The Origin Along the Cochlea of Otoacoustic Emissions Evoked by Mid-Frequency Tone Pips.

PURPOSE: Tone-pip-evoked otoacoustic emissions (PEOAEs) are transient-evoked otoacoustic emissions (OAEs) that are hypothesized to originate from reflection of energy near the best-frequency (BF) cochlear place of the stimulus frequency. However, individual PEOAEs have energy with a wide range of delays. We sought to determine whether some PEOAE energy is consistent with having been generated far from BF. METHODS: PEOAEs from 35 and 47 dB SPL tone pips were obtained by removing pip-stimulus energy by subtracting the ear-canal sound pressure from scaled-down 59 dB SPL tone pips (which evoke relatively small OAEs). PEOAE delays were measured at each peak in the PEOAE absolute-value waveforms. While measuring PEOAEs and auditory-nerve compound action potentials (CAPs), amplification was blocked sequentially from apex to base by cochlear salicylate perfusion. The perfusion time when a CAP was reduced identified when the perfusion reached the tone-pip BF place. The perfusion times when each PEOAE peak was reduced identified where along the cochlea it received cochlear amplification. PEOAEs and CAPs were measured simultaneously using one pip frequency in each ear (1.4 to 4 kHz across 16 ears). RESULTS: Most PEOAE peaks received amplification primarily between the BF place and 1-2 octaves basal of the BF place. PEOAE peaks with short delays received amplification basal of BF place. PEOAE peaks with longer delays sometimes received amplification apical of BF place, consistent with previous stimulus-frequency-OAE results. CONCLUSION: PEOAEs provide information about cochlear amplification primarily within ~ 1.5 octave of the tone-pip BF place, not about regions > 3 octaves basal of BF.

Methylene Blue in Septic Shock: A Systematic Review and Meta-Analysis.

OBJECTIVES: Although clinicians may use methylene blue (MB) in refractory septic shock, the effect of MB on patient-important outcomes remains uncertain. We conducted a systematic review and meta-analysis to investigate the benefits and harms of MB administration in patients with septic shock. DATA SOURCES: We searched six databases (including PubMed, Embase, and Medline) from inception to January 10, 2024. STUDY SELECTION: We included randomized clinical trials (RCTs) of critically ill adults comparing MB with placebo or usual care without MB administration. DATA EXTRACTION: Two reviewers performed screening, full-text review, and data extraction. We pooled data using a random-effects model, assessed the risk of bias using the modified Cochrane tool, and used Grading of Recommendations Assessment, Development, and Evaluation to rate certainty of effect estimates. DATA SYNTHESIS: We included six RCTs (302 patients). Compared with placebo or no MB administration, MB may reduce short-term mortality (RR [risk ratio] 0.66 [95% CI, 0.47-0.94], low certainty) and hospital length of stay (mean difference [MD] -2.1 d [95% CI, -1.4 to -2.8], low certainty). MB may also reduce duration of vasopressors (MD -31.1 hr [95% CI, -16.5 to -45.6], low certainty), and increase mean arterial pressure at 6 hours (MD 10.2 mm Hg [95% CI, 6.1-14.2], low certainty) compared with no MB administration. The effect of MB on serum methemoglobin concentration was uncertain (MD 0.9% [95% CI, -0.2% to 2.0%], very low certainty). We did not find any differences in adverse events. CONCLUSIONS: Among critically ill adults with septic shock, based on low-certainty evidence, MB may reduce short-term mortality, duration of vasopressors, and hospital length of stay, with no evidence of increased adverse events. Rigorous randomized trials evaluating the efficacy of MB in septic shock are needed. REGISTRATION: Center for Open Science (https://osf.io/hpy4j).

The association between applicant gender and racial or ethnic identity and success in the admissions process at a Canadian medical school: a prospective cohort study.

Background: Canadian data suggests that Black candidates may be less successful than other groups when applying to medical school. We sought to comprehensively describe the racial and/or ethnic identity, gender identity, sexual orientation, and ability of applicants to a single Canadian medical school. We also examined for an association between success at each application stage and applicant gender and racial identity. Methods: Class of 2024 applicants to a single Canadian medical school were invited to complete a demographics survey. The odds of achieving each application stage (offered an interview, offered a position, and matriculating) were determined for each demographic group. Results: There were 595 participants (32.4% response rate). The demographics of the applicant pool and matriculating class were similar. There was no difference in interview offers or matriculation between BIPOC and white candidates. Cisgender men were overrepresented in interviews compared to cisgender women (OR 0.64; 95%CI 0.43-0.95; p = 0.03) but not in matriculation. BIPOC cisgender women received more interview invitations compared to other groups (OR 2.74, 95%CI 1.20-6.25; p = 0.02). Conclusions: Differences in applicant success for differing demographic groups were most pronounced being offered an interview.

Contexte: Des données canadiennes portent à croire que les candidats noirs peuvent avoir moins de succès que d'autres groupes lorsqu'ils postulent à une faculté de médecine. Nous avons cherché à décrire de manière exhaustive l'identité raciale et/ou ethnique, l'identité de genre, l'orientation sexuelle et les capacités des candidats à une seule faculté de médecine canadienne. Nous avons également cherché à établir un lien entre la réussite à chaque étape de la candidature et le sexe et l'identité raciale du candidat ou de la candidate. Méthodes: Les candidats de la promotion 2024 à une faculté de médecine canadienne ont été invités à répondre à une enquête démographique. Les chances d'atteindre chaque étape de la candidature (entrevue offerte, place offerte et inscription) ont été déterminées pour chaque groupe démographique. Résultats: Il y a eu 595 participants (taux de réponse de 32,4 %). Les caractéristiques démographiques des candidats à l'admission et des étudiants admis étaient similaires. Il n'y avait pas de différence entre les candidats blancs et les candidats autochtones, noirs et de couleur (PANDC) en ce qui concerne les offres d'entrevue ou les admissions. Les hommes cisgenres étaient surreprésentés dans les entrevues par rapport aux femmes cisgenres (OR 0,64; 95%CI 0,43-0,95 ; p=0,03) mais pas dans les admissions. Les femmes cisgenres appartenant au groupe des PANDC ont reçu plus d'offres d'entrevue que les autres groupes (OR 2,74, 95%CI 1,20-6,25 ; p=0,02). Conclusions: Les différences les plus marquées dans la réussite des candidats à l'admission parmi les différents groupes démographiques étaient quant aux offres d'entrevue.

Merging Metabolic Modeling and Imaging for Screening Therapeutic Targets in Colorectal Cancer.

Cancer-associated fibroblasts (CAFs) play a key role in metabolic reprogramming and are well-established contributors to drug resistance in colorectal cancer (CRC). To exploit this metabolic crosstalk, we integrated a systems biology approach that identified key metabolic targets in a data-driven method and validated them experimentally. This process involved high-throughput computational screening to investigate the effects of enzyme perturbations predicted by a computational model of CRC metabolism to understand system-wide effects efficiently. Our results highlighted hexokinase (HK) as one of the crucial targets, which subsequently became our focus for experimental validation using patient-derived tumor organoids (PDTOs). Through metabolic imaging and viability assays, we found that PDTOs cultured in CAF conditioned media exhibited increased sensitivity to HK inhibition. Our approach emphasizes the critical role of integrating computational and experimental techniques in exploring and exploiting CRC-CAF crosstalk.

Vaccination with Mincle agonist UM-1098 and mycobacterial antigens induces protective Th1 and Th17 responses.

Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), is one of the top infectious killers in the world. The only licensed vaccine against TB, Bacille Calmette-Guérin (BCG), provides variable protection against pulmonary TB, especially in adults. Hence, novel TB vaccine approaches are urgently needed. Both Th1 and Th17 responses are necessary for protection against TB, yet effective adjuvants and vaccine delivery systems for inducing robust Th1 and Th17 immunity are lacking. Herein we describe a synthetic Mincle agonist, UM-1098, and a silica nanoparticle delivery system that drives Th1/Th17 responses to Mtb antigens. Stimulation of human peripheral blood mononuclear cells (hPBMCs) with UM-1098 induced high levels of Th17 polarizing cytokines IL-6, IL-1ß, IL-23 as well as IL-12p70, IL-4 and TNF-α in vitro. PBMCs from both C57BL/6 and BALB/c mice responded with a similar cytokine pattern in vitro and in vivo. Importantly, intramuscular (I.M.) vaccination with UM-1098-adjuvanted TB antigen M72 resulted in significantly higher antigen-specific IFN-γ and IL-17A levels in C57BL/6 wt mice than Mincle KO mice. Vaccination of C57BL/6 wt mice with immunodominant Mtb antigens ESAT6/Ag85B or M72 resulted in predominantly Th1 and Th17 responses and induced antigen-specific serum antibodies. Notably, in a virulent Mtb challenge model, vaccination with UM-1098 adjuvanted ESAT6/Ag85B or M72 significantly reduced lung bacterial burden when compared with unvaccinated mice and protection occurred in the absence of pulmonary inflammation. These data demonstrate that the synthetic Mincle agonist UM-1098 induces strong Th1 and Th17 immunity after vaccination with Mtb antigens and provides protection against Mtb infection in mice.

How variable are the classic ERP effects during sentence processing? A systematic resampling analysis of the N400 and P600 effects.

Although event-related potential (ERP) research on language processing has capitalized on key, theoretically influential components such as the N400 and P600, their measurement properties-especially the variability in their temporal and spatial parameters-have rarely been examined. The current study examined the measurement properties of the N400 and P600 effects elicited by semantic and syntactic anomalies, respectively, during sentence processing. We used a bootstrap resampling procedure to randomly draw many thousands of resamples varying in sample size and stimulus count from a larger sample of 187 participants and 40 stimulus sentences of each type per condition. Our resampling investigation focused on three issues: (a) statistical power; (b) variability in the magnitudes of the effects; and (c) variability in the temporal and spatial profiles of the effects. At the level of grand averages, the N400 and P600 effects were both robust and substantial. However, across resamples, there was a high degree of variability in effect magnitudes, onset times, and scalp distributions, which may be greater than is currently appreciated in the literature, especially for the P600 effects. These results provide a useful basis for designing future studies using these two well-established ERP components. At the same time, the results also highlight challenges that need to be addressed in future research (e.g., how best to analyze the ERP data without engaging in such questionable research practices as p-hacking).

FICD deficiency protects mice from hypertrophy-induced heart failure via BiP-mediated activation of the UPR ER and ER-phagy.

Cardiomyocytes require the HSP70 chaperone BiP to maintain proteostasis in the endoplasmic reticulum (ER) following cardiac stress. The adenylyl transferase (AMPylase) FICD is increasingly recognized to regulate BiP activity through the post-translational addition of an adenosine monophosphate moiety to BiP surface residues. However, the physiological impact of FICD-mediated BiP regulation in the context of cardiovascular health is unknown. Here, we find that FICD deficiency prevents pressure overload-associated heart failure, hypertrophy, and fibrosis, and that FICD knockout mice maintain normal cardiac function after cardiac pressure overload. At a cellular level, we observe that FICD-mediated BiP AMPylation blunts the induction of the unfolded protein response (UPR ER ) and impairs BiP interaction with FAM134B, an ER-phagy receptor, thus limiting ER-phagy induction under stress. In contrast, FICD loss significantly increases BiP-dependent UPR ER induction and ER-phagy in stressed cardiomyocytes. We also uncover cell type-specific consequences of FICD activity in response to ER stress, positioning FICD as a critical proteostasis regulator in cardiac tissue. Our results highlight a novel regulatory paradigm controlling stress resilience in cardiomyocytes and offer a rationale to consider FICD as a therapeutic target to treat cardiac hypertrophy.

FEASIBILITY AND SAFETY OF A DEDICATED CAUTERY-ENHANCED TUBULAR SELF-EXPANDABLE METAL STENT FOR ENDOSCOPIC ULTRASOUND-GUIDED HEPATICOGASTROSTOMY.

BACKGROUND AND STUDY AIMS: Endoscopic ultrasound-guided hepaticogastrostomy (EUS-HGS) is an alternative for biliary drainage in patients with obstructive pancreatobiliary pathology when endoscopic retrograde cholangiography (ERCP) is not feasible. Despite its effectiveness, EUS-HGS is associated with a significant risk of adverse events. This study aimed to evaluate the feasibility and safety of a newly dedicated cautery-enhanced tubular self-expandable metal stent (SEMS) for EUS-HGS. PATIENTS AND METHODS: This multicenter prospective study included patients with malignant biliary obstruction who failed ERCP because of tumor infiltration or surgically-altered anatomy. A dedicated cautery-enhanced tubular SEMS was used for EUS-HGS. Technical and clinical success rates, procedure times, and adverse events were evaluated. RESULTS: Twenty patients underwent EUS-HGS with the dedicated stent and achieved technical and clinical success rates of 100 %, with no reported severe adverse events or mortality. The mean procedure time was 16 minutes. Recurrent biliary obstruction was observed in 5% of patients. CONCLUSIONS: Dedicated cautery-enhanced tubular SEMS for EUS-HGS can simplify the procedure and enhance its safety and efficacy. This innovation shows promise for improving patient outcomes, although further studies are needed to validate these findings in a broader patient population.

Social Infrastructure Availability and Suicide Rates among Working-Age Adults in the United States.

Social infrastructure (SI) may buffer against suicide risk by improving social cohesion, social support, and information and resource sharing. This study uses an ecological approach to examine the relationship between county-level SI availability and suicide rates among working-age adults (ages 25-64) in the United States, a population for whom suicide rates are high, rising, and geographically unequal. Mortality data are from the National Vital Statistics System for 2016-2019. SI data are from the National Neighborhood Data Archive for 2013-2015 and capture the availability of typically free SI (e.g. libraries, community centers) and commercial SI (e.g. coffee shops, diners, entertainment venues). Results from negative binomial models show that suicide rates are significantly lower in counties with more SI availability, net of county demographic, socioeconomic, and health care factors. This relationship held for both typically free and commercial SI. Policymakers should consider strengthening existing and developing new social infrastructure, particularly in counties with less educated populations, as part of a broader strategy to reduce suicide rates in the United States.

Pharmacologic contraception methods for people with cystic fibrosis: A practical review for clinicians.

Over the last several decades, substantial treatment advances have improved the quality of life and median predicted survival in people with cystic fibrosis (PwCF). It is critical for CF clinicians to begin to discuss health considerations related to an aging and overall healthier CF population. Such considerations include family planning, reproductive health, and contraception. CF care teams are trusted sources of medical information and therefore often have initial discussions related to contraception for PwCF. The purpose of this article is to review the available pharmacologic contraceptive methods, with a specific focus on the benefits and risks that may be more relevant to PwCF.

A safe insect-based Chikungunya fever vaccine affords rapid and durable protection in cynomolgus macaques.

Chikungunya virus (CHIKV), which induces chikungunya fever and chronic arthralgia, is an emerging public health concern. Safe and efficient vaccination strategies are needed to prevent or mitigate virus-associated acute and chronic morbidities for preparation of future outbreaks. Eilat (EILV)/CHIKV, a chimeric alphavirus which contains the structural proteins of CHIKV and the non-structural proteins of EILV, does not replicate in vertebrate cells. The chimeric virus was previously reported to induce protective adaptive immunity in mice. Here, we assessed the capacity of the virus to induce quick and durable protection in cynomolgus macaques. EILV/CHIKV protected macaques from wild-type (WT) CHIKV infection one year after a single dose vaccination. Transcriptome and in vitro functional analyses reveal that the chimeric virus triggered toll-like receptor signaling and T cell, memory B cell and antibody responses in a dose-dependent manner. Notably, EILV/CHIKV preferentially induced more durable, robust, and broader repertoire of CHIKV-specific T cell responses, compared to a live attenuated CHIKV 181/25 vaccine strain. The insect-based chimeric virus did not cause skin hypersensitivity reactions in guinea pigs sensitized to mosquito bites. Furthermore, EILV/CHIKV induced strong neutralization antibodies and protected cynomolgus macaques from WT CHIKV infection within six days post vaccination. Transcriptome analysis also suggest that the chimeric virus induction of multiple innate immune pathways, including Toll-like receptor signaling, type I IFN and IL-12 signaling, antigen presenting cell activation, and NK receptor signaling. Our findings suggest that EILV/CHIKV is a safe, highly efficacious vaccine, and provides both rapid and long-lasting protection in cynomolgus macaques.

Effects of conflicting emotional cues on toddlers' emotion perception.

The communication of emotion is dynamic and occurs across multiple channels, such as facial expression and tone of voice. When cues are in conflict, interpreting emotion can become challenging. Here, we examined the effects of incongruent emotional cues on toddlers' interpretation of emotions. We presented 33 children (22-26 months, Mage = 23.8 months, 15 female) with side-by-side images of faces along with sentences spoken in a tone of voice that conflicted with semantic content. One of the two faces matched the emotional tone of the audio, whereas the other matched the semantic content. For both congruent and incongruent trials, toddlers showed no overall looking preference to either type of face stimuli. However, during the second exposure to the sentences of incongruent trials, older children tended to look longer to the face matching semantic content when listening to happy vs. angry content. Results inform our understanding of the early development of complex emotion understanding.

Persistence and Sexual Dimorphism of Gut Dysbiosis and Pathobiome after Sepsis and Trauma.

OBJECTIVE: To evaluate the persistence of intestinal microbiome dysbiosis and gut-plasma metabolomic perturbations following severe trauma or sepsis weeks after admission in patients experiencing chronic critical illness (CCI). SUMMARY: Trauma and sepsis can lead to gut dysbiosis and alterations in the plasma and fecal metabolome. However, the impact of these perturbations and correlations between gut dysbiosis and the plasma metabolome in chronic critical illness have not been studied. METHODS: A prospective observational cohort study was performed with healthy subjects, severe trauma patients, patients with sepsis residing in an intensive care unit (ICU) for 2-3 weeks. A high-throughput multi-omics approach was utilized to evaluate the gut microbial and gut-plasma metabolite responses in critically ill trauma and sepsis patients 14-21 days after ICU admission. RESULTS: Patients in the sepsis and trauma cohorts demonstrated strikingly depleted gut microbiome diversity, with significant alterations and specific pathobiome patterns in the microbiota composition compared to healthy subjects. Further subgroup analyses based on sex revealed resistance to changes in microbiome diversity among female trauma patients compared to healthy counterparts. Sex-specific changes in fecal metabolites were also observed after trauma and sepsis, while plasma metabolite changes were similar in both males and females. CONCLUSIONS: Dysbiosis induced by trauma and sepsis persists up to 14-21 days after onset and is sex-specific, underscoring the implication of pathobiome and entero-septic microbial-metabolite perturbations in post-sepsis and post-trauma CCI. This indicates resilience to infection or injury in females' microbiome and should inform and facilitate future precision/personalized medicine strategies in the intensive care unit.

Instantly adhesive and ultra-elastic patches for dynamic organ and wound repair.

Bioadhesive materials and patches are promising alternatives to surgical sutures and staples. However, many existing bioadhesives do not meet the functional requirements of current surgical procedures and interventions. Here, we present a translational patch material that exhibits instant adhesion to tissues (2.5-fold stronger than Tisseel, an FDA-approved fibrin glue), ultra-stretchability (stretching to >300% its original length without losing elasticity), compatibility with rapid photo-projection (<2 min fabrication time/patch), and ability to deliver therapeutics. Using our established procedures for the in silico design and optimization of anisotropic-auxetic patches, we created next-generation patches for instant attachment to tissues while conforming to a broad range of organ mechanics ex vivo and in vivo. Patches coated with extracellular vesicles derived from mesenchymal stem cells demonstrate robust wound healing capability in vivo without inducing a foreign body response and without the need for patch removal that can cause pain and bleeding. We further demonstrate a single material-based, void-filling auxetic patch designed for the treatment of lung puncture wounds.

Noninvasive Ventilation for Preoxygenation during Emergency Intubation.

BACKGROUND: Among critically ill adults undergoing tracheal intubation, hypoxemia increases the risk of cardiac arrest and death. The effect of preoxygenation with noninvasive ventilation, as compared with preoxygenation with an oxygen mask, on the incidence of hypoxemia during tracheal intubation is uncertain. METHODS: In a multicenter, randomized trial conducted at 24 emergency departments and intensive care units in the United States, we randomly assigned critically ill adults (age, ≥18 years) undergoing tracheal intubation to receive preoxygenation with either noninvasive ventilation or an oxygen mask. The primary outcome was hypoxemia during intubation, defined by an oxygen saturation of less than 85% during the interval between induction of anesthesia and 2 minutes after tracheal intubation. RESULTS: Among the 1301 patients enrolled, hypoxemia occurred in 57 of 624 patients (9.1%) in the noninvasive-ventilation group and in 118 of 637 patients (18.5%) in the oxygen-mask group (difference, -9.4 percentage points; 95% confidence interval [CI], -13.2 to -5.6; P<0.001). Cardiac arrest occurred in 1 patient (0.2%) in the noninvasive-ventilation group and in 7 patients (1.1%) in the oxygen-mask group (difference, -0.9 percentage points; 95% CI, -1.8 to -0.1). Aspiration occurred in 6 patients (0.9%) in the noninvasive-ventilation group and in 9 patients (1.4%) in the oxygen-mask group (difference, -0.4 percentage points; 95% CI, -1.6 to 0.7). CONCLUSIONS: Among critically ill adults undergoing tracheal intubation, preoxygenation with noninvasive ventilation resulted in a lower incidence of hypoxemia during intubation than preoxygenation with an oxygen mask. (Funded by the U.S. Department of Defense; PREOXI ClinicalTrials.gov number, NCT05267652.).

Patterns of recurrence after radiotherapy for high-risk neuroblastoma: Implications for radiation dose and field.

BACKGROUND: Prognosis for patients with high-risk neuroblastoma (HR-NBL) is guarded despite aggressive therapy, and few studies have characterized outcomes after radiotherapy in relation to radiation treatment fields. METHODS: Multi-institutional retrospective cohort of 293 patients with HR-NBL who received autologous stem cell transplant (ASCT) and EBRT between 1997-2021. LRR was defined as recurrence at the primary site or within one nodal echelon beyond disease present at diagnosis. Follow-up was defined from the end of EBRT. Event-free survival (EFS) and OS were analyzed by Kaplan-Meier method. Cumulative incidence of locoregional progression (CILP) was analyzed using competing risks of distant-only relapse and death with Gray's test. RESULTS: Median follow-up was 7.0 years (range: 0.01-22.4). Five-year CILP, EFS, and OS were 11.9 %, 65.2 %, and 77.5 %, respectively. Of the 31 patients with LRR and imaging review, 15 (48.4 %) had in-field recurrences (>12 Gy), 6 (19.4 %) had marginal failures (≤12 Gy), and 10 (32.3 %) had both in-field and marginal recurrences. No patients receiving total body irradiation (12 Gy) experienced marginal-only failures (p = 0.069). On multivariable analyses, MYCN amplification had higher risk of LRR (HR: 2.42, 95 % CI: 1.06-5.50, p = 0.035) and post-consolidation isotretinoin and anti-GD2 antibody therapy (HR: 0.42, 95 % CI: 0.19-0.94, p = 0.035) had lower risk of LRR. CONCLUSIONS: Despite EBRT, LRR remains a contributor to treatment failure in HR-NBL with approximately half of LRRs including a component of marginal failure. Future prospective studies are needed to explore whether radiation fields and doses should be defined based on molecular features such as MYCN amplification, and/or response to chemotherapy.

Watchful, skeptics, and system distrusters: Characteristics associated with different types of COVID-19 vaccine hesitancy among U.S. working-age adults.

COVID-19 vaccine hesitancy is complex, with adults identifying various reasons for not getting vaccinated. Using data from the 2022 National Wellbeing Survey on 7612 U.S. adults aged 18-64, we identified how age, race/ethnicity, sex, marital status, education, income, employment status, partisanship, and metropolitan status are associated with COVID-19 vaccination status and three non-mutually exclusive types of vaccine hesitancy: 1) watchful, concerned about vaccine side effects and efficacy; 2) skeptics, distrust the vaccine, and 3) system distrusters, distrust government. A third of respondents overall (N = 2643) had not received at least one dose at the time of the survey. Among respondents who were not vaccinated, 67 % are classified as watchful, 53 % are skeptics, and 32 % are system distrusters. Results from logistic regression show that concerns about side effects and safety (watchfulness) appear to be major drivers for not getting vaccinated among females and among non-Hispanic Black and unmarried adults, whereas skepticism and distrust appear to be more important barriers among ages 25-44. All three types of hesitancy appear to be important contributors to lower vaccination uptake among low-income, low-education, and unemployed adults, and among individuals who voted for Donald Trump in the 2020 election (with skepticism and distrust being most endorsed by this group). Findings suggest that universal messaging and intervention strategies are unlikely to be effective in reducing vaccine hesitancy. Different messages, messengers, and tactics must be used with different groups.

Advanced Heart Failure Characteristics and Outcomes in Women and Men.

BACKGROUND: The epidemiology and pathophysiology of heart failure (HF) differ in women and men. Whether these differences extend to the subgroup of patients with advanced HF is not well defined. METHODS AND RESULTS: This is a retrospective cohort study of all adult Olmsted County, Minnesota residents with advanced HF (European Society of Cardiology criteria) from 2007 to 2017. Differences in survival and hospitalization risks in women and men following advanced HF development were examined using Cox proportional hazard regression and Andersen-Gill models, respectively. Of 936 individuals with advanced HF, 417 (44.6%) were women and 519 (55.4%) were men (self-reported sex). Time from development of HF to advanced HF was similar in women and men (median 3.2 versus 3.6 years). Women were older at diagnosis (mean age 79 versus 75 years), less often had coronary disease and hyperlipidemia, but more often had hypertension and depression (P<0.05 for each). Advanced HF with preserved ejection fraction was more prevalent in women than men (60% versus 30%, p<0.001). There were no differences in adjusted risks of all-cause mortality (hazard ratio [HR], 0.89 [95% CI, 0.77-1.03]), cardiovascular mortality (HR, 0.85 [95% CI, 0.70-1.02]), all-cause hospitalizations (HR, 1.04 [95% CI, 0.90-1.20]), or HF hospitalizations (HR, 0.91 [95% CI, 0.75-1.11]) between women and men. However, adjusted cardiovascular mortality was lower in women versus men with advanced HF with reduced ejection fraction (HR, 0.72 [95% CI, 0.56-0.93]). CONCLUSIONS: Women more often present with advanced HF with preserved ejection fraction and men with atherosclerotic disease and advanced HF with reduced ejection fraction. Despite these differences, survival and hospitalization risks are largely comparable in women and men with advanced HF.