阿江 竜介

Losartan has a unique uricosuric property among angiotensin II receptor blockers and may therefore be advantageous in patients with hypertension and hyperuricemia or gout. The study by Xu et al. combined a meta-analysis of placebo-controlled randomized trials with a target trial emulation using UK Biobank data and demonstrated that losartan reduced serum uric acid by approximately 0.3 mg/dL. Although this effect is modest and substantially smaller than that of established uric acid-lowering therapies, it may be clinically relevant when selecting antihypertensive treatment for patients with borderline hyperuricemia, gout risk, or diuretic-associated uric acid elevation. Losartan may partially counterbalance the uric acid-raising effect of thiazide diuretics, but it should not replace appropriate treat-to-target therapy in patients with gout or marked hyperuricemia. The study is limited by the small emulated cohort and the possibility of residual confounding and selection bias. Nevertheless, the consistency of the findings across different analytical approaches supports a genuine uric acid-lowering effect. Future studies should determine whether this biochemical effect translates into fewer gout flares, improved attainment of serum uric acid targets, or reduced cardiovascular and cardiometabolic events. Overall, losartan should be regarded as an effective antihypertensive agent with a modest but favorable uric acid profile. Clinical interpretation of losartan's uric acid-lowering effect in hypertension care. ARB, angiotensin II receptor blocker; RCT, randomized controlled trial; URAT1, urate transporter 1.

BACKGROUND: Although probable sporadic Creutzfeldt-Jakob Disease (CJD) can be diagnosed without prion protein gene (PRNP) testing, some patients with genetic prion disease may meet the diagnostic criteria for sporadic CJD. We aimed to assess the potential for such misclassification in the absence of genetic information. METHODS: We analyzed data from the nationwide prospective registry of prion diseases in Japan. For patients diagnosed with probable sporadic CJD, clinical characteristics were compared according to whether PRNP testing had been performed. In addition, patients with genetic prion diseases were reclassified to evaluate potential misclassification as sporadic CJD. RESULTS: A total of 3008 patients with sporadic CJD and 1143 with genetic prion diseases were analyzed. Tested and Not-Tested groups differed in age at onset (difference, -1 year; 95% CI, -3 to -1) and CSF RT-QuIC positivity (difference, 8.2%; 95% CI, 3.4 to 13.2). The median survival time was 11.9 months for the Tested group and 9.8 months for the Not-Tested group. The proportions of misclassification after reclassification of patients with genetic prion diseases (95% CI) were 82.9% (75.5, 88.5) for E200K, 24.1% (20.9, 27.6) for V180I, 72.7% (64.6, 79.6) for M232R, 12.3% (8.1, 18.2) for P102L, 0% (0, 13.8) for P105L, and 10% (1.8, 40.4) for D178N. CONCLUSIONS: A substantial proportion of patients with genetic prion disease may meet the clinical diagnostic criteria for sporadic CJD. Opportunities for PRNP testing may be limited in patients with rapidly progressive disease.

BACKGROUND: Coronary artery aneurysm (CAA) remains the most serious cardiovascular complication of Kawasaki disease. We sought to identify consistent risk factors for CAA among large contemporary cohorts from Japan and the United States. METHODS: We conducted a retrospective cohort study including 42 350 children from the 26th and 27th Japanese Nationwide Kawasaki Disease Surveys (2019-2022) and 1216 children from a multiethnic US cohort. Multivariable logistic regression was used to evaluate associations between clinical variables and CAA at 1 month after disease onset (Z score ≥2.5). RESULTS: In both cohorts, baseline coronary artery dilation at diagnosis (Z score ≥2.5) was strongly associated with CAA 1 month after disease onset (Japan: odds ratio [OR], 22.7 [95% CI, 19.2-26.7]; United States: OR, 13.4 [95% CI, 8.6-21.0]). Age younger than 6 months and intravenous immunoglobulin resistance were also independently associated with increased risk. These associations were also observed for medium to giant CAAs. Stratified analyses demonstrated that intravenous immunoglobulin resistance was most strongly associated with subsequent CAA among children with normal coronary arteries at diagnosis. CONCLUSIONS: Among large Japanese and US cohorts, coronary artery dilation at diagnosis and age younger than 6 months were consistent predictors of CAA. These associations were also observed for medium to giant CAA, underscoring their relevance for clinically significant coronary outcomes. Early coronary artery assessment provides important prognostic information and may inform cardiovascular risk stratification and management in children with Kawasaki disease.

BACKGROUND: Solitary death (kodokushi) has emerged as a public health and social issue in Japan with rapid population aging. However, recent epidemiological data on solitary deaths remain limited. METHODS: We conducted a population-based descriptive epidemiological study using records from the Tokyo Medical Examiner's Office from 2016 to 2023. All cases that met the study definition were selected from 110,024 records and included in the analysis. Data on demographic characteristics, postmortem interval (PMI), manner and cause of death, and underlying diseases were analyzed. RESULTS: Among 46,313 solitary death cases, 32,345 were male (69.8%, median age 70 years) and 13,968 were female (30.2%, median age 80 years). Crude mortality rates per 100,000 persons increased from 69.3 to 102.5 in males and 29.7 to 41.4 in females between 2016 and 2023. Solitary deaths exhibited seasonal variation, with peaks in summer and winter. Most cases involved pensioners and welfare recipients. PMI was longer in males than females (5 days vs. 3 days). Cardiovascular diseases were the leading cause of death for both sexes. Heat stroke predominated in summer, whereas natural deaths were more frequent in winter. More than half of cases had underlying diseases, most commonly hypertension. CONCLUSIONS: Solitary death in Tokyo's 23 wards increased over the study period. Seasonal, demographic, and clinical patterns highlight the need for season-specific prevention strategies and the potential role of primary care in mitigating risk.

BACKGROUND: Coronary artery (CA) lesions (CALs) are major complications of Kawasaki disease (KD). Studies have reported that coronary outcomes (CAL regression and progression) are associated with age; however, age-stratified data remain limited. METHODS: We analyzed data from 129,950 patients with KD in Japan (2011-2022). CALs were classified as CA dilatation, CA aneurysm, or giant CA aneurysm. Coronary outcomes were assessed by comparing echocardiographic findings between baseline and the subacute phase. Patients were stratified into nine 6-month age groups. Restricted cubic splines (RCS) were used to assess nonlinear associations between age and coronary outcomes. Multivariable logistic regression analyses assessed age-specific associations using the RCS-identified reference group. RESULTS: Among patients without CALs at initial echocardiography, the 0 to 6-month group had the highest proportion with subsequent CAL development (2.8%). Among patients with CA dilatation, the 0 to 6-month group showed the lowest proportion of patients with CA regression (75.5%). RCS analyses identified the 25 to 30-month group as the most likely to show CA dilatation regression and the least likely to experience CAL progression. Multivariable analysis demonstrated that patients aged 0 to 6 months were significantly less likely to show CA dilatation regression (adjusted odds ratio [95% confidence interval]: 0.44 [0.30-0.63], reference: 25-30 months) and more likely to experience CAL progression (3.84 [3.03-4.86]). CONCLUSIONS: Coronary outcomes differed substantially across age groups; patients aged 0 to 6 months had the most adverse coronary outcomes. Even without CALs at initial echocardiography, this age group had the highest risk of subsequent CAL development.

BACKGROUND: Published cases of iatrogenic cerebral amyloid angiopathy (iCAA) are increasing; however, their geographic distribution and age-related clinical spectrum have not been systematically characterised. We aimed to characterise the published evidence, including Japan's contribution and differences in presentation by age. METHODS: A scoping review of published iCAA cases was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA). We searched MEDLINE, Scopus and Ichushi-Web-a major Japanese medical literature database-from database inception to 31 January 2026. Reports were screened using broad clinical and exposure compatibility criteria, and included cases were retrospectively classified according to the revised Queen Square framework. We summarised the global distribution and clinical profiles of published cases; comparisons of cases reported from Japan versus other countries and onset before versus at or after 55 years were exploratory. RESULTS: 57 reports describing 94 cases were included. Japan contributed the largest number of published cases although case counts cannot estimate incidence. The median age at first presentation and first exposure was 42 and 4 years, respectively; the median latency was 36 years. Cranial surgery was the main exposure event, with cadaveric dura mater identified in 44 cases. Acute intracerebral haemorrhage (ICH) was the first presentation in 58 cases. Among cases with older onset (≥55 years), acute ICH was less frequent at presentation. CONCLUSIONS: Published iCAA cases were most frequently reported from Japan; however, ascertainment and publication biases preclude geographic incidence comparisons. iCAA may present after age 55 and without acute ICH, supporting systematic exposure-history ascertainment and internationally coordinated registry-based surveillance.

IMPORTANCE: The COVID-19 pandemic may serve as a natural experiment, with pandemic-associated changes in the epidemiology of Kawasaki disease (KD) potentially informing understanding of KD pathogenesis. OBJECTIVES: To assess long-term KD incidence across 50 years and to examine pandemic-associated changes in KD epidemiology across age groups. DESIGN, SETTING, AND PARTICIPANTS: This cohort study was a descriptive epidemiologic analysis of data from the Japanese Nationwide Survey of Kawasaki Disease conducted from 2023 to 2024, along with 50 years of historical data. Data were included from patients with KD in the current 2023-2024 survey (n = 29 841) and historical and current survey data from 1975 through 2024 (n = 467 456) for trend analysis. MAIN OUTCOMES AND MEASURES: Annual KD incidence overall and stratified by 3 age groups: infants (<1 year), 1 to 4 years, and 5 to 9 years. RESULTS: The current survey registered 15 032 and 14 809 patients with KD in 2023 and 2024, respectively (overall, 57.3% male; median [IQR] age, 2 [1-4] years). Across the 50-year study period, despite the population under 5 years of age declining in Japan by 61.6%, KD incidence rates increased 16.1-fold. Across the COVID-19 pandemic period, patient numbers reached a nadir of 10 333 in 2022, then rebounded to 15 032 cases (45.5% increase) in 2023. Notably, decline and rebound patterns differed by age. Indexed incidence rates (using 2017 as a baseline of 100) demonstrated that patients 5 to 9 years of age had the largest decline (nadir of 54.2 in 2021, 45.8% below baseline) and the largest rebound (134.8 in 2024, 34.8% above baseline). In contrast, patients younger than 1 year showed the smallest decline (nadir of 73) and incidence rates did not return to baseline levels. When comparing the magnitude of rebound in KD incidence, a distinct age-dependent dose-response pattern was observed: 26.1% for infants, 38.9% for patients aged 1 year, 42.7% for patients aged 2 years, 85.8% for patients aged 3 years, 105.3% for patients aged 4 years, and 166.7% for patients aged 5 to 9 years. CONCLUSIONS AND RELEVANCE: In this nationwide cohort study of KD in Japan, KD incidence rebounded after the relaxation of COVID-19 pandemic-related restrictions, with age-dependent patterns. Nonpharmaceutical interventions (eg, mask-wearing) during the pandemic may explain the greater rebound pattern observed in older children; however, the minimal changes in infants suggest different exposure pathways to potential KD triggers. These findings support an age-stratified approach to KD pathogenesis research, distinguishing infants from older children.

The frequency of heart failure and hyperuricemia is increasing worldwide. Hyperuricemia as a complication of heart failure is known to be an indicator of poor prognosis. However, no consensus exists on whether treating hyperuricemia as a complication of heart failure would alleviate symptoms or improve prognosis in patients with heart failure. There is insufficient evidence regarding whether treatment with uric acid-lowering agents can alleviate symptoms and improve prognosis in patients with heart failure. However, considering the prevention of gout, hypertension, and chronic kidney disease caused by hyperuricemia, if the serum uric acid level does not fall below 8 mg/dL with improvement in lifestyle habits, uric acid-lowering agents can be a treatment option. In an US cohort study comprising approximately 100,000 participants using Medicare data, less aggravation of heart failure was observed in patients who were administered febuxostat compared to allopurinol. Recent evidence further suggests that serum uric acid may reflect not only a biomarker of disease severity but also underlying xanthine oxidase activity and oxidative stress, which may be therapeutically targetable in selected subgroups of heart failure patients. Moreover, differential effects among uric acid-lowering agents raise the possibility that drug-specific properties, rather than uric acid reduction per se, may influence cardiovascular outcomes. In this review, we discuss clinical trials on hyperuricemia with heart failure and its treatment. Further large-scale, high-quality, prospective intervention studies on the efficacy of treating hyperuricemia as a complication of heart failure are required.

OBJECTIVE: To evaluate clinical and epidemiological features of juvenile-onset systemic sclerosis (jSSc) in Japan and to identify racial and generational differences. METHODS: We surveyed patients with jSSc (developed < 18 years of age) who visited selected facilities in Japan between January 2016 and December 2020. We estimated the number of patients with jSSc and the annual incidence rate in Japan. Thereafter, differences in clinical characteristics by disease subtype, autoantibody, and age at investigation were analyzed and compared with previous cohorts. RESULTS: Of the 3005 institutions selected for the first survey, 1845 (61.4%) responded. The estimated number of patients with jSSc was 299, whereas the estimated annual incidence rate ranged from 0.98 to 1.59 per 1 million children (aged < 18 years) from 2016 to 2020. In the second-stage survey, 130 cases were analyzed, of which 85 (65.4%) had diffuse cutaneous SSc (dcSSc), 77.7% were female, and the median ages at onset and during the survey were 11 and 21 years, respectively. Autoantibody positivity was 62.4% for antitopoisomerase I antibody (ATA) and 12.9% for anticentromere antibody, whereas anti-PM/Scl antibody was very rare. In total, interstitial lung disease was present in 40.8% of patients (predominantly dcSSc and ATA positive), gastrointestinal lesions in 36.9%, pulmonary arterial hypertension in 7.7%, and no renal crisis. CONCLUSION: This is the largest national survey of jSSc characteristics analyzed in detail by autoantibody and disease subtype. Japanese jSSc was characterized by a very high ATA positivity rate. However, the frequency of major organ involvement was similar to previous reports of jSSc in the West.

OBJECTIVES: Nocturnal hypertension, especially with well-controlled daytime blood pressure (BP), has emerged as a significant risk factor for cardiovascular disease. This study investigated its prevalence by morning home BP cut-off values and examined associated patient characteristics using data from the Japan Morning Surge-Home Blood Pressure (J-HOP) study. METHODS: This post hoc analysis included 2675 participants from the J-HOP study who had complete data on nighttime home BP, measured using validated automatic oscillometric devices. Nocturnal hypertension was defined as a nighttime systolic BP greater than or equal to 120 mmHg and diastolic BP greater than or equal to 70 mmHg. RESULTS: Among the participants, 60.5% had nocturnal hypertension. The proportion of patients with nocturnal hypertension decreased as the cut-off value for morning home BP was lowered: 40.5, 32.1, 23.7, and 14.6% for less than 135/85 mmHg, less than 130/80 mmHg, less than 125/75 mmHg, and less than 120/70 mmHg, respectively. The prevalence of nocturnal hypertension was significantly higher in individuals with diabetes compared with those without, at morning home BP thresholds of less than 135/85 mmHg (48.1 vs. 39.3%; P = 0.03) and less than 130/80 mmHg (41.0 vs. 30.6%; P = 0.01). Individuals taking diuretics had a significantly lower prevalence of nocturnal hypertension compared with those not taking diuretics, at a morning home BP threshold of less than 135/85 mmHg (35.3 vs. 42.9%; P = 0.01). CONCLUSION: A considerable number of patients continued to show nocturnal hypertension even at lower morning home BP thresholds. Diabetes may contribute to nocturnal hypertension despite well-controlled morning BP, while diuretic use may help prevent it.

BACKGROUND: During the coronavirus disease 2019 (COVID-19) pandemic, the seasonality of Kawasaki disease (KD) in Japan shifted from winter dominance to summer dominance. However, it remains unclear whether this pattern reverted after infection mitigation measures were lifted in 2023. METHODS: We conducted a population-based retrospective survey among all hospitalized patients with KD in Shiga Prefecture, Japan, from 2015 to 2024. Monthly variations in the KD incidence from 2021 to 2024 were analyzed using the 2015-2019 period as reference. We also examined the seasonality of 10 common pediatric infectious diseases and seasonal influenza during the study period. RESULTS: A total of 2077 patients with KD were identified. The KD incidence remained low during the implementation of public health measures against COVID-19 from 2020 to 2022. Subsequently, the incidence reached the maximum in 2023 (128.2 per 100,000 person-years), coinciding with the lifting of infection mitigation measures; the incidence remained high at 118.9 in 2024. The traditional winter peak in KD incidence disappeared after 2020. Instead, peak incidence was observed in the summer from 2021 to 2022 and in the spring from 2023 to 2024. The number of patients with respiratory syncytial virus infection, which had been highest during the fall and winter from 2015 to 2019, reached the highest levels during the spring and summer from 2021 onward. CONCLUSIONS: KD seasonality in Shiga Prefecture did not revert to the traditional winter-dominant pattern after COVID-19 infection mitigation measures were lifted. Continued surveillance is warranted to determine whether the winter-dominant pattern re-emerges.

BACKGROUND: In Kawasaki disease (KD), coronary arteritis occurring in infancy can lead to long-term sequelae, such as luminal dilatation, stenosis, intimal thickening, and calcification. However, the long-term evolution of these lesions, particularly the effect of superimposed atherosclerosis in adulthood, remains poorly understood. This study aimed to investigate coronary artery lesions in adults with a history of KD and clarify the relationship between sequelae of vasculitis and atherosclerosis. METHODS: We analyzed 7 autopsy cases of sudden cardiac death in adults with a confirmed history of KD and documented coronary artery aneurysms. Clinical data, including acute-phase treatment history, body mass index, heart weight, coronary risk factors, and detailed coronary histopathology, were evaluated. RESULTS: All aneurysms were located at the coronary ostia and showed marked intimal thickening with severe calcification, leading to luminal narrowing. Thrombotic occlusion within the aneurysm was identified in 1 case. In 3 patients aged older than 30 years, atherosclerotic changes were observed in the thickened intima of persistent aneurysmal segments or dilated portions. One patient with a regressed aneurysm died of acute myocardial infarction caused by plaque rupture. Sequelae of vasculitis were widely distributed in nonaneurysmal coronary branches, and atherosclerotic changes were also noted in these regions. CONCLUSIONS: In adults with persistent coronary aneurysms due to KD, atherosclerotic lesions may develop not only in aneurysmal segments but also in nondilated arteries with scarring due to vasculitis. Individuals with prior KD and coronary aneurysms may require long-term management for thrombotic risk and the prevention of atherosclerosis, beginning in early adulthood.

Lower albumin levels are a potential risk factor for intravenous immunoglobulin (IVIG) resistance and coronary artery lesions (CALs) in patients with Kawasaki disease (KD). No age-specific studies have been conducted on the association between lower albumin levels and these outcomes. We analyzed 18,336 patients who developed KD nationwide in Japan from 2011 to 2012. These patients were divided into three age groups: <1 year, 1–4 years, and 5–9 years. Multivariable logistic regression analyses were performed to evaluate the association between serum albumin decrease and (1) IVIG resistance and (2) CALs among these age groups. Each 0.1 g/dL albumin decrease was strongly associated with IVIG resistance in the patients aged < 1 year (adjusted odds ratios [95% confidence interval]: 1.96 [1.60–2.40]). Patients aged 1–4 years demonstrated a moderate association (1.47 [1.31–1.65]), and no association was observed in those aged 5–9 years (1.24 [0.95–1.62]). Similarly, lower albumin levels had an age-specific association with CALs (1.72 [1.11–2.70] for < 1 year, 1.67 [1.19–2.33] for 1–4 years, and 0.61 [0.33–1.10] for 5–9 years). Lower albumin levels were significantly associated with an increased risk of IVIG resistance and CALs, with the association strength varying by age. When assessing risk for treatment failure and coronary complications, serum albumin levels may be stratified by age.

Backgrounds/Objectives: Advances in prevention and medical care in the field of cardiology have led to an increase in the number of older patients with heart failure. In this population, assessment of nutritional status is particularly important. However, the prognostic impact of severity-based nutritional assessment at admission remains unclear. We conducted a study to elucidate the impact of malnutrition severity at admission on the prognosis of older patients hospitalized for acute heart failure (AHF). Methods: This study investigated the relationship between the Geriatric Nutritional Risk Index (GNRI) at admission and prognosis in 214 older patients aged ≥65 years who were hospitalized for AHF (mean age, 85 ± 8 years; male, 49%) between 2019 and 2023. GNRI was assessed by dividing patients into four groups: GNRI > 98 as normal (n = 64), 92 ≤ GNRI < 98 as mild risk (n = 54), 82 ≤ GNRI < 92 as moderate risk (n = 66), and GNRI < 82 as severe risk (n = 30). The discriminative performance of GNRI for 1-year all-cause mortality was compared with that of the Controlling Nutritional Status (CONUT) score and the Prognostic Nutritional Index (PNI). Results: During a median follow-up of 356 days, 76 deaths were observed. Worse GNRI categories were associated with older age, underweight, frailty, and anemia. Multivariable Cox proportional hazards models revealed that moderate GNRI risk (hazard ratio (HR), 2.69; 95% confidence interval (CI), 1.34-5.40) and severe GNRI risk (HR, 9.75; 95% CI, 4.30-22.10) were associated with higher all-cause mortality when compared with normal GNRI, along with age (HR per 1-year increase, 1.07; 95% CI, 1.03-1.11). Sensitivity analysis using GNRI as a continuous variable demonstrated similar results; GNRI was inversely associated with all-cause mortality (HR per 1 GNRI increase, 0.92; 95% CI, 0.90-0.95). In a subgroup analysis of age ≥85 years, the inverse association between GNRI and all-cause mortality was consistent. For 1-year all-cause mortality, GNRI showed moderate discrimination (area under the curve (AUC), 0.71; 95% CI, 0.63-0.80). Although the AUC of GNRI was not significantly different from that of the CONUT score or the PNI, GNRI demonstrated significantly better risk reclassification (net reclassification improvement, 0.47 vs. CONUT, p = 0.05; 0.43 vs. PNI, p = 0.02). Conclusions: In older patients with AHF including the oldest-old, nutritional status assessed by the GNRI at admission was predictive of prognosis. The importance of evaluating nutritional status at admission in clinical settings is reaffirmed.

<h4>Background</h4>A previous study reported that among patients with complete Kawasaki Disease (KD), those exhibiting all six principal clinical features were more likely to develop coronary artery (CA) sequelae than those exhibiting only five features. We aimed to determine which specific features are associated with CA sequelae.<h4>Methods</h4>This retrospective cohort study analyzed 14,732 patients diagnosed with complete KD across Japan from January 2019 to March 2020. Separate multivariable conditional logistic regression analyses were performed to evaluate relative risk for CA sequelae in patients with all six principal clinical features, compared individually to those lacking each specific feature.<h4>Results</h4>7234 (49.1%) exhibited all six principal clinical features, while 7498 (50.9%) presented with five features. CA sequelae occurred in 2.1% of those with six features versus 1.7% with five. Multivariable conditional logistic regression analysis determined that patients with conjunctival injection were significantly more likely to develop CA sequelae compared with those lacking it (adjusted odds ratio [95% confidence interval], 3.6 [1.3-10.1]).<h4>Conclusions</h4>Among patients with complete KD, the absence of conjunctival injection-a relatively rare presentation-was associated with a lower cumulative incidence of CA sequelae. This finding may help identify distinct low-risk phenotypes of KD and support risk stratification.<h4>Impact</h4>This study emphasizes the importance of feature-specific risk for coronary artery (CA) sequelae among patients with complete Kawasaki Disease (KD). We found that among patients with complete KD, those with conjunctival injection were more likely to develop CA sequelae than were those lacking it. The absence of conjunctival injection-a relatively rare presentation in KD-is associated with a markedly lower cumulative incidence of CA sequelae. This finding may help identify a distinct low-risk phenotype of KD and aid risk stratification.

Kawasaki Disease (KD) is an acute pediatric vasculitis with unclear etiology, though environmental triggers have been proposed. This scoping review synthesized epidemiological evidence on outdoor environmental exposures and KD incidence. A systematic search up to December 2024 identified 32 eligible studies. KD incidence is highest in East Asia, particularly Japan, South Korea, and Taiwan, where most research has been concentrated. Meteorological variables and air pollutants were most studied. Approximately half of the studies on meteorological variables found associations with KD, with some suggesting the role of temperatures or wind-driven transport of airborne agents. Air pollution studies showed inconsistent short-term effects, but more consistent links with long-term or prenatal particulate matter exposure. Studies on airborne biological agents, though fewer, showed consistent positive findings. These results suggest a multifactorial etiology. However, heterogeneity in methods limits comparability. Little is known about chemical substances in soil, water, or other outdoor sources, which may also affect immune pathways relevant to KD. Standardized, multinational research is needed to clarify environmental contributions and guide prevention in high-risk regions.

BACKGROUND: Kawasaki disease (KD) is a vasculitis syndrome of unknown etiology and the leading cause of acquired heart disease in children in developed countries. The Japanese Nationwide Survey of Kawasaki Disease (JNSKD) in Japan has provided valuable epidemiological data since 1970, but has inherent limitations. We aimed to evaluate the utility of the National Database of Health Insurance Claims (NDB) for describing the epidemiologic features of KD. METHODS: We conducted retrospective cohort study compared NDB data (2013-2019) against JNSKD data for the same period. We analyzed demographic characteristics, temporal and geographic distributions, treatment modalities, and cardiac complications. RESULTS: NDB identified 120,391 KD patients (2013-2019), with JNSKD estimated to cover 94.0% of cases. Demographic characteristics showed strong concordance between datasets (male-to-female ratios: 1.32 vs 1.33; similar age distributions). Initial IVIG administration rates were highly similar (93.74% vs 93.85%). Incomplete KD was significantly underestimated in NDB (8.07% vs 19.48%). NDB revealed adjunctive therapies including urinastatin and tracked increasing infliximab use. Cardiac complication detection in NDB showed limited sensitivity for mild abnormalities (overall 5.0% vs 7.33%). NDB showed higher recorded rates of giant aneurysms (0.53% vs 0.17%) and myocardial infarction (0.15% vs 0.01%). CONCLUSIONS: The NDB provides a valid, complementary data source for KD epidemiological research with near-complete population coverage. While limitations exist for identifying disease subtypes and cardiac complications, its detailed treatment data offer significant advantages for nationwide surveillance and health policy development.

OBJECTIVE: To describe 5 confirmed cases of natalizumab-associated progressive multifocal leukoencephalopathy (NTZ-PML) in Japan. METHODS: The Nationwide PML Surveillance Committee requires mandatory registration of all natalizumab cases and reporting by affiliated facilities conducting JC DNA testing. Suspected PML cases were reviewed by the committee and classified as definite, probable, possible, or non-PML based on established diagnostic criteria. RESULTS: From 2016 to 2024, the nationwide PML surveillance committee identified 8 NTZ-PML cases, of which 5 (all women and relapsing-remitting types) were registered as clinically definite PML cases. Four cases involved a switch from other disease-modifying drugs, while one involved natalizumab as the first-line treatment for multiple sclerosis (MS). In all cases, extended interval dosing therapy (EID) every 6-8 weeks was administered for at least 1 year before PML onset, and 3 cases had received EID from the outset. At PML onset, the viral DNA levels in the CSF were ≤100 copies/mL in 3 cases. DISCUSSION: Given the high prevalence of JC virus antibody positivity in Japan, additional risk factors may contribute to NTZ-PML susceptibility. Although EID of natalizumab is expected to reduce PML risk, its effectiveness may be limited, particularly in Japanese individuals with high JC virus antibody titers.

BACKGROUND: Lower platelet count is associated with intravenous immunoglobulin (IVIG) resistance in Kawasaki disease (KD); paradoxically, higher count is associated with coronary artery (CA) sequelae. We addressed this inconsistency. METHODS: Using a large-scale nationwide KD database in Japan, we standardized platelet counts by age and hospital visit day. We evaluated associations between standardized platelet count and IVIG resistance using multivariable modified Poisson regression models. Associations between platelet count and CA sequelae were assessed separately among IVIG-resistant and IVIG-responsive patients. RESULTS: In 41,540 patients, lower standardized platelet counts were associated with IVIG resistance in all age groups and the association increased with age: adjusted risk ratios with 95% confidence intervals per standardized platelet count decrease of 1 were 1.15 [1.06-1.25] at 0-5 months, 1.08 [1.02-1.15] at 6-11 months, 1.18 [1.14-1.22] at 1-2 years, 1.22 [1.17-1.27] at 3-4 years, and 1.26 [1.19-1.33] at ≥5 years. Lower standardized platelet count was also associated with CA sequelae in IVIG-resistant patients (1.12 [1.02-1.23]), but not in IVIG-responsive patients (0.95 [0.86-1.04]). CONCLUSION: Lower platelet counts were associated with IVIG resistance and CA sequelae in IVIG-resistant patients. Early platelet evaluation may identify high-risk patients with KD. IMPACT: Previous studies of platelet counts have shown conflicting results: lower platelet counts were associated with immunoglobulin resistance, but higher platelet counts were associated with coronary artery complications. Lower platelet counts were associated with immunoglobulin resistance across all age groups. Moreover, lower platelet counts were associated with coronary artery complications, but this association was found only in immunoglobulin-resistant patients. Our study resolves previous conflicting results by properly adjusting for age, immunoglobulin responsiveness, and platelet examination timing. Early platelet count evaluation may aid in identifying patients at high risk of immunoglobulin treatment failure and subsequent coronary involvement.

BACKGROUND: This study investigated the association between the development of sarcoidosis and environmental factors, focusing on the childhood hygiene environment. METHODS: This case-control study used a questionnaire administered to patients with sarcoidosis and residence-matched controls (age 18 to <90 years) in 7 prefectures between 2018 and 2020. Logistic regression analysis was performed to identify risk factors, including adulthood lifestyle history, childhood hygiene environment, and history of infections. RESULTS: One hundred sixty-four patients with sarcoidosis and 1779 controls (641 men, 1138 women) were enrolled. Multivariate analysis showed that smoking history during adulthood was associated with developing sarcoidosis (odds ratio [OR], 2.09; 95 % confidence interval [CI], 1.16-3.75). For the childhood hygiene environment, attending nursery school (OR, 2.76; 95 % CI, 1.57-4.84) and use of well water (OR, 2.89; 95 % CI, 1.65-5.07) at age 0-2 years were associated with developing sarcoidosis. The OR of attending nursery school at age 3-6 years (OR, 1.79; 95 % CI, 0.89-3.61) was lower than that at age 0-2 years, but the OR of use of well water at age 3-6 years (OR, 2.89; 95 % CI, 1.59-5.26) was still high. By contrast, the risk of developing sarcoidosis was lower for being breastfed (OR, 0.36; 95 % CI, 0.15-0.88). Development of sarcoidosis was associated with history of tuberculosis (OR, 5.82; 95 % CI, 1.28-26.53). CONCLUSIONS: Both adulthood lifestyle history and childhood hygiene environment were associated with sarcoidosis. Daily direct exposure to diverse microorganisms during childhood may increase the likelihood of antigens for granuloma formation entering the body and also modify susceptibility to sarcoidosis.

OBJECTIVE: To determine the epidemiologic change in Kawasaki disease during the post-acute phase of the coronavirus disease 2019 pandemic compared with the pre- and acute phases. STUDY DESIGN: A follow-up epidemiological study was conducted using data obtained from hospitalised patients with Kawasaki disease in Shiga Prefecture, Japan. The study period was divided into three phases: pre-pandemic (January 2015 to March 2020), acute pandemic (April 2020 to December 2020), and post-acute pandemic (January 2021 to December 2022). The incidence of Kawasaki disease was compared among these phases, focusing on monthly variation, patient age, and regional population density. RESULTS: A total of 1,598 patients with Kawasaki disease were analysed. The per cent change in Kawasaki disease incidence from the pre-pandemic phase was -33.8% and -27.9% in the acute and post-acute phases, respectively. Monthly variation during the post-acute phase dramatically differed from that observed in the pre- and acute phases, with the highest incidence in August and the lowest in April. The Kawasaki disease reduction was larger in patients ≥4 years old during the post-acute phase. An association between population density and reduction in Kawasaki disease incidence was no longer observed during the post-acute phase, contrary to the result during the acute phase. CONCLUSIONS: The reduction in Kawasaki disease incidence in Shiga Prefecture remained in the post-acute phase of the coronavirus disease 2019 pandemic, although seasonal variation dramatically differed from the traditional pattern. Infection prevention measures by individuals might reduce Kawasaki disease development in the children ≥4 years old.

Juvenile-onset morphea can severely impact activities of daily living by causing functional disability. This study was performed to clarify the epidemiological and clinical characteristics of juvenile-onset morphea in Japan. We conducted a nationwide, two-part postal survey. The first survey aimed to estimate the number of patients with juvenile-onset morphea, while the second survey aimed to elucidate the epidemiological and clinical characteristics of juvenile-onset morphea. This study included patients of all ages with juvenile-onset morphea whose age at disease onset was <18 years and who visited a medical institution from 1 January, 2016 to 31 December, 2020. The first survey identified 371 patients with juvenile-onset morphea. The second survey collected detailed clinical information for 315 patients with juvenile-onset morphea. We estimated that the number of patients diagnosed with juvenile-onset morphea from 2016 to 2020 was 591 (95% confidence interval 479-702) among children aged <18 years. The estimated annual incidence rate of juvenile-onset morphea ranged from 2.11 to 2.87 per 1 000 000 children aged <18 years from 2016 to 2019. The mean age at onset was 7.7 years. Regarding subtypes, linear morphea was the most common, followed by circumscribed morphea. Complications and treatments varied widely by subtype, with local treatment primarily used for circumscribed morphea. By contrast, patients with linear morphea, generalized morphea, pansclerotic morphea, and mixed morphea had severe complications affecting daily life, and they received systemic immunosuppressive therapy more frequently. The prognosis of juvenile-onset morphea was generally favorable. The results of this study are expected to help in the development of appropriate diagnostic and therapeutic approaches for juvenile-onset morphea.

A 68-year-old man was admitted with hematochezia. Emergency computed tomography showed multiple diverticula throughout the colon. Initial colonoscopy on day 2 showed no active bleeding, but massive hematochezia on day 3 led to the performance of an emergency endoscopy. Substantial bleeding in the ileocecal area obscured the visual field, making it challenging to view the area around the bleeding site. Two endoscopic band ligations (EBLs) were applied at the suspected bleeding sites. Hemostasis was achieved without active bleeding after EBL. However, the patient developed lower right abdominal pain and fever (39.4°C) on day 6. Urgent computed tomography revealed appendiceal inflammation, necessitating emergency open ileocecal resection for acute appendicitis. Pathological examination confirmed acute phlegmonous appendicitis, with EBLs noted at the appendiceal orifice and on the anal side. This case illustrates the efficacy of EBL in managing colonic diverticular bleeding. However, it also highlights the risk of appendicitis due to EBL in cases of ileocecal hemorrhage exacerbated by poor visibility due to substantial bleeding. Endoscopists need to consider this rare but important complication when performing EBL in similar situations.

Arterio-enteric fistulas (AEFs) are a rare cause of gastrointestinal bleeding involving direct communication between an artery and the intestinal tract. The duodenum is the most common fistula site for AEFs, but none of the rectal cases are known. We present the case of an elderly man with hematochezia due to a rectal fistula caused by a left internal iliac artery aneurysm, which was detected on contrast-enhanced computed tomography (CT), showing typical fistula formation and ectopic gas images. This case highlights the importance of considering the occurrence of rare but potentially fatal AEFs in elderly patients with hematochezia and that the timely performance of contrast-enhanced CT is critical for an accurate diagnosis.

BACKGROUND: Few studies have assessed the potential of telemedicine to improve end-of-life care quality in rural and remote areas. We investigated health care services needed for end-of-life care at home and examined their associations with willingness to die at home, testing the hypothesis that telemedicine facilitates at-home death in rural and remote settings. METHODS: A cross-sectional survey was conducted with a target population of 6,382 residents aged ≥20 years living in designated rural and remote areas of Shunan City, Yamaguchi, Japan. Stratified random sampling was employed to select survey participants, resulting in 3,767 individuals who were mailed self-administered questionnaires. First, we assessed health care services needed for end-of-life care at home (telemedicine, home doctor visits, home nursing care, home personal care services, home support services, and senior day care). Multivariable logistic regression analysis was then performed to determine which services were independently associated with willingness to die at home. RESULTS: Of 3,767 eligible participants, 1,884 (50.0%) responded, and 1,451 were included in the analysis. Among them, 608 (41.9%) were male, 1,166 (80.3%) were aged ≥60 years, and 733 (50.5%) expressed a wish to die at home. Home doctor visits were the most frequently selected service (776 participants [53.5%]), while telemedicine was selected by 193 (13.3%). After adjustment for all measured variables, telemedicine (adjusted odds ratio, 1.41 [95% confidence interval, 1.01-1.98], p = 0.045) and home doctor visits (adjusted odds ratio [OR], 1.50 [95% confidence interval, 1.19-1.90], p < 0.001) were independently associated with willingness to die at home. DISCUSSION: These findings suggest that physician-provided services are central to enabling at-home death. Integrating telemedicine with traditional home doctor visits may improve end-of-life care and facilitate at-home death in rural and remote settings.

Background/Objectives: Obesity is associated with food intake, drinking, and nutrition. It is necessary to examine the association between body mass index (BMI), body weight changes, and the incidence of hypertension, focusing on potential sex differences. Methods: A retrospective two-point cohort study was conducted using data from the Japanese Specific Health Checkup program from 2011 to 2013. Multivariable logistic regression analyses were employed to assess associations between BMI, weight change, and hypertension onset, adjusting for age, sex, and lifestyle factors, including smoking, drinking, and exercise. Results: In total, 397,181 participants were analyzed. A higher BMI was linked to a higher risk of hypertension, with an odds ratio (OR) of 1.11 (95% confidence interval [CI]: 1.11-1.12) for both sexes. Women aged 40-65 showed higher ORs than men. Weight gain was associated with developing hypertension, with an OR (95% CI) of 1.09 (1.09-1.10) in men and 1.08 (1.07-1.08) in women. This association held across all BMI levels, even among individuals without obesity, with the effect being generally stronger in men. Conclusions: Both BMI and weight change contribute to the development of hypertension among the Japanese healthy population, with differences based on sex. Weight reduction may reduce the risk of hypertension for individuals with and without obesity, emphasizing the importance of weight stability through food and nutrition control, particularly for women.

Prion diseases, including Creutzfeldt-Jakob disease (CJD), are deadly neurodegenerative disorders characterized by the buildup of abnormal prion proteins in the brain. This accumulation disrupts neuronal functions, leading to the rapid onset of psychiatric symptoms, ataxia, and cognitive decline. The urgency of timely diagnosis for effective treatment necessitates the identification of strongly correlated biomarkers in bodily fluids, which makes our research crucial. In this study, we employed a fully automated multiplex ELISA (Ella®) to measure the concentrations of 14-3-3 protein, total tau protein, and neurofilament light chain (NF-L) in cerebrospinal fluid (CSF) and serum samples from patients with prion disease and analyzed their link to disease prognosis. However, in North American and European cases, we did not confirm a correlation between NF-L levels and survival time. This discrepancy is believed to stem from differences in treatment policies and measurement methods between Japan and the United States. Nonetheless, our findings suggest that NF-L concentrations could be an early diagnostic marker for CJD patients with further enhancements. The potential impact of our findings on the early diagnosis of CJD patients is significant. Future research should focus on increasing the number of sCJD cases studied in Japan and gathering additional evidence using next-generation measurement techniques.

Uric acid, the final product of purine metabolism, plays a significant role in hypertension Research on uric acid has advanced significantly, particularly regarding its links to hypertension and cardiovascular disease (CVD). Our 2023 review covered the relationship between uric acid, hypertension; and CVD, however, numerous new studies have emerged since then. This paper provides an update, summarizing recent findings over the past two years on hyperuricemia and its association with hypertension, preeclampsia, arteriosclerosis, kidney disease, sleep-disordered breathing, CVD, and so on. Hyperuricemia, often driven by reduced uric acid excretion or increased production, is influenced by genetic factors and lifestyle habits, including high-purine foods, alcohol, and fructose intake. While hyperuricemia has been proposed to contribute to hypertension and CVD through mechanisms like inflammasome activation and oxidative stress, its causal role remains debated. Further clinical and basic science studies on hyperuricemia and purine metabolism are necessary to clarify its impact on CVD and guide therapeutic approaches.

Background Primary care physicians (PCPs) are expected to engage in comprehensive medical care, including orthopedic and musculoskeletal problems. This study aimed to assess perceptions and current status regarding orthopedic and musculoskeletal practice among PCPs in Japan. Methodology A cross-sectional survey was conducted among PCPs who graduated from Jichi Medical University (JMU) with opportunities to treat orthopedic and musculoskeletal problems. A specific questionnaire was used to investigate perceptions of orthopedic and musculoskeletal practice. Participants were divided into groups based on their workplace (rural and remote areas/other areas) and length of career (<10 years and ≥10 years). The answers between these groups were statistically analyzed by using chi-square tests. Results Among 298 respondents, 121 (40.6%) were engaged in rural and remote areas and 69 (23.2%) had a career length of <10 years. Two hundred and eighty-one PCPs (94.3%) required orthopedic knowledge and procedural skills and mental burden was reported by 166 PCPs (55.7%). PCPs in rural and remote areas with careers <10 years in length required significantly more orthopedic knowledge and skills and were more willing to learn them. Also, they perceived a burden because of a lack of knowledge and procedural skills. Many PCPs could perform common procedures such as general care for trauma but were not confident in treating orthopedic-specific injuries such as fractures and dislocation. Conclusions PCPs in rural and remote areas with careers <10 years in length had the most varied problems in orthopedic and musculoskeletal practice. A new approach that can provide musculoskeletal and orthopedic knowledge and skills may be needed for PCPs.

OBJECTIVES: To identify clinical characteristics of patients with non-refractory Kawasaki disease (KD), which were defined as those who successfully responded to the standard initial intravenous immunoglobulin (IVIG) treatment (2 g/kg/day, single infusion) without any secondary or later additional specific treatments, and to investigate the factors associated with the development of coronary artery (CA) complications in patients with non-refractory KD. DESIGN: Retrospective cohort study. SETTING: Hospitals specialising in paediatrics and hospitals with ≥100 beds and a paediatric department throughout Japan. PATIENTS: A total of 122 489 patients who developed KD across Japan during 2011-2018. MAIN OUTCOME MEASURES: CA abnormalities identified after acute illness of KD (defined as CA sequelae). RESULTS: A total of 69 735 patients with non-refractory KD were identified, of which 672 (0.96%) experienced CA sequelae. Among patients with non-refractory KD, the presence of CA abnormalities identified at initial echocardiographic assessment was strongly associated with CA sequelae (adjusted OR (95% CI): 37.8 (31.9 to 44.7)). CA sequelae was also associated with male patients, infants (<12 months old), older patients (≥60 months old) and patients who received delayed initial IVIG treatment (>7 days from KD onset). Subgroup analyses demonstrated that delayed initial IVIG treatment was significantly associated with the development of CA sequelae in both patients with and without CA abnormalities identified at initial echocardiographic assessment. CONCLUSIONS: Approximately 1% of patients with non-refractory KD may develop CA sequelae. Our findings highlight the importance of initial echocardiographic assessment and early initiation of IVIG treatments for patients with KD.

BACKGROUND AND AIMS: Hyperuricemia is strongly linked to increased cardiovascular risk, including hypertension, coronary artery disease, arrythmia, and heart failure. Uric acid, as the end-product of purine metabolism, plays a critical role in cellular processes, but elevated levels can drive inflammation and oxidative stress. This review aims to emphasize the robust association between hyperuricemia and cardiovascular diseases, exploring whether uric acid-lowering therapies can mitigate cardiovascular events and improve patient outcomes. METHODS AND RESULTS: A comprehensive review of PubMed sources was conducted, underscoring the significant link between high uric acid levels and cardiovascular events, particularly in patients with gout. Gender differences were observed, where premenopausal women have lower uric acid levels, likely due to hormonal effects, suggesting the potential need for gender-specific definitions in assessing cardiovascular risk. Epidemiological studies demonstrate a consistent correlation between hyperuricemia and adverse cardiovascular outcomes. However, interventional trials using xanthine oxidase inhibitors, such as allopurinol and febuxostat, have shown mixed results regarding their impact on reducing cardiovascular events. Additionally, emerging evidence suggests a "xanthine oxidase withdrawal syndrome" upon discontinuation of these therapies, highlighting the need for cautious management. CONCLUSION: The strong association between elevated uric acid levels and cardiovascular diseases is well-documented. While lowering uric acid shows potential for reducing cardiovascular risk, current evidence from interventional trials remains inconclusive. Future research should focus on patient-specific therapeutic strategies, particularly for those at high cardiovascular risk with hyperuricemia and/or gout, to better define the benefits of targeted treatments.

Background/Objectives: Sporadic Creutzfeldt–Jakob disease (sCJD) is a fatal neurodegenerative disorder traditionally diagnosed based on the World Health Organization (WHO) criteria in 1998. Recently, Hermann et al. proposed updated diagnostic criteria incorporating advanced biomarkers to enhance early detection of sCJD. This study aimed to evaluate the sensitivity and specificity of Hermann’s criteria compared with those of the WHO criteria in a large cohort of patients suspected of prion disease in Japan. Methods: In this retrospective cohort study, we examined the new criteria using data of 2004 patients with suspected prion disease registered with the Japanese Prion Disease Surveillance (JPDS) between January 2009 and May 2023. Patients with genetic or acquired prion diseases or incomplete data necessary for the diagnostic criteria were excluded, resulting in 786 eligible cases. The sensitivity and specificity of the WHO and Hermann’s criteria were calculated by comparing diagnoses with those made by the JPDS Committee. Results: Of the 786 included cases, Hermann’s criteria helped identify 572 probable cases compared with 448 by the WHO criteria. The sensitivity and specificity of the WHO criteria were 96.4% and 96.6%, respectively. Hermann’s criteria demonstrated a sensitivity of 99.3% and a specificity of 95.2%, indicating higher sensitivity but slightly lower specificity. Fifty-five cases were classified as “definite” by both criteria. Conclusions: The findings suggest that Hermann’s criteria could offer improved sensitivity for detecting sCJD, potentially reducing diagnostic oversight. However, caution is advised in clinical practice to avoid misdiagnosis, particularly in treatable neurological diseases, by ensuring thorough exclusion of other potential conditions.

BACKGROUND: New employees often exhibit stress reactions to changes in their environment and some of these may result in resignations. Employees in medical institutions are no exceptions. Considering the shortage of nurses in Japan, countermeasures are needed against the resignation of newly graduated nurses. Many studies have indicated that multifaced factors affect the resignation of newly graduated nurses. Even though individual characteristics are important factors in this regard, training and support for newly graduated nurses do not focus on the nurses' characteristics. The purpose of this study is to examine the characteristics influencing the early resignation of newly graduated nurses and suggest ways to support them and prevent their early resignation based on their characteristics. METHODS: With the approval of the Ethics Committee, various characteristics of 353 newly graduated nurses (personality, interpersonal relationships, trait anxiety, nurse orientation, desire to be a nurse, and self-proclaimed academic ability) were assessed using a transactional analysis, the State-Trait Anxiety Inventory, and self-reporting numerical rating scales. The characteristics of those who resigned within 1 year (case group) and those who did not (control group) were compared using chi-square test and logistic regression analysis. RESULTS: Our sample of 353 participants included 32 nurses from the case group and 304 nurses from the control group. Most participants showed similar personality traits. However, the control group had a significantly lower percentage with negative self, strong trait anxiety, negative self and strong trait anxiety, and low orientation compared to the case group. Our logistic regression analysis showed that strong trait anxiety and low nurse orientation are significantly related with the early resignation of nurses. CONCLUSIONS: The early resignation of newly graduated nurses may be prevented by understanding their characteristics at the time of gaining employment and implementing early intervention programs, such as education programs to reduce anxiety, and helping those with strong trait anxiety and low nurse orientation to find meaning in work.

Spontaneous abdominal wall hematoma is a relatively uncommon condition triggered by various factors, including anticoagulation therapy and trauma. However, reports of unprovoked cases without anticoagulants that recur shortly after treatment are limited. We herein report an elderly woman who had been prescribed corticosteroids and experienced early recurrence of hematoma following treatment, with no discernible triggers. This case highlights the possibility that patients with underlying predisposing factors may experience early hematoma recurrence at the same site, even in the absence of apparent triggers. Clinicians should monitor these patients to promptly identify and address potential recurrences.

BACKGROUND: AO/OTA 31A3 fractures (A3 fractures) have risk for postoperative complications with major impact on morbidity and mortality. For older patients, limited information is available for factors associated with postoperative complications. We aimed to assess factors associated with postoperative complications after surgery using cephalomedullary nails. METHODS: A retrospective cohort study was conducted using the information on patients aged ≥65 years who underwent surgery using cephalomedullary nails for trochanteric fractures due to low-energy trauma in three hospitals. Postoperative complications were diagnosed when patients were identified as nonunion, cutout of lag screw, or nail breakage. First, we compared differences including age, sex, body mass index, American Society of Anesthesiologists physical status classification system, preoperative waking ability, fracture type, nail length, neck shaft angle, reduction method, reduction quality and tip apex distance between patients with and without postoperative complications. Second, multivariable logistic regression analysis was employed to assess factors associated with postoperative complications resulting from A3 fractures. RESULTS: Among 120 patients with A3 fractures, postoperative complications were identified in 12 patients (10.0%). Postoperative complications were significantly more likely to develop among patients with poor reduction quality (adjusted odds ratio [95% confidence interval], 35.0 [4.43-275.9]) and a tip-apex distance ≥25 mm (16.4 [1.92-140.3]). CONCLUSIONS: These findings suggest that surgeons should aim to perform appropriate postoperative reduction and to prevent postoperative complications when using a cephalomedullary nail for A3 fractures among older patients.

PURPOSE: This study aimed to clarify whether the range of motion (ROM), anterior and posterior (AP) stability and other clinical measures changed in patients who underwent tibia-first total knee arthroplasty (TF-TKA) using navigation with a computer-aided system after surgery. METHODS: This is a retrospective study and we conducted a matched cohort analysis of 60 measured resection (MR)-TKAs and 52 TF-TKAs performed by a single surgeon. All the surgeries used the same implant and approach. Baseline differences between the groups were adjusted using propensity score matching. We compared each patient's measured ROM and Oxford Knee Score (OKS) and performed knee AP laxity measurements by using a device during routine follow-ups. RESULTS: A total of 40 MR-TKAs with a mean age of 73.5 ± 5.6 years and sex (male 10, female 30) were compared to 40 TF-TKAs with a mean age of 74.0 ± 5.7 years and sex (male 13, female 27) at 2-year follow-ups. Two years postoperatively, there was a significant difference in the AP laxity at 30° of knee flexion between both groups (7.0 ± 3.4 mm vs. 5.2 ± 2.3 mm, p < 0.01). In contrast, no differences were found between both groups for knee flexion (120.8 ± 9° vs. 116.7 ± 9.8°, p = 0.07) and OKS score (41.8 ± 6.9 vs. 41.0 ± 5.9, p = 0.61). CONCLUSION: The AP stability in the midflexion obtained using the tibia-first technique remained consistent even after 2 years. However, OKS and ROM were not significantly different from those of the MR-TKA group. LEVEL OF EVIDENCE: Retrospective comparative LEVEL III study.

INTRODUCTION: Despite the recent increase in the use of cephalomedullary nails for trochanteric hip fractures, factors that may be associated with peri‑implant femoral fracture (PIFF) after cephalomedullary nailing for trochanteric fractures remain unknown. We investigated the factors associated with PIFF after cephalomedullary nailing of trochanteric hip fractures in older patients. METHODS: A nested case-control study was conducted using a database of patients aged ≥65 years who underwent surgery with cephalomedullary nails for trochanteric fractures caused by low-energy trauma during 2005-2021. The cases were defined as patients who developed PIFF after surgery, while controls were patients who did not develop PIFF and who were followed up for ≥3 years after surgery. Four controls were randomly matched to each case for sex and age. First, potential factors associated with PIFF were compared between cases and controls. Second, multivariable conditional logistic regression analysis was employed to assess factors possibly associated with PIFF, controlling for potential confounding factors. RESULTS: Of 1531 patients who underwent surgery with cephalomedullary nails because of trochanteric fractures, we assessed 34 cases and 136 controls (N = 170; mean age 85.7 ± 7 years; and females, 94 %). PIFF was significantly associated with patients having undergone total knee arthroplasty (adjusted odds ratios [95 % confidence intervals], 4.41 [1.16-16.8]) and those with AO/OTA classification 31A3 fracture (A3 fracture) (2.3 [1.12-4.76]), after adjusting for potential confounding factors. CONCLUSIONS: Our results showed that PIFF was more likely to develop among older patients with a clinical history of total knee arthroplasty and A3 fracture. These findings suggest that such patients may require careful follow-up with rigorous assessments after cephalomedullary nailing for trochanteric fractures.

PURPOSE: To assess how intraoperative macroscopical anterior cruciate ligament (ACL) findings affect perioperative procedures, biomarkers, and postoperative anterior-posterior (AP) laxity and range of motion (ROM) after cruciate-retaining (CR) total knee arthroplasty (TKA) and to determine how chronic ACL deficiency may affect postoperative inflammatory biomarker, AP laxity, and ROM. METHODS: A total of 121 patients with varus knee osteoarthritis without a history of ACL injury who underwent ATTUNE® (DePuy Synthes, Warsaw, IN) CR TKA were analyzed. Intraoperative ACL findings were stratified into intact, damaged, and diminished, according to the tension by probing, synovial coverage, and vascularity. C-reactive protein (CRP) levels were examined at one, seven, and 14 days after surgery. Knee AP laxity measurements using Kneelax 3 (Monitored Rehab Systems, Haarlem, The Netherlands) and postoperative knee ROM were also compared. RESULTS: One-way ANOVA showed significant differences in CRP levels examined one day after surgery observed between the three groups (8.4 (3.8), 9.8 (4.3), and 13.2 (7.7) mg/dL, respectively; P = 0.018), with post hoc analysis showing that CRP levels one day after surgery were significantly greater in the diminished group than in the intact and damaged groups (P = 0.012 and 0.023, respectively). AP laxity in 30° of knee flexion was observed between the three groups (5.4 (2.3), 5.8 (2.5), and 7.1 (2.8) mm, respectively; P = 0.039), with post hoc analysis showing that AP laxity in 30° of knee flexion was significantly greater in the diminished group than in the intact group (P = 0.038). Knee ROM showed no significant differences. CONCLUSION: Intraoperative ACL diminishment was associated with higher CRP one day after surgery and midrange AP laxity one year after surgery.

Introduction During surgery, surgeons intuitively recognize when they are using dull scissors and find them difficult to use. The purpose of this study was to objectively evaluate the physical characteristics of scissors and the comfort reported by surgeons to develop objective quality control standards for scissors used in surgery. Methods Sensory and measurement tests were conducted to evaluate the comfort and physical characteristics of ten pairs of Cooper scissors. As a sensory test, thirty-one volunteer surgeons opened and closed the scissors and selected three that felt comfortable and three that were uncomfortable. The results were scored. For measurement, a load was applied to the handle of the scissors. The load pressure and displacement of the width between each handle when the scissors were closed were measured. Results A strong negative correlation was found between the total comfort score and the mean load value between sensory and measurement tests (r=-0.717, p=0.0195). The correlation between the total score and the change in load at the tip showed a moderate negative correlation (r=-0.687, p=0.0282). Multiple regression analysis showed that the change in load at the tip was an independent factor affecting the total score. Conclusions Surgeons consider scissors with a low mean load required to close the scissors and a small change in load at the tip to be comfortable. The mean load on scissors and the change in load at the tip should be considered in the development of quality control standards for scissors used in surgery.

BACKGROUND: A gradually reducing radius (GRADIUS) design implant can facilitate a smooth transition from stability through full range of motion in total knee arthroplasty (TKA). Nonetheless, patient-specific factors associated with good knee flexion remain unclear. OBJECTIVE: This study aimed to determine the factors associated with good knee flexion after cruciate-retaining TKA with a GRADIUS prosthesis in an Asian population. METHODS: This retrospective study included 135 patients that were stratified according to postoperative knee flexion angle (KFA) into Group F (⩾ 120∘; 85 patients [63.2%]) and Group NF (< 120∘; 50 patients [36.8%]). RESULTS: Patients in Group F were taller and had a lower body mass index (BMI) smaller preoperative hipkneeankle angle and better preoperative extension and flexion angle than Group NF patients. The multivariable analysis revealed that patients' height (odds ratio [OR]: 1.07, P= 0.0150), BMI (OR: 0.85, P= 0.0049), and preoperative flexion angle (OR: 1.06, P= 0.0008) predicted good KFA. The ROC curve analysis showed that the cutoff values of a good KFA were height 155.1 cm, BMI 22.1 kg/m2, and preoperative KFA 120∘. CONCLUSIONS: Patient height, BMI, and preoperative KFA were independent factors affecting good postoperative KFA in patients of Asian descent who underwent cruciate-retaining TKA with a GRADIUS design.

BACKGROUND: Total knee arthroplasty (TKA) alleviates pain and improves daily living activities in individuals with end-stage osteoarthritis of the knee. However, up to 20% of patients have sub-optimal outcomes after TKA. OBJECTIVE: No studies have clarified the intraoperative factors that affect postoperative range of motion (ROM) after cruciate-retaining (CR) TKA. Thus, this study aims to clarify these factors. METHODS: Patients with knee osteoarthritis with varus knee deformity who underwent CR-TKA between May 2019 and December 2020 were included in this study. One year after surgery, patients were stratified into two groups based on knee flexion: Group F (over 120∘) and Group NF (below 120∘). Patient backgrounds including age, body mass index, hip knee angle, preoperative range of motion for both extension and flexion, intraoperative center joint-gap measurements of 0∘, 30∘, 45∘, 60∘, 90∘, and 120∘ of knee flexion using a tensor, intraoperative anterior-posterior (AP) laxity measurements of 30∘ and 90∘ of knee flexion using an instrumental laximeter were compared between the groups. Univariate analyses between the groups were used to construct the initial model. The receiver operating characteristic curve was also analyzed. The predictive variables included in the final model were selected by stepwise backward elimination. RESULTS: Intraoperative AP laxity with 30∘ of knee flexion smaller than 10.8 mm was a significant positive prognostic factor (OR: 1.39, 95% CI: 1.08-1.79, P= 0.011) of postoperative ROM over 120∘ of knee flexion one year after surgery. The sensitivity, specificity, PPV, and NPV were 70.9%, 82.4%, 92.9%, and 46.7%, respectively. CONCLUSION: Intraoperative AP laxity smaller than 10.8 mm was a significant positive predictive factor for obtaining knee flexion greater than 120∘ one year after surgery when using CR-TKA and its PPV was high up to 92.9%.

UNLABELLED: Using a regional population-based dataset in Japan, we identified the epidemiological characteristics of patients with fragility fractures of the pelvic ring. The incidence rate was 35.5-121.2 per 100,000 population/year. Age-specific incidence increased after 75 years. This fracture is associated with worse prognosis in terms of walking function and life expectancy. PURPOSE: Fragility fracture of the pelvic ring (FFP) is common among older patients; however, little information is available on the epidemiology of FFP worldwide. We aimed to identify the epidemiological characteristics of patients with FFP using a regional population-based dataset in Japan. METHODS: This descriptive epidemiologic study analyzed data obtained from clinical information of patients diagnosed with FFP from January 1, 2011 through December 31, 2020 at a regional dominant hospital in Japan. We calculated the crude and age-adjusted annual incidences and the age-specific incidence and described epidemiological date, injury characteristics, walking ability before and after FFP, and mortality. Additionally, we investigated factors associated with walking ability. RESULTS: We identified 66 FFP patients, of whom 55 (83.3%) were female, with a mean age of 82.2 years. The crude annual incidence of FFP ranged from 35.5-121.2 per 100,000 population/year during the study period. The age-specific incidence of FFP increased after 75 and 80 years in females and males, respectively. In total, 44.4% of patients had declines in walking ability 1 year after their FFP injuries. Patients with declining walking ability were significantly older (p < 0.01), and age ≥ 80 years was significantly associated with the decline in walking ability (p < 0.01). The 1- and 5-year mortality rates were 15.4% and 39.9%, respectively. CONCLUSION: The incidence rate of FFP was 35.5-121.2 per 100,000 population/year. Age-specific incidence of FFP increased after 75 years. Our results indicate that FFP is associated with worse prognosis of walking function and life expectancy.

Introduction Postoperative pancreatic fistula (POPF) is a critical complication occurring with a high incidence after distal pancreatectomy. To minimize the risk of POPF, we developed an innovative pancreas ligation device capable of closing the pancreatic stump without causing traumatic injury to the pancreatic duct and artery. We conducted an ex vivo follow-up study to compare the pressure resistance of the pancreas ligation device with that of a regular linear stapler. Materials and methods The pancreases were excised from 20 pigs and divided into two groups: ligation group (n = 10) and stapler group (n = 10). Distal pancreatectomy was performed, and the pancreatic stump was closed using either a pancreas ligation device or a regular linear stapler. The main pancreatic duct was cannulated with a 4-French catheter connected to a cannula and syringe filled with contrast medium. Using fluoroscopy detection, pressure resistance was defined as the maximum pressure without leakage from the pancreatic stump. Results No significant differences were found between the two groups regarding sex, age, body weight, or pancreatic thickness. In the ligation group, no leakage was observed at the stump in any pancreas. However, in the stapler group, six of 10 pancreases showed leakage at the staple line or into the parenchyma. Pressure resistance was significantly higher in the ligation group than in the stapler group (median: 42.8 vs. 34.3 mmHg, P = 0.023). Conclusions These findings suggest the effectiveness of a pancreas ligation device in reducing the incidence of POPF after distal pancreatectomy. Our ligation device is expected to be a useful alternative to a linear stapler for pancreatic stump closure.

BACKGROUND: Distal radius fracture (DRF) is very common worldwide. In particular, aging countries have numerous patients with DRF, resulting in an urgent need for active preventive measures. As few epidemiological studies have investigated DRF in Japan, we aimed to identify the epidemiological characteristics of patients of all ages with DRF in Japan. METHODS: This descriptive epidemiologic study analyzed data obtained from clinical information of patients diagnosed with DRF from January 1, 2011, to December 31, 2020, at a prefectural hospital in Hokkaido, Japan. We calculated the crude and age-adjusted annual incidences of DRF and described the age-specific incidence, injury characteristics (injury location and cause, seasonal differences, and fracture classification), and 1- and 5-year mortality rates. RESULTS: A total of 258 patients with DRF were identified, of which 190 (73.6%) were female and the mean age (standard deviation) was 67.0 (21.5) years. The crude annual incidence of DRF ranged from 158.0 to 272.6 per 100,000 population/year, and the age-adjusted incidence among female patients demonstrated a significant decreasing trend during 2011-2020 (Poisson regression analysis; p = 0.043). The age-specific incidence differed by sex, with peaks at 10-14 years for males and 75-79 years for females. The most common cause of injury was a simple fall in patients > 15 year of age and sports injuries in patients ≤ 15 years of age. DRFs were most frequently sustained outdoors and were more common in the winter season. In patients > 15 years of age, the proportions of AO/OTA fracture types A, B, and C were 78.7% (184/234), 1.7% (4/234), and 19.6% (46/234), respectively, and 29.1% (68/234) of patients received surgical treatment for DRF. The 1- and 5-year mortality rates were 2.8% and 11.9%, respectively. CONCLUSIONS: Our findings were mostly consistent with previous global studies. Although the crude annual incidence of DRF was relatively high because of recent population aging, the age-adjusted annual incidence among female patients showed a significant decreasing trend during this decade.

PURPOSE: To investigate whether the biomechanical properties of the healed superficial medial collateral ligament (sMCL) repaired by augmentation vary depending on the material properties of the suture augmentation. METHODS: In 8 of 10 porcines (16 hindlimbs), the sMCL was detached from the femoral attachment using a scalpel under intubated general anesthesia. sMCL repair was performed using an ultra-high-molecular-weight polyethylene (UHMWPE) tape for the right hindlimbs and polyester tape (PE) for the left hindlimbs. They were sacrificed at 4 weeks postoperatively. The remaining 2 animals were assigned to the native control group (left and right hindlimb; n = 4). All connective tissues and suture augmentation, except for the repaired sMCL, were removed, and their biomechanical properties were evaluated. RESULTS: No significant differences were observed in the upper yield load (PE group, 247.4 ± 116.0 N; UHMWPE group, 279.9 ± 95.7 N; and sham group, 231.6 ± 50.6 N; P = .70), maximum yield load (PE group, 310.1 ± 166.1 N; UHMWPE group, 334.6 ± 95.2 N; and sham group, 290.9 ± 42.3 N; P = .84), linear stiffness (PE group, 43.3 ± 16.5 N/mm; UHMWPE group, 52.0 ± 28.2 N/mm; and sham group, 44.7 ± 7.2 N/mm; P = .66), and elongation at failure (PE group, 9.4 ± 4.3 mm; UHMWPE group, 9.1 ± 2.7 mm; and sham group, 10.1 ± 2.1 mm; P = .89). Statistical analysis of failure modes showed no significant difference between the groups (P = .21). CONCLUSIONS: The material properties of suture augmentation used for sMCL repair did not significantly influence length changes during cyclic loading, postoperative structural properties, or failure modes. CLINICAL RELEVANCE: The results of this study provide valuable information regarding the efficacy of suture augmentation repair regardless of the materials used.

Abstract Background Mechanically aligned total knee arthroplasty (MATKA) is a well-established procedure. Kinematically aligned TKA (KATKA) has been proposed to restore and preserve pre-arthritic knee anatomy. However, normal knee anatomy varies widely, and there have been concerns regarding restoring unusual anatomy. Accordingly, restricted KATKA (rKATKA) was introduced to reproduce constitutional knee anatomy within a safe range. This network meta-analysis (NMA) aimed to evaluate the clinical and radiological outcomes of the surgeries. Methods We performed a database search on August 20, 2022, which included randomized controlled trials (RCTs) comparing any two of the three surgical TKA techniques for knee osteoarthritis. We conducted a random-effects NMA within the frequentist framework and evaluated confidence in each outcome using the Confidence in Network Meta-Analysis tool. Results Ten RCTs with 1,008 knees and a median follow-up period of 1.5 years were included. The three methods might result in little to no difference in range of motion (ROM) between methods. In patient-reported outcome measures (PROMs), the KATKA might result in a slight improvement compared with the MATKA (standardized mean difference, 0.47; 95% confidence interval [CI], 0.16–0.78; very low confidence). There was little to no difference in revision risk between MATKA and KATKA. KATKA and rKATKA showed a slight valgus femoral component (mean difference [MD], -1.35; 95% CI, -1.95–[-0.75]; very low confidence; and MD, -1.72; 95% CI, -2.63–[-0.81]; very low confidence, respectively) and a slight varus tibial component (MD, 2.23; 95% CI, 1.22–3.24; very low confidence; and MD, 1.25; 95% CI, 0.01–2.49; very low confidence, respectively) compared with MATKA. Tibial component inclination and hip–knee–ankle angle might result in little to no difference between the three procedures. Conclusions KATKA and rKATKA showed similar ROM and PROMs and a slight variation in the coronal component alignment compared with MATKA. KATKA and rKATKA are acceptable methods in short- to mid-term follow-up periods. However, long-term clinical results in patients with severe varus deformity are still lacking. Surgeons should choose surgical procedures carefully. Further trials are warranted to evaluate the efficacy, safety, and subsequent revision risk.

A direct relationship between serum uric acid levels and hypertension, cardiovascular, renal and metabolic diseases has been reported in many basic and epidemiological studies. Among these, high blood pression is one of the most common features associated with hyperuricemia. In this regard, several small-scale interventional studies have demonstrated a significant reduction in blood pressure in hypertensive or prehypertensive patients on uric acid-lowering drugs. These observation or intervention studies have led to affirm that there is a causal relationship between uric acid and hypertension. While the clinical association between uric acid and high blood pressure is notable, no clear conclusion has yet been reached as to whether lowering uric acid is beneficial to prevent cardiovascular and renal metabolic diseases. Recently, several prospective randomized controlled intervention trials using allopurinol and other uric acid-lowering drugs have been reported, and the results from these trials were almost negative, suggesting that the correlation between hyperuricemia and cardiovascular disease has no causality. However, it is important to note that in some of these recent studies there were high dropout rates and an important fraction of participants were not hyperuricemic. Therefore, we should carry caution in interpreting the results of these studies. This review article presents the results of recent clinical trials using uric acid-lowering drugs, focusing on hypertension and cardiovascular and renal metabolic diseases, and discusses the future of uric acid therapy.

Progressive multifocal leukoencephalopathy (PML) is a devastating demyelinating disease caused by JC virus (JCV), predominantly affecting patients with impaired cellular immunity. PML is a non-reportable disease with a few exceptions, making national surveillance difficult. In Japan, polymerase chain reaction (PCR) testing for JCV in the cerebrospinal fluid (CSF) is performed at the National Institute of Infectious Diseases to support PML diagnosis. To clarify the overall profile of PML in Japan, patient data provided at the time of CSF-JCV testing over 10 years (FY2011-2020) were analyzed. PCR testing for 1537 new suspected PML cases was conducted, and 288 (18.7%) patients tested positive for CSF-JCV. An analysis of the clinical information on all individuals tested revealed characteristics of PML cases, including the geographic distribution, age and sex patterns, and CSF-JCV-positivity rates among the study subjects for each type of underlying condition. During the last five years of the study period, a surveillance system utilizing ultrasensitive PCR testing and widespread clinical attention to PML led to the detection of CSF-JCV in the earlier stages of the disease. The results of this study will provide valuable information not only for PML diagnosis, but also for the treatment of PML-predisposing conditions.