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Mast cell–derived mediators induce vasodilatation and fluid extravasation, leading to cardiovascular failure in severe anaphylaxis. We previously revealed a synergistic interaction between the cytokine IL-4 and the mast cell–derived mediator histamine in modulating vascular endothelial (VE) dysfunction and severe anaphylaxis. The mechanism by which IL-4 exacerbates histamine-induced VE dysfunction and severe anaphylaxis is unknown. We sought to identify the IL-4–induced molecular processes regulating the amplification of histamine-induced VE barrier dysfunction and the severity of IgE-mediated anaphylactic reactions. RNA sequencing, Western blot, Ca2+ imaging, and barrier functional analyses were performed on the VE cell line (EA.hy926). Pharmacologic degraders (selective proteolysis-targeting chimera) and genetic (lentiviral short hairpin RNA) inhibitors were used to determine the roles of signal transducer and activator of transcription 3 (STAT3) and STAT6 in conjunction with in vivo model systems of histamine-induced hypovolemic shock. IL-4 enhancement of histamine-induced VE barrier dysfunction was associated with increased VE-cadherin degradation, intracellular calcium flux, and phosphorylated Src levels and required transcription and de novo protein synthesis. RNA sequencing analyses of IL-4–stimulated VE cells identified dysregulation of genes involved in cell proliferation, cell development, and cell growth, and transcription factor motif analyses revealed a significant enrichment of differential expressed genes with putative STAT3 and STAT6 motif. IL-4 stimulation in EA.hy926 cells induced both serine residue 727 and tyrosine residue 705 phosphorylation of STAT3. Genetic and pharmacologic ablation of VE STAT3 activity revealed a role for STAT3 in basal VE barrier function; however, IL-4 enhancement and histamine-induced VE barrier dysfunction was predominantly STAT3 independent. In contrast, IL-4 enhancement and histamine-induced VE barrier dysfunction was STAT6 dependent. Consistent with this finding, pharmacologic knockdown of STAT6 abrogated IL-4–mediated amplification of histamine-induced hypovolemia. These studies unveil a novel role of the IL-4/STAT6 signaling axis in the priming of VE cells predisposing to exacerbation of histamine-induced anaphylaxis. [ABSTRACT FROM AUTHOR]

Heart disease and chronic kidney disease are often comorbid conditions owing to shared risk factors, including diabetes and hypertension. However, the effect of congestive heart failure (CHF) on arteriovenous fistula (AVF) and AV graft (AVG) patency rates is poorly understood. We hypothesize preexisting HF may diminish blood flow to the developing AVF and worsen patency. We conducted a single-institution retrospective review of 412 patients with end-stage renal disease who underwent hemodialysis access creation from 2015 to 2021. Patients were stratified based on presence of preexisting CHF, defined as clinical symptoms plus evidence of reduced left ventricular ejection fraction (EF) (<50%) or diastolic dysfunction on preoperative echocardiography. Baseline demographics, preoperative measures of cardiac function, and dialysis access-related surgical history were collected. Kaplan-Meier time-to-event analyses were performed for primary patency, primary-assisted patency, and secondary patency using standard definitions for patency from the literature. We assessed differences in patency for patients with CHF vs patients without CHF, patients with a reduced vs a normal EF, and AVG vs AVF in patients with CHF. We included 204 patients (50%) with preexisting CHF with confirmatory echocardiography. Patients with CHF were more likely to be male and have comorbidities including, diabetes, chronic obstructive pulmonary disease, hypertension, and a history of cerebrovascular accident. The groups were not significantly different in terms of prior fistula history (P =.99), body mass index (P =.74), or type of hemodialysis access created (P =.54). There was no statistically significant difference in primary patency, primary-assisted patency, or secondary patency over time in the CHF vs non-CHF group (log-rank P >.05 for all three patency measures). When stratified by preoperative left ventricular EF, patients with an EF of <50% had lower primary (38% vs 51% at 1 year), primary-assisted (76% vs 82% at 1 year), and secondary patency (86% vs 93% at 1 year) rates than those with a normal EF. Difference reached significance for secondary patency only (log-rank P =.029). AVG patency was compared against AVF patency within the CHF subgroup, with significantly lower primary-assisted (39% vs 87% at 1 year) and secondary (62% vs 95%) patency rates for AVG (P <.0001 for both). In this 7-year experience of hemodialysis access creation, reduced EF is associated with lower secondary patency. Preoperative CHF (including HF with reduced EF and HF with preserved EF together) is not associated with significant differences in overall hemodialysis access patency rates over time, but patients with CHF who receive AVG have markedly worse patency than those who receive AVF. For patients with end-stage renal disease and CHF, the risks and benefits must be carefully weighed, particularly for those with low EF or lack of a suitable vein for fistula creation. [ABSTRACT FROM AUTHOR]

Targeted muscle reinnervation (TMR) was developed to improve myoelectric prosthesis control for amputees; however, it has become an area of interest in pain modulation. Evidences indicate that this procedure alleviates chronic pain in amputees. The primary objective of this study was to use social media analysis to understand patients' post-operative pain, satisfaction, and recovery time after TMR. Data were collected from one Facebook group via posts and comments referencing TMR. Posts published between January 1, 2020, and March 24, 2023 were analyzed. Data collected included pain prior to surgery, pain in immediate post-op period, and change in pain after surgery. Forty-three individuals commented on their TMR experience. Among them, 31 had favorable surgical outcomes, 7 felt that the surgery worsened their pain or there was no significant change in their pain levels, and 5 commented during the initial post-operative period. Twenty-four patients described their pain in the immediate post-operative period and all patients said that the post-operative pain was worse than chronic pain. Among the 28 authors who commented on overall reduction in chronic pain, 24 reported that TMR reduced their pain, whereas 4 reported no change or worsened pain. The number of patients (24) who reported improvement in chronic pain aligns with the results in current literature suggesting that TMR is a viable treatment option for pain management. With the current medical management of similar conditions, up to 80% of patients remain unsatisfied with pain management. This analysis supports the evidence that TMR is an effective treatment for patients experiencing post-amputation pain. [ABSTRACT FROM AUTHOR]

The physical demands of sports can place patients at elevated risk of use-related pathologies, including thoracic outlet syndrome (TOS). Overhead athletes in particular (eg, baseball and football players, swimmers, divers, and weightlifters) often subject their subclavian vessels and brachial plexuses to repetitive trauma, resulting in venous effort thrombosis, arterial occlusions, brachial plexopathy, and more. This patient population is at higher risk for Paget-Schroetter syndrome, or effort thrombosis, although neurogenic TOS (nTOS) is still the predominant form of the disease among all groups. First-rib resection is almost always recommended for vascular TOS in a young, active population, although a surgical benefit for patients with nTOS is less clear. Practitioners specializing in upper extremity disorders should take care to differentiate TOS from other repetitive use–related disorders, including shoulder orthopedic injuries and nerve entrapments at other areas of the neck and arm, as TOS is usually a diagnosis of exclusion. For nTOS, physical therapy is a cornerstone of diagnosis, along with response to injections. Most patients first undergo some period of nonoperative management with intense physical therapy and training before proceeding with rib resection. It is particularly essential for ensuring that athletes can return to their baselines of flexibility, strength, and stamina in the upper extremity. Botulinum toxin and lidocaine injections in the anterior scalene muscle might predict which patients will likely benefit from first-rib resection. Athletes are usually satisfied with their decisions to undergo first-rib resection, although the risk of rare but potentially career- or life-threatening complications, such as brachial plexus injury or subclavian vessel injury, must be considered. Frequently, they are able to return to the same or a higher level of play after full recovery. [ABSTRACT FROM AUTHOR]

The hypothesis of this study was that trigeminal nerve stimulation (TNS) or peripheral nerve stimulation (PNS) could improve functional outcomes of peripheral nerve injury in a rat forelimb model when compared to control rats not receiving electrical stimulation (ES). While PNS is known to improve outcomes after nerve surgery, the role of TNS has not been explored. Lewis rats were trained to perform a reach and grasp task before receiving a 2 mm gap repair of the ulnar and median nerves and randomized into four treatment groups: (1) sham injury, (2) nerve injury with sham ES, (3) nerve injury with PNS, and (4) nerve injury with TNS. Functional motor (median pull force and percent success in motor task) and sensory metrics (forelimb paw withdrawal thresholds) were collected both pre-injury and throughout rehabilitation. Nerves stained using Gomori's trichrome were assessed quantitatively and qualitatively. The sham ES group did not recover their pre-injury baseline functional outcomes. In contrast, the TNS and PNS groups fully recovered following injury, with no difference in functional outcomes between the pre-injury baseline and the final week of rehabilitation (P > 0.05, all). Histomorphology results demonstrated no quantitative difference, but qualitative differences in architecture were evident. Electrical stimulation of the trigeminal nerve or the injured nerve improved the functional outcomes of nerve regeneration in rodents. Histomorphology results of nerves from the TNS group support the proposed central mechanisms. This is an important step in translating this therapy as an adjunct, non-invasive treatment for high, mixed nerve injuries in humans. [ABSTRACT FROM AUTHOR]

This study investigated the differential impact of COVID-19 on United States (US) adolescents' physical health as a function of sociodemographic factors over 18 months. It was hypothesized that the impact of COVID-19 and its mitigation efforts on physical health factors would vary by sociodemographic factors. Data were drawn from a longitudinal study in which participants (ages 16 or 18) self-reported sleep, diet, and physical activity over 18months. Participants were enrolled between 2018 and 2022. Participants (n = 190, 73% Black/African American, 53% female) provided 1330 reports over 194 weeks (93 weeks before and 101 weeks after COVID-19 restrictions implementation). Physical health outcomes moderated by demographic factors were measured and assessed over 18 months. Multilevel models and general estimated equations estimated the impact of COVID-19 restrictions on participants' health outcomes. Sleep and physical activity worsened after COVID-19 regardless of moderating factors, but some specific outcomes varied across subgroups. This study diversifies the literature on the impact of COVID-19 and its mitigation measures on adolescents' social health. Further, it is based in the US's Deep South, largely populated by those identifying as Black/African American or of low socioeconomic status. Both subgroups are underrepresented in US-based health outcomes research. COVID-19 directly and indirectly impacted adolescents' physical health. Understanding if and how COVID-19 impacted adolescents' health will inform nursing practice to adapt to and overcome adverse sequelae to promote positive patient health outcomes. [ABSTRACT FROM AUTHOR]

Plastic surgeons play a critical role in the management of amputations and are uniquely positioned to improve the lives and functional abilities of patients with limb loss. The embodiment of a prosthesis describes how effectively it replaces a missing limb and is an important aspect of patient care. Despite its importance, the current prosthetics literature lacks a formal definition of embodiment, and descriptions are often vague or incomplete. In this narrative review, we assess the current literature on prosthetic embodiment to explore the main mechanisms of embodiment and how each allows a prosthesis to interface with the human body. In doing so, we provide a comprehensive, holistic framework for understanding this concept. [ABSTRACT FROM AUTHOR]

• Soiling after Hirschsprung disease pull-through may be related to sphincter damage which currently has no optimal treatment. • A new technique of anal sphincter reconstruction showed improvement of bowel control in these patients at one year. • Non-sedate 3D-anorectal manometry showed improvement of squeeze function and ability to complete close the anal sphincters. • In patients without Down syndrome, improvement in Baylor Continence Scale was demonstrated (4.5 vs. 0.75). In patients with Hirschsprung disease (HSCR), soiling may be related to anal sphincter damage following the initial pull-through. No optimal treatment has been developed for such patients, although enemas (rectal or antegrade) have been applied with some success. We present the one-year outcomes of a new technique for anal sphincter reconstruction. All patients with HSCR referred from other institutions for post pull-through soiling were studied. Seven patients with patulous sphincters underwent sphincter reconstruction. Six had a full preoperative evaluation and were included in the study. Their 12-month outcomes were assessed. All six patients had soiling without voluntary bowel movements (VBMs). One patient was clean on Malone flushes when referred. Three underwent pre- and post-reconstruction non-sedated three-dimensional anorectal manometry, and objectively were able to close their sphincters following the reconstruction. All patients without Down syndrome (4 of 6) showed improvement in the abbreviated Baylor Continence Scale (4.5 vs. 0.75). One patient has achieved total bowel control without antegrade flushes, three now have VBMs which they did not have before but have occasional accidents and use antegrade flushes intermittently. They reported higher productivity, the ability to participate in sports and be away from home with confidence in their regimen. Two of 6 patients have Down syndrome and required a redo pull-through for other indications and underwent empiric sphincter reconstruction. For these two patients we do not have an outcomes assessment. A new technique for sphincter reconstruction shows promising results in improvement of bowel control at one year. IV [ABSTRACT FROM AUTHOR]

• Treating refractory functional constipation requires a collaborative approach by surgeons and gastroenterologists. • The work-up should include a contrast enema, anorectal manometry for assessment of the sphincters, and a colonic motility evaluation. • Antegrade flushes are effective and colon resections can be avoided in most cases, regardless of underlying colonic dysmotility. Management of refractory constipation in children has not been standardized. We propose a protocolized approach which includes a contrast enema, anorectal manometry and exclusion of Hirschsprung disease (HD). For those without HD or with normal sphincters, an assessment of the colonic motility may be needed. The subgroups of dysmotility include (1) slow motility with contractions throughout, (2) segmental dysmotility (usually the sigmoid), or (3) a diffusely inert colon. We offered a Malone appendicostomy in all groups with the hope that this would avoid colonic resection in most cases. Patients with medically refractory constipation were reviewed at a single institution (2020 to 2021). For patients without HD or an anal sphincter problem, assessment of colonic motility using colonic manometry was performed followed by a Malone appendicostomy for antegrade flushes. Of 196 patients evaluated for constipation refractory to medical management, 22 were felt to have a colonic motility cause. These patients underwent colonic manometry and Malone appendicostomy. 13 patients (59%) had a slow colon but with HAPCs throughout, 5 (23%) had segmental dysmotility, and 4 (18%) had a diffuse colonic dysmotility. 19 (86%) responded well to antegrade flushes with 17 reporting no soiling and 2 having occasional accidents. 3 patients (14%) failed flushes and underwent a colon resection within 6-month following Malone procedure. We propose a protocol for medically refractory constipation which provides a collaborative framework to standardize evaluation and management of these patients with antegrade flushes, which aids in avoidance of colonic resection in most cases. Level IV [ABSTRACT FROM AUTHOR]

In US states, childhood immunization mandates are enforced for school registration by front-line school staff, usually secretaries. Despite substantial changes to mandate policies in several states and many countries, little attention has been paid to the people who enforce them. This qualitative pilot study aimed to uncover beliefs, attitudes, and practices regarding immunization governance of Michigan school staff. Front-line administrative workers from Michigan schools and district offices were solicited by email. Sixteen were interviewed remotely. Front-line school staff believed in vaccines, but did not advocate for vaccination while registering children. Instead, they sought low-friction bureaucratic transactions, privileging the collection of data over the promotion of public health goals. This revealed a mismatch between the goals of the front-line staff who enforce vaccine mandates in schools and the goals of the policymakers who created school vaccine mandates. This study found low mobilization of front-line enforcers of mandates in public-facing school administration roles, a problem likely to afflict the majority of American states with the 'mandates + exemptions' model of immunization governance. Schools would have stronger incentives to promote vaccination if state funding were better tied to immunization compliance. Front-line staff could better enforce vaccine mandates if they were provided with resources and training about vaccine promotion. [ABSTRACT FROM AUTHOR]