bluuebunny/crossref_metadata_2025 huggingface dataset:
Genomic and Clinicopathologic Characteristics of PRKAR1A-inactivated Melanomas
Authors: Cohen Jarish N. , Yeh Iwei , Mully Thaddeus W. , LeBoit Philip E. , McCalmont Timothy H.
Published: March 2020

Melanocytic tumors with inactivation of protein kinase A regulatory subunit-α (PRKAR1A) have large oval nuclei and intense pigmentation. Historically, these tumors have been categorized under various names, including epithelioid blue nevus, pigmented epithelioid melanocytoma (PEM) and animal-type melanoma. Although a subset of PEM harbor BRAF activating mutations and biallelic inactivation of PRKAR1A, there are only a few reports of melanomas, or of tumors with genomic alterations beyond those of PEMs. Herein, we describe the clinicopathologic and genetic features of 8 melanomas and tumors that lack PRKAR1α expression by immunohistochemistry but do not fit with conventional PRKAR1A-inactivated melanocytomas. These tumors tended to affect younger patients than conventional melanomas (median age=38 y) and presented as dark brown/black papules and nodules. Histopathologically, they demonstrated nodularity, sometimes in a background of conventional melanoma, and large vesicular nuclei with prominent nucleoli. With the exception of 1 case, the mitotic index was not significantly elevated. Immunohistochemically, all cases showed loss of PRKAR1α and of p16 expression. Seven tumors underwent massively parallel short read (next-generation) sequencing of a panel of 480 cancer-associated genes. Five tumors demonstrated truncating mutations of PRKAR1A and the 2 in which such mutations were not identified demonstrated loss of heterozygosity of the PRKAR1A locus. Four of the tumors harbored BRAF V600E mutations, and 1 harbored a FAM39B-BRAF gene fusion. Another harbored a GNA11 activating mutation. A MAP kinase activating mutation was not identified in the remaining case. Four tumors displayed TERT promoter mutations and chromosomal copy number changes supporting the diagnosis of melanoma. Two cases without these alterations and were classified as “high-grade PRKAR1A-inactivated melanocytomas”. The 1 case with widespread metastases demonstrated mutations in TP53 and RB1. Overall, we provide the first genetic characterization of PRKAR1A-inactivated melanomas, discuss the differential diagnosis of heavily pigmented epithelioid melanocytic neoplasms, and propose a new nomenclature for such tumors.
Antiretroviral Prophylaxis
Authors: Lemoine Anaïs , Michot Joëlle , Viala Jérôme , Tounian Patrick , Dollfus Catherine
Published: March 2020

An 8-year-old child experienced abdominal pain and melena due to duodenal and ileal ulcerations throughout antiretroviral prophylactic treatment after a needlestick injury. Mild to moderate adverse effects often occur with lamivudine and zidovudine, but more severe adverse effects such as intestinal ulcers resulting in melena after a prophylactic antiretroviral treatment may question the safety of the current guidelines.
Point-of-Care Ultrasound in United States Pediatric Emergency Medicine Fellowship Programs
Authors: Acuña Josie , Rubin Marina , Hahn Barry , Das Devjani , Kapoor Monica , Adhikari Srikar , Greenstein Joshua
Published: March 2020

Objectives

In 2015, the American Academy of Pediatrics (AAP) released a policy statement regarding point-of-care ultrasonography (POCUS) by pediatric emergency physicians, which included recommendations on education and training. In the 3 years since the AAP policy statement and its accompanying technical report were published, it is unclear which aspects of the recommendations set forth by this policy have been instituted by POCUS programs throughout the country. The objective of this study was to conduct a survey of pediatric emergency medicine (PEM) fellowship directors throughout the United States regarding the current state of education and training of POCUS in their department.

Methods

We conducted an online survey of all PEM fellowship program directors in the United States between April 1, 2018, and July 31, 2018.

Results

Of the 78 PEM fellowship program directors contacted, 62 (79.5%) responded. The majority reported having an ultrasound curriculum in place to educate their fellows (77%). Fellows are being taught using a variety of educational strategies. The most commonly reported barriers were lack of qualified faculty available for training (62.9%), lack of confidence or comfort in using the existing ultrasound machine(s) in their department (54.8%), and physician resistance to using new technology (50%). The majority of programs reported having processes in place for credentialing (56%) and quality assurance (72.6%). Whereas 77.4% have a system for archiving POCUS studies after they are performed, only half of the programs report utilization of middleware for their archival system. Compliance with documentation varied significantly between programs.

Conclusions

Our survey results demonstrate that, although there is still room for improvement, POCUS programs have succeeded in many of the goals set forth by the 2015 AAP policy statement, such as establishing and growing an ultrasound curriculum and using various strategies to educate PEM fellows.
The Utility of Ultrasound in Detecting Skull Fractures After Pediatric Blunt Head Trauma
Authors: Gordon Isaac , Sinert Richard , Chao Jennifer
Published: March 2020

Background

Head trauma is a common reason for evaluation in the emergency department. The evaluation for traumatic brain injury involves computed tomography, exposing children to ionizing radiation. Skull fractures are associated with intracranial bleed. Point-of-care ultrasound (POCUS) can diagnose skull fractures.

Objectives

We performed a systematic review/meta-analysis to determine operating characteristics of POCUS skull studies in the diagnosis of fractures in pediatric head trauma patients.

Methods

We searched PubMed, EMBASE, and Web of Science for studies of emergency department pediatric head trauma patients. Quality Assessment Tool for Diagnostic Accuracy Studies 2 was used to evaluate risk of bias. Point-of-care ultrasound skull study operating characteristics were calculated and pooled using Meta-DiSc.

Results

Six studies of 393 patients were selected with a weighted prevalence of 30.84%. Most studies were at low risk of bias. The pooled sensitivity (91%) and specificity (96%) resulted in pooled positive likelihood ratio (14.4) and negative likelihood ratio (0.14). Using the weighted prevalence of skull fractures across the studies as a pretest probability (31%), a positive skull ultrasound would increase the probability to 87%, whereas a negative test would decrease the probability of a skull fracture to 6%. To achieve a posttest probability of a skull fracture of ~2% would require a negative skull ultrasound in a patient with only a pretest probability of ~15%.

Conclusions

A POCUS skull study significantly increases the probability of skull fracture, whereas a negative study markedly decreases the probability if the pretest probability is very low.
Analysis of Scars and Keloids by Focused Ion Beam/Scanning Electron Microscopy
Authors: Migita Hisashi , Rikimaru Hideaki , Rikimaru-Nishi Yukiko , Koga Noriyuki , Watanabe Koichi , Ohta Keisuke , Nakamura Kei-ichiro , Kiyokawa Kensuke
Published: March 2020

Background

Histological differentiation between hypertrophic scars (HSs) and keloids has been considered difficult. In this study, we analyzed differences in the 3-dimensional tissue architecture between HSs and keloids using focused ion beam/scanning electron microscopy (FIB/SEM).

Methods

Five specimens each of normal skin, normotrophic scars (NSs), HSs, and keloids were investigated. Three sites in each specimen were observed by FIB/SEM tomography, resulting in an observation of 15 sites per tissue type. We identified fibroblasts and macrophages and assessed the contact ratio and the mode of intercellular contact (planar contact or point contact). The significance of differences among the 4 tissue types was determined by Fisher exact test.

Results

In normal skin, contact between fibroblasts and macrophages was observed at all 15 sites, and the mode of contact was always planar. There was contact at 87% of the NS sites (planar: point = 80%: 7%). In HSs, contact was seen at 80% of the sites (planar: point = 20%: 60%). In keloids, contact was found at only 15% of the sites (planar: point = 7.5%: 7.5%). The intercellular contact ratio showed no significant differences among normal skin, NSs, and HSs; however, a significant difference was noted between these tissues and keloids. The intercellular contact mode also showed no significant difference between normal skin and NSs, but a significant difference between these tissues and HSs.

Conclusions

These histopathologic findings suggest that FIB/SEM tomography is useful for distinguishing between HSs and keloids and can provide important knowledge for understanding the pathogenesis of keloids.
Surgical Treatment of Dacryocystitis by Using a Venous Catheter
Authors: Meduri Alessandro , Inferrera Leandro , Tumminello Giuseppe , Cicciù Marco , Aragona Pasquale
Published: March 2020

Purpose:

Aim of this work is to highlight the advantages of a new surgical technique performed over 15 patients affected dacryocystitis and treated by using a venous catheter.

The arrangement of a 30 mm venous catheter used at the end of a dacryocystectomy (DCT) was performed in 15 patients with dacryocystitis. The venous catheter was removed at 30 days after the surgery.

The use of the venous catheter allows washing the lacrimal drainage system, reducing the risk of postoperative infections and supports the recanalization of the lacrimal drainage system 30 days after surgery.

The presented cases demonstrated how the technique is easy and it reduces the possibility of the post-operative infection. It could be performed under regional anesthesia. Furthermore, after the surgery the recanalization of the lacrimal drainage system with a significant reduction of the epiphora in 6 months after surgery has been observed.
Impact of Upper Airway Collapse and Sleep Parameters on Daytime Sleepiness and Sleep Quality
Authors: Gurpinar Berk , Friedman Michael , Senel Gulcin Benbir , Sayin Sevgi , Boroosan Avrahan , Uyar Yavuz , Karadeniz Derya
Published: March 2020

Objective:

Standard overnight polysomnography (PSG) scores only the apneahypopnea index (AHI) as a predictor of sleep apnea. It is proven that the arousals also contribute especially to the daytime symptoms of obstructive sleep apnea syndrome (OSA). The authors aimed to search the relevance of arousals and obstruction site in the upper airway with the sleep parameters, daytime sleepiness and the sleep quality.

Materials and Methods:

A total number of 118 subjects were recruited. All of them received a full-night attended PSG and a thorough otolaryngologic examination to identify the site of obstruction in the upper airway and 2 different sleep questionnaires to present the daytime sleepiness and the sleep quality.

Results:

The level of nasal airway blockage had no impact on AHI, daytime sleepiness and the sleep quality. The increase in level of tonsillar hypertrophy had a negative impact on oxygen desaturation index (ODI) only (P = 0.021). The level of retrolingual obstruction worsen ODI (P = 0.022), AHI (P = 0.041), daytime sleepiness (P = 0.047) and sleep quality (P = 0.033).

Conclusion:

Arousals during sleep deserve better attention in scoring PSG events, as they reliably reflect daytime somnolence and sleep quality. Retrolingual obstruction was the main contributor for cortical arousals. It is imperative to cure retrolingual obstruction properly which may be easily detected in sleep endoscopy.
Comparison of Resident Self-Evaluation to Standardized Patient Evaluators in a Multi-Institutional Objective Structured Clinical Examination
Authors: Diaczok Benjamin John , Brennan Simone , Levine Diane , Hilu Raymond , Thati Neelimi , Kruer James , Ahsan Samira , McNally Patricia , Pieper David
Published: March 2020

Background

For the past 30 years, there has been a growing emphasis on communication and self-evaluation skills training in graduate medical education. This is reflected in the Next Accreditation System. The Objective Structured Clinical Examination (OSCE) is widely used in graduate medical education for assessing dimensions of interpersonal communication and counseling skills. The OSCEs may be developed to target challenging clinical scenarios difficult to capture in clinical practice and can be used as a medium for resident self-evaluation.

Objectives

The aims of the study were to evaluate residents' interpersonal, communication, and counseling skills using Kalamazoo Essential Elements Communication Checklist in 4 clinically challenging scenarios and to compare standardized patient (SP) evaluations to residents' self-evaluation by category of medical school.

Methods

South East Michigan Center for Medical Education is a consortium of teaching hospitals. Member residents participate in 4 OSCEs as part of their postgraduate 1 curriculum. The OSCEs were developed to evaluate clinically relevant but difficult to capture scenarios including: (a) error disclosure/counseling an angry patient; (b) delivering bad news/end of life; (c) domestic violence; and (d) counseling a patient with colon cancer requesting alternative treatments. At the conclusion of each OSCE, SPs evaluated and residents self-evaluated their performance. Once evaluations were completed, SPs provided residents with feedback.

Results

Six member institutions and 344 residents participated during the 2014, 2015, and 2016 academic years. There were more international medical graduates (59%) than graduates of Liaison Committee for Medical Education–accredited medical schools. There were more males (62.2%) than females. Standardized patients rated residents higher than residents rated themselves in 2014 (<0.001), but not in 2015 or 2016. When combining all years and all residents, there was no correlation of SP and resident scores. Standardized patients rated female residents higher than female residents rated themselves (P < 0.0001). Male residents scored themselves similarly to the SPs, but male residents rated themselves higher than female residents rated themselves (P < 0.001). Standardized patient scores for male and female residents were not significantly different.

Conclusions

Targeted OSCEs provide an objective format to evaluate residents in challenging clinical scenarios. Resident self-evaluations did not correlate with SPs. In addition, female residents rated themselves lower than male residents and lower than SPs. There is need to develop interventions and curricula to improve resident's self-evaluation skills and in particular address lower self-evaluation by female trainees.
Lack of Diversity in Simulation Technology
Authors: Conigliaro Rosemarie L. , Peterson Kerstin D. , Stratton Terry D.
Published: March 2020

Summary Statement

Despite increased attention on diversity in medicine and healthcare, heterogeneity in simulation technology has been slow to follow suit. In a nonsystematic review of simulation technology available in 2018 with respect to skin tone, age and sex, we found limited diversity in these offerings, suggesting limitations to educators' abilities to represent the full array of patients, conditions, and scenarios encountered in medicine and training. We highlight these limitations and propose basic strategies by which educators can increase awareness of and incorporate diversity into the simulation arena.
Transfer of Clinical Reasoning Trained With a Serious Game to Comparable Clinical Problems
Authors: Middeke Angélina , Anders Sven , Raupach Tobias , Schuelper Nikolai
Published: March 2020

Introduction

Serious Games can be used effectively for clinical reasoning training in medical education. Case specificity of learning outcome elicited by Serious Games has not been studied in detail. This study investigated whether learning outcome elicited by repeated exposure to virtual patient cases is transferable to other cases addressing similar problems.

Methods

In this monocentric, prospective, randomized trial, 69 fifth-year medical students participated in ten 90-minute sessions of using a computer-based emergency ward simulation game. Students were randomized to 3 groups (A, B, AB) and subsequently exposed to up to 46 different virtual patients. Group A was presented with 2 specific cases that were not shown in group B and vice versa. Group AB was exposed to all 4 specific cases. After 6 weeks of using the game as a learning resource, students were presented with 4 cases addressing similar problems. For each case, an aggregate score reflecting clinical reasoning was calculated, and performance was compared across groups.

Results

In the final session, there were no significant between-group differences regarding the sum score reflecting aggregated performance in all 4 cases (A: 66.5 ± 7.2% vs. B: 61.9 ± 12.4% vs. AB: 64.8 ± 11.1%, P = 0.399). An item-by-item analysis revealed that there were no between-group differences regarding correct therapeutic interventions.

Conclusions

Previous exposure had limited impact on subsequent performance in similar cases. This study suggests that case specificity of learning outcome elicited by the serious game is low and that acquired higher-order cognitive functions may transfer to similar virtual patients.
Survivors of gun violence and the experience of recovery
Authors: O'Neill Kathleen M. , Vega Cecilio , Saint-Hilaire Sidney , Jahad Leonard , Violano Pina , Rosenthal Marjorie S. , Maung Adrian A. , Becher Robert D. , Dodington James
Published: March 2020

BACKGROUND

Survivors of gun violence may develop significant mental health sequelae and are at higher risk for reinjury through repeat violence. Despite this, survivors of gun violence often return to the community where they were injured with suboptimal support for their mental health, emotional recovery, and well-being. The goal of this study was to characterize the posthospitalization recovery experience of survivors of gun violence.

METHODS

We conducted a qualitative research study with a community-based participatory research approach. In partnership with a community-based organization, we conducted in-depth one-on-one interviews and used snowball sampling to recruit survivors of gun violence. We applied the constant comparison method of qualitative analysis to catalogue interview transcript data by assigning conceptual codes and organizing them into a consensus list of themes. We presented the themes back to the participants and community members for confirmation.

RESULTS

We conducted 20 interviews with survivors of gun violence; all were black men, aged 20 years to 51 years. Five recurring themes emerged: (1) Isolation, physical and social restriction due to fear of surroundings; (2) Protection, feeling unsafe leading to the desire to carry a gun; (3) Aggression, willingness to use a firearm in an altercation; (4) Normalization, lack of reaction driven by the ubiquity of gun violence in the community; and (5) Distrust of health care providers, a barrier to mental health treatment.

CONCLUSION

Survivors of gun violence describe a disrupted sense of safety following their injury. As a result, they experience isolation, an increased need to carry a firearm, a normalization of gun violence, and barriers to mental health treatment. These maladaptive reactions suggest a mechanism for the violent recidivism seen among survivors of gun violence and offer potential targets to help this undertreated, high-risk population.

LEVEL OF EVIDENCE

Care management/Therapeutic V.
Massive transfusion and the response to prehospital plasma: It is all in how you define it
Authors: Sim Edward S. , Guyette Frank X. , Brown Joshua B. , Daley Brian J. , Miller Richard S. , Harbrecht Brian G. , Claridge Jeffrey A. , Phelan Herb A. , Neal Matthew D. , Forsythe Raquel , Zuckerbraun Brian S. , Sperry Jason L.
Published: March 2020

BACKGROUND

A recent analysis derived from the Prehospital Air Medical Plasma trial data set demonstrated no significant independent plasma survival benefit in those who required massive transfusion (≥10 units of red cells in 24 hours). The definition of massive transfusion has evolved over time to minimize bias and predict those at highest risk of death. We sought to characterize the definition of massive transfusion, their associated mortality risks and the survival benefit associated with prehospital plasma.

METHODS

A secondary analysis was performed using data from a recent prehospital plasma trial. Patients transferred directly from the scene were characterized. We defined historic massive transfusion using ≥10 units red cells in 24 hours and critical administration threshold (CAT) as ≥3 units per hour in the first hour (CAT1hr) or in any of the first 4 hours (CAT4hr) from arrival. The primary outcome was 30-day mortality. Kaplan-Meier analysis and Cox hazard regression were used to characterize the survival benefit of prehospital plasma.

RESULTS

There were a total of 390 enrolled patients who were transferred from the scene and represent the study cohort. Overall, 126 patients were positive for the CAT1hr metric, 183 patients were positive for the CAT4hr metric and 84 patients were positive for historic massive transfusion metric. The overall study mortality rate for those patients who met each transfusion definition was 13.1%, 17.4% and 10.0%, respectively. The CAT4hr metric had the lowest potential for survival bias. Kaplan-Meier survival analysis demonstrated a prehospital plasma survival benefit in the patients who were CAT4hr positive.

CONCLUSION

The current analysis demonstrates the superior utility of the CAT4hr definition with optimization of survival bias while conserving mortality risk prediction. This transfusion definition was associated with a prehospital plasma survival benefit and may be the most appropriate definition of massive transfusion for pragmatic studies which focus on hemorrhagic shock.

LEVEL OF EVIDENCE

Epidemiologic, Level II
A systematic review and meta-analysis of traumatic intracranial hemorrhage in patients taking prehospital antiplatelet therapy: Is there a role for platelet transfusions?
Authors: Alvikas Jurgis , Myers Sara P. , Wessel Charles B. , Okonkwo David O. , Joseph Bellal , Pelaez Carlos , Doberstein Cody , Guillotte Andrew R. , Rosengart Matthew R. , Neal Matthew D.
Published: March 2020

BACKGROUND

Platelet transfusion has been utilized to reverse platelet dysfunction in patients on preinjury antiplatelets who have sustained a traumatic intracranial hemorrhage (tICH); however, there is little evidence to substantiate this practice. The objective of this study was to perform a systematic review on the impact of platelet transfusion on survival, hemorrhage progression and need for neurosurgical intervention in patients with tICH on prehospital antiplatelet medication.

METHODS

Controlled, observational and randomized, prospective and retrospective studies describing tICH, preinjury antiplatelet use, and platelet transfusion reported in PubMed, Embase, Cochrane Reviews, Cochrane Trials and Cochrane DARE databases between January 1987 and March 2019 were included. Investigations of concomitant anticoagulant use were excluded. Risk of bias was assessed using the Newcastle-Ottawa scale. We calculated pooled estimates of relative effect of platelet transfusion on the risk of death, hemorrhage progression and need for neurosurgical intervention using the methods of Dersimonian-Laird random-effects meta-analysis. Sensitivity analysis established whether study size contributed to heterogeneity. Subgroup analyses determined whether antiplatelet type, additional blood products/reversal agents, or platelet function assays impacted effect size using meta-regression.

RESULTS

Twelve of 18,609 screened references were applicable to our questions and were qualitatively and quantitatively analyzed. We found no association between platelet transfusion and the risk of death in patients with tICH taking prehospital antiplatelets (odds ratio [OR], 1.29; 95% confidence interval [CI], 0.76–2.18; p = 0.346; I
2 = 32.5%). There was no significant reduction in hemorrhage progression (OR, 0.88; 95% CI, 0.34–2.28; p = 0.788; I
2 = 78.1%). There was no significant reduction in the need for neurosurgical intervention (OR, 1.00; 95% CI, 0.53–1.90, p = 0.996; I
2 = 59.1%; p = 0.032).

CONCLUSION

Current evidence does not support the use of platelet transfusion in patients with tICH on prehospital antiplatelets, highlighting the need for a prospective evaluation of this practice.

LEVEL OF EVIDENCE

Systematic Reviews and Meta-Analyses, Level III.
Putting a halt to unnecessary transfers: Do patients with isolated subarachnoid hemorrhage and Glasgow Coma Scale of 13 to 15 need a trauma center?
Authors: Sharma Jyoti , Defoe Danielle , Gillen Jenna , Kuo Yen-Hong , Perez Javier , Dalal Setu , Dayal Saraswati , Kiselak Elizabeth , Rippey Kelly , Kaul Sanjeev , Cohn Stephen
Published: March 2020

OBJECTIVES

Trauma patients with isolated subarachnoid hemorrhage (iSAH) presenting to nontrauma centers are typically transferred to an institution with neurosurgical availability. However, recent studies suggest that iSAH is a benign clinical entity with an excellent prognosis. This investigation aims to evaluate the neurosurgical outcomes of traumatic iSAH with Glasgow Coma Scale (GCS) of 13 to 15 who were transferred to a higher level of care.

METHODS

The American College of Surgeon Trauma Quality Improvement Program was retrospectively analyzed from 2010 to 2015 for transferred patients 16 years and older with blunt trauma, iSAH, and GCS of 13 or greater. Those with any other body region Abbreviated Injury Scale of 3 or greater, positive or unknown alcohol/drug status, and requiring mechanical ventilation were excluded. The primary outcome was need for neurosurgical intervention (i.e., intracranial monitor or craniotomy/craniectomy).

RESULTS

A total of 11,380 patients with blunt trauma, iSAH, and GCS of 13 to 15 were transferred to an American College of Surgeon level I/II from 2010 to 2015. These patients were 65 years and older (median, 72 [interquartile range (IQR), 59–81]) and white (83%) and had one or more comorbidities (72%). Eighteen percent reported a bleeding diathesis/chronic anticoagulation on admission. Most patients had fallen (80%), had a GCS of 15 (84%), and were mildly injured (median Injury Severity Score, 9 [IQR, 5–14]). Only 1.7% required neurosurgical intervention with 55% of patients being admitted to the intensive care unit for a median of 2 days (IQR, 1–3 days). Furthermore, 2.2% of the patients died. The median hospital length of stay was only 3 days (IQR, 2–5 days), and the most common discharge location was home with self-care (62%). Patient factors favoring neurosurgical intervention included high Injury Severity Score, low GCS, and chronic anticoagulation.

CONCLUSION

Trauma patients transferred for iSAH with GCS of 13 to 15 are at very low risk for requiring neurosurgical intervention.

LEVEL OF EVIDENCE

Therapeutic/care management, Level IV.
Identification of a new genetic variant associated with cholecystitis: A multicenter genome-wide association study
Authors: Bonde Alexander , Gaitanidis Apostolos , Breen Kerry , El Hechi Majed , Nederpelt Charlie , Christensen Mathias , Kokoroskos Nikolaos , Mendoza April , Velmahos George , Sillesen Martin , Farhat Maha R. , Kaafarani Haytham M.A.
Published: March 2020

BACKGROUND

The genomic landscape of gallbladder disease remains poorly understood. We sought to examine the association between genetic variants and the development of cholecystitis.

METHODS

The Biobank of a large multi-institutional health care system was used. All patients with cholecystitis were identified using International Statistical Classification of Diseases, 10th Revision, codes and genotyped across six batches. To control for population stratification, data were restricted to that from individuals of European genomic ancestry using a multidimensional scaling approach. The association between single nucleotide polymorphisms and cholecystitis was evaluated with a mixed linear model–based analysis, controlling for age, sex, and obesity. The threshold for significance was set at 5 × 10−8.

RESULTS

Of 24,635 patients (mean ± SD age, 60.1 ± 16.7 years; 13,022 females [52.9%]), 900 had cholecystitis (mean ± SD age, 65.4 ± 14.3 years; 496 females [55.1%]). After meta-analysis, three single nucleotide polymorphisms on chromosome 5p15 exceeded the threshold for significance (p < 5 × 10−8). The phenotypic variance of cholecystitis explained by genetics and controlling for sex and obesity was estimated to be 17.9%.

CONCLUSION

Using a multi-institutional genomic Biobank, we report that a region on chromosome 5p15 is associated with the development of cholecystitis that can be used to identify patients at risk.

LEVEL OF EVIDENCE

Prognostic and epidemiological, Level III.
Brain-Derived Neurotrophic Factor in the Cerebrospinal Fluid Increases During Electroconvulsive Therapy in Patients With Depression
Authors: Mindt Sonani , Neumaier Michael , Hellweg Rainer , Sartorius Alexander , Kranaster Laura
Published: March 2020

Objective

Preclinical evidence suggests a role for brain-derived neurotrophic factor (BDNF) in the mode of action of electroconvulsive therapy (ECT). Clinical data regarding BDNF levels in serum or plasma are more inconsistent. We measured BDNF levels from the cerebrospinal fluid (CSF) in patients with major depression before and shortly after a course of ECT.

Methods

Cerebrospinal fluid and serum BDNF levels were determined using commercially available enzyme-linked immunosorbent assay (ELISA) kits.

Results

We included 9 patients with a severe depressive episode within a major depressive disorder into the study. The CSF BDNF concentrations at baseline were lower compared with those CSF BDNF levels after the complete ECT treatment (P = 0.042), whereas no such a constellation was found for serum BDNF. No associations between the BDNF levels and the amount of individual ECT sessions or the reduction of the depressive symptoms were found.

Conclusions

For the first time, it has been shown that CSF BDNF concentrations increase during a course of ECT in patients with a severe unipolar depressive episode, which is in line with the neurotrophin hypothesis as a mode of action of ECT, although it was not possible to demonstrate either a dose-effect relation or a relationship with the actual antidepressant effects in our small sample. Major limitation is the small sample size.
Predicting Individual Remission After Electroconvulsive Therapy Based on Structural Magnetic Resonance Imaging
Authors: Takamiya Akihiro , Liang Kuo-ching , Nishikata Shiro , Tarumi Ryosuke , Sawada Kyosuke , Kurokawa Shunya , Hirano Jinichi , Yamagata Bun , Mimura Masaru , Kishimoto Taishiro
Published: March 2020

Objective

To identify important clinical or imaging features predictive of an individual's response to electroconvulsive therapy (ECT) by utilizing a machine learning approach.

Methods

Twenty-seven depressed patients who received ECT were recruited. Clinical demographics and pretreatment structural magnetic resonance imaging (MRI) data were used as candidate features to build models to predict remission and post-ECT Hamilton Depression Rating Scale scores. Support vector machine and support vector regression with elastic-net regularization were used to build models using (i) only clinical features, (ii) only MRI features, and (iii) both clinical and MRI features. Consistently selected features across all individuals were identified through leave-one-out cross-validation.

Results

Compared with models that include only clinical variables, the models including MRI data improved the prediction of ECT remission: the prediction accuracy improved from 70% to 93%. Features selected consistently across all individuals included volumes in the gyrus rectus, the right anterior lateral temporal lobe, the cuneus, and the third ventricle, as well as 2 clinical features: psychotic features and family history of mood disorder.

Conclusions

Pretreatment structural MRI data improved the individual predictive accuracy of ECT remission, and only a small subset of features was important for prediction.
Transmitter and receiver technologies for optical wireless
Authors: O'Brien Dominic , Rajbhandari Sujan , Chun Hyunchae
Published: March 2020

Providing a reliable link, with sufficient signal-to-noise ratio (SNR) and bandwidth to deliver high-capacity communications is a critical challenge for optical wireless (OW) communications and understanding and jointly optimizing the performance of the transmitter and receiver subsystems is a key part of this. At the transmitter a source of light, either a laser or a light-emitting diode, must be modulated with the communications signal. The resulting emission must be directed, using optics or steering systems, as required for the particular application, and must be within any safety levels set by relevant standards. The receiver is the most critical part of any optical link, as its design is a dominant factor in determining the received SNR, which determines the capacity and ultimately the utility of the link. A receiver must collect, filter and concentrate signal radiation, then detect and amplify the resulting electrical signal. This review surveys the state-of–the-art transmitter and receiver technologies. Details of design constraints are discussed, and potential future directions discussed.

This article is part of the theme issue ‘Optical wireless communication’.
Indoor multiuser visible light communication systems using Hadamard-coded modulation
Authors: Lian Jie , Noshad Mohammad , Brandt-Pearce Maïté
Published: March 2020

Visible light communications (VLC) is a short-range optical wireless communication technology that uses light-emitting diodes (LEDs) as lighting devices and data transmitters. This paper describes a multiuser VLC system using Hadamard-coded modulation (HCM) for indoor data transmission. Considering the peak transmitted power limit of the LEDs, a DC-reduced HCM (DCR-HCM) is used to reduce the nonlinear clipping distortion. Since the Hadamard codewords have different bandwidth requirements for a given symbol rate, they can be assigned to users with varying hardware capabilities. Optimally assigning codewords to users is found to significantly improve the average throughput, up to twice higher than a random assignment for a typical scenario. When the number of active users is less than the size of the Hadamard matrix used, more than one codeword can be assigned per user, which further improves the throughput. This paper also examines a scenario where multiple lamps in an indoor space transmit the same data. Since the time of arrival for the received signals emitted from different lamps is different, the Hadamard codes received are no longer orthogonal, resulting in multiple access interference and inter-chip interference. The number of acceptable codewords is computed based on the specific interference experienced in different parts of the indoor space. The spatial distribution of the maximum throughput is also simulated, showing that the ratio of the maximum to the minimum data rate can be as high as 10 when considering the entire area of a typical indoor room.

This article is part of the theme issue ‘Optical wireless communication’.
Organic semiconductors for visible light communications
Authors: Manousiadis Pavlos P. , Yoshida Kou , Turnbull Graham A. , Samuel Ifor D. W.
Published: March 2020

Organic semiconductors are an important class of optoelectronic material that are widely studied because of the scope for tuning their properties by tuning their chemical structure, and simple fabrication to make flexible films and devices. Although most effort has focused on developing displays and lighting from these materials, their distinctive properties also make them of interest for visible light communications (VLCs). This article explains how their properties make them suitable for VLC and reviews the main uses that have been explored. On the transmitter side, record white VLC communication has been achieved by using organic semiconductors as colour converters, while direct modulation of organic light-emitting diodes is also possible and could be of interest for display-to-display communication. On the receiver side, organic solar cells can be used to harvest power and data simultaneously, and fluorescent antennas enable fast and sensitive receivers with large field of view.

This article is part of the theme issue ‘Optical wireless communication’.
Networked multiple-input-multiple-output for optical wireless communication systems
Authors: Wang Zhaocheng , Chen Jiaxuan
Published: March 2020

With the escalation of heterogeneous data traffic, the research on optical wireless communication (OWC) has attracted much attention, owing to its advantages such as wide spectrum, low power consumption and high security. Ubiquitous optical devices, e.g. light-emitting diodes (LEDs) and cameras, are employed to support optical wireless links. Since the distribution of these optical devices is usually dense, multiple-input-multiple-output (MIMO) can be naturally adopted to attain spatial diversity gain or spatial multiplexing gain. As the scale of OWC networks enlarges, optical MIMO can also collaborate with network-level operations, like user/AP grouping, to enhance the network throughput. Since OWC is preferred for short-range communications and is sensitive to the directions/rotations of transceivers, optical MIMO links vary frequently and sharply in outdoor scenarios when considering the mobility of optical devices, raising new challenges to network design. In this work, we present an overview of optical MIMO techniques, as well as the cooperation of MIMO and user/AP grouping in OWC networks. In consideration of the challenges for outdoor OWC, key technologies are then proposed to facilitate the adoption of optical MIMO in outdoor scenarios, especially in vehicular
ad hoc
networks. Lastly, future applications of MIMO in OWC networks are discussed.

This article is part of the theme issue ‘Optical wireless communication’.
Ultra-high-capacity wireless communication by means of steered narrow optical beams
Authors: Koonen Ton , Mekonnen Ketemaw , Cao Zizheng , Huijskens Frans , Pham Ngoc Quan , Tangdiongga Eduward
Published: March 2020

The optical spectrum offers great opportunities to resolve the congestion in radio-based communication, aggravated by the booming demand for wireless connectivity. High-speed infrared optical components in the 1500 nm window have reached high levels of sophistication and are extensively used already in fibre-optic networks. Moreover, infrared light beyond 1400 nm is eye-safe and is not noticeable by the users. Deploying steerable narrow infrared beams, wireless links with huge capacity can be established to users individually, at minimum power consumption levels and at very high levels of privacy. Fully passive diffractive optical modules can handle many beams individually and accurately steer narrow beams two-dimensionally by just remotely tuning the wavelength of each beam. The system design aspects are discussed, encompassing the beam-steering transmitter, wide field-of-view optical receiver and the localization of the user's wireless devices. Prototype system demonstrators are reported, capable of supporting up to 128 beams carrying up to 112 Gbit s
−1
per beam. Hybrid bidirectional systems which use a high-speed downstream optical link and an upstream radio link at a lower speed can provide powerful asymmetric wireless connections. All-optical bidirectional beam-steered wireless communication will be able to offer the ultimate in wireless capacity to the user while minimizing power consumption.

This article is part of the theme issue ‘Optical wireless communication’.
Shigella sonnei bacteraemia in a cystic fibrosis patient: case report and literature review
Authors: Carretero-Vicario Octavio , Taravillo Irene , Corbella Laura , Catalan Mercedes , Garfia Cristina , Martinez M. Teresa , Chaves Fernando , Orellana M. Angeles
Published: March 2020

Introduction. Shigellosis has a gastrointestinal presentation of variable severity in which bacteraemia is uncommon. We describe the first reported case of

Shigella sonnei

bacteraemia and intestinal coinfection with

Clostridioides difficile

in a cystic fibrosis patient. The literature on

S. sonnei

bacteraemia in adult and paediatric populations is also reviewed.

Case presentation. A 29-year-old male with cystic fibrosis presented with profuse acute watery diarrhoea, abdominal pain, shivering and fever. The patient showed mixed cardiogenic and septic shock. Despite antibiotic therapy, volume replacement therapy and vasoactive drugs, the patient showed biventricular dysfunction and multiple organ failure requiring implantation of an intra-aortic balloon pump (IABP) with extracorporeal membrane oxygenation (ECMO).

C. difficile

and

S. sonnei

were detected in the stools.

Escherichia coli

was identified in the blood by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry, although after re-evaluation with biochemical and antiserum agglutination tests, the isolate was confirmed as

S. sonnei

. After adjustment of the antibiotic therapy to vancomycin, meropenem, amikacin and metronidazole and continuing with ECMO and IABP support for 8 days, the patient improved and was finally discharged after 44 days.

Conclusion.

S. sonnei

bacteraemia is an unusual entity that should be kept in mind because of the severity of its presentation and high mortality. In acute gastroenteritis and fever, especially in paediatric patients under 5 years old and adults with criteria for immunosuppression or chronic diseases, blood and stool cultures provide simple information that is nonetheless very important for the management and prognosis of these patients.
Lysobacter lacus sp. nov., isolated from from lake sediment
Authors: Im Wan-Taek , Siddiqi Muhammad Zubair , Kim So-Yeon , Huq Md. Amdadul , Lee Jae Hag , Choi Kang Duk
Published: March 2020

An aerobic and Gram-stain-negative bacterial strain, designated UKS-15T, was isolated from lake water in the Republic of Korea. Results of 16S rRNA gene sequence and phylogenetic analyses indicated that the novel isolate belongs to the genus

Lysobacter

and was most closely related to

Lysobacter xinjiangensis

RCML-52T (98.0 %),

Lysobacter mobilis

9 NM-14T (97.4 %) and

Lysobacter humi

FJY8T (97.2 %). The DNA G+C content was 69.1 mol%. Strain UKS-15T possessed ubiquinone-8 (Q-8) as the sole respiratory quinone and the fatty acid profile comprised iso-C15 : 0, iso-C17 : 0 and summed feature 9 (iso-C17 : 1 ω9c and/or C16 : 0 10-methyl) as its major components. The major polar lipids were phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol and one unidentified aminophospholipid. Moreover, the physiological and biochemical results and low level of DNA–DNA relatedness (<22.0 %) allowed the phenotypic and genotypic differentiation of strain UKS-15T from other

Lysobacter

species. Therefore, on the basis of the data from this polyphasic taxonomic study, strain UKS-15T should represent a novel species of the genus

Lysobacter

, for which the name Lysobacter lacus sp. nov. is proposed. The type strain is UKS-15T (=JCM 30983T=KACC 18719T).
Comparison of the performance of the Panther Fusion respiratory virus panel to R-Gene and laboratory developed tests for diagnostic and hygiene screening specimens from the upper and lower respiratory tract
Authors: Ganzenmueller Tina , Kaiser Rolf , Baier Claas , Wehrhane Marlies , Hilfrich Brigitta , Witthuhn Jenny , Flucht Sandra , Heim Albert
Published: March 2020

Introduction.Diagnosis of acute respiratory infections (ARIs) can be facilitated by the Panther Fusion (PF) automatic, random access PCR system for the detection of influenzavirus A (Flu A) and B (Flu B), parainfluenzavirus (Paraflu), respiratory syncytial virus (RSV), human metapneumovirus (hMPV), rhinovirus (RV) and human adenovirus (AdV) in nasopharyngeal swabs.

Aim.To evaluate the performance of PF in comparison with established methods, including subsets of (1) lower respiratory tract (LRT) specimens and (2) upper respiratory tract (URT) hygiene screening specimens of patients without ARI symptoms.

Methodology.The performance characteristics of PF were compared with bioMérieux R-Gene and laboratory-developed PCR tests (LDTs). Overall, 1544 specimens with 6658 individual diagnostic requests were analysed.

Results.The overall concordances of PF and LDTs for Flu A, Flu B and AdV were 98.4, 99.9 and 96.1%, respectively; by re-testing of discrepant specimens concordances increased to 99.4, 99.9 and 98.0%, respectively. Initial concordances of PF and R-Gene assays for RSV, Paraflu, hMPV and RV were 98.4, 96.3, 99.3 and 96.0%, respectively, and retest concordances were 99.7, 97.9, 99.9 and 98.9%, respectively. No differences to the overall performance were found for the subgroups of LRT and hygiene screening specimens. PCR cycle threshold (Ct) values correlated very well between methods, indicating that a semi-quantitative diagnostic approach using Ct values (e.g. highly vs. weakly positive) could augment the diagnostic information.

Conclusion.PF performed similar to R-Gene and LDTs not only for its intended use but also for LRT and hygiene screening specimens with shorter hands-on and turnaround times.
Screening of FDA-approved drugs using a MERS-CoV clinical isolate from South Korea identifies potential therapeutic options for COVID-19
Authors: Ko Meehyun , Chang So Young , Byun Soo Young , Ianevski Aleksandr , Choi Inhee , d’Alexandry d’Orengiani Anne-Laure Pham Hung , Kainov Denis E. , Shum David , Min Ji-Young , Windisch Marc P.
Published: March 2020

Therapeutic options for coronavirus remain limited. To address this unmet medical need, we screened 5,406 compounds, including United States Food and Drug Administration (FDA)- approved drugs and bioactives, for activity against a South Korean Middle East respiratory syndrome coronavirus (MERS-CoV) clinical isolate. Among 221 identified hits, 54 had therapeutic indexes (TI) greater than 6. Time-of-addition studies with selected drugs demonstrated eight and four FDA-approved drugs acted on the early and late stages of the viral life cycle, respectively. Confirmed hits included several cardiotonic agents (TI>100), atovaquone, an anti-malarial (TI>34), and ciclosonide, an inhalable corticosteroid (TI>6). Furthermore, utilizing the severe acute respiratory syndrome CoV-2 (SARS-CoV-2), combinations of remedesivir with selected dugs were evaluated, which identified ciclosonide and nelfinavir to be additive and synergistic drugsin vitro, respectively. Together, we screened FDA-approved drugs using patient-derived MERS-CoV, triaged hits to discriminate between early and late viral life cycle inhibitors, confirmed selected drugs using SARS-CoV-2, and demonstrated the added value of selected medications in combination with remedesivir. Our results identify potential therapeutic options for MERS-CoV infections, and provide a basis to treat coronavirus disease 2019 (COVID-19) and other coronavirus-related illnesses.