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Despite expensive investments in DEI programs, research within a non-profit reveals rhetorical race-consciousness rather than real-deal change.

Obesity-induced insulin resistance leads to the metabolic syndrome. Both bariatric surgery and surgical fat removal have been shown to improve metabolic health, but the metabolic benefits of nonsurgical fat removal remain uncertain. The aim of this paper is to establish whether nonsurgical fat removal exerts measurable, lasting metabolic benefits by way of changes to serum lipid profiles.PubMed, Cochrane CENTRAL, Embase, and clinical trials registers were searched using the Polyglot Search Translator to find studies examining quantitative changes in metabolic markers after nonsurgical body contouring procedures. The MethodologicAl STandard for Epidemiological Research (MASTER) scale was adopted for the quality assessment of the included studies. The robust-error meta-regression (REMR) model was employed.Twenty-two studies and 676 participants were included. Peak body compositions measures manifest as a reduction of 2 units in body mass index (BMI), 1 kg of body weight (BW), 5 cm in waist circumference (WC) and 1.5 cm in abdominal fat thickness (FT), sustained up to 60 days postprocedure. Transient increases of 15 mg/dL in low-density lipoprotein (LDL), 10 mg/dl in triglycerides (TG), and 15 mg/dl in total cholesterol (TC) were observed at 2 weeks postprocedure.While nonsurgical fat removal exerts sustained effects on body anthropometrics, changes to serum lipid profiles were transient. There is no compelling evidence at present to support the conclusion that nonsurgical fat removal is metabolically beneficial.

Although extracellular vesicles (EVs) were discovered over 40 years ago, there has been a resurgence of interest in secreted vesicles and their attendant cargo as novel modes of intracellular communication. In addition to vesicles, two amembranous nanoparticles, exomeres and supermeres, have been isolated and characterized recently. In this rapidly expanding field, it has been challenging to assign cargo and specific functions to a particular carrier. Refinement of isolation methods, well-controlled studies, and guidelines detailed by Minimal Information for Studies of Extracellular Vesicles (MISEV) are being employed to “bring order to chaos.” In this review, we will briefly summarize three types of extracellular carriers - small EVs (sEVs), exomeres, and supermeres - in the context of colorectal cancer (CRC). We found that a number of GPI-anchored proteins (GPI-APs) are overexpressed in CRC, are enriched in exosomes (a distinct subset of sEVs), and can be detected in exomeres and supermeres. This affords the opportunity to elaborate on GPI-AP biogenesis, modifications, and trafficking using DPEP1, a GPI-AP upregulated in CRC, as a prime example. We have cataloged the GPI-anchored proteins secreted in CRC and will highlight features of select CRC-associated GPI-anchored proteins we have detected. Finally, we will discuss the remaining challenges and future opportunities in studying these secreted GPI-APs in CRC.

Mapping asymptomatic malaria infections, which contribute to the transmission reservoir, is important for elimination programs. This analysis compared the spatiotemporal patterns of symptomatic and asymptomatic Plasmodium falciparum malaria infections in a cohort study of ∼25,000 people living in a rural hypoendemic area of about 179 km2 in a small area of the Chittagong Hill Districts of Bangladesh. Asymptomatic infections were identified by active surveillance; symptomatic clinical cases presented for care. Infections were identified by a positive rapid diagnostic test and/or microscopy. Fifty-three subjects with asymptomatic P. falciparum infection were compared with 572 subjects with symptomatic P. falciparum between mid-October 2009 and mid-October 2012 with regard to seasonality, household location, and extent of spatial clustering. We found increased spatial clustering of symptomatic compared with asymptomatic infections, and the areas of high intensity were only sometimes overlapping. Symptomatic cases had a distinct seasonality, unlike asymptomatic infections, which were detected year-round. In a comparison of 42 symptomatic Plasmodium vivax and 777 symptomatic P. falciparum cases from mid-October 2009 through mid-March 2015, we found substantial spatial overlap in areas with high infection rates, but the areas with the greatest concentration of infection differed. Detection of both symptomatic P. falciparum and symptomatic P. vivax infections was greater during the May-to-October high season, although a greater proportion of P. falciparum cases occurred during the high season compared with P. vivax. These findings reinforce that passive malaria surveillance and treatment of symptomatic cases will not eliminate the asymptomatic reservoirs that occur distinctly in time and space.

There has been significant progress in the study of extracellular vesicles (EVs) since the 2017 American Gastroenterological Association-sponsored Freston Conference "Extracellular Vesicles: Biology, Translation and Clinical Application in GI Disorders." The burgeoning interest in this field stems from the increasing recognition that EVs represent an understudied form of cell-to-cell communication and contain cargo replete with biomarkers and therapeutic targets. This short review will highlight recent advances in the field, with an emphasis on colorectal cancer. After a brief introduction to secreted particles, we will describe how our laboratory became interested in EVs, which led to refined methods of isolation and identification of 2 secreted nanoparticles. We will then summarize the cargo found in small EVs released from colorectal cancer cells and other cells in the tumor microenvironment, as well as those found in the circulation of patients with colorectal cancer. Finally, we will consider the continuing challenges and future opportunities in this rapidly evolving field.

Published standards for the management of open extremity fractures have improved limb salvage, fracture union, and deep infection rates, but the aesthetic and functional importance of our flap choices has been overlooked. Thin and superthin free flaps exhibit advantages over traditional free flaps in some situations but have seldom been reported in children. The aim of this paper is to present our experience of thin and superthin free flaps in pediatric extremity reconstruction.Children (≤13 years) who underwent soft tissue reconstruction using a thin and superthin free flap following major extremity trauma are presented.Five patients (5 flaps) met the inclusion criteria. The median age was 9 (range 6-13). There were 3 Gustilo IIIB open fractures and 2 multiplanar degloving injuries. The median mangled extremity severity score (MESS) was 4 (range 2-6). The median time from injury to definitive soft tissue closure was 72 h (range 28-120 h). Four anterolateral thigh (ALT) flaps were raised as thin flaps, and 1 superficial circumflex iliac artery perforator (SCIP) was raised as a superthin flap. There was one re-exploration owing to venous congestion, and a second venous anastomosis was performed to enhance flap drainage. The same ALT flap exhibited necrosis at one margin, which was debrided and grafted before discharge. There were no other flap complications. No flap-related secondary surgeries were required.Thin and superthin free flaps are viable options in pediatric extremity reconstruction. They exhibit excellent aesthetic and functional contouring when a slender fasciocutaneous flap is needed, especially when body habitus renders traditional options unfavorable.

Urine cytology is commonly used as a screening test for high-grade urothelial carcinoma for patients with risk factors or hematuria and is an essential step in longitudinal monitoring of patients with previous bladder cancer history. However, the semisubjective nature of current reporting systems for urine cytology (e.g., The Paris System) can hamper reproducibility. For instance, the incorporation of urothelial cell clusters into the classification schema is still an item of debate and perplexity among expert cytopathologists because several previous works have disputed their diagnostic relevance.In this work, an automated preprocessing tool for urothelial cell cluster assessment was developed that divides urothelial cell clusters into meaningful components for downstream assessment (ie, population-based studies, workflow automation).In this work, an automated preprocessing tool for urothelial cell cluster assessment was developed that divides urothelial cell clusters into meaningful components for downstream assessment (ie, population-based studies, workflow automation). Results indicate that cell cluster atypia (i.e., defined by whether the cell cluster harbored multiple atypical cells, thresholded by a minimum number of cells), cell border overlap and smoothness, and total number of clusters are important markers of specimen atypia when considering assessment of urothelial cell clusters.Markers established through techniques to separate cell clusters may have wider applicability for the design and implementation of machine learning approaches for urine cytology assessment.

The Costa Rican pygmy rice rat (Oligoryzomys costaricensis) is the primary reservoir of Choclo orthohantavirus (CHOV), the causal agent of hantavirus disease, pulmonary syndrome, and fever in humans in Panama. Since the emergence of CHOV in early 2000, we have systematically sampled and archived rodents from >150 sites across Panama to establish a baseline understanding of the host and virus, producing a permanent archive of holistic specimens that we are now probing in greater detail. We summarize these collections and explore preliminary habitat/virus associations to guide future wildlife surveillance and public health efforts related to CHOV and other zoonotic pathogens. Host sequences of the mitochondrial cytochrome b gene form a single monophyletic clade in Panama, despite wide distribution across Panama. Seropositive samples were concentrated in the central region of western Panama, consistent with the ecology of this agricultural commensal and the higher incidence of CHOV in humans in that region. Hantavirus seroprevalence in the pygmy rice rat was >15% overall, with the highest prevalence in agricultural areas (21%) and the lowest prevalence in shrublands (11%). Host–pathogen distribution, transmission dynamics, genomic evolution, and habitat affinities can be derived from the preserved samples, which include frozen tissues, and now provide a foundation for expanded investigations of orthohantaviruses in Panama.

Background Alcohol use disorders (AUD) are prevalent and often go untreated. Patients are commonly screened for AUD in primary care, but existing treatment programs are failing to meet demand. Digital therapeutics include novel mobile app-based treatment approaches which may be cost-effective treatment options to help fill treatment gaps. The goal of this study was to identify implementation needs and workflow design considerations for integrating digital therapeutics for AUD into primary care. Methods We conducted qualitative interviews with clinicians, care delivery leaders, and implementation staff (n = 16) in an integrated healthcare delivery system in the United States. All participants had experience implementing digital therapeutics for depression or substance use disorders in primary care. Interviews were designed to gain insights into adaptations needed to optimize existing clinical processes, workflows, and implementation strategies for use with alcohol-focused digital therapeutics. Interviews were recorded and transcribed and then analyzed using a rapid analysis process and affinity diagramming. Results Qualitative themes were well represented across health system staff roles. Participants were enthusiastic about digital therapeutics for AUD, anticipated high patient demand for such a resource, and made suggestions for successful implementation. Key insights regarding the implementation of digital therapeutics for AUD and unhealthy alcohol use from our data include: (1) implementation strategy selection must be driven by digital therapeutic design and target population characteristics, (2) implementation strategies should seek to minimize burden on clinicians given the large numbers of patients with AUD who are likely to be interested in and eligible for digital therapeutics, and (3) digital therapeutics should be offered alongside many other treatment options to accommodate individual patients’ AUD severity and treatment goals. Participants also expressed confidence that previous implementation strategies used with other digital therapeutics such as clinician training, electronic health record supports, health coaching, and practice facilitation would be effective for the implementation of digital therapeutics for AUD. Conclusions The implementation of digital therapeutics for AUD would benefit from careful consideration of the target population. Optimal integration requires tailoring workflows to meet anticipated patient volume and designing workflow and implementation strategies to meet the unique needs of patients with varying AUD severity.

Background Most people with opioid use disorder (OUD) have co-occurring substance use, which is associated with lower receipt of OUD medications (MOUD). Expanding MOUD provision and care linkage outside of substance use disorder (SUD) specialty settings is a key strategy to increase access. Therefore, it is important to understand how MOUD providers in these settings approach care for patients with co-occurring substance use. This qualitative study of Veterans Health Administration (VA) clinicians providing buprenorphine care in primary care, mental health, and pain settings aimed to understand (1) their approach to addressing OUD in patients with co-occurring substance use, (2) perspectives on barriers/facilitators to MOUD receipt for this population, and (3) support needed to increase MOUD receipt for this population. Methods We interviewed a purposive sample of 27 clinicians (12 primary care, 7 mental health, 4 pain, 4 pharmacists) in the VA northwest network. The interview guide assessed domains of the Tailored Implementation for Chronic Diseases Checklist. Interviews were transcribed and qualitatively analyzed using inductive content analysis. Results Participants reported varied approaches to identifying co-occurring substance use and addressing OUD in this patient population. Although they reported that this topic was not clearly addressed in clinical guidelines or training, participants generally felt that patients with co-occurring substance use should receive MOUD. Some viewed their primary role as providing this care, others as facilitating linkage to OUD care in SUD specialty settings. Participants reported multiple barriers and facilitators to providing buprenorphine care to patients with co-occurring substance use and linking them to SUD specialty care, including provider, patient, organizational, and external factors. Conclusions Efforts are needed to support clinicians outside of SUD specialty settings in providing buprenorphine care to patients with co-occurring substance use. These could include clearer guidelines and policies, more specific training, and increased care integration or cross-disciplinary collaboration. Simultaneously, efforts are needed to improve linkage to specialty SUD care for patients who would benefit from and are willing to receive this care, which could include increased service availability and improved referral/hand-off processes. These efforts may increase MOUD receipt and improve OUD care quality for patients with co-occurring substance use.

This manuscript aims to contribute to the next phase of mechanisms of behavior change (MOBC) science on alcohol or other drug use. Specifically, we encourage the transition from a basic science orientation (i.e., knowledge generation) to a translational science orientation (i.e., knowledge application or Translational MOBC Science). To inform that transition, we examine MOBC science and implementation science and consider how these two research areas can intersect to capitalize on the goals, strengths, and key methodologies of each. First, we define MOBC science and implementation science and offer a brief historical rationale for these two areas of clinical research. Second, we summarize similarities in rationale and discuss two scenarios where one draws from the other-MOBC science on implementation strategy outcomes and implementation science on MOBC. We then focus on the latter scenario, and briefly review the MOBC knowledge base to consider its readiness for knowledge translation. Finally, we provide a series of research recommendations to facilitate the translation of MOBC science. These recommendations include: (1) identifying and targeting MOBC that are well suited for implementation, (2) use of MOBC research results to inform broader health behavior change theory, and (3) triangulation of a more diverse set of research methodologies to build a translational MOBC knowledge base. Ultimately, it is important for gains borne from MOBC science to affect direct patient care, while basic MOBC research continues to be developed and refined over time. Potential implications of these developments include greater clinical significance for MOBC science, an efficient feedback loop between clinical research methodologies, a multi-level approach to understanding behavioral change, and reduced or eliminated siloes between MOBC science and implementation science.

Working memory (WM) is an executive function that orchestrates the use of a limited amount of information, referred to as working memory capacity (WMC), in cognitive functions. In humans,Cannabisexposure impairs WM; however, it is unclear ifCannabisfacilitates or impairs rodent WM. Existing literature also fails to address the effects ofCannabisexposure on rodent WMC using exposure paradigms that closely mirror patterns of human use. In the present study, WMC of rats was inferred by novelty preference after a short delay in spontaneous recognition-based tests. Either object or odor-based stimuli were used in different variations of the tests that present identical (IOT) and different (DOT) sets of stimuli (3 or 6) for low-and high-cognitive loads, respectively. Additionally, we present a human-machine hybrid (HYB) behavioral quantification approach which supplements stopwatch-based scoring with supervised machine learning (SML)-based classification, enabling behavioral data to be made publicly available. After validating the spontaneous tests, 6-item IOT and DOT tests with the HYB method were used to evaluate the impact of acute exposure to high-THC or high-CBDCannabissmoke on novelty preference. Under control conditions, rats showed novelty preference in all test variations. We found that high-THC, but not high-CBD,Cannabissmoke exposure impaired novelty preference for objects under a high-cognitive load. Odor-based recognition deficits were seen under both low-, and high-cognitive loads only following high-THC smoke exposure. Ultimately, these data show thatCannabissmoke exposure impacts novelty preference in a load-dependent, and stimuli-specific manner.Significance StatementWorking memory (WM) capacity is the limited amount of information that can be utilized by WM to orchestrate processes like learning and memory. Using object-and odor-based spontaneous recognition tests, the impact of high-THC or high-CBDCannabissmoke on novelty preference was evaluated. Behavioral measurements were generated using a combination of open-source analysis software and traditional stopwatch scoring to form a human-machine hybrid (HYB) scoring method. We show novelty preference deficits under high-cognitive loads in object-based tests, while impacting novelty preference under both high-and low-cognitive loads in the odor-based tests. Ultimately, we show thatCannabissmoke exposure affects cognitive functions that underly WM in rats, which has broad implications for human use.

There is an increasingly large disparity in college graduation rates among low-income and first-generation college students. Research suggests that the main reason for this discrepancy is the lack of access to information and knowledge about the college process. First-generation students have fewer people in their social network who went to college and thus cannot help them navigate the difficult and multi-step process of finding, applying, and enrolling in college. Mentoring, however, has been proven to be a successful intervention for helping these populations navigate the post-secondary process. This paper evaluates a school-based hybrid mentoring program to attempt to measure the relationship between mentors and how students in New York City navigated the post-secondary process and enrolled in college. Findings show that program lessons, number of months matched, and meeting out of program are important program elements in increasing a student’s likelihood of graduating high school and enrolling on-time in college.

Introduction Molecular testing has helped clinicians and cytopathologists to further categorize indeterminate thyroid fine needle aspiration (FNA) specimens. The purpose of the present study was to evaluate the accuracy of commercially available molecular tests, review their effects on patient treatment, and correlate the molecular alterations with the histologic findings. Materials and methods A pathology laboratory information system search identified thyroid FNAs performed at our institution between January 1, 2015 and June 30, 2020. The results of surgical follow-up and ancillary molecular testing were collected. We evaluated the accuracy of these tests and whether they could reduce the number of surgeries performed. Results Our laboratory information system search identified 510 cases reported as atypia of undetermined significance, 94 as suspicious for follicular neoplasm, and 44 as suspicious for follicular neoplasm, Hurthle cell type. Of the specimens, 343 had no ancillary molecular testing, 146 were sent for ThyGenX/ThyraMIR, and 136 were sent for ThyroSeq. Of the patients without molecular testing, 50.4% had undergone follow-up surgery compared with 30.8% after ThyGenX/ThyraMIR and 38.2% after ThyroSeq testing, resulting in 38.9% and 24.2% fewer surgeries and an odds ratio of 0.04 (95% confidence interval, 0.00-0.33) and 0.14 (95% confidence interval, 0.01-0.95), respectively. For ThyGenX/ThyraMIR testing, the risk of malignancy for high and moderate to high risk alterations was 80%, 28.6% for moderate and low to moderate risk alterations, and 23.1% for low risk alterations. For ThyroSeq, the risk of malignancy was 87.5% for high risk alterations, 36.8% for intermediate to high risk alterations, 27.3% for intermediate risk alterations, and 0% for low risk alterations. The areas under the curve for ThyGenX/ThyraMIR and ThyroSeq testing were 0.65 and 0.85, respectively. Conclusions These findings suggest that, at our institution, both ThygenX/ThyraMIR and ThyroSeq can be used to effectively stratify cytology specimens based on the risk of malignancy and reduce the number of surgeries performed at our institution.

Colorectal cancer exhibits dynamic cellular and genetic heterogeneity during progression from precursor lesions toward malignancy. Leveraging spatial molecular information to construct a phylogeographic map of tumor evolution can reveal individualized growth trajectories with diagnostic and therapeutic potential. Integrative analysis of spatial multi-omic data from 31 colorectal specimens revealed simultaneous microenvironmental and clonal alterations as a function of progression. Copy number variation served to re-stratify microsatellite stable and unstable tumors into chromosomally unstable (CIN+) and hypermutated (HM) classes. Phylogeographical maps classified tumors by their evolutionary dynamics, and clonal regions were placed along a global pseudotemporal progression trajectory. Cell-state discovery from a single-cell cohort revealed recurring epithelial gene signatures and infiltrating immune states in spatial transcriptomics. Charting these states along progression pseudotime, we observed a transition to immune exclusion in CIN+ tumors as characterized by a novel gene expression signature comprised ofDDR1, TGFBI, PAK4,andDPEP1. We demonstrated how these genes and their protein products are key regulators of extracellular matrix components, are associated with lower cytotoxic immune infiltration, and show prognostic value in external cohorts. Through high-dimensional data integration, this atlas provides insights into co-evolution of tumors and their microenvironments, serving as a resource for stratification and targeted treatment of CRC.

Urine cytology (UC) is generally considered the primary approach for screening for recurrence of bladder cancer. However, it is currently unclear how best to use cytological exams themselves for the assessment and early detection of recurrence, beyond identifying a positive finding which requires more invasive methods to confirm recurrence and decide on therapeutic options. As screening programs are frequent, and can be burdensome, finding quantitative means to reduce this burden for patients, cytopathologists and urologists is an important endeavor and can improve both the efficiency and reliability of findings. Additionally, identifying ways to risk-stratify patients is crucial for improving quality of life while reducing the risk of future recurrence or progression of the cancer. In this study, we leveraged a computational machine learning tool, AutoParis-X, to extract imaging features from UC exams longitudinally to study the predictive potential of urine cytology for assessing recurrence risk. This study examined how the significance of imaging predictors changes over time before and after surgery to determine which predictors and time periods are most relevant for assessing recurrence risk. Results indicate that imaging predictors extracted using AutoParis-X can predict recurrence as well or better than traditional cytological / histological assessments alone and that the predictiveness of these features is variable across time, with key differences in overall specimen atypia identified immediately before tumor recurrence. Further research will clarify how computational methods can be effectively utilized in high volume screening programs to improve recurrence detection and complement traditional modes of assessment.

Adopting a computational approach for the assessment of urine cytology specimens has the potential to improve the efficiency, accuracy and reliability of bladder cancer screening, which has heretofore relied on semi-subjective manual assessment methods. As rigorous, quantitative criteria and guidelines have been introduced for improving screening practices, e.g., The Paris System for Reporting Urinary Cytology (TPS), algorithms to emulate semi-autonomous diagnostic decision-making have lagged behind, in part due to the complex and nuanced nature of urine cytology reporting. In this study, we report on a deep learning tool, AutoParis-X, which can facilitate rapid semi-autonomous examination of urine cytology specimens. Through a large-scale retrospective validation study, results indicate that AutoParis-X can accurately determine urothelial cell atypia and aggregate a wide-variety of cell and cluster-related information across a slide to yield an Atypia Burden Score (ABS) that correlates closely with overall specimen atypia, predictive of TPS diagnostic categories. Importantly, this approach accounts for challenges associated with assessment of overlapping cell cluster borders, which improved the ability to predict specimen atypia and accurately estimate the nuclear-to-cytoplasm (NC) ratio for cells in these clusters. We developed an interactive web application that is publicly available and open-source, which features a simple, easy-to-use display for examining urine cytology whole-slide images (WSI) and determining the atypia level of specific cells, flagging the most abnormal cells for pathologist review. The accuracy of AutoParis-X (and other semi-automated digital pathology systems) indicates that these technologies are approaching clinical readiness and necessitates full evaluation of these algorithms via head-to-head clinical trials.

Background Experts recommend that treatment for substance use disorder (SUD) be integrated into primary care. The Digital Therapeutics for Opioids and Other SUD (DIGITS) Trial tests strategies for implementing reSET® and reSET-O®, which are prescription digital therapeutics for SUD and opioid use disorder, respectively, that include the community reinforcement approach, contingency management, and fluency training to reinforce concept mastery. This purpose of this trial is to test whether two implementation strategies improve implementation success (Aim 1) and achieve better population-level cost effectiveness (Aim 2) over a standard implementation approach. Methods/Design The DIGITS Trial is a hybrid type III cluster-randomized trial. It examines outcomes of implementation strategies, rather than studying clinical outcomes of a digital therapeutic. It includes 22 primary care clinics from a healthcare system in Washington State and patients with unhealthy substance use who visit clinics during an active implementation period (up to one year). Primary care clinics implemented reSET and reSET-O using a multifaceted implementation strategy previously used by clinical leaders to roll-out smartphone apps (“standard implementation” including discrete strategies such as clinician training, electronic health record tools). Clinics were randomized as 21 sites in a 2x2 factorial design to receive up to two added implementation strategies: (1) practice facilitation, and/or (2) health coaching. Outcome data are derived from electronic health records and logs of digital therapeutic usage. Aim 1’s primary outcomes include reach of the digital therapeutics to patients and fidelity of patients’ use of the digital therapeutics to clinical recommendations. Substance use and engagement in SUD care are additional outcomes. In Aim 2, population-level cost effectiveness analysis will inform the economic benefit of the implementation strategies compared to standard implementation. Implementation is monitored using formative evaluation, and sustainment will be studied for up to one year using qualitative and quantitative research methods. Discussion The DIGITS Trial uses an experimental design to test whether implementation strategies increase and improve the delivery of digital therapeutics for SUDs when embedded in a large healthcare system. It will provide data on the potential benefits and cost-effectiveness of alternative implementation strategies. ClinicalTrials.gov Identifier: NCT05160233 (Submitted 12/3/2021). https://clinicaltrials.gov/ct2/show/NCT05160233

BACKGROUND: Bariatric surgery averts obesity-induced insulin resistance and the metabolic syndrome. By contrast, surgical fat removal is considered merely an esthetic endeavor. The aim of this article was to establish whether surgical fat removal, similar to bariatric surgery, exerts measurable, lasting metabolic benefits. METHODS: PubMed, Embase, and Scopus were searched using the Polyglot Search Translator to find studies examining quantitative expression of metabolic markers. Quality assessment was done using the MethodologicAl STandard for Epidemiological Research scale. The robust-error meta-regression model was employed for this synthesis. RESULTS: Twenty-two studies with 493 participants were included. Insulin sensitivity improved gradually with a maximum reduction in fasting insulin and homeostatic model assessment for insulin resistance of 17 pmol/L and 1 point, respectively, at postoperative day 180. Peak metabolic benefits manifest as a reduction of 2 units in body mass index, 3 kg of fat mass, 5cm of waist circumference, 15 µg/L of serum leptin, 0.75 pg/ml of tumor necrosis factor-alpha, 0.25 mmol/L of total cholesterol, and 3.5 mmHg of systolic and diastolic blood pressure that were observed at day 50 but were followed by a return to preoperative levels by day 180. Serum high-density lipoproteins peaked at 50 days post-surgery before falling below the baseline. No significant changes were observed in lean body mass, serum adiponectin, resistin, interleukin-6, C-reactive protein, triglyceride, low-density lipoproteins, free fatty acids, and fasting blood glucose. CONCLUSION: Surgical fat removal exerts several metabolic benefits in the short term, but only improvements in insulin sensitivity last beyond 6 months.

Extracellular vesicles and exomere nanoparticles are under intense investigation as sources of clinically relevant cargo. Here we report the discovery of a distinct extracellular nanoparticle, termed supermere. Supermeres are morphologically distinct from exomeres and display a markedly greater uptake in vivo compared with small extracellular vesicles and exomeres. The protein and RNA composition of supermeres differs from small extracellular vesicles and exomeres. Supermeres are highly enriched with cargo involved in multiple cancers (glycolytic enzymes, TGFBI, miR-1246, MET, GPC1 and AGO2), Alzheimer’s disease (APP) and cardiovascular disease (ACE2, ACE and PCSK9). The majority of extracellular RNA is associated with supermeres rather than small extracellular vesicles and exomeres. Cancer-derived supermeres increase lactate secretion, transfer cetuximab resistance and decrease hepatic lipids and glycogen in vivo. This study identifies a distinct functional nanoparticle replete with potential circulating biomarkers and therapeutic targets for a host of human diseases., Zhang et al. identify and characterize supermeres as extracellular nanoparticles that exhibit unique biological and functional properties with potential prognostic and therapeutic value across distinct diseases.

To evaluate factors associated with ICU delirium in patients who underwent damage control laparotomy (DCL), with the hypothesis that benzodiazepines and paralytic infusions would be associated with increased delirium risk. We also sought to evaluate the differences in sedation practices between trauma (T) and non-trauma (NT) patients. We reviewed retrospective data from 15 centers in the EAST SLEEP-TIME registry admitted from January 1, 2017 to December 31, 2018. We included all adults undergoing DCL, regardless of diagnosis, who had completed daily Richmond Agitation Sedation Score (RASS) and Confusion Assessment Method-ICU (CAM-ICU). We excluded patients younger than 18 years, pregnant women, prisoners and patients who died before the first re-laparotomy. Data collected included age, number of re-laparotomies after DCL, duration of paralytic infusion, duration and type of sedative and opioid infusions as well as daily CAM-ICU and RASS scores to analyze risk factors associated with the proportion of delirium-free/coma-free ICU days during the first 30 days (DF/CF-ICU-30) using multivariate linear regression. A 353 patient subset (73.2% trauma) from the overall 567-patient cohort had complete daily RASS and CAM-ICU data. NT patients were older (58.9 ± 16.0 years vs 40.5 ± 17.0 years [p

Background Möbius (Moebius) and Poland’s syndromes are two rare congenital syndromes characterized by non-progressive bilateral (and often asymmetric) dysfunction of the 6th and 7th cranial nerves and hypoplasia of the pectoral muscles associated with chest wall and upper limb anomalies respectively. Manifest simultaneously as Poland-Möbius (Poland-Moebius) syndrome, debate continues as to whether this is a distinct nosological entity or represents phenotypic variation as part of a spectrum of disorders of rhomboencephalic development. Etiological hypotheses implicate both genetic and environmental factors. The PLXND1 gene codes for a protein expressed in the fetal central nervous system and vascular endothelium and is thus involved in embryonic neurogenesis and vasculogenesis. It is located at chromosome region 3q21-q22, a locus of interest for Möbius syndrome. Case presentation We present the first report of a patient with Poland-Möbius syndrome and a mutation in the PLXND1 gene. A child with Poland-Möbius syndrome and a maternally inherited missense variant (NM_015103.2:ex14:c.2890G > Ap.V964M) in the PLXND1 gene is described. In order to contextualize these findings, the literature was examined to identify other confirmed cases of Poland-Möbius syndrome for which genetic data were available. Fourteen additional cases of Poland-Möbius syndrome with genetic studies are described in the literature. None implicated the PLXND1 gene which has previously been implicated in isolated Möbius syndrome. Conclusions This report provides further evidence in support of a role for PLXND1 mutations in Möbius syndrome and reasserts the nosological link between Möbius and Poland’s syndromes. Level of evidence Level V, Descriptive Study.

Reproductive coercion (RC) is a type of intimate partner violence that includes birth control sabotage (BCS). We explored the perceived intent behind BCS to refine RC measurement, using a mixed-methods design with a clinic-based sample of Latina women (13 interviews; 482 surveys). Women perceived partners used BCS for reasons beyond pregnancy promotion. Specifically, 16.8% of participants reported any past-year RC; this decreased to 9.5% when asked if their partner used BCS with the sole intent of getting them pregnant. RC measures and assessment should separate behavior from intent in BCS questions to not underestimate the prevalence and to guide clinical response.

Alternative splicing (AS) of pre-mRNAs is an essential process that regulates gene expression and functional diversity, yet the underlying regulatory mechanisms that control this process during cancer metastasis are not clear. Here, we uncovered that a long non-coding RNA (lncRNA), MIR99AHG, mediates regulation of AS to alter chromatin remodeler function and promote invadopodia formation in colorectal cancer (CRC). We found that MIR99AHG is highly expressed in metastatic CRC cells and patient tissue samples. In vitro and in vivo assays showed that MIR99AHG potently drove CRC cell motility, invasion, and metastasis. MIR99AHG bound to and stabilized the RNA splicing factor PTBP1, which cooperatively increased cassette exon inclusion of the chromatin remodeling gene SMARCA1. Mechanistically, MIR99AHG acted as an address label for PTBP1 to fine-tune its binding pattern on SMARCA1 pre-mRNA, thereby controlling the skipping-to-inclusion splicing switch of SMARCA1 and favouring the production of a long isoform (SMARCA1-L). Canonical SMARCA1 was found to suppress cell migration and invasiveness by inhibiting invadopodia formation, but SMARCA1-L was functionally inert. Clinicaldata revealed that MIR99AHG was positively correlated with PTBP1 and SMARCA1-L in human CRC specimens and predicted patient outcome. Furthermore, we showed that the crosstalk with cancer-associated fibroblasts triggers TGF-β/SAMD signalling in CRC cells and activates MIR99AHG expression. Our findings establish a novel mechanism for a lncRNA that interacts with PTBP1 to regulate AS process, providing a potential therapeutic target and predictive biomarker of CRC.

Among people with opioid use disorder (OUD), having a co-occurring substance use disorder (SUD) is associated with lower likelihood of receiving OUD treatment medications (MOUD). However, it is unclear how distinct co-occurring SUDs are associated with MOUD receipt. This study examined associations of distinct co-occurring SUDs with initiation and continuation of MOUD among patients with OUD in the national Veterans Health Administration (VA).Electronic health record data were extracted for outpatients with OUD who received care August 1, 2016, to July 31, 2017. Analyses were conducted separately among patients without and with prior-year MOUD receipt to examine initiation and continuation, respectively. SUDs were measured using diagnostic codes; MOUD receipt was measured using prescription fills/clinic visits. Adjusted regression models estimated likelihood of following-year MOUD receipt for patients with each co-occurring SUD relative to those without.Among 23,990 patients without prior-year MOUD receipt, 12% initiated in the following year. Alcohol use disorder (adjusted incidence rate ratio [aIRR], 0.80; 95% confidence interval [CI], 0.72-0.90) and cannabis use disorder (aIRR, 0.78; 95% CI, 0.70-0.87) were negatively associated with initiation. Among 11,854 patients with prior-year MOUD receipt, 83% continued in the following year. Alcohol use disorder (aIRR, 0.94; 95% CI, 0.91-0.97), amphetamine/other stimulant use disorder (aIRR, 0.94; 95% CI, 0.90-0.99), and cannabis use disorder (aIRR, 0.95; 95% CI, 0.93-0.98) were negatively associated with continuation.In this study of national VA outpatients with OUD, those with certain co-occurring SUDs were less likely to initiate or continue MOUD. Further research is needed to identify barriers related to specific co-occurring SUDs.

Background The Bethesda System for Reporting Thyroid Cytopathology contains an atypia of undetermined significance (AUS) category with heterogeneous and distinct inclusion criteria. The purpose of this study was to investigate differences in malignancy rates and molecular alterations based on the presence of different criteria. Methods A laboratory information search was conducted to identify thyroid fine-needle aspiration specimens signed out as AUS. The cases were reclassified as architectural atypia (3A), cytologic atypia (3C), both architectural and cytologic atypia (3B), or Hurthle cell aspirate (3H). Surgical follow-up and concurrent molecular test results, if available, were collected. Results Five hundred ten specimens, including 258 reclassified as 3A, 40 reclassified as 3B, 119 reclassified as 3C, and 86 reclassified as 3H, were identified. The risks of malignancy for the subcategories were 13.4%, 26.3%, 44.1%, and 13.8%, respectively. Additionally, BRAF V600E mutations were more prevalent in specimens with cytologic atypia (3B/3C), whereas low-risk alterations, including KRAS, PTEN, and PAX8-PPARy2, were more prevalent in those with architectural atypia (3A). Conclusions Subdividing AUS specimens on the basis of the type of atypia can yield categories associated with distinct molecular alterations and risks of malignancy.

Purpose Little is known about prevalence and treatment of OUD among youth engaged in primary care (PC). Medications are the recommended treatment of opioid use disorder (OUD) for adolescents and young adults (youth). This study describes the prevalence of OUD, the prevalence of medication treatment for OUD, and patient characteristics associated with OUD treatment among youth engaged in PC. Methods This cross-sectional study includes youth aged 16–25 years engaged in PC. Eligible patients had ≥ 1 PC visit during fiscal years (FY) 2014–2016 in one of 6 health systems across 6 states. Data from electronic health records and insurance claims were used to identify OUD diagnoses, office-based OUD medication treatment, and patient demographic and clinical characteristics in the FY of the first PC visit during the study period. Descriptive analyses were conducted in all youth, and stratified by age (16–17, 18–21, 22–25 years). Results Among 303,262 eligible youth, 2131 (0.7%) had a documented OUD diagnosis. The prevalence of OUD increased by ascending age groups. About half of youth with OUD had documented depression or anxiety and one third had co-occurring substance use disorders. Receipt of medication for OUD was lowest among youth 16–17 years old (14%) and highest among those aged 22–25 (39%). Conclusions In this study of youth engaged in 6 health systems across 6 states, there was low receipt of medication treatment, and high prevalence of other substance use disorders and mental health disorders. These findings indicate an urgent need to increase medication treatment for OUD and to integrate treatment for other substance use and mental health disorders.

An oxygen-affinity-modifying drug, voxelotor, has very recently been approved by the FDA for treatment of sickle cell disease. The proposed mechanism of action is by preferential binding of the drug to the R quaternary conformation, which cannot copolymerize with the T conformation to form sickle fibers. Here, we report widely different oxygen dissociation and oxygen association curves for normal blood in the presence of voxelotor and interpret the results in terms of the allosteric model of Monod, Wyman, and Changeux with the addition of drug binding. The model does remarkably well in quantitatively explaining a complex data set with just the addition of drug binding and dissociation rates for the R and T conformations. Whereas slow dissociation of the drug from R results in time-independent dissociation curves, the changing association curves result from slow dissociation of the drug from T, as well as extremely slow binding of the drug to T. By calculating true equilibrium curves from the model parameters, we show that there would be a smaller decrease in oxygen delivery from the left shift in the dissociation curve caused by drug binding if drug binding and dissociation for both R and T were rapid. Our application of the Monod, Wyman, and Changeux model demonstrates once more its enormous power in explaining many different kinds of experimental results for hemoglobin. It should also be helpful in analyzing oxygen binding and in vivo delivery in future investigations of oxygen-affinity-modifying drugs for sickle cell disease.

ImportanceUnhealthy alcohol use is common and affects morbidity and mortality but is often neglected in medical settings, despite guidelines for both prevention and treatment.ObjectiveTo test an implementation intervention to increase (1) population-based alcohol-related prevention with brief interventions and (2) treatment of alcohol use disorder (AUD) in primary care implemented with a broader program of behavioral health integration.Design, Setting, and ParticipantsThe Sustained Patient-Centered Alcohol-Related Care (SPARC) trial was a stepped-wedge cluster randomized implementation trial, including 22 primary care practices in an integrated health system in Washington state. Participants consisted of all adult patients (aged ≥18 years) with primary care visits from January 2015 to July 2018. Data were analyzed from August 2018 to March 2021.InterventionsThe implementation intervention included 3 strategies: practice facilitation; electronic health record decision support; and performance feedback. Practices were randomly assigned launch dates, which placed them in 1 of 7 waves and defined the start of the practice’s intervention period.Main Outcomes and MeasuresCoprimary outcomes for prevention and AUD treatment were (1) the proportion of patients who had unhealthy alcohol use and brief intervention documented in the electronic health record (brief intervention) for prevention and (2) the proportion of patients who had newly diagnosed AUD and engaged in AUD treatment (AUD treatment engagement). Analyses compared monthly rates of primary and intermediate outcomes (eg, screening, diagnosis, treatment initiation) among all patients who visited primary care during usual care and intervention periods using mixed-effects regression.ResultsA total of 333 596 patients visited primary care (mean [SD] age, 48 [18] years; 193 583 [58%] female; 234 764 [70%] White individuals). The proportion with brief intervention was higher during SPARC intervention than usual care periods (57 vs 11 per 10 000 patients per month; P P = .30). The intervention increased intermediate outcomes: screening (83.2% vs 20.8%; P P = .003), and treatment initiation (7.8 vs 6.2 per 10 000; P = .04).Conclusions and RelevanceIn this stepped-wedge cluster randomized implementation trial, the SPARC intervention resulted in modest increases in prevention (brief intervention) but not AUD treatment engagement in primary care, despite important increases in screening, new diagnoses, and treatment initiation.Trial RegistrationClinicalTrials.gov Identifier: NCT02675777

BACKGROUND: Hepatitis C and HIV are associated with opioid use disorders (OUD) and injection drug use. Medications for OUD can prevent the spread of HCV and HIV. OBJECTIVE: To describe the prevalence of documented OUD, as well as receipt of office-based medication treatment, among primary care patients with HCV or HIV. DESIGN: Retrospective observational cohort study using electronic health record and insurance data. PARTICIPANTS: Adults ≥ 18 years with ≥ 2 visits to primary care during the study (2014–2016) at 6 healthcare systems across five states (CO, CA, OR, WA, and MN). MAIN MEASURES: The primary outcome was the diagnosis of OUD; the secondary outcome was OUD treatment with buprenorphine or oral/injectable naltrexone. Prevalence of OUD and OUD treatment was calculated across four groups: HCV only; HIV only; HCV and HIV; and neither HCV nor HIV. In addition, adjusted odds ratios (AOR) of OUD treatment associated with HCV and HIV (separately) were estimated, adjusting for age, gender, race/ethnicity, and site. KEY RESULTS: The sample included 1,368,604 persons, of whom 10,042 had HCV, 5821 HIV, and 422 both. The prevalence of diagnosed OUD varied across groups: 11.9% (95% CI: 11.3%, 12.5%) for those with HCV; 1.6% (1.3%, 2.0%) for those with HIV; 8.8% (6.2%, 11.9%) for those with both; and 0.92% (0.91%, 0.94%) among those with neither. Among those with diagnosed OUD, the prevalence of OUD medication treatment was 20.9%, 16.0%, 10.8%, and 22.3%, for those with HCV, HIV, both, and neither, respectively. HCV was not associated with OUD treatment (AOR = 1.03; 0.88, 1.21), whereas patients with HIV had a lower probability of OUD treatment (AOR = 0.43; 0.26, 0.72). CONCLUSIONS: Among patients receiving primary care, those diagnosed with HCV and HIV were more likely to have documented OUD than those without. Patients with HIV were less likely to have documented medication treatment for OUD. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11606-020-06389-7.

Background Emergency general surgery (EGS) has high rates of morbidity, mortality, and readmission. Therefore, it might be expected that an EGS service fields many consultations for postoperative patients. However, with the known overutilization of emergency department visits for nonurgent conditions, we hypothesized most postoperative consults received by an EGS service would be nonurgent and could be appropriately managed as an outpatient. Methods We reviewed all EGS consults at a single urban safety net hospital over a 12-month period, screening for patients who had undergone surgery in the previous 12 mo. This included consultations from the emergency room and inpatient setting. Demographics, admission status, procedures performed, and other details were abstracted from the chart and Vizient reports. Consultation questions were categorized and then reviewed by an expert panel to determine if conditions could have been managed as an outpatient. Results The EGS service received a total of 1112 consults, with 99 (9%) for a postoperative condition. Overall, 85% of postoperative consults were admitted after consultation, 19% underwent surgery and 21% underwent a procedure with gastroenterology or interventional radiology. Expert review classified slightly over one-third (36%) of consults as nonurgent. Conclusions Most postoperative consults seen at our urban safety net hospital represent true morbidity that required admission, intervention, or surgery. Despite this high acuity, one-third of postoperative consults could have been managed as an outpatient. Efforts to improve discharge instructions and set patient expectations could limit unnecessary postoperative emergency department visits.

Background Most people with opioid use disorder (OUD) never receive treatment. Medication treatment of OUD in primary care is recommended as an approach to increase access to care. The PRimary Care Opioid Use Disorders treatment (PROUD) trial tests whether implementation of a collaborative care model (Massachusetts Model) using a nurse care manager (NCM) to support medication treatment of OUD in primary care increases OUD treatment and improves outcomes. Specifically, it tests whether implementation of collaborative care, compared to usual primary care, increases the number of days of medication for OUD (implementation objective) and reduces acute health care utilization (effectiveness objective). The protocol for the PROUD trial is presented here. Methods PROUD is a hybrid type III cluster-randomized implementation trial in six health care systems. The intervention consists of three implementation strategies: salary for a full-time NCM, training and technical assistance for the NCM, and requiring that three primary care providers have DEA waivers to prescribe buprenorphine. Within each health system, two primary care clinics are randomized: one to the intervention and one to Usual Primary Care. The sample includes all patients age 16–90 who visited the randomized primary care clinics from 3 years before to 2 years after randomization (anticipated to be > 170,000). Quantitative data are derived from existing health system administrative data, electronic medical records, and/or health insurance claims (“electronic health records,” [EHRs]). Anonymous staff surveys, stakeholder debriefs, and observations from site visits, trainings and technical assistance provide qualitative data to assess barriers and facilitators to implementation. The outcome for the implementation objective (primary outcome) is a clinic-level measure of the number of patient days of medication treatment of OUD over the 2 years post-randomization. The patient-level outcome for the effectiveness objective (secondary outcome) is days of acute care utilization [e.g. urgent care, emergency department (ED) and/or hospitalizations] over 2 years post-randomization among patients with documented OUD prior to randomization. Discussion The PROUD trial provides information for clinical leaders and policy makers regarding potential benefits for patients and health systems of a collaborative care model for management of OUD in primary care, tested in real-world diverse primary care settings. Trial registration # NCT03407638 (February 28, 2018); CTN-0074 https://clinicaltrials.gov/ct2/show/NCT03407638?term=CTN-0074&draw=2&rank=1

OBJECTIVE: The authors sought to characterize the 3-year prevalence of mental disorders and nonnicotine substance use disorders among male and female primary care patients with documented opioid use disorder across large U.S. health systems. METHODS: This retrospective study used 2014–2016 data from patients ages ≥16 years in six health systems. Diagnoses were obtained from electronic health records or claims data; opioid use disorder treatment with buprenorphine or injectable extended-release naltrexone was determined through prescription and procedure data. Adjusted prevalence of comorbid conditions among patients with opioid use disorder (with or without treatment), stratified by sex, was estimated by fitting logistic regression models for each condition and applying marginal standardization. RESULTS: Females (53.2%, N=7,431) and males (46.8%, N=6,548) had a similar prevalence of opioid use disorder. Comorbid mental disorders among those with opioid use disorder were more prevalent among females (86.4% vs. 74.3%, respectively), whereas comorbid other substance use disorders (excluding nicotine) were more common among males (51.9% vs. 60.9%, respectively). These differences held for those receiving medication treatment for opioid use disorder, with mental disorders being more common among treated females (83% vs. 71%) and other substance use disorders more common among treated males (68% vs. 63%). Among patients with a single mental health condition comorbid with opioid use disorder, females were less likely than males to receive medication treatment for opioid use disorder (15% vs. 20%, respectively). CONCLUSIONS: The high rate of comorbid conditions among patients with opioid use disorder indicates a strong need to supply primary care providers with adequate resources for integrated opioid use disorder treatment.

Urine cytology is used to screen for urothelial carcinoma in patients with hematuria or risk factors (e.g., smoking, industrial dye exposure) and is an essential clinical triage and longitudinal monitoring tool for patients with known bladder cancer. However, urine cytology is semi-subjective and thus susceptible to issues including specimen quality, inter-observer variability, and “hedging” towards equivocal (“atypical”) diagnoses. These factors limit the predictive value of urine cytology and increase reliance on invasive procedures (cystoscopy). The Paris System for Reporting Urine Cytology (TPS) was formulated to provide more quantitative/reproducible endpoints with well-defined criteria for urothelial atypia. TPS is often compared to other assessment techniques to justify its adoption. TPS results in decreased use of the atypical category and better reproducibility. Previous manuscripts comparing diagnoses pre- and post-TPS lacked a longitudinal component and thus failed to consider temporal differences between diagnoses made under prior systems and TPS. By aggregating across time, studies may underestimate the magnitude of differences between assessment methods. We conducted a large-scale longitudinal reassessment of urine cytology using TPS criteria from specimens collected from 2008 to 2018, prior to the mid-2018 adoption of TPS at an academic medical center. Findings indicate that differences in atypical assignment were largest at the start of the period and these differences progressively decreased towards insignificance just prior to TPS implementation. This finding suggests that cytopathologists had begun to utilize the quantitative TPS criteria prior to official adoption, which may more broadly inform adoption strategies, communication, and understanding for evolving classification systems in cytology.

Urine cytology is commonly used as a screening test for high grade urothelial carcinoma for patients with risk factors or hematuria and is an essential step in longitudinal monitoring of patients with a prior bladder cancer history. However, the semi-subjective nature of current reporting systems for urine cytology (e.g., The Paris System) can hamper reproducibility. For instance, the incorporation of urothelial cell clusters into the classification schema is still an item of debate and perplexity amongst expert cytopathologists, as several previous works have disputed their diagnostic relevance. Recently, several machine learning and morphometric algorithms have been proposed to provide quantitative descriptors of urine cytology specimens in an effort to reduce subjectivity and include automated assessments of cell clusters. However, it remains unclear how these computer algorithms interpret/analyze cell clusters. In this work, we have developed an automated preprocessing tool for urothelial cell cluster assessment that divides urothelial cell clusters into meaningful components for downstream assessment (i.e., population-based studies, workflow automation). Results indicate that cell cluster atypia (i.e., defined by whether the cell cluster harbored multiple atypical cells, thresholded by a minimum number of cells), cell border overlap and smoothness, and total number of clusters are important markers of specimen atypia when considering assessment of urothelial cell clusters. Markers established through techniques to separate cell clusters may have wider applicability for the design and implementation of machine learning approaches for urine cytology assessment.

Background Metastasis leads to recurrence and death in colorectal cancer (CRC) patients; however, mechanisms underlying CRC metastasis, especially in its initial stages, remain largely unknown. In this study, we aim to identify long noncoding RNAs (lncRNAs) functionally involved in CRC metastasis initiation and their regulation that could lead to targeted therapeutics. Methods We performed whole transcriptome sequencing using CRC cell lines with divergent spontaneous metastatic properties. The biological roles and mechanisms of lncRNA MIR99AHG were characterized with a series of in vitro and in vivo models and molecular analyses. Results MIR99AHG was upregulated in CRC patients and associated with tumor stage and prognosis. MIR99AHG potently drove migration, invasion and metastasis in CRC cells, and these effects were dependent on its role in promoting invadopodia formation. MIR99AHG interacted with RNA splicing factor PTBP1, which cooperatively modulated alternative splicing of chromatin remodeling gene SMARCA1. Mechanistically, MIR99AHG acted as an address label for PTBP1 to direct its binding to the 5’ splice site of SMARCA1 intron 12, thereby facilitating inclusion of the alternative exon 13 to generate a long isoform (SMARCA1-L). The canonical SMARCA1 inhibited cell migration and invasion and suppressed a core set of genes involved in invadopodia, but the SMARCA1-L was functionally inert in metastasis suppression. Clinically, SMARCA1-L levels were positively correlated with MIR99AHG and PTBP1 in patients with metastatic CRC. Conclusions This study identified that invadopodia was regulated by a splicing switch of SMARCA1 due to the interaction between MIR99AHG and PTBP1, highlighting a novel regulatory mode mediated by lncRNA in alternative splicing of chromatin remodeler during CRC metastasis.

BackgroundExtremity ischemia and necrosis after jellyfish envenomation can be mutilating and cause long-term functional deficits. The best way to manage these presentations is unknown. ObjectiveThe aim of this review was to establish an evidence-based consensus for the management of extremity ischemia after jellyfish envenomation. MethodsA systematic review of cases of extremity ischemia and necrosis after envenomation by marine cnidarians was performed to clarify what is and what is not known about management and outcomes, to draw conclusions about how best to manage these rare presentations, and to establish an evidence-based algorithm. ResultsThe ischemic sequelae of envenomation typically evolves over a few days. Close medical supervision is necessary to react promptly to the evolving clinical scenario. In the literature, 15 different pharmacologic classes have been used to manage these presentations. Only IV infusions of prostaglandin derivatives and intra-arterial thrombolytics have been found to improve the clinical picture and avoid the need for surgical fasciotomy and debridement in some cases. Anticoagulants, antiplatelet agents, steroids, antibiotics, and nitrates, which are among the most commonly prescribed pharmacologic agents, have not been observed to alter the clinical picture. ConclusionsSurgery for compartment syndrome and necrosis are common sequelae of extremity envenomation by marine cnidarians. Only prompt use of IV prostaglandins or intra-arterial thrombolytics can halt ischemic progression and avoid the need for surgery. An algorithm is proposed to guide management of these rare and mutilative presentations.

Objectives Transgender people-those whose gender identity differs from their sex assigned at birth-are at risk for health disparities resulting from stressors such as discrimination and violence. Transgender people report more drug use than cisgender people; however, it is unclear whether they have higher likelihood of drug use disorders. We examined whether transgender patients have increased likelihood of documented drug use disorders relative to cisgender patients in the national Veterans Health Administration (VA). Methods Electronic health record data were extracted for VA outpatients from 10/1/09 to 7/31/17. Transgender status and past-year documentation of drug use disorders (any, opioid, amphetamine, cocaine, cannabis, sedative, hallucinogen) were measured using diagnostic codes. Logistic regression models estimated odds ratios for drug use disorders among transgender compared to cisgender patients, adjusted for age, race/ethnicity and year. Effect modification by presence of ≥1 mental health condition was tested using multiplicative interaction. Results Among 8,872,793 patients, 8619 (0.1%) were transgender. Transgender patients were more likely than cisgender patients to have any drug use disorder (Adjusted Odds Ratio [aOR] 1.67, 95% confidence interval [CI] 1.53-1.83), amphetamine (aOR 2.22, 95% CI 1.82-2.70), cocaine (aOR 1.59, 95% CI 1.29-1.95), and cannabis (aOR 1.82, 95% CI 1.62-2.05) use disorders. There was no significant interaction by presence of ≥1 mental health condition. Conclusions Transgender VA patients may have higher likelihood of certain drug use disorders than cisgender VA patients, particularly amphetamine use disorder. Future research should explore mechanisms underlying disparities and potential barriers to accessing treatment and harm reduction services faced by transgender people.

We review the underappreciated problem of elder abuse with a focus on what trauma surgeons need to know. Because of its prevalence, it is important that clinicians understand types of elder abuse, risk factors in patient and perpetrator, prevention strategies, and the appropriate referral and treatment of potential victims of elder abuse. Elder abuse affects at least 10% of older individuals in the USA. Despite much effort to address the problem via legal and societal approaches, data to support particular programs are poor. And even with extensive efforts, the utility of established prevention strategies or existing screening tools to identify victims of elder abuse in the acute care setting has yet to be established. Elder abuse is a public health problem. As a society, we have only begun to define the extent of the problem. Healthcare systems have failed to effectively prevent or to accurately screen for, diagnose, and report elder abuse. The next steps include broader public awareness, educational initiatives, improved screening tools, and effective intervention strategies. In the meantime, we as trauma surgeons can be more diligent in reporting.

Social interactions are largely dependent on the interpretation of information conveyed through facial expressions. Although facial reanimation seeks restoration of the facial expression of emotion, outcome measures have not addressed this directly. This study evaluates the use of a machine learning technology to directly measure facial expression before and after facial reanimation surgery. Fifteen study subjects with facial palsy were evaluated both before and after undergoing cross-facial nerve grafting and free gracilis muscle transfer. Eight healthy volunteers were assessed for control comparison. Video footage of subjects with their face in repose and with a posed, closed-lip smile was obtained. The video data were then analyzed using the Noldus FaceReader software application to measure the relative proportions of seven cardinal facial expressions detected within each clip. The facial expression recognition application detected a far greater happy signal in postoperative (42 percent) versus preoperative (13 percent) smile videos (p < 0.0001), compared to 53 percent in videos of control faces smiling. This increase in postoperative happy signal was achieved in exchange for a reduction in the sad signal (15 percent to 9 percent; p = 0.092) and the neutral signal (57 percent to 37 percent; p = 0.0012). For video clips of patients in repose, no significant difference in happy emotion was detected between preoperative (3.1 percent) and postoperative (1.4 percent) states (p = 0.5). This study provides the first proof of concept for the use of a machine learning software application to objectively quantify facial expression before and after surgical reanimation. CLINICAL QUESTION/LEVEL OF EVIDENCE:: Diagnostic, IV.

Background: Coronavirus disease 2019 (COVID-19) has a substantial mortality risk with increased rates in the elderly. We hypothesized that age is not sufficient, and that frailty measured by preadmission Palliative Performance Scale would be a predictor of outcomes. Improved ability to identify high-risk patients will improve clinicians’ ability to provide appropriate palliative care, including engaging in shared decision-making about life-sustaining therapies. Aim: To evaluate whether preadmission Palliative Performance Scale predicts mortality in hospitalized patients with COVID-19. Design: Retrospective observational cohort study of patients admitted with COVID-19. Palliative Performance Scale was calculated from the chart. Using logistic regression, Palliative Performance Scale was assessed as a predictor of mortality controlling for demographics, comorbidities, palliative care measures and socioeconomic status. Setting/participants: Patients older than 18 years of age admitted with COVID-19 to a single urban public hospital in New Jersey, USA. Results: Of 443 admitted patients, we determined the Palliative Performance Scale score for 374. Overall mortality was 31% and 81% in intubated patients. In all, 36% (134) of patients had a low Palliative Performance Scale score. Compared with patients with a high score, patients with a low score were more likely to die, have do not intubate orders and be discharged to a facility. Palliative Performance Scale independently predicts mortality (odds ratio 2.89; 95% confidence interval 1.42–5.85). Conclusions: Preadmission Palliative Performance Scale independently predicts mortality in patients hospitalized with COVID-19. Improved predictors of mortality can help clinicians caring for patients with COVID-19 to discuss prognosis and provide appropriate palliative care including decisions about life-sustaining therapy.

Background Identifying individuals at highest risk maximizes efficacy of prevention programs in decreasing recidivist gunshot wound (GSW) injury. Characteristics of GSW recidivists may identify this population. Hospital-based violence intervention programs (HVIPs) are one effective strategy; however, programs are expensive, therefore, when possible, epidemiologic data should guide inclusion criteria. Methods Seventeen years of all GSW patients presenting to an urban Level I trauma center were reviewed. Countywide murders were reviewed from the same timeframe. Recidivists were any patient presenting twice, either to the hospital or once to the hospital and subsequently dying by firearm. Demographics and characteristics of future recidivists were compared with nonfuture recidivists. Results There were 9,699 unique intentional, GSW cases reviewed and 1,426 died, leaving 8,273 at risk of recidivism. Five hundred fourteen (6.2%) became recidivists. Most recidivists were African-American men and were younger at first GSW. Median time between incidents was 2.5 years, with a range of 0 days to 16 years. Nearly half were treated and released from the emergency department at their first episode of GSW. For recidivists who died, 128 died at the second incident, 29 at later incidents. Mortality from a second incident of firearm injury is 10% higher than first injuries, second hospitalizations are US $5,000 more expensive, and loss of life has a societal cost of US $167 billion in this community alone. Conclusion The most appropriate population for inclusion in HVIPs at our hospital are young black men. The HVIP services are needed in the emergency department to address those treated and released at first GSW. Recidivists have higher mortality, and hospitalizations are significantly more expensive at the second injury. The investment in prevention is justified and may lead to a decrease in recidivism. Level of evidence Therapeutic/Care Management level III.

Background Sepsis in older children is often associated with the presence of developmental abnormalities and cerebral palsy. While relatively uncommon, surgical abdomen in these patients is associated with a high rate of mortality. Few reports have been described of sepsis caused by isolated cecal necrosis. Case Report We report a 13-year-old child with cerebral palsy and global developmental delay who presented to the emergency department with acute worsening abdominal distention that the mother attributed to chronic constipation. Clinical evaluation revealed that she was in severe septic shock and needed immediate stabilization after which she underwent an exploratory laparotomy. Operative findings revealed cecal necrosis that necessitated an ileocecectomy. Why Should an Emergency Physician be Aware of This? Children with intellectual disabilities presenting with sepsis to the emergency department can be particularly challenging given the communication barriers and the time-sensitive nature of the condition. When evaluating these patients, a thorough history and examination are often the only tools that assist in the early identification of the infectious source, leading to improved clinical outcomes.© 2019 Elsevier Inc.

Evidence supports index cholecystectomy as the quality of care for patients admitted with acute cholecystitis. We sought to examine the role of hospital safety-net status on whether patients received appropriate index procedures for cholecystitis. The National Inpatient Sample was queried for patients with acute cholecystitis. Proportion of Medicaid and uninsured discharges were used to define safety-net hospitals (SNHs). Multivariate logistic regression was used to calculate associations between the frequency of index cholecystectomy and prolonged length of stay (LOS), and the effect of SNH designation. SNHs and non-SNHs had similar rates of index cholecystectomy in all geographic regions, except in the northeast, where the likelihood of having an index cholecystectomy was lower at SNHs. Patients at SNHs had longer LOS for acute cholecystitis, regardless of index or delayed cholecystectomy. When controlling for insurance status, patients at SNHs had longer LOS than those at non-SNHs. There was also increased LOS in SNHs in the Midwest, in urban hospitals, and in large hospitals. Our data showed no difference in the frequency of index cholecystectomy overall between SNHs and non-SNHs, except in the northeast. The variability and increased LOS at SNHs highlight potential opportunities to improve quality and decrease cost of care at our most vulnerable hospitals.