Myocardial Injury in Patients with Hip Fracture: A HIP ATTACK Randomized Trial Substudy.

BACKGROUND: Myocardial injury after a hip fracture is common and has a poor prognosis. Patients with a hip fracture and myocardial injury may benefit from accelerated surgery to remove the physiological stress associated with the hip fracture. This study aimed to determine if accelerated surgery is superior to standard care in terms of the 90-day risk of death in patients with a hip fracture who presented with an elevated cardiac biomarker/enzyme measurement at hospital arrival. METHODS: The HIP fracture Accelerated surgical TreaTment And Care tracK (HIP ATTACK) trial was a randomized controlled trial designed to determine whether accelerated surgery for hip fracture was superior to standard care in reducing death or major complications. This substudy is a post-hoc analysis of 1392 patients (from the original study of 2970 patients) who had a cardiac biomarker/enzyme measurement (>99.9% had a troponin measurement and thus "troponin" is the term used throughout the paper) at hospital arrival. The primary outcome was all-cause mortality. The secondary composite outcome included all-cause mortality and non-fatal myocardial infarction, stroke, and congestive heart failure 90 days after randomization. RESULTS: Three hundred and twenty-two (23%) of the 1392 patients had troponin elevation at hospital arrival. Among the patients with troponin elevation, the median time from hip fracture diagnosis to surgery was 6 hours (interquartile range [IQR] = 5 to 13) in the accelerated surgery group and 29 hours (IQR = 19 to 52) in the standard care group. Patients with troponin elevation had a lower risk of mortality with accelerated surgery compared with standard care (17 [10%] of 163 versus 36 [23%] of 159; hazard ratio [HR] = 0.43 [95% confidence interval (CI) = 0.24 to 0.77]) and a lower risk of the secondary composite outcome (23 [14%] of 163 versus 47 [30%] of 159; HR = 0.43 [95% CI = 0.26 to 0.72]). CONCLUSIONS: One in 5 patients with a hip fracture presented with myocardial injury. Accelerated surgery resulted in a lower mortality risk than standard care for these patients; however, these findings need to be confirmed. LEVEL OF EVIDENCE: Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.

The Statistics of q-Statistics.

Almost two decades ago, Ernesto P. Borges and Bruce M. Boghosian embarked on the intricate task of composing a manuscript to honor the profound contributions of Constantino Tsallis to the realm of statistical physics, coupled with a concise exploration of q-Statistics. Fast-forward to Constantino Tsallis' illustrious 80th birthday celebration in 2023, where Deniz Eroglu and Ugur Tirnakli delved into Constantino's collaborative network, injecting renewed vitality into the project. With hearts brimming with appreciation for Tsallis' enduring inspiration, Eroglu, Boghosian, Borges, and Tirnakli proudly present this meticulously crafted manuscript as a token of their gratitude.

Evidence for human-caused founder effect in populations of Solanum jamesii at archaeological sites: II. Genetic sequencing establishes ancient transport across the Southwest USA.

PREMISE: The domestication of wild plant species can begin with gathering and transport of propagules by Indigenous peoples. The effect on genomic composition, especially in clonal, self-incompatible perennials would be instantaneous and drastic with respect to new, anthropogenic populations subsequently established. Reductions in genetic diversity and mating capability would be symptomatic and the presence of unique alleles and genetic sequences would reveal the origins and ancestry of populations associated with archaeological sites. The current distribution of the Four Corners potato, Solanum jamesii Torr. in the Southwestern USA, may thus reflect the early stages of a domestication process that began with tuber transport. METHODS: Herein genetic sequencing (GBS) data are used to further examine the hypothesis of domestication in this culturally significant species by sampling 25 archaeological and non-archaeological populations. RESULTS: Archaeological populations from Utah, Colorado and northern Arizona have lower levels of polymorphic loci, unique alleles, and heterozygosity than non-archaeological populations from the Mogollon region of central Arizona and New Mexico. Principle components analysis, Fst values, and structure analysis revealed that genetic relationships among archaeological populations did not correspond to geographic proximity. Populations in Escalante, Utah were related to those on the Mogollon Rim (400 km south) and had multiple origins and significant disjunctions with those populations in Bears Ears, Chaco Canyon, and Mesa Verde sites. CONCLUSIONS: Movement of tubers from the Mogollon region may have occurred many times and in multiple directions during the past, resulting in the complex genetic patterns seen in populations from across the Four Corners region.

Immune cell profiling of the ICAM1 p.K56M heart failure with preserved ejection fraction risk variant.

AIMS: Intercellular adhesion molecule-1 (ICAM-1) facilitates inflammation via leucocyte recruitment and has been implicated in heart failure with preserved ejection fraction (HFpEF). Approximately 35% of African American individuals carry a copy of an ICAM1 missense variant (rs5491; p.K56M), which is associated with an increased risk of HFpEF. The pathways by which rs5491 increases HFpEF risk are not well defined. We evaluated the circulating immune cell profile of rs5491. METHODS: Among African American individuals in the Multi-Ethnic Study of Atherosclerosis, we evaluated the associations of rs5491 with 29 circulating peripheral blood mononuclear cell subsets. The top immune cells were then related to echocardiographic measures of structure and function. RESULTS: Among 502 individuals with immune cell profiling (mean age 63 years, 51% female), 191 individuals (38%) had at least one copy of rs5491. Each additional rs5491 allele was significantly associated with higher proportions of Tc17 CD8+ cytotoxic T cells (ß = 1.34, SE = 0.45, P = 9.5 × 10-5) and Tc2 CD8+ cytotoxic T cells (ß = 1.19, SE = 0.44, P = 0.00012). There were no other associations noted between rs5491 and the remaining immune cells. A higher proportion of Tc17 cells was significantly associated with a higher left ventricular ejection fraction, E/e' average and right ventricular systolic pressure (RVSP), while a higher proportion of Tc2 cells was significantly associated with a higher RVSP. CONCLUSIONS: The ICAM1 p.K56M variant (rs5491) carries a distinct and inflammatory T-cell subset profile. These cytotoxic T cells are in turn associated with alterations in cardiac function and adverse haemodynamics later in life, thus providing insight into pathways by which rs5491 may increase the risk of HFpEF.

Perioperative and safety outcomes following tissue-sparing posterior cervical fusion to revise a pseudarthrosis: A multicenter retrospective review of 150 cases.

Background: Posterior cervical fusion (PCF) with lateral mass screws is a favorable treatment option to revise a symptomatic pseudarthrosis due to reliable rates of arthrodesis; however, this technique introduces elevated risk for wound infection and hospital readmission. A tissue-sparing PCF approach involving facet fixation instrumentation reduces the rates of postoperative complications while stabilizing the symptomatic level to achieve arthrodesis; however, these outcomes have been limited to small study cohorts from individual surgeons commonly with mixed indications for treatment. Materials and Methods: One hundred and fifty cases were identified from a retrospective chart review performed by seven surgeons across six sites in the United States. All cases involved PCF revision for a pseudarthrosis at one or more levels from C3 to C7 following anterior cervical discectomy and fusion (ACDF). PCF was performed using a tissue-sparing technique with facet instrumentation. Cases involving additional supplemental fixation such as lateral mass screws, rods, wires, or other hardware were excluded. Demographics, operative notes, postoperative complications, hospital readmission, and subsequent surgical interventions were summarized as an entire cohort and according to the following risk factors: age, sex, number of levels revised, body mass index (BMI), and history of nicotine use. Results: The average age of patients at the time of PCF revision was 55 ± 11 years and 63% were female. The average BMI was 29 ± 6 kg/m2 and 19% reported a history of nicotine use. Postoperative follow-up visits were available with a median of 68 days (interquartile range = 41-209 days) from revision PCF. There were 91 1-level, 49 2-level, 8 3-level, and 2 4±-level PCF revision cases. The mean operative duration was 52 ± 3 min with an estimated blood loss of 14 ± 1.5cc. Participants were discharged an average of 1 ± 0.05 days following surgery. Multilevel treatment resulted in longer procedure times (single = 45 min, multi = 59 min, P = 0.01) but did not impact estimated blood loss (P = 0.94). Total nights in the hospital increased by 0.2 nights with multilevel treatment (P = 0.01). Sex, age, nicotine history, and BMI had no effect on recorded perioperative outcomes. There was one instance of rehospitalization due to deep-vein thrombosis, one instance of persistent pseudarthrosis at the revised level treated with ACDF, and four instances of adjacent segment disease. In patients initially treated with multilevel ACDF, revisions occurred most commonly on the caudal level (48% of revised levels), followed by the cranial (43%), and least often in the middle level (9%). Conclusions: This chart review of perioperative and safety outcomes provides evidence in support of tissue-sparing PCF with facet instrumentation as a treatment for symptomatic pseudarthrosis after ACDF. The most common locations requiring revision were the caudal and cranial levels. Operative duration and estimated blood loss were favorable when compared to open alternatives. There were no instances of postoperative wound infection, and the majority of patients were discharged the day following surgery.

The impact of diffusion tensor imaging tractography settings on muscle fascicle architecture and diffusion parameter estimates: Tract length, completion, and curvature are most sensitive to tractography settings.

Diffusion-tensor (DT)-MRI tractography provides information about properties relevant to muscle health and function, including estimates of architectural properties such as fascicle length, pennation angle, and curvature and diffusion properties such as mean diffusivity (MD) and fractional anisotropy (FA). Tractography settings, including integration algorithms, thresholds for early tract termination, and tract smoothing approaches, impact the accuracy of the muscle property estimates. However, muscle DT-MRI tractography is performed using a variety of these settings, complicating comparisons between different studies. The effects of different tractography settings on muscle architecture estimates have not been fully explored, and optimized settings for muscle tractography have not yet been determined. We examined the influence of integration algorithm and termination check settings combined with a range of step sizes, termination criteria, and smoothing polynomial orders on tract characteristics, completion/reason for termination, and goodness of fit between fiber tracts and smoothing polynomials using 3-T DT-MR images of the lower leg muscles of seven healthy adults. We found that tract length and completion were highly sensitive to strict FA and intersegment angle thresholds (25%-69% reduction in complete fiber tracts from lowest to highest minimum FA threshold and 11%-36% reduction from highest to lowest intersegment angle threshold). Higher order polynomials (third and fourth order vs. second order) better fit the muscle fiber trajectories, but curvature estimates were highly sensitive to smoothing polynomial order (3.9-6.6 m-1 increase for second- vs. fourth-order fitting polynomials). Step size impacted curvature estimates, albeit to a lesser degree. Integration algorithm had little impact, and mean pennation angle, and tract-based FA and MD, were relatively insensitive to all parameters. The results demonstrate which muscle diffusion measures and architectural estimates are most sensitive to varying tractography settings and support the need for consistent reporting of tractography details to aid interpretation and comparison of results between studies.

Single-nucleus transcriptomics identifies separate classes of UCP1 and futile cycle adipocytes.

Adipose tissue can recruit catabolic adipocytes that utilize chemical energy to dissipate heat. This process occurs either by uncoupled respiration through uncoupling protein 1 (UCP1) or by utilizing ATP-dependent futile cycles (FCs). However, it remains unclear how these pathways coexist since both processes rely on the mitochondrial membrane potential. Utilizing single-nucleus RNA sequencing to deconvolute the heterogeneity of subcutaneous adipose tissue in mice and humans, we identify at least 2 distinct subpopulations of beige adipocytes: FC-adipocytes and UCP1-beige adipocytes. Importantly, we demonstrate that the FC-adipocyte subpopulation is highly metabolically active and utilizes FCs to dissipate energy, thus contributing to thermogenesis independent of Ucp1. Furthermore, FC-adipocytes are important drivers of systemic energy homeostasis and linked to glucose metabolism and obesity resistance in humans. Taken together, our findings identify a noncanonical thermogenic adipocyte subpopulation, which could be an important regulator of energy homeostasis in mammals.

Development of a functional beige fat cell line uncovers independent subclasses of cells expressing UCP1 and the futile creatine cycle.

Although uncoupling protein 1 (UCP1) is established as a major contributor to adipose thermogenesis, recent data have illustrated an important role for alternative pathways, particularly the futile creatine cycle (FCC). How these pathways co-exist in cells and tissues has not been explored. Beige cell adipogenesis occurs in vivo but has been difficult to model in vitro; here, we describe the development of a murine beige cell line that executes a robust respiratory response, including uncoupled respiration and the FCC. The key FCC enzyme, tissue-nonspecific alkaline phosphatase (TNAP), is localized almost exclusively to mitochondria in these cells. Surprisingly, single-cell cloning from this cell line shows that cells with the highest levels of UCP1 express little TNAP, and cells with the highest expression of TNAP express little UCP1. Immunofluorescence analysis of subcutaneous fat from cold-exposed mice confirms that the highest levels of these critical thermogenic components are expressed in distinct fat cell populations.

Identifying the earliest-occurring clinically targetable precursors of late-onset Alzheimer's disease.

Most cases of Alzheimer's disease (AD) are late-onset dementias (LOAD). However, research on AD is predominantly of early-onset disease (EOAD). The determinants of EOAD, gene variants of APP and presenilin proteins, are not the basic precursors of LOAD. Rather, multiple other genes and associated cellular processes underlie risk for LOAD. These determinants could be modified in individuals at risk for LOAD well before signs and symptoms appear. Studying brain cells produced from patient-derived induced-pluripotent-stem-cells (iPSC), in culture, will be instrumental in developing such interventions. This paper summarises evidence accrued from iPSC culture models identifying the earliest occurring clinically targetable determinants of LOAD. Results obtained and replicated, thus far, suggest that abnormalities of bioenergetics, lipid metabolism, digestive organelle function and inflammatory activity are primary processes underlying LOAD. The application of cell culture platforms will become increasingly important in research and also on LOAD detection, assessment, and treatment in the years ahead.

Single- versus Multi-Ancestry Polygenic Risk Scores for CKD in Black Americans.

BACKGROUND: Chronic kidney disease (CKD) is a risk factor for cardiovascular disease and early death. Recently, polygenic risk scores (PRS) have been developed to quantify risk for CKD. However, African ancestry populations are underrepresented in both CKD genetic studies and PRS development overall. Moreover, European-ancestry derived PRS demonstrate diminished predictive performance in African ancestry populations. METHODS: This study aimed to develop a PRS for CKD in Black Americans. We obtained score weights from a meta-analysis of genome-wide association studies (GWAS) for estimated glomerular filtration rate (eGFR) in the Million Veteran Program (MVP) and Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study to develop an eGFR PRS. We optimized the PRS risk model in a cohort of Participants from the Hypertension Genetic Epidemiology Network (HyperGEN). Validation was performed in subsets of Black participants of the Trans-Omics in Precision Medicine (TOPMed) Consortium and Genetics of Hypertension Associated Treatment (GenHAT) Study. RESULTS: The prevalence of CKD-defined as stage 3 or higher-was associated with the PRS as a continuous predictor (OR[95% CI]:1.35[1.08,1.68]) and in a threshold-dependent manner. Further, including APOL1 risk status-a putative variant for CKD with higher prevalence among those of sub-Saharan African descent-improved the score's accuracy. PRS associations were robust to sensitivity analyses accounting for traditional CKD risk factors, as well as CKD classification based on prior eGFR equations. Compared with previously published PRS, the predictive performance of our PRS was comparable to a European-ancestry derived PRS for kidney traits. However, both single-ancestry PRS were less predictive than multi-ancestry derived PRS. CONCLUSIONS: In this study, we developed a PRS that was significantly associated with CKD with improved predictive accuracy when including APOL1 risk status. However, PRS generated from multi-ancestry populations outperformed single-ancestry PRS in our study.

RAS-Mutant Follicular Thyroid Tumors: A Continuous Challenge for Pathologists.

The classification of thyroid nodules, particularly those with a follicular growth pattern, has significantly evolved. These tumors, enriched with RAS or RAS-like mutations, remain challenging for pathologists due to variables such as nuclear atypia, invasion, mitotic activity, and tumor necrosis. This review addresses the histological correlates of benign, low-risk, and malignant RAS-mutant thyroid tumors, as well as some difficult-to-classify follicular nodules with worrisome features. One prototypical RAS-mutant nodule is non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). The assessment of nuclear characteristics in encapsulated/well-demarcated non-invasive RAS-mutant follicular-patterned tumors helps distinguish between follicular thyroid adenoma (FTA) and NIFTP. Despite this straightforward concept, questions about the degree of nuclear atypia necessary for the diagnosis of NIFTP are common in clinical practice. The nomenclature of follicular nodules lacking clear invasive features with increased mitotic activity, tumor necrosis, and/or high-risk mutations (e.g., TERT promoter or TP53) remains debated. Invasion, particularly angioinvasion, is the current hallmark of malignancy in RAS-mutant follicular-patterned neoplasms, with follicular thyroid carcinoma (FTC) as the model. Assessing the tumor interface is critical, though full capsule evaluation can be challenging. Multiple levels and NRASQ61R-specific immunohistochemistry can aid in identifying invasion. Controversies around vascular invasion persist, with ancillary stains like CD31, ERG, and CD61 aiding in its evaluation. Moreover, the review highlights that invasive encapsulated follicular variant papillary thyroid carcinoma (IEFVPTC) is closely associated with FTC, suggesting the need for better nomenclature. The concept of "high-grade" differentiated carcinomas, applicable to FTC or IEFVPTC with necrosis and/or high mitotic activity, is also discussed.

ACR Appropriateness Criteria® Cerebrovascular Diseases-Stroke and Stroke-Related Conditions.

Cerebrovascular disease encompasses a vast array of conditions. The imaging recommendations for stroke-related conditions involving noninflammatory steno-occlusive arterial and venous cerebrovascular disease including carotid stenosis, carotid dissection, intracranial large vessel occlusion, and cerebral venous sinus thrombosis are encompassed by this document. Additional imaging recommendations regarding complications of these conditions including intraparenchymal hemorrhage and completed ischemic strokes are also discussed. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision process support the systematic analysis of the medical literature from peer reviewed journals. Established methodology principles such as Grading of Recommendations Assessment, Development, and Evaluation or GRADE are adapted to evaluate the evidence. The RAND/UCLA Appropriateness Method User Manual provides the methodology to determine the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where peer reviewed literature is lacking or equivocal, experts may be the primary evidentiary source available to formulate a recommendation.

Heart-specific NFAT5 knockout suppresses type I interferon signaling and aggravates coxsackievirus-induced myocarditis.

Nuclear factor of activated T cells 5 (NFAT5) is an osmosensitive transcription factor that is well-studied in renal but rarely explored in cardiac diseases. Although the association of Coxsackievirus B3 (CVB3) with viral myocarditis is well-established, the role of NFAT5 in this disease remains largely unexplored. Previous research has demonstrated that NFAT5 restricts CVB3 replication yet is susceptible to cleavage by CVB3 proteases. Using an inducible cardiac-specific Nfat5-knockout mouse model, we uncovered that NFAT5-deficiency exacerbates cardiac pathology, worsens cardiac function, elevates viral load, and reduces survival rates. RNA-seq analysis of CVB3-infected mouse hearts revealed the significant impact of NFAT5-deficiency on gene pathways associated with cytokine signaling and inflammation. Subsequent in vitro and in vivo investigation validated the disruption of the cytokine signaling pathway in response to CVB3 infection, evidenced by reduced expression of key cytokines such as interferon ß1 (IFNß1), C-X-C motif chemokine ligand 10 (CXCL10), interleukin 6 (IL6), among others. Furthermore, NFAT5-deficiency hindered the formation of stress granules, leading to a reduction of important stress granule components, including plakophilin-2, a pivotal protein within the intercalated disc, thereby impacting cardiomyocyte structure and function. These findings unveil a novel mechanism by which NFAT5 inhibits CVB3 replication and pathogenesis through the promotion of antiviral type I interferon signaling and the formation of cytoplasmic stress granules, collectively identifying NFAT5 as a new cardio protective protein.

Epigenetic and proteomic signatures associate with clonal hematopoiesis expansion rate.

Clonal hematopoiesis of indeterminate potential (CHIP), whereby somatic mutations in hematopoietic stem cells confer a selective advantage and drive clonal expansion, not only correlates with age but also confers increased risk of morbidity and mortality. Here, we leverage genetically predicted traits to identify factors that determine CHIP clonal expansion rate. We used the passenger-approximated clonal expansion rate method to quantify the clonal expansion rate for 4,370 individuals in the National Heart, Lung, and Blood Institute (NHLBI) Trans-Omics for Precision Medicine (TOPMed) cohort and calculated polygenic risk scores for DNA methylation aging, inflammation-related measures and circulating protein levels. Clonal expansion rate was significantly associated with both genetically predicted and measured epigenetic clocks. No associations were identified with inflammation-related lab values or diseases and CHIP expansion rate overall. A proteome-wide search identified predicted circulating levels of myeloid zinc finger 1 and anti-Müllerian hormone as associated with an increased CHIP clonal expansion rate and tissue inhibitor of metalloproteinase 1 and glycine N-methyltransferase as associated with decreased CHIP clonal expansion rate. Together, our findings identify epigenetic and proteomic patterns associated with the rate of hematopoietic clonal expansion.

How I Do It: Holmium laser cystolitholapaxy and enucleation of the prostate for benign prostatic hyperplasia.

Holmium enucleation of the prostate (HoLEP) is a gold-standard, size-independent surgical treatment for benign prostatic hyperplasia (BPH) distinguished for its efficacy in tissue removal, shorter catheterization durations, lower transfusion rates, and decreased hospital stays when compared to transurethral resection of the prostate (TURP). The objective of this article is to demonstrate the step-by-step procedure of holmium laser cystolitholapaxy and enucleation of the prostate for BPH, emphasizing a top-down modified two-lobe technique with early apical release which enhances visualization and irrigation flow during the enucleation process.

Multi-ancestry polygenic risk scores for venous thromboembolism.

Venous thromboembolism (VTE) is a significant contributor to morbidity and mortality, with large disparities in incidence rates between Black and White Americans. Polygenic risk scores (PRSs) limited to variants discovered in genome-wide association studies in European-ancestry samples can identify European-ancestry individuals at high risk of VTE. However, there is limited evidence on whether high-dimensional PRS constructed using more sophisticated methods and more diverse training data can enhance the predictive ability and their utility across diverse populations. We developed PRSs for VTE using summary statistics from the International Network against Venous Thrombosis (INVENT) consortium genome-wide association studies meta-analyses of European- (71 771 cases and 1 059 740 controls) and African-ancestry samples (7482 cases and 129 975 controls). We used LDpred2 and PRS-CSx to construct ancestry-specific and multi-ancestry PRSs and evaluated their performance in an independent European- (6781 cases and 103 016 controls) and African-ancestry sample (1385 cases and 12 569 controls). Multi-ancestry PRSs with weights tuned in European-ancestry samples slightly outperformed ancestry-specific PRSs in European-ancestry test samples (e.g. the area under the receiver operating curve [AUC] was 0.609 for PRS-CSx_combinedEUR and 0.608 for PRS-CSxEUR [P = 0.00029]). Multi-ancestry PRSs with weights tuned in African-ancestry samples also outperformed ancestry-specific PRSs in African-ancestry test samples (PRS-CSxAFR: AUC = 0.58, PRS-CSx_combined AFR: AUC = 0.59), although this difference was not statistically significant (P = 0.34). The highest fifth percentile of the best-performing PRS was associated with 1.9-fold and 1.68-fold increased risk for VTE among European- and African-ancestry subjects, respectively, relative to those in the middle stratum. These findings suggest that the multi-ancestry PRS might be used to improve performance across diverse populations to identify individuals at highest risk for VTE.

Epidemiologic Features of Recovery From SARS-CoV-2 Infection.

Importance: Persistent symptoms and disability following SARS-CoV-2 infection, known as post-COVID-19 condition or "long COVID," are frequently reported and pose a substantial personal and societal burden. Objective: To determine time to recovery following SARS-CoV-2 infection and identify factors associated with recovery by 90 days. Design, Setting, and Participants: For this prospective cohort study, standardized ascertainment of SARS-CoV-2 infection was conducted starting in April 1, 2020, across 14 ongoing National Institutes of Health-funded cohorts that have enrolled and followed participants since 1971. This report includes data collected through February 28, 2023, on adults aged 18 years or older with self-reported SARS-CoV-2 infection. Exposure: Preinfection health conditions and lifestyle factors assessed before and during the pandemic via prepandemic examinations and pandemic-era questionnaires. Main Outcomes and Measures: Probability of nonrecovery by 90 days and restricted mean recovery times were estimated using Kaplan-Meier curves, and Cox proportional hazards regression was performed to assess multivariable-adjusted associations with recovery by 90 days. Results: Of 4708 participants with self-reported SARS-CoV-2 infection (mean [SD] age, 61.3 [13.8] years; 2952 women [62.7%]), an estimated 22.5% (95% CI, 21.2%-23.7%) did not recover by 90 days post infection. Median (IQR) time to recovery was 20 (8-75) days. By 90 days post infection, there were significant differences in restricted mean recovery time according to sociodemographic, clinical, and lifestyle characteristics, particularly by acute infection severity (outpatient vs critical hospitalization, 32.9 days [95% CI, 31.9-33.9 days] vs 57.6 days [95% CI, 51.9-63.3 days]; log-rank P < .001). Recovery by 90 days post infection was associated with vaccination prior to infection (hazard ratio [HR], 1.30; 95% CI, 1.11-1.51) and infection during the sixth (Omicron variant) vs first wave (HR, 1.25; 95% CI, 1.06-1.49). These associations were mediated by reduced severity of acute infection (33.4% and 17.6%, respectively). Recovery was unfavorably associated with female sex (HR, 0.85; 95% CI, 0.79-0.92) and prepandemic clinical cardiovascular disease (HR, 0.84; 95% CI, 0.71-0.99). No significant multivariable-adjusted associations were observed for age, educational attainment, smoking history, obesity, diabetes, chronic kidney disease, asthma, chronic obstructive pulmonary disease, or elevated depressive symptoms. Results were similar for reinfections. Conclusions and Relevance: In this cohort study, more than 1 in 5 adults did not recover within 3 months of SARS-CoV-2 infection. Recovery within 3 months was less likely in women and those with preexisting cardiovascular disease and more likely in those with COVID-19 vaccination or infection during the Omicron variant wave.

Development and Initial Evaluation of a Cost-Effective Force Sensor for Ureteroscopic Application.

Purpose: Retrograde intrarenal surgery is the gold-standard treatment for most kidney stones. During ureteroscopy, ureteral access sheath insertion at forces greater than 8.0 Newtons (N) risks high-grade ureteral injury. To monitor force, our institution utilizes a unique, Bluetooth-equipped device (i.e., the University of California-Irvine Force Sensor). Given the unique nature of the force sensor, we sought to develop an inexpensive and accessible force sensor based on Boyle's law and the specific amount of force required to compress an occluded 1.0 mL syringe. Materials and Methods: We evaluated three brands of 1.0 mL syringes. After setting the plunger at 1.0 mL, the syringe was occluded, and the syringe plunger was compressed. The syringe volume was recorded when the applied force on the plunger reached 4.0 N, 6.0 N, and 8.0 N. Multiple trials were performed to assess reliability and reproducibility. A method for applying this clinically was also developed. Results: The precise force thresholds identified for a 1.0 mL Luer-Lok™ Syringe (Becton Dickinson, Franklin Lakes, NJ) were 0.30 mL for 4.00 N, 0.20 mL for 6.00 N, and 0.15 mL for 8.00 N. The 1.0 mL Tuberculin Syringe and 1.0 mL Luer Slip Syringe were less precise, but compression from 1.0 to 0.40 mL, 0.25 mL, and 0.20 mL corresponded to force sensor readings that did not exceed 4.00 N, 6.00 N, and 8.00 N, respectively. Conclusions: Based on volume changes, 4.00 N, 6.00 N, and 8.00 N of force can be reliably and reproducibly achieved using an occluded 1.0 mL syringe.

Opportunities to Enhance Diagnostic Testing and Antimicrobial Stewardship: A Qualitative Multinational Survey of Healthcare Professionals.

INTRODUCTION: Antimicrobial resistance (AMR) is a global public health challenge. Global efforts to decrease AMR through antimicrobial stewardship (AMS) initiatives include education and optimising the use of diagnostic technologies and antibiotics. Despite this, economic and societal challenges hinder AMS efforts. The objective of this study was to obtain insights from healthcare professionals (HCPs) on current challenges and identify opportunities for optimising diagnostic test utilisation and AMS efforts. METHODS: Three hundred HCPs from six countries (representing varied gross national incomes per capita, healthcare system structure, and AMR rates) were surveyed between November 2022 through January 2023. A targeted literature review and expert interviews were conducted to inform survey development. Descriptive statistics were used to summarise survey responses. RESULTS: These findings suggest that the greatest challenges to diagnostic test utilisation were economic in nature; many HCPs reported that AMS initiatives were lacking investment (32.3%) and resourcing (40.3%). High resistance rates were considered the greatest barriers to appropriate antimicrobial use (52.0%). Most HCPs found local and national guidelines to be very useful (≥ 51.0%), but areas for improvement were noted. The importance of AMS initiatives was confirmed; diagnostic practices were acknowledged to have a positive impact on decreasing AMR (70.3%) and improving patient outcomes (81.0%). CONCLUSION: AMS initiatives, including diagnostic technology utilisation, are pivotal to decreasing AMR rates. Interpretation of these survey results suggests that while HCPs consider diagnostic practices to be important in AMS efforts, several barriers to successful implementation still exist including patient/institutional costs, turnaround time of test results, resourcing, AMR burden, and education. While some barriers differ by country, these survey results highlight areas of opportunities in all countries for improved use of diagnostic technologies and broader AMS efforts, as perceived by HCPs. Greater investment, resourcing, education, and updated guidelines offer opportunities to further strengthen global AMS efforts.

Antimicrobials are medications used to treat infections caused by bacteria (e.g. antibiotics), viruses, parasites, and fungi. Over time, these microbes may become resistant to antimicrobials, limiting how well they work. This often happens as a result of overuse, using antimicrobials when there is not an infection, or using an inappropriate antimicrobial. Antimicrobial resistance is a growing global problem. Antimicrobial stewardship programs aim to improve appropriate use of antimicrobials. Diagnostic testing plays an important role in these programs by identifying the microbes responsible for infections so patients can be given the right treatment as quickly as possible. We aimed to obtain the perspective of healthcare professionals from six countries on the challenges of and ways to improve diagnostic testing and antimicrobial stewardship programs. We found that some of the greatest challenges were related to costs. Approximately one-third of participants said that antimicrobial stewardship initiatives were lacking investment (32.3%) and resourcing (40.3%). High rates of antimicrobial resistance were identified as the greatest barriers to appropriate antimicrobial use (52.0%). Participants said that diagnostic practices have a positive impact on decreasing antimicrobial resistance (70.3%) and improving patient outcomes (81.0%). Overall, we found that healthcare professionals consider diagnostic tests to be an important part of antimicrobial stewardship, but there are several barriers to their success, including patient/hospital costs, turnaround time of test results, resourcing, antimicrobial resistance, and education. To overcome these barriers, increased funding, education, and resourcing, regular guideline updates, and development of optimised testing algorithms may help to improve antimicrobial stewardship and ultimately decrease antimicrobial resistance.