ImmunoCloak As A Paradigm Of The Biomaterial Approach to Immunomodulation: Where Regenerative Medicine Meets Organ Transplantation: Commentary to: Underlying Mechanisms of Protection Involved in ImmunoCloak.

No abstract available

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Bone Marrow Transplantation Under Regulatory T Cell Cover to Induce Donor-Specific Tolerance.

No abstract available

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Longitudinal Pharmacokinetics of Everolimus when Combined with Low-level of Tacrolimus in Elderly Renal Transplant Recipients.

Background: Although the proportion of elderly patients among renal transplant recipients has increased, pharmacokinetic (PK) studies of immunosuppressants rarely include older patients. Methods: We studied 12-hours everolimus (EVL) PK in 16 elderly renal transplant recipients (all caucasians; 10 males; mean age, 64+/-2 years, (61-71y), in 4 separate time-points (at 7, 30, 60 and 150 days) after EVL introduction, corresponding to a mean post renal-transplantation day: PK1 (43+/-4days), PK2 (65+/-7 days), PK3 (106+/-17 days) and PK4 (206+/-40 days). Patients received EVL (target trough level (Ctrough: 3-8 ng/mL), prednisone and tacrolimus (TCL) (target Ctrough: 2-5 ng/mL). Results: Mean TCL- Ctrough was 7.2+/-3.8, 4.9+/-2.2, 4.9+/-2.2, and 4.5+/-1.2 ng/mL at PK1, PK2, PK3 and PK4, respectively. There were no differences among time-points for mean EVL daily dose (data shown as PK3) (3.5+/-1.3 mg/day), Ctrough (4.7+/-2.5 ng/mL), AUC0-12h (106+/-51 ng*h/mL), Caverage (8.8+/-4.2 ng/mL), Cmax (19.2+/-9.7ng/mL), apparent Half-life (11.7+/-4.2 hours), estimated total body Clearance (0.39+/-0.27 L/hour), or Fluctuation (166+/-65%). Also, none of those PK parameters differed statistically when adjusted for body weight. EVL-Ctrough showed a very high correlation (r2 =0.849) with AUC0-12h. Conclusions: Our data indicate that elderly renal transplant recipients starting EVL 1 month after transplantation along with a steady-state TCL level, present stable EVL-PK parameters without significant changes in dose or exposure during the first 6 months after renal transplantation. Copyright (C) 2016 Wolters Kluwer Health, Inc. All rights reserved.

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Inflammatory Markers and Outcomes in Kidney Transplant Recipients.

Background: Increased levels of TNF-Alpha and IL6 are associated with inflammation and cardiovascular disease among patients with normal kidney function. However, little is known about their association with outcomes in kidney transplant recipients. Methods: We collected socio-demographic, clinical and laboratory parameters, medical and transplant history from 977 prevalent kidney transplant recipients enrolled in the MINIT-HU study. Serum cytokine levels were measured at baseline. Associations between serum TNF-Alpha and IL6 values and death with a functioning graft over a 6-year follow-up period were examined in unadjusted and adjusted models. Results: The mean+/-SD age of the study population was 51+/-13 years, 57% were men, 21% were diabetics. Median serum TNF-Alpha and IL6 concentrations were significantly higher in patients who died with a functioning graft as compared to those who did not die during the follow-up period (TNF-Alpha: median[IQR]: 1.92[1.43-2.67] vs. 2.25[1.63-3.08, p

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Impact of Graft-versus-Graft Natural Killer Cell Alloreactivity on Single Unit Dominance After Double Umbilical Cord Blood Transplantation.

Background: Natural Killer (NK) cell alloreactivity is favored after double umbilical cord blood transplantation (dUCBT) in which cord blood (UCB) units and patients are often Human Leucocyte Antigen (HLA) class I mismatched. Generally, only 1 UCB unit persists after dUCBT. We hypothesize, that NK cell alloreactivity mediated by Killer cell Immunoglobulin-like Receptor (KIR) - HLA interactions may explain the dominance of 1UCB unit over the other after dUCBT. Methods: We investigated the impact of KIR+ NK cell alloreactivities on the dominance of 1 full UCB unit in 50 dUCBT. We analyzed the effects of the KIR/HLA genetic incompatibilities and studied cord blood cells at both the phenotypic and functional levels. Results: The genetic combination of KIR3DL1+ loser UCB unit/Bw4- winner UCB unit determined both the dominance of 1 UCB unit (Hazard Ratio=2.88[1.32-6.27], p=.0077) and correlated with an increased incidence of relapse (Hazard Ratio=4.91[1.39-17.3], p=.0134). It is interesting to note that cord blood cells exhibited extremely low HLA class I expression. Moreover, resting cord blood KIR3DL1+ NK cells exhibited a basal alloreactivity against Bw4- target cells that increased upon activation, thus triggering death by apoptosis. Conclusions: Our unicentric study suggests, for the first time, the significant impact of KIR+ NK cell alloreactivity in the determination of which UCB unit will dominate in dUCBT. Copyright (C) 2016 Wolters Kluwer Health, Inc. All rights reserved.

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Poor Glycemic Control is Associated with Decreased Survival in Lung Transplant Recipients.

Background: Diabetes mellitus (DM) is associated with increased mortality following transplantation, but the effect of glycemic control on survival is unknown. We sought to determine the relationship between glycemic control (random (RBG) and fasting (FBG) blood glucose, HbA1c) and survival in all lung transplant (LTx) recipients and those with either persistent or no DM. Methods: All 210 LTx recipients from 1 August 2010 - 1 November 2013 were included (median observation 3.0 years). All underwent oral glucose tolerance tests pre and serially post-LTx. All glucose and HbA1c results from LTx until study end were included and hazard ratios were calculated. Results: Of 210 patients, 90 had persistent DM, and 84 had no DM. Overall mortality/repeat LTx was 31%. In the whole cohort, each 1 mM (18 mg/dl) increase in mean FBG and RBG and each 1% increase in mean HbA1c was associated with mortality increases of 18% (95%CI 5-32%, p=0.006), 38% (15-65%, p

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Incidence and Indications for Late Allograft Pancreatectomy while on Continued Immunosuppression.

Background: There are limited data about the incidence and indications for late allograft pancreatectomy while on continued immunosuppression for functional kidney allografts. Methods: We analyzed recipients of simultaneous pancreas and kidney (SPK) and pancreas after kidney (PAK) transplants between January 1994 and July 2013. Patients with functional kidney but failed pancreas allografts after 90 days were included. Results: Out of 1022 SPK or PAK recipients, 246 satisfied these criteria. Of these, 50 underwent allograft pancreatectomy (Px) and 196 did not (no-Px). Eleven of these pancreatectomies were performed at the time of repeat transplant and were analyzed separately. None of the basic recipient or donor characteristics differed significantly between the Px (n=39) and no-Px groups, except for a higher proportion of females in the Px group. The most common presentation in the Px group was abdominal pain. Histopathology of the pancreas varied widely with graft thrombosis as the most common finding. In univariate and multivariate Cox regression analysis, only female recipient was associated with higher risk for allograft pancreatectomy. Px was not associated with kidney allograft survival (p=0.16). Conclusion: Despite the ongoing presence of full immunosuppression for a functioning kidney allograft, the need for Px for symptoms and radiological findings is not rare (39/246, 15.8%). Copyright (C) 2016 Wolters Kluwer Health, Inc. All rights reserved.

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Infections in de novo kidney transplant recipients treated with the RANKL inhibitor denosumab.

Background: Infections are a major cause of morbidity and mortality in kidney allograft recipients. In this posthoc analysis of a randomized clinical trial which tested the effect of denosumab on bone mineral density we assessed the impact of this drug on the incidence and severity of infections in the first year after kidney transplantation. Methods: In this clinical trial we randomized 90 de novo kidney transplant recipients shortly after transplantation to either denosumab on top of standard treatment (calcium and vitamin D) (n=46), or to standard treatment alone (n=44). Among all adverse events we analyzed all infections that occurred within the first year after transplantation, and compared their incidence and severity in both groups. Results: Overall we identified more infections (n=146) in the denosumab group than in the control group (n=99). The most common infections were urinary tract infection (cystitis) (34.9% vs 25.2%), CMV viremia (17.8% vs 24.2%), flu-like syndrome (11.6% vs 14.1%), polyoma (BK) viremia (8.2% vs 11.1%), and herpes simplex infections (5.5% vs 4.0%). Episodes of urinary tract infection (cystitis) occurred more often in the denosumab than in the control group (51 vs 25 episodes in 24 vs 11 patients, p=0.008), whereas episodes of transplant pyelonephritis or urosepsis were not more frequent (3 vs 5 episodes). Conclusions: This post-hoc analysis reveals that treatment with denosumab to prevent bone loss in first-year kidney transplant recipients was associated with more frequent episodes of urinary tract infections, whereas other infections occurred with similar frequency in both treatment groups. Copyright (C) 2016 Wolters Kluwer Health, Inc. All rights reserved.

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Alopécie androgénétique (AAG) : quoi de neuf depuis 2 ans ?

Publication date: Available online 1 November 2016
Source:Annales de Dermatologie et de Vénéréologie
Author(s): P. Reygagne




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Programme des Posters

Publication date: Available online 1 November 2016
Source:Annales de Dermatologie et de Vénéréologie





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Programme des Communications Orales

Publication date: Available online 1 November 2016
Source:Annales de Dermatologie et de Vénéréologie





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Actualités dans la rosacée

Publication date: Available online 1 November 2016
Source:Annales de Dermatologie et de Vénéréologie
Author(s): B. Cribier




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Selenium Supplementation Significantly Reduces Thyroid Autoantibody Levels in Patients with Chronic Autoimmune Thyroiditis: A Systematic Review and Meta-Analysis

Thyroid , Vol. 0, No. 0.


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MiR-20b Displays Tumor-Suppressor Functions in Papillary Thyroid Carcinoma by Regulating the MAPK/ERK Signaling Pathway

Thyroid , Vol. 0, No. 0.


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Increase of poorly proliferated p63+/Ki67+ basal cells forming multiple layers in the aberrant remodeled epithelium in nasal polyps

Abstract

Background

Aberrant epithelial remodeling with the ectopic expression of p63 (basal cell markers) is an important pathologic phenomenon seen in chronically inflamed airway epithelium such as in nasal polyps (NPs).

Methods

Biopsies were obtained from 55 NP patients and 18 healthy controls (inferior turbinate). Among NP patients, fifteen were treated with oral and nasal steroids, so that two sets of NPs biopsies were taken before and after the treatments. p63, Ki67, type IV β-tubulin and cell-cycle markers were investigated in these specimens.

Results

The number of p63⁺ cells are significantly higher in both hyperplastic (1.53-fold, p<0.0001) and squamous metaplastic (2.02-fold, p<0.0001) epithelium from NPs than from healthy controls. There are three types of proliferative basal cells (p63⁺/Ki67⁺) which are in different phases of the cell cycle, such as G1 phase (Type I cells), S to G2 phase (Type II cells), and mitosis (Type III cells). Of importance, some Type I cells may arrest after proliferation although they may still be p63⁺/Ki67⁺. In healthy epithelium, the ratio of the Types I and II cells is almost 50:50. However, less Type II cells are found in hyperplastic epithelium (34.85%, p=0.012) and in squamous metaplastic epithelium (30.77%, p=0.02) together with the presence of Type III cells (3.45%, p=0.01). These findings were not changed after steroid treatments.

Conclusions

An increase of poorly proliferated basal cells forming multiple layers, which may stain for basal cell markers but does not form a proper epidermal barrier, is an important histopathologic phenomenon in aberrant remodeled epithelium of NPs.

This article is protected by copyright. All rights reserved.

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Atrophying pityriasis versicolor as an idiosyncratic T cell–mediated response to Malassezia: A case series

Atrophying pityriasis versicolor (PV), first described in 1971, is a rare variant in which lesions appear atrophic.

http://ift.tt/2eWFVtJ

Tofacitinib for the treatment of severe alopecia areata and variants: A study of 90 patients

Alopecia areata (AA) is a common autoimmune disorder. There are no reliably effective therapies for AA.

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Tofacitinib for the treatment of alopecia areata and variants in adolescents

There are no reliably effective therapies for alopecia areata (AA).

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Systemic antifungal therapy for tinea capitis in children: An abridged Cochrane Review

The comparative efficacy and safety profiles of systemic antifungal drugs for tinea capitis in children remain unclear.

http://ift.tt/2fgATGL

Endoscopic Approach to Primary Orbital Tumors

Abstract

Purpose of Review

The purpose of this review is to summarize the principles of endoscopic orbital surgery with references to the most recent literature on the topic.

Recent Findings

The endonasal approach to the orbit is still in its infancy, and as the technique evolves, its use is being applied to more complex tumors that were traditionally approached externally. New tools, such as 3-dimensional reconstruction, allow the surgeon to determine the tumor's volume, morphology, and its relation with important structures as well as to delineate a plane of resectability.

Summary

Endoscopic intraorbital surgery is a rapidly growing field and represents the next frontier in endonasal surgery.

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Meta-analysis of teeth from European populations before and after the 18th century reveals a shift towards increased prevalence of caries and tooth loss

Publication date: January 2017
Source:Archives of Oral Biology, Volume 73
Author(s): Antonia Müller, Kais Hussein
Based on single studies, it has been hypothesised that Europeans have suffered less frequently from caries before the 18th century than after the 18th century and that females have higher caries prevalence, but systematic European-wide overviews are sparse.We collected published data on dental diseases (publication between 1981 and 2015 with reports on 29 cohorts with 4998 individuals and a total of 85817 teeth).Meta-analyses revealed that, over several hundred years, including the post-18th century era, Europeans had relatively constant frequencies of caries and ante-mortem tooth loss, but since the 18th century, the mean frequencies of these dental diseases increased (each p<0.05). Tooth loss correlated with caries and odontogenic abscesses (each p<0.05). Although the mean caries and ante-mortem tooth loss frequencies increased since the 18th century, there are overlaps with many pre-18th century cohorts. In addition, in contrast to previous hypotheses, no general increase of caries prevalence in females could in fact be verified.It is likely that changes in nutrition (more sugar) and dental health (possibly higher frequency of tooth extraction) could be the underlying factors which led to this minor to moderate shift of dental disease frequencies in Europe.



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Porphyromonas gingivalis-stimulated macrophage subsets exhibit differential induction and responsiveness to interleukin-10

Publication date: January 2017
Source:Archives of Oral Biology, Volume 73
Author(s): Andrew D. Foey, Neama Habil, Khalid Al-Shaghdali, StJohn Crean
ObjectivesOral mucosal macrophages (Mϕs) determine immune responses; maintaining tolerance whilst retaining the capacity to activate defences against pathogens. Mϕ responses are determined by two distinct subsets; pro-inflammatory M1- and anti-inflammatory/regulatory M2-Mϕs. Tolerance induction is driven by M2 Mϕs, whereas M1-like Mϕs predominate in inflammation, such as that exhibited in chronic Porphyromonas gingivalis (PG) periodontal infection. Mϕ responses can be suppressed to benefit either the host or the pathogen. Chronic stimulation by pathogen associated molecular patterns (PAMPs), such as LPS, is well established to induce tolerance. The aim of this study was to investigate the P. gingivalis-driven induction of and responsiveness to the suppressive, anti-inflammatory cytokine, IL-10, by Mϕ subsets.MethodsM1- and M2-like Mϕs were generated in vitro from the THP-1 monocyte cell line by differentiation with PMA and Vitamin D3, respectively. Mϕ subsets were stimulated by PG-LPS in the presence or absence of IL-10.ResultsPG-LPS differentially induced IL-10 secretion and endogenous IL-10 activity in M1- and M2-like subsets. In addition, these subsets exhibited differential sensitivity to IL-10-mediated suppression of TNFα, where M2 Mϕs where sensitive to IL-10 and M1 Mϕs were refractory to suppression. In addition, this differential responsiveness to IL-10 was independent of IL-10-binding and expression of the IL-10 receptor signal transducing subunit, IL-10Rβ, but was in fact dependent on activation of STAT-3.ConclusionP.gingivalis selectively tolerises regulatory M2 Mϕs with little effect on pro-inflammatory M1 Mϕs; differential suppression facilitating immunopathology at the expense of immunity.



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Roles of hypoxia inducible factor-1α in the temporomandibular joint

Publication date: January 2017
Source:Archives of Oral Biology, Volume 73
Author(s): Akiko Mino-Oka, Takashi Izawa, Takehiro Shinohara, Hiroki Mori, Akihiro Yasue, Shuhei Tomita, Eiji Tanaka
ObjectiveTemporomandibular joint osteoarthritis (TMJ-OA) is a degenerative disease characterized by permanent cartilage loss. Articular cartilage is maintained in a low-oxygen environment. The chondrocyte response to hypoxic conditions involves expression of hypoxia inducible factor 1α (HIF-1α), which induces chondrocytes to increase expression of vascular endothelial growth factor (VEGF). Here, we investigated the role of HIF-1α in mechanical load effects on condylar cartilage and subchondral bone in heterozygous HIF-1α-deficient mice (HIF-1α^+/−).DesignMechanical stress was applied to the TMJ of C57BL/6NCr wild-type (WT) and HIF-1α^+/− mice with a sliding plate for 10 days. Histological analysis was performed by HE staining, Safranin-O/Fast green staining, and immunostaining specific for articular cartilage homeostasis.ResultsHIF-1α^+/− mice had thinner cartilage and smaller areas of proteoglycan than WT controls, without and with mechanical stress. Mechanical stress resulted in prominent degenerative changes with increased expression of HIF-1α, VEGF, and the apoptosis factor cleaved Caspase-3 in condylar cartilage.ConclusionOur results indicate that HIF-1α may be important for articular cartilage homeostasis and protective against articular cartilage degradation in the TMJ under mechanical stress condition, therefore HIF-1α could be an important new therapeutic target in TMJ-OA.



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Effects of repetitive transcranial magnetic stimulation on masseter motor-neuron pool excitability

Publication date: January 2017
Source:Archives of Oral Biology, Volume 73
Author(s): Huang Huang, Wei cai Liu, Yu Han Song
ObjectiveRepetitive transcranial magnetic stimulation (rTMS) has been widely used to modulate the excitability of the cortical control of limbs muscles, but rarely in the cortical control of human masseter muscles. This study aims to investigate the effects of rTMS on masseter motor-neuron pool excitability in humans.Materials and methodsA total of 20 healthy participants were selected and received a total of three rTMS sessions involving stimulation of the right masseter-motor complex: one session of 10-Hz rTMS, one session of 1-Hz rTMS and one session of sham rTMS at an intensity of 80% of the active motor threshold (AMT). The masseter AMT, motor-evoked potentials (MEPs), cortical-silent period (CSP), and short-interval intracortical inhibition (SICI) were measured before and after each rTMS session.ResultsThe masseter SICI was significantly decreased following 10-Hz rTMS, with no significant changes in AMT, MEPs or CSP. No significant differences in masseter AMT, MEPs, CSP or SICI were observed in either the 1-Hz, or sham rTMS groups.ConclusionsThe present findings demonstrate that high-frequency rTMS increases masseter motor-neuron pool excitability.



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Erratum to: Debates in allergy medicine: specific immunotherapy efficiency in children with atopic dermatitis

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Consenso español para el tratamiento de los tumores nasosinusales

Publication date: Available online 1 November 2016
Source:Acta Otorrinolaringológica Española
Author(s): Fernando López, Juan José Grau, José Antonio Medina, Isam Alobid
Los tumores nasosinusales son neoplasias poco frecuentes. Su epidemiología, histopatología y características clínicas son diferentes a las del resto de neoplasias malignas de cabeza y cuello. El diagnóstico y tratamiento de estos tumores plantea diversos desafíos debido a su escasa incidencia, su diversidad histológica, la producción de sintomatología inespecífica en los estadios precoces y por tener un pronóstico variable en función de su histología, lugar de origen y estadificación. Su localización centrofacial y la proximidad de estructuras como la órbita y la base del cráneo hacen que su tratamiento sea difícil y complejo, conllevando una elevada morbimortalidad. La cirugía seguida de radioterapia es el tratamiento de elección en la mayor parte de los casos. Para conseguir unos buenos resultados se requiere de equipos multidisciplinares altamente especializados. En este artículo se expone un protocolo de consenso para el tratamiento de los tumores nasosinusales realizado por la Sociedad Española de Otorrinolaringología en colaboración con la Sociedad Española de Oncología Médica y la Sociedad Española de Oncología Radioterápica.Sinonasal tumors are rare neoplasms with distinctive clinical, aetiological and pathological features. The diagnosis and treatment of these tumours is challenging because of their low incidence, histological diversity and production of non-specific symptoms in the early stages. They have a variable prognosis depending on their histology, origin and staging. Their location, close to neurocritical structures, which are of special relevance to surgery and postoperative treatment, makes their treatment difficult and complex, leading to high morbidity and mortality. Surgery followed by radiotherapy is the mainstay of treatment. To provide the best possible care, patients with sinonasal cancer should be treated in clinical referral centres specializing in skull-base pathologies. Such centres should include a multidisciplinary team led by otolaryngologist surgeons. This article outlines a consensus protocol for the management of these tumours devised by the Spanish Society of Otolaryngology in collaboration with the Spanish Society of Medical Oncology and the Spanish Society for Radiation Oncology.



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Is there a role for regenerative medicine in chronic rhinosinusitis with nasal polyps?

Publication date: Available online 2 November 2016
Source:Brazilian Journal of Otorhinolaryngology
Author(s): Fabiana C.P. Valera, Leandra M. Endam, Badr Ibrahim, Emmanuelle Brochiero, Martin Y. Desrosiers




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Frequency of inadequate neuromuscular blockade during general anesthesia

We used electronic health record data to define frequency of inadequate intraoperative neuromuscular blockade (NMB).

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The effect of play distraction on anxiety before premedication administration: a randomized trial

The majority of children scheduled to undergo surgery experience substantial anxiety in the preoperative holding area before induction of anesthesia. Pharmacological interventions aimed at reducing perioperative anxiety are paradoxically a source of stress for children themselves. Midazolam is frequently used as premedication, and the formula of this drug in Turkey is bitter. We aimed to assess the role of distraction in the form of playing with play dough (Play-Doh) on reducing premedication anxiety in children.

http://ift.tt/2eWau2D

An effective compromise between cost and referral rate: A sequential hearing screening protocol using TEOAEs and AABRs for healthy newborns

Publication date: December 2016
Source:International Journal of Pediatric Otorhinolaryngology, Volume 91
Author(s): Yingying Shang, Wenyang Hao, Zhiqiang Gao, Chunxiao Xu, Ying Ru, Daofeng Ni
ObjectiveThis study evaluated the efficacy of a sequential hearing screening protocol using transient evoked otoacoustic emission (TEOAE) and automated auditory brainstem response (AABR) tests in healthy newborns.DesignA TEOAE screening was performed during the first 48–72 h of life. If the infants failed, an AABR test was performed at the same time, and they were referred for a TEOAE rescreening at six weeks old. The results of screening Protocol 1 (only TEOAE) were compared with those of screening Protocol 2 (sequential TEOAE + AABR screenings for the first screening and TEOAE for the rescreening).Study sampleA total of 1062 healthy newborns were enrolled in this research.ResultsFor Protocol 1, the first screening and rescreening referral rates were 11.1% and 2.2%, respectively. In contrast, for Protocol 2, the referral rates were significant lower at 3.8% and 0.9%, respectively. Using the two protocols, six infants were diagnosed with hearing loss (0.57%).ConclusionsAdding simultaneous AABR tests for infants who fail TEOAE testing at the first screening stage can significantly reduce referral rates without increasing misdiagnosis rates. Although this sequential screening process involves slightly more time and has a higher cost than TEOAE alone, its greater accuracy compensates for this difference.



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Development of the maxillary sinus in infants and children

Publication date: December 2016
Source:International Journal of Pediatric Otorhinolaryngology, Volume 91
Author(s): Bharat Bhushan, Karen Rychlik, James W. Schroeder
ObjectiveTo examine the age related volume change of the maxillary sinus in children by measuring the change of the height, weight, and depth using computed tomography (CT).MethodsChildren <18 years of age who underwent a CT Scan of the sinuses for reasons other than sinus related issues were included in the study.Results139 patients were included (68 females and 71 Males) and the mean age of the patients was 9.6 ± 5.4 years. The cohort was divided into three groups based on their ages – Age <6 years (n = 45), age between 6 and 12 years (n = 44) and age > 12 years (n = 50). Patients in each age group demonstrated an increase in their Maxillary sinus height (p<0.001). Patients < 6years of age and between 6 and 12 years of age had a significant increase in their maxillary sinus width and depth (p < 0.001). The maxillary sinus width, depth and volume did not increase significantly after the age of 12 years in these patients.ConclusionWe demonstrated periods of significant size increase of the maxillary sinuses as determined by different dimensions in children at various ages. The height of the maxillary sinus has steady growth from birth to at least the age of 18 years. The width and depth increase up to 12 years of age.



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BRAF/MEK and PD-1 Inhibition Tied to Better Overall Survival in Advanced Melanoma

BRAF/MEK and PD-1 inhibition significantly improves overall survival compared with other treatments for patients with advanced BRAF-mutated melanoma, Canada-based researchers say.
Reuters Health Information

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Abametapir Kills Lice and Eggs in Phase 3 Trials

An experimental treatment kills head lice after only one application and, unlike currently available treatments, also kills their eggs, according to new research.
Medscape Medical News

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Epistaxis grading in Osler's disease: comparison of comprehensive scores with detailed bleeding diaries

Background

Use of reliable grading scores to measure epistaxis severity in hereditary hemorrhagic telangiectasia (HHT) is essential in clinical routine and for scientific purposes. For practical reasons, visual analog scale (VAS) scoring and the Epistaxis Severity Score (ESS) are widely used. VAS scores are purely subjective, and a potential shortcoming of the ESS is that it is based on self-reported anamnestic bleeding data. The aim of this study was to validate the level of correlation between VAS scores, the ESS, and actual bleeding events, based on detailed epistaxis diaries of patients.

Methods

Records from daily epistaxis diaries maintained by 16 HHT patients over 112 consecutive days were compared with the monthly ESS and daily VAS scores in the corresponding time period. The Spearman rank correlation coefficient, analysis of variance models, and multiple R² measures were used for statistical analysis.

Results

Although the ESS and VAS scores generally showed a high degree of correlation with actual bleeding events, mild events were underrepresented in both scores.

Conclusions

Our results highlight the usefulness of the ESS as a standard epistaxis score in cohorts with moderate to severe degrees of epistaxis. The use of detailed epistaxis diaries should be considered when monitoring patients and cohorts with mild forms of HHT.

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Effect of posture and extracranial contamination on results of cerebral oximetry by near-infrared spectroscopy

Abstract

Background

Near-infrared spectroscopy (NIRS)-based cerebral oximetry is a noninvasive technology used to estimate regional cerebral oxygen saturation (rSO₂). Extracranial blood flow is known to substantially affect rSO₂ values measured by most clinically available devices. Several studies have also reported that the Trendelenburg position and upright position have a larger effect on rSO₂ measurements than the supine position. Therefore, we investigated the effect of these two positions (the Trendelenburg position versus the upright position) and extracranial contamination on rSO₂ measurements obtained using two commercially available devices and one prototype device.

Methods

Twelve healthy volunteers were enrolled in the study. They each had three cerebral oximetry devices applied to their forehead (FORE-SIGHT ELITE™, CAS Medical Systems Inc., Branford, CT, USA; INVOS 5100c™, Medtronic, Minneapolis, MN, USA; and NIRO-TRS, Hamamatsu Photonics, Hamamatsu, Japan). A circumferential pneumatic head cuff was positioned proximal to the NIRS cerebral oximetry sensors. We measured rSO₂, heart rate (HR), and blood pressure (BP) in six conditions (supine, Trendelenburg and upright positions, with and without scalp ischemia induced by head cuff inflation) every 5 min with each oximetry device. Total hemoglobin (tHb), which is associated with cerebral blood volume (CBV) as measured by positron emission tomography, was measured using the NIRO-TRS device to determine extracranial blood volume in each position.

Results

Measurements of rSO₂ with all the devices were affected by extracranial contamination. The percentage of extracranial contamination was highest with INVOS 5100c™ in the upright position (INVOS, 21.3%; FORE-SIGHT, 14.3%; NIRO-TRS, 3.6%). Measurements of rSO₂ obtained in the upright position were significantly lower than those obtained in the supine position, using INVOS-5100c™ and FORE-SIGHT ELITE™ (71 vs. 74% and 67 vs. 72%, respectively), but not using NIRO-TRS (62 vs. 64%). A significant decrease in tHb was observed after head cuff inflation in the supine and Trendelenburg positions (supine, 0.132–0.123 μmol/l; Trendelenburg, 0.133–0.125 μmol/l).

Conclusions

Except when using NIRO-TRS, measurements of rSO₂ in the forehead are significantly lower when measured in the upright position than in the supine position. All devices in this study were affected by extracranial contamination.

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Role of CD8+ T Cells in the Selection of HIV-1 Immune Escape Mutations

Viral Immunology , Vol. 0, No. 0.


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Symptomatic enlarged fabella

Description

A male patient aged 20 years presented to our outpatient department reporting of a 2-year history of right knee discomfort associated with snapping episodes, especially when moving from a seated to a standing position. His medical history was unremarkable and there was no history of trauma. The oblique radiograph of the knee revealed a large ossified structure at the posterolateral corner (figure 1). Routine blood tests, erythrocyte sedimentation rate and C reactive protein were within normal limits. MRI of the knee showed the large ossified structure within the lateral head of the gastrocnemius, while the rest of the examination was normal (figure 2). The tendon of the lateral head of the gastrocnemius attached to its posterior aspect and the anterior surface articulated with the lateral femoral condyle. Based on the location and anatomical characteristics, the structure was identified as a fabella and its large...

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Large schwannoma of the sciatic nerve

Description

A 40-year-old woman was referred with an 8-month history of fullness of the right posterior thigh. This was associated with pain, primarily on sitting and occasional radicular pain down the ipsilateral leg. On examination a mobile, firm lump was identified that was tender to palpate and which also elicited a shooting pain down the leg on examination. MRI demonstrated a well-defined multiloculated mass 9 cmsx6 cms which appeared to arise from the sciatic nerve, raising suspicion for a schwannoma (figure 1). A biopsy confirmed the diagnosis of schwannoma. Surgical excision was undertaken, carefully dissecting the lesion from the sciatic nerve (figure 2). The patient had an uneventful postoperative recovery without neurovascular deficits.

Figure 1

A coronal (A) and axial (B) T1-weighted MRI of a well-defined multiloculated mass 9 cmsx6 cms arising from the sciatic nerve.

Figure 2

Schwannoma lesion excised en...

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Abdominal tuberculosis: an old disease surprising young doctors

Tuberculosis remains a worldwide public health concern. Atypical extrapulmonary presentations may delay the diagnosis and treatment. We present the case of an adult woman admitted to the emergency department with bowel obstruction. The putative intraoperative diagnostic hypothesis was ovarian cancer with peritoneal dissemination. Histopathological analysis showed a chronic granulomatous inflammatory disease with acid-fast bacilli. The patient was started on an alternative parenteral antituberculosis drug combination until oral feeding was available. Currently, 5 months after surgery, she is asymptomatic. Abdominal tuberculosis is the most frequent extrapulmonary site with a wide range of clinical presentations. Emergency laparotomy may be necessary in patients who present with acute abdomen. Bowel obstruction due to adhesions and strictures is not infrequent. However, tuberculous abdominal cocoon presentation as in our patient is rare. Treatment with parenteral alternative drug regimens for tuberculosis is mandatory until the oral route is available.

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Asymptomatic free-floating vitreous cyst masquerading as cysticercosis

A male patient aged 37 years, referred with the diagnosis of right eye intravitreal cysticercosis, was diagnosed as asymptomatic free-floating vitreous cyst after thorough evaluation. The patient was kept under observation, since baseline visual acuity was unaffected. No change was noted over the period of 6 months.

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Miliary tuberculosis in an immunocompetent male with a fatal outcome

A man aged 33 years, born in Nepal, but resident in the UK for 7 years presented to the emergency department with a 4-day history of general malaise, fever (temperature 38.6°C) and a non-productive cough. His medical history was unremarkable and no high-risk behaviour was identified. Clinical examination confirmed decreased air entry bilaterally with bibasal crackles. He was tachycardic, with a heart rate of 120 bpm. Further investigation with a 12-lead ECG confirmed supraventricular tachycardia (SVT) which was terminated with vagal manoeuvres. His chest radiograph demonstrated left basal consolidation. His white cell count was 11x10⁹/L and his C reactive protein was 43.2 mg/L. His blood cultures revealed no growth. He was diagnosed with community-acquired pneumonia and started treatment with amoxicillin and clarithromycin. 3 days post admission, he was intubated for 24 hours in the Department of Intensive Care Medicine. Further episodes of SVT were observed and an ECHO showed a severely dilated and impaired left ventricle. Further chest radiographs illustrated diffuse consolidation with evidence of pulmonary oedema. HIV serology was negative. He developed transaminitis and thrombocytopenia. An ultrasound scan of his liver showed no obvious liver pathology. He remained tachypnoeic and due to worsening pulmonary oedema and extensive consolidation, he was readmitted to the intensive care unit. A CT abdomen with contrast showed an unusual pattern of lymphadenopathy with disproportionately enlarged coeliac axis nodes (5x7x5 cm) and minor para-aortic adenopathy, suspicious for lymphoma. On inserting his central venous catheter in his right internal jugular vein, pus was inadvertently aspirated from his right neck. Acid alcohol fast bacilli (AAFFB) were isolated from the pus and was subsequently identified as Mycobacterium tuberculosis. He started treatment with antitubercular medication rifater: a combination of rifampicin 720 mg od, isoniazid 300 mg po od and pyrazinamide 1750 mg. In addition, he received ethambutol 1000 mg po od and pyridoxine 5 mg. He developed worsening metabolic acidosis, pH 7.19, loss of respiratory compensation and pancytopenia. Right heart strain was evident on his Focused Intensive Care Echo. He developed an increased oxygen requirement and respiratory distress on the ventilator. An erect chest radiograph showed bilateral pneumothoraces and bronchopleural fistulae. A chest drain was inserted. Following discussion with the Cardiothoracic Surgeons, pleurodesis was not deemed possible. He developed inotropic-dependent shock with worsening lung compliance. As a result of his deteriorating ventilation, acidosis and hyperkalaemia, he started treatment with continuous veno-venous haemofiltration. With a diagnosis of miliary tuberculosis and SVT causing cardiogenic pulmonary oedema, this man sadly died with his family at his bedside 10 weeks following initial hospital presentation.

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Prenatal sonographic diagnosis of Beckwith-Wiedemann syndrome in a fetus with omphalocoele

Description

A 28 years old primigravida was referred to Department of Obstetrics and Gynaecology, King George's Medical University, as 35 weeks pregnancy with polyhydramnious with suspected fetal omphalocoele. The defect was diagnosed at 24 weeks at some external centre and the patient was counselled regarding continuation of pregnancy with postnatal surgical repair of malformation after delivery. The diagnosis of Beckwith-Wiedemann syndrome (BWS) was missed at that time.

Phenotypic presentation of BWS has several variations and low occurrence of multiple abnormalities simultaneously limits the sonograhic detection rate. The genotypic detection is feasible only if the molecular defect is known.

We are submitting images of this fetus which shows a fetus with large abdominal wall defect covered by a wall containing only bowel loops and not the liver (figure 1). Along with it the fetus also shows bilateral enlarged kidneys with a suspicious cystic lesion on upper pole of right kidney...

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Delayed diagnosis of a foreign body in the tongue

Description

A 70 year-old man presented with 1-month history of progressive pain in the tongue after eating fish. The patient stated that he had sought medical care back then, but since no foreign body was found he was discharged with paracetamol. Physical examination revealed a mass located in the middle third of the right edge of the tongue with 1.5 cm of diameter, with mild inflammatory signs.

Contrast-enhanced CT scan of the pharynx revealed the presence of an abscess embedded in the tongue surrounding a radio-opaque foreign body (figure 1). A fish bone was removed surgically by making a 1 cm incision over the mass on the right side of the tongue under general anaesthesia (figure 2). Therapy was complemented with ceftriaxone, clindamycin and methylprednisolone. On 3-month follow-up, the patient had a fully healed tongue with complete regression of the mass and with no neuromuscular sequelae.

...

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Atypical lymphocytic lobular panniculitis: an overlap condition with features of subcutaneous panniculitis-like T-cell lymphoma and lupus profundus

Description

A woman aged 45 years presented for evaluation of skin lesions. She reported an 8–9-year history of occasionally tender, waxing-and-waning skin nodules refractory to dapsone, prednisone and methotrexate. Examination revealed multiple indurated subcutaneous nodules distributed on the upper extremities, with scattered patches of lipoatrophy in areas of nodule regression (figure 1). Her medical history was unremarkable; CBC and CMP were within normal limits, with no history of radiotherapy or evidence of internal organ involvement. She had a positive ANA titre (1:160, speckled), but negative anti-dsDNA, anti-Smith, anti-Ro and anti-La antibodies.

Figure 1

Multiple erythematous subcutaneous nodules distributed over the patient's right arm.

Differential diagnosis included erythema nodosum (EN), erythema induratum of Bazin (EIB), lupus profundus (LP) and cutaneous lymphoma.

Initial wedge biopsy in 2008 disclosed a predominantly lobular panniculitic process with some septal involvement (figure 2A). Broad zones of...

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Active Surveillance of Papillary Thyroid Microcarcinoma

Condition:   Thyroid Cancer, Papillary
Intervention:  
Sponsor:   Dong Jun Lim
Recruiting - verified October 2016

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A Comparative Study of Ultrasound Versus CT Measurement of Tongue and Oral Cavity Size

Condition:   Ultrasound Airway Imaging in Determining the Oral Cavity and Tongue Size
Intervention:   Other: Ultrasound scan
Sponsor:   University Health Network, Toronto
Recruiting - verified October 2016

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Study To Compare Avelumab In Combination With Standard of Care Chemoradiotherapy (SoC CRT) Versus SoC CRT for Definitive Treatment In Patients With Locally Advanced Squamous Cell Carcinoma Of The Head And Neck (JAVELIN HEAD AND NECK 100)

Condition:   Squamous Cell Carcinoma of the Head and Neck
Interventions:   Drug: Avelumab;   Other: Chemoradiation
Sponsor:   Pfizer
Not yet recruiting - verified October 2016

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A Safety Study of SGN-2FF for Patients With Advanced Solid Tumors

Conditions:   Non-small Cell Lung Cancer;   Renal Cell Cancer;   Breast Cancer;   Bladder Cancer;   Head and Neck Cancer;   Colorectal Cancer
Intervention:   Drug: SGN-2FF
Sponsor:   Seattle Genetics, Inc.
Not yet recruiting - verified October 2016

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18F-FDG-PET Guided Dose-Painting With Intensity Modulated Radiotherapy in Oropharyngeal Tumours

Condition:   Oropharyngeal Cancer
Intervention:   Radiation: FDG-PET guided radiation dose escalation
Sponsors:   Guy's and St Thomas' NHS Foundation Trust;   Velindre NHS Trust
Recruiting - verified October 2016

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PET/MR in Radiotherapy for Head and Neck Cancer Pilot

Condition:   Head and Neck Cancer
Intervention:   Other: Imaging
Sponsor:   Guy's and St Thomas' NHS Foundation Trust
Recruiting - verified October 2016

http://ift.tt/2felerw