Bendopnea prevalence and prognostic value in older patients with heart failure: FRAGILE-HF-SONIC-HF post hoc analysis.

AIMS: This study aimed to investigate the prevalence, clinical characteristics, and prognostic value of bendopnea in older patients hospitalized for heart failure. METHODS: This post hoc analysis was performed using two prospective, multicenter, observational studies: the FRAGILE-HF (main cohort) and SONIC-HF (validation cohort) cohorts. Patients were categorized based on the presence of bendopnea, which was evaluated before discharge. The primary endpoint was 2-year all-cause mortality after discharge. RESULTS: Among the 1,243 patients (median age, 81 years; 57.2% male) in the FRAGILE-HF cohort and 225 (median age, 79 years; 58.2% men) in the SONIC-HF cohort, bendopnea was observed in 31 (2.5%) and 10 (4.4%) patients, respectively. Over a 2-year follow-up period, all-cause death occurred in 20.8% and 21.9% of the patients in the FRAGILE-HF and SONIC-HF cohorts, respectively. Kaplan-Meier survival curves demonstrated significantly higher mortality rates in patients with bendopnea than in those without bendopnea in the FRAGILE-HF (log-rank P = 0.006) and SONIC-HF cohorts (log-rank P = 0.014). Cox proportional hazard analysis identified bendopnea as an independent prognostic factor for all-cause mortality in both the FRAGILE-HF (hazard ratio [HR] 2.11, 95% confidence interval [CI] 1.18-3.78, P = 0.012) and SONIC-HF cohorts (HR 4.20, 95% CI 1.63-10.79, P = 0.003), even after adjusting for conventional risk factors. CONCLUSIONS: Bendopnea was observed in a relatively small proportion of older patients hospitalized for heart failure before discharge. However, its presence was significantly associated with an increased risk of all-cause mortality.

This study investigated how common it is for older patients with heart failure to have trouble breathing when they bend forward, and whether this affects their chances of survival. The study found that although this problem is not very common, it is linked to a higher risk of death. Key findings: Only a small number of older patients with heart failure have trouble breathing when they bend forward.However, those who do have this problem are more likely to die.

Impact of Multidomain Frailty on the Mode of Death in Older Patients With Heart Failure: A Cohort Study.

BACKGROUND: Although frailty is strongly associated with mortality in patients with heart failure (HF), the risk of which specific cause of death is associated with being complicated with frailty is unclear. We aimed to clarify the association between multidomain frailty and the causes of death in elderly patients hospitalized with HF. METHODS: We analyzed data from the FRAGILE-HF cohort, where patients aged 65 years and older, hospitalized with HF, were prospectively registered between 2016 and 2018 in 15 Japanese hospitals before discharge and followed up for 2 years. All patients were assessed for physical, social, and cognitive dysfunction, and categorized into 3 groups based on their number of frailty domains (FDs, 0-1, 2, and 3). Kaplan-Meier survival analysis was used to evaluate the association between the number of FDs and all-cause mortality, whereas Fine-Gray competing risk regression analysis was used for assessing the impact on cause-specific mortality. RESULTS: We analyzed 1181 patients with HF (81 years old in median, 57.4% were male), 530 (44.9%), 437 (37.0%), and 214 (18.1%) of whom were categorized into the FD 0 to 1, FD 2, and FD 3 groups, respectively. During the 2-year follow-up, 240 deaths were observed (99 HF deaths, 34 cardiovascular deaths, and 107 noncardiovascular deaths), and an increase in the number of FD was significantly associated with mortality (Log-rank: P<0.001). The Fine-Gray competing risk analysis adjusted for age and sex showed that FDs 2 (subdistribution hazard ratio, 1.77 [95% CI, 1.11-2.81]) and 3 (2.78, [95% CI, 1.69-4.59]) groups were associated with higher incidence of noncardiovascular death but not with HF and other cardiovascular deaths. CONCLUSIONS: Although multidomain frailty is strongly associated with mortality in older patients with HF, it is mostly attributable to noncardiovascular death and not cardiovascular death, including HF death. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: UMIN000023929.

Research autopsy programmes in oncology: shared experience from 14 centres across the world.

While there is a great clinical need to understand the biology of metastatic cancer in order to treat it more effectively, research is hampered by limited sample availability. Research autopsy programmes can crucially advance the field through synchronous, extensive, and high-volume sample collection. However, it remains an underused strategy in translational research. Via an extensive questionnaire, we collected information on the study design, enrolment strategy, study conduct, sample and data management, and challenges and opportunities of research autopsy programmes in oncology worldwide. Fourteen programmes participated in this study. Eight programmes operated 24 h/7 days, resulting in a lower median postmortem interval (time between death and start of the autopsy, 4 h) compared with those operating during working hours (9 h). Most programmes (n = 10) succeeded in collecting all samples within a median of 12 h after death. A large number of tumour sites were sampled during each autopsy (median 15.5 per patient). The median number of samples collected per patient was 58, including different processing methods for tumour samples but also non-tumour tissues and liquid biopsies. Unique biological insights derived from these samples included metastatic progression, treatment resistance, disease heterogeneity, tumour dormancy, interactions with the tumour micro-environment, and tumour representation in liquid biopsies. Tumour patient-derived xenograft (PDX) or organoid (PDO) models were additionally established, allowing for drug discovery and treatment sensitivity assays. Apart from the opportunities and achievements, we also present the challenges related with postmortem sample collections and strategies to overcome them, based on the shared experience of these 14 programmes. Through this work, we hope to increase the transparency of postmortem tissue donation, to encourage and aid the creation of new programmes, and to foster collaborations on these unique sample collections. © 2024 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Nutrition Assessment and Education of Patients with Heart Failure by Cardiologists.

Although nutritional assessment and education are important for hospitalized patients with heart failure, the extent of their implementation in real-world clinical practice is unknown. Therefore, this study aimed to investigate the evaluation and management of nutrition during hospitalization for heart failure using a questionnaire survey for cardiologists.In this cross-sectional multicenter survey, 147 cardiologists from 32 institutions completed a web-based questionnaire (response rate, 95%).The survey showed that 78.2% of the respondents performed a nutritional assessment for hospitalized patients, whereas 38.3% used objective tools. In contrast, only 9.5% of the respondents evaluated the presence or absence of cardiac cachexia. Most respondents (89.8%) reported providing nutritional education to their patients before hospital discharge. However, compared with the number of respondents who provided information on sodium (97.0%) and water (63.6%) restrictions, a limited number of respondents provided guidance on optimal protein (20.5%) and micronutrient (9.1%) intake as part of the nutritional education. Less than 50% of the respondents provided guidance on optimal calorie intake (43.2%) and ideal body weight (34.8%) as a part of the nutritional education for patients identified as malnourished.Although nutritional assessment is widely performed for hospitalized patients with heart failure, most assessments are subjective rather than objective. Nutritional education, frequently provided before hospital discharge, is limited to information on water or salt intake restrictions. Therefore, more comprehensive and individualized nutritional assessments and counselling with a scientific basis are required.

Relationship of Mild to Moderate Impairment of Left Ventricular Ejection Fraction With Fatal Ventricular Arrhythmic Events in Cardiac Sarcoidosis.

BACKGROUND: Current guidelines recommend placing an implantable cardiac defibrillator for patients with cardiac sarcoidosis and a severely impaired left ventricular ejection fraction (LVEF) of ≤35%. In this study, we determined the association between mild or moderate LVEF impairment and fatal ventricular arrhythmic event (FVAE). METHODS AND RESULTS: We retrospectively analyzed 401 patients with cardiac sarcoidosis without sustained ventricular arrhythmia at diagnosis. The primary end point was an FVAE, defined as the combined endpoint of documented ventricular tachycardia or ventricular fibrillation and sudden cardiac death. Two cutoff points for LVEF were used: a sex-specific lower threshold of normal range of LVEF (52% for men and 54% for women) and an LVEF of 35%, which is used in the current guidelines. During a median follow-up of 3.2 years, 58 FVAEs were observed, and the 5- and 10-year estimated incidences of FVAEs were 16.8% and 23.0%, respectively. All patients were classified into 3 groups according to LVEF: impaired LVEF group, mild to moderate impairment of LVEF group, and maintained LVEF group. Multivariable competing risk analysis showed that both the impaired LVEF group (hazard ratio [HR], 3.24 [95% CI, 1.49-7.04]) and the mild to moderate impairment of LVEF group (HR, 2.16 [95% CI, 1.04-4.46]) were associated with a higher incidence of FVAEs than the maintained LVEF group after adjustment for covariates. CONCLUSIONS: Patients with cardiac sarcoidosis are at a high risk of FVAEs, regardless of documented ventricular arrhythmia at the time of diagnosis. In patients with cardiac sarcoidosis, mild to moderate impairment of LVEF is associated with FVAEs.

Sarcopenia prognosis using dual-energy X-ray absorptiometry and prediction model in older patients with heart failure.

AIMS: This study aimed to determine whether there is a difference in the prognostic value of sarcopenia diagnosed using dual-energy X-ray absorptiometry (DEXA) and that predicted by prediction equations in older patients with heart failure (HF). METHODS AND RESULTS: We included 269 patients (aged ≥65 years) who were hospitalized for HF. We used two appendicular skeletal muscle mass (ASM) prediction equations: (i) Anthropometric-ASM, including age, sex, height, and weight, and (ii) Predicted-ASM, including sex, weight, calf circumference, and mid-arm circumference. ASM index (ASMI) was calculated by dividing the sum of the ASM in the extremities by the height squared (kg/m2). The cut-off values proposed by the Asian Working Group for Sarcopenia 2019 were used to define low ASMI. The prognostic endpoint was all-cause mortality. The median age of the cohort was 83 years [interquartile range (IQR): 75-87], and 135 patients (50.2%) were men. Sarcopenia diagnosed according to DEXA, Anthropometric measurements, and Predicted-ASM was observed in 134 (49.8%), 171 (63.6%), and 157 (58.4%) patients, respectively. During the median follow-up period of 690 days (IQR: 459-730), 54 patients (19.9%) died. DEXA-sarcopenia [hazard ratio (HR), 2.33; 95% confidence interval (CI), 1.26-4.31; P = 0.007] was associated with all-cause mortality after adjusting for pre-existing risk factors, whereas Predicted-sarcopenia (HR, 1.68; 95% CI, 0.87-3.25; P = 0.123) and Anthropometric-sarcopenia (HR, 1.64; 95% CI, 0.86-3.12; P = 0.132) were not. CONCLUSIONS: Sarcopenia diagnosed using DEXA was associated with poor prognosis in older patients with HF; however, the prediction equations were not.

Prognostic impact of MitraScore in elderly Asian patients with heart failure: sub-analysis of FRAGILE-HF.

AIMS: MitraScore is a novel, simple, and manually calculatable risk score developed as a prognostic model for patients undergoing transcatheter edge-to-edge repair (TEER) for mitral regurgitation. As its components are considered prognostic in heart failure (HF), we aimed to investigate the usefulness of the MitraScore in HF patients. METHODS AND RESULTS: We calculated MitraScore for 1100 elderly patients (>65 years old) hospitalized for HF in the prospective multicentre FRAGILE-HF study and compared its prognostic ability with other simple risk scores. The primary endpoint was all-cause deaths, and the secondary endpoints were the composite of all-cause deaths and HF rehospitalization and cardiovascular deaths. Overall, the mean age of 1100 patients was 80 ± 8 years, and 58% were men. The mean MitraScore was 3.2 ± 1.4, with a median of 3 (interquartile range: 2-4). A total of 326 (29.6%), 571 (51.9%), and 203 (18.5%) patients were classified into low-, moderate-, and high-risk groups based on the MitraScore, respectively. During a follow-up of 2 years, 226 all-cause deaths, 478 composite endpoints, and 183 cardiovascular deaths were observed. MitraScore successfully stratified patients for all endpoints in the Kaplan-Meier analysis (P < 0.001 for all). In multivariate analyses, MitraScore was significantly associated with all endpoints after covariate adjustments [adjusted hazard ratio (HR) (95% confidence interval): 1.22 (1.10-1.36), P < 0.001 for all-cause deaths; adjusted HR 1.17 (1.09-1.26), P < 0.001 for combined endpoints; and adjusted HR 1.24 (1.10-1.39), P < 0.001 for cardiovascular deaths]. The Hosmer-Lemeshow plot showed good calibration for all endpoints. The net reclassification improvement (NRI) analyses revealed that the MitraScore performed significantly better than other manually calculatable risk scores of HF: the GWTG-HF risk score, the BIOSTAT compact model, the AHEAD score, the AHEAD-U score, and the HANBAH score for all-cause and cardiovascular deaths, with respective continuous NRIs of 0.20, 0.22, 0.39, 0.39, and 0.29 for all-cause mortality (all P-values < 0.01) and 0.20, 0.22, 0.42, 0.40, and 0.29 for cardiovascular mortality (all P-values < 0.02). CONCLUSIONS: MitraScore developed for patients undergoing TEER also showed strong discriminative power in HF patients. MitraScore was superior to other manually calculable simple risk scores and might be a good choice for risk assessment in clinical practice for patients receiving TEER and those with HF.

Identification of uromodulin deposition in the stroma of perinephric fibromyxoid nephrogenic adenoma by mass spectrometry.

Nephrogenic adenoma (NA) is an epithelial lesion that usually occurs in the mucosa of the urinary tract. Rare cases of deep infiltrative or perinephric lesions have also been reported. Recently, NA with characteristic fibromyxoid stroma (fibromyxoid NA) has been proposed as a distinct variant. Although shedding of distal renal tubular cells due to urinary tract rupture has been postulated as the cause of NA in general, the mechanism underlying extraurinary presentation of NA and fibromyxoid stromal change in fibromyxoid NA remains unknown. In this study, we performed mass spectrometry (MS) analysis in a case of perinephric fibromyxoid NA of an 82-year-old man who underwent right nephroureterectomy for distal ureteral cancer. The patient had no prior history of urinary tract injury or radiation. Periodic acid-Schiff staining-positive eosinophilic structureless deposits in the stroma of fibromyxoid NA were microdissected and subjected to liquid chromatography/MS. The analysis revealed the presence of a substantial amount of uromodulin (Tamm-Horsfall protein). The presence of urinary content in the stroma of perinephric fibromyxoid NA suggests that urinary tract rupture and engraftment of renal tubular epithelial cells directly cause the lesion.

Predictive value of the Ishii score for sarcopenia and the prognosis of older patients hospitalized with heart failure.

AIMS: Although sarcopenia is common and associated with poor outcomes in patients with heart failure, its simple screening methods remain unclear. We aimed to investigate the predictive value of the Ishii score, which includes age, grip strength, and calf circumference, for sarcopenia and its prognostic predictability in patients with heart failure. METHODS: This was a subanalysis of the FRAGILE-HF study. Receiver operating characteristic curves were used to evaluate the predictive value for sarcopenia. Patients were stratified into the high and low Ishii score groups based on the cutoff values of the Ishii score determined by the Youden index for sarcopenia, and the 1-year mortality rates were compared. RESULTS: Of the 1262 study participants, 936 were evaluated with sarcopenia, and 184 (55 women, 129 men) were diagnosed with sarcopenia. The areas under the receiver operating characteristic curves for sarcopenia were 0.73 and 0.87 for women and men, respectively. The optimal cutoff values for predicting sarcopenia were 165 and 141 for women and men, respectively. Using these cutoff values, the sensitivity and specificity for sarcopenia were 70.9% and 68.5% for women and 88.4% and 69.7% for men, respectively. At 1 year, 151 (low Ishii score group, 98; high Ishii score group, 53) deaths were observed. Adjusted Cox proportional hazards analysis showed that the high Ishii score group was significantly associated with 1-year mortality. CONCLUSION: Among older patients hospitalized for heart failure, the Ishii score is useful for predicting sarcopenia and 1-year mortality. Geriatr Gerontol Int 2024; 24: 147-153.

Clinical characteristics and prognosis of patients with isolated cardiac sarcoidosis: Insights from the ILLUMINATE-CS study.

AIM: Data on the clinical features and prognosis of patients with isolated cardiac sarcoidosis (iCS) are limited. This study evaluated the clinical characteristics and prognostic impact of iCS. METHODS AND RESULTS: This was a secondary analysis of the ILLUMINATE-CS study, a multicentre, retrospective registry investigating the clinical characteristics and prognosis of cardiac sarcoidosis. iCS was diagnosed according to the 2016 Japanese Circulation Society (JCS) guidelines. Clinical characteristics and prognosis were compared between patients with iCS and systemic cardiac sarcoidosis (sCS). The primary outcome was a combined endpoint of all-cause death, hospitalization for heart failure, or fatal ventricular arrhythmia events. Among 475 patients with CS (mean age, 62.0 ± 10.9 years; female ratio, 59%) diagnosed by the JCS guidelines, 119 (25.1%) were diagnosed with iCS. Patients with iCS had a higher prevalence of a history of atrial fibrillation or hospitalization for heart failure, or lower left ventricular ejection fraction than those with sCS. During a median follow-up of 42.3 (interquartile range, 22.8-72.5) months, 141 primary outcomes (29.7%) occurred. Cox proportional hazard analysis revealed that iCS was a significant risk factor for the primary outcome in the unadjusted model (hazard ratio [HR] 1.62; 95% confidence interval [CI] 1.12-2.34; p = 0.011). However, this association was not retained after adjustment for other covariates (adjusted HR 1.27; 95% CI 0.86-1.88; p = 0.226). CONCLUSIONS: Patients with iCS had more impaired cardiovascular function at the time of diagnosis than those with sCS. However, iCS was not independently associated with poor prognosis after adjustment for prognostic factors.

Phase I and II randomized clinical trial of an oral therapeutic vaccine targeting human papillomavirus for treatment of cervical intraepithelial neoplasia 2 and 3.

BACKGROUND: Although many human papillomavirus (HPV)-targeted therapeutic vaccines have been examined for efficacy in clinical trials, none have been translated into clinical use. These previous agents were mostly administered by intramuscular or subcutaneous injection to induce systemic immunity. We investigated the safety and therapeutic efficacy of an HPV-16 E7-expressing lacticaseibacillus-based oral vaccine. METHODS: In a double-blind, placebo-controlled, randomized trial, a total of 165 patients with HPV-16-positive high-grade cervical intraepithelial neoplasia 2 and 3 were assigned to orally administered placebo or low, intermediate, or high doses of IGMKK16E7 (lacticaseibacillus paracasei expressing cell surface, full-length HPV-16 E7). In the 4 groups, IGMKK16E7 or placebo was administered orally at weeks 1, 2, 4, and 8 postenrollment. The primary outcomes included histopathological regression and IGMKK16E7 safety. RESULTS: In per-protocol analyses, histopathological regression to normal (complete response) occurred in 13 (31.7%) of 41 high-dose recipients and in 5 (12.5%) of 40 placebo recipients (rate difference = 19.2, 95% confidence interval [CI] = 0.5 to 37.8). In patients positive for HPV-16 only, the clinical response rate was 40.0% (12 of 30) in high-dose recipients and 11.5% (3 of 26) in recipients of placebo (rate difference = 28.5, 95% CI = 4.3 to 50.0). There was no difference in adverse events that occurred in the high-dose and placebo groups (P = .83). The number of HPV-16 E7-specific interferon-γ producing cells within peripheral blood increased with level of response (stable disease, partial, and complete responses; P = .004). The regression to normal (complete response) rates among recipients with high levels of immune response were increased in a dose-dependent manner. CONCLUSION: This trial demonstrates safety of IGMKK16E7 and its efficacy against HPV-16-positive cervical intraepithelial neoplasia 2 and 3. IGMKK16E7 is the first oral immunotherapeutic vaccine to show antineoplastic effects. TRIAL REGISTRATION: jRCT2031190034.

Association and prognostic value of multi-domain frailty defined by cumulative deficit and phenotype models in patients with heart failure.

BACKGROUNDS: Frailty is associated with a poor prognosis in older patients with heart failure (HF). However, multi-domain frailty assessment tools have not been established in patients with HF, and the association between the frailty phenotype and the deficit-accumulation frailty index in these patients is unclear. We aimed to understand this relationship and evaluate the prognostic value of the deficit-accumulation frailty index in older patients with HF. METHODS: We retrospectively analyzed the FRAGILE-HF cohort, which consisted of prospectively registered hospitalized patients with HF aged ≥65 years. The frailty index was calculated using 34 health-related items. The physical, social, and cognitive domains of frailty were evaluated using a phenotypic approach. The primary endpoint was all-cause mortality. RESULTS: Among 1,027 patients with HF (median age, 81 years; males, 58.1%; median frailty index, 0.44), a higher frailty index was associated with a higher prevalence in all domains of cognitive, physical, and social frailty defined by the phenotype model. During the two-year follow-up period, a higher frailty index was independently associated with all-cause death even after adjustment for MAGGIC score plus log-BNP (per 0.1 increase: hazard ratio, 1.21; 95% confidence interval, 1.07-1.37, P=0.002). The addition of the frailty index to the baseline model yielded statistically significant incremental prognostic value (net reclassification improvement, 0.165; 95% confidence interval, 0.012-0.318; P=0.034). CONCLUSIONS: A higher frailty index was associated with a higher prevalence of all domains of frailty defined by the phenotype model and provided incremental prognostic information with preexisting risk factors in older patients with HF.

Prevalence and prognostic value of atrial fibrillation in patients with cardiac sarcoidosis.

Aims: The prognostic value of the presence of atrial fibrillation (AF) in patients at the time of cardiac sarcoidosis (CS) diagnosis is unknown. This study aimed to investigate the association between AF at the time of CS diagnosis and patient prognosis. Methods and results: This study is a post-hoc analysis of Illustration of the Management and Prognosis of Japanese Patients with CS, a multicentre, retrospective observational study that evaluated the clinical characteristics and prognosis of patients with CS. The primary endpoint was the combined endpoint of all-cause death and hospitalization due to heart failure. After excluding patients with missing data about AF status, 445 patients (62 ± 11 years, 36% males) diagnosed with CS according to the Japanese current diagnostic guideline were analysed. Compared to patients without AF, patients with AF (n = 46, 10%) had higher levels of brain natriuretic peptide and a higher prevalence of heart failure hospitalizations. During a median follow-up period of 3.2 years (interquartile range, 1.7-5.8 years), 80 primary endpoints were observed. Kaplan-Meier curve analysis indicated that concomitant AF at the time of diagnosis was significantly associated with a high incidence of primary endpoints (log-rank P = 0.002). This association was retained after adjusting for known risk factors including log-transformed brain natriuretic peptide levels and left ventricular ejection fractions [hazard ratio, 1.96 (95% confidence interval, 1.05-3.65); P = 0.035]. Conclusion: The presence of AF at the time of CS diagnosis is associated with higher incidence of all-cause death and heart failure hospitalization.

Left Atrial Remodeling Related to Disproportionately Low B-Type Natriuretic Peptide in Acute Heart Failure Patients with Atrial Fibrillation.

The diagnostic performance of B-type natriuretic peptide (BNP) for acute heart failure (HF) is impaired in patients with atrial fibrillation (AF). Increased AF burden in HF is associated with left atrial (LA) remodeling. Recent studies have revealed that LA remodeling may affect LV filling. We hypothesized that LA remodeling affects BNP secretion in acute HF conditions. The study investigated the clinical impact of LA remodeling on admission BNP levels in acute HF patients with and without AF. Consecutive acute HF hospitalized patients (n = 899) were divided into groups with (n = 382) or without AF (n = 507) and subdivided into disproportionately low BNP (LB) (≤200 pg/ml), medium BNP (200 to 600 pg/ml) and high BNP (≥600 pg/ml) subgroups. The AF group had a higher proportion of patients with LB than the non-AF group (23.6% vs 16.6%, p = 0.009). BNP levels in both groups were positively correlated with LV end-diastolic volume and negatively correlated with LV ejection fraction in both groups. In contrast, BNP was positively correlated with LA volume index in the non-AF group, but negatively correlated in the AF group. The survival rates were significantly higher in the LB group than in the other groups in non-AF. Conversely, there were no significant differences across all groups in AF patients. In conclusion, in patients with acute HF and AF, disproportionately low BNP levels are associated with LA structural remodeling and poor prognosis.

Efficacy and Safety of Low-dose Oral Prednisolone for Patients with Refractory Hunner-type Interstitial Cystitis.

Background: Hunner-type interstitial cystitis (HIC) is an immunological, chronic inflammatory disease. The efficacy of corticosteroid as a treatment for HIC is unclear. Objective: To assess the efficacy and safety of low-dose oral prednisolone (PSL) treatment for patients with refractory HIC. Design setting and participants: This retrospective observational study reviewed the clinical outcomes of 31 patients with refractory HIC who received oral PSL daily (initial dose, 5.0 or 7.5 mg) for at least 12 mo between 2016 and 2023. The dose was tapered to the minimum that maintained symptom relief during follow-up. Outcome measurements and statistical analysis: Treatment outcomes were evaluated using a seven-graded global response assessment (scores ≥+2, moderately or markedly improved, were defined as treatment response), O'Leary and Sant symptom and problem indices (OSSI/OSPI), overactive bladder symptom score (OABSS), an 11-point pain intensity numerical rating scale, a quality of life (QOL) score, and frequency-volume chart variables. Related complications were also documented. Results and limitations: The mean follow-up period was 20.1 ± 14.6 mo. The overall response rates at 1, 3, 6, 9, and 12 mo at doses of 6.7, 6.7, 5.2, 4.0, and 3.0 mg were 38.7%, 48.4%, 54.8%, 61.3%, and 64.5%, respectively. Compared with baseline, OSSI/OSPI and pain intensity improved significantly from 1 mo after PSL induction. The OABSS, QOL score, urinary frequency, and voided volume improved significantly from 9 mo after PSL induction. No patients discontinued treatment due to adverse events, although hypertension and glucose intolerance occurred in two patients, but these were resolved by temporal medications. Conclusions: This study showed that low-dose oral PSL significantly improves bladder pain, urinary symptoms, and QOL in patients with HIC, without serious adverse events. Further prospective evaluation is warranted to verify the potential efficacy and safety of low-dose PSL for HIC. Patient summary: This retrospective observational study reviewed the clinical outcomes of 31 patients suffering from refractory Hunner-type interstitial cystitis treated with low-dose oral prednisolone. Low-dose prednisolone improved bladder pain, urinary symptoms, and quality of life significantly, without serious adverse events. The response rate of 64.5% at 12 mo was comparable with the rates reported in previous studies that used higher doses of prednisolone. This study provides a rationale for further prospective evaluation of low-dose prednisolone for this intractable disease.

Prognostic impact of cachexia by multi-assessment in older adults with heart failure: FRAGILE-HF cohort study.

BACKGROUND: Cachexia substantially impacts the prognosis of patients with heart failure (HF); however, there is no standard method for cachexia diagnosis. This study aimed to investigate the association of Evans's criteria, consisting of multiple assessments, with the prognosis of HF in older adults. METHODS: This study is a secondary analysis of the data from the FRAGILE-HF study, a prospective multicentre cohort study that enrolled consecutive hospitalized patients aged ≥65 years with HF. Patients were divided into two groups: the cachexia and non-cachexia groups. Cachexia was defined according to Evans's criteria by assessing weight loss, muscle weakness, fatigue, anorexia, a decreased fat-free mass index and an abnormal biochemical profile. The primary outcome was all-cause mortality, as assessed in the survival analysis. RESULTS: Cachexia was present in 35.5% of the 1306 enrolled patients (median age [inter-quartile range], 81 [74-86] years; 57.0% male); 59.6%, 73.2%, 15.6%, 71.0%, 44.9% and 64.6% had weight loss, decreased muscle strength, a low fat-free mass index, abnormal biochemistry, anorexia and fatigue, respectively. All-cause mortality occurred in 270 patients (21.0%) over 2 years. The cachexia group (hazard ratio [HR], 1.494; 95% confidence interval [CI], 1.173-1.903; P = 0.001) had a higher mortality risk than the non-cachexia group after adjusting for the severity of HF. Cardiovascular and non-cardiovascular deaths occurred in 148 (11.3%) and 122 patients (9.3%), respectively. The adjusted HRs for cachexia in cardiovascular mortality and non-cardiovascular mortality were 1.456 (95% CI, 1.048-2.023; P = 0.025) and 1.561 (95% CI, 1.086-2.243; P = 0.017), respectively. Among the cachexia diagnostic criteria, decreased muscle strength (HR, 1.514; 95% CI, 1.095-2.093; P = 0.012) and low fat-free mass index (HR, 1.424; 95% CI, 1.052-1.926; P = 0.022) were significantly associated with high all-cause mortality, but there was no significant association between weight loss alone (HR, 1.147; 95% CI, 0.895-1.471; P = 0.277) and all-cause mortality. CONCLUSIONS: Cachexia evaluated by multi-assessment was present in one third of older adults with HF and was associated with a worse prognosis. A multimodal assessment of cachexia may be helpful for risk stratification in older patients with HF.

Genome-wide association study identifies risk loci within the major histocompatibility complex region for Hunner-type interstitial cystitis.

Hunner-type interstitial cystitis (HIC) is a rare, chronic inflammatory disease of the urinary bladder with unknown etiology and genetic background. Here, we conduct a genome-wide association study of 144 patients with HIC and 41,516 controls of Japanese ancestry. The genetic variant, rs1794275, in the major histocompatibility complex (MHC) region (chromosome 6p21.3) is associated with HIC risk (odds ratio [OR] = 2.32; p = 3.4 × 10-9). The association is confirmed in a replication set of 26 cases and 1,026 controls (p = 0.014). Fine mapping demonstrates the contribution to the disease risk of a completely linked haplotype of three human leukocyte antigen HLA-DQß1 amino acid positions, 71, 74, and 75 (OR = 1.94; p = 5 × 10-8) and of HLA-DPß1 amino acid position 178, which tags HLA-DPB1∗04:02 (OR = 2.35; p = 7.5 × 10-8). The three HLA-DQß1 amino acid positions are located together at the peptide binding groove, suggesting their functional importance in antigen presentation. Our study reveals genetic contributions to HIC risk that may be associated with class II MHC molecule antigen presentation.

Usefulness of HANBAH Score in Japanese Patients With Acute Heart Failure.

The HANBAH score is a novel simple risk score consisting of hemoglobin level, age, sodium (N) level, blood urea nitrogen level, atrial fibrillation, and high-density lipoprotein. We aimed to validate this score in an external population. This retrospective study included 744 patients hospitalized for acute heart failure between 2015 and 2019. Each of the following criteria was scored as 1 point: hemoglobin level (<13.0 g/L for men and <12.0 g/L for women), atrial fibrillation, age (>70 years), serum blood urea nitrogen level (>26 mg/100 ml for men and >28 mg/100 ml for women), serum high-density lipoprotein level (<25 mg/100 ml), and serum sodium level (<135 mg/100 ml). HANBAH scores were available for 736 patients (age, 75 ± 13 years; 60% male; reduced [<40%] and preserved ejection fraction [≥50%]: 35% and 49%, respectively). All-cause death during follow-up, a composite of death and heart failure rehospitalization, and in-hospital death were observed in 173, 274, and 51 patients, respectively. The HANBAH score was significantly associated with these end points after adjustment for covariates (adjusted hazard ratio 1.38 [95% confidence interval 1.16 to 1.64], p <0.001; 1.27 [1.11 to 1.45], p <0.001; and 1.66 [1.18 to 2.33], p <0.001, respectively). Receiver operating characteristic and net reclassification improvement analyses showed that the HANBAH score performed significantly better than AHEAD (atrial fibrillation, hemoglobin [anemia], elderly, abnormal renal parameters, diabetes mellitus) and AHEAD-U (AHEAD with uric acid) scores and similar to the multi-domain ACUTE HF score for all end points. In conclusion, the HANBAH score showed powerful risk stratification in this external Japanese cohort. Despite its simplicity, it performed better than other simple risk scores and similar to a multidomain risk score.