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In the United States, hundreds of thousands of undocumented orphan wells have been abandoned, leaving the burden of managing environmental hazards to governmental agencies or the public. These wells, a result of over a century of fossil fuel extraction without adequate regulation, lack basic information like location and depth, emit greenhouse gases, and leak toxic substances into groundwater. For most of these wells, basic information such as well location and depth is unknown or unverified. Addressing this issue necessitates innovative and interdisciplinary approaches for locating, characterizing, and mitigating their environmental impacts. Our survey of the United States revealed the need for tools to identify well locations and assess conditions, prompting the development of technologies including machine learning to automatically extract information from old records (95%+ accuracy), remote sensing technologies like aero-magnetometers to find buried wells, and cost-effective methods for estimating methane emissions. Notably, fixed-wing drones equipped with magnetometers have emerged as cost-effective and efficient for discovering unknown wells, offering advantages over helicopters and quadcopters. Efforts also involved leveraging local knowledge through outreach to state and tribal governments as well as citizen science initiatives. These initiatives aim to significantly contribute to environmental sustainability by reducing greenhouse gases and improving air and water quality.

Lung cancer screening via annual low-dose computed tomography has poor adoption. We conducted a prospective case-control study among 958 individuals eligible for lung cancer screening to develop a blood-based lung cancer detection test that when positive is followed by a low-dose computed tomography. Changes in genome-wide cell-free DNA fragmentation profiles (fragmentomes) in peripheral blood reflected genomic and chromatin characteristics of lung cancer. We applied machine learning to fragmentome features to identify individuals who were more or less likely to have lung cancer. We trained the classifier using 576 cases and controls from study samples and validated it in a held-out group of 382 cases and controls. The validation demonstrated high sensitivity for lung cancer and consistency across demographic groups and comorbid conditions. Applying test performance to the screening eligible population in a 5-year model with modest utilization assumptions suggested the potential to prevent thousands of lung cancer deaths. Significance: Lung cancer screening has poor adoption. Our study describes the development and validation of a novel blood-based lung cancer screening test utilizing a highly affordable, low-coverage genome-wide sequencing platform to analyze cell-free DNA fragmentation patterns. The test could improve lung cancer screening rates leading to substantial public health benefits. See related commentary by Haber and Skates, p. 2025., (©2024 The Authors; Published by the American Association for Cancer Research.)

A core feature of misophonia is the emotional distress that occurs in response to specific sounds (e.g., slurping, pen clicking). Despite the theorized connection between emotion dysregulation and misophonia, there is very little research on this topic. Examining emotion dysregulation and identifying the specific emotion regulation deficits that are associated with worse misophonia symptoms would advance our understanding of potential transdiagnostic factors central to misophonia symptoms; thereby informing the development of more targeted interventions. The current study sought to: 1) characterize emotion dysregulation among individuals with misophonia, 2) compare emotion dysregulation between individuals with clinical and subclinical misophonia, and 3) examine the unique role of emotion dysregulation across three domains of misophonia symptoms. This study included a large, nationally representative sample of U.S. adults (N = 4005; 51.5% female; 62.5% White, non-Hispanic). Participants completed self-report questionnaires to assess misophonia symptoms (i.e., misophonia sounds, emotional and behavioral reactions to misophonia sounds, and misophonia-related impairment), stress, and emotion dysregulation. The results revealed participants with misophonia reported significantly worse emotion regulation abilities compared to individuals with subclinical levels of misophonia. In addition, emotion dysregulation was significantly associated with sensitivity to misophonia sounds, reactions to misophonia sounds, and misophonia-related impairment, even after accounting for covariates. Results support emotion dysregulation as an important element in misophonia and suggest certain dimensions of emotion dysregulation should be considered in future research and in the evaluation of treatment strategies used to reduce misophonia symptoms., Competing Interests: Declaration of competing interest The authors have no other competing interests to declare., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Circulating cell-free DNA (cfDNA) assays for monitoring individuals with cancer typically rely on prior identification of tumor-specific mutations. Here, we develop a tumor-independent and mutation-independent approach (DELFI-tumor fraction, DELFI-TF) using low-coverage whole genome sequencing to determine the cfDNA tumor fraction and validate the method in two independent cohorts of patients with colorectal or lung cancer. DELFI-TF scores strongly correlate with circulating tumor DNA levels (ctDNA) (r = 0.90, p < 0.0001, Pearson correlation) even in cases where mutations are undetectable. DELFI-TF scores prior to therapy initiation are associated with clinical response and are independent predictors of overall survival (HR = 9.84, 95% CI = 1.72-56.10, p < 0.0001). Patients with lower DELFI-TF scores during treatment have longer overall survival (62.8 vs 29.1 months, HR = 3.12, 95% CI 1.62-6.00, p < 0.001) and the approach predicts clinical outcomes more accurately than imaging. These results demonstrate the potential of using cfDNA fragmentomes to estimate tumor burden in cfDNA for treatment response monitoring and clinical outcome prediction., (© 2024. The Author(s).)

Shell ring archaeological sites are one of the most visible site types along the lower South Atlantic Coast of the United States. These cultural sites are large, circular to arcuate piles of mollusk shells with some reaching over three meters in elevation and over 100 m in diameter. They are comprised largely of mollusk shells (e.g., Eastern oyster, Crassostrea virginica), but also contain early pottery, nonhuman faunal remains, and other artifacts. Our work establishes that they represent the earliest widespread Native American villages occupied year-round in the Eastern Woodlands of North America. Significantly, our results from sea-level modelling and isotope geochemistry on mollusks establish that the inhabitants of these earliest villages (ca. 5000-3800 yrs. BP) lived within a fluctuating coastal environment, harvested certain resources year-round, and targeted diverse habitats across the estuaries. Both the growth and decline of these earliest villages are associated with a concomitant rise and lowering of sea level that impacted the productivity of the oyster reef fishery along the South Atlantic Coast. Despite these large-scale environmental changes, this research indicates that Native American fishing villages persisted along the coast for over 1000 years., (© 2024. The Author(s).)

The structured professional judgement (SPJ) approach was initially developed to support risk assessment and management decisions. The approach is now being adapted and applied to admission assessments for adult secure services. This systematic review aims to summarise the evidence for the effectiveness and acceptability of the SPJ approach in admission assessments of this kind. A comprehensive electronic search strategy was used to identify studies indexed in PubMed, PsycInfo, Medline and Cochrane Library (January 2007 -January 2024). Two search strategies included terms (and synonyms) for psychiatric patients (quantitative) or clinicians and clinicians' experiences (qualitative), structured professional judgement, admission, and secure services. Twelve quantitative articles (published 2007-2020) were identified. SPJ-informed guidance included were the DUNDRUM-1, DUNDRUM-2, DUNDRUM-3, DUNDRUM-4, and the HCR-20. While findings were variable, the overall pattern indicated that ratings suggestive of more problems were associated with increased likelihood of admission or movement to higher security levels. There is emerging evidence for the use of SPJ guidance to support admission decision-making. Specifically, it should be used as an adjunct to existing decision-making processes rather than as a replacement for those processes. Further research, both quantitative and qualitative, across a wider range of settings and populations is recommended., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Bowden et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Pure erythroid leukemia (PEL) is an extremely rare subtype of acute myeloid leukemia (AML). Although not specific, PEL is almost uniformly associated with complex karyotype and TP53 mutations. Given the rarity of the disease, our understanding of its cytogenetic and molecular features deems incomplete. We aim to complement existing literature by presenting an unusual case of PEL. The case is comprehensively worked up with multiple modalities. We present for the first time a case of PEL with unusual cytogenetic and molecular features: normal karyotype with absence of TP53 mutations and presence of NPM1 and NRAS mutations. This is a valuable addition to literature, expanding our understanding of molecular and cytogenetic spectra of PEL., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Creation of a tension-free colorectal anastomosis after left colon resection or low anterior resection is a key requirement for technical success. The relative contribution of each of a series of known lengthening maneuvers remains incompletely characterized., Objective: The aim of this study was to compare technical procedures for lengthening of the left colon before rectal anastomosis., Design: A series of lengthening maneuvers was performed on 15 fresh cadavers. Mean distance gained was measured for each successive maneuver, including 1) high inferior mesenteric artery ligation, 2) splenic flexure takedown, and 3) high inferior mesenteric vein ligation by the ligament of Treitz., Setting: Cadaveric study., Main Outcome Measures: The premobilization and postmobilization position of the proximal colonic end was measured relative to the inferior edge of the sacral promontory. Measurements of the colonic length relative to the sacral promontory were taken after each mobilization maneuver. The inferior mesenteric artery, sigmoid colon, and rectum specimen lengths were measured. The distance from the inferior border of the sacral promontory to the pelvic floor was measured along the sacral curvature., Results: Mean sigmoid colon resection length was 34.7 ± 11.1 cm. Before any lengthening, baseline reach was -1.3 ± 4.2 cm from the sacral promontory. Inferior mesenteric artery ligation yielded an additional 11.5 ± 4.7 cm. Subsequent splenic flexure takedown added an additional 12.8 ± 9.6 cm. Finally, inferior mesenteric vein ligation added an additional 11.33 ± 6.9 cm, bringing the total colonic length to 35.7 ± 14.7 cm. BMI and weight negatively correlated with length gained., Limitations: The study was limited by nature of being a cadaver study., Conclusions: Stepwise lengthening maneuvers allow significant additional reach to allow a tension-free left colon to rectal anastomosis. See Video Abstract ., Estudio Cadavrico De Maniobras De Alargamiento Colnico Tras Una Sigmoidectoma: ANTECEDENTES:La creación de una anastomosis colorrectal libre de tensión tras una resección de colon izquierdo o tras una resección anterior baja es un requisito clave para el éxito relacionado con la técnica quirúrgica. La relativa contribución de las diversas maniobras de alargamiento permanece caracterizada de manera incompleta.OBJETIVO:El propósito de este estudio fue la de comparar procedimientos técnicos de alargamiento del colon izquierdo previo a la anastomosis rectal.DISEÑO:Una serie de maniobras de alargamiento fueron realizados en 15 cadáveres frescos. La distancia promedio ganada fue medida para cada maniobra sucesiva, incluyendo (1) ligadura alta de la arteria mesentérica inferior, (2) descenso del ángulo esplénico, (3) ligadura alta de la vena mesentérica interior mediante el ligamento de Treitz.AJUSTES:Estudio cadavérico.PRINCIPALES MEDIDAS DE RESULTADO:La posición premobilizacion y postmobilizacion del extremo proximal del colon fue medido tomando en cuenta el borde inferior del promontorio sacro. Las mediciones de la longitud colónica en relación al sacro fueron tomadas luego de cada maniobra de movilización. Fueron tomadas así mismo las longitudes de la arteria mesentérica inferior, el colon sigmoides y recto. Las distancias desde el borde inferior del promontorio sacro al suelo pelvico fueron medidas a lo largo de la curvatura sacra.RESULTADOS:Average sigmoid colon resection length was 34.7 ± 11.1 cm. Prior to any lengthening, baseline reach was -1.3 ± 4.2 cm from the sacral promontory. Inferior mesenteric artery ligation yielded an additional 11.5 ± 4.7 cm. Subsequent splenic flexure takedown added an additional 12.8 ± 9.6 cm. Finally, inferior mesenteric vein ligation added an additional 11.33 ± 6.9 cm, bringing the total colonic length to 35.7 ± 14.7 cm. BMI and weight negatively correlated with length gained.LIMITACIONES:Este estudio tuvo como limitación la naturaleza de haber sido un estudio cadavérico.CONCLUSIONES:Maniobras de alargamiento permiten un alcance adicional significativo permitiendo de esta manera una anastomosis de colon izquierdo a recto libre de anastomosis. (Traducción-Dr Osvaldo Gauto )., (Copyright © The ASCRS 2024.)

Reducing foodborne disease incidence is a public health priority. This report summarizes preliminary 2023 Foodborne Diseases Active Surveillance Network (FoodNet) data and highlights efforts to increase the representativeness of FoodNet. During 2023, incidences of domestically acquired campylobacteriosis, Shiga toxin-producing Escherichia coli infection, yersiniosis, vibriosis, and cyclosporiasis increased, whereas those of listeriosis, salmonellosis, and shigellosis remained stable compared with incidences during 2016-2018, the baseline used for tracking progress towards federal disease reduction goals. During 2023, the incidence and percentage of infections diagnosed by culture-independent diagnostic tests (CIDTs) reported to FoodNet continued to increase, and the percentage of cases that yielded an isolate decreased, affecting observed trends in incidence. Because CIDTs allow for diagnosis of infections that previously would have gone undetected, lack of progress toward disease reduction goals might reflect changing diagnostic practices rather than an actual increase in incidence. Continued surveillance is needed to monitor the impact of changing diagnostic practices on disease trends, and targeted prevention efforts are needed to meet disease reduction goals. During 2023, FoodNet expanded its catchment area for the first time since 2004. This expansion improved the representativeness of the FoodNet catchment area, the ability of FoodNet to monitor trends in disease incidence, and the generalizability of FoodNet data., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. Tamara Rissman reports that she is an adjunct professor in the Public Health Department at Southern Connecticut State University. No other potential conflicts of interest were disclosed.

Objective: To investigate the relationship between ergonomic positions and electromyographic muscle activity during otologic drilling., Study Design: Cross-over experimental trial., Setting: Tertiary Academic Medical Center., Methods: Surgeon participants were tasked with delicate eggshell drilling in 3 different seated positions: "neutral," "slouched," and "craned." Surface electromyography (sEMG) sensors recorded the amplitude and frequency of muscle activity. The joint analysis of spectrum and amplitude (JASA) method, which combines temporal trends in frequency and amplitude, was used to identify trials that exhibited patterns of fatigue., Results: The sEMG amplitude and frequency responses demonstrated wide temporal changes. In a majority of experiments, amplitude increased over the course of the experiment, while frequency remained more stable. On analysis of variance testing, only the mean frequency of the deltoid differed significantly between postures (P = .02). Under the JASA framework, external carpi radialis and upper trapezius experienced fatigue in nearly half of the trials regardless of position (47% vs 49%). The upper trapezius demonstrated fatigue during 46% and 69% of the "craned" and "slouched" trials, respectively, compared to just 31% of the "neutral" trials. Fewer attendings demonstrated upper trapezius fatigue compared to trainees (33% vs 62%). Female surgeons experienced fatigue in more trials than male counterparts (73% vs 25%)., Conclusion: This study highlights a first step in quantifying the relationship between operating postures and muscle fatigue. Results suggest that specific muscle groups are more susceptible to fatigue; gender and experience may also impact muscle activity., (© 2024 American Academy of Otolaryngology–Head and Neck Surgery Foundation.)

Misophonia is characterized by decreased tolerance for and negative reactions to certain sounds and associated stimuli, which contribute to impairment and distress. Research has found that misophonia is common in clinical, college, and online samples; yet, fewer studies have examined rates of misophonia in population-based samples. The current study addresses limitations of prior research by investigating misophonia prevalence, phenomenology, and impairment in a large, nationally representative sample of adults in the United States. Probability-based sampling was used to administer a survey to a representative sample of U.S. households. Data were adjusted with poststratification weights to account for potential sampling biases and examined as weighted proportions to estimate the outcomes. The sample included 4,005 participants (51.5% female; 62.5% White). Sensitivity to misophonia sounds was reported by 78.5% of the sample, and 4.6% reported clinical levels of misophonia. Results demonstrated significant demographic differences in misophonia symptom severity. Specifically, significantly higher misophonia symptoms were observed for participants who identified as female, less than 55 years old, less than a high school education, never married, lower income, and those working part time, compared to each of the respective comparison groups. Those with clinically significant misophonia symptoms reported that symptoms often onset in childhood and adolescence, were persistent, and contributed to severe impairment in at least one life domain. These findings provide a prevalence estimate of misophonia in the general population of the United States and inform our understanding of who is affected by misophonia. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

The FoodNet Population Survey is a periodic survey of randomly selected residents in 10 US sites on exposures and behaviors that may be associated with acute diarrheal infections and the health care sought for those infections. This survey is used to estimate the true disease burden of enteric illness in the United States and to estimate rates of exposure to potential sources of illness. Unlike previous FoodNet Population Surveys, this cycle used multiple sampling frames and administration modes, including cell phone and web-based questionnaires, that allowed for additional question topics and a larger sample size. It also oversampled children to increase representation of this population. Analytic modeling adjusted for mode effects when estimating the prevalence estimates of exposures and behaviors. This report describes the design, methodology, challenges, and descriptive results from the 2018-19 FoodNet Population Survey., (Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health 2024.)

Previous research has found that lower limb muscle asymmetries increase with age and are linked to fall and injury risks. However, past studies lack a wide variety of muscle function modes and measures as well as comparison to a comparable younger age group. The purpose of this study was to examine age-related lower limb muscle function asymmetries across a variety of muscle action types and velocities in young and old adults. Lower limb balance, strength, power, and velocity were evaluated with concentric, isometric, isotonic, and eccentric muscle actions during a single-leg stance test and on single- and multi-joint dynamometers in 29 young (age = 21.45 ± 3.02) and 23 old (age = 77.00 ± 4.60) recreationally active men and women. Most (15 of 17) variables showed no statistical ( p > 0.05) or functional (10% threshold) limb asymmetry for either age group. There was a significant main effect ( p = 0.046; collapsed across groups) found for asymmetry (dominant > non-dominant) for the isotonic peak velocity variable. There was a significant ( p = 0.010) group × limb interaction for single-joint concentric peak power produced at a slow (60 deg/s) velocity due to the non-dominant limb of the young group being 12.2% greater than the dominant limb ( p < 0.001), whereas the old group was not asymmetrical ( p = 0.965). The findings of this investigation indicate there is largely no age-related asymmetry of the lower limbs across a range of muscle function-related variables and modes, with a couple of notable exceptions. Also, the significant asymmetries for the isotonic peak velocity variable perhaps show the sensitivity of this uncommonly used measure in detecting minimally present muscle function imbalances.

Background: Beta-2 transferrin (B2-Tf) gel electrophoresis (GE) is the preferred non-invasive diagnostic modality for confirming cerebrospinal fluid (CSF) in body fluids. While B2-Tf GE testing is highly sensitive and specific for CSF, false-positive (FP) and false-negative (FN) results can lead to diagnostic and therapeutic dilemmas. Several series have demonstrated potential causes of false B2-Tf GE results, but few studies have reported reasons for these errors. The purpose of this systematic review was to describe sources of B2-Tf GE errors., Methods: A systematic review was performed by searching OVID, EMBASE, and Web of Science databases for B2-Tf GE studies. After applying exclusion criteria, original research studies directly addressing erroneous B2-Tf GE results underwent qualitative analysis., Results: Of the 243 abstracts screened, 71 underwent full-text review and 18 studies reporting B2-Tf GE errors were included for analysis. There were 15 potential FPs, 12 actual FPs, 12 potential FNs, 19 actual FNs, and 14 indeterminate results. There were also 246 potentially indeterminate results from in vitro studies. Reasons for B2-Tf GE errors included serum transferrin alterations (n = 17; all potential), infection related (n = 13; 9 potential), orbital or salivary contamination (n = 2; 1 potential), and collection related (n = 255; 246 potential). There were 31 false or indeterminate results with unspecified reasons. There were no reported errors due to laboratory processing., Conclusions: Multiple potential or actual reasons for false or indeterminate results have been reported for B2-Tf GE testing of rhinorrhea and otorrhea. Future studies should explore reasons for B2-Tf testing errors and how these may affect clinical decision making., (© 2023 ARS‐AAOA, LLC.)

Introduction: Liver transplantation (LT) is a technically complex operation and usually performed on ill patients. A major postoperative morbidity is incisional hernia, occurring in 9.5%-32.4% of cases. There are mixed results in transplant studies regarding potential risk factors. Additionally, the literature is lacking in the relationship between specific immunosuppressive induction agents administered during LT and postoperative incisional hernia., Methods: A single center, retrospective cohort study of patients who underwent primary LT between 4/2011-1/2018 was conducted. Clinical variables including demographics and comorbidities were reviewed. The primary end point was the development of an incisional hernia following LT. Sub analysis was performed for secondary end points to determine potential risk factors, including immunosuppressive induction agent., Results: Overall, 418 patients met inclusion criteria. At 5 y post-LT, there were 66/271 (24.4%) and 53/147 (36.1%) patients diagnosed with an incisional hernia in the methylprednisolone and basiliximab groups, respectively. After propensity score matching, there was no difference in incisional hernia development between induction agents, P = 0.19. For patients with body mass index ≥30 and postoperative seroma of the abdominal wall, the hazard ratios were 2.67 (95% CI = 1.7, 4.3) and 2.03 (95% CI = 1.1, 3.9), respectively., Conclusions: Incisional hernia rate after LT was 28.5% at 5 y. Our analysis found that immunosuppressive induction agent at LT was not associated with the development of postoperative incisional hernia. However, preoperative obesity (body mass index ≥30) and postoperative seroma of the abdominal wall were potential risk factors. Further studies are needed to delineate if these risk factors remain across institutions and in alternative settings., (Copyright © 2024 Elsevier Inc. All rights reserved.)

BACKGROUNDEarly antiretroviral therapy initiation (ARTi) in HIV-1 restricts reservoir size and diversity while preserving immune function, potentially improving opportunities for immunotherapeutic cure strategies. For antibody-based cure approaches, the development of autologous neutralizing antibodies (anAbs) after acute/early ARTi is relevant but is poorly understood.METHODSWe characterized antibody responses in a cohort of 23 participants following ARTi in acute HIV (<60 days after acquisition) and early HIV (60-128 days after acquisition).RESULTSPlasma virus sequences at the time of ARTi revealed evidence of escape from anAbs after early, but not acute, ARTi. HIV-1 envelopes representing the transmitted/founder virus(es) (acute ARTi) or escape variants (early ARTi) were tested for sensitivity to longitudinal plasma IgG. After acute ARTi, no anAb responses developed over months to years of suppressive ART. In 2 of the 3 acute ARTi participants who experienced viremia after ARTi, however, anAbs arose shortly thereafter. After early ARTi, anAbs targeting those early variants developed between 12 and 42 weeks of ART and continued to increase in breadth and potency thereafter.CONCLUSIONResults indicate a threshold of virus replication (~60 days) required to induce anAbs, after which they continue to expand on suppressive ART to better target the range of reservoir variants.TRIAL REGISTRATIONClinicalTrials.gov NCT02656511.FUNDINGNIH grants U01AI169767, R01AI162646, UM1AI164570, UM1AI164560, U19AI096109, K23GM112526, T32AI118684, P30AI045008, P30AI027763, R24AI067039; Gilead Sciences grant INUS2361354; Viiv Healthcare grant A126326.

We present new chronologies that inform the timing and tempo of shell ring and shell mound construction on the South Atlantic Bight. Our project combines recently acquired dates with legacy radiocarbon dates from over 25 rings and mounds to provide a higher-resolution chronology regarding the occupation and formation of this larger landscape of the earliest fishing villages along the East Coast of the United States. We resolve the ordering and timing of occupation of these rings and mounds through Bayesian statistical modeling. These new models historicize and contextualize these shell rings in ways previously impossible. Specifically, our new chronologies of these villages indicate that the earliest villages were established prior to the invention of pottery. The early period of village establishment evidences isolated village rings, whereas later periods seem to have more villages, but these appear to have been relocated to other areas and/or islands over time. Shell mounds are fewer in number, are spread throughout the time period, and may represent special purpose sites compared to shell-rings. Once villages spread, they quickly adopted new technologies (i.e., pottery) and created new institutions and practiced village relocation, which allowed this way of life to persist for more than a thousand years., (© 2024. The Author(s).)

Background: Free tissue transfer is a mainstay treatment for lower extremity soft tissue injuries. When the traditional cross-leg flap cannot provide enough coverage, a cross-leg free flap (CLFF) is a limb-saving alternative. The aim of this study is to conduct a systematic review of the literature published on the CLFF., Methods: We conducted a systematic review of articles describing the CLFF, according to Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Inclusion criteria included articles with primary data on the CLFF. Exclusion criteria included those describing pedicled cross-leg flaps or lacking complete data. Data analysis was performed using SPSS 29.0., Results: Our review included 28 articles encompassing 130 patients who underwent free tissue transfer. Most were male (63.8%) with a mean age of 32.4 years. Latissimus dorsi was the most common flap type (30.0%), followed by vertical rectus myocutaneous (20.0%). Average flap size was 301.8 cm 2 , with trauma in the lower third of the leg being the most common indication (73.1%). The contralateral posterior tibialis was the most common recipient artery (84.1%) followed by the anterior tibialis (9.5%). Complications included amputation (1.4%), partial graft loss, thrombosis, hematoma, prolonged pain, nonunion, and seroma; a forest plot was used to illustrate the low overall adverse events rate. Although bivariate analysis identified age, flap size, type, location, and donor site as variables significantly impacting the incidence of complications (p < .05), this was not sustained in a multivariate logistic regression model., Conclusion: The CLFF remains an excellent option for limb salvage when a suitable recipient vessel is unavailable. Our review demonstrates 1.4% flap failure and an acceptable complication rate. While most cases in our review describe muscle flaps, we report a complex case of limb salvage using an unusually large anterolateral thigh flap., (© 2024 The Authors. Microsurgery published by Wiley Periodicals LLC.)

Abstract: High-risk multiple myeloma (MM) is often defined based on cytogenetic abnormalities, but patients who relapse early after initial therapy are considered a functional high-risk group. In the phase 3 CASTOR and POLLUX studies, daratumumab plus bortezomib/dexamethasone (D-Vd) or lenalidomide/dexamethasone (D-Rd) improved progression-free survival (PFS) and overall survival (OS), regardless of cytogenetic risk, and achieved higher rates of complete response or better (≥CR) and minimal residual disease (MRD) negativity vs that with Vd/Rd alone in relapsed/refractory MM. Post hoc analyses of CASTOR and POLLUX evaluated patient subgroups with 1 prior line of therapy based on timing of progression/relapse (early or late) after initiation of first line of therapy. PFS consistently favored the daratumumab-containing regimens across subgroups using both a 24- and 18-month early-relapse cutoff. In the CASTOR/POLLUX pooled data set, daratumumab reduced the risk of disease progression or death by 65% (hazard ratio [HR], 0.35; 95% confidence interval [CI], 0.26-0.48; P < .0001) in the early-relapse (<24 months) subgroup and by 65% (HR, 0.35; 95% CI, 0.26-0.47; P < .0001) in the late-relapse (≥24 months) subgroup. OS also favored the daratumumab-containing regimens in both the early-relapse (HR, 0.62; 95% CI, 0.45-0.86; P = .0036) and late-relapse (HR, 0.67; 95% CI, 0.48-0.93; P = .0183) subgroups in the pooled population using a 24-month cutoff. Rates of ≥CR and MRD negativity (10-5) were higher with daratumumab vs control, regardless of progression/relapse timing. Although daratumumab is unable to fully overcome the adverse prognosis of early relapse, our results support the use of daratumumab for patients with 1 prior line of therapy, including for those who progress/relapse early after initial therapy and are considered to have functional high-risk MM. These trials were registered at www.clinicaltrials.gov as #NCT02136134 (CASTOR) and #NCT02076009 (POLLUX)., (© 2024 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Objectives: Opioid overdose deaths remain a major health issue in the United States (US). As future physicians, medical students must receive comprehensive training to recognize and manage opioid overdoses. This study aimed to highlight training gaps at the medical student level and understand students' attitudes toward patients with opioid use disorder (OUD)., Methods: We assessed baseline knowledge of and attitudes toward the management of opioid overdoses and naloxone administration among medical students in the US. Two validated survey tools (Opioid Overdose Knowledge Scale and Opioid Overdose Attitude Scale) were administered to medical students training at accredited institutions along with supplemental questions measuring knowledge and attitudes towards opioid overdose management, naloxone administration, and prior training., Results: The final sample had N = 73 participants from US medical schools with a mean age of 25.3 (range of 22-37): 72.6% of respondents were female. Although most respondents reported personal/professional experience with OUD before medical school, they expressed interest in additional training. Knowledge surrounding opioid overdoses increased insignificantly over the 4 years of medical school. However, there was a significant increase in both perceived competence in overdose recognition/management and in concerns about intervening from the first to fourth year of medical school. Female respondents had significantly lower perceived competence and readiness to intervene sub-scores than male counterparts; however, there was no significant difference in overall attitude and knowledge scores when stratified by sex. Incorporating opioid overdose prevention training (OOPT) into early medical education was favorable among respondents, who expressed an overwhelming interest in learning and supporting patients with OUD., Conclusions: Given the ongoing opioid crisis, medical students are ideally placed to identify and manage opioid overdoses. Medical students are ready to receive this training, thus strengthening the argument for OOPT integration into early medical student curricula., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

This study aims to identify effective ways to design virtual rehabilitation to obtain physical improvement (e.g. balance and gait) and support engagement (i.e. motivation) for people with osteoporosis or other musculoskeletal disorders. Osteoporosis is a systemic skeletal disorder and is among the most prevalent diseases globally, affecting 0.5 billion adults. Despite the fact that the number of people with osteoporosis is similar to, or greater than those diagnosed with cardiovascular disease and dementia, osteoporosis does not receive the same recognition. Worldwide, osteoporosis causes 8.9 million fractures annually; it is associated with substantial pain, suffering, disability and increased mortality. The importance of physical therapy as a rehabilitation strategy to avoid osteoporosis fracture cannot be over-emphasised. However, the main rehabilitation challenges relate to engagement and participation. The use of virtual rehabilitation to address such challenges in the delivery of physical improvement is gaining in popularity. As there currently is a paucity of literature applying virtual rehabilitation to patients with osteoporosis, the authors broadened the search parameters to include articles relating to the virtual rehabilitation of other skeletal disorders (e.g. Ankylosing spondylitis, spinal cord injury, motor rehabilitation, etc.). This systematic review initially identified 130 titles, from which 23 articles (involving 539 participants) met all eligibility and selection criteria. Four groups of devices supporting virtual rehabilitation were identified: a head-mounted display, a balance board, a camera and more specific devices. Each device supported physical improvement (i.e. balance, muscle strength and gait) post-training. This review has shown that: (a) each device allowed improvement with different degrees of immersion, (b) the technology choice is dependent on the care need and (c) virtual rehabilitation can be equivalent to and enhance conventional therapy and potentially increase the patient's engagement with physical therapy., Competing Interests: Conflict of interestNo conflict of interest of declarations., (© The Author(s) 2024.)

Background: Studies have demonstrated low hepatitis A virus (HAV) vaccination rates among persons with HIV (PWH)., Methods: We conducted a retrospective study of persons entering HIV care at two clinics in Houston, Texas between 2010 and 2018. We defined those eligible for HAV vaccination as those who had no history of HAV vaccination and had a negative anti-HAV IgG at entry to care. Kaplan-Meier curves summarized time to receipt of HAV vaccines. The proportions of patients who received 1 and 2 HAV vaccines at 6, 12, and 24 months were estimated. Cox proportional hazards regression evaluated associations between patient characteristics and vaccination. Significant factors were included in a multivariable Cox proportional hazards model., Results: Of 6,515 patients, 1372 were eligible for HAV vaccination. Of eligible patients, 29.2 % received 1 HAV vaccination at 6 months, 37.1 % at 12 months, and 47.8 % at 24 months. At 6 months, 10 % received 2 HAV vaccinations, 21.1 % at 12 months, and 33.4 % at 24 months. In multivariable analysis, men who have sex with men (adjusted HR 1.35, 95 % CI 1.06, 1.73) or those who had CD4 count ≥ 200 cells/µl (adjusted HR 2.52, 95 % CI 1.89, 3.37) had their second vaccination sooner than those who were not men who have sex with men or who had CD4 counts < 200 cells/µl, respectively. Patients > 50 years of age had their second vaccination sooner than those aged 30-50 years (adjusted HR 1.47, 95 % CI 1.08, 1.99). Those with active substance history had a longer time to second vaccination compared to those with no substance use history (adjusted HR 0.57, 95 % CI 0.40, 0.82)., Conclusions: HAV vaccination rates were low and highlight the need for effective solutions to address HAV immunization gaps in PWH, especially among young patients, those with active substance use disorders, and those with significant immunocompromise., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Author(s).)

The gastrointestinal (GI) epithelium plays a major role in nutrient absorption, barrier formation, and innate immunity. The development of organoid-based methodology has significantly impacted the study of the GI epithelium, particularly in the fields of mucosal biology, immunity, and host-microbe interactions. Various effects on the GI epithelium, such as genetics and nutrition, impact patients and alter disease states. Thus, incorporating these effects into organoid-based models will facilitate a better understanding of disease progression and offer opportunities to evaluate therapeutic candidates. One condition that has a significant effect on the GI epithelium is malnutrition, and studying the mechanistic impacts of malnutrition would enhance our understanding of several pathologies. Therefore, the goal of this study was to begin to develop methodology to generate viable malnourished organoids with accessible techniques and resources that can be used for a wide array of mechanistic studies. By selectively limiting distinct macronutrient components of organoid media, we were able to successfully culture and evaluate malnourished organoids. Genetic and protein-based analyses were used to validate the approach and confirm the presence of known biomarkers of malnutrition. Additionally, as proof-of-concept, we utilized malnourished organoid-derived monolayers to evaluate the effect of malnourishment on barrier formation and the ability of the bacterial pathogen Shigella flexneri to infect the GI epithelium. This work serves as the basis for new and exciting techniques to alter the nutritional state of organoids and investigate the related impacts on the GI epithelium.

Background: Studies have demonstrated low hepatitis B virus (HBV) vaccine series completion among persons with human immunodeficiency virus (HIV)., Methods: We conducted a retrospective record review of persons entering HIV care at 2 clinics in Houston, Texas, between 2010 and 2018. Kaplan-Meier curves summarized time to receipt of HBV vaccines for those eligible for vaccination. We estimated the proportions of patients who had received 1, 2, or 3 HBV vaccine doses at 12 and 24 months after entry to care. A Prentice Williams and Peterson total time model was used to evaluate associations between patient characteristics and time to vaccination., Results: Of the 5357 patients who entered care, 2718 were eligible for HBV vaccination. After 2 years of follow-up, 51.2% of those eligible had received 1 HBV vaccine, 43.2% had received 2, and 28.4% received 3 vaccines. With adjustment for significant cofactors, patients whose CD4 cell count was ≥200/μL (adjusted hazard ratio [aHR], 1.43 [95% confidence interval (CI), 1.29-1.59]) and transgender patients (1.49 [1.08-2.04]) received any given vaccine dose sooner than those with CD4 cell counts <200/μL or cisgender patients, respectively. Compared with non-Hispanic whites, Hispanic patients were vaccinated sooner (aHR, 1.28 [95% CI, 1.07-1.53]). Those with an active substance use history had a significantly longer time to vaccination than those with no substance use history (aHR, 0.73 [95% CI, .62-.85])., Conclusions: Strategies are needed to increase HBV vaccine completion rates in our study population, particularly among those with CD4 cell counts <200/μL or with a substance use disorder., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: Increase in opioid prescribing practices has occurred with concurrent increases in the levels of abuse, addiction, and diversion of opioid pain medication. With 82.5 opioid prescriptions prescribed for every 100 U.S. citizens, the need for more effective strategies aimed at improving opioid disposal exist. Our study sought to examine the planned rates of appropriate opioid disposal after introduction of an activated charcoal home drug disposal system (Deterra®) in combination with formalized opioid disposal education., Methods: Participants were recruited from an academic, public safety-net hospital and grouped into 3 cohorts, no formalized opioid disposal education (No Education), written and verbal patient education on appropriate opioid disposal (Education), and Deterra® in addition to formalized opioid disposal education (Deterra). Outcomes included patients reporting unacceptable methods of opioid disposal, storage of unused opiates, and patient satisfaction with disposal instructions., Results: Reported unacceptable opioid disposal decreased from 80.6% (n = 87) in the no education group to 20% (n = 10) in the education group to 6% (n = 3) in the Deterra group (P < .001). Education decreased long-term storage of opioid medication after completion of usage from 42% (n = 36) to 2% (n = 1), P < .001. Between the education and Deterra groups, more patients felt that the disposal instructions were clear (94% (n = 47) vs 73% (n = 36), P = .006) and more followed acceptable disposal instructions (80% (n = 39) vs 94% (n = 47) P < .001)., Conclusion: Deterra ® along with formal opioid disposal education increases patients reporting plans for compliance with appropriate opioid disposal., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Proper centrosome number and function relies on the accurate assembly of centrioles, barrel-shaped structures that form the core duplicating elements of the organelle. The growth of centrioles is regulated in a cell cycle-dependent manner; while new daughter centrioles elongate during the S/G2/M phase, mature mother centrioles maintain their length throughout the cell cycle. Centriole length is controlled by the synchronized growth of the microtubules that ensheathe the centriole barrel. Although proteins exist that target the growing distal tips of centrioles, such as CP110 and Cep97, these proteins are generally thought to suppress centriolar microtubule growth, suggesting that distal tips may also contain unidentified counteracting factors that facilitate microtubule polymerization. Currently, a mechanistic understanding of how distal tip proteins balance microtubule growth and shrinkage to either promote daughter centriole elongation or maintain centriole length is lacking. Using a proximity-labeling screen in Drosophila cells, we identified Cep104 as a novel component of a group of evolutionarily conserved proteins that we collectively refer to as the distal tip complex (DTC). We found that Cep104 regulates centriole growth and promotes centriole elongation through its microtubule-binding TOG domain. Furthermore, analysis of Cep104 null flies revealed that Cep104 and Cep97 cooperate during spermiogenesis to align spermatids and coordinate individualization. Lastly, we mapped the complete DTC interactome and showed that Cep97 is the central scaffolding unit required to recruit DTC components to the distal tip of centrioles., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: The diagnostic workup of individuals suspected of having lung cancer can be complex and protracted because conventional symptoms of lung cancer have low specificity and sensitivity., Research Question: Among individuals with symptoms of lung cancer, can a blood-based approach to analyze cell-free DNA (cfDNA) fragmentation (the DNA evaluation of fragments for early interception [DELFI] score) enhance evaluation for the possible presence of lung cancer?, Study Design and Methods: Adults were referred to Bispebjerg Hospital (Copenhagen, Denmark) for diagnostic evaluation of initial imaging anomalies and symptoms consistent with lung cancer. Numbers and types of symptoms were extracted from medical records. cfDNA from plasma samples obtained at the prediagnostic visit was isolated, sequenced, and analyzed for genome-wide cfDNA fragmentation patterns. The relationships among clinical presentation, cancer status, and DELFI score were examined., Results: A total of 296 individuals were analyzed. Median DELFI scores were higher for those with lung cancer (n = 98) than those without cancer (n = 198; 0.94 vs 0.19; P < .001). In a multivariate model adjusted for age, smoking history, and presenting symptoms, the addition of the DELFI score improved the prediction of lung cancer for those who demonstrated symptoms (area under the receiver operating characteristic curve, 0.74-0.94)., Interpretation: The DELFI score distinguishes individuals with lung cancer from those without cancer better than suspicious symptoms do. These results represent proof-of-concept support that fragmentation-based biomarker approaches may facilitate diagnostic resolution for patients with concerning symptoms of lung cancer., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Introduction: The global nursing workforce is predominantly female, with a large proportion working in the 45-55 age group. Menopause is a transition for all women, and; therefore needs recognition as it can impact work performance and consequently staff turnover., Background: Women will go through the menopause, but not all women are affected. The menopause transition presents a range of signs and symptoms both physical and psychological which can impact the quality of life and individuals' work/life balance. The nursing workforce is predominantly women that will work through the menopause transition., Objectives: The study explored perspectives on digital health interventions as strategies to support menopausal women and to understand the requirements for designing health interventions for support in the workplace., Design: A qualitative explorative design., Settings: Nurses working in a range of clinical settings in England, Finland, Denmark, New Zealand, Australia and USA., Methods: Nurses (n = 48) participated in focus groups from six different countries from February 2020-June 2022 during the pandemic from a range of acute, primary care and education settings. Nurses were invited to participate to share their experiences. Thematic analysis was used., Results: All participants were able to describe the physical symptoms of menopause, with some cultural and possible hemisphere differences; more noticeable was the psychological burden of menopause and fatigue that is not always recognized. Four themes were identified: Managing symptoms in the workplace; Recognition in the workplace; Menopause interventions; and Expectation versus the invisible reality. These themes revealed information that can be translated for implementation into digital health interventions., Conclusions: Managers of nursing female staff in the menopausal age range need greater awareness, and menopause education should involve everyone. Finally, our results demonstrate design attributes suitable for inclusion in digital health strategies that are aligned with likely alleviation of some of the discomforts of menopause., Patient or Public Contribution: No patient or public contribution., (© 2023 The Authors. Journal of Advanced Nursing published by John Wiley & Sons Ltd.)

Centrosomes are essential parts of diverse cellular processes, and precise regulation of the levels of their constituent proteins is critical for their function. One such protein is Pericentrin (PCNT) in humans and Pericentrin-like protein (PLP) in Drosophila . Increased PCNT expression and its protein accumulation are linked to clinical conditions including cancer, mental disorders, and ciliopathies. However, the mechanisms by which PCNT levels are regulated remain underexplored. Our previous study demonstrated that PLP levels are sharply down-regulated during early spermatogenesis and this regulation is essential to spatially position PLP on the proximal end of centrioles. We hypothesized that the sharp drop in PLP protein was a result of rapid protein degradation during the male germ line premeiotic G2 phase. Here, we show that PLP is subject to ubiquitin-mediated degradation and identify multiple proteins that promote the reduction of PLP levels in spermatocytes, including the UBR box containing E3 ligase Poe (UBR4), which we show binds to PLP. Although protein sequences governing posttranslational regulation of PLP are not restricted to a single region of the protein, we identify a region that is required for Poe-mediated degradation. Experimentally stabilizing PLP, via internal PLP deletions or loss of Poe, leads to PLP accumulation in spermatocytes, its mispositioning along centrioles, and defects in centriole docking in spermatids.

Background: Despite conflicting data, intravenous lipid emulsion has emerged as a potential antidote. The "lipid sink" theory suggests that following intravenous administration of lipid, lipophilic drugs are sequestered in the vascular compartment, thereby reducing their tissue concentrations. This study sought to determine if survival is associated with the intoxicant's degree of lipophilicity., Methods: We reviewed all cases in the Toxicology Investigators Consortium's lipid sub-registry between May 2012 through December 2018. Information collected included demographics, exposure circumstances, clinical course, management, disposition, and outcome. The primary outcome was survival after lipid emulsion therapy. Survival was stratified by the log of the intoxicant's octanol-water partition coefficient. We also assessed the association between intoxicant lipophilicity and an increase in systolic blood pressure after lipid emulsion administration., Results: We identified 134 patients, including 81 (60.4%) females. The median age was 40 years (interquartile range 21-75). One hundred and eight (80.6%) patients survived, including 45 (33.6%) with cardiac arrest during their intoxication. Eighty-two (61.2%) were hypotensive, and 98 (73.1%) received mechanical ventilation. There was no relationship between survival and the log of the partition coefficient of the intoxicant on linear analysis ( P  = 0.89) or polynomial model ( P  = 0.10). Systolic blood pressure increased in both groups. The median (interquartile range) systolic blood pressure before lipid administration was 68 (60-78) mmHg for those intoxicants with a log partition coefficient < 3.6 compared with 89 (76-104) mmHg after lipid administration. Among those drugs with a log partition coefficient > 3.6, the median (interquartile range) was 69 (60-84) mmHg before lipid and 89 (80-96) mmHg after lipid administration., Conclusion: Most patients in this cohort survived. Lipophilicity was not correlated with survival or the observed changes in blood pressure. The study did not address the efficacy of lipid emulsion.

Centrosomes are multi-protein organelles that function as microtubule (MT) organizing centers (MTOCs), ensuring spindle formation and chromosome segregation during cell division. 1 , 2 , 3 Centrosome structure includes core centrioles that recruit pericentriolar material (PCM) that anchors γ-tubulin to nucleate MTs. 1 , 2 In Drosophila melanogaster, PCM organization depends on proper regulation of proteins like Spd-2, which dynamically localizes to centrosomes and is required for PCM, γ-tubulin, and MTOC activity in brain neuroblast (NB) mitosis and male spermatocyte (SC) meiosis. 4 , 5 , 6 , 7 , 8 Some cells have distinct requirements for MTOC activity due to differences in characteristics like cell size 9 , 10 or whether they are mitotic or meiotic. 11 , 12 How centrosome proteins achieve cell-type-specific functional differences is poorly understood. Previous work identified alternative splicing 13 and binding partners 14 as contributors to cell-type-specific differences in centrosome function. Gene duplication, which can generate paralogs with specialized functions, 15 , 16 is also implicated in centrosome gene evolution, 17 including cell-type-specific centrosome genes. 18 , 19 To gain insight into cell-type-specific differences in centrosome protein function and regulation, we investigated a duplication of Spd-2 in Drosophila willistoni, which has Spd-2A (ancestral) and Spd-2B (derived). We find that Spd-2A functions in NB mitosis, whereas Spd-2B functions in SC meiosis. Ectopically expressed Spd-2B accumulates and functions in mitotic NBs, but ectopically expressed Spd-2A failed to accumulate in meiotic SCs, suggesting cell-type-specific differences in translation or protein stability. We mapped this failure to accumulate and function in meiosis to the C-terminal tail domain of Spd-2A, revealing a novel regulatory mechanism that can potentially achieve differences in PCM function across cell types., Competing Interests: Declaration of interests The authors declare no competing interests., (Published by Elsevier Inc.)

In the machine learning subfield of natural language processing, a topic model is a type of unsupervised method that is used to uncover abstract topics within a corpus of text. Dynamic topic modelling (DTM) is used for capturing change in these topics over time. The study deploys DTM on corpus of electronic health record psychotherapy notes. This retrospective study examines whether DTM helps distinguish closely matched patients that did and did not die by suicide. Cohort consists of United States Department of Veterans Affairs (VA) patients diagnosed with Posttraumatic Stress Disorder (PTSD) between 2004 and 2013. Each case (those who died by suicide during the year following diagnosis) was matched with five controls (those who remained alive) that shared psychotherapists and had similar suicide risk based on VA's suicide prediction algorithm. Cohort was restricted to patients who received psychotherapy for 9+ months after initial PTSD diagnoses (cases = 77; controls = 362). For cases, psychotherapy notes from diagnosis until death were examined. For controls, psychotherapy notes from diagnosis until matched case's death date were examined. A Python-based DTM algorithm was utilized. Derived topics identified population-specific themes, including PTSD, psychotherapy, medication, communication and relationships. Control topics changed significantly more over time than case topics. Topic differences highlighted engagement, expressivity and therapeutic alliance. This study strengthens groundwork for deriving population-specific, psychosocial and time-sensitive suicide risk variables., (Published 2023. This article is a U.S. Government work and is in the public domain in the USA.)

Each year, infections from major foodborne pathogens are responsible for an estimated 9.4 million illnesses, 56,000 hospitalizations, and 1,350 deaths in the United States (1). To evaluate progress toward prevention of enteric infections in the United States, the Foodborne Diseases Active Surveillance Network (FoodNet) conducts surveillance for laboratory-diagnosed infections caused by eight pathogens transmitted commonly through food at 10 U.S. sites. During 2020-2021, FoodNet detected decreases in many infections that were due to behavioral modifications, public health interventions, and changes in health care-seeking and testing practices during the COVID-19 pandemic. This report presents preliminary estimates of pathogen-specific annual incidences during 2022, compared with average annual incidences during 2016-2018, the reference period for the U.S. Department of Health and Human Services' Healthy People 2030 targets (2). Many pandemic interventions ended by 2022, resulting in a resumption of outbreaks, international travel, and other factors leading to enteric infections. During 2022, annual incidences of illnesses caused by the pathogens Campylobacter, Salmonella, Shigella, and Listeria were similar to average annual incidences during 2016-2018; however, incidences of Shiga toxin-producing Escherichia coli (STEC), Yersinia, Vibrio, and Cyclospora illnesses were higher. Increasing culture-independent diagnostic test (CIDT) usage likely contributed to increased detection by identifying infections that would have remained undetected before widespread CIDT usage. Reducing pathogen contamination during poultry slaughter and processing of leafy greens requires collaboration among food growers and processors, retail stores, restaurants, and regulators., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. Elaine Scallan Walter reports consulting fees for a peer review of a Salmonella risk profile for the U.S. Department of Agriculture Food Safety and Inspection Service via RTI International during 2022. No other potential conflicts of interest were disclosed.

Background: Addressing racism in emergency medicine education is vital for providing optimal training and assessment of physicians in the specialty, developing physicians with the skills necessary to advocate for their patients, and recruiting and retaining a diverse group of physicians. To form a prioritized research agenda, the Society of Academic Emergency Medicine (SAEM) conducted a consensus conference at the annual meeting in May 2022 on addressing racism in emergency medicine, which included a subgroup on education., Methods: The education workgroup worked on summarizing the current literature on addressing racism in emergency medicine education, identifying critical knowledge gaps, and creating a consensus-driven research agenda for addressing racism in emergency medicine education. We used a nominal group technique and modified Delphi to develop priority questions for research. We then distributed a pre-conference survey to conference registrants to rate priority areas for research. During the consensus conference, group leaders provided an overview and background describing the rationale for the preliminary research question list. Attendees were then involved in discussions to help modify and develop research questions., Results: Nineteen questions were initially selected by the education workgroup as potential areas for research. The education workgroup's next round of consensus building resulted in a consensus of ten questions to be included in the pre-conference survey. No questions in the pre-conference survey reached consensus. After robust discussion and voting by workgroup members and attendees at the consensus conference, six questions were determined to be priority research areas., Conclusions: We believe recognizing and addressing racism in emergency medicine education is imperative. Critical gaps in curriculum design, assessment, bias training, allyship, and the learning environment negatively impact training programs. These gaps must be prioritized for research as they can have adverse effects on recruitment, the ability to promote a safe learning environment, patient care, and patient outcomes., Competing Interests: The authors declare no conflicts of interest., (© 2023 Society for Academic Emergency Medicine.)

In this study, we highlight patients' experiences with metal hypersensitivity (MH) after receiving implantable medical devices (IMDs). We aim to identify gaps in clinical care and improve outcomes for individuals who have or may be sensitive to metals. Secondary data analysis from a previous interpretative phenomenological qualitative study was utilized. Using patient journey maps, we explored the experiences of 8 individuals from outpatient settings who received IMD and have first-hand experience with MH. We documented their journey from MH symptom recognition to diagnosis and subsequent IMD management. The results reveal that the time frames from device implantation to the treatment of MH varied from 17 to 228 months. The longest phase on the patient journey maps was the symptom recognition phase, which refers to the time between symptom emergence and MH diagnosis. Participants also required extensive healthcare utilization following their initial surgery. These findings emphasize that MH should be considered in differential diagnoses for patients with IMD. Early screening and detection of MH can enhance patient safety, alleviate distress, and reduce unnecessary healthcare utilization., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2023.)

Background: Despite the increased uptake of intravascular lithotripsy (IVL) for treating severely calcified coronary lesions, there is limited patient-level data examining the effect of IVL on quality of life, symptomatology, and outcomes beyond 30 days. We sought to assess demographics, procedural characteristics, outcomes, and impact of IVL on patient-reported angina after a minimum of 6 months follow-up., Methods: A retrospective single-center study was conducted of patients treated with coronary IVL between January and October 2020. Baseline demographics were obtained from electronic patient records and SYNTAX scores were calculated from index coronary angiograms. Technical success and complications were assessed along with clinical outcomes, which included all-cause mortality, myocardial infarction (MI), target lesion revascularization (TLR), and MACE (composite of death, stroke, MI, and TLR). Canadian Cardiovascular Society (CCS) angina classification was assessed at virtual clinical follow-up., Results: Forty-seven consecutive patients were included. At a mean follow-up of 306 ± 74 days, the mean CCS angina score was reduced by 53% post-IVL-assisted PCI (2.9 vs 1.4, p < 0.001). Technical and procedural success were high (94% and 92%, respectively). One patient (2%) met the pre-specified criteria for in-hospital MACE and 4 (9%) met pre-specified MACE at follow-up, including 2 deaths and 2 TLR. Procedural complications included coronary dissection (11%) and coronary perforation (6%) and were managed either conservatively or with PCI., Conclusions: Coronary IVL is a safe and effective adjunctive therapy for treating heavily calcified coronary lesions. This cohort shows high procedural success and a significant reduction in CCS angina at follow-up., (© 2022. The Author(s), under exclusive licence to Royal Academy of Medicine in Ireland.)

Background: Vitamin B 12 (VB12) deficiency is a well-described complication post-gastrectomy. It is caused by the loss of parietal cell mass leading to megaloblastic anaemia. This closed-loop audit assesses patient understanding of and adherence with VB12 supplementation guidelines post-gastrectomy., Methods: A closed-loop audit cycle was performed. After the first cycle, an educational intervention was actioned prior to re-audit. One hundred twenty-five patients who underwent gastrectomy between 2010 and 2020 were available for study (86 total gastrectomies (TG), 39 subtotal gastrectomies (STG)). Twenty-nine patients who had not been adherent with VB12 supplementation/surveillance were eligible for re-audit., Results: 91.9% (79/86) of TG patients reported adherence in regular parenteral VB12 supplementation. Adherence was significantly lower for STG for checking (and/or replacing) their VB12, with only 53.8% (21/39) checking their VB12 levels. 67/125 (53.6%) of the patients stated that they knew it was important to supplement B 12 post-gastrectomy. 37.8% (43/113) of participants could explain why this was important, and 14.4% (18/125) had any knowledge of the complications of VB12 deficiency. Following re-audit, 5/8 (57.5%) of TG patients who had not been adherent with VB12 supplementation in the first cycle were now adherent with VB12 supplementation following our educational intervention. 7/17 (41.2%) of the STG group had received VB12 or made arrangements to receive supplemental VB12 if it was indicated., Conclusion: This study demonstrates good adherence in those undergoing TG. Patient understanding correlates with adherence, suggesting that patient education and knowledge reinforcement may be key to adherence with VB12 supplementation. A simple educational intervention can improve adherence with VB12 supplementation in patients undergoing gastrectomy., (© 2022. The Author(s), under exclusive licence to Royal Academy of Medicine in Ireland.)

Objective: To quantitatively compare the ergonomic risk of otologic surgeries performed with endoscopes and microscopes., Study Design: Observational cross-sectional study., Setting: Operating room of a tertiary academic medical center., Methods: Intraoperative neck angles of otolaryngology attendings, fellows, and residents were assessed during 17 otologic surgeries using inertial measurement unit sensors. Sensors were attached midline between the shoulder blades and on the posterior scalp of participants and were calibrated just prior to beginning each case. Quaternion data were used to calculate neck angles during periods of active surgery., Results: Endoscopic and microscopic cases included similar percentages of time in high-risk neck positions, 75% and 73%, respectively, according to a validated ergonomic risk assessment tool, the Rapid Upper Limb Assessment. However, microscopic cases included a higher percentage of time spent in extension (25%) compared to endoscopic cases (12%) (p < .001). When examining the magnitude of average flexion and extension angles, endoscopic and microscopic cases were not significantly different., Conclusion: Utilizing intraoperative sensor data, we found that both endoscopic and microscopic approaches in otologic surgery were associated with high-risk neck angles, which can result in sustained neck strain. These results suggest that optimal ergonomics may be better achieved by the consistent application of basic ergonomic principles than by changing the technology in the operating room., (© 2023 The Authors. Otolaryngology-Head and Neck Surgery published by Wiley Periodicals LLC on behalf of American Academy of Otolaryngology-Head and Neck Surgery Foundation.)

Introduction/aims: IC14 (atibuclimab) is a monoclonal anti-CD14 antibody. A previous phase 1 trial of 10 participants with amyotrophic lateral sclerosis (ALS) demonstrated initial safety of IC14 in an acute treatment setting. We provided long-term treatment with IC14 to individuals with ALS via an expanded access protocol (EAP) and documented target engagement, biomarker, safety, and disease endpoints., Methods: Participants received intravenous IC14 every 2 weeks. Consistent with United States Food and Drug Administration guidelines, participants were not eligible for clinical trials and the EAP was inclusive of a broad population. Whole blood and serum were collected to determine monocyte CD14 receptor occupancy (RO), IC14 levels, and antidrug antibodies. Ex vivo T-regulatory functional assays were performed in a subset of participants., Results: Seventeen participants received IC14 for up to 103 weeks (average, 30.1 weeks; range, 1 to 103 weeks). Treatment-emergent adverse events (TEAEs) were uncommon, mild, and self-limiting. There were 18 serious adverse events (SAEs), which were related to disease progression and unrelated or likely unrelated to IC14. Three participants died due to disease progression. Monocyte CD14 RO increased for all participants after IC14 infusion. One individual required more frequent dosing (every 10 days) to achieve over 80% RO. Antidrug antibodies were detected in only one participant and were transient, low titer, and non-neutralizing., Discussion: Administration of IC14 in ALS was safe and well-tolerated in this intermediate-size EAP. Measuring RO guided dosing frequency. Additional placebo-controlled trials are required to determine the efficacy of IC14 in ALS., (© 2022 The Authors. Muscle & Nerve published by Wiley Periodicals LLC.)

Purpose: With the initial analysis of POLLUX at a median follow-up of 13.5 months, daratumumab in combination with lenalidomide and dexamethasone (D-Rd) significantly prolonged progression-free survival versus lenalidomide and dexamethasone (Rd) alone in patients with relapsed or refractory multiple myeloma (RRMM). We report updated efficacy and safety results at the time of final analysis for overall survival (OS)., Methods: POLLUX was a multicenter, randomized, open-label, phase III study during which eligible patients with ≥ 1 line of prior therapy were randomly assigned 1:1 to D-Rd or Rd until disease progression or unacceptable toxicity. After positive primary analysis and protocol amendment, patients receiving Rd were offered daratumumab monotherapy after disease progression., Results: Significant OS benefit was observed with D-Rd (hazard ratio, 0.73; 95% CI, 0.58 to 0.91; P = .0044) at a median (range) follow-up of 79.7 months (0.0-86.5). The median OS was 67.6 months for D-Rd compared with 51.8 months for Rd. Prespecified analyses demonstrated an improved OS with D-Rd versus Rd in most subgroups, including patients age ≥ 65 years and patients with one, two, or three prior lines of therapy, International Staging System stage III disease, high-risk cytogenetic abnormalities, and refractoriness to their last prior line of therapy or a proteasome inhibitor. The most common (≥ 10%) grade 3/4 treatment-emergent adverse events with D-Rd versus Rd were neutropenia (57.6% v 41.6%), anemia (19.8% v 22.4%), pneumonia (17.3% v 11.0%), thrombocytopenia (15.5% v 15.7%), and diarrhea (10.2% v 3.9%)., Conclusion: D-Rd significantly extended OS versus Rd alone in patients with RRMM. To our knowledge, for the first time, our findings, together with the OS benefit observed with daratumumab plus bortezomib and dexamethasone in the phase III CASTOR trial, demonstrate OS improvement with daratumumab-containing regimens in RRMM (ClinicalTrials.gov identifier: NCT02076009 [POLLUX]).

Purpose: At the primary analysis of CASTOR (median follow-up, 7.4 months), daratumumab plus bortezomib and dexamethasone (D-Vd) significantly prolonged progression-free survival versus bortezomib and dexamethasone (Vd) alone in relapsed or refractory multiple myeloma (RRMM). We report updated efficacy and safety results at the final analysis for overall survival (OS)., Methods: CASTOR was a multicenter, randomized, open-label, phase III study during which eligible patients with ≥ 1 line of prior therapy were randomly assigned to Vd (up to eight cycles) with or without daratumumab (until disease progression). After positive primary analysis and protocol amendment, patients receiving Vd were offered daratumumab monotherapy after disease progression., Results: At a median (range) follow-up of 72.6 months (0.0-79.8), significant OS benefit was observed with D-Vd (hazard ratio, 0.74; 95% CI, 0.59 to 0.92; P = .0075). Median OS was 49.6 months with D-Vd versus 38.5 months with Vd. Prespecified subgroup analyses demonstrated an OS advantage with D-Vd versus Vd for most subgroups, including patients age ≥ 65 years and patients with one or two prior lines of therapy, International Staging System stage III disease, high-risk cytogenetic abnormalities, and prior bortezomib treatment. The most common (≥ 10%) grade 3/4 treatment-emergent adverse events with D-Vd versus Vd were thrombocytopenia (46.1% v 32.9%), anemia (16.0% v 16.0%), neutropenia (13.6% v 4.6%), lymphopenia (10.3% v 2.5%), and pneumonia (10.7% v 10.1%)., Conclusion: D-Vd significantly prolonged OS in patients with RRMM, with the greatest OS benefit observed in patients with one prior line of therapy. To our knowledge, our results, together with the OS benefit observed with daratumumab plus lenalidomide and dexamethasone in the phase III POLLUX study, demonstrate for the first time an OS benefit with daratumumab-containing regimens in RRMM (ClinicalTrials.gov identifier: NCT02136134 [CASTOR]).

Background: Transcatheter aortic valve replacement (TAVR) has been widely adopted for management of aortic stenosis. The purpose of this study was to examine regional access to and outcomes following TAVR in California., Methods: Patients undergoing TAVR or isolated surgical aortic valve replacement (SAVR) from 2008 to 2019 in California were identified in the Office of Statewide Health Planning and Development database. California was divided into seven regions: Northern California, San Francisco Bay Area, Central California, Los Angeles, Inland Empire, Orange, and San Diego. Regional TAVR volumes were normalized to Medicare beneficiaries or isolated SAVR volume. Outcomes included risk-adjusted 30-day mortality and major adverse cardiovascular and cerebral events (MACCE). Trends were studied using non-parametric tests, and regional outcomes using logistic regression., Results: TAVR volume increased annually since 2011, with 7148 cases performed in California in 2019. After normalization, variation in utilization of TAVR was evident, with the least performed in Central California. TAVR to SAVR ratios in 2019 were greatest in Northern California, Los Angeles, and San Diego, and least in the Inland Empire. After risk adjustment, there were no significant regional differences in 30-day mortality, but lower 30-day MACCE in the San Francisco Bay Area., Conclusions: Regional differences in TAVR utilization exist, with limited access in Central California and the Inland Empire, but risk-adjusted outcomes are similar. Efforts to reach underserved areas through existing program expansion or regional referrals may distribute transcatheter technology more equitably across California., Competing Interests: Declaration of competing interest One of the authors (RJS) serves as a consultant to the Edwards Lifesciences Advisory Board and Co-Principal Investigator on PARTNER II Trial. The remainder of the authors reports no pertinent conflicts of interest., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Spinal cord ischemia remains a devastating complication when treating patients with complex thoracoabdominal aortic aneurysms using fenestrated endovascular aortic repair. This approach is progressively deployed. However, to date, no strategy has been identified to reduce the feared risk of spinal cord ischemia., Objective: To introduce a novel bypass technique using a customized composite graft to create a direct extra-anatomic revascularization before fenestrated endovascular aortic repair in patients with high-risk of spinal cord ischemia., Methods: To demonstrate this novel concept, we present here a clinical case that reports the strategy of this novel concept in detail. An 83-year-old man with medical history of endovascular repair of an abdominal aortic aneurysm and thoracic aorta presented with a type IA endoleak, located along the posterior superior aspect of the aortic stent graft adjacent to the lumbar arteries. A multidisciplinary plan was developed, which included a novel bypass from the profunda femoris to the left L1 radicular artery before fenestrated endovascular aortic repair to prevent spinal cord ischemia., Results: The patient successfully receives the novel extra-anatomic revascularization bypass before fenestrated endovascular aortic repair. During the first implementation of this strategy, no intraoperative difficulties and postoperative complications were observed., Conclusion: This case demonstrates a novel surgical technique before fenestrated endovascular aortic repair for prevention of spinal cord ischemia. In addition, this concept provides a promising direction to not only complement the existing surgical techniques but also to generate more future innovations., (Copyright © Congress of Neurological Surgeons 2022. All rights reserved.)

Background: The American Society of Breast Surgeons recommends genetic testing (GT) for all women with breast cancer (BC), but implementation and uptake of GT has not been well-described., Methods: A retrospective chart review was performed for newly diagnosed BC patients or patients with a newly identified recurrence of BC seen in a multidisciplinary clinic (MDBC) who were offered genetic counseling (GC) and GT., Results: The 138 women attending the MDBC had a median age of 54 years and comprised non-Hispanic whites (46%), Asians (28%), Hispanics (17%), blacks (4%), and other (5%). Of the 105 (76%) patients without prior GT, 100 (95%) accepted GC, with 93 (93%) of these 100 patients undergoing GT. The patients meeting the National Comprehensive Cancer Network (NCCN) guidelines for GT were more likely to undergo GT. Testing was performed with a 67- to 84-gene panel, together with an 8- to 9-gene STAT panel if needed. Among 120 patients with reports available, including 33 patients previously tested, 15 (12%) were positive (1 BLM, 1 BRCA1, 3 BRCA2, 1 BRIP1, 1 CFTR, 1 CHEK2, 1 MUTYH, 1 PALB2, 1 PRSS1, 1 RAD50, 1 RET, and 2 TP53), 44 (37%) were negative, and 61 (51%) had an uncertain variant. The median time to STAT results (n = 50) was 8 days. The STAT results were available before surgery for 47 (98%) of the 48 STAT patients undergoing surgery., Conclusions: New BC patients attending the MDBC demonstrated high rates of acceptance of GC and GT. The combination of GC and GT can offer timely information critical to patient risk assessment and treatment planning., (© 2022. Society of Surgical Oncology.)

Sequencing herbarium specimens can be instrumental in answering ecological, evolutionary, and taxonomic inquiries. We developed a protocol for sequencing herbarium specimens of rust fungi (Pucciniales) and proceeded to sequence specimens ranging from 4 to 211 yr old from five different genera. We then obtained sequences from an economically important biological control agent, Puccinia suaveolens, to highlight the potential of sequencing herbarium specimens in an ecological sense and to evaluate the following hypotheses: (1) The population structure of a plant pathogen changes over time, and (2) introduced pathogens are more diverse in their native range. Our efforts resulted in sequences from 87 herbarium specimens that revealed a high level of diversity with a population structure that exhibited spatial-temporal patterns. The specimens sequenced from Europe showed more diversity than the ones from North America, uncovering an invasion pattern likely related to its European native host in North America. Additionally, to the best of our knowledge, the specimen from France collected in c. 1811 is the oldest herbarium specimen sequenced from kingdom Fungi. In conclusion, sequencing old herbarium specimens is an important tool that can be extrapolated to better understand plant-microbe evolution and to evaluate old type specimens to solidify the taxonomy of plant pathogenic fungi., (© 2022 His Majesty the King in Right of Canada and The Authors New Phytologist © 2022 New Phytologist Foundation. Reproduced with the permission of the Minister of Agricultural and Agri-Food Canada. This article has been contributed to by US Government employees and their work is in the public domain in the USA.)

Background and Aims: The 'inverse care law', first described in 1971, results from a mismatch of healthcare need and healthcare supply in deprived areas. GPs in such areas struggle to cope with the high levels of demand resulting in shorter consultations and poorer patient outcomes. We compare recent national GP and patient satisfaction data to investigate the ongoing existence of this disparity in Scotland., Methods and Results: Secondary analysis of cross-sectional national surveys (2017/2018) on upper and lower deprivation quintiles. GP measures; job satisfaction, job stressors, positive and negative job attributes. Patient measures; percentage positive responses per practice on survey questions on access and consultation quality. GPs in high deprivation areas reported lower job satisfaction and positive job attributes, and higher job stressors and negative job attributes compared with GPs in low deprivation areas. Patients living in high deprivation areas reported lower satisfaction with access and consultation quality than patients in low deprivation areas. These differences in GP and patient satisfaction persisted after adjusting for confounding variables., Conclusions: Lower GP work satisfaction in deprived areas was mirrored by lower patient satisfaction. These findings add to the evidence that the inverse care law persists in Scotland, over 50 years after it was first described.