Metachronous solitary metacarpal bone metastasis from rectal cancer

Abstract

Metachronous solitary metacarpal bone metastasis from rectal cancer has not been reported previously. Here, we describe a 54-year-old woman who underwent abdominoperineal resection for rectal cancer following neoadjuvant chemoradiotherapy. The resected specimen contained adenocarcinoma with no lymph node metastases (Stage II, T3N0M0); no adjuvant chemotherapy was administered. Fifteen months after surgery, the patient presented with pain and swelling of the right thumb. Radiography revealed metacarpal bone destruction, and fluorine-18 fluorodeoxyglucose positron emission tomography showed uptake only in the metacarpal bone. Open biopsy revealed an adenocarcinoma, and a right thumb resection was performed. Histological examination indicated features of adenocarcinoma similar to the findings of a rectal lesion, leading to a diagnosis of metachronous solitary metacarpal bone metastasis from rectal cancer. The patient remains free of disease after 6 years of follow-up. Our findings suggest that surgical resection may lead to favorable outcomes in patients with resectable solitary bone metastases.

http://ift.tt/2o8m3tP

Novel technique using a bioabsorbable prosthesis with fibrin glue fixation to prevent a Petersen’s space hernia

Abstract

Introduction

Laparoscopic Roux-en-Y gastric bypass is a bariatric operation that is effective for long-term weight loss. Although rare, one serious complication is an internal hernia through Petersen's space, which may result in bowel strangulation. Although the incidence of internal hernia can be reduced through closing the Petersen's defect, it does not eliminate the risk. This case describes a novel and reliable method to close Petersen's defect. We report the case of a 30-year-old female who underwent a laparoscopic Roux-en-Y gastric bypass for the management of morbid obesity. Following her Roux-en-Y reconstruction, a prosthetic bioabsorbable mesh was placed in Petersen's space and reinforced with fibrin glue to prevent internal herniation through Petersen's defect. The use of a bioabsorbable mesh in Petersen's space is a novel and easy technique that could be used to reduce the incidence of an internal hernia through Petersen's defect.

http://ift.tt/2o8m1Cd

Extra peritoneal giant pelvic hibernoma: a case report

Abstract

Abdominal hibernoma is a rare slow-growing tumor originating from brown adipose tissue. Due to its rarity, only a few case reports have been published so far. Pelvic localization is anedoctal and preoperative differential diagnosis with other malignancies may be challenging. We present the case of a woman who, due to a lower abdominal pain, underwent an abdominal ultrasonography with diagnosis of a 15 cm hyperechogenous pelvic mass. A subsequent MRI showed a 16 × 5.8 × 7.8 cm³ lesion anterior to the left iliacus muscle, with an intra- and extrapelvic component longitudinally extending from the left anterior superior iliac spine until the lesser trochanter. Surgical resection was performed and final histopathology was consistent with hibernoma. This report emphasizes the necessity to include hibernoma among differential diagnosis when a retroperitoneal abdominal mass is diagnosed and the difficulty to perform preoperatively this diagnosis due to the extreme rarity of these neoplasms.

http://ift.tt/2o8Q7oX

Phyllodes tumor masquerading as a fungating breast mass

Abstract

Phyllodes tumor of the breast is an uncommonly encountered disease. The tumor presenting as fungating breast mass or 'ruptured' breast is an even more rare presentation of an unusual disease. This report documents the case of a 60-year-old female with delayed presentation of a large exophytic mass of the left breast. Biopsy of this lesion was non-diagnostic, so excision via left total mastectomy was performed. The final pathology was consistent with malignant phyllodes tumor. This report highlights the features of a rare breast cancer, the challenges in obtaining a definitive diagnosis, and the treatment of this disease, in an effort to provide clinicians with an example of the management of such a peculiar entity.

http://ift.tt/2o8qCEo

Pulmonary Mycobacterium Avium-Intracellulare Complex Infection in an Infant: A Silent and Coincidental Finding

Pediatric Allergy, Immunology, and Pulmonology Dec 2017, Vol. 30, No. 4: 257-259.


http://ift.tt/2yvwXtC

Comparison of Blood Eosinophil Numbers Between Acute Asthma and Stable Disease in Children with Preschool Wheeze

Pediatric Allergy, Immunology, and Pulmonology Dec 2017, Vol. 30, No. 4: 210-217.


http://ift.tt/2AJwvxG

Personalized Medicine in Preschool Children with Asthma

Pediatric Allergy, Immunology, and Pulmonology Dec 2017, Vol. 30, No. 4: 260-262.


http://ift.tt/2yvv5kg

Cocaine-induced pseudo-Wellens syndrome: a Wellens phenocopy

Wellens' syndrome represents critical occlusion of the proximal left anterior descending coronary artery. Electrocardiographic changes similar to Wellens' wave are not exceptional to acute coronary occlusion and can also be seen in cardiac and non-cardiac conditions, such as left ventricular hypertrophy, persistent juvenile T wave, bundle branch blocks, cerebral haemorrhage, pulmonary oedema, pulmonary embolism, pheochromocytoma, Takotsubo syndrome, digitalis and cocaine-induced coronary vasospasm. Cocaine-induced pseudo-Wellens' syndrome should be considered as one of the differentials, since cocaine is used frequently by young adults and can cause left anterior descending coronary vasospasm mimicking Wellens' syndrome. Initiation of the beta-blocking agent in pseudo-Wellens' syndrome as a part of acute coronary syndrome management can be disastrous. We illustrated a case of cocaine-induced pseudo-Wellens' syndrome presented with typical chest pain associated with Wellenoid ECG.

http://ift.tt/2CbVpCa

Iatrogenic propagation of coronary dissection during diagnostic coronary angiography: an uncommon but important procedural consideration

Spontaneous coronary artery dissection is an uncommon cause of acute myocardial infarction in the general population but is relatively more common in the peripartum period. Regardless of clinical setting, the management strategy is individualised, ranging from conservative to invasive. We report a case of peripartum myocardial infarction due to spontaneous coronary dissection that propagated during diagnostic angiography and ultimately required emergent bypass surgery.

http://ift.tt/2B36k23

Congenital scoliosis: an anomalous association with endosulfan

Endosulfan is an organochlorine pesticide that is used extensively across the world to kill insects. Incidence of acute and chronic toxicity with endosulfan poisoning has been reported, and nearly 80 countries have banned its use. However, it is still being used in many low-income/middle-income countries. One of the most severe tragedies because of endosulfan poisoning has taken place in the Indian state of Kerala due to persistent aerial spraying of endosulfan. Even though there are reports of skeletal and other congenital abnormalities in humans and experimental animals following exposure to endosulfan, very few have been documented. We report two cases of congenital scoliosis in siblings living in a community affected by high levels of endosulfan in the environment. High index of suspicion is essential during the screening of school children exposed to endosulfan. Congenital scoliosis is a progressive deformity that leads to severe disability, unless detected and corrected at an early stage.

http://ift.tt/2C8sMGk

Stent extrusion on the external surface of the transplanted kidney: unusual occurrence

Here we present the case of a 40-year-old man, who underwent deceased donor renal transplantation. Towards the end of this operation, open-ended double J stent was inserted in the transplanted kidney. Modified Lich–Gregoir ureterovesical anastomosis was performed. Prior to the abdominal closure, it was discovered that proximal end of the stent had pierced the renal parenchyma and extruded on the external surface of the transplanted kidney. We contemplated removing the stent and reinserting it but decided against that due to various reasons. The stent was left as such. The patient was managed conservatively with satisfactory outcome in the postoperative period. To the best of our knowledge, this is first such report of conservative management of stent extrusion in transplanted kidney in the literature.

http://ift.tt/2B2tPIl

Periosteal desmoid tumour: a rare finding in the oral cavity

A 55-year-old female patient reported with an intraoral well-localised asymptomatic swelling on the right side of the mandible in relation to the right mandibular first molar along with a history of trauma 6 months back. Panoramic radiograph revealed normal trabecular bone pattern in relation to the lesion. The lesion was excised along with the associated buccal cortical plate and tooth. The microscopic examination revealed a well-circumscribed lesion consisting of spindle cells arranged in storiform pattern associated with the buccal cortical plate. The key feature to note was presence of reactive periosteum, which was in continuum with the lesion. Immunohistochemistry (IHC) revealed faint nuclear positivity for β-catenin. The above findings led to our diagnosis of periosteal desmoid, which is rarely reported in the head-and-neck region. The major challenge in the diagnosis of such lesions is good clinicopathological correlation as the differential diagnosis of spindle-cell lesions is vast and needs IHC confirmation.

http://ift.tt/2C9jaLk

Left ventricular pseudoaneurysm formation in a patient presenting with a subacute myocardial infarction

Left ventricular pseudoaneurysm is a rare mechanical complication of acute myocardial infarction. In the present case, an 80-year-old man presenting with a subacute non-ST segment elevation myocardial infarction was found to have an occluded second obtuse marginal branch of the left circumflex coronary artery. Following the implantation of two drug-eluting stents, the patient developed no-reflow phenomenon. Coronary angiography 6 weeks later revealed persistence of the no-reflow phenomenon. During the left ventriculogram, a massive pseudoaneurysm was diagnosed and the patient successfully underwent emergency surgery. The persistence of no-reflow was likely due to the fact that the myocardial territory supplied by the infarct-related artery was completely necrosed resulting in persistent flow impairment through the vessel.

http://ift.tt/2B35Fh3

Pneumatosis intestinalis with extensive intrahepatic portal venous gas secondary to intra-abdominal sepsis: a rare occurrence

Description

A 32-year-old man presented with a 3-day history of abdominal pain, vomiting and diarrhoea. He was afebrile and haemodynamically stable (saturating at 97% on air with a respiratory rate of 15, his blood pressure was 117/65 with a heart rate of 78 bpm). Clinical examination revealed right iliac fossa tenderness with localised guarding. His inflammatory markers were raised (white cell count 21 x10⁹/L , neutrophils 16 and C-reactive protein 26). He was diagnosed with acute appendicitis and had an emergency open appendectomy. The operative findings were a periappendicular mass with a necrotic tip of appendix and pus within the abdomen.

Unfortunately he had a complex postoperative course. He developed paralytic ileus by day 3 and was managed conservatively via insertion of a nasogastric tube, rehydration with intravenous fluid and correction of his electrolyte imbalance. By day 6 he became febrile (39°), increasingly short of breath with a grossly distended non-tender...

http://ift.tt/2B2P0di

Sarcoidosis-lymphoma syndrome: a diagnostic dilemma

Sarcoidosis and lymphoma are generally thought of as being two mutually exclusive diseases that need to be considered in the differential diagnosis of patients with hilar/mediastianal lymphadenopathy. However, there are rare patients in whom both of these diseases coexist. These patients constitute a diagnostic challenge because their presentation (ie, clinical symptoms, imaging abnormalities and even pathology) may all be atypical when each individual disease is considered separately. In this report, we describe a patient who presented with such atypical features and was eventually diagnosed as having both sarcoidosis and a B-cell lymphoma with features of splenic marginal zone lymphoma (SMZL) simultaneously. To our knowledge, this is only the second reported case of SMZL and sarcoidosis in the same patient.

http://ift.tt/2Ca6wM9

Table of Contents

Publication date: January–February 2018
Source:American Journal of Otolaryngology, Volume 39, Issue 1





http://ift.tt/2C9dn8G

Guidelines for Contributing Authors

Publication date: January–February 2018
Source:American Journal of Otolaryngology, Volume 39, Issue 1





http://ift.tt/2B35Vwz

Editorial Board

Publication date: January–February 2018
Source:American Journal of Otolaryngology, Volume 39, Issue 1





http://ift.tt/2C9pdzp

Voice and swallowing outcomes following hypoglossal nerve stimulation for obstructive sleep apnea

Publication date: Available online 15 December 2017
Source:American Journal of Otolaryngology
Author(s): Andrew J. Bowen, Amy S. Nowacki, Alan H. Kominsky, Douglas K. Trask, Michael S. Benninger, Paul C. Bryson
ObjectiveHypoglossal nerve stimulation is an effective treatment for a subset of patients with Obstructive Sleep Apnea (OSA). Although multiple clinical trials demonstrate its efficacy, no previous literature explores the potential impact the stimulator has on swallowing and voice. Our primary objective is to evaluate patient reported post-operative changes in voice or swallowing following hypoglossal nerve stimulator placement.Study designProspective cohort study.SettingTertiary care hospital.Subject and methodsPatients scheduled to receive a hypoglossal stimulator were enrolled. Participants completed baseline Voice Handicap Index-10 (VHI-10) and Eating Assessment Tool-10 (EAT-10) questionnaires preoperatively and again at 1week, 3months, and 6months post-operatively following placement of a hypoglossal nerve stimulator.Results9 males and 5 females completed the study. The mean pre-operative VHI-10 and EAT-10 score was 3 and 0.8 respectively. Using linear mixed models, a clinically and statistically significant increase in the mean EAT-10 score was observed post-operatively at 1week (p=0.007), which was not observed at the time points the stimulator was active. A clinically and statistically significant decrease in VHI-10 score was observed following 2months of active stimulator use (p=0.02), which was not observed at any other time point.ConclusionThe implantation and use of the hypoglossal nerve stimulator over 5months did not demonstrate any sustained, patient reported changes in voice handicap and swallowing function. While larger studies are warranted, our findings can be used to provide further informed consent for hypoglossal nerve stimulator implantation.



http://ift.tt/2B43f1G

A novel method to measure the external auditory canal: Normative data and practical implications

Publication date: Available online 14 December 2017
Source:American Journal of Otolaryngology
Author(s): Jason Barnes, Roy T. Sabo, Daniel H. Coelho
PurposeTo accurately measure external auditory canal (EAC) dimensions by high resolution computed tomography (CT), and compare results with a traditional method of EAC measurement.MethodsUsing an advanced multidimensional open source digital imaging and communications in medicine (DICOM) analysis program (OsiriX, Pixmeo, Geneva, Switzerland) 91 adult EACs were analyzed on a previously obtained temporal bone CT scan. Tympanometric data were also recorded for each ear. The methods were compared using a linear mixed effect model.ResultsEAC volume was compared between tympanometrically calculated volumes and CT measured volumes. It was found that CT measured volumes are, on average, smaller (1.12cm³, SE=0.04) than tympanometry volumes (1.27cm³, SE=0.04cm³). There was a significant difference in CT measured volume between genders (p=0.0125), with males having larger measured volumes (1.23cm³, SD=0.28cm³) than females (1.06cm³, SD=0.20cm³). There was a significant difference in average circumference between ear laterality (p=0.0071), with the right ear having a slightly larger average circumference (2.49cm, SD=0.23cm) than the left ear (2.44cm, SD=0.50cm).There was also a significant difference in minimum circumference between age groups (p=0.0448), with patients younger than 60years having larger minimum circumferences (1.89cm, SD=0.21cm) than older patients (1.78cm, SD=0.25cm).ConclusionsThis study demonstrates that CT analysis can provide more information about EAC dimensions than traditional techniques. Moreover, slight but statistically significant differences are associated with age, gender and laterality. Accurate estimation of EAC dimensions is important for the development of hearing aids and personal protective equipment and can also be helpful for surgical planning, specifically otoendoscopy. Future research will focus on simplifying computation, developing cross-cultural cohort comparisons, and application to otoendoscopic procedures.



http://ift.tt/2Ca4sE1

Future Meetings

Thyroid Dec 2017, Vol. 27, No. 12: 1586-1586.


http://ift.tt/2zdUu5G

Iodized Salt Intake and Its Association with Urinary Iodine, Thyroid Peroxidase Antibodies, and Thyroglobulin Antibodies Among Urban Chinese

Thyroid Dec 2017, Vol. 27, No. 12: 1566-1573.


http://ift.tt/2j50WDq

Validation of Three Scoring Risk-Stratification Models for Thyroid Nodules

Thyroid Dec 2017, Vol. 27, No. 12: 1550-1557.


http://ift.tt/2zdC3xS

Diastolic Dysfunction is Common in Survivors of Pediatric Differentiated Thyroid Carcinoma

Thyroid Dec 2017, Vol. 27, No. 12: 1481-1489.


http://ift.tt/2j4qZuj

Reduced Retinoblastoma Protein Expression Is Associated with Decreased Patient Survival in Medullary Thyroid Cancer

Thyroid Dec 2017, Vol. 27, No. 12: 1523-1533.


http://ift.tt/2ze9Qar

Urinary Iodine, Perchlorate, and Thiocyanate Concentrations in U.S. Lactating Women

Thyroid Dec 2017, Vol. 27, No. 12: 1574-1581.


http://ift.tt/2j2TKHC

Death by Suicide in Graves' Disease and Graves' Orbitopathy: A Nationwide Danish Register Study

Thyroid Dec 2017, Vol. 27, No. 12: 1475-1480.


http://ift.tt/2zdeKob

Laboratory Services for Managing Thyroid Disease: Different and Common Viewpoints of American Thyroid Association Members and of Members of the Endocrine Division of the American Association for Clinical Chemistry

Thyroid Dec 2017, Vol. 27, No. 12: 1583-1585.


http://ift.tt/2j4P2cG

Individualizing Surgery in Papillary Thyroid Carcinoma Based on a Detailed Sonographic Assessment of Extrathyroidal Extension

Thyroid Dec 2017, Vol. 27, No. 12: 1544-1549.


http://ift.tt/2zddwJu

Clinical Characteristics and Outcomes of Propylthiouracil-Induced Antineutrophil Cytoplasmic Antibody-Associated Vasculitis in Patients with Graves' Disease: A Median 38-Month Retrospective Cohort Study from a Single Institution in China

Thyroid Dec 2017, Vol. 27, No. 12: 1469-1474.


http://ift.tt/2j6Q5ZF

Selected Radiation Safety Aspects Including Transportation and Lodging After Outpatient 131I Therapy for Differentiated Thyroid Cancer

Thyroid Dec 2017, Vol. 27, No. 12: 1558-1565.


http://ift.tt/2j4OSC6

Chronic nasal dysfunction

Publication date: Available online 14 December 2017
Source:European Annals of Otorhinolaryngology, Head and Neck Diseases
Author(s): R. Jankowski, D.T. Nguyen, A. Russel, B. Toussaint, P. Gallet, C. Rumeau
Chronic nasal dysfunction is a clinical concept in the diagnostic and therapeutic management of sinonasal diseases, based on the evo-devo theory of formation of the nose according to which the nose is not a single organ but rather an association of three organs: olfactory nose, respiratory nose and paranasal sinuses. In chronic nasal dysfunction theory, etiological diagnosis takes account of the possible pathophysiological independence of nasal symptoms, in accordance with the different origins and physiology of the three organs constituting the nose. The diagnostic approach of the chronic nasal dysfunction concept breaks down the pathology so as to propose treatment(s) adapted to the diseased organ(s) and to the capacity for physiological resolution of dysfunction induced in one organ by pathology in a neighboring nasal organ. The ethmoid is not a sinus according to evo-devo, and therefore functional endoscopic endonasal surgery (FEES) cannot be restricted to functional endoscopic sinus surgery (FESS). Evo-devo theory and the chronic nasal dysfunction concept offer an alternative to the concept of chronic rhinosinusitis with or without polyps for the management of sinonasal diseases.



http://ift.tt/2ApTGsx

The neonatal window of opportunity – early priming for life

Publication date: Available online 14 December 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Harald Renz, Becky D. Adkins, Sina Bartfeld, Richard S. Blumberg, Donna L. Farber, Johan Garssen, Peter Ghazal, David J. Hackam, Benjamin J. Marsland, Kathy D. McCoy, John Penders, Immo Prinz, Valerie Verhasselt, Erika von Mutius, Jeffrey N. Weiser, Duane R. Wesemann, Mathias W. Hornef
The concept of the neonatal window of opportunity assigns the early postnatal period a critical role for life-long host-microbial and immune homeostasis. It is supported by epidemiological evidence that links postnatal environmental exposure with disease susceptibility and mechanisms in the neonate host that facilitate the postnatal transposition, establish a stable microbiome and promote immune maturation. During the conference on "The neonatal window of opportunity – early priming for life", postnatal microbiome and immune maturation, epidemiological evidence and fundamental mechanisms were discussed to identify new targets for future preventive and interventional measures.



http://ift.tt/2AqURrE

Multifaceted roles of basophils in health and disease

Publication date: Available online 14 December 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Hajime Karasuyama, Kensuke Miyake, Soichiro Yoshikawa, Yoshinori Yamanishi
Until recently, basophils had often been neglected in immunological studies because of their minority status among immune cells, or confused with tissue-resident mast cells due to some phenotypic similarities between them in spite of different anatomical localization. It is now appreciated that basophils and mast cells are distinct cell lineages, and that basophils play important and non-redundant roles distinct from those played by mast cells. On the one hand, basophils contribute beneficially to protective immunity, particularly against parasitic infections. On the other hand, basophils are involved in the development of various disorders, including allergy and autoimmune disease. Basophils interact with other immune cells and non-hematopoietic cells through cell to cell contact or basophil-derived factors such as cytokines and proteases, contributing to the regulation of immune and allergic responses. In this review article, we highlight recent advances in our understanding of basophil pathophysiology in humans and animal models by consolidating research findings reported during the past five years. Further studies on basophils and their products will help identify suitable targets for novel therapeutics in allergy and effective vaccines against parasitic infection.



http://ift.tt/2BoSt8B

S1PR5 is essential for human NK cell migration towards sphingosine-1 phosphate

Publication date: Available online 14 December 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Annabelle Drouillard, Anne-Laure Mathieu, Antoine Marçais, Alexandre Belot, Sébastien Viel, Michaël Mingueneau, Kevin Guckian, Thierry Walzer




http://ift.tt/2AqUQnA

Isotype-Specific Agglutination-PCR (ISAP): a sensitive and multiplex method for measuring allergen-specific IgE

Publication date: Available online 14 December 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Cheng-ting Tsai, Kaori Mukai, Peter V. Robinson, Melissa A. Gray, Malika B. Waschmann, Shu-Chen Lyu, Mindy Tsai, Rebecca S. Chinthrajah, Kari C. Nadeau, Carolyn R. Bertozzi, Stephen J. Galli




http://ift.tt/2BqFJyn

TNFAIP3/A20 acts as master switch in TNFα blockade-driven IL-17A expression

Publication date: Available online 14 December 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Paulo CM. Urbano, Raúl Aguirre-Gamboa, Angel Ashikov, Bennie van Heeswijk, Anja Krippner-Heidenreich, Henk Tijssen, Yang Li, Valderilio F. Azevedo, Lisa JT. Smits, Frank Hoentjen, Irma Joosten, Hans JPM. Koenen
BackgroundAnti-TNF inhibitors successfully improve life quality of patients suffering from inflammatory disease. Unfortunately, not all patients respond to anti-TNF therapy and some patients show paradoxical immune side-effects, which is poorly understood. Surprisingly, anti-TNF agents were shown to promote IL-17A production, with as yet unknown clinical implications.ObjectiveTo investigate the molecular mechanism underlying anti-TNF driven IL-17A expression and the clinical implications of this phenomenon.MethodsFACS, RNA-sequencing, RT-qPCR, western blotting, siRNA interference and kinase-inhibitors, were used to study the molecular mechanism in isolated human CD4⁺ T cells from healthy donors. The clinical implication was studied in blood samples of inflammatory bowel disease (IBD) patients under anti-TNF therapy.ResultsHere we show that anti-TNF treatment results in inhibition of the anti-inflammatory molecule TNFAIP3/A20 in memory CD4⁺ T cells. We found an inverse relationship between TNFAIP3/A20 expression levels and IL-17A production. Inhibition of TNFAIP3/A20 promotes kinase activity of p38-MAPK and PKC, which drives IL-17A expression. Regulation of TNFAIP3/A20 expression and cognate IL-17A production in T cells is specifically mediated via TNFR2-signaling. Ex vivo, in IBD patients treated with anti-TNF, we found further evidence for an inverse relationship between TNFAIP3/A20 expression levels and IL-17A producing T cells.ConclusionAnti-TNF treatment interferes in the TNFAIP3/A20 mediated anti-inflammatory feedback-loop in CD4⁺ T cells and promotes kinase activity. This puts TNFAIP3/A20, combined with IL-17A expression, on the map as a potential tool in predicting therapy responsiveness or side effects of anti-TNF therapy. Moreover, it provides novel targets, related to TNFAIP3/A20 activity, for superior therapeutic regimens in IBD patients.



http://ift.tt/2AqFX4I

Airway exposure initiates peanut allergy by involving the IL-1 pathway and T follicular helper cells in mice

Publication date: Available online 14 December 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Joseph J. Dolence, Takao Kobayashi, Koji Iijima, James Krempski, Li Y. Drake, Alexander L. Dent, Hirohito Kita
BackgroundLittle is currently known regarding the immunological mechanism(s) that initiate peanut allergy. Notably, peanut proteins have been detected in house dust, and their levels correlate with peanut allergy prevalence.ObjectiveThis study aimed to develop a new mouse model for peanut allergy and to investigate the immunological mechanisms involved in peanut allergen sensitization.MethodsTo mimic environmental exposure, naïve mice were exposed to peanut flour by inhalation for up to 4 weeks. We then analyzed serum levels of IgE antibody and challenged mice with peanut proteins. Immunological mechanisms involved in sensitization were analyzed using cytokine reporter mice, an adoptive cell transfer model, and gene knockout mice.ResultsWhen exposed to peanut flour by inhalation, both BALB/c and C57BL/6 mice developed peanut allergy, as demonstrated by the presence of peanut-specific IgE antibodies and manifestation of acute anaphylaxis upon challenge. A large number of follicular helper T (Tfh) cells were also detected in draining lymph nodes of allergic mice. These cells produced IL-4 and IL-21, and more robustly promoted peanut-specific IgE production than Th2 cells. Genetic depletion of Tfh cells decreased IgE antibody levels and protected mice from anaphylaxis, without affecting Th2 cells. Furthermore, peanut flour exposure increased lung levels of IL-1α and IL-1β, and mice deficient in the receptor for these cytokines showed a significant decrease in Tfh cells compared to wild-type mice.ConclusionTfh cells play a key role in peanut allergy, and the IL-1 pathway is involved in the Tfh response to peanut allergen exposure.

Graphical abstract

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Cytosolic sensing of immuno-stimulatory DNA, the enemy within

Rekha Dhanwani | Mariko Takahashi | Sonia Sharma

http://ift.tt/2yuV4sp

Developmental control of macrophage function

Johnny Bonnardel | Martin Guilliams

http://ift.tt/2AJrQfn

Guidelines for Contributing Authors

http://ift.tt/2AIdcVs

Table of Contents

http://ift.tt/2yuZZJR

Editorial Board

http://ift.tt/2AIdcoq

Adenosquamous Carcinoma of the Tongue

Abstract

A 51-year-old white female presented with a painful ulcer of the left ventrolateral tongue. An incisional biopsy confirmed a diagnosis of adenosquamous carcinoma. The adenosquamous carcinoma is an uncommon malignant tumor with histopathological features of a squamous carcinoma and an adenocarcinoma. A definitive diagnosis requires histopathological examination of a deep biopsy involving the submucosal tissue. This malignant tumor shows aggressive behavior with early invasive growth and a poor prognosis. The histopathological findings and differential diagnosis of a case of adenosquamous carcinoma of the tongue are discussed.

http://ift.tt/2CorKXA

LEF-1 is a Sensitive Marker of Cribriform Morular Variant of Papillary Thyroid Carcinoma

Abstract

Cribriform morular variant of PTC (CMV-PTC) frequently shows activation of the CTNNB1/Wnt pathway with nuclear accumulation of beta catenin. The utility of LEF-1, also in the CTNNB1/WNT pathway, in the diagnosis of CMV-PTC has not been previously studied. LEF-1 immunohistochemistry was performed on seven CMV-PTC, 52 benign cases and 101 malignant thyroid neoplasms. LEF-1 was scored by stain intensity (0 = no nuclear stain, 1 = weak nuclear stain, less than lymphocyte and 2 = strong nuclear stain, intense as lymphocyte) and percentage of positive cells at each intensity, for a maximum total score of 200. Sensitivity and specificity of LEF-1 stain for all cases and to differentiate between regular PTC and CMV-PTC was also calculated. Six of the seven CMV-PTCs showed ≥ 30% strong (2+) nuclear LEF-1 staining and a total score over 100. Beta catenin also showed strong and diffuse nuclear staining in these cases. One CMV-PTC was negative for both LEF-1 and beta catenin and did not have a history of FAP. All control PTC cases uniformly lacked LEF-1 staining at 2+ intensity. LEF-1 had a sensitivity of 86% and specificity of 98% for the diagnosis of CMV-PTC. LEF-1 is highly sensitive and specific marker for CMV-PTC, especially when used in the setting of a PTC neoplasm. The pattern of staining is important with ≥ 30% of cells showing strong 2+ nuclear staining having the highest combined sensitivity and specificity.

http://ift.tt/2o2EZtM

Adenosquamous Carcinoma of the Tongue

Abstract

A 51-year-old white female presented with a painful ulcer of the left ventrolateral tongue. An incisional biopsy confirmed a diagnosis of adenosquamous carcinoma. The adenosquamous carcinoma is an uncommon malignant tumor with histopathological features of a squamous carcinoma and an adenocarcinoma. A definitive diagnosis requires histopathological examination of a deep biopsy involving the submucosal tissue. This malignant tumor shows aggressive behavior with early invasive growth and a poor prognosis. The histopathological findings and differential diagnosis of a case of adenosquamous carcinoma of the tongue are discussed.

http://ift.tt/2CorKXA

LEF-1 is a Sensitive Marker of Cribriform Morular Variant of Papillary Thyroid Carcinoma

Abstract

Cribriform morular variant of PTC (CMV-PTC) frequently shows activation of the CTNNB1/Wnt pathway with nuclear accumulation of beta catenin. The utility of LEF-1, also in the CTNNB1/WNT pathway, in the diagnosis of CMV-PTC has not been previously studied. LEF-1 immunohistochemistry was performed on seven CMV-PTC, 52 benign cases and 101 malignant thyroid neoplasms. LEF-1 was scored by stain intensity (0 = no nuclear stain, 1 = weak nuclear stain, less than lymphocyte and 2 = strong nuclear stain, intense as lymphocyte) and percentage of positive cells at each intensity, for a maximum total score of 200. Sensitivity and specificity of LEF-1 stain for all cases and to differentiate between regular PTC and CMV-PTC was also calculated. Six of the seven CMV-PTCs showed ≥ 30% strong (2+) nuclear LEF-1 staining and a total score over 100. Beta catenin also showed strong and diffuse nuclear staining in these cases. One CMV-PTC was negative for both LEF-1 and beta catenin and did not have a history of FAP. All control PTC cases uniformly lacked LEF-1 staining at 2+ intensity. LEF-1 had a sensitivity of 86% and specificity of 98% for the diagnosis of CMV-PTC. LEF-1 is highly sensitive and specific marker for CMV-PTC, especially when used in the setting of a PTC neoplasm. The pattern of staining is important with ≥ 30% of cells showing strong 2+ nuclear staining having the highest combined sensitivity and specificity.

http://ift.tt/2o2EZtM

Voice and swallowing outcomes following hypoglossal nerve stimulation for obstructive sleep apnea

Hypoglossal nerve stimulation is an effective treatment for a subset of patients with Obstructive Sleep Apnea (OSA). Although multiple clinical trials demonstrate its efficacy, no previous literature explores the potential impact the stimulator has on swallowing and voice. Our primary objective is to evaluate patient reported post-operative changes in voice or swallowing following hypoglossal nerve stimulator placement.

http://ift.tt/2ytUhb6

A novel method to measure the external auditory canal: Normative data and practical implications

To accurately measure external auditory canal (EAC) dimensions by high resolution computed tomography (CT), and compare results with a traditional method of EAC measurement.

http://ift.tt/2AHoY2p

Adenosquamous Carcinoma of the Tongue

Abstract

A 51-year-old white female presented with a painful ulcer of the left ventrolateral tongue. An incisional biopsy confirmed a diagnosis of adenosquamous carcinoma. The adenosquamous carcinoma is an uncommon malignant tumor with histopathological features of a squamous carcinoma and an adenocarcinoma. A definitive diagnosis requires histopathological examination of a deep biopsy involving the submucosal tissue. This malignant tumor shows aggressive behavior with early invasive growth and a poor prognosis. The histopathological findings and differential diagnosis of a case of adenosquamous carcinoma of the tongue are discussed.

http://ift.tt/2CorKXA

LEF-1 is a Sensitive Marker of Cribriform Morular Variant of Papillary Thyroid Carcinoma

Abstract

Cribriform morular variant of PTC (CMV-PTC) frequently shows activation of the CTNNB1/Wnt pathway with nuclear accumulation of beta catenin. The utility of LEF-1, also in the CTNNB1/WNT pathway, in the diagnosis of CMV-PTC has not been previously studied. LEF-1 immunohistochemistry was performed on seven CMV-PTC, 52 benign cases and 101 malignant thyroid neoplasms. LEF-1 was scored by stain intensity (0 = no nuclear stain, 1 = weak nuclear stain, less than lymphocyte and 2 = strong nuclear stain, intense as lymphocyte) and percentage of positive cells at each intensity, for a maximum total score of 200. Sensitivity and specificity of LEF-1 stain for all cases and to differentiate between regular PTC and CMV-PTC was also calculated. Six of the seven CMV-PTCs showed ≥ 30% strong (2+) nuclear LEF-1 staining and a total score over 100. Beta catenin also showed strong and diffuse nuclear staining in these cases. One CMV-PTC was negative for both LEF-1 and beta catenin and did not have a history of FAP. All control PTC cases uniformly lacked LEF-1 staining at 2+ intensity. LEF-1 had a sensitivity of 86% and specificity of 98% for the diagnosis of CMV-PTC. LEF-1 is highly sensitive and specific marker for CMV-PTC, especially when used in the setting of a PTC neoplasm. The pattern of staining is important with ≥ 30% of cells showing strong 2+ nuclear staining having the highest combined sensitivity and specificity.

http://ift.tt/2o2EZtM

T-Cell Inhibitors for Atopic Dermatitis

The management of atopic dermatitis is changing with the development of novel biological agents to target specific molecules in the inflammatory cascade. Dupilumab has proven its ability to act on the IL-4 receptor in treating atopic dermatitis. Thymic stromal lymphopoietin (TSLP) monoclonal antibody (AMG157/ MEDI9929) and OX40 blocking antibody (GBR 830) were developed by target the same pathway as dupilumab. The clinical data on the efficacy for these drugs is not yet known. There is some early evidence that AMG157/ MEDI9929 attenuates most measures of allergen-induced asthmatic responses.

http://ift.tt/2kv8SOf

Monoclonal Antibodies Against IL-13 and IL-31RA in Development for Atopic Dermatitis

The IL-13 and IL-31 cytokines and inflammatory pathways have been identified as important for atopic dermatitis (AD) pathophysiology. Monoclonal antibodies against IL-13 have been studied for the treatment of asthma since 2011. More recently, two phase two trials have been completed with these antibodies in atopic dermatitis treatment. In both trials, significant reductions of Eczema Area and Severity Index (EASI) scores were seen. IL-31 is thought to play a role transmitting itch sensation to the central nervous system, and blocking IL-31 activity reduces itch in atopic dermatitis patients.

http://ift.tt/2CmrTKT

Emerging Therapies for Atopic Dermatitis: Jak Inhibitors

The Janus Kinase-Signal Transducer and Activator of Transcription (JAK-STAT) pathway is a conserved master regulator of immunity and myeloproliferation. Advanced understanding of this pathway has led to development of targeted inhibitors of Janus Kinases (Jakinibs). As a class, Jakinibs effectively treat a multitude of hematologic and inflammatory diseases. Given such success, use of Jakinibs for mitigation of atopic dermatitis is under active investigation. Herein, we review the evolving data on the safety and efficacy of Jakinibs in treatment of atopic dermatitis.

http://ift.tt/2CnAe0S

Phosphodiesterase 4 (PDE4) Inhibitors

Historically, drugs available for treating atopic dermatitis (AD) have been limited to topical corticosteroids (TCS) and topical calcineurin inhibitors (TCI), with systemic immunosuppressants and phototherapy reserved for severe AD. Despite their efficacy, with long term use, these agents have associated safety concerns and limitations. More targeted options with fewer systemic and cutaneous side effects are needed for treating atopic dermatitis. Phosphodiesterase 4 is involved in the regulation of proinflammatory cytokines via the degradation of cAMP.

http://ift.tt/2kujahC

Emerging Therapies for Atopic Dermatitis: The Prostaglandin/Leukotriene Pathway

The role of leukotrienes and prostaglandins in development of atopy has been prototypically established in studies of asthma pathogenesis. Likewise, both in vitro and in vivo studies of atopic dermatitis have demonstrated that these molecules maintain important pathophysiologic roles. Thus, it follows that targeted therapies against these molecules may be promising in management of atopic dermatitis. Montelukast has had questionable efficacy in patients with atopic dermatitis, while small pilots using zileuton did have some clinically significant improvement.

http://ift.tt/2Cm0hpp

New Therapies for Atopic Dermatitis: Additional Treatment Classes

A wide array of miscellaneous agents is being studied for the treatment of atopic dermatitis (AD), including targeted topical, oral systemic and biologic agents.

http://ift.tt/2CicZp3

The Future is Finally Here: Advances in the Treatment of Atopic Dermatitis

http://ift.tt/2ksXh2x

Active Surveillance of Low-Risk Papillary Microcarcinoma of the Thyroid Proposed as First-Line Management

New Rochelle, NY, December 14, 2017—A 10-year study of more than 1,200 patients with low-risk papillary microcarcinoma (PMC) of the thyroid led researchers to conclude that close and continuous monitoring is an acceptable first-line approach to patient management instead of immediate surgery to remove the tumor. The article entitled "Insights into the Management of Papillary Microcarcinoma of the Thyroid" is part of a special section on Japanese Research led by Guest Editor Yoshiharu Murata, Nagoya University, Japan, in the January 2018 issue of Thyroid, a peer-reviewed journal from Mary Ann Liebert, Inc., publishers and the official journal of the American Thyroid Association (ATA). The article is available free on the Thyroid website.

Coauthors Akira Miyauchi, Yasuhiro Ito, and Hitomi Oda, Kuma Hospital, Kobe, Japan, report that in only 8% of patients with PMC evaluated during the study period did the tumor increase in size by 3 mm or more, and only 3.8% of patients had a new metastasis. PMCs were least likely to grow in older patients (60 years of age or older). Furthermore, compared to a management approach of "active surveillance," patients who underwent immediate surgery had significantly higher risks of unfavorable events and more than 4 times the total cost of PMC treatment.

"The seminal observations by the groups from Kuma Hospital and the Cancer Institute Hospital in Tokyo from Japan indicate that the vast majority of papillary thyroid microcarcinomas have an indolent behavior and that active surveillance may be an alternative approach in many patients," says Peter A. Kopp, MD, Editor-in-Chief of Thyroid and Professor of Medicine, Division of Endocrinology, Metabolism, and Molecular Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL. "Similar prospective studies are now underway in other parts of the world. Ultimately, the goal is to avoid unnecessary treatment. The challenge that lies ahead of us is to identify the small group of patients with papillary thyroid microcarcinomas that require active intervention."

About the Journal
Thyroid, the official journal of the American Thyroid Association, is an authoritative peer-reviewed journal published monthly online with open access options and in print. The Journal publishes original articles and timely reviews that reflect the rapidly advancing changes in our understanding of thyroid physiology and pathology, from the molecular biology of the cell to clinical management of thyroid disorders. Complete tables of content and a sample issue may be viewed on the Thyroid website The complete Thyroid Journal Program includes the highly valued abstract and commentary publication Clinical Thyroidology, led by Editor-in-Chief Jerome M. Hershman, MD and published monthly, and the groundbreaking videojournal companion VideoEndocrinology, led by Editor Gerard Doherty, MD and published quarterly. Complete tables of content and sample issues may be viewed on the Thyroid website.

About the Society
The American Thyroid Association (ATA) is the leading worldwide organization dedicated to the advancement, understanding, prevention, diagnosis, and treatment of thyroid disorders and thyroid cancer. ATA is an international membership medical society with over 1,700 members from 43 countries around the world. Celebrating its 94th anniversary, the ATA delivers its mission — of being devoted to thyroid biology and to the prevention and treatment of thyroid disease through excellence in research, clinical care, education, and public health — through several key endeavors: the publication of highly regarded professional journals, Thyroid, Clinical Thyroidology, and VideoEndocrinology; annual scientific meetings; research grant programs for young investigators, biennial clinical and research symposia; support of online professional, public and patient educational programs; and the development of guidelines for clinical management of thyroid disease and thyroid cancer. The ATA promotes thyroid awareness and information through its online Clinical Thyroidology for the Public (distributed free of charge to over 11,000 patients and public subscribers) and extensive, authoritative explanations of thyroid disease and thyroid cancer in both English and Spanish. The ATA website serves as the clinical resource for patients and the public who look for reliable information on the Internet.

About the Publisher
Mary Ann Liebert, Inc., publishers is a privately held, fully integrated media company known for establishing authoritative peer-reviewed journals in many promising areas of science and biomedical research, including Diabetes Technology & Therapeutics, Journal of Women's Health, and Metabolic Syndrome and Related Disorders. Its biotechnology trade magazine, GEN (Genetic Engineering & Biotechnology News), was the first in its field and is today the industry's most widely read publication worldwide. A complete list of the firm's more than 80 journals, books, and newsmagazines is available on the Mary Ann Liebert, Inc., publishers website.

The post Active Surveillance of Low-Risk Papillary Microcarcinoma of the Thyroid Proposed as First-Line Management appeared first on American Thyroid Association.

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Matrix metalloproteinase-8 analysis in patients with periodontal disease with prediabetes or type 2 diabetes mellitus: A systematic review

Publication date: March 2018
Source:Archives of Oral Biology, Volume 87
Author(s): Everton Freitas de de Morais, Afonso Nóbrega Dantas, Juliana Campos Pinheiro, Rafaella Bastos Leite, Carlos Augusto Galvao Barboza, Bruno Cesar de Vasconcelos Gurgel, Roseana de Almeida Freitas
ObjectivesThe objective of this systematic review was to evaluate information on the levels of MMP-8 in patients diagnosed with prediabetes or type 2 diabetes mellitus with periodontal disease, analyzing its validity as a possible biomarker for the diagnosis and progression of periodontal disease (PD).MethodsA systematic search of the following databases was performed: PubMed/Medline, CENTRAL (The Cochrane Library), EMBASE and Web of Science. Studies involving the evaluation of MMP-8 in patients with prediabetes or patients presenting type 2 diabetes mellitus concomitantly with PD were selected. The evaluation of the methodological quality of the selected studies was based on the methodological bias risk analysis (QUADAS-2).ResultsEight of the initially identified 2683 articles were selected. In all the selected studies, evaluator calibration and the use of clear methods for patient diagnosis with periodontal disease were present. Studies have demonstrated significantly higher MMP-8 concentrations in PD patients compared to controls, as well as in patients presenting more advanced stages of PD. However, controversies regarding MMP-8 levels in prediabetes/diabetes type 2 patients with PD.ConclusionsHigher MMP-8 levels in patients with PD compared to controls imply the potential use of MMP-8 in the diagnosis of PD. The influence of patient glycemic state, as well as medications these patients make use of, are factors that possibly contribute to the modulation of MMP-8 concentrations in patients with diabetes and should be analyzed, aiming at a better understanding of the relationship between glycemic state and MMP-8 levels in patients with PD.



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Acute Chest Syndrome in Children with Sickle Cell Disease

Pediatric Allergy, Immunology, and Pulmonology Dec 2017, Vol. 30, No. 4: 191-201.


http://ift.tt/2jWYTCf

Kikuchi–Fujimoto Disease in an Old Italian Woman: Case Report and Review of the Literature

Kikuchi–Fujimoto disease (KFD) is a rare, benign, generally self-limiting disease that has higher prevalence in Asian people with a few cases reported in European countries. It generally affects young subjects under 40 years of age and is characterized by regional lymphadenopathy. Here, we present a case of a 66-year-old Italian woman who was extensively examined for right unilateral laterocervical lymph nodes associated with fever, night sweats, fatigue, and weight loss. She was diagnosed as having the KFD only after an excision biopsy of the largest laterocervical lymph node and was then managed symptomatically with NSAIDs. We also made a review of the literature for better awareness of the disease among physicians especially in those countries, like Italy, where the disease is not prevalent and may be frequently misdiagnosed. In fact, to our best knowledge, only seven Italian cases of KFD have been published in the last 15 years with patients being younger than 40 years. We finally highlight that it is noteworthy to consider KFD as differential diagnosis of lymphadenopathy even in old patients, and, since a misdiagnosis of lymphoma is actually feasible, an early biopsy has to be taken into account for confirming diagnosis and helping in the timely and appropriate management.

http://ift.tt/2j2Tbh9

Outcomes Following Cordotomy by Coblation for Bilateral Vocal Fold Immobility

This case series of 19 patients examines outcomes of coblation in cordotomy for treatment of patients with bilateral vocal fold immobility.

http://ift.tt/2zdoI8X

Cerebrospinal Fluid Rhinorrhea and a Lytic-Appearing Lesion

A man with a recent history of meningitis presented with a 1-month history of intermittent clear drainage from his left naris during activity; temporal bone computed tomography demonstrated a lytic-appearing lesion of the posterior fossa and partial opacification of the mastoid air cells. What is your diagnosis?

http://ift.tt/2j1XUzz

FDA Clears Another Remicade Biosimilar (Ixifi)

The FDA has approved Pfizer's infliximab-qbtx (Ixifi) for all eligible indications for the US-licensed reference product.
FDA Approvals

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New FDA Web Page Has Latest Info on Best Antibiotic Choice

A new FDA Web page will streamline how the agency updates information to help healthcare providers choose an appropriate antibiotic or antifungal agent for a patient's infection.


http://ift.tt/2jTYkZQ

Teen Acne Tied to Prostate Cancer Risk

Swedish researchers report an association between acne -- particularly severe acne -- in the late teen years and later prostate cancer risk, a finding that validates other research.
Medscape Medical News

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Early Probiotics to Prevent Eczema or Asthma? No Luck So Far

A promising strategy doesn't pan out, but is this the final word on probiotics to prevent childhood atopic disease?
Medscape Pediatrics

http://ift.tt/2ktmTw7

Correlation between sinus and lung cultures in lung transplant patients with cystic fibrosis

Background

Lung transplantation has revolutionized the treatment of end-stage pulmonary disease due to cystic fibrosis. However, infection of the transplanted lungs can lead to serious complications, including graft failure and death. Although many of these patients have concurrent sinusitis, it is unclear whether bacteria from the sinuses can infect the allograft.

Methods

This is a single-institution retrospective study of all patients who underwent lung transplantation for cystic fibrosis from 2005 to 2015 at Duke University Hospital. Pre- and posttransplant nasal and pulmonary cultures obtained via nasal endoscopy and bronchoalveolar lavage (BAL), respectively, were analyzed.

Results

A total of 141 patients underwent 144 lung transplants. Sinus cultures were available for 76 patients (12 pretransplant, 42 posttransplant, 22 both pre- and posttransplant). Pretransplant BAL cultures were available for 139 patients, and posttransplant BAL cultures were available for all patients. Pseudomonas aeruginosa (PsA) and methicillin-resistant Staphylococcus aureus (MRSA) were the most common organisms cultured. There was a significant correlation between pretransplant sinus and posttransplant BAL cultures for PsA (p = 0.003), MRSA (p = 0.013), and Burkholderia cepacia (p = 0.001).

Conclusion

There was a high correlation between pretransplant sinus cultures and posttransplant BAL cultures for PsA, MRSA, and Burkholderia sp. This suggests that the paranasal sinuses may act as a reservoir for allograft colonization in patients with cystic fibrosis. Further studies are needed to determine whether treatment of sinusitis affects allograft colonization and transplant outcomes.

http://ift.tt/2ysRQ8w

The Terracol and Ardouin developmental model of frontal sinus drainage pathway and surrounding spaces: a radiologic validation

Background

The complexity of the frontal sinus drainage pathway (FSDP) can be challenging even for expert surgeons. Several classifications have been proposed to simplify the understanding of FSDP, whose anatomical variability can be simplified based on the knowledge of its developmental mechanisms.

Methods

Cone-beam computed tomography studies performed at the Unit of Radiology of the University of Brescia between March and November 2012 were retrospectively analyzed. FSDP was classified as medial or lateral to the vertical portion of the uncinate process and the following anatomical variants were studied: agger nasi cell, Kuhn's cells, suprabullar cell, supraorbital ethmoid cell, suprabullar frontal cell, and frontal septal cell. The developmental model of the FSDP proposed by Terracol and Ardouin was analyzed and expected associations between the position of the drainage pathway and anatomical variants were formulated. Statistical associations between anatomical variants and the position of FSDP were calculated and compared with expected associations to validate the developmental model.

Results

The anatomical variants of FSDP statistically validated the developmental model of Terracol and Ardouin.

Conclusion

Knowledge of the possible developmental patterns of FSDP helps the surgeon in the understanding of the complexity of the frontoethmoidal region.

http://ift.tt/2AH97RB

Bacteriophage effectively kills multidrug resistant Staphylococcus aureus clinical isolates from chronic rhinosinusitis patients

Background

Bacteriophage (phage) therapy has been proposed as an alternative to antibiotics. Phages have been shown to kill antibiotic resistant Staphylococcus aureus strains; however, it is unknown whether stress-induced antibiotic tolerance affects S. aureus susceptibility to phages. Our objective was to determine the effectiveness of 2 phages currently in clinical development, against antibiotic-resistant and induced antibiotic-tolerant clinical S. aureus isolates.

Methods

Antibiotic tolerant S. aureus strains were induced by incubation with increasing concentrations of gentamicin, mupirocin, and ciprofloxacin over time and their susceptibility to 2 clinically relevant phages (Sa83 and Sa87) was assessed. In addition, phage susceptibility was tested in relation to the antibiotic sensitivity of 65 clinical S. aureus isolates, harvested from the sinonasal cavities of chronic rhinosinusitis (CRS) patients. Phage sensitivity was assessed using a plaque spot assay and by measuring optical density values to observe planktonic S. aureus growth in the presence of the phage. Alamar Blue assays were used to assess biofilm viability after phage treatment.

Results

Frequency of antibiotic resistance amongst clinical S. aureus isolates was 90.7% (59/65) with 13 of 65 (20.0%) identified as multidrug-resistant. Tolerance to gentamicin, mupirocin, and ciprofloxacin was rapidly induced by incubation with increasing concentrations of respective antibiotics. There was no significant difference in phage sensitivity between antibiotic-sensitive and resistant/tolerant S. aureus clinical isolates in planktonic and biofilm form.

Conclusion

Clinical S. aureus isolates from CRS patients have a high (20%) incidence of multidrug resistance. Antibiotic resistance or tolerance did not affect phage susceptibility of those isolates.

http://ift.tt/2ysSByl

Johns Hopkins Scientists Chart How Brain Signals Connect to Neurons

Scientists at Johns Hopkins have used supercomputers to create an atomic scale map that tracks how the signaling chemical glutamate binds to a neuron in the brain. The findings, say the scientists, shed light on the dynamic physics of the chemical's pathway, as well as the speed of nerve cell communications.

http://ift.tt/2ClHLNI

Superior canal dehiscence syndrome

Abstract

Background

Superior canal dehiscence syndrome (SCDS) is a relatively rare neurotological disorder that is characterized by a heterogeneous clinical picture. Recently, vestibular evoked myogenic potential (VEMP) measurement was established for the diagnosis of SCDS. In the present study, a case series of patients with SCDS were analyzed, with a focus on VEMP.

Methods

Four patients with SCDS were prospectively examined with ocular VEMP (oVEMP) and cervical VEMP (cVEMP). The clinical features and the standard audiovestibular test battery results are summarized and analyzed. The diagnostic accuracy of VEMP testing is evaluated.

Results

The increased oVEMP amplitudes had a specificity of 100% in this patient population. All patients had normal caloric function and head impulse testing. The Tullio sign was observed in two patients. Three patients had autophony. The air-bone gap was not greater than 10 dB in any of the patients. Two patients had marked fremitus nystagmus. All patients had a bony dehiscence of the superior semicircular canal on computed tomography imaging.

Conclusion

The subjective and clinical features in this case series of SCDS patients were heterogeneous. However, objective oVEMP testing had the highest diagnostic value. Furthermore, we describe a new diagnostic clinical sign: fremitus nystagmus.

http://ift.tt/2o6V5mk

Schleimhautpemphigoid

Zusammenfassung

Das Schleimhautpemphigoid (SHP) gehört zur Gruppe der Pemphigoiderkrankungen. Die Erkrankung ist definiert durch das Auftreten von Autoantikörpern gegen die dermoepidermale Junktionszone und den vorwiegenden Befall der Schleimhäute. Die Diagnose des SHP wird bei entsprechendem klinischem Phänotyp durch lineare Ablagerungen von IgG und/oder IgA und/oder Komplement C3 an der dermoepidermalen Junktionszone in der direkten Immunfluoreszenz einer periläsionalen Biopsie gestellt. Zirkulierende Autoantikörper lassen sich meist mittels indirekter Immunfluoreszenz auf humaner Spalthaut und ELISA („enzyme-linked immunosorbent assay") oder Immunoblotuntersuchungen unter Verwendung zellulärer oder rekombinanter Antigene nachweisen. Zur systemischen Therapie des SHP werden Kortikosteroide, Dapson, Mykophenole und Azathioprin eingesetzt. Bei schweren Fällen und rascher Progression kommen zusätzlich Cyclophosphamid, Rituximab, hoch dosierte intravenöse Immunglobuline und Immunadsorption zum Einsatz. Entscheidend für die erfolgreiche Behandlung des SHP ist die Zusammenarbeit mit Kollegen anderer Fachrichtungen, wie Zahn-, Augen- und HNO-Ärzten sowie Gastroenterologen und Gynäkologen.

http://ift.tt/2kru1Jm

The influence of cochlear morphology on the final electrode array position

Abstract

Objective

Preoperative information about cochlear morphology and size increasingly seems to be a defining factor of electrode choice in cochlear implant surgery. Different types of electrodes differ in length and diameter to accommodate individual cochlear anatomy. Smaller cochlear size results in increased insertion depth with a higher risk to dislocate and causes cochlear trauma with reduced postoperative outcome. The objective of the current study is to describe the three-dimensional size of the cochlea, to compare interindividual differences, to determine the relationship between cochlear size and insertion angle, and to define risk factors for dislocation during insertion.

Design

Four hundred and three patients implanted between 2003 and 2010 inserted via cochleostomy with a perimodiolar electrode array (Cochlear™ Contour Advance^® electrode array) have been compared. CBCT (Cone beam computed tomography) was used to determine electrode array position (scala tympani versus scala vestibuli insertion, intracochlear dislocation, and insertion angle) and cochlear size (diameters and height). The trajectory of the electrode array and the lateral wall have been measured, and the position of the electrode array has been estimated.

Results

The mean value of the largest diameter was 9.95 mm and that of the perpendicular distance was 6.54 mm. There was a statistically significant correlation between those values. Mean height was 3.85 mm. The intracochlear relation of the electrode array and the modiolus showed a statistically significant relationship with the cochlear expanse. The electrode array was more likely to dislocate in cochleae with a smaller diameter and a lower height. Cochleae with insertions into scala vestibuli exhibited a smaller height compared to scala tympani insertions with statistical significance.

Conclusion

Cochlear size and shape is variable, and the measured data of this study confirm the finding of other researchers. This study established two heights by two different planes to achieve a three-dimensional understanding of the cochlea. The electrode array was more likely to dislocate in cochleae with smaller diameter and smaller height. It can be assumed that the height established in this study seems to be a new preoperative parameter to underline the risk of scalar dislocation and not favored scala vestibuli insertion if using a cochleostomy approach. In conclusion, cochlear size, especially the height, is influencing the final position of the electrode array. Using preoperative scans of the cochlear diameters and cochlear height, a next step to custom-sized arrays is available.

http://ift.tt/2BoKg4c

Diagnostic accuracy of high resolution T2-weighted MRI versus contrast enhanced T1-weighted MRI to screen for cerebellopontine angle lesions in symptomatic patients

Abstract

Objective

To evaluate diagnostic accuracy of high resolution T2-weighted MRI (T2w) for detecting cerebellopontine angle (CPA) lesions compared to a combined protocol including gadolinium enhanced T1-weighted MRI (GdT1w).

Setting

Department of Radiology & Nuclear Medicine, Radboud University Medical Centre, Nijmegen, the Netherlands.

Participants

A random sample of MRIs from 350 patients (700 CPAs) with asymmetrical audiovestibular complaints was used, acquired between 2013-2016.

Main outcome measures

Sensitivity, specificity, positive and negative predictive values of T2w results compared to GdT1w and, in patients with any suggestion of CPA pathology, to the complete examination (T1w, GdT1w and T2w). Inter-rater agreement between an experienced neuroradiologist and a less experienced observer was calculated.

Results

Results of 678 CPAs in 340 patients were analyzed. On T2w the neuroradiologist identified all 27 lesions >2 mm in size out of a total of 30 CPA lesions (sensitivity: 90% [95%CI:73.5-97.9%]). Negative predictive value reached 99.5% [95%CI:98.7-99.9]. One missed lesion of 2 mm would have been detected in clinical practice, as this was one of 14 patients for which additional GdT1w would have been ordered based on T2w alone, increasing sensitivity to 93% [95%CI:77.9-99.2%] and negative predictive value to 99.7% [95%CI:98.9-100%]. Inter-rater agreement for T2w was 98% [95%CI:96.4-98.8].

Conclusion

T2w has a very high diagnostic accuracy for the presence of CPA lesions in patients with asymmetrical audiovestibular complaints. However, in a screening protocol with T2w only, smallest vestibular schwannomas as well as rare differential diagnoses that probably only would be detected on GdT1w may remain unnoticed.

http://ift.tt/2ku2dnI

Garden terror – case series of twenty eight serious ear injuries caused by yucca plants

Abstract

The yucca plant (genus Yucca, family Asparagaceae, subfamily Agavoideae) is a ubiquitous plant whose long and sharp leaf spines (Fig 1) are accountable for an increasing number of ear injuries presenting to the Emergency Department of our specialised tertiary hospital. Whereas most cases presented as easy-to-diagnose traumatic tympanic membrane perforations (TMP) which healed quickly, 4 cases were complicated by perilymphatic fistula (PLF), and these presented a diagnostic dilemma that resulted in late diagnoses.

This article is protected by copyright. All rights reserved.

http://ift.tt/2jUOPJX

Surgical Anatomy of the Round Window – Implications for Cochlear Implantation

Abstract

Background

The round window is an important portal for the application of active hearing aids and cochlear implants. The anatomical and topographical knowledge about the round window region is a prerequisite for successful insertion for a cochlear implant electrode.

Objective of review

To sum up current knowledge about the round window anatomy and to give advice to the cochlear implant surgeon for optimal placement of an electrode.

Type of review

Systematic Medline search.

Search strategy

Search term "round window[Title]" with no date restriction. Only publications in the English Language were included. All abstracts were screened for relevance, i.e. a focus on surgical anatomy of the round window. The search results were supplemented with hand searching of selected reviews and reference lists from included studies.

Evaluation method

Subjective assessment.

Results

There is substantial variability in size and shape of the round window. The round window is regarded as the most reliable surgical landmark to safely locate the scala tympani. Factors affecting the optimal trajectory line for atraumatic electrode insertion are anatomy of the round window, the anatomy of the intracochlear hook region and the variable orientation and size of the cochlea's basal turn.

Conclusions

The very close relation to the sensitive inner ear structures necessitates a thorough anatomic knowledge and careful insertion technique, especially when implanting patients with residual hearing. In order to avoid electrode migration between the scalae and to achieve protect the modiolus and the basilar membrane, it is recommended to aim for an electrode insertion vector from postero-superior to antero-inferior.

This article is protected by copyright. All rights reserved.

http://ift.tt/2krokLu

Liquid Biopsy Results Differed Substantially Between Two Providers

Two Johns Hopkins prostate cancer researchers found significant disparities when they submitted identical patient samples to two different commercial liquid biopsy providers. Liquid biopsy is a new and noninvasive alternative to tumor tissue sequencing, and it is intended to specifically detect and sequence tumor DNA circulating in patients' blood. The results are used to help guide doctors to tailor the best treatment for patients at each point of their disease.

http://ift.tt/2C6dilV

Minichromosome maintenance complex component 6 (MCM6) expression correlates with histological grade and survival in endometrioid endometrial adenocarcinoma

Abstract

Minichromosome maintenance complex component 6 (MCM6) is involved in initiating DNA replication and is upregulated during licensed G0 phase of the cell cycle. This early expression permits its labeling of more proliferating cells than those by Ki-67. Here using a cohort of 89 endometrioid adenocarcinoma, we report findings made on the prognostic value of MCM6 based on immunohistochemical labeling index (LI) of the protein in comparison with that of Ki67 as no such information is currently available. Additionally, we examined the prognostic values of these markers based on their mRNA expression using a cohort of uterine corpus endometrial carcinoma (UCEC, n = 307) taken from The Cancer Genome Atlas (TCGA) database. Our evidence indicated the presence of a positive correlation between the LI of MCM6 and the histological grade of endometrioid endometrial adenocarcinoma (grade I, 66.7%; grade II, 75.3%; grade III, 81.4%; p < 0.001) and an inverse correlation between the LI of MCM6 and the overall and progression-free survival (p = 0.02 for both). The LI of Ki-67 correlated with grade (p < 0.001), but not survival. The MCM6 and Ki-67 inter-observer intra-class correlation coefficients were excellent: 0.84 (95% confidence interval, 0.83–0.91) and 0.84 (0.77–0.90), respectively. For in silico analyses of the TCGA cohort, both univariate and multivariate Cox analyses (p = 0.003 and p = 0.03, respectively) revealed high MCM6 mRNA Z-scores associated with reduced overall survival. This association was absent for Ki-67. MCM6 is thus a highly reproducible marker of poor prognosis in endometrial cancer. Evaluation of MCM6 should thus be considered in daily practice for risk stratification.

http://ift.tt/2C70L1T

Comparative analysis of 2 robotic thyroidectomy procedures: Transoral versus bilateral axillo-breast approach

Abstract

Background

The surgical outcomes of a single surgeon's initial cases of transoral robotic thyroidectomy (TORT) were compared with the surgeon's initial cases of a bilateral axillo-breast approach (BABA) robotic thyroidectomy.

Methods

The medical reports were retrospectively reviewed. The BABA robotic thyroidectomies were performed between 2008 and 2009, and TORTs were performed between 2012 and 2016.

Results

Each group comprised 50 patients. Operative time for total thyroidectomy was shorter, the pain scores were lower, and hospital stays were shorter in the TORT group than in the BABA robotic thyroidectomy group. There were no significant differences between groups in either vocal cord palsy or hypoparathyroidism rates. There were 9 cases of mental nerve injury in the first 12 cases of TORT, but none subsequently.

Conclusion

The TORT procedure could be performed safely and showed comparable outcomes with BABA robotic thyroidectomy in selected patients. Therefore, TORT may be an alternative approach for patients who prefer a scar-free thyroidectomy.

http://ift.tt/2C63HeV

Predictors of returns to the emergency department after head and neck surgery

Abstract

Background

Thirty-day hospital readmissions have become a measure of quality of care. Many readmissions enter through the emergency department. The purposes of this study were to determine the rate, risk factors, and costs of 30-day returns to the emergency department (30dEDRs) after head and neck surgery.

Methods

All adult patients undergoing head and neck surgery at the University of Florida from 2012 to 2014 were reviewed. Univariate and multivariate logistic regression analyses were performed to identify risk factors for 30dEDRs.

Results

We found 1065 patients who underwent 1173 procedures. There were 88 cases (7.5%) that resulted in 30dEDRs and 55 patients (4.7%) who had 30-day unplanned readmissions (30dURs). Significant predictors of 30dEDRs included: smoking; hypothyroidism; and intensive care unit (ICU) stays. Significant predictors of readmission from an emergency department visit were Charlson Comorbidity Index (CCI) and cancer stage. Total costs of 30dEDRs and any subsequent readmissions topped $500 000.

Conclusion

The rate of 30dEDRs after head and neck surgery is low; however, these visits increase the hospitals' financial burden as well as patient morbidity. Predictors of 30dEDRs may be utilized to formulate preventative measures.

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How to Take a Child’s Temperature

One of the first questions your pediatrician will ask when you call in with a sick child is whether he or she has a fever. With so many devices on the market, what's the best way to take a child's temperature? Different pediatricians have different suggestions, but I think a rectal temperature offers the most accurate read. Here's how to take a proper temperature.

The post How to Take a Child's Temperature appeared first on ChildrensMD.

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Molecular Fluorescence Endoscopy of (Pre)Malignant Esophageal Lesions

Conditions:   Barrett Esophagus;   Esophageal Cancer;   Dysplasia in Barrett Esophagus
Interventions:   Drug: IV-administation of EMI-137;   Device: Molecular Fluorescence Endoscopy platform
Sponsor:   University Medical Center Groningen
Recruiting

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Editorial Board

Publication date: January 2018
Source:Molecular Immunology, Volume 93





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External signals regulate germinal center fate-determining transcription factors in the A20 lymphoma cell line

Publication date: January 2018
Source:Molecular Immunology, Volume 93
Author(s): Juan Feng, Xin Liu, Xingya Ni, Hai Qi
Due to the apoptosis-prone nature of primary germinal center B (GCB) cells, it remains a huge challenge to dissect signals that guide their differentiation towards memory B cells and plasma cells in vitro. Here we show that the murine lymphoma cell line A20 resembles primary GCB cells in expression of GC-specific surface markers and the master transcription factor BCL6 and may serve as a useful system to model certain GCB cell behaviors in vitro. Using these cells, we found that both CD40 and B cell receptor (BCR) signaling are able to drive BCL6 downregulation, which is a prerequisite of post-GC B-cell differentiation. Under the steady state, BCL6 is constantly and rapidly degraded in A20 cells by the proteasome in a strictly FBXO11-dependent manner. This process can be further enhanced by signals downstream of the BCR. Both CD40 and BCR stimulation can upregulate IRF4, a transcription factor that suppresses BCL6 expression. However, only BCR signaling downregulate PAX5 and BACH2, two transcription factors that help maintain the GCB identity. Together, these results validate the A20 cell line as an experimental system suitable for studying regulation of BCL6 and potentially other transcription factors relevant to post-GC fate determination, and they support that combined signaling from BCR and CD40 receptors would drive termination of the GC program.



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Case 38-2017: A 20-Year-Old Woman with Seizures and Progressive Dystonia

Presentation of Case. Dr. Andrew J. Cole (Neurology): A 20-year-old woman was seen in the neurology clinic of this hospital because of seizures and progressive dystonia. The patient had been well until she was 3 years of age, when she began to have recurrent falls, difficulty walking, and seizures.…

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Breast milk is conditionally perfect

Publication date: Available online 14 December 2017
Source:Medical Hypotheses
Author(s): Miriam Erick
Breast milk is the universal preferred nutrition for the newborn human infant. New mother have been encouraged to exclusively breastfeed by health care professionals and consumer-advocacy forums for years, citing "breast milk is the perfect food". The benefits are numerous and include psychological, convenience, economical, ecological and nutritionally superior.Human milk is a composite of nutritional choices of the mother, commencing in the pre-conceptual era. Events influencing the eventual nutritional profile of breast milk for the neonate start with pre-conceptual dietary habits through pregnancy and finally to postpartum. Food choices do affect the nutritional profile of human breast milk.It is not known who coined the phrase "breast milk is the perfect food" but it is widely prevalent in the literature. While breast milk is highly nutritive, containing important immunological and growth factors, scientific investigation reveals a few short-falls. Overall, human breast milk has been found to be low in certain nutrients in developed countries: vitamin D, iodine, iron, and vitamin K. Additional nutrient deficiencies have been documented in resource-poor countries: vitamin A, vitamin B 12, zinc, and vitamin B 1/ thiamin.Given these findings, isn't it more accurate to describe breast milk as "conditionally perfect"? Correcting the impression that breast milk is an inherently, automatically comprehensive enriched product would encourage women who plan to breastfeed an opportunity to concentrate on dietary improvement to optimizes nutrient benefits ultimately to the neonate. The more immediate result would improve pre-conceptual nutritional status.Here, we explore the nutritional status of groups of young women; some of whom will become pregnant and eventually produce breast milk. We will review the available literature profiling vitamin, mineral, protein and caloric content of breast milk. We highlight pre-existing situations needing correction to optimize conception and fetal development.While alternative forms of infant nutrition carry standard product labels of nutrient adequacy, this information does not apply universally to all breast milk. Infant formulas are fortified with various amounts of vitamins, minerals, supplemental protein concentrates, nucleic factors, omega 3 fatty acids and any important new nutritional finding. Infant formulas are manufactured to be consistent in composition and are monitored closely for quality. Not true for human breast milk.Any nutrient deficiency existing in pregnancy will ultimately be carried forward via lactation. It is a biological impossibility for a lactating woman to transfer nutrients via breast milk she does not have!



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How many melanomas might be prevented if more people applied sunscreen regularly?

Summary

Background

Ultraviolet radiation causes cutaneous melanoma. Sunscreen prevents sunburn and protects skin cells against mutations. High-quality epidemiological studies suggest regular sunscreen use prevents melanoma.

Objectives

To calculate the potential impact fraction (PIF) for melanoma in the U.S.A. and Australia assuming a range of different intervention scenarios intended to increase sunscreen use.

Methods

We calculated the PIF, the proportional difference between the observed number of melanomas arising under prevailing levels of sunscreen use compared with the number expected under counterfactual scenarios. We used published melanoma incidence projections for Australia and the white population in the U.S.A. from 2012 through to 2031 as the baseline condition, with estimates for protective effects of 'regular sunscreen use' from the literature. Sunscreen prevalence was sourced from national or state surveys.

Results

Under a plausible public health intervention scenario comprising incremental increases in sunscreen prevalence over a 10-year implementation programme, we estimated that cumulatively to 2031, 231 053 fewer melanomas would arise in the U.S. white population (PIF 11%) and 28 071 fewer melanomas would arise in Australia (PIF 10%). Under the theoretical maximum model of sunscreen use, almost 797 000 (PIF 38%) and approximately 96 000 (PIF 34%) melanomas would be prevented in the U.S.A. and Australia, respectively between 2012 and 2031. A sensitivity analysis using weaker effect estimates resulted in more conservative PIF estimates.

Conclusions

Overall, interventions to increase use of sunscreen would result in moderate reductions in melanoma incidence, assuming no compensatory overexposure to the sun. Countries with a high incidence of melanoma should monitor levels of sunscreen use in the community.

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The Diagnostic Utility and Clinical Impact of After-Hours CT Scans of the Abdomen and Pelvis Investigating Abdominal Pain

Introduction. The aim of this study was to evaluate the diagnostic utility and impact on clinical management of after-hours CT scans investigating abdominal pain in surgical patients. Methods. After-hours CT A/P reports investigating the acute surgical abdomen were compared with clinical outcomes and histopathological findings to assess sensitivity and specificity of CT reporting. Comparisons between CT reports and clinical notes were made. CT scans were categorised as having direct effects on clinical management, ruling out a serious pathology, ruling out a nonserious pathology, or having no effect. Discrepancies between information in case-notes and information provided to radiologists were also analysed. Results. 79 clinical notes were located. After-hours CT demonstrated 91% sensitivity and 82% reporting specificity using clinical outcomes as the standard. In the 26 patients with histopathological findings, CT reports demonstrated 91% sensitivity. In 79.7% of cases, CT scanning had an impact on management. In 35.4% of cases, an indication for scanning was not documented with variation in clinical information in 8.9% of cases. Discussion. This study demonstrates after-hours CT A/P reports result in significant impacts on clinical management of surgical patients with acute abdominal pain. Improvements in providing information when requesting scans are however needed to facilitate accurate reporting.

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A Bispecific Antibody Based on Pertuzumab Fab Has Potent Antitumor Activity

Human epidermal growth factor receptor 2 (HER2) is frequently overexpressed and activated in metastatic breast cancers. Monoclonal antibodies targeting Her2, such as trastuzumab and pertuzumab, have become important targeted therapies for patients with HER2-positive breast cancer. Both trastuzumab and pertuzumab can reduce Her2 positive tumor burden by inhibiting Her2 signaling and inducing ADCC activities (antibody dependent cell-mediated cytotoxicity). In this study, we have generated a bispecific antibody, Her2(Per)-S-Fab, by linking the pertuzumab Fab to an anti-CD16 single domain antibody. The Her2(Per)-S-Fab can be expressed and purified efficiently from Escherichia coli. In vitro and in vivo experiments showed Her2(Per)-S-Fab had potent cytotoxicity against Her2-positive tumor cells. Thus, Her2(Per)-S-Fab may provide an alternative to treat Her2-positive cancer patients.

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CD11c-targeted Delivery of DNA to Dendritic Cells Leads to cGAS- and STING-dependent Maturation

Immunotherapeutic activation of tumor-specific T cells has proven to be an interesting approach in anticancer treatment. Particularly, anti-CTLA-4 and anti–PD-1/PD-L1 treatment looks promising, and conceivably, even better clinical results might be obtained if such treatment could be combined with boosting the existing tumor-specific T-cell response. One way to achieve this could be by increasing the level of maturation of dendritic cells locally and in the draining lymph nodes. When exposed to cancer cells, dendritic cells may spontaneously mature because of danger-associated molecular patterns derived from the tumor cells. Double-stranded DNA play a particularly important role in the activation of the dendritic cells, through engagement of intracellular DNA-sensors, and signaling through the adaptor protein STING. In the present study, we have investigated the maturational response of human monocyte-derived dendritic cells (moDC) and human monocytic THP-1 cells to targeted and untargeted DNA. We used an anti-CD11c antibody conjugated with double-stranded DNA to analyze the maturation status of human moDCs, as well as maturation using a cGAS KO and STING KO THP-1 cell maturation model. We found that dendritic cells can mature after exposure to cytoplasmic double-stranded DNA delivered through CD11c-mediated endocytosis. Moreover, we show that THP-1 cells matured using IL-4, GM-CSF, and ionomycin upregulate DC-maturation markers after CD11c-targeted delivery of double-stranded DNA. This upregulation is completely abrogated in cGAS KO and STING KO cells.

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Development of Bell’s Palsy After Treatment With Ipilimumab and Nivolumab for Metastatic Melanoma: A Case Report

Ipilimumab is a human monoclonal antibody that targets cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), and it is FDA approved for the treatment of unresectable or metastatic melanoma. Immune-related adverse events (irAEs) of gastrointestinal, dermatologic, and endocrine origin are commonly seen, ranging between 18% and 44%, with immune checkpoint inhibitors (anti-CTLA-4 and anti-PD-1/PD-L1). Rare irAEs include neurological, renal, and hematologic toxicities. Bell's palsy is a form of neurological toxicity that presents as an idiopathic paralysis of the muscles on one side of the face. We report a case of Bell's palsy in a 45-year-old male patient who received 1 dose of both ipilimumab and nivolumab for the treatment of metastatic melanoma. After the resolution of symptoms, ipilimumab was permanently discontinued and single-agent nivolumab administered. The patient has remained free of neurological symptoms. This case suggests that Bell's palsy is an irAE induced by ipilimumab.

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Preclinical Optimization of a CD20-specific Chimeric Antigen Receptor Vector and Culture Conditions

Chimeric antigen receptor (CAR)-based adoptive T-cell therapy is a highly promising treatment for lymphoid malignancies, and CD20 is an ideal target antigen. We previously developed a lentiviral construct encoding a third generation CD20-targeted CAR but identified several features that required additional optimization before clinical translation. We describe here several improvements, including replacement of the immunogenic murine antigen-binding moiety with a fully human domain, streamlining the transgene insert to enhance lentiviral titers, modifications to the extracellular IgG spacer that abrogate nonspecific activation resulting from binding to Fc receptors, and evaluation of CD28, 4-1BB, or CD28 and 4-1BB costimulatory domains. We also found that restimulation of CAR T cells with an irradiated CD20+ cell line boosted cell growth, increased the fraction of CAR-expressing cells, and preserved in vivo function despite leading to a reduced capacity for cytokine secretion in vitro. We also found that cryopreservation of CAR T cells did not affect immunophenotype or in vivo antitumor activity compared with fresh cells. These optimization steps resulted in significant improvement in antitumor activity in mouse models, resulting in eradication of established systemic lymphoma tumors in 75% of mice with a single infusion of CAR T cells, and prolonged in vivo persistence of modified cells. These results provide the basis for clinical testing of a lentiviral construct encoding a fully human CD20-targeted CAR with CD28 and 4-1BB costimulatory domains and truncated CD19 (tCD19) transduction marker.

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Life-threatening Autoimmune Cardiomyopathy Reproducibly Induced in a Patient by Checkpoint Inhibitor Therapy

Checkpoint inhibitors induce a plethora of immune-related adverse events (irAEs) including autoimmune colitis, hepatitis, endocrinopathies, and rarer side effects like neuritis. Here, a case of autoimmune cardiomyopathy (grade 3 CTCAE) and myocarditis under combination therapy with nivolumab plus ipilimumab in a 72-year-old melanoma patient is reported. Treatment induced a partial response for 14 months. However, after 10 infusions the patient developed dyspnea, edema of the legs, ascites and a weight gain of 10 kg because of a decompensated heart insufficiency with a reduced ejection fraction from formerly 48%–50% to 15%. Ischemia and viral infections were ruled out. Histopathology showed hypertrophic myocarditis with interstitial lymphocytes. Prednisolone improved the patient's condition within 3 days, leading to a 25% and 30% ejection fraction after 2 and 8 weeks, respectively, and clinical symptoms subsided completely. Importantly, reinduction of anti-PD1 therapy resulted in a flare of myocarditis. Awareness for potentially life-threatening irAE of checkpoint inhibitors like autoimmune cardiomyopathy and myocarditis is crucial to rapidly initiate adequate treatment.

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Management of Immune-mediated Cytopenias in the Era of Cancer Immunotherapy: A Report of 4 Cases

Recent advancements in immunotherapy have brought promising drugs to fight cancers; a subset of immunotherapy medications are known as checkpoint inhibitors. Their mechanism of action relies on upregulating antitumor response by reversing T-cell suppression; as a consequence the effect can also result in a spectrum of immune related complications. Reported complications to date include: skin, gastrointestinal mucosa, hypophysis, liver, endocrine system, nervous system, kidney, musculoskeletal system and the hematologic system. The management of immune related complications typically includes the use of steroids and other strategies of immunosuppression. The current recommendations are not organ-specific and little is known about the response and outcomes related to the hematologic system. Hereby we report four cases evaluated at the hematology service at the University of Texas MD Anderson Cancer Center for cytopenias after check point inhibitor therapies. All cases were responsive to conventional interventions for immune-mediated cytopenias.

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Acute Flare of Bullous Pemphigus With Pembrolizumab Used for Treatment of Metastatic Urothelial Cancer

In the past decade, the resurgence of immunotherapy has changed the landscape of cancer therapy. Checkpoint inhibitors targeting cytotoxic T-lymphocyte antigen-4, programmed death-1 on lymphocytes, and programmed death ligand-1 on tumors cells are currently utilized in the management of several cancers. These agents are double-edged sword with the positive effect being robust antitumor response but on the other side they can throttle up the normal immunologic homeostasis in a negative way, leading to adverse autoimmune toxicities. These adverse toxicities are frequent if patients have active autoimmune disorders. Here, we report a rare case of quiescent bullous pemphigoid which flared after initiation of pembrolizumab, a programmed death ligand-1 inhibitor.

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Wichtige Informationen zur Leitlinie zur (allergen)spezifischen Immuntherapie (SIT)

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Chronic Central Serous Chorioretinopathy-Like Maculopathy as Atypical Presentation of Chorioretinal Folds

Purpose: The purpose of this case report was to present the clinical data and management of a 69-year-old female patient with chorioretinal folds who developed chronic central serous chorioretinopathy-like maculopathy. Case Presentation: A 69-year-old female patient presented with a recent-onset slight decrease in visual acuity in her left eye. Her past ocular history was clear. Regarding her medical history, she had only hypertension, treated with per os medications. The patient underwent a complete ophthalmological examination. At presentation, the visual acuity was 6/6 in the right eye and 6/7.5 in the left eye. Intraocular pressure was 16 mm Ηg in both eyes. On fundoscopy, chorioretinal folds were noticed in the left eye. Spectral-domain optical coherence tomography, fluorescein angiography, and indocyanine green angiography confirmed the diagnosis of chronic central serous chorioretinopathy-like maculopathy in the left eye, since other causes of chorioretinal folding were excluded. The right eye was normal. No treatment was given to the patient, and at the 6-month follow-up there was improvement in visual acuity, which was 6/6, and decreased subretinal fluid. Conclusions: Central serous chorioretinopathy-like maculopathy should be taken into account for the differential diagnosis of patients with chorioretinal folds.
Case Rep Ophthalmol 2017;8:568–573

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Successful Subcutaneous Allergen-Specific Immunotherapy in Refractory Atopic Keratoconjunctivitis: A Case Report

Purpose: We report a case of refractory atopic keratoconjunctivitis (AKC) which was successfully treated with subcutaneous immunotherapy (SCIT). Case Report: A 22-year-old woman presented with severe allergic conjunctivitis for one and a half year. She failed to respond to conventional topical anti-allergic medications, topical corticosteroid, as well as topical cyclosporine A. Therefore, oral corticosteroids had to be prescribed to control the exacerbation for 1 year. Due to refractory AKC and to avoid long-term corticosteroid use, we referred her to an allergy clinic for considering the role of SCIT. Allergology investigations showed positive skin prick test and strongly elevated serum-specific IgE to Dermatophagoides farinae (Der f) and Dermatophagoides pteronyssinus (Der p). She received a conventional protocol of SCIT using Der f and Der p allergen extracts. Results: The patient's ocular signs and symptoms were dramatically improved 2 months after the initiation of SCIT, and oral corticosteroids could be discontinued within 3 months of the treatment. She was maintained with mast cell stabilizers and preservative-free tears without any episodes of exacerbation. Conclusions: SCIT may contribute to successful outcomes in controlling symptoms and preventing exacerbation in AKC patient. It should be considered as an alternative or even a primary treatment for patients with refractory AKC. However, the optimal SCIT protocol must be discussed with an allergist on an individual basis for the best outcome.
Case Rep Ophthalmol 2017;8:562–567

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Unilateral Keratoconus after Chronic Eye Rubbing by the Nondominant Hand

Introduction: To report the development of unilateral keratoconus in a healthy male after persistent unilateral eye rubbing by the nondominant hand which was not needed for professional activities. Methods: Observational case report. Results: A 60-year-old male was first seen in our clinic due to decreased vision in his left eye. Slit-lamp biomicroscopy of the left eye revealed Vogt's striae, stromal thinning, and a stromal scar. Corneal topography showed a stage 4 keratoconus. Clinical examination and corneal topography of the right eye were normal. Medical history revealed a habit of chronic eye rubbing only in the left eye because of the right hand being occupied for professional needs. During follow-up of 5 years, Scheimpflug images of the right eye stayed normal while the left eye showed a stable cone. Discussion: This case report supports the hypothesis of mechanical fatigue of the cornea due to repetitive shear stress on the surface caused by eye-rubbing.
Case Rep Ophthalmol 2017;8:558–561

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Application of Arterial Spin Labelling in Detecting Retinal Ischemia

Purpose: Here, we have tried to quantify the chorioretinal blood perfusion in patients who are clinically identified to be suffering from retinal ischemia using arterial spin labelling (ASL) MRI. Method: Four participants, diagnosed with retinal ischemia based on their structural OCT and angiography test, were then scanned using anatomical MRI as well as ASL. We optimized MR parameters to maximize resolution and target fixation, blinking, and breathing ques to minimize motion artifacts. Results: Participants had a maximum of ∼50 mL/100 mL/min of blood perfusion, which is below the normal values of ∼200 mL/100 mL/min. It also appeared that thinning of the choroid contributes more to the measured decreased chorioretinal perfusion, compared to slowed arterial filling time. Conclusion: Decreased chorioretinal perfusion is a multifactorial event and has been implicated in several posterior eye pathologies. Based on our current results, it seems that ischemia of the eye could be due to anatomy (tissue volume) and/or functionality (arterial flow).
Case Rep Ophthalmol 2017;8:545–557

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Refractive Lens Exchange with Multifocal Intraocular Lens for Treatment of Chronic Intermittent Spasm of the Near Reflex

We report the case of an emmetropic 32-year-old female with decreased uncorrected visual acuity and diplopia due to intermittent episodes of spasm of the near reflex. Neurologic, general, and ophthalmic examination could not find an organic cause. Attempts at spontaneous recovery, psychogenic therapy, and cycloplegic therapy were unsuccessful and the symptoms persisted for almost 5 years, leading to psychogenic distress. Final treatment with refractive lens exchange and implantation of a toric trifocal intraocular lens resolved the spasm of the near reflex, resulting in an uncorrected distance and near visual acuity of 20/20.
Case Rep Ophthalmol 2017;8:539–544

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DRESS et virus. Comment avancer ?

Publication date: Available online 13 December 2017
Source:Annales de Dermatologie et de Vénéréologie
Author(s): A. Barbaud, N. Dupin, J.-C. Roujeau




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Gut microbiome: a new player in gastrointestinal disease

Abstract

The gastrointestinal (GI) tract harbors a diverse and host-specific gut microbial community. Whereas host-microbe interactions are based on homeostasis and mutualism, the microbiome also contributes to disease development. In this review, we summarize recent findings connecting the GI microbiome with GI disease. Starting with a description of biochemical factors shaping microbial compositions in each gut segment along the longitudinal axis, improved histological techniques enabling high resolution visualization of the spatial microbiome structure are highlighted. Subsequently, inflammatory and neoplastic diseases of the esophagus, stomach, and small and large intestines are discussed and the respective changes in microbiome compositions summarized. Finally, approaches aiming to restore disturbed microbiome compositions thereby promoting health are discussed.

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Cross-over clinical trial for evaluating the safety of camel's milk intake in patients who are allergic to cow's milk protein

Publication date: Available online 6 December 2017
Source:Allergologia et Immunopathologia
Author(s): E.M. Navarrete-Rodríguez, L.A. Ríos-Villalobos, C.R. Alcocer-Arreguín, B.E. Del-Rio-Navarro, J.M. Del Rio-Chivardi, O.J. Saucedo-Ramírez, J.J.L. Sienra-Monge, R.V. Frias
BackgroundCow's milk protein allergy (CMPA) affects between 0.6 and 0.9% of the general population, and its treatment implies the total elimination of the intake of this protein. Camel's milk has been suggested as an alternative for patients over one year of age who suffer from CMPA due to the difference in the amino acid sequence from that of cow's milk. The objective of this study was to evaluate the safety and tolerability of camel's milk in children with CMPA.MethodsCrossed clinical trial for the use of camel's milk vs. amino acid formula, carried out at the Dr. Federico Gómez Children's Hospital of Mexico (HIMFG) on patients between one and 18 years of age with diagnosed CMPA confirmed through double-blind, placebo-controlled food challenges (DBPCFCs). Only those whose allergies were confirmed were randomly placed into two groups: those to be administered camel's milk and those to be administered the amino-acid formula for two weeks, followed by a six-week wash-out period, and then a group crossing for a further two weeks.Results49 patients with suspected CMPA were included in the study; the diagnosis was confirmed through DBPCFCs in 15 patients, who were those who participated in the study. After having been administered camel's milk, none of the patients presented adverse effects.Conclusions and clinical relevanceCamel's milk is safe and tolerable in patients above one year of age with CMPA and can be considered as a good alternative given the benefit of its taste compared to other formulas.



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