Functional outcomes of Fournier's gangrene: a multi-institutional experience.

INTRODUCTION: Fournier's gangrene (FG), is a progressive, necrotizing soft tissue infection of the external genitalia, perineum, and/or anorectal region. How treatment and recovery from FG impacts quality of life related to sexual and general health is poorly characterized. Our purpose is to evaluate the long term impact of FG on overall and sexual quality of life using standardized questionnaires through a multi-institutional observational study. MATERIALS AND METHODS: Multi-institutional retrospective data were collected by standardized questionnaires on patient-reported outcome measures including the Changes in Sexual Functioning Questionnaire (CSFQ) and the Veterans RAND 36 (VR-36) survey of general health-related quality of life. Data were collected via telephone call, email, and certified mail, with a 10% response rate. There was no incentive for patient participation. RESULTS: Thirty-five patients responded to the survey, with 9 female and 26 male patients. All patients in the study underwent surgical debridement between 2007-2018 at three tertiary care centers. Further reconstructions were performed for 57% of respondents. Values for respondents with overall lower sexual function were reduced in all component categories (pleasure, desire/ frequency, desire/interest, arousal/excitement, orgasm/ completion), and trended toward male sex, older age, longer time from initial debridement to reconstruction, and poorer self-reported general health-related quality of life metrics. CONCLUSION: FG is associated with high morbidity and significant decreases in quality of life across general and sexual functional domains.

Structure of Ddi2, a highly inducible detoxifying metalloenzyme from Saccharomyces cerevisiae.

Cyanamide (H2N-CN) is used to break bud dormancy in woody plants and to deter alcohol use in humans. The biological effects of cyanamide in both these cases require the enzyme catalase. We previously demonstrated that Saccharomyces cerevisiae exposed to cyanamide resulted in strong induction of DDI2 gene expression. Ddi2 enzymatically hydrates cyanamide to urea and belongs to the family of HD-domain metalloenzymes (named after conserved active-site metal-binding His and Asp residues). Here, we report the X-ray structure of yeast Ddi2 to 2.6 Å resolution, revealing that Ddi2 is a dimeric zinc metalloenzyme. We also confirm that Ddi2 shares structural similarity with other known HD-domain proteins. HD residues His-55, His-88, and Asp-89 coordinate the active-site zinc, and the fourth zinc ligand is a water/hydroxide molecule. Other HD domain enzymes have a second aspartate metal ligand, but in Ddi2 this residue (Thr-157) does not interact with the zinc ion. Several Ddi2 active-site point mutations exhibited reduced catalytic activity. We kinetically and structurally characterized H137N and T157V mutants of Ddi2. A cyanamide soak of the Ddi2-T157V enzyme revealed cyanamide bound directly to the Zn2+ ion, having displaced the zinc-bound water molecule. The mode of cyanamide binding to Ddi2 resembles cyanamide binding to the active-site zinc of carbonic anhydrase, a known cyanamide hydratase. Finally, we observed that the sensitivity of ddi2Δ ddi3Δ to cyanamide was not rescued by plasmids harboring ddi2-H137N or ddi2-TI57V variants, demonstrating that yeast cells require a functioning cyanamide hydratase to overcome cyanamide-induced growth defects.

Effects of employer management on employee recruitment, satisfaction, engagement, and retention on large US dairy farms.

Lack of employee engagement and satisfaction and high turnover rate of employees are major problems on some US dairy farms. Farm adoption of human resource management (HRM) practices varies widely. Using feedback from 168 employees from 12 large dairy farms, our objectives were to understand employee perceptions of HRM strengths and weaknesses and their influence on (1) employee satisfaction, (2) retention of employees, (3) willingness of employees to recommend the farm as a place to work, and (4) level of employee engagement on the farm. Employees who rated their employers higher for almost any management-related question (MRQ) were more satisfied in their jobs and more likely to recommend their place of work to other potential employees. Employees reported a higher intention to stay on the farm when employers scored higher on MRQs connected to employer-employee relationships. Employees who rated "Relationships" (a component consisting of 5 MRQs) higher were more likely to have a higher rate of satisfaction, were more likely to intend to stay at their job, and were more likely to recommend their place of work to others. No single management question was positively related to employee engagement (as measured by employees having and sharing ideas to improve the business); however, ethnicity, gender, job role, duration of employment, and employee's self-appraisal of their desire to learn and commitment to the farm were each associated with engagement. Female employees were less likely to provide ideas to their employers (compared with male employees), as were Spanish-speaking employees (compared with English-speaking employees). Differences between Spanish- and English-speaking employees were also present in measures such as intention to stay (shorter) and willingness to recommend the farm as a place to work (higher). Employees who rated themselves higher on their desire to learn and commitment to the farm were more likely to provide ideas to their employers, as were longer-term employees. In conclusion, we inferred that dairy farm management can improve employee retention and engagement through improved use of HRM practices.

Does Early Follow-Up Improve the Outcomes of Sepsis Survivors Discharged to Home Health Care?

BACKGROUND: There is little evidence to guide the care of over a million sepsis survivors following hospital discharge despite high rates of hospital readmission. OBJECTIVE: We examined whether early home health nursing (first visit within 2 days of hospital discharge and at least 1 additional visit in the first posthospital week) and early physician follow-up (an outpatient visit in the first posthospital week) reduce 30-day readmissions among Medicare sepsis survivors. DESIGN: A pragmatic, comparative effectiveness analysis of Medicare data from 2013 to 2014 using nonlinear instrumental variable analysis. SUBJECTS: Medicare beneficiaries in the 50 states and District of Columbia discharged alive after a sepsis hospitalization and received home health care. MEASURES: The outcomes, protocol parameters, and control variables were from Medicare administrative and claim files and the home health Outcome and Assessment Information Set (OASIS). The primary outcome was 30-day all-cause hospital readmission. RESULTS: Our sample consisted of 170,571 mostly non-Hispanic white (82.3%), female (57.5%), older adults (mean age, 76 y) with severe sepsis (86.9%) and a multitude of comorbid conditions and functional limitations. Among them, 44.7% received only the nursing protocol, 11.0% only the medical doctor protocol, 28.1% both protocols, and 16.2% neither. Although neither protocol by itself had a statistically significant effect on readmission, both together reduced the probability of 30-day all-cause readmission by 7 percentage points (P=0.006; 95% confidence interval=2, 12). CONCLUSIONS: Our findings suggest that, together, early postdischarge care by home health and medical providers can reduce hospital readmissions for sepsis survivors.

Evaluation by employees of employee management on large US dairy farms.

Employees, many of whom are not native English speakers, perform the majority of work on large US dairy farms. Although management of employees is a critical role of dairy owners and managers, factors that improve employee engagement and retention are not well known. Objectives were to (1) identify key dairy farm employee management issues based on employee perceptions, (2) evaluate strengths and weaknesses of farms based on employee responses, (3) investigate differences between Latino and English-speaking employees, and (4) investigate differences in perception between employers and employees. Employees from 12 US dairy farms (each with a minimum of 10 employees) were interviewed by phone following a questionnaire provided. Employees provided their responses to 21 Likert scale questions and 8 open-ended questions. There was a wide range in employee turnover among farms (<10 to >100%). Latino employees had much shorter tenure and were more often employed in milking and livestock care than English-speaking employees. Employee perceptions differed among farms regarding whether they would recommend their farm as a place to work, teamwork within the dairy, whether rules were fairly applied, availability of tools and equipment, clear lines of supervision, and recognition for good work in the previous 15 d. Latino employees (n = 91) were more positive in many of these measures than their English-speaking counterparts (n = 77) but less often provided ideas to their employer on how to improve the business. Employers, surveyed on how they thought their employees would answer, underestimated employee responses on several questions, particularly the interest of employees in learning about dairy. When asked to cite 3 goals of the operation, there were differences among owners, managers, and employees. Although employees rated their commitment to the farm and their interest in learning as high, based on turnover, there was an obvious disparity between reality and ideal employee management. Consequently, employers should act on identified management shortfalls to improve employee retention.

Two duplicated genes DDI2 and DDI3 in budding yeast encode a cyanamide hydratase and are induced by cyanamide.

Two DNA damage-inducible genes in Saccharomyces cerevisiae, DDI2 and DDI3, are identical and encode putative HD domain-containing proteins, whose functions are currently unknown. Because Ddi2/3 also shows limited homology to a fungal cyanamide hydratase that converts cyanamide to urea, we tested the enzymatic activity of recombinant Ddi2. To this end, we developed a novel enzymatic assay and determined that the Km value of the recombinant Ddi2/3 for cyanamide is 17.3 ± 0.05 mm, and its activity requires conserved residues in the HD domain. Unlike most other DNA damage-inducible genes, DDI2/3 is only induced by a specific set of alkylating agents and surprisingly is strongly induced by cyanamide. To characterize the biological function of DDI2/3, we sequentially deleted both DDI genes and found that the double mutant was unable to metabolize cyanamide and became much more sensitive to growth inhibition by cyanamide, suggesting that the DDI2/3 genes protect host cells from cyanamide toxicity. Despite the physiological relevance of the cyanamide induction, DDI2/3 is not involved in its own transcriptional regulation. The significance of cyanamide hydratase activity and its induced expression is discussed.

Helicobacter pylori FlgN binds its substrate FlgK and the flagellum ATPase FliI in a similar manner observed for the FliT chaperone.

In bacterial flagellum biogenesis, secretion of the hook-filament junction proteins FlgK and FlgL and completion of the flagellum requires the FlgN chaperone. Similarly, the related FliT chaperone is necessary for the secretion of the filament cap protein FliD and binds the flagellar export gate protein FlhA and the flagellum ATPase FliI. FlgN and FliT require FliJ for effective substrate secretion. In Helicobacter pylori, neither FlgN, FliT, nor FliJ have been annotated. We demonstrate that the genome location of HP1120 is identical to that of flgN in other flagellated bacteria and that HP1120 is the homolog of Campylobacter jejuni FlgN. A modeled HP1120 structure contains three α-helices and resembles the FliT chaperone, sharing a similar substrate-binding pocket. Using pulldowns and thermophoresis, we show that both HP1120 and a HP1120Δ126-144 deletion mutant bind to FlgK with nanomolar affinity, but not to the filament cap protein FliD, confirming that HP1120 is FlgN. Based on size-exclusion chromatography and multi-angle light scattering, H. pylori FlgN binds to FlgK with 1:1 stoichiometry. Overall structural similarities between FlgN and FliT suggest that substrate recognition on FlgN primarily involves an antiparallel coiled-coil interface between the third helix of FlgN and the C-terminal helix of the substrate. A FlgNΔ126-144 N100A, Y103A, S111I triple mutant targeting this interface significantly impairs the binding of FlgK. Finally, we demonstrate that FlgNΔ126-144 , like FliT, binds with sub-micromolar affinity to the flagellum ATPase FliI or its N-terminal domain. Hence FlgN and FliT likely couple delivery of low-abundance export substrates to the flagellum ATPase FliI.

Blunt traumatic female urethral and bladder neck injuries: a 15-year single-institution experience.

PURPOSE: To describe our experience in the management and outcomes of female patients with urethral or bladder neck (BN) injury at a high-volume Level 1 trauma center. METHODS: A retrospective chart review of all female patients with urethral or BN injury by blunt trauma mechanism admitted to a Level 1 trauma center between 2005 and 2019 was performed. RESULTS: Ten patients met study criteria with median age 36.5 years. All had concomitant pelvic fractures. All injuries were confirmed operatively, with no delayed diagnoses. Two patients were lost to follow up. One patient was not eligible for early repair of urethral injury and had two repairs of a urethrovaginal fistula. Two of seven (29%) patients who underwent early repair of their injury had an early Clavien grade > 2 complication, with none reporting long-term complications at median follow-up of 15.2 months. CONCLUSIONS: Intraoperative evaluation is critical in the diagnosis of female urethral and BN injury. In our experience, acute surgical complications are not uncommon after the management of such injuries. However, there were no reported long-term complications in those patients who had prompt management of their injury. This aggressive diagnostic and surgical strategy is instrumental in attaining excellent surgical outcomes.

Autoantibodies Neutralizing Type III Interferons Are Uncommon in Patients with Severe Coronavirus Disease 2019 Pneumonia.

Autoantibodies (AABs) neutralizing type I interferons (IFN) underlie about 15% of cases of critical coronavirus disease 2019 (COVID-19) pneumonia. The impact of autoimmunity toward type III IFNs remains unexplored. We included samples from 1,002 patients with COVID-19 (50% with severe disease) and 1,489 SARS-CoV-2-naive individuals. We studied the prevalence and neutralizing capacity of AABs toward IFNλ and IFNα. Luciferase-based immunoprecipitation method was applied using pooled IFNα (subtypes 1, 2, 8, and 21) or pooled IFNλ1-IFNλ3 as antigens, followed by reporter cell-based neutralization assay. In the SARS-CoV-2-naive cohort, IFNλ AABs were more common (8.5%) than those targeting IFNα2 (2.9%) and were related with older age. In the COVID-19 cohort the presence of autoreactivity to IFNλ did not associate with severe disease [odds ratio (OR) 0.84; 95% confidence interval (CI) 0.40-1.73], unlike to IFNα (OR 4.88; 95% CI 2.40-11.06; P < 0.001). Most IFNλ AAB-positive COVID-19 samples (67%) did not neutralize any of the 3 IFNλ subtypes. Pan-IFNλ neutralization occurred in 5 patients (0.50%), who all suffered from severe COVID-19 pneumonia, and 4 of them neutralized IFNα2 in addition to IFNλ. Overall, AABs to type III IFNs are rarely neutralizing, and do not seem to predispose to severe COVID-19 pneumonia on their own.

Draft genome sequences of Helicobacter pylori strains 17874 and P79.

Helicobacter pylori is a human pathogen that colonizes the human gastric mucosa, causing gastritis, duodenal and gastric ulcers, and gastric carcinoma. Here we announce the draft genomes of H. pylori strain 17874, commonly used for studying motility, and P79, a strain for which plasmid vectors have been developed.

Clinical and Demographic Profiles of Home Care Patients With Alzheimer's Disease and Related Dementias: Implications for Information Transfer Across Care Settings.

Home health care (HHC) clinicians serving individuals with Alzheimer's disease and related dementias (ADRD) do not always have information about the person's ADRD diagnosis, which may be used to improve the HHC plan of care. This retrospective cohort study examined characteristics of 56,652 HHC patients with varied documentation of ADRD diagnoses. Data included clinical assessments and Medicare claims for a 6-month look-back period and 4-year follow-up. Nearly half the sample had an ADRD diagnosis observed in the claims either prior to or following the HHC admission. Among those with a prior diagnosis, 63% did not have it documented on the HHC assessment; the diagnosis may not have been known to the HHC team or incorporated into the care plan. Patients with ADRD had heightened risk for adverse outcomes (e.g., urinary tract infection and aspiration pneumonia). Interoperable data across health care settings should include ADRD-specific elements about diagnoses, symptoms, and risk factors.

Structure of the cytoplasmic domain of the flagellar secretion apparatus component FlhA from Helicobacter pylori.

Using x-ray crystallography we have determined the structure of the cytoplasmic fragment (residues 384-732) of the flagellum secretion system protein FlhA from Helicobacter pylori at 2.4-A resolution (r = 0.224; R(free) = 0.263). FlhA proteins and their type III secretion homologues contain an N-terminal integral membrane domain (residues 1-350), a linker segment, and a globular C-terminal cytoplasmic region. The tertiary structure of the cytoplasmic fragment contains a thioredoxin-like domain, an RNA recognition motif-like domain inserted within the thioredoxin-fold, a helical domain, and a C-terminal beta/alpha domain. Inter-domain contacts are extensive and the H. pylori FlhA structure appears to be in a closed conformation where the C-terminal domain closes against the RNA recognition motif-fold domain. Highly conserved surface residues in FlhA proteins are concentrated on a narrow surface strip comprising the thioredoxin-like and helical domains, possibly close to the export channel opening. The conformation of the FlhA N-terminal linker segment suggests a likely orientation for the FlhA cytoplasmic fragment relative to the membrane-embedded export pore. Comparison with the recently published structures of the Salmonella FlhA cytoplasmic fragment and its type III secretion counterpart InvA highlight a conformational change where the C-terminal beta/alpha domain in H. pylori FlhA moves 15 A relative to Salmonella FlhA. The conformational change is complex but primarily involves hinge-like movements of the helical and C-terminal domains. Interpretation of previous mutational screens suggest that the C-terminal domain of FlhA(C) plays a regulatory role in substrate class switching in flagellum export.

Structural and biochemical studies on the chromo-barrel domain of male specific lethal 3 (MSL3) reveal a binding preference for mono- or dimethyllysine 20 on histone H4.

We have determined the human male specific lethal 3 (hMSL3) chromo-barrel domain structure by x-ray crystallography to a resolution of 2.5 Å (r = 0.226, R(free) = 0.270). hMSL3 contains a canonical methyllysine binding pocket made up of residues Tyr-31, Phe-56, Trp-59, and Trp-63. A six-residue insertion between strands ß(1) and ß(2) of the hMSL3 chromo-barrel domain directs the side chain of Glu-21 into the methyllysine binding pocket where it hydrogen bonds to the NH group of a bound cyclohexylamino ethanesulfonate buffer molecule, likely mimicking interactions with a histone tail dimethyllysine residue. In vitro binding studies revealed that both the human and Drosophila MSL3 chromo-barrel domains bind preferentially to peptides representing the mono or dimethyl isoform of lysine 20 on the histone H4 N-terminal tail (H4K20Me(1) or H4K20Me(2)). Mutation of Tyr-31 to Ala in the hMSL3 methyllysine-binding cage resulted in weaker in vitro binding to H4K20Me(1). The same mutation in the msl3 gene compromised male survival in Drosophila. Combined mutation of Glu-21 and Pro-22 to Ala in hMSL3 resulted in slightly weaker in vitro binding to H4K20Me(1), but the corresponding msl3 mutation had no effect on male survival in Drosophila. We propose MSL3 plays an important role in targeting the male specific lethal complex to chromatin in both humans and flies by binding to H4K20Me(1). Binding studies on the related dMRG15 chromo-barrel domain revealed that MRG15 prefers binding to H4K20Me(3).

Getting out what you put in: Copper in mitochondria and its impacts on human disease.

Mitochondria accumulate copper in their matrix for the eventual maturation of the cuproenzymes cytochrome c oxidase and superoxide dismutase. Transport into the matrix is achieved by mitochondrial carrier family (MCF) proteins. The major copper transporting MCF described to date in yeast is Pic2, which imports the metal ion into the matrix. Pic2 is one of ~30 MCFs that move numerous metabolites, nucleotides and co-factors across the inner membrane for use in the matrix. Genetic and biochemical experiments showed that Pic2 is required for cytochrome c oxidase activity under copper stress, and that it is capable of transporting ionic and complexed forms of copper. The Pic2 ortholog SLC25A3, one of 53 mammalian MCFs, functions as both a copper and a phosphate transporter. Depletion of SLC25A3 results in decreased accumulation of copper in the matrix, a cytochrome c oxidase defect and a modulation of cytosolic superoxide dismutase abundance. The regulatory roles for copper and cuproproteins resident to the mitochondrion continue to expand beyond the organelle. Mitochondrial copper chaperones have been linked to the modulation of cellular copper uptake and export and the facilitation of inter-organ communication. Recently, a role for matrix copper has also been proposed in a novel cell death pathway termed cuproptosis. This review will detail our understanding of the maturation of mitochondrial copper enzymes, the roles of mitochondrial signals in regulating cellular copper content, the proposed mechanisms of copper transport into the organelle and explore the evolutionary origins of copper homeostasis pathways.

Mitochondrial copper and phosphate transporter specificity was defined early in the evolution of eukaryotes.

The mitochondrial carrier family protein SLC25A3 transports both copper and phosphate in mammals, yet in Saccharomyces cerevisiae the transport of these substrates is partitioned across two paralogs: PIC2 and MIR1. To understand the ancestral state of copper and phosphate transport in mitochondria, we explored the evolutionary relationships of PIC2 and MIR1 orthologs across the eukaryotic tree of life. Phylogenetic analyses revealed that PIC2-like and MIR1-like orthologs are present in all major eukaryotic supergroups, indicating an ancient gene duplication created these paralogs. To link this phylogenetic signal to protein function, we used structural modeling and site-directed mutagenesis to identify residues involved in copper and phosphate transport. Based on these analyses, we generated an L175A variant of mouse SLC25A3 that retains the ability to transport copper but not phosphate. This work highlights the utility of using an evolutionary framework to uncover amino acids involved in substrate recognition by mitochondrial carrier family proteins.

Sex-biased transcription enhancement by a 5' tethered Gal4-MOF histone acetyltransferase fusion protein in Drosophila.

BACKGROUND: In male Drosophila melanogaster, the male specific lethal (MSL) complex is somehow responsible for a two-fold increase in transcription of most X-linked genes, which are enriched for histone H4 acetylated at lysine 16 (H4K16ac). This acetylation requires MOF, a histone acetyltransferase that is a component of the MSL complex. MOF also associates with the non-specific lethal or NSL complex. The MSL complex is bound within active genes on the male X chromosome with a 3' bias. In contrast, the NSL complex is enriched at promoter regions of many autosomal and X-linked genes in both sexes. In this study we have investigated the role of MOF as a transcriptional activator. RESULTS: MOF was fused to the DNA binding domain of Gal4 and targeted to the promoter region of UAS-reporter genes in Drosophila. We found that expression of a UAS-red fluorescent protein (DsRed) reporter gene was strongly induced by Gal4-MOF. However, DsRed RNA levels were about seven times higher in female than male larvae. Immunostaining of polytene chromosomes showed that Gal4-MOF co-localized with MSL1 to many sites on the X chromosome in male but not female nuclei. However, in female nuclei that express MSL2, Gal4-MOF co-localized with MSL1 to many sites on polytene chromosomes but DsRed expression was reduced. Mutation of conserved active site residues in MOF (Glu714 and Cys680) reduced HAT activity in vitro and UAS-DsRed activation in Drosophila. In the presence of Gal4-MOF, H4K16ac levels were enriched over UAS-lacZ and UAS-arm-lacZ reporter genes. The latter utilizes the constitutive promoter from the arm gene to drive lacZ expression. In contrast to the strong induction of UAS-DsRed expression, UAS-arm-lacZ expression increased by about 2-fold in both sexes. CONCLUSIONS: Targeting MOF to reporter genes led to transcription enhancement and acetylation of histone H4 at lysine 16. Histone acetyltransferase activity was required for the full transcriptional response. Incorporation of Gal4-MOF into the MSL complex in males led to a lower transcription enhancement of UAS-DsRed but not UAS-arm-lacZ genes. We discuss how association of Gal4-MOF with the MSL or NSL proteins could explain our results.

The HP0256 gene product is involved in motility and cell envelope architecture of Helicobacter pylori.

BACKGROUND: Helicobacter pylori is the causative agent for gastritis, and peptic and duodenal ulcers. The bacterium displays 5-6 polar sheathed flagella that are essential for colonisation and persistence in the gastric mucosa. The biochemistry and genetics of flagellar biogenesis in H. pylori has not been fully elucidated. Bioinformatics analysis suggested that the gene HP0256, annotated as hypothetical, was a FliJ homologue. In Salmonella, FliJ is a chaperone escort protein for FlgN and FliT, two proteins that themselves display chaperone activity for components of the hook, the rod and the filament. RESULTS: Ablation of the HP0256 gene in H. pylori significantly reduced motility. However, flagellin and hook protein synthesis was not affected in the HP0256 mutant. Transmission electron transmission microscopy revealed that the HP0256 mutant cells displayed a normal flagellum configuration, suggesting that HP0256 was not essential for assembly and polar localisation of the flagella in the cell. Interestingly, whole genome microarrays of an HP0256 mutant revealed transcriptional changes in a number of genes associated with the flagellar regulon and the cell envelope, such as outer membrane proteins and adhesins. Consistent with the array data, lack of the HP0256 gene significantly reduced adhesion and the inflammatory response in host cells. CONCLUSIONS: We conclude that HP0256 is not a functional counterpart of FliJ in H. pylori. However, it is required for full motility and it is involved, possibly indirectly, in expression of outer membrane proteins and adhesins involved in pathogenesis and adhesion.

Risk Factors for Long-term Mortality and Patterns of End-of-Life Care Among Medicare Sepsis Survivors Discharged to Home Health Care.

Importance: Despite a growing recognition of the increased mortality risk among sepsis survivors, little is known about the patterns of end-of-life care among this population. Objective: To describe patterns of end-of-life care among a national sample of sepsis survivors and identify factors associated with long-term mortality risk and hospice use. Design, Setting, and Participants: This cohort study assessed sepsis survivors who were Medicare fee-for-service beneficiaries discharged to home health care using national Medicare administrative, claims, and home health assessment data from 2013 to 2014. The initial and final primary analyses were conducted in July 2017 and from July to August 2019, respectively. Exposures: Sepsis hospital discharge and 1 or more home health assessments within 1 week. Main Outcomes and Measures: Outcomes were 1-year mortality among all sepsis survivors and hospitalization in the last 30 days of life, death in an acute care hospital, and hospice use among decedents. Multivariate logistic regression was used to identify factors associated with 1-year mortality and hospice use. Results: Among 87 581 sepsis survivors who were Medicare fee-for-service beneficiaries discharged to home health care, 49 323 (56.3%) were aged 75 years or older, 69 499 (79.4%) were non-Hispanic white, and 48 472 (55.3%) were female. Among the total survivors, 24 423 (27.9%) people died within 1 year of discharge, with a median (interquartile range) survival time of 119 (51-220) days. Among these decedents, 16 684 (68.2%) were hospitalized in the last 30 days of life, 6560 (26.8%) died in an acute care hospital, and 12 573 (51.4%) were enrolled in hospice, with 5729 (45.6%) using hospice for 7 or fewer days. Several factors were associated with 1-year mortality, including a cancer diagnosis (odds ratio [OR], 3.66; 95% CI, 3.50-3.83; P < .001), multiple dependencies of activities of daily living or instrumental activities of daily living (OR, 2.80; 95% CI, 2.57-3.05; P < .001), and an overall poor health status (OR, 2.21; 95% CI, 2.01-2.44; P < .001) documented on home health assessment. Among the decedents, cancer was associated with hospice use (OR, 2.25; 95% CI, 2.11-2.41; P < .001), patients aged 85 years or older (OR, 1.49; 95% CI, 1.37-1.61; P < .001), and living in an assisted living setting (OR, 1.93; 95% CI, 1.69-2.19; P < .001). Conclusions and Relevance: The findings of this study suggest that death within 1 year after sepsis discharge may be common among Medicare beneficiaries discharged to home health care. Although 1 in 2 decedents used hospice, aggressive care near the end of life and late hospice referral were common. Readily identifiable risk factors suggest opportunities to target efforts to improve palliative and end-of-life care among high-risk sepsis survivors.