Establishing an Acute Pain Service in Private Practice and Updates on Regional Anesthesia Billing

Publication date: September 2018

Source: Anesthesiology Clinics, Volume 36, Issue 3

Author(s): Christopher A.J. Webb, T. Edward Kim

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Enhanced Recovery After Shoulder Arthroplasty

Publication date: September 2018

Source: Anesthesiology Clinics, Volume 36, Issue 3

Author(s): Taras Grosh, Nabil M. Elkassabany

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Forthcoming Issues

Publication date: September 2018

Source: Anesthesiology Clinics, Volume 36, Issue 3

Author(s):

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Contents

Publication date: September 2018

Source: Anesthesiology Clinics, Volume 36, Issue 3

Author(s):

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Contributors

Publication date: September 2018

Source: Anesthesiology Clinics, Volume 36, Issue 3

Author(s):

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Copyright

Publication date: September 2018

Source: Anesthesiology Clinics, Volume 36, Issue 3

Author(s):

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Regional Anesthesia

Publication date: September 2018

Source: Anesthesiology Clinics, Volume 36, Issue 3

Author(s): Nabil M. Elkassabany, Edward R. Mariano

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Conservative management of pelvic sepsis with severe shock and multiple organ dysfunction syndrome after rubber-band ligation of internal haemorrhoids: surgery is not the only option

Abstract

Rubber-band ligation (RBL) is a safe and cost-effective approach to internal haemorrhoids. Potential side effects include pain, bleeding, urinary retention and occasionally pelvic sepsis and systemic inflammatory response syndrome (SIRS). At-risk patients are mainly those with immunocompromising conditions. Although aggressive surgical debridement or diverting colostomy appear to be obvious options when patients' life is threatened, their superiority to conservative measures has not been proven. We present the case of a 58-year-old female patient who presented 48 h after a RBL with pelvic pain, dysuria and leukocytosis. Her condition deteriorated rapidly that ventilator and inotropic support were required for a severe SIRS for almost 10 days. Laparoscopic exploration and imaging showed a rectosigmoiditis, ascites and superficial rectal necrosis with no transmural damage requiring an emergent surgery. Conservative management could possibly be a valid option in post-RBL pelvic sepsis even when severe associated multiple organ failure is present.

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Primary greater omental torsion as a cause of acute abdomen—a rare case report

Abstract

Greater omental torsion is a rare entity that can cause acute abdominal pain, may mimick other abdominal pathologies, and is difficult to be diagnosed preoperatively. We present a case of a male patient with greater omental torsion mimicking the symptoms of acute appendicitis. A 31-year-old male patient presented with right scrotal pain, initially treated by the urologists, however, 24 h later, he presented right lower quadrant pain, with characteristics of acute appendicitis. After finding in ischemic inflammatory mass on McBurney incision, an exploratory laparotomy was performed, revealing torsion of the greater omentum. Torsion of the greater omentum can be a cause of acute abdomen and could be misdiagnosed with acute appendicitis. Preoperative diagnosis is not easy and resection of the affected tissue is the preferred treatment of choice.

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Adenomyomatous hyperplasia of distal common bile duct: a case report and review of the literature

Abstract

Adenomyomatous hyperplasia (AH) is commonly found in the gallbladder and is considered a tumor-like inflammatory lesion arising from Rokitansky-Aschoff sinus. It is extremely rare in the extrahepatic bile duct and only 15 cases have been reported to date. We describe a 63-year-old male patient who presented with cholangitis, underwent an extensive diagnostic workup, and ultimately had a Whipple procedure. Final pathology showed a 2.0 × 1.5 × 0.5 cm³ granular lesion in the distal common bile duct. There was prominent biliary epithelial proliferation with tubular–papillary architecture and minimal nuclear atypia in association with chronic inflammation, stroma reaction and smooth muscle proliferation. AH of the extrahepatic bile duct is a benign process but often requires a major operation to definitively diagnose.

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Fulminant descending mediastinitis secondary to infectious mononucleosis

Abstract

Descending mediastinitis is a rare, life-threatening condition caused by contiguous spread of oropharyngeal or cervical infection into the mediastinum. Infectious mononucleosis generally results in a self-limited illness characterized by fever, pharyngitis and lymphadenopathy. We present an exceptional case of an 18-year-old with infectious mononucleosis complicated by progressive bacterial superinfection and fulminant descending mediastinitis. After resuscitation, broad spectrum antibiotics, critical care support and definitive surgical management, they made a full recovery.

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Tracheal segmental resection for tracheal cancer: comparison of cervical collar incision with median sternotomy and posterolateral incision

Abstract

We compare two surgical approaches for segmental tracheal resection for tracheal cancer: cervical collar incision with median sternotomy and right posterolateral incision. In case one, a 46-year-old woman presented with adenoid cystic carcinoma, measuring 4.5 cm longitudinally, located at the junction of the cervical and mediastinal trachea. Cervical collar incision with median sternotomy provided a good exposure of the entire trachea. Although a relatively long tracheal resection (5.0 cm) was required, sufficient mobilization of the entire trachea facilitated low-tension anastomosis. In case 2, a 39-year-old man presented with squamous cell carcinoma, measuring 1.8 cm longitudinally, located at the lower trachea 1.8 cm from the carina to the proximal side. Right posterolateral incision provided a good exposure of the lower trachea. Although the required tracheal resection was relatively short (3.0 cm), the anastomotic tension was high. The high anastomotic tension was likely attributed to the limited mobilization of the proximal trachea.

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Acute appendicitis as the first presentation of appendiceal metastasis of gastric cancer—report of a rare case

Abstract

Metastatic tumors of the appendix is a rare entity, whereas only limited data involving metastasis arising from gastric cancer has been reported. Herein, the case of gastric adenocarcinoma metastasis presenting as acute appendicitis is reported. A 53-year-old male, with a history of subtotal gastrectomy due to gastric adenocarcinoma 3 years before, was referred to the Emergency Department with symptoms of acute appendicitis. While this condition was confirmed intraoperatively, histology examination and comparison with the previously excised gastric specimen indicated that metastasis of gastric adenocarcinoma to the appendix was present. Metastatic appendiceal carcinoma arising from the stomach is an extremely rare condition, associated with poor prognosis. Aggressive treatment of the solitary lesion may present favorable results.

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Subacute carbon monoxide poisoning presenting as vertigo and fluctuating low frequency hearing loss

Abstract

It is estimated that up to 25 000 UK residents are exposed to small amounts of carbon monoxide (CO) annually. Symptoms of chronic exposure to CO are vague and non-specific and include dizziness and hearing loss. We describe a case of 38-year-old lady presenting with a 4-month history of vertigo and hearing loss. Initially diagnosed as Meniere's disease, the patient was investigated and followed up in the clinic. She reported leakage of carbon monoxide from her gas fire identified during a routine safety check. Her symptoms fully resolved after disconnecting the faulty gas fire. A rare cause of fluctuating hearing loss and vertigo is described, and the diagnostic challenges are discussed.

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Necrotizing fasciitis of the lower extremity caused by perforated sigmoid diverticulitis—a case report

Abstract

Diverticulosis of the sigmoid colon is a common condition and occurs more often in elderly patients. A well-known complication is infection or even perforation which often requires surgery. Necrotizing fasciitis as a complication of perforated diverticulitis is very rare. Here, we present a case of a covered perforated diverticulitis in an immunosuppressed patient leading to life-threatening necrotizing fasciitis requiring extracorporeal membrane oxygenation. Either hematogenous or local dissemination via the inguinal canal seemed the most probable mechanism of leg infection leading to hip articulation.

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Olfactory ensheathing cells in facial nerve regeneration

Publication date: Available online 7 August 2018

Source: Brazilian Journal of Otorhinolaryngology

Author(s): Manyi Li, Qiubei Zhu, Jisheng Liu

Abstract

Introduction

Olfactory ensheathing cell is a unique kind of glia cells, which can promote axon growth. Little is known about the differences between olfactory mucosa-olfactory ensheathing cells and olfactory bulb-olfactory ensheathing cells in the capability to promote nerve regeneration.

Objective

To study the recovery of the rat facial nerve after olfactory ensheathing cell transplantation, and to compare the differences between the facial nerve regeneration of olfactory mucosa-olfactory ensheathing cells and olfactory bulb olfactory bulb-olfactory ensheathing cells transplantation.

Methods

Institutional ethical guideline was followed (201510129A). Olfactory mucosa-olfactory ensheathing cells and olfactory bulb-olfactory ensheathing cells were cultured and harvested after 7 days in vitro. 36 Sprague Dawley male rats were randomly divided into three different groups depending on the transplanting cells: Group A, olfactory mucosa-olfactory ensheathing cells; Group B, olfactory bulb-olfactory ensheathing cells; Group C, DF-12 medium/fetal bovine serum. The main trunk of the facial nerve was transected and both stumps were inserted into a polylactic acid/chitosan conduit, then the transplanted cells were injected into the collagen in the conduits. After 4 and 8 weeks after the transplant, the rats of the three groups were scarified and the facial function score, facial nerve evoked potentials, histology analysis, and fluorescent retrograde tracing were tested and recorded, respectively, to evaluate the facial nerve regeneration and to analysis the differences among the three groups.

Results

Olfactory ensheathing cells can promote the facial nerve regeneration. Compared with olfactory bulb-olfactory ensheathing cells, olfactory mucosa-olfactory ensheathing cells were more effective in promoting facial nerve regeneration, and this difference was more significant 8 weeks after the transplantation than 4 weeks.

Conclusion

We discovered that olfactory ensheathing cells with nerve conduit could improve the facial nerve recovery, and the olfactory mucosa-olfactory ensheathing cells are more effective for facial nerve regeneration compared with olfactory bulb-olfactory ensheathing cells 8 weeks after the transplantation. These results could cast new light in the therapy of facial nerve defect, and furnish the foundation of auto-transplantation of olfactory mucosa-olfactory ensheathing cells in periphery nerve injury.

Resumo

Introdução

A célula embainhante olfatória é um tipo especial de célula glial que pode promover o crescimento do axônio. Pouco se sabe sobre as diferenças entre as células embainhantes olfatórias da mucosa olfatória e as células embainhantes olfatórias do bulbo olfatório em relação à sua capacidade de promover a regeneração nervosa.

Objetivo

Estudar a regeneração do nervo facial de ratos após o transplante de células embainhantes olfatórias e comparar as diferenças entre a regeneração do nervo facial com o transplante de células embainhantes olfatórias da mucosa olfatória e de células embainhantes olfatórias do bulbo olfatório.

Método

As recomendações éticas da instituição (201510129A) foram seguidas. Células embainhantes olfatórias da mucosa olfatória e células embainhantes olfatórias do bulbo olfatório foram cultivadas in vitro e coletadas após 7 dias. Trinta e seis ratos Sprague Dawley machos foram divididos aleatoriamente em três grupos diferentes, dependendo das células transplantadas: Grupo A, células embainhantes olfatórias da mucosa olfatória; Grupo B, células embainhantes olfatórias do bulbo olfatório; Grupo C, meio de DF-12/soro fetal bovino. O tronco principal do nervo facial foi seccionado e ambos os cotos foram inseridos em um conduto de ácido polilático/quitosana; em seguida, as células transplantadas foram injetadas em colágeno nos condutos. Após 4 e 8 semanas do transplante, os ratos dos três grupos foram agitados para a obtenção do escore da função facial, potenciais evocados do nervo facial, análise histológica e marcador fluorescente retrógrado, que foram testados e registrados, respectivamente, para avaliar a regeneração do nervo facial e analisar as diferenças entre os três grupos.

Resultados

Células embainhantes olfatórias podem promover a regeneração do nervo facial. Em comparação com as células embainhantes olfatórias do bulbo olfatório, as células embainhantes olfatórias da mucosa olfatória foram mais eficazes na promoção da regeneração do nervo facial, e essa diferença foi mais significativa 8 semanas após o transplante comparando-se com 4 semanas.

Conclusão

Verificamos que células embainhantes olfatórias com conduto nervoso podem melhorar a recuperação do nervo facial, e as células embainhantes olfatórias da mucosa olfatória são mais eficazes para a regeneração do nervo facial em comparação com as células embainhantes olfatórias do bulbo olfatório 8 semanas após o transplante. Esses resultados podem lançar uma nova luz ao tratamento de defeitos do nervo facial e fornecer a base do autotransplante de células embainhantes olfatórias da mucosa olfatória em lesões do nervo periférico.

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Increased expression of pendrin in eosinophilic chronic rhinosinusitis with nasal polyps

Publication date: Available online 7 August 2018

Source: Brazilian Journal of Otorhinolaryngology

Author(s): Taku Ito, Satoshi Ikeda, Tomoaki Asamori, Keiji Honda, Yoshiyuki Kawashima, Ken Kitamura, Keiko Suzuki, Takeshi Tsutsumi

Abstract

Introduction

Chronic rhinosinusitis with nasal polyps is heterogeneous disease and appropriate diagnostic algorithms in individual cases are necessary for effective medical treatment.

Objective

The purpose of this study was to clarify the relationship between the pendrin expression of nasal polyps and clinical and pathological characteristic features of eosinophilic chronic rhinosinusitis.

Methods

A total of 68 patients were classified into eosinophilic chronic rhinosinusitis or non-eosinophilic chronic rhinosinusitis groups according to the degree of eosinophilic infiltration into the nasal polyps. Clinical, hematological, and immunohistochemical analyses were performed and statistically compared between both groups.

Results

Thirty-eight were classified into eosinophilic chronic rhinosinusitis and 30 into non-eosinophilic chronic rhinosinusitis groups. There were no significant differences in age distribution, sex ratio, prevalence of asthma, or any other complications between the groups. The mean Lund–Mackay score and the number of serum eosinophils was significantly higher in the eosinophilic chronic rhinosinusitis than in the non-eosinophilic chronic rhinosinusitis groups. The pendrin expression was more frequently detected in the epithelial surface layer of nasal polyps in the eosinophilic chronic rhinosinusitis than in the non-eosinophilic chronic rhinosinusitis groups. In addition, MUC5AC was more widely expressed in the eosinophilic chronic rhinosinusitis than in the non-eosinophilic chronic rhinosinusitis.

Conclusion

Increased expression of pendrin and MUC5AC in the nasal polyps would be associated with development of eosinophilic chronic rhinosinusitis. This finding could allow the development of a novel therapeutic agent targeted specifically to patients with eosinophilic chronic rhinosinusitis.

Resumo

Introdução

A rinossinusite crônica com pólipos nasais é uma doença heterogênea e algoritmos diagnósticos apropriados em casos individuais são necessários para um tratamento médico eficaz.

Objetivo

O objetivo deste estudo foi esclarecer a relação entre a expressão da pendrina de pólipos nasais e propriedades clínicas e patológicas características da rinossinusite crônica eosinofílica.

Método

Um total de 68 pacientes foram classificados como tendo rinossinusite crônica eosinofílica ou rinossinusite crônica não eosinofílica de acordo com o grau de infiltração eosinofílica nos pólipos nasais. Análises clínicas, hematológicas e imunohistoquímicas foram realizadas e comparadas estatisticamente entre os dois grupos.

Resultados

Entre os pacientes, 38 pacientes apresentavam rinossinusite crônica eosinofílica e constituíram o grupo 1 e 30 tinham rinossinusite crônica não eosinofílica, constituindo o grupo 2. Não houve diferenças significantes na distribuição etária, razão entre os sexos, prevalência de asma ou qualquer outra complicação entre os grupos. O escore médio de Lund-Mackay e o número de eosinófilos séricos foram significantemente maiores no grupo com rinossinusite crônica eosinofílica do que no grupo com rinossinusite crônica não eosinofílica. A expressão da pendrina foi mais frequentemente detectada na camada epitelial superficial dos pólipos nasais na rinossinusite crônica eosinofílica do que no grupo com rinossinusite crônica não eosinofílica. Além disso, MUC5AC foi mais amplamente expresso na rinossinusite crônica eosinofílica do que na rinossinusite crônica não eosinofílica.

Conclusão

O aumento da expressão da pendrina e MUC5AC nos pólipos nasais estaria associado ao desenvolvimento de rinossinusite crônica eosinofílica. Esse achado pode permitir o desenvolvimento de um novo agente terapêutico voltado especificamente para pacientes com rinossinusite crônica eosinofílica.

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The effect of adenotonsillar hypertrophy and other obstructive diseases on sleep disorders in children

Publication date: Available online 7 August 2018

Source: Brazilian Journal of Otorhinolaryngology

Author(s): Fatma Caylakli

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Assessment of treatment‐seeking behaviour in patients with psoriasis

British Journal of Dermatology, EarlyView.


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Harvested vs estimated follicular units in hair transplantation

Journal of Cosmetic Dermatology, EarlyView.


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Efficacy of a moisturizer containing a pseudo‐ceramide and a eucalyptus extract for Japanese patients with mild atopic dermatitis in the summer

Journal of Cosmetic Dermatology, EarlyView.


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Introducing a novel model: The special theory of relativity for attractiveness to define a natural and pleasing outcome following cosmetic treatments

Journal of Cosmetic Dermatology, EarlyView.


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Ultrasound to improve the safety of hyaluronic acid filler treatments

Journal of Cosmetic Dermatology, EarlyView.


https://ift.tt/2AYtwCf

Sensitive scalp is associated with excessive sebum and perturbed microbiome

Journal of Cosmetic Dermatology, EarlyView.


https://ift.tt/2voJGQ3

Antera 3D camera: A novel method for evaluating the therapeutic efficacy of fractional CO2 laser for surgical incision scars

Journal of Cosmetic Dermatology, EarlyView.


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Validation of novel Mycobacterium tuberculosis isoniazid resistance mutations not detectable by common molecular tests [PublishAheadOfPrint]

Resistance to the first-line anti-tuberculosis (TB) drug, isoniazid (INH), is widespread, and the mechanism of resistance is unknown in approximately 15% of INH-resistant (INH-R) strains. To improve molecular detection of INH-R TB, we used whole genome sequencing (WGS) to analyze 52 phenotypically INH-R Mycobacterium tuberculosis complex (MTBC) clinical isolates that lacked the common katG S315T or inhA promoter mutations. Approximately 94% (49/52) of strains had mutations at known INH-associated loci that were likely to confer INH resistance. All such mutations would be detectable by sequencing more DNA adjacent to existing target regions. Use of WGS minimized the chances of missing infrequent INH resistance mutations outside commonly targeted hotspots. We used recombineering to generate 12 observed clinical katG mutations in the pansusceptible H37Rv reference strain and determined their impact on INH resistance. Our functional genetic experiments have confirmed the role of seven suspected INH resistance mutations and discovered five novel INH resistance mutations. All recombineered katG mutations conferred resistance to INH at a minimum inhibitory concentration of ≥0.25 μg/mL and should be added to the list of INH resistance determinants targeted by molecular diagnostic assays. We conclude that WGS is a useful tool for detecting uncommon INH resistance mutations that would otherwise be missed by current targeted molecular testing methods, and suggest that its use (or use of expanded conventional or NGS-based targeted sequencing) may provide earlier diagnosis of INH-R TB.

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Mutation-driven evolution of Pseudomonas aeruginosa in the presence of either ceftazidime or ceftazidime/avibactam [PublishAheadOfPrint]

Ceftazidime/avibactam is a combination of beta-lactam/beta-lactamases inhibitor, which use is restricted to some clinical cases including cystic fibrosis patients infected with multidrug resistant Pseudomonas aeruginosa, in which mutation is the main driver of resistance. This study aims to predict the mechanisms of mutation-driven resistance that are selected for when P. aeruginosa is challenged with either ceftazidime or ceftazidime/avibactam. For this purpose, P. aeruginosa PA14 was submitted to experimental evolution in the absence of antibiotics and in the presence of increasing concentrations of ceftazidime or ceftazidime/avibactam for 30 consecutive days. Final populations were analysed by whole-genome sequencing. All evolved populations reached similar levels of ceftazidime resistance. Besides, they were more susceptible to amikacin and produced pyomelanin. A first event in the evolution was the selection of large chromosomal deletions containing hmgA (involved in pyomelanin production), galU (involved in β-lactams resistance) and mexXY-oprM (involved in aminoglycoside resistance). Besides mutations in mpl and dacB that regulate β-lactamase expression, mutations related to MexAB-OprM overexpression were prevalent. Ceftazidime/avibactam challenge selected mutants in the putative efflux pump PA14_45890-45910 and in a two-component system (PA14_45870-45880), likely regulating its expression. All populations produce pyomelanin and were more susceptible to aminoglycosides likely due to the selection of large chromosomal deletions. Since pyomelanin-producing mutants, presenting similar deletions are regularly isolated from infections, the potential aminoglycosides hyper-susceptiblity and reduced β-lactams susceptibility of pyomelanin-producing P. aeruginosa should be taken into consideration for treating infections by these isolates.

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Ex vivo characterisation of effects of renal replacement therapy modalities and settings on pharmacokinetics of meropenem and vaborbactam [PublishAheadOfPrint]

The combination product meropenem/vaborbactam, with activity against KPC-producing carbapenem resistant Enterobacteriaceae, is likely to be used during renal replacement therapy. The aim of this work was to describe the extracorporeal removal (adsorption and clearance) of meropenem/vaborbactam during continuous venovenous hemofiltration (CVVH). An ex vivo model was used to examine the effects of a matrix of operational settings. Vaborbactam did not adsorb to AN69 (acrylonitrile and sodium-methallylsulfonate copolymer) ST100 (surface area, 1m²) hemofilter; whilst mean (± SD) meropenem adsorption was 9% (± 1%). The mean (± SD) sieving coefficients with AN69 ST100 and ST150 (surface area, 1.5m²) filters ranged from 0.97 ± 0.16 to 1.14 ± 0.12 and from 1.13 ± 0.01 to 1.53 ± 0.28, respectively, for meropenem; and for vaborbactam from 0.64 ± 0.39 to 0.90 ± 0.14 and 0.78 ± 0.18 to 1.04 ± 0.28, respectively. At identical settings, vaborbactam sieving coefficients were 25% to 30% lower than that of meropenem. Points of dilution, blood flow rates or effluent flow rates did not affect sieving coefficients for either drug. However, doubling the effluent flow rate resulted in > 50 to 100% increase in filter clearance for both drugs. Post-filter dilution resulted in 40 to 80% increase in filter clearance at high effluent flow rate (4000mL/h) compared with ~15% increase at low effluent flow rate (1000mL/h) for both drugs. For all combinations of setting and filters tested, vaborbactam clearance was lower than that of meropenem by ~20 to 40 %. Overall, meropenem/vaborbactam is efficiently cleared in CVVH mode.

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Effect of pregnancy on the pharmacokinetic interaction between efavirenz and lumefantrine in HIV-malaria co-infection [PublishAheadOfPrint]

Background: Artemether-lumefantrine is often co-administered with efavirenz-based antiretroviral therapy for malaria treatment in HIV-infected women during pregnancy. Previous studies showed changes in lumefantrine pharmacokinetics due to interaction with efavirenz in non-pregnant adults. The influence of pregnancy on this interaction has not been reported.

Method: This pharmacokinetic study involved 35 pregnant and 34 non-pregnant HIV-malaria co-infected women receiving efavirenz-based antiretroviral therapy and was conducted in four health facilities in Nigeria. Participants received three-day standard regimen of artemether-lumefantrine for malaria treatment and intensive pharmacokinetic sampling was conducted 0.5-96 hours after the last dose. Plasma efavirenz, lumefantrine and desbutyl-lumefantrine were quantified using validated assays and pharmacokinetic parameters were derived using noncompartmental analysis.

Results: Median (interquartile range) mid-dose plasma concentrations of efavirenz was significantly lower in pregnant (n = 32) compared with non-pregnant (n = 32) women at 1820 (1300-2610) ng/mL vs 2760 (2020-5640) ng/mL, p = 0.006. Lumefantrine AUC_0-96 was significantly higher in pregnant women (n = 27) at 155,832 (102,400-214,011) ng/mL*h compared with non-pregnant women at 90,594 (58,869-149,775) ng/mL*h, p = 0.03. A similar trend was observed for lumefantrine C₁₂, 2870 (2180-4880) vs 2080 (1190-2970) ng/mL, respectively (p = 0.02). Lumefantrine to desbutyl-lumefantrine ratio also tended to be lower in pregnant than non-pregnant women (P = 0.076).

Conclusion: Overall, pregnancy tempered the extent of efavirenz-lumefantrine interactions resulting in increased lumefantrine exposure. However, any consideration of dosage adjustment for artemether-lumefantrine to enhance exposure in this population needs to be based on data from a prospective study with safety and efficacy end points.

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Biopharmaceutical Characterization of Nebulized Antimicrobial Agents in Rats. 6. Aminoglycosides [PublishAheadOfPrint]

Amikacin and gentamicin pharmacokinetic behaviors after nebulization were determined by comparing plasma and pulmonary epithelial lining fluid (ELF) concentrations in rats after intra-tracheal and intravenous administrations. ELF areas under concentrations time-curves were 874 and 162 times higher after nebulization than after IV administration for amikacin and gentamicin respectively. Even if both molecules appear as good candidates for nebulization, these results demonstrate a much higher targeting advantage of nebulization for amikacin than for gentamicin.

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PA3177 encodes an active diguanylate cyclase that contributes to the biofilm antimicrobial tolerance but not biofilm formation by P. aeruginosa [PublishAheadOfPrint]

A hallmark of biofilms is their heightened resistance to antimicrobial agents. Recent findings suggested a role of c-di-GMP in the susceptibility of bacteria to antimicrobial agents, however, no c-di-GMP modulating enzyme(s) contributing to the drug tolerance phenotype of biofilms has been identified. The goal of this study was to determine whether c-di-GMP modulating enzyme(s) specifically contribute to the biofilm drug tolerance of Pseudomonas aeruginosa. Using RNA-Seq combined with biofilm susceptibility assays, we identified PA3177 encoding a probable diguanylate cyclase. PA3177 was confirmed to be an active diguanylate cyclase, with overexpression affecting swimming and swarming motility, and inactivation affecting cellular c-di-GMP levels of biofilm but not planktonic cells. Inactivation of PA3177 rendered P. aeruginosa PAO1 biofilms susceptible to tobramycin and hydrogen peroxide. Inactivation of PA3177 furthermore eliminated the recalcitrance of biofilms to killing by tobramycin, with multicopy expression of PA3177 but not PA3177_GGAAF harboring substitutions in the active site, restoring tolerance to wild-type levels. Susceptibility was linked to BrlR, a previously described transcriptional regulator contributing to biofilm tolerance, with inactivation of PA3177 negatively impacting BrlR levels and BrlR-DNA binding. While PA3177 contributed to biofilm drug tolerance, inactivation of PA3177 had no effect on attachment and biofilm formation. Our findings demonstrate for the first time that biofilm drug tolerance by P. aeruginosa is linked to a specific c-di-GMP modulating enzyme, PA3177, with the pool of PA3177-generated c-di-GMP only contributing to biofilm drug tolerance but not to biofilm formation.

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Clinical and molecular correlates of Escherichia coli bloodstream infection from two geographically diverse centers in Rochester, Minnesota and Singapore [PublishAheadOfPrint]

Escherichia coli bacteremia is caused mainly by sequence type complex (STc) 131 and two clades within its fluoroquinolone resistance-associated H30 subclone, H30R1 and H30Rx. We examined clinical and molecular correlates of E. coli bacteremia in two geographically distinct centers. We retrospectively studied 251 unique E. coli bloodstream isolates from 246 patients (48 from the Mayo Clinic, Rochester, Minnesota [MN], 198 from Tan Tock Seng Hospital, Singapore [SG]), from October 2013 through March 2014. Isolates underwent PCR for phylogroup, STc, bla_CTX-M type, and virulence gene profiles, and medical records reviewed. Although STc131 accounted for 25-27% of all E. coli bacteremia isolates at each site, its extended-spectrum β-lactamase-associated H30Rx clade was more prominent in SG than MN (15% versus 4%, P = 0.04). In SG only, patients with STc131 (versus other E. coli) were more likely to receive inactive initial antibiotics (odds ratio [OR] 2.8, P = 0.005); this was true specifically for patients with H30Rx (OR 7.0, P = 0.005). H30Rx comprised 16% of community-onset bacteremia episodes in SG, but none in MN. In SG, virulence scores were higher for H30Rx, as compared to H30R1, non-H30 STc131, and non-STc131 isolates (P < 0.02, all comparisons). At neither site did mortality differ by clonal status. The ESBL-associated H30Rx clade was more prevalent and more often of community-onset in SG, where it predicted inactive empiric treatment. Clonal distribution varies geographically and has potentially important clinical implications. Rapid susceptibility testing and clonal diagnostics for H30/H30Rx might facilitate earlier prescribing of active therapy.

https://ift.tt/2M5QF9V

Assessing the effectiveness of curative benznidazole treatment in preventing chronic cardiac pathology in experimental models of Chagas disease [PublishAheadOfPrint]

Chagasic heart disease develops in 30% of those infected with the protozoan parasite Trypanosoma cruzi, but can take decades to become symptomatic. Because of this, it has been difficult to assess the extent to which anti-parasitic therapy can prevent the development of pathology. We sought to address this question using experimental murine models, exploiting highly sensitive bioluminescent imaging to monitor curative efficacy. Mice were inoculated with bioluminescent parasites and then cured with benznidazole in either the acute or chronic stage of infection. At the experimental end-point (5-6 months post-infection), heart tissue was removed and assessed for inflammation and fibrosis, two widely used markers of cardiac pathology. Infection of BALB/c and C3H/HeN mice with distinct T. cruzi lineages resulted in greatly increased myocardial collagen content at a group level, indicative of fibrotic pathology. When mice were cured by benznidazole in the acute stage, the development of pathology was completely blocked. However, if treatment was delayed until the chronic stage, cardiac fibrosis was observed in the BALB/c model, although the protective effect was maintained in the case of C3H/HeN mice. These experiments therefore demonstrate that curative benznidazole treatment early in murine T. cruzi infections can prevent the development of cardiac fibrosis. They also show that treatment during the chronic stage can block pathology, but the effectiveness varies between infection models. If these findings are extendable to humans, it implies that widespread chemotherapeutic intervention targeted at early-stage infections could play a crucial role in reducing Chagas disease morbidity at a population level.

https://ift.tt/2Ms6zbx

Studies on Aminoglycoside Susceptibility Identified a Novel Function of KsgA to Secure Translational Fidelity during Antibiotic Stress [PublishAheadOfPrint]

Antibiotic resistance has become a global crisis. Studies on the mechanism of bacterial tolerance to antibiotics will not only increase our conceptual understanding of bacterial death but also provide potential targets for novel inhibitors. We screened a mutant library containing a full set of in-frame deletion mutants of Escherichia coli K-12 and identified 140 genes that possibly contribute to gentamicin tolerance. Deletion of ksgA increased the inhibition and killing potency against mid-log phase bacteria by aminoglycosides. Initially identified as a 16S rRNA methyltransferase, KsgA also has additional functions as a ribosomal biogenesis factor and a DNA glycosylase. We found that the methyltransferase activity of KsgA is responsible for the tolerance, as demonstrated by a site-directed mutagenesis analysis. In contrast to the mechanism for cold sensitivity, the decreased tolerance to aminoglycoside is not related to the failure of ribosomal biogenesis. Furthermore, the DNA glycosylase activity of KsgA plays little role in kanamycin tolerance. Importantly, we discovered that KsgA secures protein translational fidelity upon kanamycin killing, in contrast to its role during cold stress and kasugamycin treatment. The results suggest that the compromise in protein translational fidelity in the absence of KsgA is the root cause of increased sensitivity to a bactericidal aminoglycoside. In addition, KsgA in the pathogenic Acinetobacter baumannii contributes not only to the tolerance against aminoglycoside killing but also to virulence in the host, warranting potential application as a target for inhibitors that potentiate aminoglycoside therapeutic killing as well as disarm bacterial virulence simultaneously.

https://ift.tt/2MmHuPb

Trend and pattern of antimicrobial resistance in molluscan Vibrio species sourced to Canadian estuaries [PublishAheadOfPrint]

Emergence of antimicrobial resistance (AMR) in foodborne bacteria is a growing concern worldwide. AMR surveillance is a key element in understanding the implications resulting from the use of antibiotics for therapeutic as well as prophylactic needs. The emergence and spread of AMR in foodborne human pathogens is an indirect health hazard. This surveillance study reports the trend and pattern of AMR detected in Vibrio species isolated from molluscs harvested in Canada, between 2006 and 2012, against 19 commonly used antibiotics. Five common antibiotics, ampicillin, cephalothin, erythromycin, kanamycin and streptomycin, predominantly contributed to AMR including multi-drug resistance (MDR) in the molluscan Vibrio spp. isolated in 2006. A prospective follow-up analysis of these drugs showed a declining trend in the frequency of MDR/AMR-Vibrio spp. in subsequent years until 2012. The observed decline appears to have been influenced by the specific downturn in resistance to the aminoglycosides, kanamycin and streptomycin. Frequently observed MDR/AMR-Vibrio spp. in seafood is a potential health concern associated with seafood consumption. Our surveillance study provided an indication of the antibiotics that challenged the marine bacteria, sourced to Canadian estuaries, during and/or prior to the study period.

https://ift.tt/2vq0kyz

Crystal structures of penicillin-binding protein D2 from Listeria monocytogenes: Structural basis for antibiotic specificity [PublishAheadOfPrint]

β-lactam antibiotics that inhibit penicillin-binding proteins (PBPs) have been widely used in the treatment of bacterial infections. However, the molecular basis underlying the different inhibitory potencies of β-lactams against specific PBPs is not fully understood. Here, we present the crystal structures of PBPD2 from Listeria monocytogenes, a Gram-positive food-borne bacterial pathogen that causes listeriosis in humans. The acylated structures in complex with four antibiotics (penicillin G, ampicillin, cefotaxime, and cefuroxime) revealed that the β-lactam core structures were recognized by a common set of residues; however, the R1 side chains of each antibiotic participate in different interactions with PBPD2. In addition, the structural complementarities between the side chains of β-lactams and the enzyme were found to be highly correlated with the relative reactivities of penam or cephem antibiotics against PBPD2. Our study provides the structural basis for the inhibition of PBPD2 by clinically important β-lactam antibiotics that are commonly used in listeriosis treatment. Our findings imply that the modification of β-lactam side chains based on structural complementarity could be useful for the development of potent inhibitors against β-lactam-resistant PBPs.

https://ift.tt/2OhevNv

Local skin inflammation in cutaneous leishmaniasis as a source of variable pharmacokinetics and therapeutic efficacy of liposomal amphotericin B [PublishAheadOfPrint]

Disfiguring skin lesions caused by several species of the Leishmania parasite characterize cutaneous leishmaniasis (CL). Successful treatment of CL with intravenous (IV) liposomal amphotericin B (LAmB) relies on the presence of adequate antibiotic concentrations at the dermal site of infection within the inflamed skin. Here, we have investigated the impact of the local skin inflammation on the pharmacokinetics (PK) and efficacy of LAmB in two murine models of localized CL (Leishmania major and Leishmania mexicana) at three different stages of disease (papule, initial nodule and established nodule). Twenty-four hours after administration of 1 x 25 mg/kg LAmB (IV) to infected BALB/c mice (n=5), drug accumulation in skin was found to be dependent on the causative parasite species (L. major > L. mexicana) and the disease stage (papule > initial nodule > established nodule > healthy skin). Elevated tissue drug levels were associated with increased vascular permeability (Evans Blue assay) and macrophage infiltration (histomorphometry) in the infected skin, two pathophysiological parameters linked to tissue inflammation. After identical treatment of CL in the two models with 5 x 25 mg/kg LAmB (IV), intralesional drug concentrations and reductions in lesion size and parasite load (qPCR) were all ≥ 2-fold higher for L. major compared to L. mexicana. In conclusion, drug penetration of LAmB into CL skin lesions could depend on the disease stage and the causative Leishmania species due to the influence of local tissue inflammation.

https://ift.tt/2vpTqt7

Limited ERG11 mutations identified in isolates of Candida auris directly contribute to reduced azole susceptibility [PublishAheadOfPrint]

Multiple Erg11 amino acid substitutions were identified within clinical isolates of Candida auris originating from India and Colombia. Elevated azole MICs were detected in Saccharomyces cerevisiae upon heterologous expression of C. auris ERG11 alleles that encoded for Y132F or K143R substitutions; however, expression of alleles encoding for I466M, Y501H, or other clade-defined amino acid differences yielded susceptible MICs. Similar to other Candida species, specific C. auris ERG11 mutations directly resulted in reduced azole susceptibility.

https://ift.tt/2MpGJFb

Co-occurring superior mesenteric artery syndrome and nutcracker syndrome requiring Roux-en-Y duodenojejunostomy and left renal vein transposition: a case report and review of the literature

The duodenum and the left renal vein occupy the vascular angle made by the superior mesenteric artery and the aorta. When the angle becomes too acute, compression of either structure can occur. Each type of co...

https://ift.tt/2M5a1fs

Real-world outcomes in hereditary angioedema: first experience from the Icatibant Outcome Survey in the United Kingdom

Hereditary angioedema (HAE) is a potentially life-threatening, bradykinin-mediated disease, often misdiagnosed and under-treated, with long diagnostic delays. There are limited real-world data on best-practice...

https://ift.tt/2Mp7WYD

Content and construct validity, predictors and distribution of self-reported atopic dermatitis severity in US adults

Publication date: Available online 6 August 2018

Source: Annals of Allergy, Asthma & Immunology

Author(s): JI Silverberg, ZC Chiesa Fuxench, JM Gelfand, DJ Margolis, M Boguniewicz, L Fonacier, MH Grayson, EL Simpson, PY Ong

https://ift.tt/2OPqKSD

Association of atopic dermatitis with allergic, autoimmune and cardiovascular comorbidities in US adults

Publication date: Available online 6 August 2018

Source: Annals of Allergy, Asthma & Immunology

Author(s): JI Silverberg, JM Gelfand, D Margolis, M Boguniewicz, L Fonacier, MH Grayson, EL Simpson, P Ong, ZC Chiesa Fuxench

https://ift.tt/2AJ4cA0

Inflammation cutanée de contiguïté secondaire à une sinusite aspergillaire

Publication date: Available online 6 August 2018

Source: Annales de Dermatologie et de Vénéréologie

Author(s): H. Lefranc, C. Brugière, L. Plisson, F. Comoz, L. Verneuil, A. Dompmartin

Résumé

Introduction

L'inflammation cutanée de contiguïté est une entité peu décrite. Elle correspond à la manifestation cutanée d'un processus évolutif qui lui est sous-jacent (infectieux, inflammatoire, néoplasique). Les sinusites en sont une cause connue.

Observation

Nous rapportons le cas d'un homme de 70 ans, qui consultait pour une plaque inflammatoire centro-faciale évolutive. La biopsie cutanée montrait un infiltrat inflammatoire polymorphe et les prélèvements microbiologiques cutanés étaient négatifs. La tomodensitométrie (TDM) du massif facial montrait une sinusite maxillaire gauche. Les prélèvements chirurgicaux intra-sinusiens mettaient en évidence de l'aspergillus. Un traitement par voriconazole, associé à une chirurgie du sinus maxillaire, permettait une guérison de la plaque inflammatoire faciale.

Discussion

Seuls deux cas d'inflammation cutanée de contiguïté liée à une sinusite ont été rapportés dans la littérature, aucun en lien avec une sinusite aspergillaire. Nous rapportons donc le troisième cas d'inflammation cutanée de contiguïté liée à une sinusite, et le premier en rapport avec une sinusite aspergillaire.

Summary

Background

Contiguous skin inflammation is a poorly described entity. It constitutes a cutaneous manifestation of an underlying ongoing process (infectious, inflammatory or neoplastic). Sinusitis is a known cause.

Patients and methods

We report the case of a 70-year-old patient consulting for an ongoing centrofacial inflammatory plaque. Cutaneous biopsy revealed a polymorphic inflammatory infiltrate, and cutaneous microbiological specimens were negative. A facial CT-scan showed left maxillary sinusitis. Intra-sinus samples obtained at surgery showed aspergillus. Voriconazole combined with maxillary sinus surgery resulted in healing of the facial plaque.

Discussion

There have been only two published cases of contiguous skin inflammation related to sinusitis but no reported cases caused by aspergillus sinusitis. Herein we report the third case of contiguous skin inflammation associated with sinusitis, which is also the first related to aspergillus sinusitis.

https://ift.tt/2vnRX6v

Adulte collodion : une forme clinique originale de dermite caustique

Publication date: Available online 6 August 2018

Source: Annales de Dermatologie et de Vénéréologie

Author(s): H. Barailler, V. Cales, C. Salzes, T. Jouary

https://ift.tt/2ANzBRJ

Janus kinase 2 activation mechanisms revealed by analysis of suppressing mutations

Publication date: Available online 6 August 2018

Source: Journal of Allergy and Clinical Immunology

Author(s): Henrik M. Hammarén, Anniina T. Virtanen, Bobin George Abraham, Heidi Peussa, Stevan R. Hubbard, Olli Silvennoinen

Abstract

Background

Janus kinases (JAK1–3, TYK2) mediate cytokine signals in the regulation of hematopoiesis and immunity. JAK2 clinical mutations cause myeloproliferative neoplasms and leukemia and the mutations strongly concentrate in the regulatory pseudokinase domain, JAK homology 2, JH2. Current clinical JAK inhibitors target the tyrosine kinase domain and lack mutation- and pathway-selectivity.

Objective

To characterize mechanisms and differences for pathogenic and cytokine-induced JAK2 activation to enable design of novel selective JAK inhibitors.

Methods

Systematic analysis of JAK2 activation requirements using structure-guided mutagenesis, cell signaling assays, microscopy, and biochemical analysis.

Results

Distinct structural requirements identified for activation of different pathogenic mutations. Specifically, the predominant JAK2 mutation V617F is the most sensitive to structural perturbations in multiple JH2 elements (C helix (αC), SH2-JH2 linker and ATP-binding site). In contrast, activation of K539L is resistant to most perturbations. Normal cytokine signaling shows distinct differences in activation requirements: JH2 ATP-binding site mutations have only a minor effect on signaling, while JH2 αC mutations reduce homomeric (JAK2-JAK2) EPO signaling, and almost completely abrogate heteromeric (JAK2-JAK1) IFNγ signaling, potentially by disrupting a dimerization interface on JH2.

Conclusions

These results suggest that therapeutic approaches targeting the JH2 ATP-binding site and αC could be effective in inhibiting most pathogenic mutations. JH2 ATP-site targeting have potential for reduced side-effects by retaining EPO and IFNγ functions. Simultaneously, however, we identify the JH2 αC interface as a potential target for pathway-selective JAK inhibitors in diseases with unmutated JAK2, thus providing new insights for the development of novel pharmacological interventions.

https://ift.tt/2nn6xXT

Jakinibs for the Treatment of Immunodysregulation in Patients with Gain of Function STAT1 or STAT3 Mutations

Publication date: Available online 6 August 2018

Source: Journal of Allergy and Clinical Immunology

Author(s): Lisa R. Forbes, Tiphanie P. Vogel, Megan A. Cooper, Johana Castro-Wagner, Edith Schussler, Katja G. Weinacht, Ashley S. Plant, Helen C. Su, Eric J. Allenspach, Mary Slatter, Mario Abinun, Desa Lilic, Charlotte Cunningham-Rundles, Olive Eckstein, Peter Olbrich, R. Paul Guillerman, Niraj C. Patel, Yesim Y. Demirdag, Christa Zerbe, Alexandra F. Freeman

Brief Summary

Treatment of the autoimmune and immune-dysregulatory features of patients with STAT1 GOF or STAT3 GOF disease remains challenging. Jakinibs have been used to treat the severe immune-dysregulation in patients with either STAT1 GOF or STAT3 GOF mutations.

https://ift.tt/2M0lPjW

Allergic Airway Sensitization Impairs Anti-Bacterial IgG Antibody Responses During Bacterial Respiratory Infections

Publication date: Available online 6 August 2018

Source: Journal of Allergy and Clinical Immunology

Author(s): Arthur H. Totten, Li Xiao, Danlin Luo, David Briles, Joanetha Y. Hale, Donna M. Crabb, Trenton R. Schoeb, Ammar Saadoon Alishlash, Ken B. Waites, T. Prescott Atkinson

Abstract

Background

Mycoplasma pneumoniae (Mpn), an atypical human pathogen, has been associated with asthma initiation and exacerbation. Asthmatics have been reported to have higher carriage rates of Mpn compared to non-asthmatics, and are at greater risk for invasive respiratory infections.

Objective

To study whether prior allergen sensitization affects the host response to chronic bacterial infection.

Methods

BALB/cJ and IL-4Rα^-/- mice were sensitized with ovalbumin (OVA), and then infected with Mpn or Streptococcus pneumoniae (Spn). Immune parameters were analyzed at 30 days post-infection and included cellular profiles in bronchoalveolar lavage (BAL), and serum IgG and IgE antibody levels to whole bacterial lysate, recombinant P1 (rP1) adhesin, and OVA. Total lung RNA was examined for transcript levels and BAL fluid for cytokine protein profiles.

Results

Anti-Mpn antibody responses were decreased in allergen-sensitized, Mpn-infected animals compared to controls, but OVA-specific IgG responses were unaffected. Similar decreases in anti-Spn antibody levels were found in OVA-sensitized animals. However, Mpn, but not Spn, infection augmented anti-OVA IgE antibody responses. Loss of IL-4 receptor signaling partially restored anti-Mpn antibody responses in IgG2a and IgG2b subclasses. Inflammatory cytokine levels in BAL fluid from OVA-sensitized, Mpn- or Spn-infected animals were reduced compared to uninfected OVA-sensitized controls. Unexpectedly, airway hyperreactivity to methacholine was essentially ablated in Mpn-infected, OVA-sensitized animals.

Conclusions

An established Type 2-biased host immune response impairs the host immune response to respiratory bacterial infection in a largely pathogen independent manner. Some pathogens, e.g. Mpn, can augment ongoing allergic responses and inhibit pulmonary T2 cytokine responses and allergic airway hyperreactivity.

https://ift.tt/2Kup916

Kommentar der Schriftleitung

Laryngo-Rhino-Otol 2018; 97: 520-521
DOI: 10.1055/a-0589-3559

© Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
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Tonsillotomie verursacht weniger indirekte Kosten als Tonsillektomie

Laryngo-Rhino-Otol 2018; 97: 523-524
DOI: 10.1055/a-0465-0081

Gudnadottir G et al. Indirect costs related to caregivers' absence from work after paediatric tonsil surgery. Eur Arch Otorhinolaryngol 2017; 275: 2629–2636. doi:10.1007/s00405–0174526–7 Bei Kindern mit schlafbezogenen Atemwegsobstruktionen durch vergrößerte Rachenmandeln hat die Tonsillotomie die Tonsillektomie heute weitgehend ersetzt. Vorteil könnte neben geringerer Schmerzen und kürzerer Rekonvaleszenzzeit auch eine Reduktion indirekter Kosten durch kürzere Arbeitsausfallzeiten der Eltern oder Betreuer sein. Dies wurde im Rahmen einer schwedischen Kohortenstudie untersucht.
[...]

© Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
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Prävention von Infekten der oberen Atemwege

Laryngo-Rhino-Otol 2018; 97: 529-536
DOI: 10.1055/a-0589-3591

© Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
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https://ift.tt/2ngPKW9

Weniger akute Atemwegsinfekte durch Vitamin-D-Supplementation?

Laryngo-Rhino-Otol 2018; 97: 524-525
DOI: 10.1055/a-0648-6964

Martineau AR. et al. Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data. BMJ 2017; 356: i6583 Vitamin D spielt Studien zufolge auch eine Rolle bei der Abwehr pathogener Keime: 25-Hydroxy-Vitamin D (25[OH] Vitamin D) unterstützt z. B. die Synthese antimikrobieller Peptide. Es gibt also eine mögliche Erklärung für die Beobachtung, dass Personen mit niedrigen Vitamin-D-Spiegeln besonders empfindlich gegenüber respiratorischen Infekten sind. Untersuchungen zu einer präventiven Wirkung des Vitamin D verliefen jedoch zum Teil widersprüchlich.
[...]

© Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
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https://ift.tt/2KycbiO

Rhinoplastik

Laryngo-Rhino-Otol 2018; 97: 581-590
DOI: 10.1055/a-0589-3679

© Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
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https://ift.tt/2LY9BZ1

Unter welchen Bedingungen ist eine ambulante Tonsillektomie sicher?

Laryngo-Rhino-Otol 2018; 97: 525-526
DOI: 10.1055/a-0621-2042

Morris S et al. Overnight in-hospital observation following tonsillectomy: retrospective study of post-operative intervention. J Laryngol Otol 2018; 132: 46–52 Die Sicherheit der ambulanten oder tagesklinischen Tonsillektomie ist gut dokumentiert. Allerdings existieren keine evidenzbasierten Leitlinien, die empfehlen, bei bestimmten Patienten keine ambulante Tonsillektomie auszuführen. Daher wollten australische Ärzte herausfinden, unter welchen Umständen eine ambulante Tonsillektomie als unsicher angesehen werden kann.
[...]

© Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
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https://ift.tt/2Okarw7

Umgang mit suizidalen Patienten

Laryngo-Rhino-Otol 2018; 97: 560-562
DOI: 10.1055/a-0589-3624

© Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
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https://ift.tt/2nfYg7R

Stimmlippenknötchen

Laryngo-Rhino-Otol 2018; 97: 527-528
DOI: 10.1055/a-0589-3602

Eine zu hohe Stimmbelastung kann zu Stimmlippenknötchen führen, einer subepithelialen Schwellung des Stimmlippenrandes. Die Therapie erfolgt aufeinander aufbauend durch Stimmruhe, Stimmübungen und Phonochirurgie mit anschließenden Stimm- oder Gesangsübungen.
[...]

© Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
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https://ift.tt/2KDwdZu

Fragen für die Facharztprüfung

Laryngo-Rhino-Otol 2018; 97: 579-580
DOI: 10.1055/a-0589-3635

© Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
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https://ift.tt/2LW859Z

Diagnostik und operative Therapie der Otosklerose

Laryngo-Rhino-Otol 2018; 97: 563-578
DOI: 10.1055/a-0589-3613

Die Otosklerose ist eine für den HNO-Arzt/Ärztin wichtige, oft in (Differenzial-)Diagnostik und Therapie anspruchsvolle Erkrankung. Wenngleich bis heute eine kausale Therapieoption nicht besteht, kann bei richtiger Diagnosestellung eine operative oder apparative Hörrehabilitation mit sehr hohen Erfolgschancen in Aussicht gestellt werden.
[...]

© Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
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https://ift.tt/2KDw9Je

Intertriginous mastocytosis: a rare presentation of an uncommon disease

International Journal of Dermatology, EarlyView.


https://ift.tt/2vpwUAB

A case of Carvajal syndrome associated with cervical neuroblastoma in an 8‐year‐old girl

International Journal of Dermatology, EarlyView.


https://ift.tt/2MnYWTs

Issue Information

International Journal of Dermatology, Volume 57, Issue 9, Page i-iii,1019-1020, September 2018.


https://ift.tt/2vn5z29

Teaching & Learning Tips 11: Teaching a procedure

International Journal of Dermatology, Volume 57, Issue 9, Page 1114-1117, September 2018.


https://ift.tt/2MnYK6G

Sterol profiles are valuable biomarkers for phenotype expression of Conradi–Hünermann–Happle syndrome with EBP mutations

British Journal of Dermatology, EarlyView.


https://ift.tt/2M1hlsD

Mycophenolate mofetil extravasation resulting in extensive local tissue necrosis

Chemotherapy extravasation is an important complication of intravenous (IV) medication administration and can cause severe, irreversible local tissue damage, potential disfigurement, and functional impairment. Mycophenolate mofetil (MM) is an antiproliferative immunosuppressant used for prevention of organ rejection in solid organ transplant. We report a case of a 58-year-old man with a recent history of cardiac transplantation, with postsurgical course complicated by allograft failure, who was being treated with IV MM for prevention of transplant rejection.

https://ift.tt/2ANsMzL

Mycobacterium marinum infection associated with infliximab therapy in a patient with pulmonary and skin sarcoidosis

Mycobacterium marinum is a nontuberculous acid-fast organism that is an infrequent infection of the skin and soft tissues. The organism is often encountered after exposure to certain fish species and marine environments. High risk patients are those with underlying autoimmune diseases (e.g., sarcoidosis, Crohn's, ankylosing spondylitis) being treated with immunosuppressive therapies such as infliximab and other anti–tumor necrosis factor agents. We present one of the first cases of M. marinum infection associated with infliximab therapy in a patient with pulmonary and skin sarcoidosis.

https://ift.tt/2vlnCWk

Rapid repigmentation of vitiligo with tofacitinib plus low-dose narrowband ultraviolet B (nbUVB), even following depigmentation with monobenzyl ether of hydroquinone

Background: Vitiligo is an autoimmune disease that results in disfiguring white patches of skin due to destruction of melanocytes via cell-mediated immunity. Recent advances in our understanding of vitiligo pathogenesis have led to Janus kinase (JAK) inhibitors, including tofacitinib, as a promising class of targeted therapy with IFN-γ and CD8+ T cells as important mediators.

https://ift.tt/2AIv1nP

Randomized side-by-side comparison of 755-nm diode laser alone and combined with topical photoenhancer gel for hair removal in patients with Fitzpatrick skin type I-V: Efficacy and safety study

Background: Improving laser hair removal (LHR) procedure with novel protocols techniques and photoenhancer ingredients are constantly evolving primarily in an attempt to enhance hair follicle photothermolytic damage and at the same time improve treatment safety and efficacy. Since laser technology advancement feeds market demand-cost relations improving laser hair removal paradigm that will boost clinical outcome and reduce operation costs is deemed necessary in today's LHR competitive market.

https://ift.tt/2OMA9KD

Clinical findings, histology, and management of nonmelanoma skin cancer in cancer survivors previously treated with radiotherapy

Purpose: Radiotherapy is a well known risk factor for nonmelanoma skin cancer (MNSC). This study aims to describe the clinical findings, histology and management of NMSC in cancer survivors previously treated with radiotherapy.

https://ift.tt/2vlnjuE

Clinical manifestations, management, and diagnostic techniques used in hematopoietic stem cell transplant patients with skin infections: A five-year review

The clinical management of infections depends on many factors including location of the patient presentation, specialty of the health care provider, and utilization of diagnostic tests. Appropriate management is especially critical when managing hematopoietic stem cell transplantation (HSCT) patients due to their susceptibility to infection. This retrospective chart review aimed to identify (1) clinical manifestations of skin infections, (2) clinical management methods, and (3) diagnostic testing patterns.

https://ift.tt/2ANsitr

Clinical response after guselkumab treatment among adalimumab PASI 90 nonresponders: Results from the VOYAGE 1 and 2 trials

Objective: To evaluate the levels of response to guselkumab (GUS) among adalimumab (ADA) PASI 90 nonresponders in the VOYAGE 1 and VOYAGE 2 trials.

https://ift.tt/2vreaRe

Coexistence of cutaneous Langerhans cell histiocytosis and reticulohistiocytosis with initial presentation of skull lesions

Coexistence of Langerhans cell histiocytosis (LCH) and reticulohistiocytosis (RH) in different organ and the same skin area is never reported in the literature. We present a 20-year-old female adult with coexistence of bone LCH and diffuse cutaneous RH initially, and then progressed to multisystem LCH with synchronous development of LCH and RH in the skin after chemotherapy for one year. In our patient, multifocal bone LCH and diffuse cutaneous RH coexisted before chemotherapy. After she completed cytarabine (Ara-C) for 12 times, bone LCH much improved but cutaneous LCH developed on previous RH lesions.

https://ift.tt/2OPofj1

Collision tumor of basal cell carcinoma and nevus: Dermoscopic and confocal features

Introduction: A collision tumor is two or more independent neoplasms superimposed on one another. As a result of their overlapping clinical and dermoscopic features they may be diagnostically challenging. Reflectance confocal microscopy (RCM) allows for evaluation of the skin lesions in vivo and better planning concerning their management.

https://ift.tt/2AIuG4x

Combination use of systemic therapies in psoriasis: Baseline characteristics from the Corrona Psoriasis Registry

Background: For patients with moderate to severe psoriasis or psoriatic arthritis, systemic monotherapy can be insufficient in attaining the desired level of control. As such, combination therapies are frequently used in difficult cases. The aim of this study was to analyze the baseline characteristics of patients who require combination therapy using preliminary data from the Corrona Psoriasis Registry.

https://ift.tt/2AIuxy1

Severe bullous pemphigoid with flares triggered by pychosocial stressors

Introduction: Bullous pemphigoid is a rare life-long skin condition that is typically characterized by areas of large fluid-filled blisters and scattered urticarial papules and plaques on the trunk, arms, and legs. It can be induced by medications including furosemide, captopril, or penicillin. Often misdiagnosed as urticaria, the classic manifestations of tense vesicels and bullae which develop on an urticarial base do not develop until later in the course of the disease. It is an immunobullous disorder caused by autoantibodies against basement membrane protein.

https://ift.tt/2OMzGrR

The use of asynchronous remote teledermatology to support frontline health workers: A case example

Introduction: Persistent dermatologic disorders are prevalent in underserved settings with little access to specialized care. We are presenting the case of a pediatric patient with a three month history of unidentified rash. A local nurse collaborated with a volunteer dermatologist through asynchronous remote teledermatology (ARTD) to determine an appropriate treatment plan, avoiding a referral outside of the community.

https://ift.tt/2ANrLrr

Utility of TLE1 immunohistochemistry in melanoma

Background: TLE1 immunohistochemistry (IHC) is widely used as a biomarker of synovial sarcoma. Recently, we described moderate to strong TLE1 expression in 57% of dermal spindle cell melanomas with an additional 33% with weak expression. The utility of TLE1 IHC in melanoma has not been well described. The aim of this study was to investigate TLE1 expression in melanoma.

https://ift.tt/2vo7t2j

Sweet syndrome in a patient with granulomatosis with polyangiitis

Sweet syndrome (acute febrile neutrophilic dermatosis) is rarely known to be associated with Granulomatosis with polyangiitis (GPA), a necrotizing vasculitis of small- and medium-sized blood vessels predominantly affecting respiratory tract, and kidneys. A 66-year-old woman with history of rhinosinusitis, adult onset asthma was seen in medicine clinic for recurrent epistaxis, paranasal sinus congestion, wheezing, dyspnea for 2 years despite maximal medical therapy and sinus surgery. Labs were significant for acute kidney injury (AKI); positive C-anti-neutrophil cytoplasmic antibody (1:5,120); high ESR, CRP, and anti-PR3 (anti–proteinase 3); and microscopic hematuria.

https://ift.tt/2ANrWD7

Reflectance confocal microscopy and image analysis to evaluate the efficacy of a topical facial serum with 20% vitamin C in improving signs of aging

Vitamin C is known for its antioxidant potential and activity in prevents and reverts signs of aging, also by the collagen biosynthetic pathway. Photoprotective properties of topically applied vitamin C have also been demonstrated, placing this molecule as a potential candidate for use in the prevention and treatment of skin aging. A topically applied serum containing 20% vitamin C in different forms (ascorbic acid, ascorbyl methylsilanol pectinate and ascorbyl glucoside) associated with ferulic acid and Ginkgo biloba extract was tested on healthy female volunteers presenting photoaged skin on face to evaluate clinical efficacy of such treatment.

https://ift.tt/2vo7pzB

Treatment of hydroxyurea-induced ulcers with topical timolol

Introduction: Hydroxyurea is an antimetabolite used to treat myeloproliferative disorders, solid tumors, and sickle cell anemia, which has been well documented to cause lower extremity ulcers. Discontinuing the medication may result in spontaneous ulcer resolution. However, hydroxyurea-induced skin ulcers often heal slowly over months to years, causing considerable morbidity.

https://ift.tt/2ANrqFb

The effects of postoperative intralesional corticosteroids in the prevention of recurrent earlobe keloids: A multispecialty retrospective review

Background: Effective treatment of keloids is challenging as the recurrence rate after surgical excision is high. Earlobe keloids are unique due to the low tension in this area, their tendency to respond better to therapy, and their lower recurrence rates after excision. Combination therapy with intralesional corticosteroids is commonly utilized to maximize treatment success. Data on the best treatment practices are lacking.

https://ift.tt/2OQanFt

Who needs penicillin allergy testing?

All individuals with an unconfirmed penicillin allergy should have their penicillin allergy evaluated, and if appropriate, tested to confirm current hypersensitivity or tolerance.

https://ift.tt/2vlwiMe

Content and construct validity, predictors and distribution of self-reported atopic dermatitis severity in US adults

Atopic dermatitis (AD) is a chronic inflammatory skin disease that is associated with variable lesional severity and extent, a broad symptom-burden, including itch, skin pain1, sleep2, 3 and mental health disturbance4, and negative impact on quality of life (QOL)5. Each of these domains differentially and cumulatively affects AD patients and contributes to overall AD severity. Many different scales exist that measure various aspects of AD severity6-13. However, there is no single patient-reported outcome (PRO) that fully captures all aspects of disease severity.

https://ift.tt/2ANe7Ex

Association of atopic dermatitis with allergic, autoimmune and cardiovascular comorbidities in US adults

Atopic Dermatitis (AD) is a chronic inflammatory disorder that affects 7% of US adults (Silverberg et al., 2018; Hua & Silverberg, 2018), and causes significant quality of life impairment and disease burden (Silverberg et al., 2018), and has been found to be associated with a wide range of allergic and non-allergic comorbid disorders (Silverberg & Silverberg, 2014; Silverberg & Hanifin, 2013; Silverberg & Simpson, 2013; Narla & Silverberg, 2017). However, the relationship between AD and comorbid health disorders is complex.

https://ift.tt/2ONporr

Eficacia del corticoide intratimpánico como tratamiento de rescate en sordera súbita neurosensorial idiopática

Publication date: Available online 6 August 2018

Source: Acta Otorrinolaringológica Española

Author(s): Elizabeth Amarillo, Mónica Hernando, Gustavo Eisenberg, Mónica Granda, Guillermo Plaza

Resumen

Introducción

La hipoacusia súbita neurosensorial idiopática (SSI) es la pérdida de al menos 30 dB de causa desconocida. Dado que la recuperación auditiva en SSI es variable, el rescate con corticoides intratimpánicos (CIT) podría contribuir a la recuperación auditiva. Nuestro objetivo es analizar la respuesta auditiva tras CIT como rescate, en ausencia de recuperación completa tras tratamiento sistémico.

Material y método

Realizamos un estudio observacional de cohortes históricas de los 125 casos detectados de SSI entre 2006 y 2014. De ellos, 16 obtuvieron a la semana recuperación completa según los criterios de Siegel. Los 109 casos restantes se analizaron en dos grupos: el que recibió CIT (grupo de tratamiento) y otro que no lo recibió (grupo control). Evaluamos la recuperación auditiva a los 6 meses y a 2 años.

Resultados

La media de audición en la audiometría al diagnóstico no tenía diferencias significativas entre los grupos. Al séptimo día del tratamiento sistémico, el PTA obtenido fue de 53,13 dB en el grupo control y de 66,11 dB en el grupo de estudio (p < 0,01). Tras 6 meses, la ganancia en decibelios obtenida tras el tratamiento con CIT de rescate fue de 10,84 dB, y en el grupo control, de 1,13 dB (p < 0,0001). Tras CIT, solo se consiguió la recuperación completa en 10 pacientes. Ningún paciente del grupo control obtuvo recuperación completa.

Conclusión

Encontramos que el tratamiento de rescate con CIT en la SSI favorece la mejoría auditiva tras la ausencia de recuperación después de un tratamiento sistémico. Sin embargo, en la mayoría de los pacientes no consigue obtener una recuperación completa según criterios de Siegel.

Abstract

Introduction

Idiopathic sudden sensorineural hearing loss (ISSHL) is defined as an abrupt hearing loss of at least 30 dB of unknown cause. The hearing response obtained after intratympanic steroid injection as a salvage treatment after a prior failure of initial systemic steroid treatment was analysed.

Material and method

An observational study was performed on 125 cases of ISSHL who were diagnosed from 2006 to 2014. Sixteen achieved complete recovery after one week according to Siegel's criteria. The remaining 109 cases were analysed in two groups: one that received intratympanic corticosteroid salvage therapy (treatment group) and one that did not (control group). The recovery was analysed after 6 months and 2 years of follow-up.

Results

The difference between each group at baseline were not statistically significant. After systemic treatment for 7 days, PTA in the control group was 53.13 dB and 66.11 dB in the treatment group (P < .01). After 6 months, the mean PTA improvement was 10.84 dB in the treatment group, and 1.13 dB in the control group, a significant difference (P < .0001). Only 10 cases achieved full hearing recovery after intratympanic corticosteroid salvage therapy, none of the patients did so in the control group.

Conclusion

Intratympanic corticosteroid rescue for ISSHL acheived hearing improvement for the cases with failure of initial systemic corticosteroid treatment. However, this treatment did not provide complete hearing recovery according to Siegel's criteria in most cases.

https://ift.tt/2vpMqMN

Actualización del consenso sobre el diagnóstico y tratamiento de la sordera súbita idiopática

Publication date: Available online 6 August 2018

Source: Acta Otorrinolaringológica Española

Author(s): Mayte Herrera, José Ramón García Berrocal, Ana García Arumí, María José Lavilla, Guillermo Plaza, Grupo de Trabajo de la Comisión de Audiología de la SEORL

Resumen

Introducción

La sordera súbita idiopática (SSI) es aquella hipoacusia neurosensorial de inicio súbito de causa desconocida.

Objetivos

Actualización del consenso sobre el diagnóstico, tratamiento y seguimiento de la SSI.

Material y métodos

Presentamos una tercera actualización del consenso de SSI, mediante revisión sistemática de la literatura sobre la SSI desde 1966 hasta marzo de 2018, sobre los términos MESH «(acute or sudden) hearing loss or deafness», con 1.508 artículos relevantes.

Resultados

En cuanto al diagnóstico, ante una sospecha clínica de SSI, las pruebas diagnósticas que se consideran necesarias son las siguientes: otoscopia, acumetría, audiometría tonal, audiometría verbal y timpanograma para descartar causas transmisivas de sordera. Una vez hecho el diagnóstico clínico de SSI, antes de comenzar el tratamiento, se solicitará una batería analítica. Deberá completarse más tarde el estudio con RM de oído interno, idealmente en los primeros 15 días, para descartar causas específicas de sordera súbita neurosensorial y para contribuir a elucidar posibles mecanismos fisiopatológicos. A pesar de la controversia en cuanto al tratamiento de SSI, se recomienda, por los efectos en la calidad de vida de la SSI y los raros eventos indeseables con esteroides a corto plazo, que el tratamiento de la SSI esté basado fundamentalmente en los corticoides, que pueden utilizarse por vía oral o intratimpánica, en función del paciente. En caso de fracaso de la vía sistémica, se recomienda usar corticoides intratimpánicos como rescate. Respecto al seguimiento, se realizará un control a la semana del inicio, a los 7 días y hasta los 12 meses.

Conclusiones

Como consenso, el resultado de los tratamientos aplicados debería presentarse tanto en cantidad de decibelios recuperados en el umbral auditivo tonal como con parámetros de audiometría verbal.

Abstract

Introduction

Idiopathic sudden sensorineural hearing loss (ISSNHL) is a sudden, unexplained unilateral hearing loss.

Objectives

To update the Spanish Consensus on the diagnosis, treatment and follow-up of ISSNHL.

Material and methods

After a systematic review of the literature from 1966 to March 2018, on MESH terms «(acute or sudden) hearing loss or deafness», a third update was performed, including 1508 relevant papers.

Results

Regarding diagnosis, 11 ISSNHL is clinically suspected, the following diagnostic tests are mandatory: otoscopy, acumetry, tonal audiometry, speech audiometry, and tympanometry, to discount conductive causes. After clinical diagnosis has been established, and before treatment is started, a full analysis should be performed. An MRI should then be requested, ideally performed during the first 15 days after diagnosis, to discount specific causes and to help to understand the physiopathological mechanisms in each case. Although treatment is very controversial, due to its effect on quality of life after ISSNHL and the few rare adverse effects associated with short-term steroid treatment, this consensus recommends that all patients should be treated with steroids, orally and/or intratympanically, depending on each patient. In the event of failure of systemic steroids, intratympanic rescue is also recommended. Follow-up should be at day 7, and after 12 months.

Conclusion

By consensus, results after treatment should be reported as absolute decibels recovered in pure tonal audiometry and as improvement in speech audiometry.

https://ift.tt/2Mo6l5v

Tratamiento quirúrgico del angiofibroma nasofaríngeo juvenil en pacientes pediátricos

Publication date: Available online 6 August 2018

Source: Acta Otorrinolaringológica Española

Author(s): Juan Francisco Oré Acevedo, Luis Martín La Torre Caballero, Rosmery Janet Urteaga Quiroga

Resumen

Introducción y objetivos

El nasoangiofibroma juvenil es una neoplasia benigna sumamente vascularizada de tratamiento complejo, tanto en su preparación quirúrgica como en la cirugía a realizar, los riesgos y las recurrencias.

El objetivo es analizar el manejo y tratamiento quirúrgico para el nasoangiofibroma juvenil.

Materiales y métodos

Se revisaron las historias clínicas e imágenes de los pacientes intervenidos por la especialidad de cirugía de cabeza, cuello y maxilofacial con resultado de proceso patológico compatible con nasoangiofibroma juvenil, en el periodo comprendido entre enero de 2008 a diciembre de 2016.

Resultados

Se intervinieron 61 casos, todos ellos tratados con el mismo acceso quirúrgico por medio de una osteotomía Le Fort I. La totalidad de los pacientes fue de sexo masculino, con un promedio de edad de 13,3 años. Se utilizó la clasificación de Andrew-Fish para la estadificación de los casos, obteniendo los grados ii y i la mayor cantidad de casos.

Conclusiones

El abordaje descrito provee un acceso quirúrgico extenso, el cual es adecuado para los diferentes estadios de la tumoración. Requiere de experiencia para poder llevar a cabo la resección de la tumoración con el menor sangrado posible.

Abstract

Introduction and objectives

The juvenile nasopharyngeal angiofibroma is a highly vascularised benign neoplasm of complex treatment in its surgical preparation, surgery to be performed, risks and recurrences.

The aim of the study was to analyze the management and surgical treatment for the pathology of juvenile nasoangiofibroma.

Materials and methods

We reviewed the clinical histories and images of the patients who underwent surgery with a pathology result of juvenile nasoangiofibroma in the period from January 2008 to December 2016.

Results

Sixty-one cases were treated; all of them treated using the same surgical access by means of a Le Fort I osteotomy. All of the patients were male, with an average age of 13.3 years. The Andrew-Fish classification was used for staging the cases, most were staged as grade II and I.

Conclusions

The described approach provided extensive surgical access, which was adequate for the different stages of the tumour. It requires experience to be able to resect the tumour with the least possible bleeding.

https://ift.tt/2M1blQD

In vitro effect of a resin infiltrant on different artificial caries-like enamel lesions

Publication date: Available online 6 August 2018

Source: Archives of Oral Biology

Author(s): Maria Cristina Carvalho de Almendra Freitas, Larissa Vasconcellos Nunes, Lívia Picchi Comar, Rios Daniela, Ana Carolina Magalhães, Heitor Marques Honório, Wang Linda

Abstract

Objectives

A resin infiltrant was employed for the treatment of active white spot lesions due to its ability to penetrate into the enamel pores and prevent the progression of the lesion. However, limited information is available about its mechanical effect on different artificial enamel lesions as well as on its resistance to further demineralization. Therefore, this study aimed to evaluate the effects of the Icon® infiltrant on different artificial caries-like enamel lesions and its resistance to new acid challenges.

Design

Artificial lesions were produced in bovine enamel using three different protocols (demineralization/remineralization cycling, DE-RE; 8% methylcellulose gel, MC; and methyl ethyl diphosphonate solution, MHDP; n = 13). The specimens were treated with Icon® and subjected to a new acid challenge using DE-RE cycling. The surface and cross-sectional hardness were evaluated in sound, demineralized, treated and further demineralized enamel areas. Data were statistically analyzed using ANOVA and Tukey's test (p < 0.05).

Results

All of the demineralizing protocols produced subsurface artificial caries lesions. The infiltrant was able to partially recover the surface hardness and prevent further surface hardness loss in enamel previously demineralized using the DE-RE and MHDP protocols. In regard to cross-sectional hardness, no positive effect was found.

Conclusions

The effect of the infiltrant depends on the type of lesion created in vitro, and its action is limited to the lesion surface.

https://ift.tt/2ASwOGK

Clinical and Genetic Signatures of Local Recurrence in Oral Squamous Cell Carcinoma

Publication date: Available online 6 August 2018

Source: Archives of Oral Biology

Author(s): Yasmine Ghantous, Zaher Bahouth, Imad Abu El-naaj

Abstract

Purpose

Recurrent and metastatic Oral Squamous Cell Carcinoma (OSCC) is often incurable. There are large gaps in the understanding of the clinical course, biology and genetic biomarkers of OSCC which could help us identify patients with high-risk of recurrence who may benefit from intensified therapy or novel targeted therapy trials.

The purpose of this study was to identify significant clinical, pathological and genomic risk factors for local recurrence in OSCC.

Patients and methods

Molecular data sets and clinicopathological characteristics of 159 head and neck carcinoma patients were obtained from The Cancer Genome Atlas (TCGA) data portal and analyzed using the Genome Data Analysis Center and cBioPortal to find significant risk factors for tumor recurrence.

Results

The local recurrence rate was 24%. OSCC originating from the buccal mucosa composed 13% of all the tumors in the recurrent group, making it a statistically significant risk of recurrence (P value = .03). Likewise, positive surgical margins, pathological T staging, and alcohol consumption were found to be significantly associated with recurrence (P value < .05).

Genetic profiling revealed the top 5 mutated genes (using the MutSigCV analysis). Only one of these genes, CASP8 was the only gene that was significantly altered only in the recurrent group (Q value = 8.7 × 10^-11). The fingerprint of 5 mutated genes was found in 97% of the patients in the recurrence group. Moreover, copy number alterations in cytoband 5p15.33, which involved amplification in telomerase reverse-transcriptase (TERT) gene, was found to be significant only in the recurrent group.

Conclusions

In the current study, we found several clinical and genetic characteristics that could define patients with high-risk of OSCC recurrence. This provides a means of identifying patients that may benefit from intensified therapy or novel targeted therapy trials.

https://ift.tt/2vpeFeK

Qualified Biolayer Interferometry Avidity Measurements Distinguish the Heterogeneity of Antibody Interactions with Plasmodium falciparum Circumsporozoite Protein Antigens [NOVEL IMMUNOLOGICAL METHODS]

Ab avidity is a measure of the overall strength of Ab–Ag interactions and hence is important for understanding the functional efficiency of Abs. In vaccine evaluations, Ab avidity measurements can provide insights into immune correlates of protection and generate hypotheses regarding mechanisms of protection to improve vaccine design to achieve higher levels of efficacy. The commonly used Ab avidity assays require the use of chaotropic reagents to measure avidity index. In this study, using real-time detection of Ab–Ag binding by biolayer interferometry (BLI) technique, we have developed a qualified assay for measuring avidity of vaccine-induced Abs specific for Plasmodium falciparum circumsporozoite protein (CSP) Ags. Human mAb derived from plasmablasts of recipients of RTS,S/AS01 (RTS,S), the most advanced malaria vaccine candidate, were used in the assay development to measure Ag-specific binding responses and rate constants of association and dissociation. The optimized BLI binding assay demonstrated 1) good precision (percentage of coefficient of variation <20), 2) high specificity, 3) a lower limit of detection and quantitation in the 0.3–3.3 nM range, and 4) a range of linearity up to 50–100 nM for the CSP Ags tested. Analysis of polyclonal sera of malaria vaccinees demonstrated the suitability of this method to distinguish among vaccinees and rank Ab responses by avidity. These results demonstrate that precise, specific, and sensitive BLI measurements of Ab avidity in polyclonal sera from malaria vaccinees can map Ab response heterogeneity and potentially help to determine the role of Ab avidity as an immune correlate of protection for vaccines.

https://ift.tt/2OhhxRI

Tumor Dendritic Cells (DCs) Derived from Precursors of Conventional DCs Are Dispensable for Intratumor CTL Responses [TUMOR IMMUNOLOGY]

The success of adoptive CTL therapy for cancer depends on interactions between tumor-infiltrating CTLs and cancer cells as well as other cells and molecules in the tumor microenvironment. Tumor dendritic cells (DCs) comprise several subsets: CD103⁺CD11b^– DC1 and CD11b⁺CD64^– DC2, which originate from circulating precursors of conventional DCs, and CD11b⁺CD64⁺ DC3, which arise from monocytes. It remains controversial which of these subset(s) promotes intratumor CTL proliferation, expansion, and function. To address this issue, we used the Zbtb46-DTR–transgenic mouse model to selectively deplete DC1 and DC2 from tumors and lymphoid tissues. Wild-type and Zbtb46-DTR bone marrow chimeras were inoculated with B16 melanoma cells that express OVA and were treated with OT-1 CTLs. We found that depletion of DCs derived from precursors of conventional DCs in Zbtb46-DTR bone marrow chimeras abolished CTL proliferation and expansion in tumor-draining lymph nodes. By contrast, intratumor CTL accumulation, proliferation, and IFN- expression were unaffected by their absence. We found that adoptive cell therapy increases the frequency of monocyte-derived tumor DC3, which possess the capacity to cross-present tumor Ags and induce CTL proliferation. Our findings support the specialized roles of different DC subsets in the regulation of antitumor CTL responses.

https://ift.tt/2LXvGah

Variation in Genome-Wide NF-{kappa}B RELA Binding Sites upon Microbial Stimuli and Identification of a Virus Response Profile [SYSTEMS IMMUNOLOGY]

NF-B transcription factors are master regulators of the innate immune response. Activated downstream of pathogen recognition receptors, they regulate the expression of genes to help fight infections as well as recruit the adaptive immune system. NF-B responds to a wide variety of signals, but the processes by which stimulus specificity is attained remain unclear. In this article, we characterized the response of one NF-B member, RELA, to four stimuli mimicking infection in human nasopharyngeal epithelial cells. Comparing genome-wide RELA binding, we observed stimulus-specific sites, although most sites overlapped across stimuli. Specifically, the response to poly I:C (mimicking viral dsRNA and signaling through TLR3) induced a distinct RELA profile, binding in the vicinity of antiviral genes and correlating with corresponding gene expression. This group of binding sites was also enriched in IFN regulatory factor motifs and showed overlapping with IFN regulatory factor binding sites. A novel NF-B target, OASL, was further validated and showed TLR3-specific activation. This work showed that some RELA DNA binding sites varied in activation response following different stimulations and that interaction with more specialized factors could help achieve this stimulus-specific activity. Our data provide a genomic view of regulated host response to different pathogen stimuli.

https://ift.tt/2OhhzJk

CX3CR1+ Macrophages and CD8+ T Cells Control Intestinal IgA Production [MUCOSAL IMMUNOLOGY]

Secretory IgA is a key host defense mechanism that controls the intestinal microbiota. We investigated the role of CD11c⁺CX₃CR1⁺CD64⁺ macrophages in IgA production in the intestine. Intestinal CX₃CR1⁺ macrophages directly induced IgA secretion by B cells. Ag delivery to lamina propria (LP) CX₃CR1⁺ macrophages specifically induced intestinal IgA production. The induction of IgA by CX₃CR1⁺ macrophages required BAFF, a proliferation-inducing ligand, and TNF-α, but was surprisingly independent of TLR-mediated microbial recognition and retinoic acid signaling. IgA secretion by CX₃CR1⁺ macrophages was enhanced by LP CD8⁺ T cells through the secretion of IL-9 and IL-13. CX₃CR1⁺ macrophages and CD8⁺ T cells induced IgA production by B cells independently of mesenteric lymph nodes and Peyer patches. Our data reveal a previously unrecognized cellular circuitry in which LP CX₃CR1⁺ macrophages, B cells, and CD8⁺ T cells coordinate the protective Ig secretion in the small intestine upon peripheral Ag delivery.

https://ift.tt/2LXTJG2

Cellular Mechanisms Controlling Surfacing of AICL Glycoproteins, Cognate Ligands of the Activating NK Receptor NKp80 [MOLECULAR AND STRUCTURAL IMMUNOLOGY]

AICL glycoproteins are cognate activation-induced ligands of the C-type lectin-like receptor NKp80, which is expressed on virtually all mature human NK cells, and NKp80–AICL interaction stimulates NK cell effector functions such as cytotoxicity and cytokine secretion. Notably, AICL and NKp80 are encoded by adjacent genes in the NK gene complex and are coexpressed by human NK cells. Whereas AICL is intracellularly retained in resting NK cells, exposure of NK cells to proinflammatory cytokines results in AICL surfacing and susceptibility to NKp80-mediated NK fratricide. In this study, we characterize molecular determinants of AICL glycoproteins that cause intracellular retention, thereby controlling AICL surface expression. Cys⁸⁷ residing within the C-type lectin-like domain not only ensures stable homodimerization of AICL glycoproteins by disulfide bonding, but Cys⁸⁷ is also required for efficient cell surface expression of AICL homodimers and essential for AICL–NKp80 interaction. In contrast, cytoplasmic lysines act as negative regulators targeting AICL for proteasomal degradation. One atypical and three conventional N-linked glycosylation sites in the AICL C-type lectin-like domain critically impact maturation and surfacing of AICL, which is strictly dependent on glycosylation of at least one conventional glycosylation site. However, although the extent of conventional N-linked glycosylation positively correlates with AICL surface expression, the atypical glycosylation site impairs AICL surfacing. Stringent control of AICL surface expression by glycosylation is reflected by the pronounced interaction of AICL with calnexin and the impaired AICL expression in calnexin-deficient cells. Collectively, our data demonstrate that AICL expression and surfacing are tightly controlled by several independent cellular posttranslational mechanisms.

https://ift.tt/2Od6mJQ

Glucocorticoids Inhibit Group 3 Innate Lymphocyte IL-22 Production [INNATE IMMUNITY AND INFLAMMATION]

Glucocorticoids (GCs) are commonly prescribed to patients with a variety of inflammatory disorders, including inflammatory bowel disease (IBD). GCs mediate their immunomodulatory effects through many different mechanisms and target multiple signaling pathways. The GC dexamethasone downmodulates innate and adaptive immune cell activation. IBD is the manifestation of a dysregulated immune response involving many different immune cells. Group 3 innate lymphocytes (ILC3s) have critical roles in mucosal inflammation. ILC3s secrete high levels of the cytokine IL-22, promoting epithelial proliferation, antimicrobial peptides, and mucins. In this study, we examined the effects of dexamethasone on IL-22 production by ILC3s. We found that dexamethasone suppressed IL-23–mediated IL-22 production in human and mouse ILC3s. This was mediated in part through dexamethasone modulation of the NF-B pathway. Inhibition of NF-B signaling with a small molecule inhibitor also downmodulated IL-23– and IL-1β–mediated IL-22 production in ILC3s. These findings implicate NF-B as a regulator of IL-22 in ILC3s and likely have repercussions on GC treatment of IBD patients.

https://ift.tt/2neNNcR

CD4+ Regulatory T Cells Exert Differential Functions during Early and Late Stages of the Immune Response to Respiratory Viruses [INFECTIOUS DISEASE AND HOST RESPONSE]

Acute respiratory virus infection (ARI) induces CD8⁺ T cells with diminished cytokine production and functional impairment. The role of cellular mediators of immune impairment, specifically CD4⁺ regulatory T cells (Tregs), is incompletely understood in ARI. Tregs are known suppressors of effector T cell function, but whether they are detrimental or beneficial in ARI remains controversial. We show in this paper that Treg depletion leads to increased CD8⁺ T cell function and lower virus titer in mice infected with human metapneumovirus. We further demonstrate that Tregs play a temporal role in the immune response to human metapneumovirus and influenza: Treg depletion before infection pathologically reduces virus-specific CD8⁺ T cell numbers and delays virus clearance, whereas depletion 2 d postinoculation enhances CD8⁺ T cell functionality without reducing virus-specific CD8⁺ T cell numbers. Mechanistically, Treg depletion during immune priming led to impaired dendritic cell and CD8⁺ T cell migration. Further, early Treg depletion was associated with immune skewing toward a type 2 phenotype characterized by increased type 2 innate lymphoid cells and T_H2 CD4⁺ T cells, which was not observed when Treg depletion was delayed until after inoculation. These results indicate that the presence of Tregs at inoculation is critical for efficient priming of the CD8⁺ T cell response to ARI, whereas later in infection, Tregs are dispensable for virus clearance.

https://ift.tt/2OdfAWz