Regulation of PGC1α Downstream of the Insulin Signaling Pathway Plays a Role in the Hepatic Proteotoxicity of Mutant α1-Antitrypsin Deficiency Variant Z.

BACKGROUND & AIMS: Insulin signaling is known to regulate essential proteostasis mechanisms. METHODS: The analyses here examined effects of insulin signaling in the PiZ mouse model of α1-antitrypsin deficiency in which hepatocellular accumulation and proteotoxicity of the misfolded α1-antitrypsin Z variant (ATZ) causes liver fibrosis and cancer. RESULTS: We first studied the effects of breeding PiZ mice to liver-insulin-receptor knockout (LIRKO) mice (with hepatocyte-specific insulin-receptor gene disruption). The results showed decreased hepatic ATZ accumulation and liver fibrosis in PiZ x LIRKO vs PiZ mice, with reversal of those effects when we bred PiZ x LIRKO mice onto a FOXO1-deficient background. Increased intracellular degradation of ATZ mediated by autophagy was identified as the likely mechanism for diminished hepatic proteotoxicity in PiZ x LIRKO mice and the converse was responsible for enhanced toxicity in PiZ x LIRKO x FOXO1-KO animals. Transcriptomic studies showed major effects on oxidative phosphorylation and autophagy genes, and significant induction of peroxisome proliferator-activated-receptor-γ-coactivator-1α (PGC1α) expression in PiZ-LIRKO mice. Because PGC1α plays a key role in oxidative phosphorylation, we further investigated its effects on ATZ proteostasis in our ATZ-expressing mammalian cell model. The results showed PGC1α overexpression or activation enhances autophagic ATZ degradation. CONCLUSIONS: These data implicate suppression of autophagic ATZ degradation by down-regulation of PGC1α as one mechanism by which insulin signaling exacerbates hepatic proteotoxicity in PiZ mice, and identify PGC1α as a novel target for development of new human α1-antitrypsin deficiency liver disease therapies.

Multidisciplinary Care for Refractory Pediatric Functional Abdominal Pain Decreases Emergency and Inpatient Utilization.

ABSTRACT: Children with refractory functional abdominal pain (FAP) experience functional disability and may utilize emergency department (ED) and/or inpatient services. Whether multidisciplinary programs which help care for children with refractory FAP affect acute healthcare utilization is unknown. A retrospective chart review of children initially evaluated by the outpatient Multidisciplinary Abdominal Pain Program (MAPP) from October 2016 to May 2019 was completed. Patient characteristics and number of ED visits and hospitalizations for abdominal pain in the year prior to versus year after MAPP evaluation were captured. Thirty-eight children (ages 9-17 years [median 13 years]) were included. The median number of ED visits/patient/year decreased from 1 (range: 0-7) to 0 (range: 0-3) (P < 0.0001). Seven (18%) children had been hospitalized and, in these children, the median number of hospitalizations/patient/year decreased from 1 (range: 1-5) to 0 (range: 0-1) (P < 0.05). These data suggest multidisciplinary outpatient intervention for refractory FAP is associated with significant decreases in acute healthcare utilization.

Foxl1-Cre-marked adult hepatic progenitors have clonogenic and bilineage differentiation potential.

Isolation of hepatic progenitor cells is a promising approach for cell replacement therapy of chronic liver disease. The winged helix transcription factor Foxl1 is a marker for progenitor cells and their descendants in the mouse liver in vivo. Here, we purify progenitor cells from Foxl1-Cre; RosaYFP mice and evaluate their proliferative and differentiation potential in vitro. Treatment of Foxl1-Cre; RosaYFP mice with a 3,5-diethoxycarbonyl-1,4-dihydrocollidine diet led to an increase of the percentage of YFP-labeled Foxl1(+) cells. Clonogenic assays demonstrated that up to 3.6% of Foxl1(+) cells had proliferative potential. Foxl1(+) cells differentiated into cholangiocytes and hepatocytes in vitro, depending on the culture condition employed. Microarray analyses indicated that Foxl1(+) cells express stem cell markers such as Prom1 as well as differentiation markers such as Ck19 and Hnf4a. Thus, the Foxl1-Cre; RosaYFP model allows for easy isolation of adult hepatic progenitor cells that can be expanded and differentiated in culture.

Interventional magnetic resonance imaging guided carotid embolectomy using a novel resonant marker catheter: demonstration of preclinical feasibility.

To assess the visualization and efficacy of a wireless resonant circuit (wRC) catheter system for carotid artery occlusion and embolectomy under real-time MRI guidance in vivo, and to compare MR imaging modality with x-ray for analysis of qualitative physiological measures of blood flow at baseline and after embolectomy. The wRC catheter system was constructed using a MR compatible PEEK fiber braided catheter (Penumbra, Inc, Alameda, CA) with a single insulated longitudinal copper loop soldered to a printed circuit board embedded within the catheter wall. In concordance with IACUC protocol (AN103047), in vivo carotid artery navigation and embolectomy were performed in four farm pigs (40-45 kg) under real-time MRI at 1.5T. Industry standard clots were introduced in incremental amounts until adequate arterial occlusion was noted in a total of n=13 arteries. Baseline vasculature and restoration of blood flow were confirmed via MR and x-ray imaging, and graded by the Thrombolysis in Cerebral Infarction (TICI) scale. Wilcoxon signed-rank tests were used to analyze differences in recanalization status between DSA and MRA imaging. Successful recanalizations (TICI 2b/3) were compared to clinical rates reported in literature via binomial tests. The wRC catheter system was visible both on 5° sagittal bSSFP and coronal GRE sequence. Successful recanalization was demonstrated in 11 of 13 occluded arteries by DSA analysis and 8 of 13 by MRA. Recanalization rates based on DSA (0.85) and MRA (0.62) were not significantly different from the clinical rate of mechanical aspiration thrombectomy reported in literature. Lastly, a Wilcoxon signed rank test indicated no significant difference between TICI scores analyzed by DSA and MRA. With demonstrated compatibility and visualization under MRI, the wRC catheter system is effective for in vivo endovascular embolectomy, suggesting progress towards clinical endovascular interventional MRI.

Alcaligenes faecalis Cellulitis After a Dog Bite: Case Report and Literature Review.

Alcaligenes faecalis is a gram-negative organism that is commonly found in the environment and may also be a part of normal fecal flora in humans. Although various infections with this bacteria have been described in the pediatric population, it has not been previously identified in infections as the pathogen after a dog bite. A case of a 19-month-old boy is presented with a cellulitis secondary to a dog bite, which failed oral antibiotic therapy, and progressed to worsening fever and swelling. The patient ultimately required hospitalization, intravenous antibiotics, and incision and drainage. The wound culture grew A. faecalis, whose identity was confirmed through recombinant DNA sequence analysis. Although it has been identified in cat bite wounds, A. faecalis has not been cited in the literature before in an infection after a dog bite.

Spontaneous Subclavian Vein Thrombosis in a Healthy Adolescent Cheerleader: A Case of Paget-Schroetter Syndrome.

We present the case of a healthy 13-year-old female adolescent who developed acute progressive swelling and pain in her right upper extremity that was secondary to an acute deep venous thrombosis of her right subclavian vein. Dynamic imaging revealed subclavian vein compression at the junction of the first rib and proximal third of the clavicle consistent with Paget-Schroetter syndrome, also known as effort-related thrombosis. The compressive etiology of her thrombus was most likely related to her cheerleading activity, in which she served as the pyramid base. The patient received multimodal therapy including anticoagulation, mechanical and site-directed thrombolysis, and a first rib resection. This case illustrates that frontline providers should have a high index of suspicion for an upper extremity thrombosis in pediatric patients who present with unilateral arm swelling.

Endovascular MR-guided Renal Embolization by Using a Magnetically Assisted Remote-controlled Catheter System.

Purpose To assess the feasibility of a magnetically assisted remote-controlled (MARC) catheter system under magnetic resonance (MR) imaging guidance for performing a simple endovascular procedure (ie, renal artery embolization) in vivo and to compare with x-ray guidance to determine the value of MR imaging guidance and the specific areas where the MARC system can be improved. Materials and Methods In concordance with the Institutional Animal Care and Use Committee protocol, in vivo renal artery navigation and embolization were tested in three farm pigs (mean weight 43 kg ± 2 [standard deviation]) under real-time MR imaging at 1.5 T. The MARC catheter device was constructed by using an intramural copper-braided catheter connected to a laser-lithographed saddle coil at the distal tip. Interventionalists controlled an in-room cart that delivered electrical current to deflect the catheter in the MR imager. Contralateral kidneys were similarly embolized under x-ray guidance by using standard clinical catheters and guidewires. Changes in renal artery flow and perfusion were measured before and after embolization by using velocity-encoded and perfusion MR imaging. Catheter navigation times, renal parenchymal perfusion, and renal artery flow rates were measured for MR-guided and x-ray-guided embolization procedures and are presented as means ± standard deviation in this pilot study. Results Embolization was successful in all six kidneys under both x-ray and MR imaging guidance. Mean catheterization time with MR guidance was 93 seconds ± 56, compared with 60 seconds ± 22 for x-ray guidance. Mean changes in perfusion rates were 4.9 au/sec ± 0.8 versus 4.6 au/sec ± 0.6, and mean changes in renal flow rate were 2.1 mL/min/g ± 0.2 versus 1.9 mL/min/g ± 0.2 with MR imaging and x-ray guidance, respectively. Conclusion The MARC catheter system is feasible for renal artery catheterization and embolization under real-time MR imaging in vivo, and quantitative physiologic measures under MR imaging guidance were similar to those measured under x-ray guidance, suggesting that the MARC catheter system could be used for endovascular procedures with interventional MR imaging. (©) RSNA, 2016.

Is severe progressive liver disease caused by alpha-1-antitrypsin deficiency more common in children or adults?

The classical form of alpha-1-antitrypsin deficiency (A1ATD) is known to cause liver disease in children and adults, but there is relatively little information about the risk of severe, progressive liver disease and the need for liver transplantation. To better understand how newly evolving pharmacological, genetic, and cellular therapies may be targeted according to risk for progressive liver disease, we sought to determine the age distribution of A1ATD as a cause of severe liver disease, as defined by the need for liver transplantation. Using 3 US liver transplantation databases for the period 1991-2012, we found 77.2% of 1677 liver transplants with a reported diagnosis of A1ATD were adults. The peak age range was 50-64 years. Using 2 of the databases which included specific A1AT phenotypes, we found that many of these adults who undergo liver transplantation with A1ATD as the diagnosis are heterozygotes and have other potential causes of liver disease, most notably obesity and ethanol abuse. However, even when these cases are excluded and only ZZ and SZ phenotypes are considered, severe liver disease requiring transplantation is more than 2.5 times as likely in adults. The analysis also showed a markedly increased risk for males. In the pediatric group, almost all of the transplants are done in children less than 5 years of age. In conclusion, A1ATD causes progressive liver disease most commonly in adults with males in the highest risk category. In the pediatric group, children less than 5 years of age are highest in risk. These results suggest that A1ATD most commonly causes liver disease by mechanisms similar to age-dependent degenerative diseases and more rarely in children by powerful modifiers. Liver Transplantation 22 886-894 2016 AASLD.

A Healthy Infant With an Ulcerated Genital Lesion: Diagnostic and Therapeutic Considerations.

We present the case of a 1-year-old healthy boy who was taking oral antibiotics for an otitis media and then developed an erythematous penile lesion that rapidly became ulcerated. He was admitted to the hospital for further diagnostic studies and intravenous therapy, and his wound culture grew Pseudomonas aeruginosa, consistent with the diagnosis of ecthyma gangrenosum. Serial blood counts also demonstrated a progressive neutropenia, and an immunodeficiency evaluation resulted in the diagnosis of autoimmune neutropenia of childhood. This case illustrates the importance of culturing wounds and the need for clinicians to recognize the characteristic features of ecthyma gangrenosum, to initiate appropriate antipseudomonal antibiotic therapy empirically, and to evaluate for a possible immunodeficiency, even in the apparently healthy child.

Acute disseminated encephalomyelitis following meningoencephalitis: case report and literature review.

Meningoencephalitis and acute disseminated encephalomyelitis (ADEM) are both neurological disease processes, but there have been few cases of meningoencephalitis progressing to ADEM in the pediatric population. A case of a 4-year-old girl with an initial diagnosis of meningoencephalitis is presented here, whose initial presentation was manifested by prolonged fever, gray matter signal abnormality on brain magnetic resonance imaging, cerebrospinal fluid pleocytosis, and a markedly irritable mental status. As her neurological examination changed with focal abnormalities, a repeat magnetic resonance imaging demonstrated new areas of both gray and white matter signal abnormality, consistent with ADEM. Her symptoms and imaging findings completely resolved with a course of methylprednisolone. Based on the literature and this current case, it is our recommendation to consider ADEM as a diagnosis if meningoencephalitis is not improving.

The Role of Large Language Models in Transforming Emergency Medicine: Scoping Review.

BACKGROUND: Artificial intelligence (AI), more specifically large language models (LLMs), holds significant potential in revolutionizing emergency care delivery by optimizing clinical workflows and enhancing the quality of decision-making. Although enthusiasm for integrating LLMs into emergency medicine (EM) is growing, the existing literature is characterized by a disparate collection of individual studies, conceptual analyses, and preliminary implementations. Given these complexities and gaps in understanding, a cohesive framework is needed to comprehend the existing body of knowledge on the application of LLMs in EM. OBJECTIVE: Given the absence of a comprehensive framework for exploring the roles of LLMs in EM, this scoping review aims to systematically map the existing literature on LLMs' potential applications within EM and identify directions for future research. Addressing this gap will allow for informed advancements in the field. METHODS: Using PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews) criteria, we searched Ovid MEDLINE, Embase, Web of Science, and Google Scholar for papers published between January 2018 and August 2023 that discussed LLMs' use in EM. We excluded other forms of AI. A total of 1994 unique titles and abstracts were screened, and each full-text paper was independently reviewed by 2 authors. Data were abstracted independently, and 5 authors performed a collaborative quantitative and qualitative synthesis of the data. RESULTS: A total of 43 papers were included. Studies were predominantly from 2022 to 2023 and conducted in the United States and China. We uncovered four major themes: (1) clinical decision-making and support was highlighted as a pivotal area, with LLMs playing a substantial role in enhancing patient care, notably through their application in real-time triage, allowing early recognition of patient urgency; (2) efficiency, workflow, and information management demonstrated the capacity of LLMs to significantly boost operational efficiency, particularly through the automation of patient record synthesis, which could reduce administrative burden and enhance patient-centric care; (3) risks, ethics, and transparency were identified as areas of concern, especially regarding the reliability of LLMs' outputs, and specific studies highlighted the challenges of ensuring unbiased decision-making amidst potentially flawed training data sets, stressing the importance of thorough validation and ethical oversight; and (4) education and communication possibilities included LLMs' capacity to enrich medical training, such as through using simulated patient interactions that enhance communication skills. CONCLUSIONS: LLMs have the potential to fundamentally transform EM, enhancing clinical decision-making, optimizing workflows, and improving patient outcomes. This review sets the stage for future advancements by identifying key research areas: prospective validation of LLM applications, establishing standards for responsible use, understanding provider and patient perceptions, and improving physicians' AI literacy. Effective integration of LLMs into EM will require collaborative efforts and thorough evaluation to ensure these technologies can be safely and effectively applied.

Serum D-2-hydroxyglutarate and the ratio of D-2HG/L-2HG predict IDH mutation in acute myeloid leukemia.

This study investigates whether serum D-2HG (D-2-hydroxyglutarate) produced by the mutated isocitrate dehydrogenase (IDH) can predict IDH mutations in acute myeloid leukemia (AML) at diagnosis. D-2HG and L-2HG are measured by liquid chromatography-tandem mass spectrometry. D-2HG, total 2HG and the D/L ratio (D-2HG/L-2HG) are significantly higher in IDH mutated cases than in IDH wild cases. The optimal cutoff values to predict IDH mutations at 100% sensitivity (specificity 91%-94%) are >588 ng/mL for D-2HG and >2.33 for the D/L ratio. Our study indicates that elevated serum D-2HG and the D/L ratio may serve as noninvasive biomarkers of IDH mutation in AML.

Adult mixed phenotype acute leukemia (MPAL): B/myeloid MPALisoMPO is distinct from other MPAL subtypes.

INTRODUCTION: Myeloperoxidase (MPO) is considered a specific marker of myeloid/non-monocytic lineage in the diagnosis of mixed phenotype acute leukemia (MPAL). However, the clinical significance of isolated dim MPO expression in otherwise typical B lymphoblastic leukemia (B-ALL; referred to as B/myeloid MPALisoMPO ) in adult patients is unknown. METHODS: We compared flow cytometric immunophenotype and clinicopathological findings among cases of B/myeloid MPALisoMPO (n = 13), other MPAL subtypes (n = 10, B/myeloid and T/myeloid MPAL), B-ALL (n = 64), and acute myeloid leukemia (AML, n = 58), using the 2016 WHO classification. For MPAL cases, MPO was reported as the percent of MPO positive blasts and its intensity (dim or moderate/strong). The pattern of heterogenous antigen expression (inversely coordinated expression between myeloid and lymphoid markers and cell size) was assessed. RESULTS: Cases of B/myeloid MPALisoMPO showed a fairly homogenous single B-lineage blast population with dim MPO expression whereas cases of other MPAL subtypes displayed heterogeneous antigen expression and moderate/strong MPO expression. The percent of MPO positive blasts in these two groups was similar. Expressions of CD15, CD117, and monocytic markers were more common in other MPAL than in B/myeloid MPALisoMPO . B/myeloid MPALisoMPO patients had similar overall and leukemia free survivals as B-ALL patients and better than other MPAL patients. CONCLUSION: This is the first study to investigate the clinical significance of adult B/myeloid MPALisoMPO using the 2016 WHO classification. Our results suggest that B/myeloid MPALisoMPO clinically behaves more similarly to B-ALL than to other MPAL subtypes, supporting the 2016 WHO classification to segregate this entity from other MPAL subtypes.

Cholangiocyte cilia are abnormal in syndromic and non-syndromic biliary atresia.

Biliary atresia (BA) is a neonatal disorder characterized by aggressive fibroinflammatory obliteration of the biliary tract. Approximately 20 percent of BA patients demonstrate left-right laterality defects (syndromic BA). Cilia participate in important physiological functions in cholangiocytes, and as some ciliopathies have been associated with both laterality defects and hepatic fibrosis, we hypothesized that patients with syndromic BA exhibit abnormalities of cholangiocyte cilia that disrupt cholangiocyte homeostasis. Nine BA specimens were studied, including pre-Kasai diagnostic biopsies (n=7) and liver explants (n=2). Five specimens were from patients with laterality defects. These were compared with normal pediatric livers, as well as livers affected by primary sclerosing cholangitis, Wilson's disease, and cardiac cirrhosis. Biopsy sections were stained with antibodies against keratin 19 (a cholangiocyte marker) and acetylated α-tubulin (a cilia marker) and were visualized by confocal microscopy. Computer-assisted relative quantification was used to compare staining of cilia within bile ducts among samples. Surprisingly, cilia in BA specimens were significantly shorter, abnormal in their orientation, and less abundant compared with normal liver and disease controls regardless of the presence of a laterality defect. There are significant abnormalities of cholangiocyte cilia in both syndromic and non-syndromic BA livers compared with normal livers and livers affected by other cholestatic diseases. Although this may result from severe cholestasis or inflammation, it may also reflect common mechanistic pathways in different forms of BA and may have important implications for understanding the progression of the disease.

Lineage tracing demonstrates no evidence of cholangiocyte epithelial-to-mesenchymal transition in murine models of hepatic fibrosis.

UNLABELLED: Whether or not cholangiocytes or their hepatic progenitors undergo an epithelial-to-mesenchymal transition (EMT) to become matrix-producing myofibroblasts during biliary fibrosis is a significant ongoing controversy. To assess whether EMT is active during biliary fibrosis, we used Alfp-Cre × Rosa26-YFP mice, in which the epithelial cells of the liver (hepatocytes, cholangiocytes, and their bipotential progenitors) are heritably labeled at high efficiency with yellow fluorescent protein (YFP). Primary cholangiocytes isolated from our reporter strain were able to undergo EMT in vitro when treated with transforming growth factor-ß1 alone or in combination with tumor necrosis factor-α, as indicated by adoption of fibroblastoid morphology, intracellular relocalization of E-cadherin, and expression of α-smooth muscle actin (α-SMA). To determine whether EMT occurs in vivo, we induced liver fibrosis in Alfp-Cre × Rosa26-YFP mice using the bile duct ligation (BDL) (2, 4, and 8 weeks), carbon tetrachloride (CCl(4) ) (3 weeks), and 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC; 2 and 3 weeks) models. In no case did we find evidence of colocalization of YFP with the mesenchymal markers S100A4, vimentin, α-SMA, or procollagen 1α2, although these proteins were abundant in the peribiliary regions. CONCLUSION: Hepatocytes and cholangiocytes do not undergo EMT in murine models of hepatic fibrosis.

Seeds in the Lungs: A Pseudo-Miliary Pattern of Sarcoidosis.

We present a 26-year-old African-American gentleman with no significant past medical history who presented with a three-day history of dry cough. Computerized tomography of the chest showed scattered infiltrates consistent with a pseudo-miliary pattern. A transbronchial biopsy showed non-caseating granulomas confirming our suspicion for pulmonary sarcoidosis. Miliary sarcoidosis is rare; therefore, health care providers should consider other diagnoses such as tuberculosis, malignancy, and pneumoconiosis.

Reengineering the specificity of the highly selective Clostridium botulinum protease via directed evolution.

The botulinum neurotoxin serotype A (BoNT/A) cuts a single peptide bond in SNAP25, an activity used to treat a wide range of diseases. Reengineering the substrate specificity of BoNT/A's protease domain (LC/A) could expand its therapeutic applications; however, LC/A's extended substrate recognition (≈ 60 residues) challenges conventional approaches. We report a directed evolution method for retargeting LC/A and retaining its exquisite specificity. The resultant eight-mutation LC/A (omLC/A) has improved cleavage specificity and catalytic efficiency (1300- and 120-fold, respectively) for SNAP23 versus SNAP25 compared to a previously reported LC/A variant. Importantly, the BoNT/A holotoxin equipped with omLC/A retains its ability to form full-length holotoxin, infiltrate neurons, and cleave SNAP23. The identification of substrate control loops outside BoNT/A's active site could guide the design of improved BoNT proteases and inhibitors.

A role for microRNA in cystic liver and kidney diseases.

The polycystic liver and kidney diseases are a family of disorders with heterogeneous etiologies. Proposed mechanisms of disease include ciliary dysfunction, excess cell proliferation, and altered cell-cell or cell-matrix interactions. In this issue of the JCI, Lee and colleagues provide data to support a novel mechanism for cystogenesis involving microRNA (miRNA) (see the related article beginning on page 3714). They demonstrate that levels of the miRNA miR15a are decreased in livers of patients with autosomal recessive and autosomal dominant polycystic kidney disease (ARPKD and ADPKD, respectively) and congenital hepatic fibrosis as well as in the PKC rat model of ARPKD. This results in increased expression of the cell-cycle regulator Cdc25A, which is a direct target of miR15a, and increased cellular proliferation and cystogenesis in vitro. These findings suggest that other miRNAs may also participate in the molecular pathogenesis of cystic liver and kidney diseases.

A random-walk-based epidemiological model.

Random walkers on a two-dimensional square lattice are used to explore the spatio-temporal growth of an epidemic. We have found that a simple random-walk system generates non-trivial dynamics compared with traditional well-mixed models. Phase diagrams characterizing the long-term behaviors of the epidemics are calculated numerically. The functional dependence of the basic reproductive number [Formula: see text] on the model's defining parameters reveals the role of spatial fluctuations and leads to a novel expression for [Formula: see text]. Special attention is given to simulations of inter-regional transmission of the contagion. The scaling of the epidemic with respect to space and time scales is studied in detail in the critical region, which is shown to be compatible with the directed-percolation universality class.

STAT: Mobile app helps clinicians manage inpatient emergencies.

In response to the unprecedented surge of patients with COVID-19, Massachusetts General Hospital created both repurposed and de-novo COVID-19 inpatient general medicine and intensive care units. The clinicians staffing these new services included those who typically worked in these care settings (e.g., medicine residents, hospitalists, intensivists), as well as others who typically practice in other care environments (e.g., re-deployed outpatient internists, medical subspecialists, and other physician specialties). These surge clinicians did not have extensive experience managing low frequency, high acuity emergencies, such as those that might result from COVID-19. Physician-innovators, in collaboration with key hospital stakeholders, developed a comprehensive strategy to design, develop, and distribute a digital health solution to address this problem. MGH STAT is an intuitive mobile application that empowers clinicians to respond to medical emergencies by providing immediate access to up-to-date clinical guidelines, consultants, and code-running tools at the point-of-care. 100% of surveyed physicians found STAT to be easy to use and would recommend it to others. Approximately 1100 clinicians have downloaded the app, and it continues to enjoy consistent use over a year after the initial COVID-19 surge. These results suggest that STAT has helped clinicians manage life threatening emergencies during and after the pandemic, although formal studies are necessary to evaluate its direct impact on patient care.