apnea

Objective: To evaluate the relationship between the hyoid-related cephalometric measurements and the apnea-hypopnea index (AHI) in patients diagnosed with obstructive sleep apnea (OSA). Methods: A total of 56 subjects were evaluated by lateral cephalometric radiography and polysomnography (PSG). The OSA diagnosis was made according to the patients' AHI. Included were 13 primary snoring, 16 mild OSA, 10 moderate OSA, and 17 severe OSA. C3-hyoid distance and mentum-hyoid distance were measured on lateral cephalogram. Cephalometric measurements and PSG parameters were compared among the different OSA groups. Results: The distance between the mentum and hyoid was significantly longer in the severe OSA group than in the primary snoring, mild OSA, and moderate OSA groups (P = 0.029). There was a significant positive correlation between the AHI value and the distance of the mentum hyoid (r = 0.368, P = 0.005). The C3-hyoid distance among the groups was not statistically significant different (P = 0.889). Conclusion: The mentum-hyoid distance of patients with severe OSA was longer compared to the other OSA groups. These patients might have more benefit from the surgeries that have an impact on the position of the hyoid bone compared to other patients with OSA. Address correspondence and reprint requests to Suat Bilici, MD, Department of Otorhinolaryngology, University of Health Sciences, Istanbul Training and Research Hospital, Istanbul 34500, Turkey; E-mail: suatbilici@yahoo.com Received 25 May, 2017 Accepted 27 January, 2018 The authors report no conflicts of interest. © 2018 by Mutaz B. Habal, MD.

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Transplantation of Autogenous Bone Block With an Osseointegrated Implant: Seedling Technique With Twelve-Month Follow-Up

Objective: Loss of teeth frequently results in compound horizontal and vertical alveolar bone defects. An appropriate bone structure is the key for implant placement and bony support of soft tissues. Advanced bone augmentation techniques are required for the reconstruction of these defects. This report will present a new bone block grafting technique with 12-month follow-up. Method: The seedling technique was used to augment the alveolar bone 3-dimensionally with autologous bone block and an osseointegrated implant in a 2-stage procedure. Horizontal and vertical bone loss is revealed after cone beam radiographic examination in the right maxillary lateral incisor area. Initially, the implant was placed at the right maxillary tuber area, where the bone was abundant. After 2-months healing phase, the osseointegrated implant was harvested with the surrounding bone and transplanted to the anterior region of maxilla to augment the horizontal and the vertical components of the recipient site. Transplanted implant inserted into autogenous bone block was fixed with mini plate to the adjacent native bone. Prosthetic restoration was applied 4 months after the transplantation. Results: Seven months after the first surgery, treatment of anterior bone deficiency was accomplished. The patient was fully satisfied with the function and the esthetics of the restoration. The radiological and clinical examinations at 1-year follow-up evaluation showed successful outcome of transplanted autogenous bone block without any resorption. Conclusion: This clinical report demonstrated that anterior maxillary single-tooth replacement, according to seedling concept of autogenous bone block with osseointegrated implant, is a successful and predictable treatment modality. Address correspondence and reprint requests to Tolga F. Tözüm, DDS, PhD, Department of Periodontics, College of Dentistry, University of Illinois at Chicago, 801 S Paulina street, 60612 Chicago, IL; E-mail: ttozum@icloud.com Received 10 December, 2017 Accepted 27 January, 2018 The authors report no conflicts of interest. © 2018 by Mutaz B. Habal, MD.

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Postoperative Complications Associated With Different Fixation Methods of Isolated Mandibular Angle Fractures

The objective of this study was to review the medical records of patients with a history of mandibular angle fracture who were attended at the Service of Oral and Maxillofacial Surgery and Traumatology of FOAr/UNESP in the last 5 years. The data collected were subjected to chi-squared test (significance level of 5%). The authors reviewed 19 medical records. The main cause was physical aggression (58.00%), but with no statistical difference in relation to the other etiologies (P > 0.05). Regarding the type of fixation, one 2.0-mm system plate associated with one 2.4-mm system plate and the fixation using only two 2.0-mm system plates were used in 7 patients each. The fixation method with a monocortical plate at the upper border was used in 5 patients. However, there was no statistically significant difference in the frequency of complications among the 3 fixation methods used (P > 0.05). In 52.64% of the patients, the third molar was removed intraoperatively. Despite this, there was no statistically significant difference in the frequency of complications when the third molar was in the fracture line or when it was removed postoperatively (P > 0.05). The complications observed were dehiscence associated with pain (44.44%), trismus (22.22%), infection (22.22%), and presence of bone spicules (11.11%). However, no statistical differences were observed between the frequency of different types of complications (P = 0.779). In the sample studied, there were no differences in the frequency of complications among the fixation methods applied. Address correspondence and reprint requests to Rafael Ferreira e Costa, DDS, Rua Professor Moraes, 72, apartamento 403, Bairro Funcionários, CEP 30150370 Belo Horizonte, MG, Brazil; E-mail: rafaelfcosta87@yahoo.com.br Received 25 May, 2017 Accepted 27 January, 2018 The authors report no conflicts of interest. © 2018 by Mutaz B. Habal, MD.

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Complications of Cranioplasty

Cranioplasty is a time-honoured surgical procedure to restore the calvarial form and function that is associated with a relatively high complication rate. The present article analyzed various complications and reviewed the complications based on study of the relevant research in the craniofacial literature. Complications were broadly divided into 2 groups, intraoperative and postoperative, for ease of understanding. The etiological factors, local and systemic condition of the patient, prevention, and management of various complications were widely discussed. The article also highlighted problems and complications associated with various reconstructive materials. Insights into various complications of cranioplasty enable surgeon to understand them better, minimize the chances of occurrence, and improve surgical outcome. In spite of reported high rate of complications, serious complications like meningitis, air embolism, and death are rare. Address correspondence and reprint requests to Dr. Nanda Kishore Sahoo, MDS, FIBOMS, Department of Oral & Maxillofacial Surgery, CMDC (CC), Lucknow 226002, Uttar Pradesh, India; E mail colnksahoo@gmail.com. Received 21 August, 2017 Accepted 25 January, 2018 The authors report no conflicts of interest. © 2018 by Mutaz B. Habal, MD.

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The Progress on Noma Disease and Its Surgical Treatment

No abstract available

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Vasoactive intestinal peptide overexpression mediated by lentivirus attenuates lipopolysaccharide-induced acute lung injury in mice by inhibiting inflammation

Publication date: May 2018
Source:Molecular Immunology, Volume 97
Author(s): Guo-Ying Sun, Hui-Hui Yang, Xin-Xin Guan, Wen-Jing Zhong, Yong-Ping Liu, Ming-Yuan Du, Xiao-Qin Luo, Yong Zhou, Cha-Xiang Guan
Vasoactive intestinal peptide (VIP) is one of the most abundant neuropeptides in the lungs with various biological characters. We have reported that VIP inhibited the expressions of TREM-1 and IL-17A, which are involved in the initiation and amplification of inflammation in acute lung injury (ALI). However, the overall effect of VIP on ALI remains unknown. The aim of this study is to investigate the therapeutic effect of VIP mediated by lentivirus (Lenti-VIP) on lipopolysaccharide (LPS)-induced murine ALI. We found that the expression of intrapulmonary VIP peaked at day7 after the intratracheal injection of Lenti-VIP. Lenti-VIP increased the respiratory rate, lung compliance, and tidal volume, while decreased airway resistance in ALI mice, detected by Buxco system. Lenti-VIP significantly reduced inflammatory cell infiltration and maintained the integrity of the alveolar septa. Lenti-VIP also remarkably decreased the total protein level, the number of neutrophil and lactate dehydrogenase activity in the bronchoalveolar lavage fluid of LPS-induced ALI mice. In addition, Lenti-VIP down-regulated pro-inflammatory tumor necrosis factor (TNF)-α mRNA and protein expression, while up-regulated anti-inflammatory interleukin-10 mRNA and protein expression in lungs of ALI mice. Furthermore, we observed that VIP reduced the TNF-α expression in murine macrophages under LPS stimulation through protein kinase C and protein kinase A pathways. Together, our findings show that in vivo administration of lentivirus expressing VIP exerts a potent therapeutic effect on LPS-induced ALI in mice via inhibiting inflammation.

http://ift.tt/2FWjaUJ

Modulation of autophagy as a strategy for development of new vaccine candidates against tuberculosis

Publication date: May 2018
Source:Molecular Immunology, Volume 97
Author(s): Mario Alberto Flores-Valdez, Cristian Alfredo Segura-Cerda, Jorge Gaona-Bernal
Effective prevention of tuberculosis (Tb) would undoubtedly be of paramount relevance in the control of its global burden, which resulted in more than 6 million new cases in 2016. Research aimed to improve the current vaccine, Bacillus Calmette- Guérin (BCG), or directed to develop new candidates, has taken into account the interaction between the host and Mycobacterium tuberculosis (Mtb). Recently, autophagy, an intracellular process of the host, has been shown to act as a mechanism that contributes to bacilli clearance in vitro and in vivo. Stimulation of autophagy, if correctly balanced, is an approach that has the potential to enhance the immune response of the host, and offers new avenues for developing immunogens that may give an improved protection upon immunization, given that in fact, some recent rBCG vaccine candidates have been shown to modulate autophagy. In this Discussion, we analyze the role of autophagy in the context of mycobacterial infection, its modulation via mycobacterial elements, and the management of host response as an alternative to develop new, hopefully improved, Tb-vaccine candidates.

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Oral Manifestation of Lymphomatoid Granulomatosis

Abstract

http://ift.tt/2GvTEn7

Neurogenic pulmonary oedema

Description

A 42-year-old healthy woman was found unresponsive with a peripheral oxygen saturation of 80% after having a thunderclap headache. She had copious pink respiratory secretions. Emergency intubation was performed. Cerebral CT showed subarachnoid haemorrhage from a right internal carotid aneurysm. Thoracic CT revealed extensive bilateral patchy consolidations with air bronchograms, mainly in dependent lung areas (figure 1: coronal plane; figure 2: transverse plane). Her PaO₂/FiO₂ ratio was initially 157 mm Hg and improved significantly over 24 hours. These findings were consistent with acute neurogenic pulmonary oedema (ie, interstitial and alveolar fluid) which results from changes in cardiopulmonary physiology caused by extreme sympathetic discharge after an acute neurological insult. Serial echocardiography showed initially impaired left ventricular function that fully recovered over 2 days. Extubation was successful after 30 hours. The clinical course supports the diagnosis of neurogenic pulmonary oedema. After a complicated recovery (due to vasospasms and hydrocephalus),...

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Asymmetric proptosis as a presenting symptom of Hashimotos thyroiditis with hypothyroidism

Description

Thyroid ophthalmopathy is usually associated with Graves' disease; however, in 6.2% of patients with thyroid eye disease it can be associated with hypothyroidism.1 A 54-year-old woman from Tamil Nadu presented to our outpatient department with sudden onset of binocular diplopia for the past 5 months. She subsequently noticed that her right eye became more prominent than her left eye. She had no other focal deficits or features of raised intracranial pressure. Along with these ocular symptoms, the patient had fatigue and increased drowsiness over the past 5 months and had gained around 3 kg of weight over the same duration. She however did not complain of constipation, voice changes, pedal swelling, cold intolerance or facial puffiness. She had no features suggestive of hyperthyroidism in the form of tremors, increased sweating, palpitations, hyperdefecation or restlessness. She had no history of hyperthyroidism. She had no history of receiving treatment for hypothyroidism...

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Neglected parasitic infection: toxocariasis

Description

A healthy 34-year-old Japanese man presented with a 10-day history of epigastralgia. He had eaten seared chicken sashimi several times. Physical examination findings were not remarkable. Laboratory findings revealed marked eosinophilia (20 x10⁹/L). Chest CT revealed multiple nodules in the lung surrounded by a halo (figure 1). Abdominal contrast-enhanced CT revealed multiple low-attenuating nodules in the liver (figure 2). An ELISA for Toxocara was strongly positive; thus, a diagnosis of toxocariasis was established. After treatment with albendazole, his symptoms and eosinophilia improved, and the pulmonary and liver lesions disappeared.

Figure 1

Chest CT image showing multiple nodules surrounded by a halo.

Figure 2

Contrast-enhanced abdominal CT image showing multiple low-attenuation lesions in the liver.

Toxocariasis is a parasitic disease caused by the larvae of the roundworm Toxocara canis or Toxocara cati. Toxocariasis...

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Oral Manifestation of Lymphomatoid Granulomatosis

Abstract

http://ift.tt/2GvTEn7

Asthma-Related Mortality in the United States of America, 1999-2015: A Multiple Causes of Death Analysis

Publication date: Available online 13 March 2018
Source:Annals of Allergy, Asthma & Immunology
Author(s): Vijay Kodadhala, Jennifer Obi, Priscilla Wessly, Alem Mehari, R.F. Gillum
BackgroundAsthma mortality based on the underlying cause of death (UCOD) underestimates disease burden.ObjectiveTherefore, in this study, asthma mortality in the US 1999-2015 was analyzed, as well as the pattern of reporting of asthma and its co-morbidities in death certificates, using multiple-cause of death (MCOD) records.MethodsAll 156,517 death certificates with any mention of asthma were analyzed for 1999-2015. Asthma was defined by ICD-10 code J45 based either on the UCOD or MCOD. Annual age-adjusted asthma death rates were computed according to age, gender and race/ethnicity. The 6,304 MCOD coded status asthmaticus (J46) were also examined.ResultsIn years of 1999-2015 a total of 59,067 deaths with UCOD of asthma occurred, of which 37,832 were females and 21,235 were males (F/M = 1.78). A total of 156,517 deaths with MCOD of asthma occurred, of which 101,371 were females and 55,146 were males (F/M=1.83). Hence 37.7% of deaths with any mention of asthma had asthma as the UCOD, 37.3% females and 38.45% males. Percents were White Hispanics (HW), 41.7% in non-Hispanic blacks (NHB) and 36% in non-Hispanic whites (NHW). Between 1999-2015, age adjusted MCOD death rates changed as follows: Females HW -38.1%, NHB -34.1%, and NHW -15.1%; Males HW -28.5%, NHB -21.3% and NHW -25.0%. NHB females and males had the highest MCOD and UCOD rates throughout the period.ConclusionAmong deaths with any mention of asthma, asthma was chosen as UCOD most often in NHBM and least often in NHWF. Age-adjusted MCOD rates declined most in NHWM and least in NHWF.

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Multiple laser pulses in conjunction with an optical clearing agent to improve the curative effect of cutaneous vascular lesions

Abstract

Port-wine stain (PWS) birthmark is a congenital microvascular malformation of the skin. A 1064-nm Nd:YAG laser can achieve a deeper treatment, but the weak absorption by blood limits its clinical application. Multiple laser pulses (MLPs) are a potential solution to enhance the curative effect of a Nd:YAG laser. To reduce the pulse number (p_n) required for the thermal destruction of the blood vessel, the effect of glucose in conjunction with MLP was investigated. In vivo experiments were performed on a dorsal skin chamber model. Different concentrations (20, 25, 30, and 40%) of glucose were applied to the sub-dermal side of the hamster skin before laser irradiation. Identical vessels with diameters of 200 ± 30 and 110 ± 20 μm were chosen as representatives of typical PWS vessels. Instant thermal responses of the blood vessel were recorded by a high-speed camera. The required p_n for blood vessel damage was compared with that without glucose pretreatment. Results showed that the use of glucose with a concentration of 20% combined with MLP Nd:YAG laser to damage blood vessels is more appropriate because severe hemorrhage or carbonization easily appeared in blood vessels at higher glucose concentration of 25, 30, and 40%. When 20% glycerol is pretreated on the sub-dermal hamster skin, the required p_n for blood vessel damage can be significantly decreased for different power densities. For example, p_n can be reduced by 40% when the power density is 57 J/cm². In addition, generation of cavitation and bubbles in blood vessels is difficult upon pretreatment with glucose. The combination of glucose with MLP Nd:YAG laser could be an effective protocol for reducing the p_n required for blood vessel damage. Randomized controlled trial (RCT) and human trials will be conducted in the future.

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Promoting Zero-time Exercise in Patients With Coronary Heart Disease

Condition: Exercise Adherence
Intervention: Behavioral: Zero-time exercise
Sponsor: The University of Hong Kong
Recruiting

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Prevalence of Helicobacter pylori among Alaskans: Factors associated with infection and comparison of urea breath test and anti-Helicobacter pylori IgG antibodies

Abstract

Background

Helicobacter pylori is one of the most common human infections in the world, and studies in Alaska Native people, as well as other Indigenous peoples, have shown a high prevalence of this gastric infection. This study was undertaken to determine the prevalence of H. pylori infection by urea breath test (UBT) and anti- H. pylori IgG among Alaskans living in four regions of the state and to identify factors associated with infection.

Methods

A convenience sample of persons > 6 months old living in five rural and one urban Alaskan community were recruited from 1996 to 1997. Participants were asked about factors possibly associated with infection. Sera were collected and tested for anti- H. pylori IgG antibodies; a UBT was administered to participants > 5 years old.

Results

We recruited 710 people of whom 571 (80%) were Alaska Native and 467 (66%) were from rural communities. Rural residents were more likely to be Alaska Native compared with urban residents (P < .001). Of the 710 people, 699 (98%) had a serum sample analyzed, and 634 (97%) persons > 5 years old had a UBT performed. H. pylori prevalence was 69% by UBT and 68% by anti- H. pylori IgG. Among those with a result for both tests, there was 94% concordance. Factors associated with H. pylori positivity were Alaska Native racial status, age ≥ 20 years, rural region of residence, living in a crowded home, and drinking water that was not piped or delivered.

Conclusions

Helicobacter pylori prevalence is high in Alaska, especially in Alaska Native persons and rural residents. Concordance between UBT and serology was also high in this group. Two socioeconomic factors, crowding and drinking water that was not piped or delivered, were found to be associated with H. pylori positivity.

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Beer, hyponatraemia and cardiac conduction defects

The authors report a case of a 68-year-old man who was diagnosed with an irreversible second-degree atrioventricular (AV) Mobitz II 2:1 block temporally associated with profound hyponatraemia. The cause of the hyponatraemia was beer potomania. The co-occurrence of reversible first, second and third-degree heart blocks and hyponatraemia has been described in a few published case reports. However, this case is noteworthy as the AV block persisted, despite correction of serum sodium concentration as opposed to other published cases, which meant that the patient required a permanent pacemaker.

http://ift.tt/2paBgsa

Toll-like receptor 4 deficient mice do not develop remifentanil-induced mechanical hyperalgesia: An experimental randomised animal study

BACKGROUND Drugs with antagonistic actions on the Toll-like receptor 4 (Tlr4), such as naloxone at ultra low doses, have been used to inhibit opioid-induced hyperalgesia in rodents suggesting the involvement of this receptor and pathway on opioid-induced hyperalgesia. OBJECTIVE The aim of this study was to determine whether mice without the Tlr4 gene (Tlr4−/−) would not develop remifentanil-induced hyperalgesia. DESIGN An experimental randomised animal study. SETTING Experimental Unit, Complutense University of Madrid, Madrid, Spain. ANIMALS Twelve adult female wild-type mice and 12 adult Tlr4−/− mice. INTERVENTIONS Under sevoflurane anaesthesia, a 1-h, constant rate subcutaneous infusion of remifentanil (4 μg kg−1 min−1) or 0.9% saline. MAIN OUTCOME MEASURES Mechanical nociceptive thresholds were evaluated using a von Frey hair test before (baseline) and on days 5, 6 and 7 after treatment. Hyperalgesia was considered to be a decrease in the mechanical nociceptive threshold. Changes in mechanical nociceptive thresholds in the different groups were compared with one-sided paired t tests. RESULTS Baseline mechanical nociceptive thresholds were similar in all groups (2.2 ± 0.1 g). Remifentanil produced a 24% decrease in mechanical nociceptive thresholds in the wild-type mice (1.7 ± 0.0 g, averaged over 3 days, P = 0.00021), whereas the nociceptive thresholds were not changed in Tlr4−/− mice (2.2 ± 0.1 g, P = 0.857) or in mice receiving 0.9% saline (Tlr4−/−, 2.2 ± 0.1 g, P = 0.807; wild-type, 2.2 ± 0.1 g, P = 0.962). CONCLUSION Tlr4 receptor involvement is suggested in the development of remifentanil-induced hyperalgesia in mice. TRIAL REGISTRATION CEA-UCM 107/2012). Correspondence to Ignacio A. Gómez de Segura, Department of Animal Medicine and Surgery, Veterinary Faculty, Complutense University of Madrid, Avda. Puerta de Hierro, 28040 Madrid, Spain Tel: +34 913 943 858; fax: +34 913 943 808; e-mail: iagsegura@vet.ucm.es © 2018 European Society of Anaesthesiology

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Prediction of bilateral cerebral oxygen desaturations from a single sensor in adult cardiac surgery: A prospective observational study

BACKGROUND Monitoring regional cerebral oxygen saturation (rcSO2) with near-infrared spectroscopy is increasingly being performed in patients scheduled for cardiac surgery. It is sometimes difficult to monitor both frontal lobes due to anatomical or space compromises. However, it remains unclarified whether the use of only one lateral or medial probe can provide adequate bilateral monitoring. OBJECTIVE To evaluate the efficacy of using a single lateral or medial probe to detect substantial desaturations on both sides. DESIGN A prospective observational study. SETTING Tertiary university teaching hospital. PATIENTS Seventeen adult patients undergoing elective cardiac surgery monitored with three near-infrared spectroscopy probes (two lateral and one medial) using an INVOS 5100C monitor. INTERVENTIONS The value of rcSO2 was registered up to 19 times during each procedure. Substantial desaturation was defined as an absolute rcSO2 value of 50% or less or a decrease of more than 20% compared with basal values on spontaneous ventilation with 21% oxygen. MAIN OUTCOME MEASURES The agreement between the three probes using the Bland–Altman method for repeated measures, and the grade of concordant and discordant results between probes by means of contingency tables and the κ coefficient. RESULTS We obtained 244 records per probe. Greater agreement was observed between the two lateral probes (mean of the differences between recordings was -0.9 ± 5.5 points); mean difference between left and medial, and right and medial probes was 2.4 ± 7.3 and 3.3 ± 6.7, respectively. The rate of discordant results between the two lateral probes was 5.7% [κ coefficient of 0.6 [95% confidence interval (95% CI) 0.4 to 0.8)], and between the left and medial, and right and medial of 8.2 and 7.4%, with κ coefficients of 0.57 (95% CI 0.38 to 0.76) and 0.5 (95% CI 0.29 to 0.71), respectively. CONCLUSION In cardiac surgery patients in whom there is difficulty in accommodating two rcSO2 probes, a single lateral probe can effectively measure bilateral rcSO2 in specific scenarios. Correspondence to Manuel de la Matta, Department of Anaesthesia, Hospital General, Hospital Universitario Virgen del Rocío, Avda Manuel Siurot s/n, Sevilla 41013, Spain. E-mail: mdlmattam@hotmail.com © 2018 European Society of Anaesthesiology

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Psychological Characteristics of Chronic Pain: a Review of Current Evidence and Assessment Tools to Enhance Treatment

Abstract

Purpose of Review

The complicated nature of chronic pain involves an interplay between psychological and physical factors, often resulting in increased emotional distress and reduced quality of life. This review is designed to help the medical practitioner who is working with chronic pain patients to be aware of psychological assessment techniques that can add to comprehensive patient understanding and more effectively guide treatment. Enhanced ability to assess and understand the emotional life of the chronic pain patient provides a basis for intervening and treating more successfully.

Recent Findings

There are a broad range of assessment techniques, some of which require a background in psychology and some that do not, that can identify psychological differences in chronic pain patients and serve to guide intervention strategies. Chronic pain is often comorbid with depression, anxiety, catastrophizing, and various ineffective coping strategies. Some patients, however, have demonstrated more adaptive and effective strategies for cognitively and behaviorally coping with pain and normalizing their lives. Proper assessment enables the individualization of treatment to overcome and/or build upon each patient's psychological frame of mind to maximize the potential for effective functioning.

Summary

The use of standardized and documented psychological assessment techniques can lead to a better understanding of chronic pain patients and contribute in ways that can enhance response to medical treatment and improve quality of life. It is recommended that certain psychological tools be included to supplement the medical assessment of patients who have chronic pain. A basic assessment can include a short psychological-based clinical interview along with brief measures of depression, anxiety, and coping strategies. It is also recommended that the pain physician have access to professional psychological practitioners as a resource for more complicated assessments and psychological intervention services.

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Unilateral Vision Loss after a Dental Visit

Intraoral local anesthetics are widely used for performing painless dental treatments; however, in some cases, they may cause ocular complications such as meiosis, diplopia, nystagmus, ophthalmoplegia, ptosis, and amaurosis. Mostly, the symptoms disappear after several hours; rarely, they have a prolonged character. We describe the case of a 38-year-old young man who had reduced vision in the left eye 5 days after having received intraoral local anesthesia. A diagnosis of cilioretinal artery occlusion with optic disc swelling was made. Ten weeks later, the patient's visual acuity had increased to 20/20, and the swelling of the optic disc had subsided. Although various possible mechanisms for ocular complications after intraoral local anesthetic administration were suggested in the literature, the exact etiology remains unclear. In this case, inadvertent intravascular injection is believed to be the cause.
Case Rep Ophthalmol 2018;9:204–209

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Stable Isotope Ecology and Human Palaeodiet in the Northern Coast of Santa Cruz (Argentine Patagonia)

Abstract

The aim of this paper is to provide information on the analysis of stable isotopes obtained from bones of marine and terrestrial fauna used as potential food by hunter-gatherers on the northern coast of Santa Cruz province (Argentine Patagonia). The results from the isotopic ecology are analyzed to contribute to dietary interpretations of the human populations who lived in this area. The mean of terrestrial resources is -19.1 ‰ ± 1.8 ‰ and 9.2 ‰ ± 2.6 ‰ for δ¹³C and δ¹⁵N respectively. Meanwhile, marine resources recorded a mean of δ¹³C -12.5 ‰ ± 1.2 ‰ and δ¹⁵N of 19.4 ‰ ± 2.4 ‰. The analyzed human samples come from different types of burials dated mainly in the Late Holocene. The δ¹³C and δ¹⁵N isotopic values on human remains suggest the existence of different diets during the Late Holocene, including people who consumed mainly marine, terrestrial and mixed proteins, with a range between -18 ‰ to -10.4 ‰ and 12.4 ‰ to 23.4 ‰ for δ¹³C and δ¹⁵N respectively. Some of these isotopic values, which indicate marine diets, are the highest recorded for Patagonia. The influence of the marine spray on the terrestrial trophic chains is suggested for the Patagonian Atlantic coast, evidenced by higher values in the δ¹⁵N of guanacos from the coast in relation to others studied from the hinterland.

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Impact of Mitochondrial Permeability on Endothelial Cell Immunogenicity in Transplantation

ABSTRACTBackgroundMicrovascular endothelial cells (ECs) are central to an allograft's immunogenicity. Cold ischemia and reperfusion injury associated with static cold storage and warm reperfusion activates ECs and increases the immunogenicity of the allograft. Following reperfusion, mitochondrial permeability transition pore (mPTP) opening contributes to mitochondrial dysfunction in the allograft, which correlates to alloimmune rejection. Current understanding of this relationship, however, centers on the whole allograft instead of ECs. This study aimed to elucidate the relationship between EC mPTP opening and their immuno-phenotype.MethodsMitochondrial metabolic fitness and glycolysis in ECs were assessed in parallel with metabolic gene microarray postreperfusion. NIM811 was used to inhibit mPTP opening to rescue mitochondrial fitness. The immunogenicity of NIM811-treated ECs was determined via levels of EC's pro-inflammatory cytokines and allogeneic CD8+ T cell co-cultures. Finally, EC surface expression of adhesion, co-stimulatory, co-inhibitory, MHC-I molecules, and MHC-I machinery protein levels were characterized.ResultsGenes for glycolysis, tricarboxylic acid cycle, fatty acid synthesis, gluconeogenesis were upregulated at 6 hours postreperfusion but either normalized or downregulated at 24 hours postreperfusion. As mitochondrial fitness was reduced, glycolysis increased during the first 6 hours postreperfusion. EC treatment with NIM811 during the early postreperfusion period rescued mitochondrial fitness and reduced EC immunogenicity by decreasing CCL2, KC release, and VCAM-1, MHC-I, TAP1 expression.ConclusionsStatic cold storage and warm reperfusion leads to a reduction in mitochondrial fitness in microvascular ECs due to mPTP opening. Further, mPTP opening promotes increased EC immunogenicity that can be prevented by NIM811 treatment. Background Microvascular endothelial cells (ECs) are central to an allograft's immunogenicity. Cold ischemia and reperfusion injury associated with static cold storage and warm reperfusion activates ECs and increases the immunogenicity of the allograft. Following reperfusion, mitochondrial permeability transition pore (mPTP) opening contributes to mitochondrial dysfunction in the allograft, which correlates to alloimmune rejection. Current understanding of this relationship, however, centers on the whole allograft instead of ECs. This study aimed to elucidate the relationship between EC mPTP opening and their immuno-phenotype. Methods Mitochondrial metabolic fitness and glycolysis in ECs were assessed in parallel with metabolic gene microarray postreperfusion. NIM811 was used to inhibit mPTP opening to rescue mitochondrial fitness. The immunogenicity of NIM811-treated ECs was determined via levels of EC's pro-inflammatory cytokines and allogeneic CD8+ T cell co-cultures. Finally, EC surface expression of adhesion, co-stimulatory, co-inhibitory, MHC-I molecules, and MHC-I machinery protein levels were characterized. Results Genes for glycolysis, tricarboxylic acid cycle, fatty acid synthesis, gluconeogenesis were upregulated at 6 hours postreperfusion but either normalized or downregulated at 24 hours postreperfusion. As mitochondrial fitness was reduced, glycolysis increased during the first 6 hours postreperfusion. EC treatment with NIM811 during the early postreperfusion period rescued mitochondrial fitness and reduced EC immunogenicity by decreasing CCL2, KC release, and VCAM-1, MHC-I, TAP1 expression. Conclusions Static cold storage and warm reperfusion leads to a reduction in mitochondrial fitness in microvascular ECs due to mPTP opening. Further, mPTP opening promotes increased EC immunogenicity that can be prevented by NIM811 treatment. Correspondence information: Satish N. Nadig, MD PhD, FACS, 96 Jonathan Lucas Street, MSC 613, CSB 409, Charleston, SC 29425. nadigsn@musc.edu Authorship statement: D.T. participated in research design, performance of the research, data analysis, and manuscript preparation. C.A., S.N. participated in research design, data analysis, and manuscript preparation. J.K. participated in research design and data analysis. S.M. participated in research design. S.E. participated in performance of the research Disclosure: The authors declare no conflicts of interest. Funding: NIH/NIBIB K08 EB019495-01A1 NIH/NHLBI Predoctoral Fellowship T32 HL007260 NIH/MSTP Predoctoral Fellowship T32 GM008716 NIH/NCATS KL2 TR001452 & UL1 TR001450 Patterson Barclay Memorial Foundation Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Disruption of the Gut Microbiota With Antibiotics Exacerbates Acute Vascular Rejection

ABSTRACTBackgroundThe gut microbiota influences many immunological processes but how its disruption affects transplant rejection is poorly understood.MethodsInterposition grafting of aortic segments was used to examine vascular rejection. The gut microbiota was disrupted in graft recipients using an antibiotic cocktail (ampicillin, vancomycin, metronidazole, neomycin sulfate) in their drinking water.ResultsTreatment of mice with antibiotics severely reduced total bacterial content in the intestine and disrupted the bacterial composition. Short-term treatment of mice for only the first 3 weeks of life resulted in the population of the intestine in mature mice with bacterial communities that were mildly different from untreated mice, containing slightly more Clostridia and less Bacteroides. Antibiotic disruption of the gut microbiota of graft recipients, either for their entire life or only during the first 3 weeks of life, resulted in increased medial injury of allograft arteries that is reflective of acute vascular rejection but did not affect intimal thickening reflective of transplant arteriosclerosis. Exacerbated vascular rejection resulting from disruption of the gut microbiota was related to increased infiltration of allograft arteries by neutrophils.ConclusionDisruption of the gut microbiota early in life results in exacerbation of immune responses that cause acute vascular rejection. Background The gut microbiota influences many immunological processes but how its disruption affects transplant rejection is poorly understood. Methods Interposition grafting of aortic segments was used to examine vascular rejection. The gut microbiota was disrupted in graft recipients using an antibiotic cocktail (ampicillin, vancomycin, metronidazole, neomycin sulfate) in their drinking water. Results Treatment of mice with antibiotics severely reduced total bacterial content in the intestine and disrupted the bacterial composition. Short-term treatment of mice for only the first 3 weeks of life resulted in the population of the intestine in mature mice with bacterial communities that were mildly different from untreated mice, containing slightly more Clostridia and less Bacteroides. Antibiotic disruption of the gut microbiota of graft recipients, either for their entire life or only during the first 3 weeks of life, resulted in increased medial injury of allograft arteries that is reflective of acute vascular rejection but did not affect intimal thickening reflective of transplant arteriosclerosis. Exacerbated vascular rejection resulting from disruption of the gut microbiota was related to increased infiltration of allograft arteries by neutrophils. Conclusion Disruption of the gut microbiota early in life results in exacerbation of immune responses that cause acute vascular rejection. Address correspondence to: Jonathan Choy, PhD, Department of Molecular Biology and Biochemistry, Simon Fraser University, 8888 University Drive, Burnaby, BC, Canada V5A 1S6. E-mail: jonathan.choy@sfu.ca AUTHOR CONTRIBUTIONS: K.R., T.V., K.B., R.D.M., F.S.L.B and J.C.C designed the experiments; K.R., S.M., W.E., T.V., and K.B. performed the experiments; K.R., S.M., T.V., K.B., R.D.M., F.S.L.B., and J.C.C analyzed and interpreted the data; K.R., T.V., K.B., R.D.M., F.S.L.B., and J.C.C wrote the manuscript. DISCLOSURES: The authors declare no conflicts of interest. FUNDING: This work was supported by funding from the Heart and Stroke Foundation of Canada (J.C.C), Genome Canada and AllerGen NCE (F.S.L.B), and Natural Sciences and Engineering Research Council of Canada (T.V.R). J.C.C and R.D.M are recipients of Michael Smith Foundation for Health Research Scholar awards. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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OVERCOMING COAGULATION DYSREGULATION IN PIG SOLID ORGAN TRANSPLANTATION IN NONHUMAN PRIMATES: RECENT PROGRESS

There has recently been considerable progress in the results of pig organ transplantation in nonhuman primates (NHPs), largely associated with the availability of (i) pigs genetically-engineered to overcome coagulation dysregulation, and (ii) novel immunosuppressive agents. The barriers of thrombotic microangiopathy and/or consumptive coagulation were believed to be associated with (i) activation of the graft vascular endothelial cells (VECs) by a low level of anti-pig antibody binding and/or complement deposition and/or innate immune cell activity, and (ii) molecular incompatibilities between the NHP and pig coagulation-anticoagulation systems. The introduction of a human coagulation-regulatory transgene, eg, thrombomodulin, endothelial protein C receptor, into the pig VECs has contributed to preventing a procoagulant state from developing, resulting in a considerable increase in graft survival. In the heterotopic (non-life-supporting) heart transplant model, graft survival has increased from a maximum of 179 days in 2005 to 945 days. After life-supporting kidney transplantation, survival has been extended from 90 days in 2004 to 499 days. In view of the more complex coagulation dysfunction seen after pig liver and, particularly, lung transplantation, progress has been less dramatic, but the maximum survival of a pig liver has been increased from 7 days in 2010 to 29 days, and of a pig lung from 4 days in 2007 to 9 days. There is a realistic prospect that the transplantation of a kidney or heart, in combination with a conventional immunosuppressive regimen, will enable long-term recipient survival. Address for correspondence: Hayato Iwase MD, PhD, Xenotransplantation Program, University of Alabama at Birmingham (UAB), ZRB 701, 1720 2nd Avenue South, Birmingham, AL 35294-0007, USA. Tel: 205-975-3938; Fax: 205-934-8344. E-mail: hiwase@uabmc.edu Authorship Data were collected by LW, LB, YW, HI, and DKCC. The manuscript was prepared by LW, LB, YW, HI, and DKCC, and revised and approved by all authors. Disclosure The authors declare no conflicts of interest. Funding Work on xenotransplantation at the University of Alabama at Birmingham is supported in part by NIH NIAID U19 grant AI090959. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

http://ift.tt/2DrrN3Y

Initiating maintenance dialysis prior to living kidney donor transplantation when a donor candidate evaluation is well underway

AbstractBackgroundPreemptive kidney transplants result in better outcomes and patient experiences than transplantation after dialysis onset. It is unknown how often a person initiates maintenance dialysis prior to living kidney donor transplantation when their donor candidate evaluation is well underway.MethodsUsing healthcare databases, we retrospectively studied 478 living donor kidney transplants from 2004-2014 across 5 transplant centres in Ontario, Canada where the recipients were not receiving dialysis when their donor's evaluation was well underway. We also explored some factors associated with a higher likelihood of dialysis initiation before transplant.ResultsA total 167/478 (35%) persons with kidney failure initiated dialysis a median 9.7 (25th-75th percentile 5.4-18.7) months after their donor candidate began their evaluation, and received dialysis for a median 8.8 (3.6-16.9) months before kidney transplantation. The total cohort's dialysis cost was $8.1 million and 44/167 (26%) recipients initiated their dialysis urgently in hospital. The median total donor evaluation time (time from evaluation start to donation) was 10.6 (6.4-21.6) months for preemptive transplants and 22.4 (13.1-38.7) months for donors whose recipients started dialysis prior to transplant. Recipients were more likely to start dialysis if their donor was female, nonwhite, lived in a lower-neighbourhood income, and if the transplant centre received the recipient referral later.ConclusionOne-third of persons initiated dialysis prior to receiving their living kidney donor transplant, despite their donor's evaluation being well underway. Future studies should consider whether some of these events can be prevented by addressing inappropriate delays to improve patient outcomes and reduce healthcare costs. Background Preemptive kidney transplants result in better outcomes and patient experiences than transplantation after dialysis onset. It is unknown how often a person initiates maintenance dialysis prior to living kidney donor transplantation when their donor candidate evaluation is well underway. Methods Using healthcare databases, we retrospectively studied 478 living donor kidney transplants from 2004-2014 across 5 transplant centres in Ontario, Canada where the recipients were not receiving dialysis when their donor's evaluation was well underway. We also explored some factors associated with a higher likelihood of dialysis initiation before transplant. Results A total 167/478 (35%) persons with kidney failure initiated dialysis a median 9.7 (25th-75th percentile 5.4-18.7) months after their donor candidate began their evaluation, and received dialysis for a median 8.8 (3.6-16.9) months before kidney transplantation. The total cohort's dialysis cost was $8.1 million and 44/167 (26%) recipients initiated their dialysis urgently in hospital. The median total donor evaluation time (time from evaluation start to donation) was 10.6 (6.4-21.6) months for preemptive transplants and 22.4 (13.1-38.7) months for donors whose recipients started dialysis prior to transplant. Recipients were more likely to start dialysis if their donor was female, nonwhite, lived in a lower-neighbourhood income, and if the transplant centre received the recipient referral later. Conclusion One-third of persons initiated dialysis prior to receiving their living kidney donor transplant, despite their donor's evaluation being well underway. Future studies should consider whether some of these events can be prevented by addressing inappropriate delays to improve patient outcomes and reduce healthcare costs. Corresponding author: Amit X Garg MD, PhD Institute for Clinical Evaluative Sciences Western facility (ICES Western) Victoria Hospital. 800 Commissioners Rd, Victoria Hospital, Room ELL-215. London, Ontario, Canada N6A 5W9 Tel: 519-685-8502. Email: amit.garg@lhsc.on.ca Authorship Participated in research design: Steven Habbous, Eric McArthur, Stephanie N. Dixon, Susan McKenzie, Carlos Garcia-Ochoa, Ngan N. Lam, Krista L. Lentine, Christine Dipchand, Kenneth Litchfield, Mehmet A. Begen, Sisira Sarma, Amit X. Garg Participated in the writing of the paper: Steven Habbous, Eric McArthur, Stephanie N. Dixon, Susan McKenzie, Carlos Garcia-Ochoa, Ngan N. Lam, Krista L. Lentine, Christine Dipchand, Kenneth Litchfield, Mehmet A. Begen, Sisira Sarma, Amit X. Garg Participated in the performance of the research: Steven Habbous, Eric McArthur, Stephanie N. Dixon, Susan McKenzie, Carlos Garcia-Ochoa, Sisira Sarma, Amit X. Garg Contributed new reagents or analytic tools: N/A Participated in data analysis: Steven Habbous, Eric McArthur, Stephanie N. Dixon, Carlos Garcia-Ochoa, Sisira Sarma, Amit X. Garg Disclosures Dr. Garg received partnership funding from Astellas for a research grant funded by the Canadian Institutes of Health Research. The other authors have no conflicts of interest to disclose. Funding Funding for this analysis was provided by Ontario's Trillium Gift of Life Network. Canadians Seeking Solutions and Innovations to Overcome Chronic Kidney Disease (CAN-SOLVE CKD) is a patient-orientated research network to transform the care of people affected by kidney disease. It is led by Drs. Adeera Levin and Braden Manns. Patient partnerships in this project were supported by CAN-SOLVE. Steven Habbous is supported by the Canadian Institutes of Health Research Frederick Banting and Charles Best Canada Doctoral Scholarship. Dr. Ngan N. Lam was supported by a Kidney Research Scientist Core Education and National Training Program (KRESCENT) New Investigator Award. Dr. Amit Garg is supported by the Dr. Adam Linton Chair in Kidney Health Analytics, and a Canadian Institutes of Health Research Clinician Investigator Award. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Αρχειοθήκη ιστολογίου

Τετάρτη 14 Μαρτίου 2018

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