Nationwide Cohort Research Articles

Risk factors for readmission following esophagectomy and gastrectomy for cancer.

Hospital readmission after surgery is a key quality indicator. This nationwide cohort study aimed to assess readmission rates following esophagectomy and gastrectomy for cancer and identify associated risk factors. Data were extracted from the Dutch Upper GI Cancer Audit (DUCA) for patients with esophagogastric cancer who underwent esophagectomy or gastrectomy with curative intent between January 2011 and June 2016. Logistic regression analysis identified risk factors for 30-day readmission. In total, 5566 patients were included. Readmission within 30days occurred in 483 of 3488 (13.8%) patients after esophagectomy and 243 of 2078 patients (11.7%) after gastrectomy. Both minor (Clavien Dindo 1-2) and major (Clavien Dindo ≥3) postoperative complications were independent predictors of readmission after esophagectomy (OR 2.99; 95%CI 2.23-4.02; p< 0.001 and OR 5.20; 95%CI 3.82-7.09; p< 0.001). Specific complications included pulmonary (OR 1.49; 95%CI 1.20-1.85; p< 0.001), gastrointestinal (OR 2.43; 95%CI 1.94-3.05; p< 0.001), and infectious (OR 2.27; 95%CI 1.60-3.22; p< 0.001). Prolonged length of stay (pLOS) was associated with higher readmission rates in patients without complications following esophagectomy (OR 1.91 95% CI 1.19-3.07; p= 0.008), but lower rates in those with complications (OR 0.65 95% CI 0.51-0.83; p< 0.001). For gastrectomy, postoperative complications were also linked to readmission (OR 3.18; 95%CI 2.30-4.40; p< 0.001), particularly gastrointestinal (OR 2.16; 95%CI 1.40-3.32; p< 0.001), and infectious (OR 3.80; 95%CI 2.53-5.71; p< 0.001). Readmission after esophagogastric resection is common, particularly among patients with both minor and major postoperative complications. Prolonged stay after esophagectomy impacts readmission risk differently based on the presence of complications.

Prognosis of apparent treatment-resistant hypertension and poor adherence: a nationwide cohort study.

Large-scale studies of the prognosis of resistant hypertension in Asian populations are limited, and the impact of poor adherence on clinical prognosis in patients with apparent treatment-resistant hypertension has not been studied. A nationwide cohort analysis was done utilizing the National Health Insurance Service database in Korea, covering patients who participated in health examinations from 2013 to 2018. A total of 935,002 patients were classified into apparent treatment-resistant (N = 69,372) or nonresistant (N = 865,630) hypertension based on blood pressure control and antihypertensive medication use. Medication adherence was assessed using the proportion of days covered. The primary composite outcome included all-cause mortality, myocardial infarction, stroke, and heart failure. Other outcomes were the development of atrial fibrillation and progression to end-stage renal disease (ESRD). The median follow-up duration was 6.0 (interquartile range [IQR], 4.1-7.0) years. Patients with apparent treatment-resistant hypertension were at a higher risk for the primary composite outcome than those with nonresistant hypertension (hazard ratio [HR], 1.32; 95% confidence interval [CI], 1.29-1.35). The incidence rates of ESRD were notably higher in the resistant hypertension group (HR, 3.02; 95% CI, 2.85-3.20). Among participants with resistant hypertension, 3852 (5.7%), 11,667 (17.3%), and 51,879 (77%) had poor, suboptimal, and optimal adherence, respectively. Poor medication adherence in apparent treatment-resistant hypertension was associated with a higher risk of the primary composite outcome compared to optimal adherence (HR, 1.49; 95% CI, 1.36-1.63). Apparent treatment-resistant hypertension is associated with significant cardiovascular risks in the Korean population. Poor adherence to antihypertensive medication significantly elevates the risk of adverse clinical outcomes in patients with apparent treatment-resistant hypertension, underscoring the need for stringent management of these patients.

Fertility treatment and risk of ovarian cancer in a large nationwide cohort of infertile Danish women.

Whether fertility treatment increases the risk of ovarian cancer has been a concern for many decades, but previous research has yielded conflicting findings. We therefore investigated this association within a large population-based cohort study of infertile women aged 20-45 years and living in Denmark between 1995 and 2017, as identified in the Danish Infertility Cohort (n = 146,110). The study cohort was linked to nationwide registers to obtain information on fertility drug use, cancer diagnoses, covariates, emigration, and vital status was. Hazard ratios (HR) and 95% confidence intervals (CI) with adjustment for potential confounders for ovarian cancer overall and for serous ovarian cancer were estimated using Cox proportional hazard models. During a median 10.3 years of follow-up, 114 women were diagnosed with ovarian cancer of which 65 had serous ovarian cancer. Our results showed that the rate of serous ovarian cancer (HR 1.92; 95% CI 1.16-3.17) was increased after every use of progesterone but the association was not affected by increased follow-up time since first use or with increased cumulative dose. We performed a secondary analysis adding less extensive data from 1971 through 1994 from the Danish Infertility Cohort. In this study cohort, 332 women developed ovarian cancer of which 192 had serous ovarian cancer. The overall results were similar, including the association between every use of progesterone and serous ovarian cancer (HR 2.05: 95% CI: 1.31-3.21). In conclusion, the novel finding that use of progesterone is associated with an increased rate of serous ovarian cancer warrants further investigation.

Reoperations After Operatively and Non-Operatively Treated Periprosthetic Knee Fractures: A Nationwide Study on 1,931 Fractures After Primary Total Knee Arthroplasty.

Periprosthetic knee fracture (PPKF) following total knee arthroplasty (TKA) can be difficult to treat. A PPKF can be treated both operatively and non-operatively, and the treatment varies between fracture sites. This study aimed to assess the risk of reoperation according to the fracture site and treatment of the PPKF. This study is a nationwide cohort study using register data from 1997 to 2022. Cruciate-retaining or posterior-stabilized primary TKA were identified from the Danish Knee Arthroplasty Register (DKR). Subsequent PPKFs, fracture treatments, and later reoperations were identified through the International Classification of Diseases (ICD-10) diagnosis and procedure codes in the Danish National Patient Register. Additionally, indications for revision TKA (rTKA) in the DKR were used to identify PPKFs and the reason for reoperation. We included 1,931 PPKFs (1,494 femoral, 207 patellae, and 230 tibial) with an overall two-year reoperation risk of 20% (95% CI [confidence interval]: 18 to 23). Femoral PPKFs had a two-year reoperation risk of 16% (12 to 22) after non-operative treatment and 21% (18 to 24) after operative treatment. Patellar PPKFs had a two-year reoperation risk in five to 17 after non-operative treatment and 46% (30 to 69) after operative treatment. Tibial PPKFs had a two-year reoperation risk of 17% (11 to 27) after non-operative treatment, and 36% (25 to 53) after operative treatment. The overall two-year reoperation risk was 20% (18 to 23). Operative-treated PPKFs had a higher risk of reoperation across all fracture locations. The highest reoperation risk was found after operatively treated patella and tibial PPKFs (46 and 36%, respectively), and the lowest reoperation risk was found after non-operative treated patella PPKFs.

Use of Aspirin and Initial Cardiovascular and Bleeding Risk in Patients with Chronic Kidney Disease

Background: Despite the high cardiovascular risk in patients with chronic kidney disease (CKD), the role of aspirin in primary prevention remains unclear. This study aimed to investigate the association between aspirin initiation in adults with CKD without prior cardiovascular disease (CVD) and the first cardiovascular and bleeding events using Korean nationwide cohort data. Methods: Among individuals aged 40–79 years with an estimated glomerular filtration rate between 15 and 59 mL/min/1.73 m2 who underwent routine health examinations between 2011 and 2016, 15,861 individuals who were newly prescribed aspirin at a dose of 100 mg/day were matched with 79,305 aspirin non-users by propensity score matching. The primary efficacy outcome was a composite of nonfatal atherosclerotic CVD or cardiovascular death. The primary safety outcome was hospitalization due to intracranial or gastrointestinal bleeding. Results: During a mean follow-up of 6.9±2.9 years, the incidence rates for the primary efficacy outcome in aspirin users and non-users were 8.0 and 9.0 per 1,000 person-years, respectively. Aspirin therapy initiation was not associated with the primary efficacy outcome (hazard ratio [HR], 0.93; 95% confidence intervals [CI], 0.86-1.04). However, the primary safety outcome of major bleeding was more frequent in aspirin users than in non-users (6.7 versus 4.7 per 1,000 person-years). The HR for this outcome in aspirin users versus non-users was 1.45 (95% CI, 1.32-1.59). Conclusions: No association was observed between aspirin use and the risk of nonfatal atherosclerotic CVD or cardiovascular death in patients with CKD stages G3 and G4 without prior CVD. Aspirin use was associated with higher risk of major bleeding.

Primary glomerular diseases and long-term adverse health outcomes: A nationwide cohort study.

Although glomerular diseases are the third most frequent cause of end-stage kidney disease worldwide, little is known about their long-term outcomes. In patients with chronic kidney disease (CKD) stage 3-5 enrolled in the Swedish Renal Registry, we compared risks of hospitalization, kidney replacement therapy (KRT), major cardiovascular events (MACE), and death of the four most frequent primary glomerular diseases (IgA nephropathy [IgAN], focal segmental glomerulosclerosis [FSGS], minimal change disease [MCD], and membranous nephropathy [MN]), and patients with CKD due to the most common non-communicable diseases (control-CKD). We identified 2396 patients with glomerular disease (97% biopsy-proven, 69% men, 57 years, eGFR 29mL/min/1.73m2, uACR 88mg/mmol, 1524 with IgAN, 398 FSGS, 94 MCD, and 380 MN) and 37,697 controls (64% men, 74 years, eGFR 25mL/min/1.73m2, uACR 23mg/mmol), mainly with diabetic nephropathy and nephroangiosclerosis. The median follow-up was 6.3 (3.3; 9.9) years. Compared with control-CKD, patients with primary glomerular diseases generally had a lower risk of hospitalization, MACE (adjusted hazard ratios [HRs] ranging from 0.44 to 0.88 depending on the etiology) and death (HRs ranging 0.45-0.76). Patients with IgAN and FSGS had a faster eGFR decline and a higher rate of KRT (HRs 1.26 [95%CI: 1.15-1.37] and 1.34 [1.15-1.57], respectively). Conversely, patients with MN and MCD had a lower KRT rate and slower eGFR decline. Despite having a lower relative risk of hospitalization, cardiovascular events and mortality, patients with IgAN and FSGS are at higher risk of CKD progression than the most common etiologies of CKD, emphasizing the need for more stringent treatment strategies in these patients.

In-hospital outcomes of healthcare-associated COVID-19 (Omicron) versus healthcare-associated influenza: a retrospective, nationwide cohort study in Switzerland.

As COVID-19 is integrated into existing infectious disease control programs, it is important to understand the comparative clinical impact of COVID-19 and other respiratory diseases. We conducted a retrospective cohort study of patients with symptomatic healthcare-associated COVID-19 or influenza reported to the nationwide, hospital-based surveillance system in Switzerland. Included patients were adults (≥18 years) hospitalized for ≥3 days in tertiary care and large regional hospitals. Patients had COVID-19 symptoms and a RT-PCR-confirmed SARS-CoV-2 infection ≥3 days after hospital admission between 1 February 2022 and 30 April 2023, or influenza symptoms and a RT-PCR-confirmed influenza A or B infection ≥3 days after hospital admission between 1 November 2018 and 30 April 2023. Primary and secondary outcomes were 30-day in-hospital mortality and admission to intensive care unit (ICU), respectively. Cox regression (Fine-Gray model) was used to account for time-dependency and competing events, with inverse probability weighting to adjust for confounding. We included 2901 patients with symptomatic healthcare-associated COVID-19 (Omicron) and 868 patients with symptomatic healthcare-associated influenza from nine hospitals. We found a similar case fatality ratio between healthcare-associated COVID-19 (Omicron) (6.2%) and healthcare-associated influenza (6.1%) patients; after adjustment, patients had a comparable subdistribution hazard ratio for 30-day in-hospital mortality (0.91, 95%CI 0.67-1.24). A similar proportion of patients were admitted to ICU (2.4% COVID-19; 2.6% influenza). COVID-19 and influenza continue to cause severe disease among hospitalized patients. Our results suggest that in-hospital mortality risk of healthcare-associated COVID-19 (Omicron) and healthcare-associated influenza are comparable.

Long-term risk of heart failure in patients with postoperative atrial fibrillation following non-cardiac surgery: Insights from a nationwide cohort.

Atrial fibrillation (AF) is associated with heart failure (HF). However, it is unclear if postoperative AF (POAF) following non-cardiac surgery differs from non-surgical AF in terms of the risk of HF. We compared the long-term rate of incident HF in patients developing new-onset POAF following non-cardiac surgery with patients who did not develop POAF following non-cardiac surgery and patients with non-surgical non-valvular AF (NVAF). Using Danish nationwide registries, all patients aged ≥30 years who developed POAF following non-cardiac surgery (1996-2020) were identified and matched in a 1:3 ratio by age, sex, surgery type (only for the surgery group), selected comorbidities, and inclusion year with patients without POAF following non-cardiac surgery and individuals with NVAF, respectively. A total of 2270 patients with POAF were matched with 6810 patients without POAF following non-cardiac surgery, and 1846 patients with POAF were matched with 5538 patients with NVAF. The median follow-up was 7.2 years. Compared with patients without POAF, those with POAF had a higher associated long-term rate of incident HF (2.6 vs. 1.2 events per 100 person-years; adjusted hazard ratio [HR] 2.39, 95% confidence interval [CI] 2.06-2.78). Compared with individuals with NVAF, patients with POAF did not have a significantly different rate of incident HF (2.7 vs. 3.0 events per 100 person-years; adjusted HR 0.89, 95% CI 0.78-1.03). Patients with new-onset POAF following non-cardiac surgery had a higher associated long-term rate of incident HF compared to those without POAF, with no significant difference in the rate of incident HF when compared to patients with NVAF.

JCCG ALL-B12: Evaluation of Intensified Therapies With Vincristine/Dexamethasone Pulses and Asparaginase and Augmented High-Dose Methotrexate for Pediatric B-ALL.

The JCCG ALL-B12 clinical trial aimed to evaluate the effectiveness of unvalidated treatment phases for pediatric ALL and develop a safety-focused treatment framework. Patients age 1-19 years with newly diagnosed B-ALL were enrolled in this study. These patients were stratified into standard-risk (SR), intermediate-risk (IR), and high-risk (HR) groups. Randomized comparisons assessed the effectiveness of vincristine (VCR)/dexamethasone pulses in the SR group, evaluated the effects of L-asparaginase (ASP) intensification in the IR group, and compared standard consolidation including block-type treatment with experimental consolidation with high-dose methotrexate (HD-MTX) intensified with VCR and ASP in the HR group. Of 1,936 patients enrolled, 1,804 were eligible for the experimental treatment. The overall 5-year event-free survival and overall survival rates were 85.2% (95% CI, 83.5 to 86.8) and 94.3% (95% CI, 93.1 to 95.3), respectively. The cumulative incidence of relapse and postremission nonrelapse mortality was 13.2% (95% CI, 11.6 to 14.8) and 0.6% (95% CI, 0.3 to 1.0), respectively. Random assignment in the SR group showed no significant benefit from pulse therapy. In the IR group, ASP intensification had limited effects. In the HR group, standard block therapy and HD-MTX yielded equivalent outcomes. The ALL-B12 trial achieved favorable outcomes in a nationwide cohort by stratifying treatment on the basis of risk and balancing treatment intensity. This study not only demonstrated that existing standard of care can be further refined but also indicated that improvement in outcomes with intensified chemotherapy has reached a plateau.

Income-Related Disparities in Mortality Among Young Adults With Type 2 Diabetes.

Previous studies have indicated an inverse association between income and mortality. However, differences in health outcomes according to the income level of young adults with type 2 diabetes (T2D) compared with older adults with T2D have not been elucidated. To estimate the overall and cause-specific mortality risks among patients with T2D according to income and age. This retrospective nationwide cohort study in South Korea included adults aged 20 to 79 years who were diagnosed with T2D between January 1, 2008, and December 31, 2013, and followed up until December 31, 2019, and age- and sex-matched controls without diabetes. Data were analyzed between January 1, 2023, and August 27, 2024. Risks of all-cause, cardiovascular, and cancer mortality were estimated according to participants' income, which was categorized into 3 levels (low, middle, and high) based on the health insurance premium. Logistic regression analyses and Cox proportional hazard regression analyses were performed according to age groups (20-39, 40-59, and 60-79 years). A total of 1 240 780 adults (604 975 patients with T2D and 635 805 age- and sex-matched controls without diabetes) were included in the analyses. Their mean (SD) age was 56.9 (11.8) years, and 626 176 (50.5%) were men. Overall, the risk of mortality increased with lower income among patients with T2D, as well as in comparison with controls without diabetes. There was an inverse association between income and mortality risk in younger individuals (adjusted hazard ratios of all-cause mortality in the low income vs high income subgroups with T2D were 2.88 [95% CI, 2.25-3.69] in those aged 20 to 39 years, 1.90 [95% CI, 1.81-2.00] in those aged 40 to 59 years, and 1.26 [95% CI, 1.23-1.29] in those aged 60 to 79 years; P < .001 for comparing risk ratios between age groups). The pattern of income-related disparities in younger individuals was observed in cardiovascular mortality but less in cancer mortality. In this cohort study of 1 240 780 individuals aged 20 to 79 years, the risk of mortality with low income was most prominent among individuals with T2D aged 20 to 39 years. These findings highlight the need for socioeconomic support to reduce income-related health disparities in younger individuals.

Association Between Atopic Dermatitis and Meniere's Disease: Nationwide Cohort Study.

Atopic dermatitis (AD) is a chronic inflammatory skin condition characterized by relapsing and remitting episodes. Although AD is well-known for its association with other allergic conditions, its relationship with Meniere's disease has not been thoroughly investigated. This study aimed to explore the potential correlation between AD and Meniere's disease. This study utilized data from the National Health Insurance Service-National Sample Cohort, a nationwide population-based database. The AD group was selected from a cohort of 1 million individuals randomly extracted from database. A non-AD group was obtained through Propensity Score Matching. The AD group comprised 84,579 individuals, with an equal number of individuals in the non-AD (control) group. The overall hazard ratio (HR) for Meniere's disease in the AD group was 1.44 (95% confidence interval (CI): 1.31-1.6). Subgroup analysis showed an adjusted HR of 0.42 (95% CI: 0.38-0.48) for Meniere's disease in males, 4.99 (95% CI: 4.45-5.62) in the middle-aged group (40-59 years), and 8.21 (95% CI: 7.21-9.35) in the older age group (≥60 years). Additionally, the adjusted HRs for developing Meniere's disease were higher in patients with comorbidities, including allergic rhinitis (1.18 [95% CI, 1.07-1.32]), allergic contact dermatitis (1.32 [95% CI, 1.19-1.48]), and allergic conjunctivitis (1.54 [95% CI, 1.32-1.82]). Long-term follow-up revealed that the prevalence of Meniere's disease was 1.44 times higher in the AD group compared to the control group. Moreover, older age, female sex, allergic rhinitis, allergic contact dermatitis, and allergic conjunctivitis were identified as factors that increase the risk of developing Meniere's disease. 3 Laryngoscope, 2024.

Abstract 4138035: Inclisiran in Routine Clinical Practice: Results from a Nationwide Study of &gt;5,000 Patients

Introduction: Inclisiran is a small interfering RNA drug which inhibits proprotein convertase subtilisin/kexin type 9 (PCSK9). Inclisiran was recently approved for the treatment of hypercholesterolemia and durably lowers LDL levels by around 50% with injections once every six months based on the results of large, randomized controlled trials. However, no nationwide studies have evaluated the use or effectiveness of Inclisiran in routine clinical practice. Goals/Aims: To characterize the use and effectiveness of Inclisiran in routine clinical practice in a large nationwide cohort. Methods/Approach: We used the Truveta healthcare database, a large nationwide database of electronic health records, to study patients who were administered Inclisiran up to September 2023. Patient demographic characteristics and lipid levels before and after treatment were summarized. Means and 95% confidence intervals were estimated using t-tests. Results/Data: A total of 5,256 patients (median age 71, first quartile 65, third quartile 76) were prescribed Inclisiran, of whom 2,919 (55.5%) were Female. In terms of race, most of the patients identified as White (81.0%), and a smaller proportion as African American (7.3%), Asian (2.1%), or American Indian/Alaska Native (0.5%); 7.3% of patients identified as more than one race or did not provide race data. Mean LDL and HDL levels (mg/dL) before Inclisiran were 125 (95% CI 123-127) and 51 (95% CI 51-52) respectively and after Inclisiran were 88 (95% CI 85-90) and 50 (95% CI 49-51) respectively. The mean difference in LDL after treatment was -39 (95% CI -42 to -37) mg/Dl for a mean percent change of -22% (95% CI -25% to -19%). Effects of Inclisiran on LDL levels are shown in Figure 1. At the conference, we will compare effects of Inclisiran to those of Alirocumab and Evolocumab (two older monoclonal antibodies against PCSK9) using a propensity score overlap weighting design. Conclusions: In a large cohort of patients administered Inclisiran in routine clinical practice, Inclisiran use was associated with substantial decreases in LDL levels, but those decreases were nonetheless smaller than the effects seen in randomized controlled trials of the drug.

21-Hydroxylase Deficiency Detected in Neonatal Screening: High Probability of False Negativity in Late Onset Form.

Despite the high sensitivity of neonatal screening in detecting the classical form of congenital adrenal hyperplasia due to 21-hydroxylase deficiency, one of the unclear issues is identifying asymptomatic children with late onset forms. The aim of this nationwide study was to analyse the association between genotype and screened level of 17-hydroxyprogesterone in patients with the late onset form of 21-hydroxylase deficiency and to quantify false negativity. In the Czech Republic, 1,866,129 neonates were screened (2006-2022). Among this cohort, 159 patients were confirmed to suffer from 21-hydroxylase deficiency, employing the 17-hydroxyprogesterone birthweight/gestational age-adjusted cut-off limits, and followed by the genetic confirmation. The screening prevalence was 1:11,737. Another 57 patients who were false negative in neonatal screening were added to this cohort based on later diagnosis by clinical suspicion. To our knowledge, such a huge nationwide cohort of false negative patients has not been documented before. Overall, 57 patients escaped from neonatal screening in the monitored period. All false negative patients had milder forms. Only one patient had simple virilising form and 56 patients had the late onset form. The probability of false negativity in the late onset form was 76.7%. The difference in 17-hydroxyprogesterone screening values was statistically significant (p<0.001) between severe forms (median 478.8 nmol/L) and milder (36.2 nmol/L) forms. Interestingly, the higher proportion of females with milder forms was statistically significant compared with the general population. A negative neonatal screening result does not exclude milder forms of 21-hydroxylase deficiency during the differential diagnostic procedure of children with precocious pseudopuberty.

General practice-related variation in oral anticoagulant treatment of atrial fibrillation: a nationwide cohort study.

Guideline-adherent oral anticoagulant treatment (OAC) in atrial fibrillation (AF) remains a challenge. In Denmark, most patients with AF are treated in general practice. Nevertheless, determinants of OAC prescription in primary care are poorly understood. To investigate variation in OAC adherence between general practice clinics and identify clinic characteristics associated with a lower propensity to prescribe OAC. Nationwide register-based cohort study including prevalent and incident patients with AF and CHA2DS2-VASc score≥2 (n=165,731) listed with Danish general practice clinics (n=1666) in 2021. The main outcome was OAC adherence assessed as proportion of days covered. We used clinic OAC propensity to evaluate variation. OAC propensity was quantified as ratios between observed and expected adherence. Expected adherence was estimated based on the composition of the clinic patient populations. Sampled reference populations were constructed to account for random variation. Linear regression models examined associations between OAC propensity and clinic characteristics. The proportion of days covered with OAC in the AF-population was 78%. OAC propensity in clinics in the 90th percentile was 20% higher compared to clinics in the 10th percentile, however this difference was reduced to 3% when accounting for random variation. Modest associations were observed between clinic characteristics and OAC propensity. The most significant difference was in the correlation between geographic location and OAC propensity, showing an 8% gap between top- and bottom-performing regions. The study suggests persistent underutilisation of OAC in AF patients and little variation in OAC prescription patterns across general practice clinics.

Novel Gene Variants in a Nationwide Cohort of Patients with Pheochromocytoma and Paraganglioma

Pheochromocytomas (PCCs) and paragangliomas (PGLs), denoted PPGLs, are rare neuroendocrine tumours and are highly heterogeneous. The phenotype–genotype correlation is poor; therefore, additional studies are needed to understand their pathogenesis. We describe the clinical characteristics of 63 patients with PPGLs and perform a genetic study. Genetic screening was performed via a targeted gene panel, and clinical variables were compared among patients with a positive molecular diagnosis and negative ones in both PCC and PGL cohorts. The mean age of patients with PCC was 50.0, and the mean age of those with PGL was 54.0. Disease-causing germline variants were identified in 16 individuals (25.4%), twelve and five patients with PCC and PGL, respectively. Genetically positive patients were younger at diagnosis in both cohorts. Variants in genes associated with either isolated PPGLs or syndromic forms of the disease were detected in a cohort of PPGLs. We have identified novel variants in known genes and set the importance of genetic screening to every patient with PPGLs, with a special focus on the young. A longer follow up of patients with variants in genes associated with syndromic forms is of clinical value.

Acute diverticulitis requiring hospitalization according to regional discrepancies in France between 2013 and 2022: a nationwide study

PurposeThe prevention of colon diverticulitis tends to be tailored according to the patients. In order to improve the public health policy to prevent diverticulitis, the influence of regional parameters at a department scale has to be assessed.ObjectiveThis analysis aimed to assess the occurrence of acute diverticulitis in France in general and according to environmental factors suspected to affect such diseases.MethodsAll patients above 18 years old admitted to a general hospital with a diverticulitis diagnosis between 2013 and 2022 in France were included. Data were extracted from the French national hospital discharge database. The primary outcome was the occurrence of diverticulitis according to French territories and known risk factors.ResultsIn this nationwide cohort study, the 10-years cumulative occurrence of diverticulitis in France was 3.45% (n = 2 0.248.099 patients). Diverticulitis was influenced by older age and male gender but was not significantly associated with ecological parameters (obesity, alcohol consumption, smoking or economic discrepancies) at a departmental scale. Of all patients diagnosed with diverticulitis, 5% had at least one surgical intervention. The surgical management of diverticulitis was associated with an increased number of surgeons in the department, even after adjustment for age and sex.ConclusionsExcept for smoking, the frequency of diverticulitis requiring an hospitalization was independent of regional parameters (nor alcohol intake, nor obesity nor the economic discrepancies).

Long-Term Ozone Exposure, COPD, and Asthma Mortality: A Retrospective Cohort Study in the Republic of Korea

Ozone concentrations have increased in recent decades, and several studies have reported that long-term exposure to ozone increases the mortality risk induced by respiratory conditions. However, research on cause-specific mortality related to ozone exposure and respiratory diseases remains scarce. We constructed a retrospective cohort of 5,360,032 adults aged ≥ 65 years from the National Health Insurance Service of Republic of Korea, and death certificates were obtained from Statistics Republic of Korea to determine the cause of death between 2010 and 2019. The daily maximum 8 h average levels of ozone during the warm season annually (May–September) and other air pollutants were determined for the residential district. We analyzed the data using a time-varying Cox proportional hazards model with individual- and district-level covariates, incorporating a competing risk framework to address deaths from causes other than chronic obstructive pulmonary disease (COPD) and asthma. In our single-pollutant model with a 3-year moving average, a 1 ppb increase in ozone exposure was associated with a hazard ratio (HR) of 1.011 (95% confidence interval [CI]: 1.008–1.013) for COPD mortality and an HR of 1.016 (95% CI: 1.011–1.022) for asthma mortality. In our model adjusted for the presence of underlying diseases and district-level variables, the HRs were 1.009 (95% CI: 1.008–1.014) for COPD and 1.017 (95% CI: 1.011–1.023) for asthma, respectively. These associations remained robust in our two-pollutant model, except for NO2 and COPD. A linear concentration–response relationship was identified between ozone concentration, COPD, and asthma mortality. In this large nationwide cohort study, long-term exposure to ozone was associated with an increased risk of death from COPD and asthma in older Korean adults.

Psoriasis Risk With Immune Checkpoint Inhibitors

Immune checkpoint inhibitors (ICIs) are recognized as revolutionary cancer therapies but have raised concerns about immune-related adverse events, including the development of autoimmune diseases. To evaluate the psoriasis risk associated with the use of ICIs in patients with cancer. This nationwide cohort study with a target trial emulation design used data from the Taiwan National Health Insurance database and the Taiwan Cancer Registry. The participants included were patients who received antineoplastic medications for cancer at stages III and IV between January 1, 2019, and June 30, 2021. Data were analyzed from May 2023 to July 2024. Patients treated with ICIs were classified as ICI users, while those who received chemotherapy or targeted therapies were categorized as non-ICI users. The primary outcome was the incidence of psoriasis during the follow-up period. Stabilized inverse probability of treatment weighting (IPTW) was used to mitigate potential confounders. Cox and Fine-Gray hazard models were used to calculate hazard ratios (HRs) for psoriasis risk between groups. Of 135 230 patients who received antineoplastic medications (mean [SD] age, 62.94 [13.01] years; 45.1% female), 3188 patients were eligible for the ICI user group, while 132 042 patients were eligible for the non-ICI user group. ICI users experienced a higher incidence of psoriasis at 5.76 cases per 1000 person-years, compared to 1.44 cases in the non-ICI group. After adjusting for demographics and comorbidities, ICI users were found to have a 2-fold increase in the risk of developing psoriasis (IPTW-adjusted HR, 3.31; IPTW-adjusted subdistribution HR, 2.43). Both as-started design and on-treatment design showed consistent findings, and the results were consistent and robust across all follow-up intervals and all sensitivity analyses. In this cohort study, patients with cancer treated with ICIs faced an increased risk of psoriasis. Medical professionals should be aware of the potential adverse effects of immunotherapy to ensure optimal cancer care.

Exploring the relationship between polycystic ovarian syndrome, testosterone, and multiple sclerosis in women: A nationwide cohort study and genome-wide cross-trait analysis.

Women have a higher risk of developing multiple sclerosis (MS), potentially due to hormonal factors. Elevated testosterone levels, common in polycystic ovary syndrome (PCOS), might influence MS risk. To investigate the relationship between PCOS, as a proxy for elevated testosterone levels, and MS risk through phenotypic and genomic analysis. Cox regression models analysed the association between PCOS and MS risk. The genome-wide cross-trait analysis examined the genetic architecture. In a Swedish cohort of 1,374,529 women, 77 (0.3%) with PCOS and 3,654 (0.3%) without PCOS were diagnosed with MS. After adjusting for birth year and obesity, no association was found between PCOS and MS (HR = 0.91, 95% CI = 0.72-1.15), which was confirmed by Mendelian randomization analysis, where genetically predicted PCOS propensity, sex hormone-binding globulin (SHBG), or testosterone levels did not causally affect MS risk (all p-values > 0.05). By exploring horizontal pleiotropy, we identified shared genetic regions and 19 independent pleiotropic SNPs for SHBG with MS and 11 for testosterone with MS. We did not find evidence for a causal role of PCOS, as a proxy of elevated testosterone, in reducing the risk of MS in women. The shared genetic loci between testosterone, SHBG, and MS provide biological insights.

Machine Learning-Based Prediction for Incident Hypertension Based on Regular Health Checkup Data: Derivation and Validation in 2 Independent Nationwide Cohorts in South Korea and Japan.

Worldwide, cardiovascular diseases are the primary cause of death, with hypertension as a key contributor. In 2019, cardiovascular diseases led to 17.9 million deaths, predicted to reach 23 million by 2030. This study presents a new method to predict hypertension using demographic data, using 6 machine learning models for enhanced reliability and applicability. The goal is to harness artificial intelligence for early and accurate hypertension diagnosis across diverse populations. Data from 2 national cohort studies, National Health Insurance Service-National Sample Cohort (South Korea, n=244,814), conducted between 2002 and 2013 were used to train and test machine learning models designed to anticipate incident hypertension within 5 years of a health checkup involving those aged ≥20 years, and Japanese Medical Data Center cohort (Japan, n=1,296,649) were used for extra validation. An ensemble from 6 diverse machine learning models was used to identify the 5 most salient features contributing to hypertension by presenting a feature importance analysis to confirm the contribution of each future. The Adaptive Boosting and logistic regression ensemble showed superior balanced accuracy (0.812, sensitivity 0.806, specificity 0.818, and area under the receiver operating characteristic curve 0.901). The 5 key hypertension indicators were age, diastolic blood pressure, BMI, systolic blood pressure, and fasting blood glucose. The Japanese Medical Data Center cohort dataset (extra validation set) corroborated these findings (balanced accuracy 0.741 and area under the receiver operating characteristic curve 0.824). The ensemble model was integrated into a public web portal for predicting hypertension onset based on health checkup data. Comparative evaluation of our machine learning models against classical statistical models across 2 distinct studies emphasized the former's enhanced stability, generalizability, and reproducibility in predicting hypertension onset.