bluuebunny/crossref_metadata_2025 huggingface dataset:
Epidermal Inclusion Cysts following Dupuytren’s Percutaneous Needle Fasciotomy: A Case Report
Authors: Turner Jessica , Foroughi Forough , Jacob Jeeth
Published: August 2021

Percutaneous needle fasciotomy (PNF) is a favorable approach to Dupuytren’s contracture management, usually reserved for Tubiana stage 1–2, uncomplicated disease. It is growing in popularity globally. Epidermal inclusion cysts are benign, commonly encountered cavities usually found on acral skin, rarely glabrous skin, and often following trauma. We present a 43-year-old laborer with two incidentally found epidermal inclusion cysts in the open excision of painful, Tubiana 3 and 2 Dupuytren’s recurrence of his middle and ring fingers. He had undergone PNF to same 4 years prior. One cyst had ruptured. Both seemed to have migrated distally over time from the initial PNF site with progression of the Dupuytren’s disease. This may be the only case of multiple epidermal inclusion cysts post PNF for Dupuytren’s disease in the literature. The authors discuss factors contributing to epidermal inclusion cyst formation, and postulate whether needle choice may impact the risk of their development as a complication of PNF.
Negative Pressure Wound Therapy as a Salvage Procedure in Venous Congestion of Microsurgical Procedures
Authors: Quintero Jorge I. , Cárdenas Laura L. , Achury Adriana C. , Vega-Hoyos Daniela , Bermúdez Julio
Published: August 2021

Negative pressure wound therapy (NPWT) is widely used in skin defects, active infection, and surgical reconstruction; lately, it is being used after skin graft to improve the adhesion on the receptor area. During the last decade, another indication has been identified: the use of NPTW to avoid complications after free flaps such as venous congestion and the risk of necrosis. NPWT can be used in the initial complication of a free flap, and the venous congestions can be treated with this technique, with very good outcomes. NPWT can be established as a part of a postoperative protocol in microsurgical procedures to avoid major complications.
Percutaneous Tracheostomy in Respiratory Failure Due to COVID-19
Authors: Cohen Samuel E. , Lopez Angelena R. , Ng Philip K. , Friedman Oren A. , Chaux George E.
Published: August 2021

Background:

Coronavirus disease 2019 (COVID-19) can lead to hypoxemic respiratory failure resulting in prolonged mechanical ventilation. Typically, tracheostomy is considered in patients who remain ventilator dependent beyond 2 weeks. However, in the setting of this novel respiratory virus, the safety and benefits of tracheostomy are not well-defined. Our aim is to describe our experience with percutaneous tracheostomy in patients with COVID-19.

Materials and Methods:

This is a single center retrospective descriptive study. We reviewed comorbidities and outcomes in patients with respiratory failure due to COVID-19 who underwent percutaneous tracheostomy at our institution from April 2020 to September 2020. In addition, we provide details of our attempt to minimize aerosolization by using a modified protocol with brief periods of planned apnea.

Results:

A total of 24 patients underwent percutaneous tracheostomy during the study. The average body mass index was 33.0±10.0. At 30 days posttracheostomy 17 (71%) patients still had the tracheostomy tube and 14 (58%) remained ventilator dependent. There were 3 (13%) who died within 30 days. At the time of data analysis in November 2020, 9 (38%) patients had died and 7 (29%) had been decannulated. None of the providers who participated in the procedure experienced signs or symptoms of COVID-19 infection.

Conclusion:

Percutaneous tracheostomy in prolonged respiratory failure due to COVID-19 appears to be safe to perform at the bedside for both the patient and health care providers in the appropriate clinical context. Morbid obesity did not limit the ability to perform percutaneous tracheostomy in COVID-19 patients.
Appropriate selection of candidates for outpatient thyroidectomy
Authors: Romero Arenas Minerva Angélica
Published: August 2021

Purpose of review

Although traditionally an inpatient procedure, outpatient thyroidectomy has gained traction as a viable and well tolerated alternative for selected patients, with an added benefit of cost savings.

Recent findings

Research on outpatient thyroidectomy has focused on establishing its noninferiority in outcomes compared to the standard inpatient or overnight observation. Numerous studies have found comparable low rates of postoperative complications and no increase in readmission. Selection criteria have been well established by professional societies and research studies support the selection bias benefitting appropriately selected patients. The primary benefit of outpatient thyroidectomy reported is a decrease in cost, though additional theoretical benefits such as decreased exposure to nosocomial infections.

Outpatient thyroidectomy is a well tolerated approach in appropriately selected candidates, with cost reduction benefits. Adherence to societal guidelines for patient selection is paramount.
Gender disparities in transplantation
Authors: Sheikh Saulat S. , Locke Jayme E.
Published: August 2021

Purpose of review

Transplantation is the life-saving therapy for patients suffering from end-organ failure, and as such, equitable access to transplantation (ATT) is of paramount importance. Unfortunately, gender/sex-based disparities exist, and despite the transplant community's awareness of this injustice, gender/sex-based disparities have persisted for more than two decades. Importantly, no legislation or allocation policy has addressed inequity in ATT that women disproportionately face. In fact, introduction of the model for end-stage liver disease-based liver allocation system in 2002 widened the gender disparity gap and it continues to be in effect today. Moreover, women suffering from kidney disease are consistently less likely to be referred for transplant evaluation and subsequently less likely to achieve a kidney transplant, yet they comprise the majority of living kidney donors.

Recent findings

Acknowledging gender/sex-based disparities in ATT is the first step toward interventions aimed at mitigating this long-standing injustice in healthcare.

This article provides a background of end-stage liver and kidney disease in women, summarizes the existing literature describing the issue of gender disparity in ATT, and identifies potential areas of intervention and future investigation.
The functioning and the complication rate of extreme long existing urinary diversions
Authors: Van Ginkel Charlotte J. , Cobussen-Boekhorst Hanny , Martens Frank , Feitz Wout F.J. , Heesakkers John P.F.A.
Published: August 2021

Purpose of review

This review is timely and relevant because many patients live many years with urinary diversions. Knowledge about the long term outcome with respect to function and complications are important for patient counseling and for the manner to follow-up patients. This study was performed to investigate the functioning of urinary diversions constructed > 25 years earlier.

Recent findings

Most studies have a relatively shorter follow-up, mainly focussing on short term postoperative complications. Focussing on the long term, urinary tract infections (UTI) including pyelonephritis are common. Mild kidney function deterioration is described.

Retrospective study (2018–2019); 43 patients with regular follow-up at the Radboud University Medical Centre Nijmegen the Netherlands. Ileal conduit (n = 19) and ureterosigmoidostomy (n = 11) are the most common diversion types for reasons such as: bladder exstrophy (n = 15), urinary incontinence (n = 9) and malignancy (n = 8). This series with a median follow-up of 40 years, shows it is possible to live and cope with a urinary diversion for a very long time. Ureterosigmoidostomies give relatively good results. Ileal conduits are functioning properly with acceptable complication rates. 95% suffers from chronic UTI's. Kidney function deterioration was mild. Diversions for benign reasons have more complex complications compared to diversion constructed for malignant reasons.

Video abstract

http://links.lww.com/COU/A32.
Survival Outcomes Based on Sequence of Therapy Using FOLFIRINOX and Nab-Paclitaxel + Gemcitabine in Metastatic Pancreatic Ductal Adenocarcinoma
Authors: Baron Margaret Kelsey , Wang Xuechen , Nevala-Plagemann Christopher , Moser Justin C. , Haaland Benjamin , Garrido-Laguna Ignacio
Published: August 2021

Objectives

Optimal sequence of therapy for patients with metastatic pancreatic ductal adenocarcinoma is unknown. Combination chemotherapy with fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) and nab-paclitaxel + gemcitabine (nab-p/gem) are standard first-line (1L) therapies. They have never been prospectively compared. We retrospectively compared overall survival (OS) of patients treated with 1L nab-p/gem and second-line (2L) FOLFIRINOX with those treated with the reverse sequence.

Methods

Patients with metastatic pancreatic ductal adenocarcinoma treated with 1L FOLFIRINOX and 2L nab-p/gem or vice versa were identified using an electronic health record–derived real-world database. Using an intent-to-treat analysis, we compared OS from initiation of 1L therapy. A Cox model, stratified by deciles of propensity score, estimated the effect of treatment sequence on OS.

Results

The study included 3027 patients. The median OS for 1L FOLFIRINOX versus nab-p/gem was 8.6 versus 6.1 months (hazard ratio, 0.77; 95% confidence interval, 0.70–0.84). The median OS for 1L FOLFIRINOX and 2L nab-p/gem versus 1L nab-p/gem and 2L FOLFIRINOX was 11.9 versus 11.5 months (hazard ratio, 0.97; 95% confidence interval, 0.79–1.18).

Conclusions

In this analysis of real-world data, 1L FOLFIRINOX was associated with increased OS in propensity analysis. For patients who received both FOLFIRINOX and nab-p/gem, median OS was similar regardless of sequence.
Use of Chromogranin A for Monitoring Patients With Pancreatic Neuroendocrine Neoplasms
Authors: Yu Fei , Fu Jingjing , Zhang Chuan , Wu Wenyu , Ai Shuyue , Yao Xiaochen , Meng Qingle , Huang Yue , Lu Guangming , Wang Feng , Qu Wei
Published: August 2021

Objective

We aimed to assess the role of serum chromogranin A (CgA) in monitoring disease status and treatment response in patients with pancreatic neuroendocrine neoplasms (pNENs).

Methods

We included posttherapy pNENs patients with measured serum CgA levels who underwent 68Ga-labeled tetraazacyclododecanetetraacetic acid-peptide positron emission tomography (PET) imaging between April 2017 and January 2020. Serum CgA levels were determined by enzyme-linked immunosorbent assay. Tumor response was assessed according to the PET response evaluation criteria in solid tumors.

Results

Seventy-seven patients with 101 events were included in this study. Serum CgA levels were significantly higher in patients with active disease and metastasis. The optimal cutoff values for CgA for active and metastatic pNENs diagnosis after treatment were 52.39 (77.8% sensitivity, 80.7% specificity) and 60.18 ng/mL (73.9% sensitivity, 73.1% specificity), respectively. Based on 18 patients with serial CgA measurements and PET imaging, the optimal changes in CgA levels for predicting disease remission and progression were a 28.5% decrease (71.4% sensitivity, 88.2% specificity) and a 21.0% increase (100.0% sensitivity, 75.0% specificity), respectively.

Conclusions

We concluded that serum CgA levels are associated with disease status and treatment response and may thus provide a helpful biomarker for the monitoring and clinical management of patients with pNENs.
Incidence, Treatment, and Survival of Synchronous Peritoneal Metastases in Pancreatic Cancer
Authors: Rijken Anouk , Bakkers Checca , van Erning Felice N. , van der Geest Lydia G. , de Vos-Geelen Judith , Besselink Marc G. , Lemmens Valery E. , de Hingh Ignace H.J.T. ,   for the Dutch Pancreatic Cancer Group
Published: August 2021

Objective

The aim of the study was to gain insight in the incidence, treatment, and survival of patients with synchronous pancreatic peritoneal metastases.

Methods

All patients diagnosed with pancreatic cancer between 2008 and 2018 in the Netherlands Cancer Registry were evaluated. The patients were subcategorized as (1) synchronous peritoneal metastases, (2) synchronous systemic metastases, and (3) no metastases.

Results

In total, 25,334 patients with pancreatic cancer were included. Among them, 3524 (14%) presented with synchronous peritoneal metastases, 10,659 (42%) with systemic metastases, and 11,151 (44%) without metastases at the time of diagnosis. The proportion of the patients diagnosed with peritoneal metastases increased over time (11%, 2008; 16%, 2018; P < 0.001). Of these patients, 964 (27%) received cancer treatment and 2560 (73%) received best supportive care. The median overall survival in patients with peritoneal metastases, systemic metastases, and without metastases was 1.9, 2.4, and 8.0 months, respectively (P < 0.001). In the patients with peritoneal metastases, the median overall survival was 5.0 months when undergoing cancer treatment and 1.3 months with best supportive care (P < 0.001).

Conclusions

Patients with pancreatic cancer are increasingly diagnosed with synchronous peritoneal metastases. Given the current dismal prognosis, research to improve treatment is designated for this patient category.
Interrater Reliability in the American Board of Physical Medicine and Rehabilitation Part II Certification Examination
Authors: Kinney Carolyn L. , Raddatz Mikaela M. , Robinson Lawrence R. , Garrison Christopher J. , Sabharwal Sunil
Published: August 2021

Objective

The design of medical board certification examinations continues to evolve with advances in testing innovations and psychometric analysis. The potential for subjectivity is inherent in the design of oral board examinations, making improvements in reliability and validity especially important. The purpose of this quality improvement study was to analyze the impact of using two examiners on the overall reliability of the oral certification examination in physical medicine and rehabilitation.

Design

This was a retrospective quality improvement study of 422 candidates for the American Board of Physical Medicine and Rehabilitation Part II Examination in 2020. Candidates were examined by examiner pairs, each of whom submitted independent scores. Training for all 116 examiners included examination case review, scoring guidelines, and bias mitigation. Examiner performance was analyzed for both internal consistency (intrarater reliability) and agreement with their paired examiner (interrater reliability).

Results

The reliability of the Part II Examination was high, ranging from 0.93 to 0.94 over three administrations. The analysis also demonstrated high interrater agreement and examiner internal consistency.

Conclusions

A high degree of interrater agreement was found using a new, two-examiner format. Comprehensive examiner training is likely the most significant factor for this finding. The two-examiner format improved the overall reliability and validity of the Part II Examination.
Policy and planning for large epidemics and pandemics – challenges and lessons learned from COVID-19
Authors: Sharp Ashley , Jain Vageesh , Alimi Yewande , Bausch Daniel G.
Published: August 2021

Purpose of review

The COVID-19 pandemic is a global catastrophe that has led to untold suffering and death. Many previously identified policy challenges in planning for large epidemics and pandemics have been brought to the fore, and new ones have emerged. Here, we review key policy challenges and lessons learned from the COVID-19 pandemic in order to be better prepared for the future.

Recent findings

The most important challenges facing policymakers include financing outbreak preparedness and response in a complex political environment with limited resources, coordinating response efforts among a growing and diverse range of national and international actors, accurately assessing national outbreak preparedness, addressing the shortfall in the global health workforce, building surge capacity of both human and material resources, balancing investments in public health and curative services, building capacity for outbreak-related research and development, and reinforcing measures for infection prevention and control.

In recent years, numerous epidemics and pandemics have caused not only considerable loss of life, but billions of dollars of economic loss. The COVID-19 pandemic served as a wake-up call and led to the implementation of relevant policies and countermeasures. Nevertheless, many questions remain and much work to be done. Wise policies and approaches for outbreak control exist but will require the political will to implement them.
Evaluation of Computed Tomography Attenuation Value of Proximal Femoral Marrow to Diagnose and Differentiate Hematologic Malignancies, Myelofibrosis, and Aplastic Anemia
Authors: Ishii Shiro , Ohkawara Hiroshi , Endo Yoshiki , Hara Junko , Hotsumi Hirotoshi , Yamakuni Ryo , Sugawara Shigeyasu , Sekino Hirofumi , Ito Hiroshi
Published: August 2021

Objective

The aim of this study was to diagnose hematologic diseases using computed tomography (CT) number of proximal femoral marrow.

Methods

The average CT number of marrow in hematologic diseases was measured on the caudal side of the greater trochanter.

Results

The CT numbers were −60.3 ± 16.8 in 12 patients with aplastic anemia, −53.2 ± 19.4 in 11 patients with monoclonal gammopathy of undetermined significance, −44.2 ± 21.1 in 10 normal controls, −30.9 ± 42.3 in 9 patients with chronic lymphatic leukemia, −29.8 ± 29.9 in 17 patients with benign anemia, −13.7 ± 40.9 in 33 patients with multiple myeloma, 0.32 ± 44.6 in 17 patients with myelodysplastic syndrome (MDS), 18.7 ± 40.0 in 44 patients with acute myeloid leukemia, 50.3 ± 27.4 in 13 patients with acute lymphatic leukemia, 51.5 ± 16.8 in 8 patients with myelofibrosis, and 56.4 ± 15.6 in 9 patients with chronic myeloid leukemia. Significant differences were observed between acute myeloid leukemia and MDS, between MDS and aplastic anemia, and between multiple myeloma and monoclonal gammopathy of undetermined significance (P < 0.01).

Conclusion

The marrow CT numbers may be indicators of hematologic diseases and can be used as a diagnostic tool.
Reader Performance as a Function of Patient Size for the Detection of Hepatic Metastases
Authors: Gong Hao , Yu Lifeng , Leng Shuai , Fletcher Joel G. , McCollough Cynthia H.
Published: August 2021

Objective

To investigate reader performance as a function of patient size for the detection of hepatic metastases when an automatic exposure control (AEC) system is used, which varies image noise as a function of patient size.

Methods

Abdominal computed tomograhy examinations across 100, 120, 160, and 200 quality reference tube current-time product were collected, involving a cohort of 83 patients. Three radiologists identified hepatic metastases across all dose levels. Partial Spearman rank correlation and multivariate logistic regression were used to evaluate correlations between reader performance and patient size and lesion size/contrast while accounting for potential confounding effects. Analyses were repeated on an emulated less-variable noise AEC.

Results

No statistically significant correlation was observed between patient size and radiologist performance (for variable-noise AEC: range of partial Spearman ρ, −0.157 to −0.035]; range of adjusted odds ratios, 0.987, 1.006).

Conclusions

Reader performance was independent of patient size, suggesting that variable-noise AEC provides better modulation for larger patients than constant-noise AEC.
Application of Flat-Panel Volume Computed Tomography to Evaluate Cerebral Hemorrhage After Mechanical Thrombectomy of Acute Embolic Stroke of the Anterior Circulation
Authors: Yen Ho-Hsian , Chien Chun , Lee I-Hui , Chen Shih-Pin , Luo Chao-Bao , Lin Chung-Jung , Chen Shu-Ting , Yuan Wei-Hsin , Kuo Yu , Wu Chia-Hung , Chang Feng-Chi
Published: August 2021

Objective

The aim of the study was to evaluate cerebral hemorrhage (CH) and contrast media leakage (CML or commonly synonymous with “contrast staining”) differentiation on flat-panel volume computed tomography (FPVCT) after intra-arterial mechanical thrombectomy.

Methods

We evaluated patients with hyperattenuation on FPVCT after intra-arterial mechanical thrombectomy between 2018 and 2021 by multiple parameters on CT angiography, FPVCT, CT, and/or magnetic resonance imaging.

Results

The CH (n = 43) versus CML (n = 24) groups revealed: (1) regional anatomical characteristics (preserved and distorted): 7 of 43 (9.6%) and 36 of 43 (83.7%) versus 22 of 24 (91.7%) and 2 of 24 (8.3%, P < 0.001); (2) thrombus in proximal two-thirds versus distal one-thirds M1 segment of middle cerebral artery (preserved and distorted): 17 of 21 (81.0%) and 4 of 21 (19.0%) versus 5 of 11 (45.5%) and 6 of 11 (54.5%, P = 0.040); and (3) average density ratio: 1.83 ± 0.65 versus 1.35 ± 0.13 (P = 0.004).

Conclusions

Contrast media leakage can be differentiated from CH by preserved regional anatomical characteristics and relatively low average density ratio on FPVCT. Patients with CML who have embolism in proximal two thirds of M1 segment are more likely to develop hyperattenuation with preserved regional anatomy.
Local Pterional Advancement Flap: A Minimally Invasive Option to Reconstruct Spheno-Temporal Extracranial Soft Tissues Dehiscences in Fragile Patients
Authors: Gagliardi Filippo , Giordano Leone , Bussi Mario , Mortini Pietro
Published: August 2021

Background:

Late-onset, extracranial soft tissues dehiscence in the spheno-temporal region after major neurosurgical procedures might represent a potentially life-threatening complication.

Due to surgery-related galeal/pericranial and myofascial temporal atrophy, classical regional flaps are often unavailable, enforcing potential indication for free vascularized flaps.

Nevertheless, in elderly multioperated patients, who are not eligible for major surgery, it becomes mandatory to consider less invasive options for reconstruction.

Authors describe the application of a reconstructive option for late-onset, pterional soft tissues dehiscence in fragile patients, using a local pterional advancement flap.

Methods:

Technique is stepwise described and illustrated in its clinical application.

Results:

Local pterional advancement flap provides an excellent coverage, being extremely pliable, and flexible in contents and design. Vascular pedicle is independent from distal branches of the superficial temporal artery and provides adequate blood flow. Pedicle length enables a good arc of rotation, which facilitates its transposition. Flap preparation is very easy and minimally time consuming, due to its immediate regional availability and the easy harvesting technique.

Conclusions:

Local pterional advancement flap represents an effective option as regional flap for the reconstruction of late-onset, pterional soft tissues dehiscence in fragile patients.
A Digital Approach to Evaluating Tooth Root Position Without Repeated Cone-beam Computed Tomography Scans
Authors: Lee Kyungmin Clara
Published: August 2021

The purpose of this report is to introduce a digital approach to evaluating three-dimensional root position without radiation using virtual tooth model which is composed of intraoral-scanned crown and cone-beam computed tomography (CBCT)-scanned root. Successful treatment depends not only on the formulation of a proper initial diagnosis, but also on an accurate assessment of treatment progress, which should include the monitoring and evaluation of tooth and root movements. Although CBCT allows the visualization of the true root position and angulation in three-dimensions, the obtaining of serial CBCT scans for this purpose is associated with concerns regarding radiation exposure. This report introduces a method for monitoring three-dimensional root position following tooth movement during treatment that does not require repeated CBCT scans. This method uses an individual virtual tooth model composed of intraoral-scanned crowns and CBCT-scanned roots. When an evaluation of root positions is needed during treatment, only additional intraoral scan is needed and is integrated into the tooth model; this allows root positions to be estimated without the need for another CBCT scan. The use of a virtual tooth model can potentially allow clinicians to accurately monitor tooth position in routine clinical practice, without the hazards of increased radiation exposure.
Diverting Enterostomy Improves Overall Survival of Patients With Severe Steroid-refractory Gastrointestinal Acute Graft-Versus-Host Disease
Authors: Khodr Justine , Zerbib Philippe , Rogosnitzky Moshe , Magro Leonardo , Truant Stéphanie , Yakoub-Agha Ibrahim , Duhamel Alain , Seguy David
Published: August 2021

Objective:

The aim of this study was to evaluate the benefit of diverting enterostomy (DE) in patients with severe steroid-refractory (SR) gastrointestinal acute graft-versus-host-disease (GI-aGVHD) following allogeneic hematopoietic stem-cell transplantation (ASCT).

Summary and Background Data:

Severe GI-aGVHD refractory to the first-line steroid therapy is a rare but dramatic life-threatening complication. Second lines of immunosuppressors have limited effects and increase the risk of sepsis. Data suggest that limiting GI bacterial translocation by DE could restrain severe GI-aGVHD.

Methods:

From 2004 to 2018, we retrospectively reviewed all consecutive patients undergoing ASCT for hematologic malignancies who developed severe SR GI-aGVHD. We compared patients in whom a proximal DE was performed (Enterostomy group) with those not subjected to DE (Medical group). The primary endpoint was the 1-year overall survival (OS) measured from the onset of GI-aGVHD. Secondary endpoints were the 2-year OS and causes of death.

Results:

Of the 1295 patients who underwent ASCT, 51 patients with severe SR GI-aGVHD were analyzed (13 in Enterostomy group and 38 in Medical group). Characteristics of patients, transplantation modalities, and aGVHD severity were similar in both groups. The 1-year OS was better after DE (54% vs 5%, P = 0.0004). The 2-year OS was also better in “Enterostomy group” (31% vs 2.5%; P = 0.0015), with a trend to lower death by sepsis (30.8% vs 57.9%; P = 0.091).

Conclusion:

DE should be considered for severe GI-aGVHD as soon as resistance to the corticosteroid is identified.
Survey of Clinical Neurophysiology and Epilepsy Fellowship Programs in the United States During COVID-19
Authors: Nakhleh Lauren , Gavvala Jay R. , Haneef Zulfi
Published: August 2021

Purpose:

The COVID-19 pandemic impacted clinical practice, education, and research in Neurophysiology/Epilepsy. Although there is published literature on clinical impact, its educational impact is not well described. A national survey of Clinical Neurophysiology (CNP) and Epilepsy fellowship programs was conducted to assess the impact of COVID-19 on fellowship education.

Methods:

A list of accredited Clinical Neurophysiology and Epilepsy fellowship programs was obtained from the Accreditation Council for Graduate Medical Education. Program directors at individual locations were contacted to complete a brief survey about the program and impact of COVID-19. Fellows from responding programs were subsequently invited to share their perceptions about the impact of the pandemic on their training.

Results:

From 176 programs, 40 PDs responded (22.7%). From these 40 programs, fellows from 26 completed surveys (65.0% response). There was a reduction in EEG and epilepsy monitoring unit volumes post-COVID-19, with a trend of change for EMG, whereas continuous EEG volumes were mostly unchanged. The impact of the pandemic on training was rated as moderate to severe (≥50%) by 30.0% of PDs and 49.0% of trainees. In remarkable agreement, 20.0% of PDs and 20.4% of fellows believed that additional fellowship training was needed before graduation. Lack of fellow satisfaction was correlated with the perceived impact of the pandemic on education (p = 0.008).

Conclusions:

This survey revealed a considerable impact on EEG/EMG clinical volume because of COVID-19, although continuous EEG was not as impacted. More fellows than PDs believed that training was considerably impacted by COVID-19, but a similar number thought that additional training was needed. It was unclear from this study whether the fellows' perception of educational impact was solely because of the pandemic or in addition to preexisting training deficiencies in the training programs.
Explore the role of CR1 genetic variants in late-onset Alzheimer’s disease susceptibility
Authors: Lu Liu , Yao Qing-yu , Ruan Sha-Sha , Hu Jia-Wei , Long Wen-jun , Dai Wen-Zhuo , Ma Tao , Zhu Xi-Chen
Published: August 2021

Background

Complement component (3b/4b) receptor 1 (CR1) is an interesting candidate gene which has a close connection with Alzheimer’s disease, and its polymorphisms have been reported to link to the late-onset Alzheimer’s disease (LOAD) susceptibility. However, the findings of these related studies are inconsistent. Objective To explore the effect of CR1 genetic variants in LOAD susceptibility. MethodsWe searched relevant studies for the period up to 1 November 2020. And odds ratios (ORs) and their 95% confidence intervals (CIs) were utilized to assess the strength of the association. In addition, we carried out a case-control association study to assess their genetic association.

Results

Finally, a total of 30 articles with 30108 LOAD cases and 37895 controls were included. Significant allele frequency between LOAD patients and controls was observed in rs3818361 and rs6656401 (rs3818361, T vs. C: OR,1.18; 95% CI, 1.13–1.23; rs6656401, A vs. G: OR, 1.23; 95% CI, 1.10–1.36). Moreover, these results remain significant in subgroup of rs3818361 in Asia or America (OR,1.26; 95% CI,1.06–1.45; OR, 1.18; 95% CI, 1.13–1.24, respectively) and rs6656401 in Europe (OR = 1.26; 95% CI, 1.09–1.42). In addition, the two single nucleotide polymorphisms were proved to significantly increase LOAD risk in the overall population under the dominant model (OR = 1.12; 95% CI, 1.02–1.21; OR = 1.18, 95% CI, 1.15–1.22, respectively). Our case–control study showed that the distribution of rs6656401 genotype was significant (P = 0.000; OR, 6.889; 95% CI, 2.709–17.520), suggesting the A allele of rs6656401 is the risk allele.

Conclusion

These available data indicate that rs6656401 in CR1 is significant to increase LOAD risk.
Diverse clinical manifestations of X-linked adrenoleukodystrophy in a Chinese family with identical multisite variants of ABCD1 gene
Authors: Zhang Lin , Zhao Su Li , Wang Zhi Hong
Published: August 2021

Objective

This study summarized the clinical characteristics of X-linked adrenoleukodystrophy (X-ALD) patients in this family, and two different manifestations of the same variants in a Chinese family were reported in this article. That conducted a follow-up study to further clarify the characteristics of this disease.

Basic methods

Clinical data and test results were analyzed, and the exon region of ALD-related gene ABCD1 was sequenced by Sanger sequencing.

Main results

Gene analysis showed that there were three ABCD1 variants in the proband, c.1047C>A, c.1415-1416delAG and c.1548G>A. The elder brother of the proband had the same three variants as the proband, but showed different clinical symptoms. The mother was the carrier of three variants. Multisite variants were uncovered in this family, which caused two different manifestations of adult-onset childhood cerebral ALD and adrenomyeloneuropathy.

Principal conclusion

These findings further increase our knowledge about ABCD1 mutations and the associated phenotypes, which is beneficial for the genetic counseling of patients with X-ALD.
A new straightforward method for semi-automated segmentation of trabecular bone from cortical bone in diverse and challenging morphologies
Authors: Herbst Eva C. , Felder Alessandro A. , Evans Lucinda A. E. , Ajami Sara , Javaheri Behzad , Pitsillides Andrew A.
Published: August 2021

Many physiological, biomechanical, evolutionary and clinical studies that explore skeletal structure and function require successful separation of trabecular from cortical compartments of a bone that has been imaged by X-ray micro-computed tomography (micro-CT) prior to analysis. Separation often involves manual subdivision of these two similarly radio-opaque compartments, which can be time-consuming and subjective. We have developed an objective, semi-automated protocol which reduces user bias and enables straightforward, user-friendly segmentation of trabecular from the cortical bone without requiring sophisticated programming expertise. This method can conveniently be used as a ‘recipe’ in commercial programmes (Avizo herein) and applied to a variety of datasets. Here, we characterize and share this recipe, and demonstrate its application to a range of murine and human bone types, including normal and osteoarthritic specimens, and bones with distinct embryonic origins and spanning a range of ages. We validate the method by testing inter-user bias during the scan preparation steps and confirm utility in the architecturally challenging analysis of growing murine epiphyses. We also report details of the recipe, so that other groups can readily re-create a similar method in open access programmes. Our aim is that this method will be adopted widely to create a reproducible and time-efficient method of segmenting trabecular and cortical bone.
How the African house gecko (Hemidactylus mabouia) conquered the world
Authors: Agarwal Ishan , Ceríaco Luis M. P. , Metallinou Margarita , Jackman Todd R. , Bauer Aaron M.
Published: August 2021

Alien species are among the greatest threats to biodiversity, but the evolutionary origins of invasiveness remain obscure. We conducted the first range-wide sampling ofHemidactylus mabouiafrom more than 120 localities across Africa, Madagascar and the Neotropics to understand the evolutionary history of one of the most widely distributed, invasive vertebrates in the world. We used a multi-locus phylogeny, species delimitation, fossil-calibrated timetree, ancestral area reconstruction and species distribution models (SDMs) to determine how many putative species-level lineages are contained withinH. mabouia, the timing and tempo of diversification, and the origins of commensality—providing insights into the evolutionary origins of invasiveness. Our analyses suggest ‘H. mabouia’ originated in the Miocene in the Zambezian biogeographic region and includes as many as 20 putative species-level lineages, of which onlyHemidactylus mabouia sensu strictois invasive and widely distributed, including all Neotropical records. Zambezia is the hotspot for diversity within the group with 14 species in southeastern Zambezia. SDMs suggest thatH. mabouiawas able to establish in the Neotropics due to habitat suitability, and globalization and the slave trade probably allowed it to cross the Atlantic. Distribution models for theH. mabouiacomplex overpredict the range of the invasiveH. mabouia sensu stricto—highlighting the importance of taxonomy in invasive species management.
An observer model of tilt perception, sensitivity and confidence
Authors: Arnold Derek H. , Saurels Blake W. , Anderson Natasha L. , Johnston Alan
Published: August 2021

Humans experience levels of confidence in perceptual decisions that tend to scale with the precision of their judgements; but not always. Sometimes precision can be held constant while confidence changes—leading researchers to assume precision and confidence are shaped by different types of information (e.g. perceptual and decisional). To assess this, we examined how visual adaptation to oriented inputs changes tilt perception, perceptual sensitivity and confidence. Some adaptors had a greater detrimental impact on measures of confidence than on precision. We could account for this using an observer model, where precision and confidence rely on different magnitudes of sensory information. These data show that differences in perceptual sensitivity and confidence can therefore emerge, not because these factors rely on different types of information, but because they rely on different magnitudes of sensory information.
Zobellia roscoffensis sp. nov. and Zobellia nedashkovskayae sp. nov., two flavobacteria from the epiphytic microbiota of the brown alga Ascophyllum nodosum, and emended description of the genus Zobellia
Authors: Barbeyron Tristan , Thiébaud Manon , Le Duff Nolwen , Martin Marjolaine , Corre Erwan , Tanguy Gwenn , Vandenbol Micheline , Thomas François
Published: August 2021

Four marine bacterial strains were isolated from a thallus of the brown algaAscophyllum nodosumcollected in Roscoff, France. Cells were Gram-stain-negative, strictly aerobic, non-flagellated, gliding, rod-shaped and grew optimally at 25–30 °C, at pH 7–8 and with 2–4 % NaCl. Phylogenetic analyses of their 16S rRNA gene sequences showed that the bacteria were affiliated to the genusZobellia(familyFlavobacteriaceae, phylumBacteroidetes). The four strains exhibited 97.8–100 % 16S rRNA gene sequence similarity values among themselves, 97.9–99.1 % to the type strains ofZobellia amurskyensisKMM 3526TandZobellia laminariaeKMM 3676T, and less than 99 % to other species of the genusZobellia. The DNA G+C content of the four strains ranged from 36.7 to 37.7 mol%. Average nucleotide identity and digital DNA–DNA hybridization calculations between the new strains and other members of the genusZobelliaresulted in values of 76.4–88.9 % and below 38.5 %, respectively. Phenotypic, phylogenetic and genomic analyses showed that the four strains are distinct from species of the genusZobelliawith validly published names. They represent two novel species of the genusZobellia, for which the namesZobellia roscoffensissp. nov. andZobellia nedashkovskayaesp. nov. are proposed with Asnod1-F08T(RCC6906T=KMM 6823T=CIP 111902T) and Asnod2-B07-BT(RCC6908T=KMM 6825T=CIP 111904T), respectively, as the type strains.
Generalizable characteristics of false-positive bacterial variant calls
Authors: Bush Stephen J.
Published: August 2021

Minimizing false positives is a critical issue when variant calling as no method is without error. It is common practice to post-process a variant-call file (VCF) using hard filter criteria intended to discriminate true-positive (TP) from false-positive (FP) calls. These are applied on the simple principle that certain characteristics are disproportionately represented among the set of FP calls and that a user-chosen threshold can maximize the number detected. To provide guidance on this issue, this study empirically characterized all false SNP and indel calls made using real Illumina sequencing data from six disparate species and 166 variant-calling pipelines (the combination of 14 read aligners with up to 13 different variant callers, plus four ‘all-in-one’ pipelines). We did not seek to optimize filter thresholds but instead to draw attention to those filters of greatest efficacy and the pipelines to which they may most usefully be applied. In this respect, this study acts as a coda to our previous benchmarking evaluation of bacterial variant callers, and provides general recommendations for effective practice. The results suggest that, of the pipelines analysed in this study, the most straightforward way of minimizing false positives would simply be to use Snippy. We also find that a disproportionate number of false calls, irrespective of the variant-calling pipeline, are located in the vicinity of indels, and highlight this as an issue for future development.
Combined Metabolic Activators Improve Cognitive Functions without Altering Motor Scores in Parkinson’s Disease
Authors: Yulug Burak , Altay Ozlem , Li Xiangyu , Hanoglu Lutfu , Cankaya Seyda , Lam Simon , Yang Hong , Coskun Ebru , İdil Ezgi , Nogaylar Rahim , Hacımuftuoglu Ahmet , Arif Muhammad , Shoaie Saeed , Zhang Cheng , Nielsen Jens , Turkez Hasan , Borén Jan , Uhlén Mathias , Mardinoglu Adil
Published: August 2021

The neuropathologic hallmarks of Parkinson’s disease (PD) are associated with mitochondrial dysfunction and metabolic abnormalities. We have reported that the Combined Metabolic Activators (CMA), consisting of L-serine, nicotinamide riboside, N-acetyl-L-cysteine, and L-carnitine tartrate can be used in treating metabolic abnormalities. These metabolic activators are the precursors of nicotinamide adenine dinucleotide (NAD+) and glutathione (GSH) and used in activation of mitochondrial and global metabolism. We have performed a placebo-controlled, phase-2 study in Alzheimer’s disease (AD) patients and reported that the cognitive functions in AD patients is significantly improved 29% in the CMA group whereas it is improved only 14% in the placebo group after 84 days of CMA administration. Here, we designed a randomized, double-blinded, placebo-controlled, phase-2 study in PD patients with CMA administration. We found that the cognitive functions in PD patients is significantly improved 21% in the CMA group, whereas it is improved only 11% in the placebo group after 84 days of CMA administration. We also found that the administration of CMA did not affect motor functions in PD patients. We performed a comprehensive multi-omics analysis of plasma proteins and metabolites, and revealed the molecular mechanism associated with the treatment of the patients. In conclusion, our results show that treating PD patients with CMAs leads to enhanced cognitive function, as recently reported in AD patients.
Multi-trait genome-wide association study identifies novel endometrial cancer risk loci that are associated with obesity or female testosterone levels
Authors: Wang Xuemin , Kho Pik Fang , Ramachandran Dhanya , Bafligil Cemsel , Amant Frederic , Goode Ellen L. , Scott Rodney J. , Tomlinson Ian , Evans D. Gareth ,   Endometrial Cancer Association Consortium, Crosbie Emma J. , Dörk Thilo , Spurdle Amanda B. , Glubb Dylan M. , O’Mara Tracy A.
Published: August 2021

We have performed genetic correlation and Mendelian randomization analyses using publicly available genome-wide association study (GWAS) data to identify endometrial cancer risk factors. These and previously established risk factors of endometrial cancer were then included in a multi-trait Bayesian GWAS analysis to detect endometrial cancer susceptibility variants, identifying three novel loci (7q22.1, 8q24.3 and 16q12.2); two of which were replicated in an independent endometrial cancer GWAS dataset. These loci are hypothesized to affect endometrial cancer risk through altered sex-hormone levels or through effects on obesity. Consistent with this hypothesis, several genes with established roles in these pathways (CYP11B1, CYP3A7, IRX3 and IRX5) were prioritized as candidate endometrial cancer risk genes by interrogation of quantitative trait loci data and chromatin capture assays in endometrial cell lines. The findings of this study identify additional opportunities for hormone treatment and further support weight loss to reduce the risk of developing endometrial cancer.

Statement of Significance

This study prioritizes four genes related to testosterone and obesity as candidate endometrial cancer risk genes, as well as identifies additional opportunities for hormone treatment and further supports weight loss to reduce endometrial cancer risk.
Initial Antidepressant Choice by Non-Psychiatrists: Learning from Large-scale Electronic Health Records
Authors: Sheu Yi-han , Magdamo Colin , Miller Matthew , Smoller Jordan W. , Blacker Deborah
Published: August 2021

Introduction

Pharmacological treatment of depression mostly occurs in non-psychiatric settings, but factors that determine the initial choice of antidepressant treatment in these settings are not well-understood. This study models how non-psychiatrists choose among four antidepressant classes at first prescription (selective serotonin reuptake inhibitors [SSRI], bupropion, mirtazapine, or serotonin-norepinephrine reuptake inhibitors [SNRI]), by analyzing electronic health record (EHR) data.

Methods

EHR data were from the Mass General Brigham Healthcare System (Boston, Massachusetts, USA) for the period from 1990 to 2018. From a literature search and expert consultation, we selected 64 variables that may be associated with antidepressant choice. Patients who participated in the study were aged 18 to 65 at the time of first antidepressant prescription with a co-occurring International Classification of Diseases (ICD) code for a depressive disorder. Multinomial logistic regression with main effect terms for all 64 variables was used to model the choice of antidepressant. Using SSRI as the reference class, odds ratios, 95% confidence intervals (CI), and likelihood ratio-based p-values for each variable were reported. We used a false discovery rate (FDR) with the Benjamini–Hochberg procedure to correct for multiple comparisons.

Findings

A total of 47,107 patients were included after application of inclusion/exclusion criteria. We observed significant associations for 36 of 64 variables after multiple comparison corrections. Many of these associations suggested that antidepressants’ known pharmacological properties/actions guided choice. For example, there was a decreased likelihood of bupropion prescription among patients with epilepsy (adjusted OR 0.41, 95% CI: 0.33–0.51, p < 0.001), an increased likelihood of mirtazapine prescription among patients with insomnia (adjusted OR 1.58, 95% CI: 1.39–1.80, p < 0.001), and an increased likelihood of SNRI prescription among patients with pain (adjusted OR 1.22, 95% CI: 1.11–1.34, p = 0.001).

Interpretation

Non-psychiatrists’ selection of antidepressant class appears to be guided by clinically relevant pharmacological properties, indications, and contraindications, suggesting that broadly speaking they choose antidepressants based on meaningful differences among medication classes.
Liposomal Dexamethasone Reduces A/H1N1 Influenza-Associated Morbidity in Mice
Authors: Kwon Jung Won , Quan Hailian , Song Juha , Chung Hyewon , Jung Daun , Hong Jung Joo , Na Yi Rang , Seok Seung Hyeok
Published: August 2021

Re-emerging viral threats have continued to challenge the medical and public health systems. It has become clear that a significant number of severe viral infection cases are due to an overreaction of the immune system, which leads to hyperinflammation. In this study, we aimed to demonstrate the therapeutic efficacy of the dexamethasone nanomedicine in controlling the symptoms of influenza infection. We found that the A/Wisconsin/WSLH34939/2009 (H1N1) infection induced severe pneumonia in mice with a death rate of 80%, accompanied by significant epithelial cell damage, infiltration of immune cells, and accumulation of pro-inflammatory cytokines in the airway space. Moreover, the intranasal delivery of liposomal dexamethasone during disease progression reduced the death rate by 20%. It also significantly reduced the protein level of tumor necrosis factor-alpha (TNFα), interleukin1β (IL-1β), IL-6, and the C-X-C motif chemokine ligand 2 (CXCL2) as well as the number of infiltrated immune cells in the bronchoalveolar lavage fluids as compared to the free drug. It was found that the liposomal dexamethasone was mainly distributed into the monocyte/macrophages in the lungs, suggesting its mode of action via the specific delivery of the drug into myeloid cells as a major cell population for inducing the cytokine storm. Taken together, the intranasal delivery of liposomal dexamethasone may serve as a novel promising therapeutic strategy for the treatment of influenza A-induced pneumonia.

Importance

Influenza A virus causes annual epidemics and sporadic pandemics of respiratory diseases. An excessive immune response, called a cytokine storm, caused by the influenza virus is the most common complication of influenza infection that is associated with high levels of morbidity and mortality. Here, we report that the liposomal dexamethasone targeting the monocytes/macrophages during disease progression reduced the death rate as well as the protein level of inflammatory cytokines and the number of immune cells. Therefore, the findings of this study may be applied to address the limitations of the current strategies for the treatment of influenza.