bluuebunny/crossref_metadata_2025 huggingface dataset:
Diagnostic Utility of Diffusion-Weighted Imaging and Apparent Diffusion Coefficient for Common Orbital Lesions: A Review
Authors: Cameron Cassie A. , Tong Jessica Y. , Juniat Valerie , Patel Sandy , Selva Dinesh
Published: November 2021

Purpose:

To review and summarize the existing literature surrounding the clinical use of diffusion-weighted imaging and apparent diffusion coefficient (ADC) as diagnostic tools in differentiating common orbital lesions.

Methods:

A systematic literature review on the use of ADC and diffusion-weighted imaging sequences for orbital imaging was performed. Only original research articles that reported ADC values for benign or malignant lesions were included.

Results:

Malignant orbital tumors have an overall lower mean ADC value than benign masses. Orbital lymphoma is characterized by consistently lower ADC values compared with other malignant orbital masses; a threshold value less than 0.775 × 10−3 mm2/s has been proposed to distinguish orbital lymphoma from other neoplastic and non-neoplastic orbital masses. To differentiate orbital inflammatory disease from lymphoma, an ADC threshold greater than 0.92 × 10−3 mm2/s has been proposed.

Conclusions:

Orbital masses encompass a host of benign and malignant etiologies and can present a diagnostic challenge on both clinical and radiological assessment. Recent advanced MRI techniques such as diffusion-weighted imaging and ADC can improve the diagnostic specificity for orbital disease, particularly in differentiating benign from malignant lesions and lymphoma from orbital inflammatory disease.
Transfemoral Prosthetic Socket Designs: A Review of the Literature
Authors: Brodie Melissa , Murray Laura , McGarry Anthony
Published: November 2021

Introduction

The prosthetic socket is the interface that connects the human body to the artificial limb and allows transmission of body weight and forces during gait. The review purpose is to assess the quality of scientific evidence and compare this for a variety of available transfemoral socket designs. Comparisons will be made of socket biomechanics, metabolic efficiency and comfort, and the advantages/disadvantages associated with each design.

Methods

Socket designs included were quadrilateral (quad), ischial containment (IC), Marlo Anatomical Socket, subischial, high-fidelity (HiFi), and the Socket-less Socket. A literature review was conducted in five online databases: Compendex, Embase, PubMed, ProQuest Materials Science, and ProQuest Biological Science, using Boolean search terms and truncation of relevant keywords. Included articles were published between 1989 and 2018. A predetermined methodological criterion was used in conjunction with a modified version of the Oxford Levels of Evidence to assess and grade the quality of selected articles.

Results

Thirteen clinical studies were included in this review. Based on the chosen search strategy and quality criterion, this review found a limited, low-quality evidence base for all included socket designs. All articles, except one, compared the various socket designs (quad, quad and MAS, MAS, subischial, and HiFi) against an IC socket as this was deemed the “standard of care” design.

Conclusions

Although IC attained the highest volume of evidence, this socket design was not proven to be superior. The variety of biomechanical features pertaining to each socket design provides several advantages/disadvantages. Recommendations are made for future research.

Clinical Relevance

Findings from this literature review promote knowledge and understanding of transfemoral socket design by highlighting the underlying theory, strengths, and weaknesses of each design acknowledged to facilitate improved evidence-based practice.
Upper-Limb Prosthetic Maintenance Data: A Retrospective Analysis Study
Authors: Nagaraja Vikranth H. , Cheng Runbei , Slater David Henderson , Thompson Mark S. , Bergmann Jeroen H.M.
Published: November 2021

Introduction

Understanding repair patterns of upper-limb (UL) prosthetic devices have received little attention compared with their lower-limb counterparts. This study focuses on a retrospective analysis of anonymized UL prosthetic maintenance data to establish if there were any patterns of repairs at a regional prosthetic limb-fitting center in the United Kingdom. A secondary aim of this study is to describe the patient demographics of this center.

Methods

Data containing prosthetic repair log and demographic description (n = 212) were acquired through our clinical partners and subjected to statistical analyses.

Results

On average, each client visited the center 0.2 times/year for a new device and 0.9 times/year for maintenance-related activities. It is found that the repair rates are generally higher for body-powered devices (1.28 visits/device per year) compared with passive (0.94 visits/device per year) and externally powered devices (0.90 visits/device per year). In keeping with the typical UK UL-deficient population, there is a high male-to-female ratio, and higher instances of traumatic amputations were noticed for males at the center. There is a very high preponderance of congenital cases and an overall emphasis on prescribing passive devices to a majority of patients at the center.

Conclusions

The data from our study are similar to previously published data from other centers and show a consistent pattern in terms of relative rates of maintenance attendances for different types of UL prostheses.

Clinical Relevance

This study provides a longitudinal perspective and insights on ever-changing requirements (prostheses and related care) of the users at the level of a regional limb-fitting center. This study underscores current gaps in prosthetic device durability/reliability and opens up avenues for improvement of prosthetic services and devices.
Combining Foot Drop Stimulation Devices with Gait Training Improves Gait, Active Ankle Movement of Chronic Poststroke Individuals
Authors: Cunha Maira Jaqueline da , Pinto Camila , Zanfir Bruna , Cimolin Veronica , Pagnussat Aline Souza
Published: November 2021

Introduction

Foot drop stimulator (FDS) devices induce positive clinical effects on foot drop secondary to stroke. Literature does not establish a recommended period or a standard intensity of stimulation to achieve training and therapeutic effects in individuals after stroke.

The objective of this study was to evaluate the training and therapeutic effects of 2 weeks of FDS use combined with intensive treadmill gait training in chronic poststroke individuals.

Materials and Methods

The study design was a quasiexperimental clinical trial. Participants underwent gait training on a treadmill associated with FDS stimulation for 20 minutes, five times a week for 2 weeks. Gait analysis was measured at pre-training and 2 weeks after the training with FDS off/on mode.

Results

Sixteen chronic poststroke individuals were included. One participant was excluded from the analysis due to data processing fault. After the period of training, and with the orthosis on mode on, individuals ameliorated the active dorsiflexion and increased the distance covered, that is, positive training effect of FDS use. Training and therapeutic effects were not observed in other outcomes.

Conclusions

Our results demonstrated a positive training effect on ankle active movement during gait. FDS combined with gait training is able to increase the total distance walked after 2 weeks of treatment.

Clinical Relevance

FDS ameliorated the active dorsiflexion and increased the distance covered in people with chronic poststroke. Our results suggest a positive training effect of FDS that can guide physiotherapists in their clinical practice.
Examination of Near Point of Convergence Scores in High-School Athletes: Implications for Identifying Binocular Vision Dysfunction After Concussion Injury
Authors: Del Rossi Gianluca
Published: November 2021

Objective:

To identify normative near point of convergence (NPC) data for healthy high-school–aged athletes (13-19 years old) and determine the percentage of individuals with NPC scores that fall outside the currently accepted clinical cutoff value of 5 cm. Another objective was to determine the relationship between sex, concussion history, and attention deficit disorder/attention deficit hyperactivity disorder (ADD/ADHD) with NPC scores, if any.

Design:

Case series.

Setting:

High-school sports medicine clinic.

Patients (or Participants):

Near point of convergence was assessed in 718 high-school student athletes (141 females and 577 males) with an average age of 15.96 ± 1.16 years.

Interventions:

None.

Main Outcome Measures:

An accommodation convergence ruler was used to measure NPC. Near point of convergence scores were repeated a total of 3 times and the mean used for all statistical analyses.

Results:

The NPC scores for all participants averaged 3.58 cm, and the intraclass correlation coefficient for the 3 repeated measurements was 0.956. Approximately 20% of mean NPC scores were above the accepted upper limit of 5 cm. Although a statistically significant effect for sex was identified, the difference between them was considered clinically insignificant. No relationship between NPC and history of concussion or ADD/ADHD was identified.

Conclusions:

Results indicate that in high-school–aged subjects, approximately 20% of individuals may have NPC values that fall outside the current critical cutoff value and may lead to incorrect diagnosis of ocular dysfunction. In addition, NPC does not seem to be affected by the history of concussion or a diagnosis of ADD/ADHD.
The nurse practitioner's role in addressing chronic sequelae of Lyme disease as a climate change related disease
Authors: Nicholas Patrice , Evans Linda A. , Albert Marisa , Kelly Debra , Michelson Naomi
Published: November 2021

A major health consequence of climate change is an increased prevalence of vector-borne diseases due to changes in temperatures and the environments in which vectors can survive and carry out transmissible activity. Because of climate change, emerging health challenges related to the warming of the planet have led to an increase in vector-borne diseases in broadening geographic areas. Individuals affected with Lyme disease may present with a variety of symptoms, which highlights the importance of illness recognition to ensure that a patient can receive timely treatment and effective support. Despite the focus on early detection and treatment of acute Lyme disease, chronic health problems associated with Lyme disease are an emerging problem in the 21st century. This article focuses on the role of nurse practitioners and members of the health professional team in the recognition, clinical care, patient education, and management of increasing rates of chronic Lyme disease.
What Determines the Arterial Partial Pressure of Carbon Dioxide on Venovenous Extracorporeal Membrane Oxygenation?
Authors: Joyce Christopher J. , Udy Andrew , Weeden Mark , Shekar Kiran , Cook David A.
Published: November 2021

Rapid reductions in PaCO2 during extracorporeal membrane oxygenation (ECMO) are associated with poor neurologic outcomes. Understanding what factors determine PaCO2 may allow a gradual reduction, potentially improving neurologic outcome. A simple and intuitive arithmetic expression was developed, to describe the interactions between the major factors determining PaCO2 during venovenous ECMO. This expression was tested using a wide range of input parameters from clinically feasible scenarios. The difference between PaCO2 predicted by the arithmetic equation and PaCO2 predicted by a more robust and complex in-silico mathematical model, was <10 mm Hg for more than 95% of the scenarios tested. With no CO2 in the sweep gas, PaCO2 is proportional to metabolic CO2 production and inversely proportional to the “total effective expired ventilation” (sum of alveolar ventilation and oxygenator ventilation). Extracorporeal blood flow has a small effect on PaCO2, which becomes more important at low blood flows and high recirculation fractions. With CO2 in the sweep gas, the increase in PaCO2 is proportional to the concentration of CO2 administered. PaCO2 also depends on the fraction of the total effective expired ventilation provided via the oxygenator. This relationship offers a simple intervention to control PaCO2 using titration of CO2 in the sweep gas.
Readability and quality assessment of internet-based patient education materials related to deep vein thrombosis
Authors: Qadeer Muhammad Abrar , Kelly Martin , Lenehan Brian
Published: November 2021

Access to health-related internet information has increased dramatically during the past decade. A significant proportion of this information has been demonstrated to be set at too high a level for general comprehension. The goal of this study was to evaluate the readability and quality of information available on the internet relating to deep vein thrombosis (DVT). A search for ‘DVT’ and ‘Deep Vein Thrombosis’ was performed on five most commonly accessed search engines. Top hundred websites were reviewed. Website authorship was classified. Each site was assessed using the recognized quality and readability scoring systems. The presence of the health on the net foundation code of conduct (HON-code), a reported quality-assurance marker, was noted.

The majority of web sites (45%) were academic or physician compiled. Only 36% of the websites were HON-code certified. HON-code certified sites achieved significantly greater DISCERN and Journal of the American Medical Association (JAMA) scores. Seventy-three percent of the websites were above the recommended sixth-grade readability level. Flesch--Kincaid readability test (FRES) of more than half of the websites (56%) was below 60, which makes them fairly difficult to read by general public.

Internet information relating to DVT is of variable quality and largely set at an inappropriate readability level. Given this variability in quality, healthcare providers should direct patients to known sources of reliable, readable online information. Identification of reliable sources may be aided by known markers of quality such as HONcode certification and to educate them to use academic and physician-provided sites which have been shown to contain better-quality information. Moreover, academic and physician-compiled websites should be written in a fashion appropriate for general public consumption.
Assessment of clinical characteristics and treatment outcomes of pediatric patients with intracardiac thrombosis: a single-center experience
Authors: Odaman Al Işik , Oymak Yeşim , Erdem Melek , Tahta Neryal , Okur Acar Sultan , Mese Timur , Yilmazer Murat Muhtar , Gözmen Salih , Zihni Cuneyt , Calkavur Sebnem , Karapinar Tuba Hilkay
Published: November 2021

The prevalence of intracardiac thrombus (ICT) is gradually increasing, though it is rare among children. Data related to the occurrence of ICT among children are limited, and treatment recommendations have been made utilizing adult guidelines. The primary objective of this study is to determine associated factors, management, and outcomes of intracardiac thrombosis in children. Between January 2013 and January 2020, patients diagnosed with ICT at the Pediatric Hematology-Oncology and Pediatric Cardiology departments in our hospital were included in the study. Demographic characteristics, clinical and laboratory findings, treatment protocols, and outcomes were analyzed retrospectively. The median age at diagnosis was 10.5 months (2 days to 14.5 years), and the median follow-up period was 6.5 months (1 month to 3.1 years). The most common primary diagnoses of the patients, in order of frequency, were heart disease (n: 8), metabolic disease (n: 3), prematurity and RDS (n: 3), burns (n: 2), pneumonia (n: 2), and asphyxia (n: 2). CVC was present in 19/23 of the patients. The reasons for CVC insertion were the need for plasmapheresis in one patient with a diagnosis of HUS and the need for well tolerated vascular access because of long-term hospitalization in others. LMWH was administered to all patients as first-line therapy. Complete response was achieved in 19 (79%) of 24 patients and 4 patients (16.6%) were unresponsive to medical treatment. It was found out that the thrombus location, type, sepsis, and hemoculture positivity, as well as the presence of CVC, had no impact on treatment response (chi-square P = 0.16, 0.12, 0.3, 0.49, 0.56). Moreover, no correlation was determined between thrombus size and treatment response (Mann Whitney U test P = 0.47). The mortality rate was determined to be 12.5% (3/24). Spontaneous occurrence of ICT is rare in childhood, without any underlying primary disease or associated factor. The presence of CVC, sepsis, and heart disease are factors associated with ICT. The success rate is increased with medical treatment. There was no significant difference in treatment response between the newborn and 1 month to 18-year-old patient group. It has been demonstrated that thrombus size, type, localization; sepsis, and hemoculture positivity had no impact on the treatment response.
Genetic analysis of compound heterozygous pathogenic variants of the F11 gene in two Chinese patients with hereditary factor XI deficiency
Authors: Wang Huanhuan , Jiang Shuting , Xie Haixiao , Yang Lihong , Jin Yanhui , Wang Mingshan
Published: November 2021

The aim of this study was to explore the molecular pathogenesis of two families with compound heterozygous hereditary factor XI deficiency. All the exons, flanking sequences, 5’ and 3’ untranslated regions of the F11 gene were analysed by direct DNA sequencing. The suspected variants were confirmed by reverse sequencing. Bioinformatics softwares were used to analysis the conservation and the possible impact of these pathogenic variants. Genetic analysis revealed c.689G > T and c.1556G > A variants of F11 gene in family A; c.1107C > A and c.1557G > C variants of F11 gene in family B. These variants sites were highly conserved among homologous species. Bioinformatics and structural analysis demonstrated these variants were pathogenic and could affect the protein structure. The c.689G > T, c.1556G > A, c.1107C > A and the c.1557G > C heterozygous variants might be responsible for the decrease of FXI levels in probands. In addition, c.689G > T (NM_000128.4) is a novel pathogenic variant site, which has not been reported.
Fatty liver and cerebrovascular disease: plausible association and possible mechanisms
Authors: Khanna Sahil , Parikh Neal S. , VanWagner Lisa B.
Published: November 2021

Purpose of review

Nonalcoholic fatty liver disease (NAFLD) is a common comorbidity and has wide ranging extrahepatic manifestations, including through cardiometabolic pathways. As such, there is growing interest in the impact of NAFLD on cerebrovascular disease and brain health more broadly. In this review, we assess recent research into understanding the association between NAFLD and brain health while highlighting potential clinical implications.

Recent findings

Mechanistically, NAFLD is characterized by both a proinflammatory and proatherogenic state, which results in vascular inflammation and neurodegeneration, potentially leading to clinical and subclinical cerebrovascular disease. Mounting epidemiological evidence suggests an association between NAFLD and an increased risk and severity of stroke, independent of other vascular risk factors. Studies also implicate NAFLD in subclinical cerebrovascular disease, such as carotid atherosclerosis and microvascular disease. In contrast, there does not appear to be an independent association between NAFLD and cognitive impairment.

The current literature supports the formulation of NAFLD as a multisystem disease that may also have implications for cerebrovascular disease and brain health. Further prospective studies are needed to better assess a temporal relationship between the two diseases, confirm these early findings, and decipher mechanistic links.
Are robots the future? A case for robotic pyeloplasty as the gold standard treatment in ureteropelvic junction obstruction
Authors: Beale Robert , Sicilila Sabrina , Riestra Paola , Albala David M.
Published: November 2021

Purpose of review

Robotic pyeloplasty is still a relatively novel procedure. Clinically, early studies have shown high success rates, decreased complication rates, decreased length of hospital stay, and better cosmetic results. This goal of this article is to argue for the use of robotic pyeloplasty as the gold standard of ureteropelvic junction obstruction (UPJO) treatment. Results of studies that have compared robotic pyeloplasty with other procedures currently used are reviewed.

Recent findings

Our study, a comprehensive review of published outcomes of robotic pyeloplasty and alternative therapies, consisted of 666 pediatric patients and 653 adult patients. Our review coincided with the previously established studies that robotic pyeloplasty shows equivalent surgical success rates as previous standard of care treatments. Open pyeloplasty has fallen out of favor as standard of care due to the increased length of hospital stay, increased adverse events, and the undesirable aesthetics.

The use of robotic pyeloplasty has shown to have clinical outcomes that are consistent with other intervention for UPJO, with a potential decrease in length of stay and morbidity. More work has to be done to develop ways to decrease cost of the robot to help establish it as the gold standard for UPJO treatment.
Extramammary Paget's Disease of genitourinary origin
Authors: Narayan Vikram M. , Master Viraj A.
Published: November 2021

Purpose of review

Extramammary Paget's Disease (EMPD) is an uncommon intra-epithelial malignancy, affecting primarily apocrine gland-bearing skin. EMPD is often considered an orphan diagnosis given its rarity. This review provides a contemporary overview of EMPD management.

Recent findings

The mainstay of EMPD treatment centers around a high index of suspicion to allow for an early and accurate diagnosis, wide local or Mohs micrographic surgical excision with care paid toward the margin status, and thoughtful consideration for lymphadenectomy in patients with clinically positive regional disease. There is currently no consensus regarding adjuvant therapies or systemic therapies although with ongoing improvements in tumor biology and genomics, including molecular pathways and alterations specific to EMPD, targeted or combinatorial therapies may be on the horizon.

Clinicians caring for patients with EMPD should seek consultation from or if feasible, consider referral to high-volume, experienced centers with patients counseled and provided with frequent and close follow-up for disease recurrence or progression. Collaboration with groups such as the Global Society for Rare Genitourinary Tumors, and especially patient groups will be vital to designing trials and collaborative databases.
Why do African–American men face higher risks for lethal prostate cancer?
Authors: Nair Sujit S. , Chakravarty Dimple , Dovey Zachary S. , Zhang Xiangfu , Tewari Ashutosh K.
Published: November 2021

Purpose of review

African–American men in the USA have a higher incidence of and mortality from prostate cancer (PCa), with a longstanding debate about the cause for these worse outcomes. This review examines differences in tumour biology and socioeconomics for African–American and Non-Hispanic White (NHW) men to answer the question ‘why AA men face higher risks for lethal PCa’ and draw a management consensus to redress the imbalance.

Recent findings

Recent evidence from over the past 2 years suggests the reasons why African–American men face a higher risk of lethal PCa are multifactorial, with contributions from differences in tumour biology as well as socioeconomic and healthcare access factors. Regarding tumour biology, genomic and transcriptome profiling suggests African–American men have upregulated expression of genes related to inflammatory pathways with downregulation of DNA repair genes. In contrast, NHW men have higher DNA repair pathways and metabolic pathways involving glycolysis and cell cycle activity. In addition, epidemiological evidence suggests equal healthcare access ensures equal PCa specific outcomes, implying African–American men's disease is not inherently more lethal. However, differences in tumour biology remain, which may explain specific differences in PCa incidence and the clinical findings of African–American men's increased response to immunotherapy and radiotherapy in recent trials.

Regardless of racial differences in disease outcomes and the factors causing them, African–American and NHW men seem to have diseases unique to their ancestry. This supports the exploration of personalized PCa treatment approaches, leveraging translational basic science research to uncover these differences and devise specific individualized methods therapeutic regimes to address them.
Creation and Implementation of a Preoperative Malignant Hyperthermia Screening Tool
Authors: Johnson Tirzah , Simmons Virginia C. , Figer Schwartz Sharon , Tola Denise H.
Published: November 2021

Background:

Malignant hyperthermia (MH) is a potentially lethal pharmacogenetic disorder triggered by certain anesthetic agents. There is currently no standardized preoperative screening tool utilized to identify MH-susceptible individuals.

Local Problem:

This quality improvement (QI) project aimed to enhance preoperative screening for MH susceptibility (MHS) by implementing an evidence-based screening tool for surgical patients at 2 sites.

Methods:

This prospective descriptive QI project evaluated the success of implementing an MHS screening tool preoperatively and its impact on the anesthesia plan.

Interventions:

Anesthesia professionals included the screening tool in their preoperative interview for surgical patients so that positively screened patients could receive MH prevention measures.

Results:

A total of 95 patients at site A and 234 patients at site B were screened using the MH tool, a cumulative total of 21 patients were positively screened, and 1 anesthetic plan was altered.

Conclusions:

This MHS screening tool has the potential to prevent MH episodes when used consistently by staff.
Microsatellite Instability in Near East Sebaceous Neoplasms: Toward Improved Prediction
Authors: El Hajj Rana , Saliba Maelle , Shaheen Muhammad , Abbas Fatmeh I. , Bashir Shaarif , Sheikh Umer N. , Loya Asif , Khalifeh Ibrahim
Published: November 2021

Sebaceous neoplasms (SN) comprise a heterogeneous spectrum of tumors with different biological behaviors. In the Near-East Region (NER), microsatellite instability (MSI) in SN’s development, and its correlation with the clinicopathologic features of tumors is not well elucidated. A cohort of 225 SN patients (40 benign SNs and 185 sebaceous carcinomas) from the NER was retrospectively reviewed. Clinical variables and available follow-up information were recorded. MSI proteins (MLH1, MSH2, MSH6, and PMS2) as well as P53, P16, EMA, CD8, and PDL-1 expressions were examined by immunohistochemistry. Detection of human papilloma virus was determined by polymerase chain reaction. Microscopic features such as mitotic count and tumor-infiltrating lymphocytes were documented. A minority of SNs from benign (n=2) or malignant (n=3) tumors in the NER exhibit MSI (2.2%). MSI is exclusively found in patients with extraocular lesions (back, n=5) and presented a poor outcome. Among these, PMS2 protein was mostly lost (average=80%, n=4). SN with MSI exhibited a significant increase in p53 expression, (average=62.10%, P=0.002). There was no significant correlation between MSI status and any of the following: PD-L1, CD8, p16, and human papilloma virus infection. Microscopically, SN with MSI show significantly higher mitotic count, cystic changes and increased tumor-infiltrating lymphocytes. MSI is rarely found in NER’s SN. When detected, it is exclusively in extraocular SNs with minimal predicative microscopic features and worse outcome.
Testing Algorithms for the Diagnosis of Malignant Glandular Tumors of the Uterine Cervix Histotyped per the International Endocervical Adenocarcinoma Criteria and Classification (IECC) System
Authors: Duggan Máire A. , Duan Qiuli , Pfeiffer Ruth M. , Brett Mary Anne , Lee Sandra , Abubakar Mustapha , Köbel Martin , Rodriguez Monica , Sar Aylin
Published: November 2021

The International Endocervical adenocarcinoma Criteria and Classification (IECC) categorizes tumors into human papilloma virus (HPV) associated (HPVA), not associated (NHPV), and invasive adenocarcinoma not otherwise specified (IA NOS). HPVA and NHPV encompass 11 histotypes and an algorithm of mucin content, HPV ribonucleic acid (RNA), estrogen receptor and GATA3 is proposed for the diagnosis of most. In this study, the IECC algorithm’s diagnoses were compared with hematoxylin and eosin (H&E) based IECC histotyping. Kappa statistics measured performance agreement. With additional markers, hierarchical clustering by random forest (RF) classification identified the most discriminating between tumor types, and investigated other algorithms. Three pathologists independently reviewed digitized H&E images of n=152 primary cervical adenocarcinomas for IECC histotype and mucin content, and tissue microarrays for expression of HPV RNA by in situ hybridization and 16 antibodies by immunohistochemistry. Results were finalized by consensus. There were n=113 HPVA, n=22 NHPV, and n=17 IA NOS. Mucin was obvious in n=36 and limited in n=116. Among n=124 with satisfactory test results, HPV RNA was positive in n=96, estrogen receptor in n=72, and GATA3 in n=15. The IECC algorithm diagnosed n=99 which agreed with H&E histotyping in n=64 for a fair κ of 0.36 (95% confidence interval, 0.21-0.50): n=12 were undiagnosed and n=13 were IA NOS. Small sample sizes restricted RF to HPVA versus NHPV which were discriminated by p16, HPV RNA, and MUC6 with an area under the curve of 0.74 (95% confidence interval, 0.58-0.90). The IECC algorithm for histotyping under-performed. The RF algorithmin for categorization was favorable, but validation in larger studies and investigation of additional algorithms to discriminate between all IECC histotypes are needed.
Resistance of B-Cell Lymphomas to CAR T-Cell Therapy Is Associated With Genomic Tumor Changes Which Can Result in Transdifferentiation
Authors: Laurent Camille , Syrykh Charlotte , Hamon Maxime , Adélaïde José , Guille Arnaud , Escudié Frederic , Jalowicki Gael , Fina Frederic , Bardet Alexandre , Mescam Lenaïg , Molina Thierry J. , Dartigues Peggy , Parrens Marie , Sujobert Pierre , Besson Caroline , Birnbaum Daniel , Xerri Luc
Published: November 2021

Despite the impressive efficacy of chimeric antigen receptor (CAR) T-cell therapy (CART) in B-cell non-Hodgkin lymphomas, durable responses are uncommon. The histopathologic and molecular features associated with treatment failure are still largely unknown. Therefore, we have analyzed 19 sequential tumor samples from 9 patients, prior anti-CD19 CART (pre-CART) and at relapse (post-CART), using immunohistochemistry, fluorescence in situ hybridization, array comparative genomic hybridization, next-generation DNA and RNA sequencing, and genome-scale DNA methylation. The initial diagnosis was diffuse large B-cell lymphoma (n=6), double-hit high-grade B-cell lymphoma (n=1), and Burkitt lymphoma (n=2). Histopathologic features were mostly retained at relapse in 7/9 patients, except the frequent loss of 1 or several B-cell markers. The remaining 2 cases (1 diffuse large B-cell lymphoma and 1 Burkitt lymphoma) displayed a dramatic phenotypic shift in post-CART tumors, with the drastic downfall of B-cell markers and emergence of T-cell or histiocytic markers, despite the persistence of identical clonal immunoglobulin gene rearrangements. The post-CART tumor with aberrant T-cell phenotype showed reduced mRNA expression of most B-cell genes with increased methylation of their promoter. Fluorescence in situ hybridization and comparative genomic hybridization showed global stability of chromosomal alterations in all paired samples, including 17p/TP53 deletions. New pathogenic variants acquired in post-CART samples included mutations triggering the PI3K pathway (PIK3R1, PIK3R2, PIK3C2G) or associated with tumor aggressiveness (KRAS, INPP4B, SF3B1, SYNE1, TBL1XR1). These results indicate that CART-resistant B-cell non-Hodgkin lymphomas display genetic remodeling, which may result in profound dysregulation of B-cell differentiation. Acquired mutations in the PI3K and KRAS pathways suggest that some targeted therapies could be useful to overcome CART resistance.
Sinusoidal Growth Pattern of Hepatic Melanoma Metastasis
Authors: Szczepanski Julianne M. , Mendiratta-Lala Mishal , Fang Jiayun M. , Choi Won-Tak , Karamchandani Dipti M. , Westerhoff Maria
Published: November 2021

Metastatic tumors interface with liver in multiple patterns, of which, the rare “sinusoidal” growth pattern can be subtle and easily overlooked on biopsy. We sought to characterize the metastasis-to-liver interface patterns of melanoma compared with other tumor types and assess the incidence of metastatic melanoma in histologically normal-appearing targeted liver lesion biopsies. Liver lesion samples from 54 melanoma patients were assessed. Nearly normal-appearing cases, defined as no obvious malignancy on routine hematoxylin and eosin stain (n=24), were stained with SOX10 and confirmed with MelanA. Tumor-to-liver interface patterns were determined in biopsies overtly positive for metastatic melanoma (n=30) versus other hepatic metastases as controls (colon, n=28; breast, n=20; pancreaticobiliary, n=20; and neuroendocrine, n=28). Of the 24 nearly normal-appearing liver biopsies from melanoma patients, 3 had subtle melanoma cells detected in sinusoids, confirmed with immunohistochemistry. Of 30 livers overtly positive for melanoma, 8 showed the sinusoidal pattern, compared with none in other metastases. In total, 11/33 (33%) cases of metastatic melanoma liver biopsies demonstrated the sinusoidal pattern. We describe 11 metastatic melanoma cases in liver with the rare sinusoidal pattern, 3 of which were subtle and easy to miss on routine hematoxylin and eosin stain. Given that sinusoidal metastasis does not elicit a tissue reaction, it is prudent for the pathologists to be aware of this pattern of metastases and have a low threshold to order immunostains for accurate diagnosis and optimal patient care.
“Magic” Number of Treadmill Sessions Needed to Achieve Meaningful Change in Gait Speed After Stroke
Authors: Balinski Mariah , Madhavan Sangeetha
Published: November 2021

The purpose of this systematic review was to determine the number of treadmill training sessions needed to make a meaningful change in gait speed for chronic stroke survivors. Relevant databases were searched up through February 2020. Articles were included if they fit the following criteria: stroke onset more than 5 mos, intention to treat with traditional treadmill training, and gait speed included as an outcome. Change in gait speed after intervention was used to classify treadmill groups as responders (at least 0.1 m/sec change) or nonresponders (less than 0.1 m/sec change). Seventeen articles met our criteria, resulting in a total of 19 intervention groups. Ten groups were classified as responders and completed a mean of 30.5 sessions within 6 wks, whereas nonresponders completed 20.4 sessions within 10 wks, indicating that at least 30 treadmill sessions (preferably in a period of 10 wks and at least 40 mins per session) is necessary to reach a meaningful change in gait speed. Although these trends were noted between the responder and nonresponder groups, no firm conclusions can be drawn regarding the “magic” number of sessions chronic stroke survivors should perform given the low correlation between number of sessions and change in gait speed.
Effect of Extensor Muscle Strength on Meniscus Damage Progression in Subjects Without Radiologic Knee Osteoarthritis
Authors: Li Mingyang , Nie Yong , Li Kang , Zeng Yi , Wu Yuangang , Liu Yuan , Wu Limin , Shen Bin
Published: November 2021

Background

It has been demonstrated that high extensor strength decreases knee osteoarthritis symptomatic progression. However, few studies have detected a significant association between extensor strength and structural progression.

Methods

Participants in the Osteoarthritis Initiative with both muscle strength and meniscus assessment, Kellgren-Lawrence grade 1 or less, and body mass index less than 30 were enrolled. In a separate-sex analysis, participants were divided into the high and low strength groups, referring to the median value. Meniscus progression according to the Magnetic Resonance Imaging Osteoarthritis Knee Score was compared between the two groups at 12 mos (393 females and 229 males) and 24 mos (340 females and 208 males).

Results

In females, less overall medial meniscus progression (11.1% [17/153] vs. 23.2% [32/138], P = 0.04), less medial meniscal medial extrusion (5.2% [8/155] vs. 12.5% [18/144], P = 0.04), and less medial meniscal anterior extrusion progression (0% [0/108] vs. 5.3% [6/113], P = 0.03) were present in the high strength group at 24 mos. In males, no significant difference was detected between the high strength group and the low strength group.

Conclusions

In females, higher extensor muscle strength was associated with a decreased risk of medial meniscus progression in medial and anterior extrusion.
Focal Peripheral Neuropathies Observed in Patients Diagnosed With COVID-19
Authors: Liu Eric A. , Salazar Tomas , Chiu Elisa , Fleming Talya K. , Bagay Leslie , Brown David P. , Cuccurullo Sara J.
Published: November 2021

A growing number of studies have documented a wide variety of neurological manifestations associated with the novel SARS-CoV-2 (COVID-19). Of the available literature, cranial neuropathies and central nervous system disorders, such as encephalopathy and ischemic strokes, remain the predominant discussion. Limited investigations exist examining peripheral neuropathies of those with COVID-19. This case series discusses eight patients who tested positive for COVID-19 and presented with localized weakness after a prolonged course of mechanical ventilation (>21 days). We retrospectively reviewed all patients’ charts who received electrodiagnostic evaluation between March and November 2020 in the outpatient clinic or in the acute care hospital at the JFK Medical Center/JFK Johnson Rehabilitation Institute and Saint Peter's University Hospital of New Jersey. A total of eight COVID-19–positive patients were identified to have a clinical presentation of localized weakness after a prolonged course of mechanical ventilation. All patients were subsequently found to have a focal peripheral neuropathy of varying severity that was confirmed by electrodiagnostic testing. Patient demographics, clinical, and electrodiagnostic findings were documented. The findings of local weakness and focal peripheral neuropathies after diagnosis of COVID-19 raise significant questions regarding underlying pathophysiology and overall prognosis associated with COVID-19.
Adipose-Derived Stem Cells, Obesity, and Inflammation
Authors: Miller Dana , Grant Austin , Durgam Sushmitha , El-Hayek Kevin , Flanigan David C. , Malanga Gerard , Vasileff William Kelton , Baria Michael R.
Published: November 2021

Adipose is a known source of mesenchymal stem cells that can be used to treat musculoskeletal disorders, such as osteoarthritis. Because obesity often coexists with osteoarthritis, excess adiposity may be a useful source of mesenchymal stem cells. However, obesity is associated with systemic inflammation, which may influence the quality of adipose-derived stem cells. We performed a systematic review of the literature examining adipose-derived stem cell behavior, cytokine, and growth factor profiles from obese and nonobese patients. Two independent reviewers applied the inclusion/exclusion criteria and independently extracted data including mesenchymal stem cell count/viability/behavior, growth factor, and/or cytokine expression. Twenty-two articles met criteria for inclusion. Samples from obese patients had increased mesenchymal stem cell content (n = 6), but decreased proliferative ability (n = 3), and increased expression of interleukin 1 (n = 3), interleukin 6 (n = 3), and tumor necrosis factor α (n = 6). There was also greater macrophage content (n = 4). Weight loss normalized cellular function. In vitro behavior and quality of adipose-derived stem cell are significantly different between obese and nonobese patients. Samples from obese patients had greater adipose-derived stem cell content, lower proliferative ability, increased senescence, and increased proinflammatory cytokine expression. Differences in cellular function should be considered when using adipose to treat musculoskeletal pathology in obese and nonobese patients.
Frailty in people living with HIV: an update
Authors: Jones Howell T. , Levett Tom , Barber Tristan J.
Published: November 2021

Purpose of review

The HIV population is ageing with rising rates of frailty though strategies of how best to manage it remain ill-defined. It also remains unclear what the prevalence of frailty is within this cohort, how best to diagnose it and what factors are associated.

Recent findings

The prevalence of frailty remains unclear because of heterogenous results. Routine screening in those 50+ is recommended and whilst the Fried Frailty Phenotype is currently preferred the Clinical Frailty Scale could be considered. No biomarkers are currently recommended. Looking at associated factors, HIV neurocognitive impairment and long-term alcohol usage has been shown to be associated with developing frailty whilst those who are frail have been shown to be less active and more likely to fall. NAFLD with fibrosis has been shown to be an indicator of metabolic age and the Pooled Cohort Equations has been shown to be more effective in diagnosing cardiovascular risk in frail people living with HIV.

Whilst the prevalence of frailty differs between countries, with the addition of prefrailty, this represents a large proportion of people living with HIV. Services must ensure strategies are in place to support those living with HIV and frailty. Further longitudinal studies are required.
Challenges of sexually transmitted infections and sexual health among people who inject drugs
Authors: Dumchev Kostyantyn
Published: November 2021

Purpose of review

This review provides a summary of recently published research on sexually transmitted infections (STI) and related behaviors among people who inject drugs (PWID), covering three major areas: sexual behavior and its role in STI transmission among PWID, multilevel factors associated with STI risk, and strategies addressing sexual health of PWID. This review is timely given the growing priority of combination prevention approaches and integrated care for PWID.

Recent findings

Modern research improves the understanding that PWID have an increased risk of STI, which varies by gender, setting, type of substance used, and presence of mental disorders. Major socioeconomic and structural factors, specific and nonspecific to PWID, facilitate inequality and sexual risk behavior. Sexual transmission continues to contribute substantially to the spread of bloodborne infections among PWID, accounting for at least 10% of new HIV cases according to epidemiological modeling. Despite the substantial evidence that behavioral interventions can improve sexual health and reduce sex-related risks among PWID, there is a research-practice gap, reflected in the scarcity of implementation studies published recently.

Integration of sexual health into prevention programs for PWID is essential to curb transmission of STI, including HIV, among PWID and their sexual partners.
Intravenous thrombolysis for acute ischemic stroke: why not?
Authors: Psychogios Klearchos , Tsivgoulis Georgios
Published: November 2021

Purpose of review

The aim of this study was to summarize available evidence regarding the safety and efficacy of intravenous thrombolysis (IVT) using recombinant tissue-plasminogen activator (rt-PA) in acute ischemic stroke (AIS) patients with specific comorbidities and potential contraindications to systemic reperfusion therapy. Recent advances in IVT implementation in wake-up stroke and in extended time window using advanced neuroimaging will also be highlighted.

Recent findings

Despite theoretical concerns of a higher bleeding risk with IVT, there are no data showing increased risk of symptomatic intracerebral haemorrhage (sICH) in patients with stroke mimics, including seizures, increasing age and dual antiplatelet pretreatment. In addition, recent randomized evidence allows us to expand the time window of IVT for AIS using advanced neuroimaging both in wake-up stroke patients and in patients presenting within 4.5–9 h from symptom onset fulfilling certain neuroimaging criteria (based on DWI/FLAIR mismatch or perfusion mismatch).

IVT is a highly effective systemic reperfusion therapy that counts 25 years of everyday clinical experience but still presents several challenges in its application. Appropriate patient selection and adherence to rt-PA protocol is paramount in terms of safety. The effort to simplify the indications, expand the therapeutic time window and eliminate specific initial contraindications is continuously evolving.
Network dysfunction in pre and postsurgical epilepsy: connectomics as a tool and not a destination
Authors: Johnson Graham W. , Doss Derek J. , Englot Dario J.
Published: November 2021

Purpose of review

Patients with focal drug-resistant epilepsy (DRE) sometimes continue to have seizures after surgery. Recently, there is increasing interest in using advanced network analyses (connectomics) to better understand this problem. Connectomics has changed the way researchers and clinicians view DRE, but it must be applied carefully in a hypothesis-driven manner to avoid spurious results. This review will focus on studies published in the last 18 months that have thoughtfully used connectomics to advance our fundamental understanding of network dysfunction in DRE – hopefully for the eventual direct benefit to patient care.

Recent findings

Impactful recent findings have centered on using patient-specific differences in network dysfunction to predict surgical outcome. These works span functional and structural connectivity and include the modalities of functional and diffusion magnetic resonance imaging (MRI) and electrophysiology. Using functional MRI, many groups have described an increased functional segregation outside of the surgical resection zone in patients who fail surgery. Using electrophysiology, groups have reported network characteristics of resected tissue that suggest whether a patient will respond favorably to surgery.

If we can develop accurate models to outline functional and structural network characteristics that predict failure of standard surgical approaches, then we can not only improve current clinical decision-making; we can also begin developing alternative treatments including network approaches to improve surgical success rates.
Symptomatic and asymptomatic transmission of SARS-CoV-2 in K-12 schools, British Columbia, April to June 2021
Authors: Choi Alex , Mâsse Louise C. , Bardwell Samantha , Zhao Yanjie , Xu Yang Xin Zi , Markarian Ani , Coombs Daniel , Watts Allison , Macdonald Adrienne , Dhillon Nalin , Irvine Michael , O’Reilly Collette , Lavoie Pascal M. , Goldfarb David
Published: November 2021

We prospectively studied SARS-CoV-2 transmission at schools in an era of Variants of Concern (VoCs), offering all close contacts serial viral asymptomatic testing up to 14 days. Of 229 school close contacts, 3 tested positive (1.3%), of which 2 were detected through asymptomatic testing. Most secondary transmission (90%) occurred in households. Routine asymptomatic testing of close contacts should be examined in the context of local testing rates, preventive measures, programmatic costs, and health impacts of asymptomatic transmission.