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Importance: Over 580 000 people in the US experience homelessness, with one of the largest concentrations residing in San Francisco, California. Unhoused individuals have a life expectancy of approximately 50 years, yet how sudden death contributes to this early mortality is unknown., Objective: To compare incidence and causes of sudden death by autopsy among housed and unhoused individuals in San Francisco County., Design, Setting, and Participants: This cohort study used data from the Postmortem Systematic Investigation of Sudden Cardiac Death (POST SCD) study, a prospective cohort of consecutive out-of-hospital cardiac arrest deaths countywide among individuals aged 18 to 90 years. Cases meeting World Health Organization criteria for presumed SCD underwent autopsy, toxicologic analysis, and medical record review. For rate calculations, all 525 incident SCDs in the initial cohort were used (February 1, 2011, to March 1, 2014). For analysis of causes, 343 SCDs (incident cases approximately every third day) were added from the extended cohort (March 1, 2014, to December 16, 2018). Data analysis was performed from July 1, 2022, to July 1, 2023., Main Outcomes and Measures: The main outcomes were incidence and causes of presumed SCD by housing status. Causes of sudden death were adjudicated as arrhythmic (potentially rescuable with implantable cardioverter-defibrillator), cardiac nonarrhythmic (eg, tamponade), or noncardiac (eg, overdose)., Results: A total of 868 presumed SCDs over 8 years were identified: 151 unhoused individuals (17.4%) and 717 housed individuals (82.6%). Unhoused individuals compared with housed individuals were younger (mean [SD] age, 56.7 [0.8] vs 61.0 [0.5] years, respectively) and more often male (132 [87.4%] vs 499 [69.6%]), with statistically significant racial differences. Paramedic response times were similar (mean [SD] time to arrival, unhoused individuals: 5.6 [0.4] minutes; housed individuals: 5.6 [0.2] minutes; P = .99), while proportion of witnessed sudden deaths was lower among unhoused individuals compared with housed individuals (27 [18.0%] vs 184 [25.7%], respectively, P = .04). Unhoused individuals had higher rates of sudden death (incidence rate ratio [IRR], 16.2; 95% CI, 5.1-51.2; P < .001) and arrhythmic death (IRR, 7.2; 95% CI, 1.3-40.1; P = .02). These associations remained statistically significant after adjustment for differences in age and sex. Noncardiac causes (96 [63.6%] vs 270 [37.7%], P < .001), including occult overdose (48 [31.8%] vs 90 [12.6%], P < .001), gastrointestinal causes (8 [5.3%] vs 15 [2.1%], P = .03), and infection (11 [7.3%] vs 20 [2.8%], P = .01), were more common among sudden deaths in unhoused individuals. A lower proportion of sudden deaths in unhoused individuals were due to arrhythmic causes (48 of 151 [31.8%] vs 420 of 717 [58.6%], P < .001), including acute and chronic coronary disease., Conclusions and Relevance: In this cohort study among individuals who experienced sudden death in San Francisco County, homelessness was associated with greater risk of sudden death from both noncardiac causes and arrhythmic causes potentially preventable with a defibrillator.

Background: This study aimed to compare the amount of artifacts induced by the titanium and zirconium implants on cone-beam computed tomography (CBCT) and assess the effect of different exposure settings on the image quality for both materials., Methods: In this experimental study, 30 zirconium and 30 titanium implants were placed in bovine rib bone blocks. CBCT images were taken in two different fields of view (FOV: 4 × 6 cm 2 and 6 × 8 cm 2 ) and at two resolutions (133 µ and 200 µ voxel size). Subsequently, two observers assessed the images and detected the amount of artifacts around the implants through gray values. Data were analyzed by paired t test and independent t test using SPSS 21 and the 0.05 significance level., Results: The results showed that titanium implants caused lower amounts of artifacts than zirconium implants, which was statistically significant (P < 0.001). The larger FOV (6 × 8 cm 2 ) resulted in a lower amount of artifacts in both groups, although the results were only statistically significant in the zirconium group (P < 0.001). The amount of artifacts was increased when using the 133 µ voxel size in both groups, which was only significant in the zirconium group (P < 0.001)., Conclusion: Our results suggest that zirconium implants induce higher amounts of artifacts than titanium ones. We also concluded that the artifacts could be minimized using the larger FOV and voxel size., (© 2022. The Author(s).)

Background: Patients hospitalized with acute myocardial infarction (AMI) have a high mortality rate. Despite increasing recognition of the role for comfort focused care, little is known about the prevalence of comfort measures only (CMO) care among patients with AMI. The objective of this study was to investigate patient- and hospital-level patterns and predictors of CMO care among patients admitted with AMI., Methods: This retrospective cohort study used the National Cardiovascular Data Registry Chest Pain-MI Registry, which contains data on patients admitted with AMI. Data were analyzed in 6-month increments from January 2015 to June 2018., Results: Among 483 696 patients with AMI across 827 hospitals, 13 955 (2.9%) had CMO status at discharge (2.6% non-ST-segment-elevation myocardial infarction and 3.4% ST-segment-elevation myocardial infarction). There was a modest decline in CMO rates over time (3.0% to 2.8%). Independent patient characteristics associated with CMO status included male gender, White race, nonprivate insurance, frailty, and higher estimated bleeding and mortality risks. There was substantial variation in CMO rates across hospitals, with the proportion of CMO patients ranging from 0% to 17.1% and a median odds ratio of 1.59 (95% CI, 1.56-1.62). Among the 13 955 patients who were CMO by discharge, 8134 (58.3%) underwent diagnostic catheterization. This is despite significantly elevated risks predicted using precatheterization models, specifically the ACTION Registry GWTG in-hospital major bleeding and mortality risk scores. Patients who were initially managed invasively but later made CMO experienced high rates of procedural complications, including cardiogenic shock (38.3%), dialysis (10.1%), and bleeding (33.3%)., Conclusions: Most patients with AMI who were CMO by discharge had aggressive initial management and became CMO following in-hospital complications of their care. Early identification of high-risk patients and appropriate transition of such patients to CMO, if aligned with their values, remain important areas for future quality programs in AMI.

Introduction: Point-of-care ultrasound (POCUS) is a powerful clinical tool that has seen widespread adoption, including in Internal Medicine (IM), yet standardized curricula designed by trained faculty are scant. To address the demand for POCUS education at our institution, we created a resident-championed curriculum with support from skilled faculty across multiple specialties. Our objective was to teach postgraduate year (PGY)-3 IM residents the basics of POCUS for evaluation of the pulmonary, cardiac, and abdominal systems through resident-developed workshops. The goal of acquisition of these skills was for resident education and to inform decisions to pursue further patient testing. Methods: Three half-day workshops were created to teach residents how to obtain and interpret ultrasound images of the pulmonary, cardiac, and abdominal systems. Workshops were comprised of didactic teaching and practical ultrasound instruction with expert supervision of clinicians within and outside of IM. Residents were asked to complete a written survey before and after each workshop to assess confidence, knowledge, and likelihood of future POCUS use. Results: Across the three workshops (pulmonary, cardiac, and abdominal), 66 sets of pre- and post-workshop surveys (32 pulmonary, 25 cardiac, and 9 abdominal) were obtained and analyzed. Confidence in and knowledge regarding POCUS use increased significantly across all three workshops. Likelihood of future use increased in the cardiac workshop. Conclusions: We implemented a resident-championed POCUS curriculum that led to improved attitudes and increased knowledge of POCUS for PGY-3 IM residents., Competing Interests: All authors declare that they have no conflict of interest., (Copyright (c) 2021 Leila Haghighat, Heyley Israel, Eric Jordan, Ethan L. Bernstein, Merilyn Varghese, Benjamin M. Cherry, Reinier Van Tonder, Shyoko Honiden, Rachel Liu, Christopher Sankey.)

Importance: Many older survivors of acute myocardial infarction (AMI) experience functional decline, an outcome of primary importance to older adults. Mobility impairment has been proposed as a risk factor for functional decline but has not been evaluated to date in older patients hospitalized for AMI., Objective: To examine the association of mobility impairment, measured during hospitalization, as a risk marker for functional decline among older patients with AMI., Design, Setting, and Participants: Prospective cohort study among 94 academic and community hospitals in the United States. Participants were 2587 hospitalized patients with AMI who were 75 years or older. The study dates were January 2013 to June 2017., Main Outcomes and Measures: Mobility was evaluated during AMI hospitalization using the Timed "Up and Go," with scores categorized as preserved mobility (≤15 seconds to complete), mild impairment (>15 to ≤25 seconds to complete), moderate impairment (>25 seconds to complete), and severe impairment (unable to complete). Self-reported function in activities of daily living (ADLs) (bathing, dressing, transferring, and walking around the home) and walking 0.4 km (one-quarter mile) was assessed at baseline and 6 months after discharge. The primary outcomes were worsening of 1 or more ADLs and loss of ability to walk 0.4 km from baseline to 6 months after discharge. The association between mobility impairment and risk of functional decline was evaluated with multivariable-adjusted logistic regression., Results: Among 2587 hospitalized patients with AMI, the mean (SD) age was 81.4 (4.8) years, and 1462 (56.5%) were male. More than half of the cohort exhibited mobility impairment during AMI hospitalization (21.8% [564 of 2587] had mild impairment, 16.0% [414 of 2587] had moderate impairment, and 15.2% [391 of 2587] had severe impairment); 12.8% (332 of 2587) reported ADL decline, and 16.7% (431 of 2587) reported decline in 0.4-km mobility. Only 3.8% (30 of 800) of participants with preserved mobility experienced any ADL decline compared with 6.9% (39 of 564) of participants with mild impairment (adjusted odds ratio [aOR], 1.24; 95% CI, 0.74-2.09), 18.6% (77 of 414) of participants with moderate impairment (aOR, 2.67; 95% CI, 1.67-4.27), and 34.7% (136 of 391) of participants with severe impairment (aOR, 5.45; 95% CI, 3.29-9.01). Eleven percent (90 of 800) of participants with preserved mobility declined in ability to walk 0.4 km compared with 15.2% (85 of 558) of participants with mild impairment (aOR, 1.51; 95% CI, 1.04-2.20), 19.0% (78 of 411) of participants with moderate impairment (aOR, 2.03; 95% CI, 1.37-3.02), and 24.6% (95 of 386) of participants with severe impairment (aOR, 3.25; 95% CI, 2.02-5.23)., Conclusions and Relevance: This study's findings suggest that mobility impairment assessed during hospitalization may be a potent risk marker for functional decline in older survivors of AMI. These findings also suggest that brief, validated assessments of mobility should be part of the care of older hospitalized patients with AMI to identify those at risk for this important patient-centered outcome.

Critical limb ischemia (CLI) is a highly morbid disease with many patients considered poor surgical candidates. The lack of treatment options for CLI has driven interest in developing molecular therapies within recent years. Through these translational medicine studies in CLI, much has been learned about the pathophysiology of the disease. Here, we present an overview of the macrovascular and microvascular changes that lead to the development of CLI, including impairment of angiogenesis, vasculogenesis, and arteriogenesis. We summarize the randomized clinical controlled trials that have used molecular therapies in CLI, and discuss the novel imaging modalities being developed to assess the efficacy of these therapies.

Critical limb ischemia (CLI) is a terminal stage of peripheral arterial disease that, in the absence of intervention, may lead to lower extremity amputation or death. Endovascular interventions have become a first-line approach to the management of CLI and have advanced considerably within the past decade. This review summarizes the types of percutaneous devices and the techniques that are available for the management of CLI and the data supporting their use. These include devices that establish and maintain vessel patency, including percutaneous transluminal angioplasty, drug-coated balloons, bare metal stents, drug-eluting stents, bioresorbable vascular scaffolds, and atherectomy; devices that provide protection from embolization; and, cell-based therapies. Additionally, ongoing trials with important implications for the field are discussed., Competing Interests: Dr. Mena-Hurtado reports receiving consulting fees from Bard, Medtronic, Cook and Abbott.

Lactobacillus sp. are commensal organisms that are increasingly reported to cause invasive infections among immunosuppressed persons. However, few data exist regarding the occurrence and risk factors of these infections among HIV-infected persons. Further, the safety of products that contain lactobacilli (e.g. probiotics) in certain populations, including those with HIV/AIDS, is unclear. We report a case of Lactobacillus acidophilus bacteraemia in a patient with AIDS temporally related to excessive consumption of probiotic-enriched yogurt, and provide a comprehensive review of the literature of Lactobacillus sp. infections among HIV-infected persons., (© The Author(s) 2015.)

Rationale: Schistosomiasis is a major cause of pulmonary arterial hypertension (PAH). Mutations in the bone morphogenetic protein type-II receptor (BMPR-II) are the commonest genetic cause of PAH., Objectives: To determine whether Bmpr2(+/-) mice are more susceptible to schistosomiasis-induced pulmonary vascular remodeling., Methods: Wild-type (WT) and Bmpr2(+/-) mice were infected percutaneously with Schistosoma mansoni. At 17 weeks postinfection, right ventricular systolic pressure and liver and lung egg counts were measured. Serum, lung and liver cytokine, pulmonary vascular remodeling, and liver histology were assessed., Measurements and Main Results: By 17 weeks postinfection, there was a significant increase in pulmonary vascular remodeling in infected mice. This was greater in Bmpr2(+/-) mice and was associated with an increase in egg deposition and cytokine expression, which induced pulmonary arterial smooth muscle cell proliferation, in the lungs of these mice. Interestingly, Bmpr2(+/-) mice demonstrated dilatation of the hepatic central vein at baseline and postinfection, compared with WT. Bmpr2(+/-) mice also showed significant dilatation of the liver sinusoids and an increase in inflammatory cells surrounding the central hepatic vein, compared with WT. This is consistent with an increase in the transhepatic passage of eggs., Conclusions: This study has shown that levels of BMPR-II expression modify the pulmonary vascular response to chronic schistosomiasis. The likely mechanism involves the increased passage of eggs to the lungs, caused by altered diameter of the hepatic veins and sinusoids in Bmpr2(+/-) mice. Genetically determined differences in the remodeling of hepatic vessels may represent a new risk factor for PAH associated with schistosomiasis.

Idiopathic pulmonary arterial hypertension (PAH [IPAH]) is an insidious and potentially fatal disease linked to a mutation or reduced expression of bone morphogenetic protein receptor 2 (BMPR2). Because intravascular inflammatory cells are recruited in IPAH pathogenesis, we hypothesized that reduced BMPR2 enhances production of the potent chemokine granulocyte macrophage colony-stimulating factor (GM-CSF) in response to an inflammatory perturbation. When human pulmonary artery (PA) endothelial cells deficient in BMPR2 were stimulated with tumor necrosis factor (TNF), a twofold increase in GM-CSF was observed and related to enhanced messenger RNA (mRNA) translation. The mechanism was associated with disruption of stress granule formation. Specifically, loss of BMPR2 induced prolonged phospho-p38 mitogen-activated protein kinase (MAPK) in response to TNF, and this increased GADD34-PP1 phosphatase activity, dephosphorylating eukaryotic translation initiation factor (eIF2α), and derepressing GM-CSF mRNA translation. Lungs from IPAH patients versus unused donor controls revealed heightened PA expression of GM-CSF co-distributing with increased TNF and expanded populations of hematopoietic and endothelial GM-CSF receptor α (GM-CSFRα)-positive cells. Moreover, a 3-wk infusion of GM-CSF in mice increased hypoxia-induced PAH, in association with increased perivascular macrophages and muscularized distal arteries, whereas blockade of GM-CSF repressed these features. Thus, reduced BMPR2 can subvert a stress granule response, heighten GM-CSF mRNA translation, increase inflammatory cell recruitment, and exacerbate PAH.

Dysfunctional bone morphogenetic protein receptor-2 (BMPR2) signaling is implicated in the pathogenesis of pulmonary arterial hypertension (PAH). We used a transcriptional high-throughput luciferase reporter assay to screen 3,756 FDA-approved drugs and bioactive compounds for induction of BMPR2 signaling. The best response was achieved with FK506 (tacrolimus), via a dual mechanism of action as a calcineurin inhibitor that also binds FK-binding protein-12 (FKBP12), a repressor of BMP signaling. FK506 released FKBP12 from type I receptors activin receptor-like kinase 1 (ALK1), ALK2, and ALK3 and activated downstream SMAD1/5 and MAPK signaling and ID1 gene regulation in a manner superior to the calcineurin inhibitor cyclosporine and the FKBP12 ligand rapamycin. In pulmonary artery endothelial cells (ECs) from patients with idiopathic PAH, low-dose FK506 reversed dysfunctional BMPR2 signaling. In mice with conditional Bmpr2 deletion in ECs, low-dose FK506 prevented exaggerated chronic hypoxic PAH associated with induction of EC targets of BMP signaling, such as apelin. Low-dose FK506 also reversed severe PAH in rats with medial hypertrophy following monocrotaline and in rats with neointima formation following VEGF receptor blockade and chronic hypoxia. Our studies indicate that low-dose FK506 could be useful in the treatment of PAH.

Previously, we reported that murine gammaherpesvirus-68 (M1-MHV-68) induces pulmonary artery (PA) neointimal lesions in S100A4-overexpressing, but not in wild-type (C57), mice. Lesions were associated with heightened lung elastase activity and PA elastin degradation. We now investigate a direct relationship between elastase and PA neointimal lesions, the nature and source of the enzyme, and its presence in clinical disease. We found an association exists between the percentage of PAs with neointimal lesions and elastin fragmentation in S100A4 mice 6 months after viral infection. Confocal microscopy documented the heightened susceptibility of S100A4 versus C57 PA elastin to degradation by elastase. A transient increase in lung elastase activity occurs in S100A4 mice, 7 days after M1-MHV-68, unrelated to inflammation or viral load and before neointimal lesions. Administration of recombinant elafin, an elastase-specific inhibitor, ameliorates early increases in serine elastase and attenuates later development of neointimal lesions. Neutrophils are the source of elevated elastase (NE) in the S100A4 lung, and NE mRNA and protein levels are greater in PA smooth muscle cells (SMC) from S100A4 mice than from C57 mice. Furthermore, elevated NE is observed in cultured PA SMC from idiopathic PA hypertension versus that in control lungs and localizes to neointimal lesions. Thus, PA SMC produce NE, and heightened production and activity of NE is linked to experimental and clinical pulmonary vascular disease., (Copyright © 2011 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Mycobacteriophages are viruses that infect mycobacterial hosts such as Mycobacterium smegmatis and Mycobacterium tuberculosis. All mycobacteriophages characterized to date are dsDNA tailed phages, and have either siphoviral or myoviral morphotypes. However, their genetic diversity is considerable, and although sixty-two genomes have been sequenced and comparatively analyzed, these likely represent only a small portion of the diversity of the mycobacteriophage population at large. Here we report the isolation, sequencing and comparative genomic analysis of 18 new mycobacteriophages isolated from geographically distinct locations within the United States. Although no clear correlation between location and genome type can be discerned, these genomes expand our knowledge of mycobacteriophage diversity and enhance our understanding of the roles of mobile elements in viral evolution. Expansion of the number of mycobacteriophages grouped within Cluster A provides insights into the basis of immune specificity in these temperate phages, and we also describe a novel example of apparent immunity theft. The isolation and genomic analysis of bacteriophages by freshman college students provides an example of an authentic research experience for novice scientists.