Meniscus Injuries in Soccer.

Soccer is considered the most popular sport in the world. The game involves frequent agile maneuvers, such as rapid accelerations/decelerations and pivoting, and carries an inherent risk of high-speed collisions, which can lead to lower extremity injury. Knee and meniscus injuries can cause significant pain and disability, precluding participation in the sport. Understanding the diagnosis and management of meniscal injuries in soccer players is essential to the care of these athletes. This paper reviews meniscal anatomy, biomechanics, and mechanisms of injury; discusses the work-up, diagnosis, and management of meniscus injuries; and reports on rehabilitation, return to sport, and outcomes after meniscal injuries in soccer players.

DefendFL: A Privacy-Preserving Federated Learning Scheme Against Poisoning Attacks.

Federated learning (FL) has become a popular mode of learning, allowing model training without the need to share data. Unfortunately, it remains vulnerable to privacy leakage and poisoning attacks, which compromise user data security and degrade model quality. Therefore, numerous privacy-preserving frameworks have been proposed, among which mask-based framework has certain advantages in terms of efficiency and functionality. However, it is more susceptible to poisoning attacks from malicious users, and current works lack practical means to detect such attacks within this framework. To overcome this challenge, we present DefendFL, an efficient, privacy-preserving, and poisoning-detectable mask-based FL scheme. We first leverage collinearity mask to protect users' gradient privacy. Then, cosine similarity is utilized to detect masked gradients to identify poisonous gradients. Meanwhile, a verification mechanism is designed to detect the mask, ensuring the mask's validity in aggregation and preventing poisoning attacks by intentionally changing the mask. Finally, we resist poisoning attacks by removing malicious gradients or lowering their weights in aggregation. Through security analysis and experimental evaluation, DefendFL can effectively detect and mitigate poisoning attacks while outperforming existing privacy-preserving detection works in efficiency.

Repeat treatment of organotypic airway cultures with ethyl methanesulfonate causes accumulation of somatic cell mutations without expansion of bronchial-carcinoma-specific cancer driver mutations.

The human in vitro organotypic air-liquid-interface (ALI) airway tissue model is structurally and functionally similar to the human large airway epithelium and, as a result, is being used increasingly for studying the toxicity of inhaled substances. Our previous research demonstrated that DNA damage and mutagenesis can be detected in human airway tissue models under conditions used to assess general and respiratory toxicity endpoints. Expanding upon our previous proof-of-principle study, human airway epithelial tissue models were treated with 6.25-100 µg/mL ethyl methanesulfonate (EMS) for 28 days, followed by a 28-day recovery period. Mutagenesis was evaluated by Duplex Sequencing (DS), and clonal expansion of bronchial-cancer-specific cancer-driver mutations (CDMs) was investigated by CarcSeq to determine if both mutation-based endpoints can be assessed in the same system. Additionally, DNA damage and tissue-specific responses were analyzed during the treatment and following the recovery period. EMS exposure led to time-dependent increases in mutagenesis over the 28-day treatment period, without expansion of clones containing CDMs; the mutation frequencies remained elevated following the recovery. EMS also produced an increase in DNA damage measured by the CometChip and MultiFlow assays and the elevated levels of DNA damage were reduced (but not eliminated) following the recovery period. Cytotoxicity and most tissue-function changes induced by EMS treatment recovered to control levels, the exception being reduced proliferating cell frequency. Our results indicate that general, respiratory-tissue-specific and genotoxicity endpoints increased with repeat EMS dosing; expansion of CDM clones, however, was not detected using this repeat treatment protocol. DISCLAIMER: This article reflects the views of its authors and does not necessarily reflect those of the U.S. Food and Drug Administration. Any mention of commercial products is for clarification only and is not intended as approval, endorsement, or recommendation.

Clinical validation of commercial deep-learning based auto-segmentation models for organs at risk in the head and neck region: a single institution study.

Purpose: To evaluate organ at risk (OAR) auto-segmentation in the head and neck region of computed tomography images using two different commercially available deep-learning-based auto-segmentation (DLAS) tools in a single institutional clinical applications. Methods: Twenty-two OARs were manually contoured by clinicians according to published guidelines on planning computed tomography (pCT) images for 40 clinical head and neck cancer (HNC) cases. Automatic contours were generated for each patient using two deep-learning-based auto-segmentation models-Manteia AccuContour and MIM ProtégéAI. The accuracy and integrity of autocontours (ACs) were then compared to expert contours (ECs) using the Sørensen-Dice similarity coefficient (DSC) and Mean Distance (MD) metrics. Results: ACs were generated for 22 OARs using AccuContour and 17 OARs using ProtégéAI with average contour generation time of 1 min/patient and 5 min/patient respectively. EC and AC agreement was highest for the mandible (DSC 0.90 ± 0.16) and (DSC 0.91 ± 0.03), and lowest for the chiasm (DSC 0.28 ± 0.14) and (DSC 0.30 ± 0.14) for AccuContour and ProtégéAI respectively. Using AccuContour, the average MD was<1mm for 10 of the 22 OARs contoured, 1-2mm for 6 OARs, and 2-3mm for 6 OARs. For ProtégéAI, the average mean distance was<1mm for 8 out of 17 OARs, 1-2mm for 6 OARs, and 2-3mm for 3 OARs. Conclusions: Both DLAS programs were proven to be valuable tools to significantly reduce the time required to generate large amounts of OAR contours in the head and neck region, even though manual editing of ACs is likely needed prior to implementation into treatment planning. The DSCs and MDs achieved were similar to those reported in other studies that evaluated various other DLAS solutions. Still, small volume structures with nonideal contrast in CT images, such as nerves, are very challenging and will require additional solutions to achieve sufficient results.

Biogenesis of lysosome-related organelles complex-2 is an evolutionarily ancient proto-coatomer complex.

Hermansky-Pudlak syndrome (HPS) is an inherited disorder of intracellular vesicle trafficking affecting the function of lysosome-related organelles (LROs). At least 11 genes underlie the disease, encoding four protein complexes, of which biogenesis of lysosome-related organelles complex-2 (BLOC-2) is the last whose molecular action is unknown. We find that the unicellular eukaryote Dictyostelium unexpectedly contains a complete BLOC-2, comprising orthologs of the mammalian subunits HPS3, -5, and -6, and a fourth subunit, an ortholog of the Drosophila LRO-biogenesis gene, Claret. Lysosomes from Dictyostelium BLOC-2 mutants fail to mature, similar to LROs from HPS patients, but for all endolysosomes rather than a specialized subset. They also strongly resemble lysosomes from WASH mutants. Dictyostelium BLOC-2 localizes to the same compartments as WASH, and in BLOC-2 mutants, WASH is inefficiently recruited, accounting for their impaired lysosomal maturation. BLOC-2 is recruited to endolysosomes via its HPS3 subunit. Structural modeling suggests that all four subunits are proto-coatomer proteins, with important implications for BLOC-2's molecular function. The discovery of Dictyostelium BLOC-2 permits identification of orthologs throughout eukaryotes. BLOC-2 and lysosome-related organelles, therefore, pre-date the evolution of Metazoa and have broader and more conserved functions than previously thought.

2024 Update of The Society of Thoracic Surgeons Short-term Esophagectomy Risk Model: More Inclusive and Improved Calibration.

BACKGROUND: The Society of Thoracic Surgeons General Thoracic Surgery Database (STS-GTSD) previously reported short-term risk models for esophagectomy for esophageal cancer. We sought to update existing models using more inclusive contemporary cohorts, with consideration of additional risk factors based on clinical evidence. METHODS: The study population consisted of adult patients in the STS-GTSD who underwent esophagectomy for esophageal cancer between January 2015 and December 2022. Separate esophagectomy risk models were derived for 3 primary end points: operative mortality, major morbidity, and composite morbidity or mortality. Logistic regression with backward selection was used, with predictors retained in models if P < .10. All derived models were validated using 9-fold cross-validation. Model discrimination and calibration were assessed for the overall cohort and specified subgroups. RESULTS: A total of 18,503 patients from 254 centers underwent esophagectomy for esophageal cancer. Operative mortality, morbidity, and composite morbidity or mortality rates were 3.4%, 30.5%, and 30.9%, respectively. Novel predictors of short-term outcomes in the updated models included body surface area and insurance payor type. Overall discrimination was similar or superior to previous STS-GTSD models for operative mortality (C statistic = 0.72) and for composite morbidity or mortality (C statistic = 0.62), Model discrimination was comparable across procedure- and demographic-specific subcohorts. Model calibration was excellent in all patient subgroups. CONCLUSIONS: The newly derived esophagectomy risk models showed similar or superior performance compared with previous models, with broader applicability and clinical face validity. These models provide robust preoperative risk estimation and can be used for shared decision making, assessment of provider performance, and quality improvement.

Fecal Immunochemical Test Screening and Risk of Colorectal Cancer Death.

Importance: The fecal immunochemical test (FIT) is widely used for colorectal cancer (CRC) screening, but evidence of its effectiveness is limited. Objective: To evaluate whether FIT screening is associated with a lower risk of dying from CRC overall, according to cancer location, and within demographic groups. Design, Setting, and Participants: This nested case-control study in a cohort of screening-eligible people was conducted in 2 large, integrated health systems of racially, ethnically, and socioeconomically diverse members with long-term programs of mailed FIT screening outreach. Eligible participants included people aged 52 to 85 years who died from colorectal adenocarcinoma between 2011 and 2017 (cases); cases were matched in a 1:8 ratio based on age, sex, health-plan membership duration, and geographic area to randomly selected persons who were alive and CRC-free on case's diagnosis date (controls). Data analysis was conducted from January 2002 to December 2017. Exposures: Completing 1 or more FIT screenings in the 5-year period prior to the CRC diagnosis date among cases or the corresponding date among controls; in secondary analyses, 2- to 10-year intervals were evaluated. Main Outcomes and Measures: The primary study outcome was CRC death overall and by tumor location. Secondary analyses were performed to assess CRC death by race and ethnicity. Results: From a cohort of 2 127 128 people, a total of 10 711 participants (3529 aged 60-69 years [32.9%]; 5587 male [52.1%] and 5124 female [47.8%]; 1254 non-Hispanic Asian [11.7%]; 973 non-Hispanic Black [9.1%]; 1929 Hispanic or Latino [18.0%]; 6345 non-Hispanic White [59.2%]) was identified, including 1103 cases and 9608 controls. Among controls during the 10-year period prior to the reference date, 6101 (63.5%) completed 1 or more FITs with a cumulative 12.6% positivity rate (768 controls), of whom 610 (79.4%) had a colonoscopy within 1 year. During the 5-year period, 494 cases (44.8%) and 5345 controls (55.6%) completed 1 or more FITs. In regression analysis, completing 1 or more FIT screening was associated with a 33% lower risk of death from CRC (adjusted odds ratio [aOR], 0.67; 95% CI, 0.59-0.76) and 42% lower risk in the left colon and rectum (aOR, 0.58; 95% CI, 0.48-0.71). There was no association with right colon cancers (aOR, 0.83; 95% CI, 0.69-1.01) but the difference in the estimates between the right colon and left colon or rectum was statistically significant (P = .01). FIT screening was associated with lower CRC mortality risk among non-Hispanic Asian (aOR, 0.37; 95% CI, 0.23-0.59), non-Hispanic Black (aOR, 0.58; 95% CI, 0.39-0.85) and non-Hispanic White individuals (aOR, 0.70; 95% CI, 0.57-0.86) (P for homogeneity = .04 for homogeneity). Conclusions and Relevance: In this nested case-control study, completing FIT was associated with a lower risk of overall death from CRC, particularly in the left colon, and the associations were observed across racial and ethnic groups. These findings support the use of FIT in population-based screening strategies.

The Predictors of Surgery for Symptomatic, Atraumatic Full-Thickness Rotator Cuff Tears Change Over Time: Ten-Year Outcomes of the MOON Shoulder Prospective Cohort.

BACKGROUND: A prospective cohort study was conducted to assess the predictors of failure of nonoperative treatment, defined as the patient undergoing surgery for symptomatic, atraumatic full-thickness rotator cuff tears. We present the 10-year follow-up data of this population to determine if predictors for surgery change over time, and secondarily we report the outcomes of the cohort. METHODS: At the time of enrollment, demographic, symptom, rotator cuff anatomy, and patient-reported outcome data were collected in patients with symptomatic, atraumatic full-thickness rotator cuff tears. Patients underwent a standard physical therapy protocol for 6 to 12 weeks. Patient data were then collected at 1, 2, 5, 7, and 10 years. Failure of nonoperative treatment was defined as the patient electing to undergo surgery. RESULTS: Of the 452 patients in the original cohort, 20 patients (5%) withdrew from the study, 37 (9%) died before 10 years, and 40 (9%) were otherwise lost to follow-up. A total of 115 patients (27.0%) underwent a surgical procedure at some point during the 10-year follow-up period. Of these patients, 56.5% underwent surgery within 6 months of enrollment and 43.5%, between 6 months and 10 years. Low patient expectations regarding the efficacy of physical therapy were found to be a predictor of early surgery. Workers' Compensation status and activity level were more important predictors of later surgery. Patient-reported outcome measures all improved following physical therapy. For patients who did not undergo a surgical procedure, patient-reported outcome measures did not decline over the 10-year follow-up period. CONCLUSIONS: Low patient expectations regarding the efficacy of physical therapy were found to be a predictor of early surgery, whereas Workers' Compensation status and activity level were predictors of later surgery. Physical therapy was successful in >70% of patients with symptomatic, atraumatic full-thickness rotator cuff tears at 10 years. Outcome measures improved with physical therapy and did not decline over the 10-year follow-up period. LEVEL OF EVIDENCE: Prognostic Level I. See Instructions for Authors for a complete description of levels of evidence.

Circulating KRAS G12D but not G12V is associated with survival in metastatic pancreatic ductal adenocarcinoma.

While high circulating tumor DNA (ctDNA) levels are associated with poor survival for multiple cancers, variant-specific differences in the association of ctDNA levels and survival have not been examined. Here we investigate KRAS ctDNA (ctKRAS) variant-specific associations with overall and progression-free survival (OS/PFS) in first-line metastatic pancreatic ductal adenocarcinoma (mPDAC) for patients receiving chemoimmunotherapy ("PRINCE", NCT03214250), and an independent cohort receiving standard of care (SOC) chemotherapy. For PRINCE, higher baseline plasma levels are associated with worse OS for ctKRAS G12D (log-rank p = 0.0010) but not G12V (p = 0.7101), even with adjustment for clinical covariates. Early, on-therapy clearance of G12D (p = 0.0002), but not G12V (p = 0.4058), strongly associates with OS for PRINCE. Similar results are obtained for the SOC cohort, and for PFS in both cohorts. These results suggest ctKRAS G12D but not G12V as a promising prognostic biomarker for mPDAC and that G12D clearance could also serve as an early biomarker of response.

Correction to "Thermally Driven Field Emission from ZnO Wires on a Nanomembrane Used as a Detector for Time-of-Flight Mass Spectrometry".

[This corrects the article DOI: 10.1021/acsomega.3c08932.].

A Reliable System for Quantitative G-Protein Activation Imaging in Cancer Cells.

Fluorescence resonance energy transfer (FRET) biosensors have proven to be an indispensable tool in cell biology and, more specifically, in the study of G-protein signalling. The best method of measuring the activation status or FRET state of a biosensor is often fluorescence lifetime imaging microscopy (FLIM), as it does away with many disadvantages inherent to fluorescence intensity-based methods and is easily quantitated. Despite the significant potential, there is a lack of reliable FLIM-FRET biosensors, and the data processing and analysis workflows reported previously face reproducibility challenges. Here, we established a system in live primary mouse pancreatic ductal adenocarcinoma cells, where we can detect the activation of an mNeonGreen-Gαi3-mCherry-Gγ2 biosensor through the lysophosphatidic acid receptor (LPAR) with 2-photon time-correlated single-photon counting (TCSPC) FLIM. This combination gave a superior signal to the commonly used mTurquoise2-mVenus G-protein biosensor. This system has potential as a platform for drug screening, or to answer basic cell biology questions in the field of G-protein signalling.

Investigational and emerging gastric inhibitory polypeptide (GIP) receptor-based therapies for the treatment of obesity.

INTRODUCTION: One billion people live with obesity. The most promising medications for its treatment are incretin-based therapies, based on enteroendocrine peptides released in response to oral nutrients, specifically glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP). The mechanisms by which GLP-1 receptor agonism cause weight reduction are becoming increasingly understood. However, the mechanisms by which GIP receptor-modulating medications cause weight loss remain to be clarified. AREAS COVERED: This review describes GLP-1 and GIP physiology and explores the conflicting data regarding GIP and weight management. It details examples of how to reconcile the contradictory findings that both GIP receptor agonism and antagonism cause weight reduction. Specifically, it discusses the concept of 'biased agonism' wherein exogenous peptides cause different post-receptor signaling patterns than native ligands. It discusses how GIP effects in adipose tissue and the central nervous system may cause weight reduction. It describes GIP receptor-modulating compounds and their most current trials regarding weight reduction. EXPERT OPINION: Effects of GIP receptor-modulating compounds on different tissues have implications for both weight reduction and other cardiometabolic diseases. Further study is needed to understand the implications of GIP agonism on not just weight reduction, but also cardiovascular disease, liver disease, bone health and fat storage.

Antithrombotic and Antimicrobial Potential of S-Nitroso-1-Adamantanethiol-Impregnated Extracorporeal Circuit.

This study presents the utilization of a novel, highly lipophilic nitric oxide (NO) donor molecule, S-nitroso-1-adamantanethiol (SNAT), for developing an NO-emitting polymer surface aimed at preventing thrombus formation and bacterial infection in extracorporeal circuits (ECCs). S-nitroso-1-adamantanethiol, a tertiary nitrosothiol-bearing adamantane species, was synthesized, characterized, and used to impregnate polyvinyl chloride (PVC) tubing for subsequent in vivo evaluation. The impregnation process with SNAT preserved the original mechanical strength of the PVC. In vitro assessments revealed sustained NO release from the SNAT-impregnated PVC tubing (iSNAT), surpassing or matching endothelial NO release levels for up to 42 days. The initial NO release remained stable even after 1 year of storage at -20°C. The compatibility of iSNAT with various sterilization techniques (OPA Plus, hydrogen peroxide, EtO) was tested. Acute in vivo experiments in a rabbit model demonstrated significantly reduced thrombus formation in iSNAT ECCs compared with controls, indicating the feasibility of iSNAT to mitigate coagulation system activation and potentially eliminate the need for systemic anticoagulation. Moreover, iSNAT showed substantial inhibition of microbial biofilm formation, highlighting its dual functionality. These findings underscore the promising utility of iSNAT for long-term ECC applications, offering a multifaceted approach to enhancing biocompatibility and minimizing complications.

Development of machine learning models predicting mortality using routinely collected observational health data from 0-59 months old children admitted to an intensive care unit in Bangladesh: critical role of biochemistry and haematology data.

INTRODUCTION: Treatment in the intensive care unit (ICU) generates complex data where machine learning (ML) modelling could be beneficial. Using routine hospital data, we evaluated the ability of multiple ML models to predict inpatient mortality in a paediatric population in a low/middle-income country. METHOD: We retrospectively analysed hospital record data from 0-59 months old children admitted to the ICU of Dhaka hospital of International Centre for Diarrhoeal Disease Research, Bangladesh. Five commonly used ML models- logistic regression, least absolute shrinkage and selection operator, elastic net, gradient boosting trees (GBT) and random forest (RF), were evaluated using the area under the receiver operating characteristic curve (AUROC). Top predictors were selected using RF mean decrease Gini scores as the feature importance values. RESULTS: Data from 5669 children was used and was reduced to 3505 patients (10% death, 90% survived) following missing data removal. The mean patient age was 10.8 months (SD=10.5). The top performing models based on the validation performance measured by mean 10-fold cross-validation AUROC on the training data set were RF and GBT. Hyperparameters were selected using cross-validation and then tested in an unseen test set. The models developed used demographic, anthropometric, clinical, biochemistry and haematological data for mortality prediction. We found RF consistently outperformed GBT and predicted the mortality with AUROC of ≥0.87 in the test set when three or more laboratory measurements were included. However, after the inclusion of a fourth laboratory measurement, very minor predictive gains (AUROC 0.87 vs 0.88) resulted. The best predictors were the biochemistry and haematological measurements, with the top predictors being total CO2, potassium, creatinine and total calcium. CONCLUSIONS: Mortality in children admitted to ICU can be predicted with high accuracy using RF ML models in a real-life data set using multiple laboratory measurements with the most important features primarily coming from patient biochemistry and haematology.

Extended Length of Stay After Mechanical Thrombectomy for Stroke: A Single-Center Analysis of 703 Patients.

BACKGROUND AND OBJECTIVES: Mechanical thrombectomy (MT) is crucial for improving functional outcomes for acute ischemic stroke. Length of stay (LOS) is a reimbursement metric implemented to incentivize value-based care. Our study aims to identify predictors of LOS in patients undergoing MT at a high-volume center in the United States. METHODS: This was a retrospective study of patients who underwent MT at a single institution from 2017 to 2023. Patients who experienced mortality during their course of hospital stay were excluded from this study. Extended LOS (eLOS) was defined as the upper quartile (≥75th) of the median duration of hospital stay. Univariate and multivariate analyses were performed, with P values < .05 denoting statistical significance. RESULTS: Seven hundred three patients met criteria for inclusion. The median age of the cohort was 72 years (IQR: 61-82), and 57.2% was female. The median LOS was 6, IQR: 4-10. A total of 28.9% of the cohort (n = 203) patients experienced eLOS. The multivariate regression model identified age (odds ratio [OR]: 0.98, 95% CI: 0.97-0.99), diabetes mellitus (OR: 1.68, 95% CI: 1.15-2.44), and hemorrhagic transformation of stroke (OR: 2.89, 95% CI: 0.39-0.90) as predictors of eLOS, whereas antiplatelet use before admission (OR: 0.55, 95% CI: 0.34-0.89) and higher baseline modified Rankin Scale before stroke were associated with lower odds (OR: 0.59 [0.39-0.90]; P < .05) of eLOS. CONCLUSION: By identifying predictors of eLOS, we provide a foundation for targeted interventions aimed at optimizing post-thrombectomy care pathways and improving patient outcomes. The implications of our study extend beyond clinical practice, offering insights into healthcare resource utilization, reimbursement strategies, and value-based care initiatives.

Revealing the evolutionary history and contemporary population structure of Pacific salmon in the Fraser River through genome resequencing.

The Fraser River once supported massive salmon returns. However, over the last century, the largest returns have consistently been less than half of the recorded historical maximum. There is substantial interest from surrounding communities and governments to increase salmon returns for both human use and functional ecosystems. To generate resources for this endeavor, we resequenced genomes of Chinook (Oncorhynchus tshawytscha), coho (O. kisutch), and sockeye salmon (O. nerka) from the Fraser River at moderate coverage (∼16x). A total of 954 resequenced genomes were analyzed, with 681 collected specifically for this study from tissues sampled between 1997 and 2021. An additional 273 were collected from previous studies. At the species level, Chinook salmon appeared to have 1.6-2.1x more SNPs than coho or sockeye salmon, respectively. This difference may be attributable to large historical declines of coho and sockeye salmon. At the population level, three Fraser River genetic groups were identified for each species using principal component and admixture analyses, which is consistent with previous research and supports the continued use of these groups in conservation and management efforts. Environmental factors and a migration barrier were identified as major factors influencing the boundaries of these genetic groups. Additionally, 20 potentially adaptive loci were identified among the genetic groups. This information may be valuable in new management and conservation efforts. Furthermore, the resequenced genomes are an important resource for contemporary genomics research on Fraser River salmon and have been made publicly available.

Initial Experience with the Eclipse Double-lumen Balloon Catheter for Embolization of Cranial Vascular Malformations.

BACKGROUND AND OBJECTIVES: Double lumen balloon catheters (DLBCs) have emerged as a potential alternative to single lumen balloon catheters (SLBCs) for endovascular embolization of arteriovenous malformations (AVMs) and dural arteriovenous fistulas (dAVFs). This study describes our preliminary experience with the Eclipse 2L DLBC in treating AVMs and dAVFs. METHODS: Patients who underwent embolization of cranial dAVFs or AVMs at our institution from August 2021 to March 2024 were included. Spinal vascular malformations were excluded. Descriptive statistics were used to analyze procedural outcomes, technical nuances and post-operative outcome on follow-up. RESULTS: 25 patients who underwent 38 embolization procedures (15 AVMs and 23 dAVFs) met criteria for inclusion in this study. The mean age of the cohort was 52.44 (standard deviation (SD)= 17.26), and 48% of the overall cohort (n= 13) was female. The average procedure times for AVMs and dAVFs were 80.4 minutes and 96.73 minutes, respectively. There was one instance of catheter entrapment. Two patients in the AVM cohort experienced mortality and one experienced post-operative rupture. CONCLUSION: Our preliminary experience using the Eclipse 2L balloon catheter for Onyx embolization reported procedural outcomes comparable to other DLBCs despite relatively higher procedure times and radiation doses. Further long-term studies on its efficacy as primary modality in treating AVMs and dAVFs are encouraged.

Sample-to-Answer Detection of SARS-CoV-2 Viremia Using Thermally Responsive Alkane Partitions.

The diagnosis of bloodborne viral infections (viremia) is currently relegated to central laboratories because of the complex procedures required to detect viruses in blood samples. The development of point-of-care diagnostics for viremia would enable patients to receive a diagnosis and begin treatment immediately instead of waiting days for results. Point-of-care systems for viremia have been limited by the challenges of integrating multiple precise steps into a fully automated (i.e., sample-to-answer), compact, low-cost system. We recently reported the development of thermally responsive alkane partitions (TRAPs), which enable the complete automation of diagnostic assays with complex samples. Here we report the use of TRAPs for the sample-to-answer detection of viruses in blood using a low-cost portable device and easily manufacturable cassettes. Specifically, we demonstrate the detection of SARS-CoV-2 in spiked blood samples, and we show that our system detects viremia in COVID-19 patient samples with good agreement to conventional RT-qPCR. We anticipate that our sample-to-answer system can be used to rapidly diagnose SARS-CoV-2 viremia at the point of care, leading to better health outcomes for patients with severe COVID-19 disease, and that our system can be applied to the diagnosis of other life-threatening bloodborne viral diseases, including Hepatitis C and HIV.

De-escalation and Discontinuation of Disease-Modifying Therapies in Multiple Sclerosis.

PURPOSE OF REVIEW: Long-term use of multiple sclerosis (MS) disease-modifying therapies (DMTs) is standard practice to prevent accumulation of disability. Immunosenescence and other age-related changes lead to an altered risk-benefit ratio for older patients on DMTs. This article reviews recent research on the topic of de-escalation and discontinuation of MS DMTs. RECENT FINDINGS: Observational and interventional studies have shed light on what happens to patients who de-escalate or discontinue DMTs and the factors, such as age, treatment type, and presence of recent disease activity, that influence outcomes. Though many questions remain, recent findings have been valuable for the development of an evidence-based approach to making de-escalation and discontinuation decisions in MS.

Anti-spike antibody responses to SARS-CoV-2 mRNA vaccines in people with schizophrenia and schizoaffective disorder.

Importance: Individuals with schizophrenia are at higher risk for severe COVID-19 illness and severe breakthrough infection following vaccination. It is unclear whether immune response to vaccination differs in this population. Objective: To assess whether anti-SARS-CoV-2 spike antibody titers after vaccination differ in people with a diagnosis of schizophrenia or schizoaffective disorder (SZ) compared to controls without a psychiatric disorder. Design: This cohort study assessed antibody response following the first and second dose of mRNA vaccines at longitudinal timepoints, up to 7 weeks following the first dose of vaccine. Setting: A multi-center study including psychiatric healthcare settings in the United States and Europe. Participants: 205 adults with no history of COVID-19 infection, including 106 individuals with SZ and 99 controls without a psychiatric disorder, who received their first dose of SARS-CoV-2 mRNA vaccine between December 20, 2020 and May 27, 2021. Main outcomes and measures: Mean SARS-CoV-2 anti-Spike IgG antibody levels within 7 weeks after the first dose of vaccination. Results: A total of 205 individuals (mean [SD] age, 44.7 [12.0] years; 90 [43.9%] male) were included, of which 106 (51.7%) were diagnosed with SZ. SZ was associated with lower mean log antibody levels (-0.15; 95% CI, -0.27 to -0.03, P = 0.016) after adjusting for age, sex, body mass index, smoking, days since vaccination, and vaccine manufacturer. In secondary analyses of dose-specific responses, SZ was associated with a lower mean log antibody level after the second dose of vaccine (-0.23; 95% CI -0.39 to -0.06, P = 0.006), but not the first dose of vaccine (0.00; 95% CI -0.18- 0.19, P = 0.96). Conclusions and Relevance: In this cohort study of individuals with SZ and a control group without psychiatric disorders, SZ was associated with lower SARS-CoV-2 anti-spike antibody levels following 2 doses of SARS-CoV-2 mRNA vaccination. This highlights the need for further studies assessing vaccine immunogenicity in individuals with schizophrenia.