5-year Incidence Research Articles

Suspected Fatal Arrhythmic Events in Japanese Patients With Coronary Artery Disease - From the CREDO-Kyoto PCI/CABG Registries Cohorts-2 and -3.

Fatal arrhythmic events (FAEs), such as sudden cardiac death (SCD) and fatal ventricular arrhythmias, are a devastating complication in patients with coronary artery disease (CAD). Therefore, in this study we aimed to assess the incidence of FAEs in more recent Japanese patients with CAD and to examine whether risk stratification of FAEs can still be feasible using the left ventricular ejection fraction (LVEF). In the CREDO Kyoto PCI/CABG registry cohorts-2 and -3, there were 25,843 patients with LVEF data who received a first coronary revascularization (LVEF ≤35% group: N=1,671, 35%<LVEF≤40% group: N=1,075, 40%<LVEF≤45% group: N=1,594, and LVEF >45%: N=21,503). FAEs were defined as a composite of SCD or hospitalization for serious ventricular arrhythmias. The cumulative 5-year incidence of FAEs was 2.4% and it increased with decreasing LVEF (LVEF ≤35%: 8.84%, 35%<LVEF≤40%: 6.99%, 40%<LVEF≤45%: 4.49%, and LVEF >45%: 1.67%, log-rank P<0.0001). The adjusted risk of FAEs also increased with decreasing LVEF. LVEF is still a strong independent factor for predicting FAEs in patients with CAD in the PCI era. There was no obvious decrease in the incidence of FAEs between the 2 cohorts. The risk factors for FAEs through the 2 cohorts, other than low LVEF, included age ≥75 years, diabetes, heart failure, hemodialysis, atrial fibrillation, and anemia.

Proximal junctional disease 5 years after surgery for L4 degenerative spondylolisthesis: comparing PLIF versus minimally invasive decompression.

This study aimed to compare the incidence of radiological adjacent segment disease (R-ASD) at L3/4 between patients with L4/5 degenerative spondylolisthesis (DS) who underwent L4/5 posterior lumbar interbody fusion (PLIF) and those who underwent microscopic bilateral decompression via a unilateral approach (MBDU) at L4/5. Our ultimate goal was to distinguish the course of natural lumbar degeneration from fusion-related degeneration while eliminating L4/5 decompression as a confounder. Ninety patients with L4/5 DS who underwent L4/5 PLIF (n = 53) or MBDU (n = 37) and were followed for at least 5 years were retrospectively analyzed. Various radiographic parameters at L3/4 and L4/5 were measured before surgery and at last follow-up. Progression of facet degeneration was measured on computed tomography (Japanese Orthopaedic Association [JOA] classification); disc degeneration and spinal stenosis were measured on magnetic resonance imaging (Pfirrmann and Imagama classifications, respectively). R-ASD on plain radiography (X-ASD) was defined as reported by Okuda et al. [1]. R-ASD on CT or MRI (C/M-ASD) was defined as at least a one-grade progression in the relevant classification. JOA score for low back pain and incidence of reoperation were also evaluated. The mean parameters at L3/4 in the PLIF group were as follows (before surgery/at last follow-up): (1) % slip: 0.8%/1.9%, (2) change in slip: 0.7/0.4mm, (3) segmental lordosis: 11.9°/12.1°, (4) disc arc: 7.7°/7.5°, and (5) disc height: 8.6/7.7mm. Corresponding data in the MBDU group was: (1) % slip: 1.8%/2.4%, (2) change in slip: 0.6/0.5mm, (3) segmental lordosis: 9.6°/10.8°, (4) disc arc: 7.7°/8.7°, and (5) disc height: 7.8/6.5mm. Disc height at last follow-up significantly differed between the groups (p = 0.002). Progression of facet degeneration was detected in 55.1% of PLIF patients and 77.8% of MBDU patients. Progression of disc degeneration and spinal stenosis was observed in 45.2% and 36.8% of PLIF patients, respectively, and 58.9% and 36.0% of MBDU patients, respectively. Overall, the incidence of X-ASD was 17.0% in the PLIF group and 16.2% in the MBDU group. Among the patients who underwent plain radiography plus CT or MRI, the total incidence of R-ASD was 70.6% in the PLIF group and 60.0% in the MBDU group. The above rates did not significantly differ between the groups. The mean improvement rate in the JOA score for low back pain was 52.8% in the PLIF group and 52.1% in the MBDU group (p = 0.867). The incidence of revision surgery at L3/4 was 1.9% in the PLIF group and 5.4% in the MBDU group (p = 0.62). The 5-year incidence of R-ASD at L3/4 after PLIF and MBDU in patients undergoing surgery for L4/5 DS is similar, indicating that naturally occurring lumbar degeneration is probably responsible, not fusion.

Highly hypofractionated biaxially rotational dynamic radiation therapy (BROAD-RT) for high-risk prostate cancer.

To report clinical outcomes following highly hypofractionated biaxially rotational dynamic radiation therapy (BROAD-RT), a unique radiation therapy method that facilitates non-coplanar volumetric-modulated arc therapy (VMAT) without the need to rotate the couch or reposition the patient, for high-risk prostate cancer (PCa) with simultaneous integrated boost (SIB) for intra-prostatic dominant lesions (IPDLs), we performed a single-center prospective pilot study. In this study, patients with high-risk PCa according to the D'Amico classification or those with cT3aN0M0 PCa were eligible. VMAT was performed using BROAD-RT, and a dose of 54 Gy in 15 fractions was prescribed for the prostate in combination with SIB for IPDLs at a dose of 57 Gy in 15 fractions. Short-term neoadjuvant androgen-deprivation therapy (median: 6.9 months) was conducted. Neither adjuvant androgen-deprivation therapy nor fiducial marker implantation to the prostate was applied for any patient. In total, 26 patients were registered in this study between August 2018 and November 2020. Their median age was 73 years at the initiation of RT. The median follow-up period was 49.7 months. The 4-year cumulative incidence rates of grade 2 late GU and GI toxicities were 15.4 and 3.8%, respectively. No grade 3 or higher acute or late toxicities were observed. The 4-year biochemical failure-free survival rates were 87.7%. In conclusion, highly hypofractionated RT using BROAD-RT for high-risk PCa with SIB for IPDLs was feasible and facilitated favorable oncological outcomes. Therefore, this approach is considered a promising method to achieve safe dose escalation and shorten the treatment duration.

Comparative Outcomes of Left Main and Non-Left Main Percutaneous Coronary Intervention from the Excellence in Coronary Artery Disease (XLCAD) Registry.

There are limited comparative data on real-world outcomes of patients undergoing percutaneous coronary intervention (PCI) of the left main (LM) and non-LM coronary arteries. 873 consecutive patients undergoing LM PCI (n=256) and non-LM PCI (n=617) were enrolled between September 2019-March 2023 in the Excellence in Coronary Artery Disease (XLCAD) Registry. Primary outcome was 1-year incidence of major adverse cardiovascular events (MACE), a composite of all-cause death, non-fatal myocardial infarction, clinically driven repeat revascularization and ischemic stroke. The secondary outcome was periprocedural (≤30 days) events. Study cohort included 68% men, mean age 71.9 ± 10.3 in LM and 67.2 ± 11.1 years in non-LM PCI groups (p<0.001). LM PCI patients had significantly greater co-morbidities (diabetes mellitus, hyperlipidemia, prior stroke, prior myocardial infarction, prior coronary revascularization, peripheral artery disease, chronic lung and kidney disease and heart failure) compared with non-LM. Acute coronary syndrome indication was the most prevalent (69%). Mechanical circulatory support was employed in 3.1% LM vs 1% non-LM PCI patients (p=0.026). Mean number of lesions treated were 2.2 ± 1.0 in LM and 1.4 ± 0.6 in non-LM PCI groups (p<0.001). Multivessel PCI was performed in 68.8% LM and 21% non-LM PCI patients (p<0.001). Overall, drug-eluting stent use (96.7%), bifurcation PCI (24.7%) and atherectomy (2.4%) were similar across groups. Technical and procedural success rates were high across groups, however significantly higher in non-LM group. Periprocedural (≤30 days post-procedure) events included mortality in 3.5% LM and 1.5% non-LM PCI (p=0.334) and MACE 4.7% LM vs 2.4% non-LM PCI (p=0.080) groups. One-year MACE was significantly higher in LM vs. non-LM PCI (12.9% vs. 8.4%, respectively; p=0.043), driven mainly by higher repeat percutaneous revascularization in LM group (12.1% vs 6.2%; p=0.003). Mortality at 1-year in LM vs non-LM PCI were 10.2% vs 5.8% (p=0.074). In a real-world experience, LM PCI is performed in patients with significantly greater comorbidities compared with non-LM PCI, with high procedural success. Thirty-day mortality and 1-year MACE are significantly higher in LM group.

Increased Non-Relapse Mortality in Older People With Allogeneic Hematopoietic Stem Cell Transplantation Using Fludarabine and Myeloablative Dose of Busulfan-Based Regimen.

Fludarabine and myeloablative busulfan (FluBu4) in allogeneic hematopoietic stem cell transplantation (HSCT) for older people have not been adequately examined. This retrospective study analyzed data from a large-scale, nationwide database in Japan. Adult patients (> 15 years old, y/o) who received their first HSCT with FluBu4 for hematological malignancies were included. They were categorized into the younger (< 60 y/o, N = 1295) and the older group (≥ 60 y/o, N = 993). The 3-year overall survival (OS) rate after HSCT was significantly worse in the older group than in the other (p < 0.01, 39.9% vs. 48.5%). The 3-year non-relapse mortality (NRM) was significantly higher in the older group than in the other (p < 0.01, 30.9% vs. 23.0%), and the 3-year cumulative incidence of relapse was comparable between them. According to the multivariate analysis, age ≥ 60 years was significantly associated with poor OS and high NRM. In a subgroup analysis of the older group, the use of additional chemotherapeutic drugs to FluBu4 was significantly associated with poor OS and high NRM. Total body irradiation was significantly associated with high NRM and 1-year incidence of sinusoidal obstruction syndrome but not with OS. Thus, FluBu4 should be used with caution in older people.

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.

Prevalence and incidence of sarcopenia in Swiss postmenopausal women: findings from the OsteoLaus Cohort

STUDY AIMS: Sarcopenia is a progressive, age-related loss of muscle mass, strength and function. Given the ageing population and the adverse outcomes associated with sarcopenia, monitoring its epidemiology is particularly important. This study aimed to describe sarcopenia prevalence, 5-year incidence and agreement between definitions using the latest operational criteria in Swiss postmenopausal women. METHODS: Postmenopausal women from the last 5 years of the CoLaus/OsteoLaus prospective population-based cohort were included based on complete case analysis (April 2015 to October 2022; Lausanne, Switzerland). We assessed appendicular lean mass via Dual X-ray Absorptiometry (GE Lunar iDXA), handgrip strength using a Jamar Dynamometer and 6-metre gait speed at multiple visits. Sarcopenia was defined based on handgrip strength and/or appendicular lean mass and/or gait speed using 11 definitions, including that from the European Working Group on Sarcopenia in Older People (EWGSOPII, 2019). Prevalence was measured as the number and rate of sarcopenic cases at the last visit, while incidence was measured as the number and rate of new sarcopenic cases over 2.5 or 5 years. RESULTS: A total of 930 women were included, with a mean (standard deviation) age of 72.9 (6.9) years, BMI of 25.7 (4.8) kg/m2, appendicular lean mass 16.8 (2.5) kg, handgrip strength 21.2 (5.5) kg, gait speed 1.1 (0.2) m/s. Sarcopenia prevalence based on EWGSOPII definitions ranged from 2.2% to 5.7%, while other definitions varied from 0.5% to 13.4%. The 5-year incidence rates based on EWGSOPII were 1.9% to 4.7%. Prevalence and incidence increased significantly between the lowest and highest age tertiles (Fisher’s exact test, p &lt;0.05) for most definitions. Agreement between definitions was predominantly “none” or “minimal” according to the Cohen Kappa score. CONCLUSION: This population-based cohort of postmenopausal women highlights an increase in sarcopenia prevalence and incidence beginning in the seventh decade of life, underscoring the accelerated decline in muscle health with age. The minimal agreement between the definitions highlights the need for a consensus, which would improve future research and clinical implementations.

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.

The 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). This 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. The 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 < 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 < 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. AIP 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.

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). 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. 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%). 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.

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.

Impact of White Blood Cell Count After Percutaneous Coronary Intervention on Long-Term Prognosis in Patients with Unstable Angina Pectoris: A Single-Center Retrospective Observational Cohort Study.

An association between white blood cell count (WBC-C) before percutaneous coronary intervention (PCI) and prognosis has been established in patients undergoing PCI. However, the effect of WBC-C after PCI on the long-term prognosis of patients with unstable angina pectoris (UA) is unclear. A retrospective cohort study was conducted in 1811 consecutive patients with UA. The changes of WBC and subgroup counts before and in the early postoperative stages after PCI were observed by paired Wilcoxon signed-rank test. The Kaplan-Meier method and COX proportional regression model were used to evaluate the association between the incidence of 5-year endpoint events and post-PCI leukocytosis. Leukocytosis and neutrocytosis within 24hours after PCI were observed in majority of patients with UA, while lymphocyte count significantly decreased after PCI in those patients. There were no significant differences in 5-year all-cause mortality and major adverse cardiovascular and cerebrovascular events (MACCE) between patients in the post-PCI leukocytosis and the control group. However, the 5-year incidence of major adverse cardiovascular events (MACE) was significantly increased in the post-PCI leukocytosis group (p = 0.017, Log rank test). Leukocytosis after PCI was independently associated with the occurrence of MACE (hazard ratio: 1.36; 95% confidence interval: 1.06-1.75; p = 0.015). Peripheral WBC and neutrophil counts within 24hours after PCI significantly increased in response to PCI in patients with UA, while lymphocyte count significantly decreased after PCI in those patients. The post-PCI leukocytosis offered predictive value for an increased risk of MACE for up to 5 years in patients with UA.

Trends in the incidence and mutational landscape of advanced uterine cancer.

The aim of this study was to examine disparities in 20-year incidence trends and mutations in advanced-stage uterine cancer in the United States, given poor survival rates. Data were obtained from the United States Cancer Statistics for patients from 2001 to 2019 with International Federation of Gynecology and Obstetrics 2009 stage IVA and IVB uterine cancer. SEER∗Stat 8.3.9.2 and Joinpoint Regression Program 4.9.0.0 were used to calculate cancer incidence per 100,000 women, annual percentages, and average annual percent change (AAPC). The mutational landscape of advanced uterine cancer was explored using data from the Genomic Data Commons. In United States Cancer Statistics, 75,450 patients with advanced uterine cancer were identified with an annual percentage increase of 2.63% between 2001 and 2019 and significantly higher rates in Black, Hispanic, and Asian patients compared with White patients (AAPC Black: 3.56%, AAPC Hispanic: 3.12%, and AAPC Asian 3.06% vs AAPC White: 2.07%, each p < .001). AAPC in patients with serous carcinomas increased by 6.32% in Black vs 3.91% in White patients (p < .001). Furthermore, AAPC was 3.0% for Black patients vs 0.7% for White patients with leiomyosarcoma (p < .001). In the Genomic Data Commons, TP53 mutations were more common, and PTEN was less common in Black vs White patients, older vs younger patients, advanced vs early stage, or high- vs low-risk histologic subtypes (p < .05). Mutations in BRCA1, BRCA2, POLE, and PMS2 were less common in high- vs low-risk histologic subtypes (p < .05). Advanced-stage uterine cancer rates are rising in the United States, particularly affecting Black and Hispanic women. Molecular differences exist by age, race, stage, and histology.

Risk of Cancer and Reoperation After Ileorectal Anastomosis and Ileal Pouch-Anal Anastomosis in Familial Adenomatous Polyposis.

To prevent colorectal cancer, 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 after 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 after 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%) had IPAA. Median age at IRA and IPAA was 23 and 27 years, and the 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 was 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 after IPAA. The number of postoperative endoscopic surveillance endoscopies was higher in patients with an IRA compared with those with an IPAA ( P < 0.001). Over the past 3 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.