Kokura Memorial Hospital

Osteoporosis causes fractures which further increase the disease burden of rheumatoid arthritis (RA), however, osteoporosis treatment rates remain low. While several studies have reported that biologic or targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) can prevent or improve osteoporosis in RA, our large-scale, real-world study showed that 1 year-b/tsDMARDs use did not arrest osteoporosis progression. This study aimed to examine longer-term changes in bone mineral density (BMD). BMD was observed for up to 5 years in patients receiving b/tsDMARDs for active RA. The primary endpoint was change in BMD (T-score), and the secondary endpoint was change in T-score-related factors. In total, 797 patients (anti-osteoporosis (-), n = 645; anti-osteoporosis (+), n = 152) were included, with a median 3.1-year follow-up (2,489 patient-years). Clinical disease activity index (CDAI) improved in both groups (26.0/24.4 → 6.6/6.8). T-scores decreased significantly in the femoral neck and radius in the anti-osteoporosis (-) group but not in the anti-osteoporosis (+) group [anti-osteoporosis (-): mean change -0.11/-0.33, both p < 0.001; anti-osteoporosis (+):-0.01/-0.10, p = 0.830/0.071]. Overall, 460 patients (58%) experienced a decrease in T-score. A high baseline T-score correlated with a subsequent decrease, while longer osteoporosis treatment duration correlated with an increase. Unexpectedly, the duration of b/tsDMARD use and mean CDAI during observation were not associated with BMD maintenance. Even when RA activity was controlled with b/tsDMARDs, BMD still decreased. This study emphasizes the importance of considering osteoporosis as an independent aspect of RA, beyond inflammation control.

We evaluated the prognostic significance and implications of a major pathologic response (MPR) after preoperative treatment for pancreatic ductal adenocarcinoma (PDAC). Preoperative treatment is increasingly used for PDAC to improve oncologic outcomes. The pathologic response represents a potential indicator of treatment efficacy; however, its prognostic value in PDAC remains unclear. We retrospectively analyzed 739 patients who underwent pancreatectomy for PDAC after preoperative treatment at 21 institutions in Japan. The pathologic response was graded using Evans' classification, with MPR defined as Evans grade III/IV. Survival outcomes and prognostic factors were evaluated, and factors associated with achieving MPR were analyzed to develop a predictive model. MPR was achieved in 11.5% of patients. The MPR group had a significantly longer median overall survival (71.5 vs. 40.9mo) and recurrence-free survival (55.5 vs. 15.2mo) than the non-MPR group. Multivariate analysis identified MPR as an independent prognostic factor for overall survival. In the MPR subgroup, neither overall nor recurrence-free survival differed according to adjuvant chemotherapy administration; multivariate analysis did not identify adjuvant therapy as an independent prognostic factor. Predictive factors for achieving MPR included chemoradiotherapy, preoperative duration ≥6 months, normal carbohydrate antigen 19-9 after preoperative treatment, and complete or partial radiologic response. Finally, we developed a simplified predictive model for achieving MPR. MPR was independently associated with favorable survival in PDAC. The prognostic impact of adjuvant chemotherapy was not observed among patients who achieved MPR, suggesting that MPR may inform individualized postoperative management and warrants prospective validation.

The role of transcatheter aortic valve replacement (TAVR) in nonagenarians remains uncertain, especially regarding long-term outcomes and prognostic factors. This study aimed to evaluate long-term outcomes of TAVR in nonagenarians, focusing on cause-specific mortality and the prognostic influence of frailty and malnutrition. We analyzed 4,623 patients who underwent transfemoral TAVR in a multicenter Japanese registry, including 700 aged ≥90 years. Outcomes were followed for 5 years. We analyzed all-cause mortality, cause-specific mortality, and the prognostic impact of the Clinical Frailty Scale and Geriatric Nutritional Risk Index. At 5 years, all-cause mortality was higher in patients aged ≥90 years than in those <90 years (53.2% vs37.0%, P < 0.001), primarily due to noncardiovascular deaths such as senility and infections (32.5% vs 19.9%; P < 0.001). Cardiovascular mortality was similar (20.3% vs 17.0%; P = 0.198). Multivariable analysis showed that age ≥90 years was not an independent predictor; frailty and malnutrition were the strongest prognostic factors. A Clinical Frailty Scale-Geriatric Nutritional Risk Index heatmap revealed marked heterogeneity, identifying subgroups of nonagenarians with preserved nutrition and low frailty who achieved favorable long-term survival. In this large multicenter registry, excess mortality in nonagenarians after TAVR was driven mainly by noncardiovascular causes. Frailty and malnutrition, rather than chronological age, were central determinants of long-term outcomes. These findings emphasize that TAVR candidacy in nonagenarians should be guided on geriatric assessment of frailty and nutrition to identify patients most likely to achieve meaningful survival while avoiding futile interventions.

Zinc deficiency is widely recognized as a cause of anemia, but no studies have clarified the impact of zinc deficiency on achieving target hemoglobin levels in patients undergoing peritoneal dialysis (PD) and receiving high-dose erythropoiesis-stimulating agent (ESA) therapy. This study aimed to investigate the relationship between zinc deficiency and ESA-hyporesponsive anemia in patients on PD. This cross-sectional study included 164 patients on PD aged ≥ 18years. The target hemoglobin level was 11-13g/dL. ESA dosage was categorized as low-dose (< 120µg/month) or high-dose (≥ 120µg/month), while zinc deficiency was defined as a serum zinc level < 60µg/dL. A logistic regression model was used to calculate the odds ratio (OR) for achieving the target hemoglobin level. The proportion of patients achieving the target hemoglobin level was 48.2% in the low-dose ESA and non-zinc-deficient group, and 12.2% in the high-dose ESA and zinc-deficient group. Compared with the low-dose ESA and non-zinc-deficient group, the adjusted OR for achieving the target hemoglobin level was significantly lower in the high-dose ESA and zinc-deficient group (OR: 0.19, 95% confidence interval 0.05-0.72). Stratified analyses based on serum albumin, serum C-reactive protein, and transferrin saturation did not change the association between the high-dose ESA and zinc-deficient group and the achievement of the target hemoglobin level. Zinc deficiency in patients on PD is a significant barrier to achieving the target hemoglobin level, and serum zinc levels should be routinely monitored in patients with ESA-hyporesponsive anemia.

The management of very low-gradient (LG) severe aortic stenosis (AS) remains challenging. Moreover, limited evidence exists regarding the outcomes of patients with very LG severe AS following transcatheter aortic valve implantation (TAVI). Weaimedto elucidate the prognosis of patients with very LG severe AS after TAVI and the influence of flow status. Data were retrospectively collected from the OCEAN-TAVI multicenter registry in Japan, including patients with severe AS who underwent TAVI. In total, 7103 patients were classified into three groups based on their baseline mean pressure gradient (MPG): very LG (MPG ≤ 20 mmHg), LG (20 < MPG < 40 mmHg), and high-gradient (HG) (MPG ≥ 40 mmHg). The primary endpoint was a composite of all-cause mortality and hospitalization for heart failure. During a median follow-up period of 741 days, the composite endpoint was reached in 2081 patients. Patients with very LG severe AS had a higher prevalence of comorbidities. Kaplan-Meier analysis showed that very LG severe AS was associated with significantly lower event-free survival compared to that with LG and HG severe AS. Multivariable Cox regression analysis identified very LG severe AS as an independent poor prognostic indicator, regardless of the flow state. Moreover, within the very LG severe AS group, a low body mass index and myocardial infarction history were associated with worse outcomes. This study indicates that patients with very LG severe AS have worse prognoses compared to those with LG or HG severe AS following TAVI, regardless of the flow state.

Atrial fibrillation (AF) after bioprosthetic valve (BPV) replacement is common in older patients with multiple comorbidities and is associated with a heightened risk of thromboembolism. Anticoagulation therapy is often indicated, but renal impairment and other comorbidities elevate bleeding risk, making clinical decisions complex. This study compared clinical outcomes between warfarin and direct oral anticoagulants (DOACs) in this high-risk population. This subgroup analysis of the BPV-AF Registry included 612 patients treated with oral anticoagulants after BPV replacement, stratified by renal function: normal or mild impairment (creatinine clearance [CCr] ≥50 mL/min), mild-to-moderate impairment (30 mL/min ≤ CCr < 50 mL/min), and moderate-to-severe impairment (15 mL/min ≤ CCr < 30 mL/min). Baseline characteristics and outcomes were analyzed within each stratum. The composite outcome of stroke, systemic embolism, and cardiovascular events was numerically less frequent in the DOAC than warfarin group across all strata, although the differences were not statistically significant. Major bleeding also tended to be lower in the DOAC group. In this study from a Japanese nationwide registry comparing outcomes of AF patients after BPV replacement with severe renal impairment between those treated with DOACs and those treated with warfarin, comparative conclusions between DOACs and warfarin cannot be drawn because of the small sample size. Nonetheless, both anticoagulants may be acceptable in clinical practice, highlighting the need for individualized decision-making based on patient risk.

Abstract Background Transcatheter left atrial appendage closure (LAAC) with the WATCHMAN device has emerged as an alternative treatment option to oral anticoagulants. The WATCHMAN device was introduced in Japan in 2019, followed by the newer WATCHMAN FLX device in 2021. However, few studies have investigated sex differences in the outcomes of the LAAC procedure. Objective This study aimed to evaluate sex differences in LAAC procedures in Japan. To adjust for confounding factors, we employed two innovative matching methods: propensity score (PS) and inverse probability of treatment weighting (IPTW). Methods The TERMINATOR (Transcatheter Modification of Left Atrial Appendage by Obliteration with Device) registry is a multicenter, real-world registry involving 23 institutions in Japan. This study enrolled 1,817 patients with atrial fibrillation who underwent LAAC at these institutions between September 2019 and September 2023. The primary efficacy endpoint was a composite of ischemic stroke, transient ischemic attack, or systemic embolism at 12 months. The primary safety endpoint was a composite of hemorrhagic stroke or anemia requiring transfusion at 12 months. The secondary endpoint was all-cause mortality through 12 months. A retrospective analysis was performed to compare clinical outcomes following LAAC, using propensity score matching (PSM) at a 1:1 ratio and IPTW to minimize potential bias. Results Of the 1,171 patients analyzed, 332 (28.4%) were women. Compared with men, women were older (78.1 ± 7.7 years vs. 74.86 ± 8.1 years; P &amp;lt; 0.001) and more likely to have paroxysmal atrial fibrillation (45.2% vs. 36.6%; P = 0.007). The CHA2DS2-VA and HAS-BLED scores were comparable between the sexes (4.4 ± 1.3 vs. 4.5 ± 1.4; P = 0.751 and 3.3 ± 0.8 vs. 3.3 ± 0.9; P = 1.000, respectively). After PSM, 330 men and 330 women were selected for the final analysis. As shown in the Kaplan–Meier analysis (Figure), no statistical differences were observed between the sexes in the primary efficacy and safety endpoints or the secondary endpoint. The IPTW method produced similar results. Conclusion In patients with atrial fibrillation undergoing LAAC, women demonstrated similar safety and efficacy outcomes compared with men.

Abstract Background Heart failure (HF) is a significant public health concern, and early detection of worsening HF can improve clinical outcomes. The HeartInsight (HI) system is an advanced heart failure risk prediction tool that utilizes physiological and clinical parameters to identify patients at risk of worsening HF. In November 2023, the HI remote monitoring system became available in Japan for Biotronik Implantable Cardioverter Defibrillator (ICD) and Cardiac Resynchronization Therapy Defibrillator (CRT-D) users. However, the impact of sex differences on the accuracy of HI predictions remains unclear, particularly in Japanese patients. Purpose This study aims to assess the system’s predictive accuracy in female versus male patients with HF in a Japanese cohort. Methods We retrospectively analyzed 293 patients (female: 59 [20%]; age: 70 ± 3 years; non-ischemic cardiomyopathy: 160 [55%]) who underwent Biotronik ICD or CRT-D implantation at two Japanese institutions between March 2019 and February 2025. An HI alert was defined as a score of 45 or higher sustained for three consecutive days. Patient demographics, HI alert status, and remote monitoring parameters were analyzed. Results The HI scores were available for 183 patients, including 43 with female and 140 with male. Between September 2024 and February 2025, 14 and 44 patients experienced HI score alerts and one and 9 patients required HF hospitalization or outpatient treatment, yielding a positive predictive value of 7 and 20% in patients with female and male, respectively. Among 29 and 96 patients without HI alerts, only one and 4 required HF hospitalization, yielding a negative predictive value of 97 and 96% in patients with female and male, respectively. The positive predictive value and negative predictive value were statistically equivalent between the two groups (p=0.42, p=1.00). Conclusions The HI system demonstrated comparable predictive accuracy for worsening HF in both female and male Japanese patients with an Bitronik ICD or CRT-D. These findings suggest that while the HI system effectively identifies patients at low risk of HF events regardless of sex, its ability to predict HF deterioration may vary between female and male patients. Further research with larger cohorts is warranted to explore potential sex-specific factors influencing HI score performance and to optimize predictive models for improved clinical application.

Abstract Background Previous studies have suggested that performing multivessel percutaneous coronary intervention (PCI) in a single session yields short- to mid-term outcomes comparable to staging the procedures, in both ST-elevation myocardial infarction and in non–ST-elevation acute coronary syndrome (NSTE-ACS) or chronic coronary syndrome (CCS). However, the long-term outcomes of single-session versus staged multivessel PCI in elective (non-ST-elevation) patients remain unclear. Purpose To assess the association between a single-session vs. staged multivessel PCI strategy and long-term clinical outcomes in patients with NSTE-ACS or CCS undergoing elective multivessel PCI. Methods We analyzed a multicenter PCI registry (Coronary REvascularisation Demonstrating Outcome Study in Kyoto [CREDO-Kyoto] cohort-2 [2005–2007] and cohort-3 [2011–2013]) that enrolled 30,866 consecutive patients undergoing first coronary revascularization. From this pooled cohort, 3,953 patients with multivessel coronary artery disease who underwent elective PCI (for NSTE-ACS or CCS) were identified. Among these, 1,450 patients (36.7%) received single-session multivessel PCI and 2,503 (63.3%) underwent staged multivessel PCI. Baseline clinical and angiographic characteristics were compared between the groups. The primary outcome measure was all-cause death up to 5 years. A 1-year landmark analysis was conducted to evaluate differences in mortality beyond the first year. Results Patients treated with a single-session strategy had less extensive disease at baseline and less complex interventions: the prevalence of three-vessel disease was lower in the single-session group than in the staged group (43% vs. 54%, p&amp;lt;0.0001). Despite less extensive baseline disease in the single-session group, the 5-year all-cause mortality was significantly higher in the single-session group compared to the staged group (18.2% vs. 13.2%; log-rank p&amp;lt;0.0001). In multivariable analysis, single-session PCI remained independently associated with a higher risk of all-cause death (adjusted hazard ratio 1.35, 95% confidence interval 1.14–1.60; p=0.0004). In the 1-year landmark analysis, there was no significant difference in mortality between the two strategies within the first year; however, beyond 1 year, the mortality curves diverged, with the single-session group experiencing a continuously higher mortality rate and an increasing gap in survival compared to the staged group. Conclusions In patients with NSTE-ACS or CCS undergoing elective multivessel PCI, a single-session revascularization strategy was associated with higher 5-year all-cause mortality compared to a staged PCI strategy. Notably, this mortality difference only became apparent after the first year.Kaplan-Meier curves:all-cause death 1 year landmark analysis