5-year Incidence Research Articles

Lactulose use among patients with alcohol-related liver cirrhosis as a surrogate marker of hepatic encephalopathy: prevalence and association with mortality - a Danish nationwide cohort study

Background & aims: Hepatic encephalopathy (HE), one of the most serious prognostic factors for mortality in alcohol-related cirrhosis (ALD cirrhosis), is not recorded in Danish healthcare registries. However, treatment of HE with lactulose, the universal first-line treatment, can be identified through data on filled prescriptions. This study aimed to investigate if lactulose can be used as a surrogate marker of HE. Methods: We used Danish healthcare registries to establish a cohort of patients with ALD cirrhosis diagnosed in 2000–2018. Lactulose users were identified using data on filled prescriptions. We computed the prevalence and cumulative incidence of lactulose use, and then matched lactulose users with cohort members who were not using lactulose. This matched dataset was used to identify predictors of lactulose initiation, and to examine the association between lactulose use and all-cause mortality. Results: We included 23,089 patients, among whom we identified 4,789 first-time lactulose users. The prevalence of lactulose usage rose to 11% within the first 6 months after ALD diagnosis and reached 19% 5 years after inclusion. The 1-year cumulative incidence of lactulose use was 31%, and predictors of initiating lactulose use were history of severe liver disease (ascites, portal hypertension, spontaneous bacterial peritonitis or gastrointestinal bleeding) or hepatocellular carcinoma. Lactulose use was associated with higher mortality (adjusted hazard ratio 1.61 [95% confidence interval 1.53; 1.69]). Conclusions: Lactulose is used by 10–20% of patients with ALD cirrhosis, primarily those with severe cirrhosis, and lactulose users have a markedly higher mortality than nonusers. We conclude that lactulose use can be used to estimate the prevalence of HE and to reduce confounding from HE, but it should not be used as a surrogate for HE in studies with HE as an outcome.

Incidence of hospital-acquired infections due to carbapenem-resistant Enterobacterales and Pseudomonas aeruginosa in critically ill patients in Italy: a multicentre prospective cohort study

BackgroundCarbapenem-Resistant Gram-Negative Bacteria, including Carbapenem-Resistant Enterobacterales (CRE) and Carbapenem-Resistant Pseudomonas aeruginosa (CRPA), are common causes of infections in intensive care units (ICUs) in Italy.ObjectiveThis prospective observational study evaluated the epidemiology, management, microbiological characterization, and outcomes of hospital-acquired CRE or CRPA infections treated in selected ICUs in Italy.MethodsThe study included patients with hospital-acquired infections due to CRE and CRPA treated in 20 ICUs from June 2021 to February 2023. The primary endpoint was the 1-year incidence of CRE/CRPA infections. Secondary endpoints included the rate of CRE/CRPA infections, mortality in ICU, infection outcome, and microbiological characterization.ResultsAmong 13,088 patients admitted over the 12-month study period across each of the 20 ICUs, 283 had CRE infections, and 138 had CRPA infections. The incidence of CRE and CRPA infections was 3.57 per 1000 patient days and 1.74 per 1000 patient days, respectively. The proportion of CRE and CRPA infections over the total number of infections due to Enterobacterales and Pseudomonas aeruginosa was 19.2% and 26.8%, respectively. Among 158 patients included in the full analysis, 98 (62%) had CRE infections and 60 (38%) had CRPA infections. Ventilator-associated pneumonia and bloodstream infections were the most common infections, occurring in 53.8 and 34.2% of cases. Empirical therapy targeting gram-negative pathogens resulted inappropriate in 59.2% of analysed patients (77/130). The overall crude mortality in ICU rate was 30.4%, with a higher rate in CRE patients (36.7%) than in CRPA patients (20.0%). Clinical success, including microbiological eradication, was achieved in 50.6% of cases. Klebsiella pneumoniae was observed as the predominant CRE species, and all CRE isolates, including metallo-β-lactamases-producing CRE (MBL-CRE), were susceptible to Aztreonam-Avibactam.ConclusionsThese results highlight the high prevalence of CRE/CRPA infections in Italian ICUs and emphasize the need for enhanced prevention and surveillance strategies.

Brisk Walking Pace Offsets Venous Thromboembolism Risk Equivalent to Established Monogenic Mutations.

Mendelian mutations in the Prothrombin gene (F2) and the factor V Leiden gene (F5) genes are established risk factors for venous thromboembolism (VTE). Walking pace is associated with the risk of coronary artery diseases, but no study has investigated its association with VTE. This study aimed to investigate the association and causality between walking pace and VTE, compare its population risk with established Mendelian mutations, and determine if blood biomarkers mediate its effect. We followed up 445,261 UK Biobank participants free of VTE at baseline. Self-reported walking pace was collected via touchscreen questionnaire at baseline. The carrier status of two Mendelian mutations in F2 and F5 genes was determined by the genotypes of rs1799963 (G20210A, c.*97 G > A) and rs6025 (p.R534Q), respectively. Cox proportional hazard model was used to estimate the effect of walking pace on incident VTE. We conducted a bidirectional Mendelian randomization (MR) analysis, by using 70 single-nucleotide polymorphisms (SNPs) from a walking pace genome-wide association studies (GWAS) and 93 SNPs from a VTE GWAS as instrumental variables. We used both individual-level data and GWAS summary statistics for mediation analysis. Over a median follow-up period of 12.8 years, 11,155 incident VTE cases were identified. The 10-year incidence rates for brisk and slow walking pace were 1.32% (confidence interval [CI]: 1.27-1.37%) and 3.90% (CI: 3.71-4.09%), respectively. For noncarriers, F2 and F5 carriers, the 10-year incidence rates were 1.70% (CI: 1.66-1.73%), 2.94% (CI: 2.66-3.22%), and 3.62% (CI: 3.39-3.84%), respectively. The overall risk of VTE for F5 mutation carriers with a brisk walking pace (2.65%) was smaller than that for noncarriers with a slow walking pace (3.66%). For F5 mutation carriers, brisk pace (but not steady pace) reduces the risk of VTE (p interaction < 0.05). MR analyses displayed a causal relationship (inverse variance weighted: p = 3.21 × 10-5) from walking pace to VTE incidence. Mediation analysis showed that serum albumin (ALB) and cystatin C (CYS) levels partially mediated the effect of brisk walking pace on the risk of VTE incidence, with mediation proportions of 8.7 to 11.7%, respectively. On the population scale, the protective effect of brisk walking pace offsets the risk of VTE caused by Mendelian mutations. We provided preliminary evidence that a brisk walking pace causally reduces the risk of VTE. Serum ALB and CYS partially mediate this effect.

Prognostic value of atherogenic index of plasma in pulmonary hypertension

BackgroundThe atherogenic index of plasma (AIP) is a brand-new lipid parameter that has been used to assess various cardiovascular events. This study aimed to investigate the prognostic value of AIP in patients with pulmonary hypertension (PH).MethodsThis retrospective study was conducted at Shanghai Jiao Tong University School of Medicine affiliated Renji Hospital, and included data from 125 PH patients treated during 2014–2018. The endpoint events of this study were clinical worsening outcomes. PH patients include those from group 1 and group 4. AIP was determined as the logarithm of the blood triglycerides ratio to high-density lipoprotein cholesterol.ResultsThe 1-year, 3-year, and 5-year incidence rates of clinical worsening outcomes in PH patients in this study were 20.0, 44.8, and 54.4%, respectively. The median age of the PH patients was 38.00 years, with females accounting for 90.4%. After controlling for multivariable factors, the results of Cox regression analysis indicated that AIP was an independent predictor of adverse outcomes with a hazard ratio and 95% confident interval (CI) of 2.426 (1.021–5.763). The positive linear relationship of AIP was evaluated using restricted cubic spline analysis. Kaplan–Meier curves showed a significantly higher events rate in patients with AIP ≥ 0.144 compared to those with AIP &amp;lt; 0.144 (p = 0.002). Four potential prognostic variables, including AIP, were identified by LASSO regression to construct a nomogram. Compared to the model minus AIP, the AUC of the nomogram displayed a non-significant improvement (0.749 vs. 0.788, p = 0.298). In contrast, the results of net reclassification improvement (0.306, 95% CI: 0.039–0.459, p &amp;lt; 0.001) and integrated discrimination improvement (0.049, 95% CI: 0.006–0.097, p = 0.020) demonstrated significant enhancements in the predictive ability of the model when AIP was added to the clinical model.ConclusionAIP is an independent predictor of long-term clinical worsening in PH patients, and its inclusion in prognostic models could improve risk stratification and management.

Incidence and Prevalence of Bone Metastases in Different Solid Tumors Determined by Natural Language Processing of CT Reports

Background/Objectives: Improved survival due to advances in medical therapy has resulted in increasing numbers of cancer patients living with bone metastases; however, our understanding of the prognostic implications of bone metastases requires larger population-based studies outlining their incidence and prevalence in different primary cancer types, including those with lower incidence. This study aimed to evaluate the incidence and prevalence of bone metastases in solid organ tumors by analyzing reports of staging CT studies with natural language processing (NLP). Methods: In this retrospective study, 639,470 reports representing 129,326 unique patients were analyzed; 6279 randomly selected reports were manually annotated and labeled for the presence or absence of bone metastases. From these data, a BERT-based NLP model was developed and applied to the patient database. The cumulative incidence at 5 years and prevalence of bone metastases in each cancer type were calculated. Results: The accuracy of the NLP model on a validation set was 97.1%, with a positive predictive value (precision) of 88.0% and a sensitivity (recall) of 86.3%. The 5-year incidence rate of bone metastases was highest in prostate, breast, head and neck, and lung cancer (52%, 41%, 36%, 33%). Incidence was lowest in central nervous system cancer and testicular cancer (8%, 5%). Prevalence was highest in prostate, breast, and lung cancer (32%, 25% and 23%), and lowest in central nervous system cancer and testicular cancer (4%, 4%). Conclusions: NLP was utilized to demonstrate patterns of bone metastases in a broad range of cancer types and is a valuable tool in population-based assessment of bone metastases.

Transcatheter versus Surgical Aortic Valve Replacement in Patients Younger than 65 Years in the US.

To characterize trends and outcomes of aortic valve replacement in patients <65 with aortic stenosis between 2013 and 2021. This retrospective analysis included 9,557 patients who underwent biological aortic valve replacement in California, New York, and New Jersey from 2013 through 2021. Patients were stratified by approach: transcatheter aortic valve replacement (TAVR) versus surgical aortic valve replacement (SAVR). Our primary outcomes were 30-day and 6-year mortality and morbidity (stroke, heart failure rehospitalization, reintervention, and new pacemaker implantation). After propensity score matching, Cox-proportional hazard and Fine-Gray models were used to compare outcomes following TAVR and SAVR. The proportion of patients <65 years with aortic stenosis undergoing TAVR versus SAVR increased from 7.1% in 2013 to 54.7% in 2021. After propensity score matching, 30-day mortality was similar between both groups (1.0% vs. 1.5%, p=0.33). TAVR had a higher 6-year mortality (23.3% vs. 10.5%, HR: 2.27; CI: 1.82-2.83; p<0.001). The 30-day rate of new pacemaker implantation was higher after TAVR (10.7 vs. 6.2%, p<0.001). There was no difference in the 6-year cumulative incidence of stroke, heart failure hospitalizations, or reoperations. Multiple sensitivity analyses confirmed these findings. Despite clinical guidelines, the utilization of TAVR has increased in patients <65. TAVR in this population is associated with a higher 6-year mortality and a higher rate of new permanent pacemaker implantation when compared to a matched cohort treated with biologic SAVR. These findings support the need for a randomized controlled trial comparing long-term outcomes of TAVR versus SAVR in patients <65.

The interplay between sex, lifestyle factors and built environment on 20-year cardiovascular disease incidence; the ATTICA study (2002–2022)

The interplay between sex, lifestyle factors and built environment on 20-year cardiovascular disease incidence; the ATTICA study (2002–2022)

Prevalence and Clinical Outcomes of Discordant Lesions Between Fractional Flow Reserve and Nonhyperemic Pressure Ratios in Clinical Practice: The J-PRIDE Registry.

Limited large-scale, real-world data exist on the prevalence and clinical impact of discordance between fractional flow reserve (FFR) and nonhyperemic pressure ratios (NHPRs). The J-PRIDE registry (Clinical Outcomes of Japanese Patients With Coronary Artery Disease Assessed by Resting Indices and Fractional Flow Reserve: A Prospective Multicenter Registry) prospectively enrolled 4304 lesions in 3200 patients from 20 Japanese centers. The lesions were classified into FFR+/NHPR-, FFR-/NHPR+, FFR+/NHPR+, or FFR-/NHPR groups according to cutoff values of 0.89 for NHPRs and 0.80 for FFR. The primary study end point was the cumulative 1-year incidence of target vessel failure (a composite of cardiac death, target vessel-related myocardial infarction, and clinically driven target vessel revascularization) on a lesion basis. An NHPR cutoff value of 0.89, determined using online software, predicted an FFR of 0.80 across various NHPR types. Discordance between FFR and NHPRs was observed in 20% of lesions (FFR+/NHPR-, 11.2%; FFR-/NHPRs+, 8.8%). Revascularization was deferred in 42.9% and 88.4% of the FFR+/NHPR- and FFR-/NHPR+ groups, respectively. In deferred vessels, the FFR+/NHPR- and FFR-/NHPR+ groups showed a higher 1-year incidence of target vessel failure compared with the FFR-/NHPR- group (7.9% versus 5.5% versus 1.7%; for FFR+/NHPR-, adjusted hazard ratio [aHR], 4.89 [95% CI, 2.68-8.91]; P<0.001; for FFR-/NHPR+, aHR, 2.64 [95% CI, 1.49-4.69]; P<0.001). In revascularized vessels, the 1-year target vessel failure rate was numerically higher in the FFR-/NHPR+ group than in the FFR+/NHPR+ group (9.6% versus 3.4%; aHR, 2.27 [95% CI, 0.70-7.34]; P=0.17), although with similar outcomes between the FFR+/NHPR- and FFR+/NHPR+ groups (2.3% versus 3.4%; aHR, 0.96 [95% CI, 0.37-2.38]; P=0.93). The FFR+/NHPR- group benefited from revascularization compared with medical treatment (aHR, 0.26 [95% CI, 0.08-0.86]; P=0.027); the FFR-/NHPR+ group did not (aHR, 2.39 [95% CI, 0.62-9.21]; P=0.20). Discordance between FFR and NHPRs was noted in 20% of lesions, and discordant deferred lesions resulted in worse outcomes than concordant negative lesions. Although the outcomes after deferring revascularization were comparable between the FFR+/NHPR- and FFR-/NHPR+ lesions, only FFR+/NHPR- lesions showed a benefit from revascularization compared with medical treatment, suggesting that an FFR-guided strategy is superior to an NHPR-guided strategy in discordant lesions. URL: https://www.umin.ac.jp; Unique identifier: UMIN000038403.

Testosterone Replacement Therapy Is Associated With Increased Incidence Rate of Vertebral Fractures: A Matched Retrospective Analysis.

Whether testosterone replacement therapy (TRT) can mitigate the risk of vertebral fractures has not been well-studied. PearlDiver was queried to identify patients with and without the history of TRT. Groups were matched 1:1 by demographic variables and 2-year vertebral fracture incidence rate was compared. Multivariate logistic regression was done to identify independent predictors of vertebral fractures. Among 77,491 matched patients, mean age was 54.7 ± 10.4 years, 74.3% were males, and mean Charlson Comorbidity Index was 0.17 ± 0.54. Testosterone replacement therapy patients had higher rates of vertebral fractures (0.31% vs 0.04%, P < 0.001), and these rates were observed to increase with age. Both men alone (0.36% vs 0.04%, P < 0.001) and women alone (0.16% vs 0.03%, P < 0.001) on TRT had higher rates of vertebral fractures. Multivariate analysis revealed that TRT (OR = 7.7, 95%CI = 5.1-11.7, P < 0.001), as well as chronic kidney disease (OR = 1.4, 95%CI = 1.1-2.0, P = 0.026), alcohol abuse (OR = 2.5, 95%CI = 1.8-3.5, P < 0.001), and diphosphonate use (OR = 2.2, 95%CI = 1.4-3.5, P < 0.001), increased vertebral fracture rates. Exogenous testosterone use was associated with increased 2-year incidence of vertebral fractures. Although a causal relationship could not be established, our findings highlight the need to use screening measures, such as dual-energy X-ray absorptiometry (DEXA) scan, to identify patients at risk of vertebral fractures.

Epidemiology of Soft Tissue Sarcoma in Iran: Four-Year National Cancer Registry Data Report (2014-2017).

An uncommon and diverse class of cancers originating from mesenchymal tissues is designated as soft tissue sarcoma (STS). To develop effective preventive and treatment strategies for STS, it is essential to gain a deeper understanding of the epidemiological trends associated with the disease. This research will analyze the 4-year age-standardized incidence rate (ASIR) and geographical distribution of STS in Iran in great detail. The study population comprised 4968 cases of STS recorded in the Cancer Registry System between 2014 and 2017. The demographic data examined included gender, place of residence, and year of diagnosis. The age-standardized rate (ASR) of STS incidence was calculated for each location using the World Standard Population. The data were examined using the program ArcMap10.5. The geographic distribution of STS was investigated using the Moran test. The ASRs for STS in Iran from 2014 to 2017 were recorded as 1.25 (ASR in male: 1.47, ASR in female: 1.06), 1.36 (ASR in male: 1.46, ASR in female: 1.29), 1.37 (ASR in male: 1.52, ASR in female: 1.21), and 1.78 (ASR in male: 1.58, ASR in female: 1.98), respectively. In 2014 and 2015, age-standardized incidence at the national level showed a statistically significant regional dispersion that appeared as a clustering pattern, according to Moran's test. However, in 2016 and 2017, this dispersion failed to become statistically significant. Interestingly, men had a greater rate of STS incidence than females. As age grows, ASIR shows a steadily rising trend. The most important gains are shown in the 55-59 age group, which peaked at 4.535 in 2017, and the 80-84 age group, which peaked at 10.848 in the same year. The incidence of STS in Iran is lower than the global average. The discrepancies in gender disparities, regional distribution, and incidence rates underscore the complexity of STSs. The findings of this study may assist healthcare professionals and policymakers in the development of region-specific plans for the treatment, early detection, and prevention of STSs.

Simplifying coronary artery disease risk stratification: development and validation of a questionnaire-based alternative comparable to clinical risk tools.

Coronary artery disease (CAD) comprises one of the leading causes of morbidity and mortality both in the European population and globally. All established clinical risk stratification scores and models require blood lipids and physical measurements. The latest reports of the European Commission suggest that attracting health professionals to collect these data can be challenging, both from a logistic and cost perspective, which limits the usefulness of established models and makes them unsuitable for population-wide screening in resource-limited settings, i.e., rural areas. Therefore, the aim of this study was to develop and externally validate a questionnaire-based risk stratification model on a population scale at minimal cost, i.e., the Questionnaire-Based Evaluation for Estimating Coronary Artery Disease (QUES-CAD) to stratify the 10-year incidence of coronary artery disease. Cox proportional hazards (CoxPH) and Cox gradient boosting (CoxGBT) models were trained with 10-fold cross-validation using combinations of ten questionnaire variables on the White population of the UK Biobank (n=448,818) and internally validated the models in all ethnic minorities (n=27,433). The Lifelines cohort was employed as an independent external validation population (n=97,770). Additionally, we compared QUES-CAD's performance, containing only questionnaire variables, to clinically established risk prediction tools, i.e., Framingham Coronary Heart Disease Risk Score, American College of Cardiology/American Heart Association pooled cohort equation, World Health Organization cardiovascular disease risk charts, and Systematic Coronary Risk Estimation 2 (SCORE2). We conducted partial log-likelihood ratio (PLR) tests and C-index comparisons between QUES-CAD and established clinical prediction models. In the external validation set, QUES-CAD exhibited C-index values of CoxPH: 0.692 (95% Confidence Interval [CI]: 0.673-0.71) and CoxGBT: 0.699 (95% CI: 0.681-0.717) for the male population and CoxPH: 0.771 (95% CI: 0.748-0.794) and CoxGBT: 0.759 (95% CI: 0.736-0.783) for the female population. The addition of measurement-based variables and variables that require a prior medical examination (i.e., insulin use, number of treatments/medications taken, prevalent cardiovascular disease [other than CAD, and stroke diagnosed by a doctor]) and the further addition of biomarkers/other measurements (i.e., high-density lipoprotein [HDL] cholesterol, total cholesterol, and glycated haemoglobin) did not significantly improve QUES-CAD's performance in most instances. C-index comparisons and PLR tests showed that QUES-CAD performs and fits the data at least as well as the clinical prediction models. QUES-CAD performs comparably to established clinical prediction models and enables a population-wide identification of high-risk individuals for CAD. The model developed and validated herein relies solely on ten questionnaire variables, overcoming the limitations of existing models that depend on physical measurements or biomarkers. University Medical Center Groningen.

The prognostic value of anti-gp210 and anti-centromere antibodies in patients with primary biliary cholangitis: Enhancing the prognostic utility on the GLOBE scoring system.

Positivity for anti-gp210 and anti-centromeric antibodies (ACA) in patients with primary biliary cholangitis (PBC) have been associated with the progression of liver failure and portal hypertension (PH), respectively. The value of combining risk autoantibody assessments with prognostic scoring systems in improving risk assessment in patients with PBC remains unclear. To investigate the prognostic significance of various combinations of anti-gp210 and ACA statuses and their enhancing the prognostic utility on the GLOBE scoring system. Stepwise Cox regression was used to estimate the relationship between anti-gp210 antibodies or ACA and liver transplant (LT)-free survival. The GLOBE scoring system was used to stratify the patients. A total of 1412 patients with confirmed PBC were included in the study. The anti-gp210+ status was a significant risk factor for LT/liver-related death, whereas the ACA+ status was a significant risk factor for variceal bleeding (P = 0.002 and 0.007, respectively). The anti-gp210 + ACA + status was a risk indicator for the entire cohort independent of the GLOBE score (P = 0.001, hazard ratio [HR]: 2.649, 95 % confidence interval [CI]: 1.492-4.703) and liver stiffness measurements (LSM; P = 0.039, HR: 4.969, 95 % CI: 1.088-22.692). A significant difference was observed in the area under the receiver operating characteristic curve between the fitted scoring model (consisting of the GLOBE score, anti-gp210 + ACA+ status, and albumin level) and the GLOBE scoring system alone (P = 0.034). When enrolled patients were classified as high-, medium-, and low-risk by the GLOBE scoring system (1.8 and 0.5), the anti-gp210 + ACA+ status was associated with a 1.6- and 3.3-fold higher 5-year incidence of LT/liver-related death in the high- and medium-risk groups, respectively, in comparison with the anti-gp210 + ACA- cases. The anti-gp210 + ACA+ status was also a risk indicator for the presentation of the hepatic failure phenotype in comparison with the anti-gp210- status (P = 0.007, odds ratio [OR]: 6.419, 95 % CI: 1.645-25.042), and the presentation of PH phenotype in comparison with the anti-ACA- status (OR: 3.473, 95 % CI: 1.328-9.018, P = 0.011). The anti-gp210 + ACA+ status was an independent prognostic marker that could predict a poor prognosis in patients with PBC at diagnosis and may further optimise risk stratification in combination with the GLOBE scoring system.

Risk of cancer and reoperation after ileorectal anastomosis and ileal pouch-anal anastomosis in familial adenomatous polyposis.

To prevent colorectal cancer (CRC), most patients with familial adenomatous polyposis (FAP) undergo (procto)colectomy with ileorectal anastomosis (IRA) or ileal pouch-anal anastomosis (IPAA). After surgery, these patients remain at risk of developing cancer in the remnant rectum or rectal cuff/pouch. We aimed to compare the long-term risk of cancer following IRA or IPAA in FAP. We performed an international multicenter historical cohort study of FAP patients undergoing IRA or IPAA from 1990 to 2023. The proportion of patients developing cancer following surgery was estimated using the Kaplan-Meier method. (Procto)colectomy was performed in 685 patients (53.6% female); 366 (53.4%) had IRA and 319 (46.6%) IPAA. Median age at IRA and IPAA was 23 and 27 years, and median follow-up was 12 and 15 years, respectively. Overall, 8 patients (2.2%) developed rectal and/or rectal cuff/pouch cancer after IRA and 0.9% after IPAA. The estimated 10- and 20-year cancer incidence after IRA vs IPAA were 1.6% vs 0.4% and 2.5% vs 0.9%, respectively (log-rank p=0.15. Reoperations, mainly for extensive polyposis, were performed in 39 (10.7%) patients with an IRA and 24 (7.5%) patients following IPAA. The number of post-operative endoscopic surveillance endoscopies was higher in patients with an IRA compared to those with an IPAA (p<0.001). Over the last three decades, few patients were diagnosed with cancer in the rectum or rectal cuff/pouch after (procto)colectomy in FAP. This might be due to an improved selection of the type of (procto)colectomy and close endoscopic surveillance including prophylactic polypectomies.

Long-Term Risk of Acute Myocardial Infarction in Patients With a Transient Ischemic Attack: A Danish Nationwide Cohort Study.

Sparse information regarding the long-term risk of acute myocardial infarction (MI) following a transient ischemic attack (TIA) emphasizes further research to guide preventive strategies and risk stratification in patients with a TIA. We conducted a nationwide cohort study to investigate the 5-year risk of MI and all-cause mortality in patients with a first-time TIA. Patients with a first-time TIA were identified in the Danish Stroke Registry (2013-2020), matched on age, sex, and calendar year (1:4) with the general population and (1:1) with patients with first-time ischemic stroke. The 5-year risks of MI and all-cause mortality were estimated by the Aalen-Johansen and Kaplan-Meier estimators. The groups were compared using Cox regression, while adjusting for cardiovascular comorbidities. We identified 21 743 patients with TIA, 86 972 matched individuals from the general population, and 21 743 matched control patients with ischemic stroke. Median age was 70 (25th to 75th percentile, 60-78) years; 52% were male. Comorbidity burden was the lowest in general population controls, intermediate in patients with TIA, and the highest in patients with ischemic stroke. The 5-year risk of MI was 2.0% in patients with TIA, 1.5% in the general population (P<0.001), and 2.2% in the ischemic stroke population (P<0.001). After adjustment, these differences in MI rate were similar (TIA versus general population; hazard ratio, 0.99 [95% CI, 0.98-1.02] and TIA versus ischemic stroke; hazard ratio, 0.99 [95% CI, 0.96-1.01]). The 5-year risk of mortality was 17.0% in patients with TIA compared with 14.0% in the general population (P<0.001) and 27.0% in ischemic stroke population (P<0.001). The differences in mortality persisted following adjustments for patients with TIA versus general population (hazard ratio, 1.25 [95% CI, 1.19-1.31]) and for patients with TIA versus ischemic stroke (hazard ratio, 0.43 [95% CI, 0.41-0.46]). Patients with first-time TIA had a low 5-year incidence of MI, which was not significantly different from that of the general population and patients with first-time ischemic stroke after adjustments for comorbidities. However, patients with TIA had a 25% higher all-cause mortality rate than the general population, which was not readily explained by MI risk. Hence, the findings do not endorse the need to raise further awareness regarding MI in patients with TIA.

Five-Year Fracture Rate for Transgender and Gender Diverse Patients on Gender-Affirming Hormone Therapy.

Gender-affirming hormone therapy (GAHT) is a cornerstone of gender-affirming care for transgender and gender diverse (TGD) patients, with a direct biological role on bone metabolism. However, a paucity of data describes how GAHT influences fracture rate over time. The study's primary objective was to describe the 5-year all-cause fracture incidence rate (IR) among TGD patients initiating estrogen-based GAHT (E-GAHT) or testosterone-based GAHT (T-GAHT), compared with TGD patients not using GAHT (non-GAHT). This retrospective cohort study of TGD adults aged 18 to 65 years used insurance data from the Merative MarketScan Commercial Database (MarketScan) from January 1, 2009, to December 31, 2019. The main outcome was IR (IR with 95% confidence intervals [CIs]) of all-cause fracture after up to 5 years of follow-up. The IR ratio was estimated by comparing E-GAHT and T-GAHT groups with the non-GAHT group. Cox proportional hazards regression models estimated the hazard ratio (HR) of fracture after adjusting for age, comorbidity status using Charlson Comorbidity Index (CCI), recent fractures, and study start year. Nine thousand six hundred ninety-six TGD adults (E-GAHT [n = 1,131]; T-GAHT [n = 1,046]; non-GAHT [n = 7,519]) were identified using clinical and enrollment criteria. No differences in age (mean age [SD], 33.4 [13.2] years, 30.8 [11.7] years, and 33.2 [13.6] years, respectively) and CCI (percent with CCI = 0 [%CCI = 3+]; 86.7% [2.2%], 84.9% [1.4%], and 85.3% [1.9%]) were observed by group. The fracture IR was 13.9 (95% CI, 9.1 to 18.8) for E-GAHT, 15.3 (95% CI, 10.1 to 20.4) for T-GAHT, and 19.2 (95% CI, 16.9 to 21.4) for non-GAHT. Compared with non-GAHT, the crude IR ratio and fully adjusted HR was 0.73 (95% CI, 0.51 to 1.04) and 0.71 (95% CI, 0.49 to 1.02), respectively, for E-GAHT and 0.80 (95% CI, 0.56 to 1.14) and 0.78 (95% CI, 0.55 to 1.12), respectively, for T-GAHT. Based on United States commercial claims data, the use of GAHT was not associated with 5-year all-cause fracture IR. III.

Improved Overall Survival with Checkpoint Inhibition and Allogeneic Transplantation in Relapsed Hodgkin Lymphoma.

Patients with relapsed classic Hodgkin lymphomas receive salvage therapy with immune checkpoint inhibitors (ICI) or chemotherapy (no-ICI). Patients responding to therapy often undergo consolidation with allogeneic blood or marrow transplantations (alloBMT). We previously reported that relapsed cHL patients treated with ICI followed by alloBMT experienced improved 3-year progression-free survival (PFS) compared to patients treated with salvage chemotherapy without ICI, followed by alloBMT. In this retrospective analysis, we report the 5-year OS, PFS, and GVHD incidence in cHL patients treated with ICI before alloBMT with post-transplantation cyclophosphamide (PTCy) GVHD prophylaxis. Among the 147 relapsed/refractory patients with cHL, 71 (48.3%) received ICIs and 76 (51.7%) received chemotherapy without ICIs (no-ICI) before alloBMT. We observed an improved 5-year estimated OS of 91% (ICI) versus 66% (no-ICI), (hazard ratio [HR], 0.39; 95% confidence interval [CI], 0.16 to 0.98; P = 0.046) and a 5-year estimated PFS of 84% (ICI) versus 53% (no-ICI) (HR, 0.4; 95% CI, 0.2 to 0.81; P = 0.011). The 12-month cumulative incidence of grade III-IV GVHD was 20% (ICI) and 7% (no-ICI) (SDHR 3.16; 95% CI, 1.13 to 8.81 p = 0.03. More frequent grade III-IV acute GVHD was likely due to the higher incidence of grade III-IV acute GVHD in the subset of patients with pre-transplant exposure to ICI and shortened duration (60 days) of immunosuppression versus patients with long immunosuppression (day 180). These data suggest that cHL patients treated with ICI and alloBMT experience improved OS and the GVHD risk can be mitigated by immunosuppression until day 180.

Safety of Calcium Channel Blockers in Patients With Severe Aortic Stenosis and Hypertension.

There is a paucity of data on safety of calcium channel blockers (CCB) in patients with severe aortic stenosis (AS) and hypertension. Among 2,460 patients with severe AS and hypertension receiving antihypertensive therapy in the CURRENT AS registry-2, we compared the clinical outcomes between patients taking antihypertensive therapy with CCB (CCB group) and without CCB (no CCB group). In the entire study population, CCB was prescribed in 1,763 patients (71.7%), which was the most commonly prescribed antihypertensive agents. The prescription rates of angiotensin converting enzyme inhibitors or angiotensin receptor blockers, beta-blockers, and thiazides were 61.9%, 25.6%, and 7.3% in the CCB group, and 75.8%, 54.4%, and 6.0% in the no CCB group. In the propensity score matched cohort, the cumulative 3-year incidence of all-cause death or hospitalization for heart failure was not different between the CCB and no CCB groups (38.3% vs. 38.7%, log-rank P=0.65; HR, 0.94; 95%CI, 0.77-1.15; P=0.56). The cumulative 3-year incidence of syncope was low regardless of CCB prescription (1.1% vs. 1.0%, P=0.74). Among patients with severe AS and hypertension, CCB was the most commonly prescribed antihypertensive agents, and antihypertensive therapy with CCB was associated with comparable clinical outcomes to antihypertensive therapy without CCB. Syncope was rarely seen in patients with severe AS and hypertension receiving antihypertensive therapy regardless of CCB prescription.

10-Year Risk of Gallstones in Congenital Red Blood Cell Disorder Patients: A Nationwide Cohort Study.

Chronic hemolysis potentially elevates the risk of gallstones in several types of congenital red blood cell (RBC) disorders. However, the magnitude of the risk is unknown. We investigate the risk of gallstone disease in congenital RBC disorder patients, compared with general population comparators. Patients were identified from the Danish National Patient Registry covering all Danish hospitals and the National Reference Laboratory for RBC disorders during 1980-2016. Patients were matched by sex, age, and region of origin with up to 50 general population comparators. Gallstone events were identified using hospital-registered diagnoses and surgery codes. Our study included 9354 congenital RBC disorder patients, grouped according to type of congenital RBC disorder, and 416 994 general population comparators. The cumulative 10-year incidence of gallstone disease was 4.2% in patients with congenital RBC disorders and 1.7% among comparators. Adjusted csHR's [95% confidence interval] were 8.1 [6.8, 9.7] for hereditary spherocytosis; 3.3 [1.6, 6.8] for glucose-6-phosphate dehydrogenase deficiency; 21.6 [10.6, 44.1] for pyruvate kinase deficiency; 3.7 [1.9, 7.0] for sickle cell disease; 0.8 [0.4, 1.6] for sickle cell trait; 1.5 [1.1, 2.2] for α-thalassemia trait; 1.8 [1.4, 2.3] for β-thalassemia minor; and 2.1 [1.8, 2.6] for other congenital hemolysis. We found a markedly higher risk of hospital-registered gallstone diseases in nearly all groups of patients with congenital RBC disorders compared with the general population.

Wound formation in patients with Rutherford category IV disease after endovascular therapy: rates and risk factors

BackgroundLower limb peripheral artery disease classified as Rutherford category IV, is characterized by lower limb ischemic pain both during exertion and at rest. This disease has an unclear course. We aimed to evaluate outcome predictors in this patient group after endovascular therapy. This single-center, retrospective, observational study included 234 consecutive patients (264 limbs), between April 2007 and December 2020. We investigated the disease clinical course after endovascular therapy. The primary endpoint was the wound formation rate 3 years after endovascular therapy.ResultsThe mean observation period was 48.2 ± 8.9 months. The patients (61.9% male; mean age, 76 ± 10 years) presented with diabetes (64.1%), and received hemodialysis with chronic kidney disease (35.0%) and ambulatory treatment (85.0%). The average ankle-brachial index before endovascular therapy was 0.69 ± 0.23. Skin perfusion pressure on the dorsal and plantar sides was 38 ± 13 mmHg and 36 ± 12 mmHg, respectively. The wound incidence rates at 1, 2, and 3 years after endovascular therapy were 8.3%, 11.4%, and 14.4%, respectively. Multivariate analysis revealed the following factors associated with wound formation: P2 in inframalleolar/pedal disease category in the Global Limb Anatomical Staging System (hazard ratio: 1.73, 95% confidence interval: 1.22–2.83, P = 0.01), non-ambulatory status (hazard ratio: 1.09, 95% confidence interval: 1.11–1.36, P = 0.02), intervention up to infrapopliteal lesion (hazard ratio: 1.55, 95% confidence interval: 1.17–2.46, P = 0.03), and patient with chronic kidney disease on hemodialysis (hazard ratio: 1.61, 95% confidence interval: 1.32–2.18, P = 0.03).ConclusionsThe 3-year incidence of wound onset in this study was 14.4%. Factors associated with this outcome included P2 in the Global Limb Anatomical Staging System, non-ambulatory status, intervention up to infrapopliteal lesion, and patient with chronic kidney disease on hemodialysis.

Cardiovascular health and economic outcomes under improved air quality in China: a modelling study

IntroductionChina faces the dual challenge of high air pollution and an increasing burden of cardiovascular disease (CVD). We aimed to estimate the healthcare costs associated with CVD and the quality-adjusted...