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    Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

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    Background: Regular, detailed reporting on population health by underlying cause of death is fundamental for public health decision making. Cause-specific estimates of mortality and the subsequent effects on life expectancy worldwide are valuable metrics to gauge progress in reducing mortality rates. These estimates are particularly important following large-scale mortality spikes, such as the COVID-19 pandemic. When systematically analysed, mortality rates and life expectancy allow comparisons of the consequences of causes of death globally and over time, providing a nuanced understanding of the effect of these causes on global populations. Methods: The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 cause-of-death analysis estimated mortality and years of life lost (YLLs) from 288 causes of death by age-sex-location-year in 204 countries and territories and 811 subnational locations for each year from 1990 until 2021. The analysis used 56 604 data sources, including data from vital registration and verbal autopsy as well as surveys, censuses, surveillance systems, and cancer registries, among others. As with previous GBD rounds, cause-specific death rates for most causes were estimated using the Cause of Death Ensemble model—a modelling tool developed for GBD to assess the out-of-sample predictive validity of different statistical models and covariate permutations and combine those results to produce cause-specific mortality estimates—with alternative strategies adapted to model causes with insufficient data, substantial changes in reporting over the study period, or unusual epidemiology. YLLs were computed as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 1000-draw distribution for each metric. We decomposed life expectancy by cause of death, location, and year to show cause-specific effects on life expectancy from 1990 to 2021. We also used the coefficient of variation and the fraction of population affected by 90% of deaths to highlight concentrations of mortality. Findings are reported in counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2021 include the expansion of under-5-years age group to include four new age groups, enhanced methods to account for stochastic variation of sparse data, and the inclusion of COVID-19 and other pandemic-related mortality—which includes excess mortality associated with the pandemic, excluding COVID-19, lower respiratory infections, measles, malaria, and pertussis. For this analysis, 199 new country-years of vital registration cause-of-death data, 5 country-years of surveillance data, 21 country-years of verbal autopsy data, and 94 country-years of other data types were added to those used in previous GBD rounds. Findings: The leading causes of age-standardised deaths globally were the same in 2019 as they were in 1990; in descending order, these were, ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and lower respiratory infections. In 2021, however, COVID-19 replaced stroke as the second-leading age-standardised cause of death, with 94·0 deaths (95% UI 89·2–100·0) per 100 000 population. The COVID-19 pandemic shifted the rankings of the leading five causes, lowering stroke to the third-leading and chronic obstructive pulmonary disease to the fourth-leading position. In 2021, the highest age-standardised death rates from COVID-19 occurred in sub-Saharan Africa (271·0 deaths [250·1–290·7] per 100 000 population) and Latin America and the Caribbean (195·4 deaths [182·1–211·4] per 100 000 population). The lowest age-standardised death rates from COVID-19 were in the high-income super-region (48·1 deaths [47·4–48·8] per 100 000 population) and southeast Asia, east Asia, and Oceania (23·2 deaths [16·3–37·2] per 100 000 population). Globally, life expectancy steadily improved between 1990 and 2019 for 18 of the 22 investigated causes. Decomposition of global and regional life expectancy showed the positive effect that reductions in deaths from enteric infections, lower respiratory infections, stroke, and neonatal deaths, among others have contributed to improved survival over the study period. However, a net reduction of 1·6 years occurred in global life expectancy between 2019 and 2021, primarily due to increased death rates from COVID-19 and other pandemic-related mortality. Life expectancy was highly variable between super-regions over the study period, with southeast Asia, east Asia, and Oceania gaining 8·3 years (6·7–9·9) overall, while having the smallest reduction in life expectancy due to COVID-19 (0·4 years). The largest reduction in life expectancy due to COVID-19 occurred in Latin America and the Caribbean (3·6 years). Additionally, 53 of the 288 causes of death were highly concentrated in locations with less than 50% of the global population as of 2021, and these causes of death became progressively more concentrated since 1990, when only 44 causes showed this pattern. The concentration phenomenon is discussed heuristically with respect to enteric and lower respiratory infections, malaria, HIV/AIDS, neonatal disorders, tuberculosis, and measles. Interpretation: Long-standing gains in life expectancy and reductions in many of the leading causes of death have been disrupted by the COVID-19 pandemic, the adverse effects of which were spread unevenly among populations. Despite the pandemic, there has been continued progress in combatting several notable causes of death, leading to improved global life expectancy over the study period. Each of the seven GBD super-regions showed an overall improvement from 1990 and 2021, obscuring the negative effect in the years of the pandemic. Additionally, our findings regarding regional variation in causes of death driving increases in life expectancy hold clear policy utility. Analyses of shifting mortality trends reveal that several causes, once widespread globally, are now increasingly concentrated geographically. These changes in mortality concentration, alongside further investigation of changing risks, interventions, and relevant policy, present an important opportunity to deepen our understanding of mortality-reduction strategies. Examining patterns in mortality concentration might reveal areas where successful public health interventions have been implemented. Translating these successes to locations where certain causes of death remain entrenched can inform policies that work to improve life expectancy for people everywhere. Funding: Bill & Melinda Gates Foundation

    Feasibility of Gamma Knife Radiosurgery for Brain Arteriovenous Malformations According to Nidus Type

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    Objective: Gamma Knife radiosurgery (GKRS) is an effective and noninvasive treatment for high-risk arteriovenous malformations (AVMs). Since differences in GKRS outcomes by nidus type are unknown, this study evaluated GKRS feasibility and safety in patients with brain AVMs. Methods: This single-center retrospective study included patients with AVM who underwent GKRS between 2008 and 2021. Patients were divided into compact-and diffuse-type groups according to nidus characteristics. We excluded patients who performed GKRS and did not follow-up evaluation with magnetic resonance imaging or digital subtraction angiography within 36 months from the study. We used univariate and multivariate analyses to characterize associations of nidus type with obliteration rate and GKRS-related complications. Results: We enrolled 154 patients (mean age, 32.14±17.17 years; mean post-GKRS follow-up, 52.10±33.67 months) of whom 131 (85.1%) had compact-and 23 (14.9%) diffuse-type nidus AVMs. Of all AVMs, 89 (57.8%) were unruptured, and 65 (42.2%) had ruptured. The mean Spetzler-Martin AVM grades were 2.03±0.95 and 3.39±1.23 for the compact-and diffuse-type groups, respectively (p<0.001). During the follow-up period, AVM-related hemorrhages occurred in four individuals (2.6%), three of whom had compact nidi. Substantial radiation-induced changes and cyst formation were observed in 21 (13.6%) and one patient (0.6%), respectively. The AVM complete obliteration rate was 46.1% across both groups. Post-GKRS complication and complete obliteration rates were not significantly different between nidus types. For diffuse-type nidus AVMs, larger AVM size and volume (p<0.001), lower radiation dose (p<0.001), eloquent area location (p=0.015), and higher Spetzler-Martin grade (p<0.001) were observed. Conclusion: GKRS is a safe and feasible treatment for brain AVMs characterized by both diffuse-and compact-type nidi

    Widespread Use of Imaging-Guided PCI in Asia: Time for Extended Application

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    In recent years, a wealth of clinical data has emerged regarding intravascular imaging involving either intravascular ultrasound or optical coherence tomography. This surge in data has propelled the adoption of intravascular imaging–guided percutaneous coronary intervention (PCI) in daily clinical practice. The findings of current randomized clinical trials regarding imaging guidance have lent strong support to the benefits of intravascular imaging–guided PCI. This holds especially true for the diagnosis and treatment of complex lesions, such as left main disease, diffuse long lesions, chronic total occlusion, severely calcified lesions, bifurcations, and in-stent restenosis, as well as in high-risk patients such as those with acute myocardial infarction or chronic kidney disease. During intravascular imaging–guided PCI, operators attempt to achieve stent optimization for maximized benefits of imaging guidance. This paper provides a comprehensive review on the updated clinical data of intravascular imaging–guided PCI and intravascular ultrasound/optical coherence tomography–derived stent optimization criteria

    Lymphadenectomy in clinically early epithelial ovarian cancer and survival analysis (LILAC): a Gynecologic Oncology Research Investigators Collaboration (GORILLA-3002) retrospective study

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    Objective: This study aimed to evaluate the therapeutic role of lymphadenectomy in patients surgically treated for clinically early-stage epithelial ovarian cancer (EOC). Methods: This retrospective, multicenter study included patients with clinically early-stage EOC based on preoperative abdominal-pelvic computed tomography or magnetic resonance imaging findings between 2007 and 2021. Oncologic outcomes and perioperative complications were compared between the lymphadenectomy and non-lymphadenectomy groups. Independent prognostic factors were determined using Cox regression analysis. Disease-free survival (DFS) was the primary outcome. Overall survival (OS) and perioperative outcomes were the secondary outcomes. Results: In total, 586 patients (lymphadenectomy group, n=453 [77.3%]; non-lymphadenectomy groups, n=133 [22.7%]) were eligible. After surgical staging, upstaging was identified based on the presence of lymph node metastasis in 14 (3.1%) of 453 patients. No significant difference was found in the 5-year DFS (88.9% vs. 83.4%, p=0.203) and 5-year OS (97.2% vs. 97.7%, p=0.895) between the two groups. Using multivariable analysis, lymphadenectomy was not significantly associated with DFS or OS. However, using subgroup analysis, the lymphadenectomy group with serous histology had higher 5-year DFS rates than did the non-lymphadenectomy group (86.5% vs. 74.4%, p=0.048; adjusted hazard ratio=0.281; 95% confidence interval=0.107–0.735; p=0.010). The lymphadenectomy group had longer operating time (p<0.001), higher estimated blood loss (p<0.001), and higher perioperative complication rate (p=0.004) than did the non-lymphadenectomy group. Conclusion: In patients with clinically early-stage EOC with serous histology, lymphadenectomy was associated with survival benefits. Considering its potential harm,lymphadenectomy should be performed according to histologic subtype and subsequent chemotherapy in patients with clinically early-stage EOC

    The Association of Smoking Status with Diabetic Microvascular Complications in Korean Patients with Type 2 Diabetes

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    Purpose: Few studies have investigated the association between smoking and microvascular complications in the Asian population with type 2 diabetes mellitus (T2DM). We aimed to investigate the relationship between smoking status and microvascular complications in Korean patients with T2DM. Materials and Methods: From the Korean National Diabetes Program cohort, we included 2316 Korean male with T2DM who had baseline clinical information available, including their smoking status, and underwent diabetic complication studies. Results: Compared to non-smokers, current smokers had higher odds of any-microvascular complications [adjusted odds ratio (aOR) 1.45, 95% confidence interval (CI) 1.07–1.97, p=0.016]. The odds of neuropathy were significantly higher; however, the odds of retinopathy were significantly lower in current smokers than in nonsmokers (all p<0.05). Among those who underwent repeated complication tests after 3 years, the risk of newly developed retinopathy was significantly increased in ex-smokers [aOR 3.77 (95% CI 1.61–8.87), p=0.002]. Within ex-smokers, long smoking duration and smoking cessation within the recent 5 years were associated with an increased risk of newly developed retinopathy (all p<0.05). Conclusion: Male smokers had higher odds of having overall diabetic microvascular complications, including neuropathy. However, the odds of having retinopathy were significantly lower among current smokers. More attention and research are needed regarding the increased risk of retinopathy development in ex-smokers who have recently stopped smoking after a long history of smoking

    Prognostic value of nutrition and immune-related biomarkers in patients with locally advanced rectal cancer treated with chemoradiotherapy

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    The ability of nutrition and immune-related biomarkers to predict outcomes in patients with locally advanced rectal cancer (LARC) treated with neoadjuvant therapy followed by surgery remains controversial due to the lack of evidence regarding the accuracy and reliability of these biomarkers in predicting outcomes for such patients. Therefore, the present study aimed to investigate the prognostic potential of nutrition and immune-related biomarkers in patients with LARC who underwent chemoradiotherapy followed by curative surgery. The clinical data of patients with LARC treated with neoadjuvant therapy followed by surgery between January 2010 and December 2019 were analyzed. In total, 214 consecutive patients were enrolled into the present study, who were then categorized into low and high prognostic nutritional index (PNI) groups. The X-tile 3.6.1 program was used to calculate and then determine the optimal cut-off values for PNI. Disease-free survival (DFS) and overall survival (OS) were compared between the low and high PNI groups. Cox regression analysis demonstrated that low PNI and high post-chemoradiotherapy carcinoembryonic antigen levels were significantly associated with reduced disease-free survival and overall survival. Specifically, a low PNI was associated with inferior 5-year DFS (P=0.025) and OS (P=0.018). These findings suggest that amongst the nutritional and immune-related biomarkers, PNI is a significant predictive factor for disease recurrence and mortality in patients with LARC treated with neoadjuvant therapy followed by surgery

    Safety, effectiveness, and usefulness of higher-dose tablets of generic pirfenidone in patients with IPF: a nationwide observational study in South Korea

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    Background: Pirfenidone is an antifibrotic medication approved for idiopathic pulmonary fibrosis (IPF). Fybro®, a generic version of pirfenidone developed in South Korea, gained approval and is available in 200 mg and in higher-dose formulations of 400 and 600 mg. This real-world prospective cohort study investigated the safety and effectiveness of Fybro®. Methods: A nationwide observational study was conducted in patients with IPF. Patients were followed up for 6 months, with a subset of patients being followed up for 12 months. Data on lung function and adverse events were collected. Patient adherence to fewer-pill (400 and/or 600 mg tablets) and multiple-pill (200 mg tablets) regimens were compared. Results: Of the 359 enrolled patients, 352 received pirfenidone (Fybro®) at least once and were included in the analysis. The mean age was 69.0 years and 82.4% of patients were male. The median treatment duration was 186.0 days. A total of 253 patients (71.9%) experienced adverse events, with decreased appetite being the most common (16.5%). The adjusted decline rates in lung function were −1.5% and −2.2% predicted per year for forced vital capacity and diffusing capacity, respectively. No significant differences were observed based on the pirfenidone dose. For a daily intake of 1,200 or 1800 mg of pirfenidone, a significantly longer duration of drug administration was observed with the fewer-pill regimen than with multiple-pill regimen. Conclusion: The safety and effectiveness of Fybro® observed in this real-world cohort study are consistent with previous studies. Using higher-strength tablets to reduce pill burden may improve medication adherence

    Deep learning-based fully automatic Risser stage assessment model using abdominal radiographs

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    Background: Artificial intelligence has been increasingly used in medical imaging and has demonstrated expert level performance in image classification tasks. Objective: To develop a fully automatic approach for determining the Risser stage using deep learning on abdominal radiographs. Materials and methods: In this multicenter study, 1,681 supine abdominal radiographs (age range, 9–18 years, 50% female) obtained between January 2019 and April 2022 were collected retrospectively from three medical institutions and graded manually using the United States Risser staging system. A total of 1,577 images from Hospitals 1 and 2 were used for development, and 104 images from Hospital 3 for external validation. From each radiograph, right and left iliac crest patch images were extracted using the pelvic bone segmentation model DeepLabv3 + with the EfficientNet-B0 encoder trained with 90 digitally reconstructed radiographs from pelvic computed tomography scans with a pelvic bone mask. Using these patch images, ConvNeXt-B was trained to grade according to the Risser classification. The model’s performance was evaluated using accuracy, area under the receiver operating characteristic curve (AUROC), and mean absolute error. Results: The fully automatic Risser stage assessment model showed an accuracy of 0.87 and 0.75, mean absolute error of 0.13 and 0.26, and AUROC of 0.99 and 0.95 on internal and external test sets, respectively. Conclusion: We developed a deep learning-based, fully automatic segmentation and classification model for Risser stage assessment using abdominal radiographs. Graphical Abstract: (Figure presented.

    Do Balloon Catheters have a Different Radial Force Along Their Longitudinal Axis?

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    Purpose: This experimental study was designed to compare radial forces between the central portion and both ends of balloon catheters when dilating stenosis. Materials and Methods: Three balloon catheters of 6 and 8 mm in diameter and of variable length were tested: Mustang, Conquest, and Genoss PTA. Cylindrical modules to position balloon catheters and install the measuring tip during radial force measurements were made using a 3D printer. The measuring tip created 20% stenosis at the inner lumen. Both ends and center of the balloon catheter were located at the measuring tip. The radial force was measured after inflating the balloon catheter to the rated burst pressure. Results: For the different diameters and lengths of balloon catheters and cylinder sizes, the median inccenter, the radial rease in radial force at the distal end compared to the center was 16.5% (range: 9.8–35.2%) for Mustang, 12.4% (range: 10.3–25.5%) for Genoss, and 7.4% (range: −0.3–13.1%) for Conquest balloon catheters. Similarly, compared to that at the force at the proximal end was 10.8% greater (range: −2.9–18.3%) for Mustang, 9.9% greater (range: 3.9–22.3%) for Genoss, and 7.3% greater (range: −1.3–12.4%) for Conquest catheters. Conclusion: The radial force is greater at both ends of the balloon than at the central portion, especially at the distal end. Dilation using the distal end of the balloon catheter is a practical method that can be applied in clinical practice without additional devices when encountering resistant stenosis, especially with semi-compliant balloons. Graphical Abstract: (Figure presented.

    Rapid identification and management of stress-induced cardiomyopathy using POCUS after strangulation: A case report

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    RATIONALE: Stress-induced cardiomyopathy (SCMP), also known as Takotsubo syndrome, is a transient cardiac condition often precipitated by severe emotional or physical stress. It is commonly mistaken for acute coronary syndrome due to similar clinical presentations. The use of point-of-care ultrasound (POCUS) provides a noninvasive, rapid diagnostic alternative that can potentially reduce the need for invasive coronary angiography, especially in emergency settings. PATIENT CONCERNS: A 26-year-old woman with type 1 diabetes presented to the emergency department following a suicidal hanging attempt. Upon arrival, she was conscious but confused, with stable vital signs. There were visible signs of strangulation, but no other immediate physical abnormalities. Laboratory tests revealed elevated cardiac enzymes and hyperglycemia. DIAGNOSES: Initial bedside POCUS revealed a reduced ejection fraction and regional wall motion abnormalities in the midportion of the left ventricle, suggesting SCMP. These findings, combined with the patient's history and absence of other contributory factors, led to a provisional diagnosis of SCMP. INTERVENTIONS: The patient was admitted to the intensive care unit for close monitoring. Serial POCUS examinations were performed to track cardiac function. Due to the rapid improvement in regional wall motion abnormalities observed through POCUS, the planned coronary angiography was deferred. OUTCOMES: The patient exhibited significant clinical improvement within 24 hours, with normalization of cardiac function as demonstrated by follow-up POCUS. Cardiac enzyme levels also returned to normal. The patient was discharged directly from the intensive care unit without the need for further invasive procedures. LESSONS: This case underscores the diagnostic value of POCUS in rapidly identifying SCMP in emergency settings, which can guide timely and appropriate management. The noninvasive nature of POCUS may reduce the need for invasive diagnostics, minimize hospital stay duration, and enhance cost-effectiveness in managing SCMP

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