Abstract Background Guideline-directed medical therapy (GDMT) is essential for reducing morbidity and mortality in HFrEF. However, real-world optimization remains suboptimal. Women are particularly less likely to receive optimized GDMT, often due to smaller body size, physiological differences, and increased susceptibility to adverse reactions. Despite these known gaps, sex-specific data on the prognostic impact of GDMT adherence are limited, therefore, we aimed to investigate sex differences in GDMT adherence and its association with clinical outcomes in patients with HFrEF. Methods This study analyzed data from the KorAHF III registry, a nationwide, prospective, multicenter cohort enrolling patients hospitalized with acute heart failure in Korea. We included patients with HFrEF and assessed outcomes over a 12-month follow-up period. Physician adherence to guideline-recommended treatment was quantified using a standardized score based on the prescription and target dosing of key heart failure medications. The primary outcome was a composite of cardiovascular death and heart failure hospitalization. Results Among a total of 4,153 patients, prescription rates for RAS inhibitors (59.7% vs. 55.3%, P < 0.001), MRAs (39.9% vs. 36.0%, P = 0.039), and SGLT2 inhibitors (20.1% vs. 15.2%, P < 0.001) were significantly higher in men, whereas no significant sex-based difference was observed for beta-blockers (55.4% vs. 54.3%, P = 0.818). In whole study population, 2,925 (70.4%) were classified into the poor adherence group, 1,133 (27.3%) into the moderate adherence group, and 95 (2.3%) into the good adherence group. The mean adherence score was significantly higher in men than in women (0.31±0.26 vs. 0.26± 0.24, P < 0.001). The proportion of patients in the poor adherence group was higher in women than men (76.1% vs. 67.4%), while the proportion of patients with good adherence was higher in men (2.6% vs. 1.7%, P<0.001). Kaplan-Meier analysis demonstrated that the poor adherence group had the worst prognosis regardless of sex (figure). Specifically, the poor adherence group showed a significantly higher risk of mortality and heart failure rehospitalization compared to the good (P < 0.001) and moderate (P = 0.036) adherence groups. However, there were no significant sex-specific differences in survival outcomes within the same adherence levels (Poor: P = 0.322; Moderate: P = 0.845; Good: P = 0.555). Conclusion In this nationwide cohort of patients with HFrEF, women were less likely to receive GDMT than men. Higher adherence to GDMT was associated with better clinical outcomes in both sexes, underscoring the importance of improving GDMT implementation in routine practice. Notably, in this Asian population, moderate adherence was not associated with substantially worse outcomes compared with good adherence, suggesting that optimal dosing strategies may need to be tailored to patient characteristics, including sex and ethnicity.For image description, please refer to the figure legend and surrounding text.
Background/Aims:: Morphological and functional changes occur after loop ileostomy surgery such as villous atrophy and decreased contractility. This study aims to examine the changes in motility of the proximal and distal limbs of the ileostomy. Morphological, molecular and functional approaches of smooth muscle are attempted to elucidate the cause of the changes in motility. Methods:: Full thickness strips of circular muscle were prepared from 25 patients (median age 64 years). Western blot was performed to quantify the expression of contractile proteins. Expression of genes was quantified using quantitative real-time polymerase chain reaction. Results:: The distal limb showed morphological atrophy and a significant reduction in the contractile response to acetylcholine and potassium chloride, as well as a reduced relaxation response to sodium nitroprusside. However, no changes in the number of platelet derived growth factor receptor-α-positive (PDGFRα+) cells and interstitial cell of Cajal (ICC) were observed between the proximal and distal limbs. Western blot analysis confirmed that the expression levels of proteins associated with contraction such as myosin phosphatase targeting subunit 1, protein kinase C-potentiated phosphatase inhibitor protein-17 kDa, and Rho-associated, coiled-coil containing protein kinase 1, were significantly down-regulated in the distal limb. Despite the decrease in the expression of these proteins, neuronal cells and smooth muscle cells were preserved in the distal limb that has been diverted after ileostomy. Conclusions:: Although morphological, molecular and motility changes including down-regulation of contractile protein expression were observed in the distal loop, number of PDGFRα+ cells, ICCs, and neuronal cells were preserved. These results may explain restoration of the bowel motility after ileostomy take-down with low incidence of ileus.
Background The clinical and prognostic implications of asymptomatic tuberculosis remain poorly understood. Methods We conducted a multicentre prospective cohort study to evaluate the association between asymptomatic tuberculosis (TB) and treatment outcomes. Individuals with rifampicin-susceptible pulmonary TB were enrolled from the Cohort Study of Pulmonary Tuberculosis. Asymptomatic TB was defined as the absence of any TB-related symptoms at diagnosis. The primary outcome was a favourable outcome, defined as treatment success without recurrence. Multivariable logistic regression models were used to assess associations between asymptomatic TB and favourable outcomes. The Cox proportional hazards model was applied to evaluate effect of asymptomatic TB on failure to complete treatment within 1 year. Stratified analyses by symptom status and mode of detection were performed to examine stratum-specific effects. Results Of 1071 individuals with pulmonary TB, 32.7% were asymptomatic. Compared to symptomatic patients, asymptomatic individuals were younger, less likely to be underweight and more often diagnosed through population health screening rather than clinical presentation or opportunistic testing. Asymptomatic TB was associated with higher likelihood of favourable outcome in multivariable models (adjusted odds ratio (aOR) 1.50, 95% CI 1.04-2.20) and a reduced risk of failing to complete treatment within one year in survival analyses (adjusted hazard ratio 0.66, 95% CI 0.45-0.95). Asymptomatic TB detected through health screening had the most favourable outcomes (aOR 2.41, 95% CI 1.34-4.66). Conclusion Asymptomatic TB was significantly associated with treatment success without recurrence and particularly in patients identified through health screening. Our results support symptom-agnostic screening in TB control programmes.
Objective : Early oral or enteral nutrition (EN) is recommended for critically ill patients; however, individuals with traumatic brain injury (TBI) often fail to meet their nutritional goals. Supplementary parenteral nutrition (SPN) in this instance may be of benefit, but evidence is lacking. This study examined the association between early SPN and nutritional adequacy and clinical outcomes in patients with TBI.Methods : This retrospective, non-randomized, single-center cohort study analyzed adult patients with TBI admitted to a trauma intensive care unit (ICU) from January 2023 to December 2024. Patients who received oral nutrition or EN on hospital day 4 (HD4) were included and classified based on their use of SPN. We assessed total caloric and protein intake on HD4, as well as survival rates, lengths of ICU and hospital stays, the occurrence of infectious complications, and unplanned ICU readmissions.Results : Among 260 screened patients, 122 were included in the study. The SPN group achieved higher caloric intake (1508 vs. 852 kcal; p<0.05) and total protein intake (79 vs. 41 g; p<0.05). Additionally, SPN was associated with lower rates of urinary tract infections (19.7% vs. 44.3%; p=0.004) and unplanned ICU readmissions (9.8% vs. 31.1%; p=0.004). Logistic regression analysis revealed a reduced risk for urinary tract infections (odds ratio [OR], 0.38; p=0.026) and unplanned ICU readmissions (OR, 0.25; p=0.007).Conclusion : Early SPN was associated with improved caloric and protein delivery and fewer infectious complications and unplanned ICU readmissions in TBI patients. Despite several limitations, these results suggest that SPN may be a beneficial strategy when oral or EN alone is inadequate.
Abstract Background Current guideline-directed medical therapy (GDMT) for HFrEF is based on clinical trials with male-dominant cohorts. Because of sex-related differences in body size and pharmacokinetics, women might be exposed to higher effective drug concentrations and greater susceptibility to adverse effects at standard doses. However, sex-specific data on optimal dosing remain scarce, especially in Asian patients. This study investigated sex differences in the dose–response relationship of renin–angiotensin system (RAS) blockers and beta-blockers to identify sex-specific dose–response patterns and optimal dosing in Asian patients. Methods This study analyzed data from the KorAHF III registry, a nationwide, prospective, multicenter cohort enrolling patients hospitalized with acute heart failure in Korea. We included patients with HFrEF (LVEF≤40%) and assessed outcomes over a 12-month follow-up period. The primary outcome was a composite of cardiovascular death and heart failure hospitalization. Multivariable Cox models with polynomial terms were used to identify optimal dosages for each sex. Results A total of 4,155 patients (M/F: 2,718/1,437) were analyzed. Women were significantly older (69.8 vs. 63.0 years, p<0.001) and had slightly lower BMI (24.0 vs. 24.8 kg/m2, p<0.001) than men. The proportions of reaching the target dose were significantly lower in women for ARNI (11.9% vs. 17.9%, p = 0.003) and beta-blockers (2.7% vs.5.2%, p = 0.005), while no significant difference was observed for ACEi/ARB (3.6% vs. 2.8%, p=0.653). During the 12-month follow-up, the incidence of the primary outcome was not different between sexes (37.4% in women vs. 34.2% in men, p = 0.153). Nonlinear dose-response analysis revealed that for RAS blockers (ACEi/ARB and ARNI), both sexes derived clinical benefits from even low-dose initiation, while men demonstrated incremental benefits with further titration, women reached a therapeutic plateau at lower dose levels. For beta-blockers, men showed a continuous risk reduction with increasing doses, meanwhile women exhibited a J-shaped pattern, with maximal risk reduction occurring at approximately 20% of the target dose and an increased risk at higher doses. Conclusion Optimal dosing for HFrEF medications appears to differ by sex. Our findings support a shift from a uniform target-dose strategy toward a sex-specific, Asia-tailored approach, emphasizing that while low-dose initiation is effective for both sexes, optimal maintenance doses differ significantly by sex.Relative risk of the PO of medicationsFor image description, please refer to the figure legend and surrounding text.
