What Happens Post-Malone? An Investigation of Long-Term Postoperative Management of Antegrade Continence Enemas.

BACKGROUND: An option for medically refractory fecal incontinence and/or constipation is the antegrade continence enema (ACE). We investigated ACE usage and its perceptions, including whether patients were able to discontinue use of the appendicostomy/cecostomy tube. METHODS: Patients who underwent appendicostomy creation or cecostomy tube placement at two institutions between 2012 and 2021 were reviewed. Patients or parents/guardians were contacted for completion of a survey. Summary statistics for clinical data were tabulated and associations were evaluated with chi-square analysis. RESULTS: A total of 165 patients were included, including 92 (55.8%) males. Eighty-two (49.7%) surveys were completed. Most patients (51.5%) presented with fecal incontinence; 38 (23.3%) presented with constipation. More patients had a primary underlying diagnosis of anorectal malformation (39.4%), followed by functional constipation (21.2%), Hirschsprung disease (18.8%), and spinal malformation (17.6%). Thirty-six (21.8%) patients discontinued flushes by time of contact, with switch to laxatives being the most common reason (19%), followed by appendicostomy stricture/obstruction/closure (17%), switch to ileostomy/colostomy (17%), and patient preference (14%). There was no difference in patients' ability to stop using flushes based on underlying diagnosis (p = 0.31). The majority (84.1%) of respondents were "very likely" to recommend antegrade enemas to other children with similar diagnosis and 76.8% reported being "very satisfied" that the operation was done. CONCLUSIONS: There remains a high degree of satisfaction with antegrade continence enemas for children with constipation and fecal incontinence; some children may be able to stop using antegrade enemas with varied mechanisms including patient/family weaning versus with assistance and laxative trials. TYPE OF STUDY: Retrospective cohort study. LEVEL OF EVIDENCE: III.

Derivation and validation of generalized sepsis-induced acute respiratory failure phenotypes among critically ill patients: a retrospective study.

BACKGROUND: Septic patients who develop acute respiratory failure (ARF) requiring mechanical ventilation represent a heterogenous subgroup of critically ill patients with widely variable clinical characteristics. Identifying distinct phenotypes of these patients may reveal insights about the broader heterogeneity in the clinical course of sepsis, considering multi-organ dynamics. We aimed to derive novel phenotypes of sepsis-induced ARF using observational clinical data and investigate the generalizability of the derived phenotypes. METHODS: We performed a multi-center retrospective study of ICU patients with sepsis who required mechanical ventilation for ≥ 24 h. Data from two different high-volume academic hospital centers were used, where all phenotypes were derived in MICU of Hospital-I (N = 3225). The derived phenotypes were validated in MICU of Hospital-II (N = 848), SICU of Hospital-I (N = 1112), and SICU of Hospital-II (N = 465). Clinical data from 24 h preceding intubation was used to derive distinct phenotypes using an explainable machine learning-based clustering model interpreted by clinical experts. RESULTS: Four distinct ARF phenotypes were identified: A (severe multi-organ dysfunction (MOD) with a high likelihood of kidney injury and heart failure), B (severe hypoxemic respiratory failure [median P/F = 123]), C (mild hypoxia [median P/F = 240]), and D (severe MOD with a high likelihood of hepatic injury, coagulopathy, and lactic acidosis). Patients in each phenotype showed differences in clinical course and mortality rates despite similarities in demographics and admission co-morbidities. The phenotypes were reproduced in external validation utilizing the MICU of Hospital-II and SICUs from Hospital-I and -II. Kaplan-Meier analysis showed significant difference in 28-day mortality across the phenotypes (p < 0.01) and consistent across MICU and SICU of both Hospital-I and -II. The phenotypes demonstrated differences in treatment effects associated with high positive end-expiratory pressure (PEEP) strategy. CONCLUSION: The phenotypes demonstrated unique patterns of organ injury and differences in clinical outcomes, which may help inform future research and clinical trial design for tailored management strategies.

Understanding 'error' in the forensic sciences: A primer.

This paper distils seven key lessons about 'error' from a collaborative webinar series between practitioners at Victoria Police Forensic Services Department and academics. It aims to provide the common understanding of error necessary to foster interdisciplinary dialogue, collaboration and research. The lessons underscore the inevitability, complexity and subjectivity of error, as well as opportunities for learning and growth. Ultimately, we argue that error can be a potent tool for continuous improvement and accountability, enhancing the reliability of forensic sciences and public trust. It is hoped the shared understanding provided by this paper will support future initiatives and funding for collaborative developments in this vital domain.

Extracorporeal life support use in patients with bronchopulmonary dysplasia: A single center case series.

PURPOSE: Preterm pediatric patients with bronchopulmonary dysplasia (BPD) represent a subgroup previously deemed high risk candidates for ECLS (extracorporeal life support) due to suspected high mortality or increased post ECLS morbidity. The aim of this study was to determine outcomes for patients with an established history of BPD who subsequently required ECLS. METHODS: A single center retrospective review was performed between 01/2010-06/2022 for patients less than 2 years of age, born prematurely (<32 weeks) with a subsequent diagnosis of BPD, and who required ECLS for respiratory failure. Demographic and clinical data, including ECLS data, were collected. Speech, language, feeding/swallowing, cognitive, hearing, vision, or motor function deficits were obtained with a median follow up of 42 months following discharge. RESULTS: Nineteen patients met criteria. The median birth weight and gestational age was 0.86 kg (IQR 0.73, 1.0) and 26 weeks (IQR 25, 27), respectively. The median chronological age at cannulation was 12.1 months. The most common etiologies for respiratory failure requiring ECLS were viral (68.4%) and bacterial (21.1%) pneumonia. Survival to decannulation was 78.9% (15/19) and survival to hospital discharge was 63.2% (12/19). Amongst survivors to discharge, 42% (5/12) required new or additional home oxygen and 50% (6/12) were noted to have neurodevelopmental/behavioral concerns on follow up at 1 year with 25% (3/12) with concerns beyond a year. CONCLUSION: Patients with underlying BPD who require ECLS have comparable mortality and long-term neurodevelopmental outcomes to non-BPD patients with respiratory failure. This information can be useful when considering ECLS candidacy and providing family counseling.

Derivation and Validation of Generalized Sepsis-induced Acute Respiratory Failure Phenotypes Among Critically Ill Patients: A Retrospective Study.

Background: Septic patients who develop acute respiratory failure (ARF) requiring mechanical ventilation represent a heterogenous subgroup of critically ill patients with widely variable clinical characteristics. Identifying distinct phenotypes of these patients may reveal insights about the broader heterogeneity in the clinical course of sepsis. We aimed to derive novel phenotypes of sepsis-induced ARF using observational clinical data and investigate their generalizability across multi-ICU specialties, considering multi-organ dynamics. Methods: We performed a multi-center retrospective study of ICU patients with sepsis who required mechanical ventilation for ≥24 hours. Data from two different high-volume academic hospital systems were used as a derivation set with N=3,225 medical ICU (MICU) patients and a validation set with N=848 MICU patients. For the multi-ICU validation, we utilized retrospective data from two surgical ICUs at the same hospitals (N=1,577). Clinical data from 24 hours preceding intubation was used to derive distinct phenotypes using an explainable machine learning-based clustering model interpreted by clinical experts. Results: Four distinct ARF phenotypes were identified: A (severe multi-organ dysfunction (MOD) with a high likelihood of kidney injury and heart failure), B (severe hypoxemic respiratory failure [median P/F=123]), C (mild hypoxia [median P/F=240]), and D (severe MOD with a high likelihood of hepatic injury, coagulopathy, and lactic acidosis). Patients in each phenotype showed differences in clinical course and mortality rates despite similarities in demographics and admission co-morbidities. The phenotypes were reproduced in external validation utilizing an external MICU from second hospital and SICUs from both centers. Kaplan-Meier analysis showed significant difference in 28-day mortality across the phenotypes (p<0.01) and consistent across both centers. The phenotypes demonstrated differences in treatment effects associated with high positive end-expiratory pressure (PEEP) strategy. Conclusion: The phenotypes demonstrated unique patterns of organ injury and differences in clinical outcomes, which may help inform future research and clinical trial design for tailored management strategies.

CD8+ T cells are necessary for improved sepsis survival induced by CD28 agonism in immunologically experienced mice.

Introduction: A hallmark of T cell dysregulation during sepsis is the downregulation of costimulatory molecules. CD28 is one of T cell costimulatory molecules significantly altered on memory T cells during sepsis. We recently showed that treatment with a αCD28 agonist in septic immunologically experienced mice led to improved survival. Therefore, here we aimed to identify the cell subset(s) necessary for the survival benefit observed in the context of CD28 agonism, and to further investigate the mechanism by which CD28 agonism improves sepsis survival in immunologically experienced mice. Methods: Mice received specific pathogen inoculation to generate memory T cell populations similar in frequency to that of adult humans. Once these infections were cleared and the T cell response had transitioned to the memory phase, animals were rendered septic via cecal ligation and puncture in the presence or absence of an agonistic anti-CD28 mAb. Results: Results demonstrated that CD8+ T cells, and not bulk CD4+ T cells or CD25+ regulatory T cells, were necessary for the survival benefit observed in CD28 agonist-treated septic immunologically experienced mice. Upon examination of these CD8+ T cells, we found that CD28 agonism in septic immunologically experienced mice was associated with an increase in Foxp3+ CD8+ T cells as compared to vehicle-treated controls. When CD8+ T cells were depleted in septic immunologically experienced mice in the setting of CD28 agonism, a significant increase in levels of inflammatory cytokines in the blood was observed. Discussion: Taken together, these results indicate that CD28 agonism in immunologically experienced mice effectively suppresses inflammation via a CD8+-dependent mechanism to decrease mortality during sepsis.

Light-activated BioID - an optically activated proximity labeling system to study protein-protein interactions.

Proximity labeling with genetically encoded enzymes is widely used to study protein-protein interactions in cells. However, the accuracy of proximity labeling is limited by a lack of control over the enzymatic labeling process. Here, we present a light-activated proximity labeling technology for mapping protein-protein interactions at the cell membrane with high accuracy and precision. Our technology, called light-activated BioID (LAB), fuses the two halves of the split-TurboID proximity labeling enzyme to the photodimeric proteins CRY2 and CIB1. We demonstrate, in multiple cell lines, that upon illumination with blue light, CRY2 and CIB1 dimerize, reconstitute split-TurboID and initiate biotinylation. Turning off the light leads to the dissociation of CRY2 and CIB1 and halts biotinylation. We benchmark LAB against the widely used TurboID proximity labeling method by measuring the proteome of E-cadherin, an essential cell-cell adhesion protein. We show that LAB can map E-cadherin-binding partners with higher accuracy and significantly fewer false positives than TurboID.

Uncertainty-Aware Convolutional Neural Network for Identifying Bilateral Opacities on Chest X-rays: A Tool to Aid Diagnosis of Acute Respiratory Distress Syndrome.

Acute Respiratory Distress Syndrome (ARDS) is a severe lung injury with high mortality, primarily characterized by bilateral pulmonary opacities on chest radiographs and hypoxemia. In this work, we trained a convolutional neural network (CNN) model that can reliably identify bilateral opacities on routine chest X-ray images of critically ill patients. We propose this model as a tool to generate predictive alerts for possible ARDS cases, enabling early diagnosis. Our team created a unique dataset of 7800 single-view chest-X-ray images labeled for the presence of bilateral or unilateral pulmonary opacities, or 'equivocal' images, by three blinded clinicians. We used a novel training technique that enables the CNN to explicitly predict the 'equivocal' class using an uncertainty-aware label smoothing loss. We achieved an Area under the Receiver Operating Characteristic Curve (AUROC) of 0.82 (95% CI: 0.80, 0.85), a precision of 0.75 (95% CI: 0.73, 0.78), and a sensitivity of 0.76 (95% CI: 0.73, 0.78) on the internal test set while achieving an (AUROC) of 0.84 (95% CI: 0.81, 0.86), a precision of 0.73 (95% CI: 0.63, 0.69), and a sensitivity of 0.73 (95% CI: 0.70, 0.75) on an external validation set. Further, our results show that this approach improves the model calibration and diagnostic odds ratio of the hypothesized alert tool, making it ideal for clinical decision support systems.

Optimizing the Synergistic Potential of Pseudo-Labels from Radiology Notes and Annotated Ground Truth in Identifying Pulmonary Opacities on Chest Radiographs for Early Detection of Acute Respiratory Distress Syndrome.

Acute Respiratory Distress Syndrome (ARDS) is a life-threatening lung injury, hallmarks of which are bilateral radiographic opacities. Studies have shown that early recognition of ARDS could reduce severity and lethal clinical sequela. A Convolutional Neural Network (CNN) model that can identify bilateral pulmonary opacities on chest x-ray (CXR) images can aid early ARDS recognition. Obtaining large datasets with ground truth labels to train CNNs is challenging, as medical image annotation requires clinical expertise and meticulous consideration. In this work, we implement a natural language processing pipeline that extracts pseudo-labels CXR images by parsing radiology notes for abnormal findings. We obtain ground-truth annotations from clinicians for the presence of pulmonary opacities for a subset of these images. A knowledge distillation-based teacher-student training framework is implemented to leverage the larger dataset with noisy pseudo-labels. Our results show an AUC of 0.93 (95%CI 0.92-0.94) for the prediction of bilateral opacities on chest radiographs.

Video-Assisted Thoracoscopic Internal Rib Fixation.

Rib fractures result in serious morbidity and mortality after trauma. Although there is ongoing debate about surgical rib fixation, it is increasingly important for some patients. Minimally invasive techniques for rib fixation are gaining traction within the trauma community. We present an observational experience at our level 1 trauma center with our first 10 cases of video-assisted thoracoscopic surgery (VATS) internal rib fixation. Video-assisted thoracoscopic surgery internal plates are especially helpful for rib fractures under the scapula, which are difficult to access traditionally. This technique is also excellent at reducing complex segmental fractures as the bridge can span across multiple fractures with a single post on either side. They also work well for posterior fractures where multiple screws cannot be placed. Video-assisted thoracoscopic surgery internal rib fixation is a viable and exciting option for surgical fixation. The plates work particularly well for certain fracture patterns.

Femoral-Femoral Bypass for Limb Salvage to Correct Common Iliac Occlusion after Lower Extremity Trauma.

BACKGROUND: Roadway injuries are a leading cause of lower extremity vascular trauma. Treating these injuries involves controlling life-threatening hemorrhage and restoring distal perfusion. MATERIALS AND METHODS: We describe a unique presentation of chronic iliac artery occlusion in the setting of blunt trauma requiring extra-anatomic bypass for maximal limb salvage. RESULTS: A 50-year-old male presented after a pedestrian versus auto accident. He had mangled bilateral lower extremities and was taken emergently for lower extremity amputations. He was found to have chronic left common iliac occlusion and a femoral-femoral bypass was performed to assist with healing his left below-the-knee amputation. DISCUSSION: Lack of adequate perfusion can cause poor outcomes in limb salvage. This case demonstrated that lower extremity trauma can be complicated by chronic vascular disease. Reperfusion and adequate wound healing can be accomplished by using bypass grafting after more traditional reperfusion techniques fail.

An expanded palette of dopamine sensors for multiplex imaging in vivo.

Genetically encoded dopamine sensors based on green fluorescent protein (GFP) enable high-resolution imaging of dopamine dynamics in behaving animals. However, these GFP-based variants cannot be readily combined with commonly used optical sensors and actuators, due to spectral overlap. We therefore engineered red-shifted variants of dopamine sensors called RdLight1, based on mApple. RdLight1 can be combined with GFP-based sensors with minimal interference and shows high photostability, permitting prolonged continuous imaging. We demonstrate the utility of RdLight1 for receptor-specific pharmacological analysis in cell culture, simultaneous assessment of dopamine release and cell-type-specific neuronal activity and simultaneous subsecond monitoring of multiple neurotransmitters in freely behaving rats. Dual-color photometry revealed that dopamine release in the nucleus accumbens evoked by reward-predictive cues is accompanied by a rapid suppression of glutamate release. By enabling multiplexed imaging of dopamine with other circuit components in vivo, RdLight1 opens avenues for understanding many aspects of dopamine biology.

The financial and employment effects of coronavirus disease 2019 on physicians in the United States.

Although the coronavirus disease 2019 (COVID-19) pandemic has created havoc with the U.S healthcare system and physicians, the financial and contractual implications for physicians are now beginning to come to the forefront. Financial assistance from the federal government has mainly been received by hospitals, which have borne the brunt of the COVID-19 illness. Some physician groups have, or are, receiving assistance through a few programs, although the accelerated and advance payments have been suspended. Employed surgeons are now being furloughed, terminated, or persuaded to agree to a significant cut in pay, forego bonuses, or take leave without pay as healthcare systems and some physician groups have started to experience the consequences of halting elective procedures. Newly hired surgeons might be forced in a few cases to agree to delays in starting their employment, new amendments, changes in employment status, and other terms for fear of losing their employment. In the present report, we have explained some agreement terminology and options available to allow physicians to understand the terms of their employment agreement and make their decisions after consulting with an expert healthcare attorney.

Refining a Church-Based Lifestyle Intervention Targeting African-American Adults at Risk for Cardiometabolic Diseases: A Pilot Study.

OBJECTIVE: The pilot study was intended to test the feasibility of a multiple-component lifestyle intervention targeting African American adults in a weight control and cardiometabolic risk reduction program on diet, activity, and stress, using community-engagement principles. METHODS: Applying mixed qualitative and quantitative measures, the intervention had a two-part sequential study design consisting of 12 weekly small group sessions that provided individual and group counseling in nutrition, exercise, and mindfulness, while incorporating focus group and interactive techniques to learn about barriers and acceptable practices for this population. The program was implemented at an African-American church in Nashville, Tennessee. RESULTS: Thirty-four participants (aged 56.1 ± 11 years, body mass index (BMI) 36.7 ± 6.6 kg/m2) completed the intervention. Lifestyle changes after the 12 weekly sessions showed some positive trends including reduced sodium intake (from 2725.3 ± 326.5 to 2132 ± 330, mg/day, P = 0.008), increased walking steps (from 4392.1 ± 497.2 to 4895.3 ± 497.9, steps/day, not significant), and slightly decreased Perceived Stress Scale (PSS) scores (from 13.7 ± 1.4 to 12.4 ± 1.5, not significant). Body fat % among male participants decreased significantly (from 33.8 ± 2.6 to 28 ± 2.6, %, P = 0.043). Among cardiometabolic risk biomarkers, hemoglobin A1c (HbA1c) decreased significantly (from 6.6 ± 0.2 to 6.1 ± 0.2, %, P < 0.001). The baseline PSS score was positively associated with baseline adiposity levels (e.g., weight, ß = 2.4, P = 0.006). Twenty-one participants took part in focus groups during the program to identify barriers to healthy lifestyle changes. Primary barriers reported were price, time for preparing healthy meals, unfamiliarity with mindfulness activities, their health condition, and daily schedule available for physical activities. CONCLUSIONS: This church-based pilot intervention was proven feasible by showing modest progress in reducing adiposity and decreasing HbA1c levels. The focus group and interactive methods facilitated program direction. Future full-scale studies are warranted to identify key strategies that provide more personalized approaches and supportive environments to sustain a healthy lifestyle among these at risk minorities with limited resources.

Adopting evidence-based medically assisted treatments in substance abuse treatment organizations: roles of leadership socialization and funding streams.

This paper examines the organizational adoption of medically assisted treatments (MAT) for substance use disorders (SUDs) in a representative sample of 555 US for-profit and not-for-profit treatment centers. The study examines organizational adoption of these treatments in an institutionally contested environment that traditionally has valued behavioral treatment, using sociological and resource dependence frameworks. The findings indicate that socialization of leadership, measured by formal clinical education, is related to the adoption of MAT. Funding patterns also affect innovation adoption, with greater adoption associated with higher proportions of earned income from third party fees for services, and less adoption associated with funding from criminal justice sources. These findings may generalize to other social mission-oriented organizations where innovation adoption may be linked to private and public benefit values inherent in the type of socialization of leadership and different patterns of funding support.

The potential role of sports psychology in the obesity epidemic.

Sports psychologists play an important role in enhancing performance among athletes. In conjunction with team physicians, they can also shed light on psychological disorders common in athletes, such as mood and eating disorders, and overtraining syndrome. Sports psychologists can also lend their expertise to assist with injury prevention and recovery and compliance issues. Sports psychology has a role in helping to reverse the growing obesity epidemic among school-aged children. These professionals, working with coaches, can increase children's levels of physical activity. Cognitive-behavioral techniques could lead to enhanced enjoyment, increased participation, improved school performance, and a reduction in obesity.

Chronic Methamphetamine Causes Differential Expression of Immediate Early Genes in the Nucleus Accumbens and Midbrain of Rats.

The present study investigated whether chronic methamphetamine (METH) would suppress METH-induced mRNA expression of immediate early genes (IEGs) in the rat brain. Rats were given METH or saline over two weeks. After an overnight withdrawal, saline- and METH-pretreated rats received an acute saline or METH challenge. The acute METH challenge increased expression of members of activator protein 1 (AP-1) and Nr4a IEG families in the nucleus accumbens (NAc) and midbrain of saline-pretreated rats. Chronic METH exposure attenuated the effects of acute METH challenge on AP-1 IEG expression in the NAc. However, chronic METH failed to attenuate acute METH-induced increases of Nr4a1 and Nr4a3 expression in the NAc. In contrast to observations in the NAc, chronic METH did not prevent acute METH-induced changes in IEG expression in the midbrain. These results suggest that these two brain regions that are implicated in neuroplastic effects of illicit substances might be differentially affected by psychostimulants.

Blood transfusions in critical care: improving safety through technology & process analysis.

A multidisciplinary safety initiative transformed blood transfusion practices at St. Luke's Episcopal Hospital in Houston, Texas. An intense analysis of a mistransfusion using the principles of a Just Culture and the process of Cause Mapping identified system and human performance factors that led to the transfusion error. Multiple initiatives were implemented including technology, education and human behaviour change. The wireless technology of Pyxis Transfusion Verification by CareFusion is effective with the rapid infusion module efficient for use in critical care. Improvements in blood transfusion safety were accomplished by thoroughly evaluating the process of transfusions and by implementing wireless electronic transfusion verification technology. During the 27 months following implementation of the CareFusion Transfusion Verification there have been zero cases of transfusing mismatched blood.

Latino adolescent mothers and fathers in south Texas managing violence.

During the course of this study young Latino parents living in San Antonio, TX shared their stories. Their stories draw attention to the multiple forms of violence they experienced in the past, continue to experience, and are forced to manage. Their lives occur within the context of enduring social disparities and exposure to violence. At a young age they develop strategies to manage violence, but new challenges with violence manifest themselves as they enter into intimate partner relationships. For some of these youth, parenthood is perceived as a transforming experience that offers an opportunity for a positive change in their life trajectory. They recognize the need to find non-violent ways to manage their relationships with their intimate partner and their children. Culturally-appropriate intervention strategies that focus on developing relationships of equality and balance are needed.