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Background Myocardial injury is common after brain injury; however, few studies have reported serial cardiac troponin (cTn) measurements to distinguish whether the myocardial injury is acute or chronic. The fourth Universal Definition of Myocardial Infarction introduced for the first time the criteria for acute myocardial injury (AMI). We aimed to investigate the prevalence and prognostic implications of AMI in primary intracerebral hemorrhage. Methods and Results We retrospectively analyzed patients with primary intracerebral hemorrhage within 48 hours after symptom onset. All patients included had at least 2 cTn measurements: 1 obtained at the time of emergency admission and at least 1 more within the first 2 days of hospitalization. AMI was defined as an elevated cTn above the upper‐reference limit (14 ng/L) along with a rise/fall >20%. Patients were followed for up to 5 years. Outcomes included major adverse cardiac events (MACEs; a composite of vascular death, nonfatal coronary events, and nonfatal stroke) and 90‐day unfavorable outcomes (modified Rankin scale score ≥4). Cox proportional hazards models, multivariable logistic regression models, and Kaplan–Meier analyses were used to evaluate the association between AMI and outcomes. Of 600 patients included, 115 had AMI (19.2%). AMI independently conferred an increased risk for major adverse cardiac events (adjusted hazard ratio, 1.69 [95% CI, 1.12–2.53]) and 90‐day unfavorable outcomes (adjusted odds ratio, 2.15 [95% CI, 1.26–3.67]) compared with patients without AMI. Conclusions AMI is relatively common in patients with intracerebral hemorrhage and is associated with both long‐term major adverse cardiac events and 90‐day unfavorable outcomes.

Precision radiotherapy is a critical and indispensable cancer treatment means in the modern clinical workflow with the goal of achieving “quality-up and cost-down” in patient care. The challenge of this therapy lies in developing computerized clinical-assistant solutions with precision, automation, and reproducibility built-in to deliver it at scale. In this work, we provide a comprehensive yet ongoing, incomplete survey of and discussions on the recent progress of utilizing advanced deep learning, semantic organ parsing, multimodal imaging fusion, neural architecture search and medical image analytical techniques to address four corner-stone problems or sub-problems required by all precision radiotherapy workflows, namely, organs at risk (OARs) segmentation, gross tumor volume (GTV) segmentation, metastasized lymph node (LN) detection, and clinical tumor volume (CTV) segmentation. Without loss of generality, we mainly focus on using esophageal and head-and-neck cancers as examples, but the methods can be extrapolated to other types of cancers. High-precision, automated and highly reproducible OAR/GTV/LN/CTV auto-delineation techniques have demonstrated their effectiveness in reducing the inter-practitioner variabilities and the time cost to permit rapid treatment planning and adaptive replanning for the benefit of patients. Through the presentation of the achievements and limitations of these techniques in this review, we hope to encourage more collective multidisciplinary precision radiotherapy workflows to transpire.

Accurate organ at risk (OAR) segmentation is critical to reduce the radiotherapy post-treatment complications. Here, the authors develop an automated OAR segmentation system to delineate a comprehensive set of 42 H&N OARs.

Abstract Background Radiation recall pneumonitis (RRP) is unpredictable but associated with severe radiation damage in previously irradiated fields. Chemotherapy and targeted drugs have been reported to contribute to RRP. Here we report a case of a patient with non-small cell lung cancer (NSCLC) who developed RRP following administration of immune checkpoint inhibitor (ICI) 18 months after the end of re-irradiation. Case presentation A 69-year-old man received adjuvant chemoradiotherapy post-operatively. He underwent thoracic re-irradiation for oligometastatic NSCLC. On second recurrence, pembrolizumab combined with nab-paclitaxel were administered. After six months, he developed symptoms of persistent cough and dyspnea, with consistent pneumonitis on CT images. The clinical time frame and significant radiographic evidence raised suspicion for RRP. Symptoms resolved after steroids. Conclusions RRP is a rare occurrence. Patients undergoing immunotherapy after prior irradiation may be at increased risk of this rare radiation pneumonitis.

ObjectiveTo identify the predominant type of cerebral small vessel disease (SVD) and outcomes in patients with simultaneous multiple intracerebral hemorrhages (SMICH).MethodsConsecutive patients with intracerebral hemorrhage (ICH) from a single-center prospective cohort were retrospectively reviewed. Presumed etiology was classified according to the SMASH-U criteria. Demographics, clinical and laboratory variables, and neuroimaging data were compared between patients with primary SMICH and those with single ICH. Functional outcomes were assessed using the modified Rankin scale 90 days after ICH.ResultsOf the 598 enrolled patients, 37 (6.2%) met the criteria for SMICH. Risk factors for SMICH included a high burden of deep cerebral microbleeds (CMBs) (odds ratio [OR] 1.06, 95% confidence interval [CI], 1.00–1.12; p = 0.040), white matter hyperintensity scores (OR 1.27, 95% CI 1.04–1.57; p = 0.021), history of ICH (OR 3.38, 95% CI 1.31–8.05; p = 0.008), and low serum magnesium levels (OR 0.01, 95% CI 0.00–0.25; p = 0.007). Based on the SMASH-U classification, 15(40.5%) SMICH were classified as hypertension, whereas 17 (45.9%) as undetermined-etiology. To further explore the potential microangiopathy underlying undetermined-SMICH, these patients with undetermined-etiology were compared to those with cerebral amyloid angiopathy-ICH, and were associated with a higher burden of deep CMBs but less severe centrum semiovale enlarged perivascular spaces. Likewise, compared with hypertension-ICH patients, those with undetermined SMICH were consistently associated with a higher deep CMB counts. Moreover, multivariate analysis revealed that SMICH was independently associated with poor outcomes (OR 2.23, 95%CI 1.03–4.76; p = 0.038).ConclusionOur results suggest that most patients with primary SMICH harbor hypertensive-SVD as principal angiopathy. Patients with SMICH are at a high risk of poor outcomes. (ClinicalTrials.gov Identifier: NCT 04803292).

Abstract Background The epidemiology of esophageal cancer (EC) can elucidate its causes and risk factors and help develop prevention strategies. We aimed to provide an overview of the burden, trends, and risk factors of EC in China from 1990 to 2017. We also investigated the differences between China, Japan, and South Korea and discussed the possible causes of the disparities. Methods We used the Global Burden of Disease Study 2017 to obtain data on incident cases, deaths, disability-adjusted life-year (DALY) cases, age-standardized incidence rate (ASIR), age-standardized death rate (ASDR), and age-standardized DALY rate of EC in China, Japan, and South Korea from 1990 to 2017. Trend analysis was performed using joinpoint analysis. We measured the associations between ASIR, ASDR, and age-standardized DALY rate and the socio-demographic index (SDI) for 1990–2017. We also analyzed the risk factors associated with EC deaths and DALYs. Results China recorded 234,624 (95% uncertainty intervals: 223,240–246,036) incident cases of and 212,586 (202,673–222,654) deaths from EC in 2017. The ASIR and ASDR declined from 1990 to 2017. Until 2017, the ASIR was 12.23, and ASDR was 11.25 per 100,000 persons. The DALYs were 4,464,980 (4,247,816–4,690,846) with an age-standardized rate of 222.58 per 100,000 persons in 2017. The ASIR, ASDR, and age-standardized DALY rate in China were twice those of Japan and South Korea. These three indicators showed a decreasing trend, whereas SDI increased, in all three countries from 1990 to 2017. Tobacco and alcohol use remained the major risk factors for EC death and DALYs, especially for men in China and women in Japan and South Korea. High body mass index (BMI) and low-fruit diet were the main risk factors for women in China. Conclusions The incident cases and deaths of EC in China, Japan, and South Korea increased from 1990 to 2017, whereas the ASIR, ASDR, and age-standardized DALY rate declined. China had the greatest burden of EC among three countries. SDI and aging along with tobacco use, alcohol use, high BMI, and low-fruit diet were the main risk factors of death and DALYs and should be paid more attention.

Abstract Background Investigations of disease incidence, mortality, and disability-adjusted life years (DALYs) are valuable for facilitating preventive measures and health resource planning. We examined the tracheal, bronchus, and lung (TBL) cancer burdens worldwide according to sex, age, and social development index (SDI) at the global, regional, and national levels. Methods We assessed the TBL cancer burden using data from the Global Burden of Disease (GBD) database, including 21 regions, 195 countries, and territories in the diagnostic period 1990–2017. The data of TBL cancer-related mortality and DALYs attributable to all known risk factors were also analyzed. Age-standardized rates (ASRs) and their estimated annual percentage changes (EAPCs) were calculated. Results Incident cases, deaths, and DALYs of TBL cancer increased worldwide (100.44%, 82.30%, and 61.27%, respectively). The age-standardized incidence rate (ASIR) was stable (EAPC = 0.02, 95% confidence interval [CI] − 0.03 to 0.08), but the age-standardized death (EAPC = − 0.34, 95%CI − 0.38 to − 0.3) and DALY rate decreased generally (EAPC = − 0.74, 95%CI − 0.8 to − 0.68). However, the change trend of ASIR and ASDR among sexes was on the contrary. China and the USA always had the highest incidence, mortality, and DALYs of TBL cancer. Significant positive correlations between ASRs and SDI were observed, especially among females. High (36.86%), high-middle (28.78%), and middle SDI quintiles (24.91%) carried the majority burden of TBL cancer. Tobacco remained the top cause of TBL cancer death and DALYs, followed by air pollution, the leading cause in the low-middle and low-SDI quintiles. Metabolic risk-related TBL cancer mortality and DALYs among females increased but was stable among males. The main ages of TBL cancer onset and death were > 50 years, and the DALYs concentrated in 50 − 69 years. Conclusions To significantly reduce the growing burden of TBL cancer, treatment resources need to be skewed according to factors such as risks and geography, especially for high-risk groups and high-burden areas. Asia had the greatest TBL cancer burden, followed by high-income North America. Tobacco remains the leading cause of death and DALYs, followed by air pollution. Effective prevention measures against tobacco and air pollution should be strengthened.

BackgroundThe current clinical workflow for esophageal gross tumor volume (GTV) contouring relies on manual delineation with high labor costs and inter-user variability.PurposeTo validate the clinical applicability of a deep learning multimodality esophageal GTV contouring model, developed at one institution whereas tested at multiple institutions.Materials and MethodsWe collected 606 patients with esophageal cancer retrospectively from four institutions. Among them, 252 patients from institution 1 contained both a treatment planning CT (pCT) and a pair of diagnostic FDG-PET/CT; 354 patients from three other institutions had only pCT scans under different staging protocols or lacking PET scanners. A two-streamed deep learning model for GTV segmentation was developed using pCT and PET/CT scans of a subset (148 patients) from institution 1. This built model had the flexibility of segmenting GTVs via only pCT or pCT+PET/CT combined when available. For independent evaluation, the remaining 104 patients from institution 1 behaved as an unseen internal testing, and 354 patients from the other three institutions were used for external testing. Degrees of manual revision were further evaluated by human experts to assess the contour-editing effort. Furthermore, the deep model’s performance was compared against four radiation oncologists in a multi-user study using 20 randomly chosen external patients. Contouring accuracy and time were recorded for the pre- and post-deep learning-assisted delineation process.

Background: Colorectal cancer remains a public health problem worldwide. Dietary risk factors play a key role in the carcinogenesis and progression of colorectal cancer. This study aimed to explore the geographical and temporal trends in various dietary factor-related colorectal cancers.Methods: Data were extracted from the Global Burden of Disease (GBD) 2019 study, including the deaths, disability-adjusted life-years (DALYs), age-standardized rate (ASR), and summary exposure value (SEV) among 4 world regions, 11 age groups, 21 regions, and 204 countries and territories between 1990 and 2019. The estimated annual percentage changes (EAPCs) were calculated to evaluate the variation trend of ASR.Results: Dietary factors were the leading cause of colorectal cancer death and DALY rate, regardless of age. Dietary factor-related deaths and DALYs accounted for 32 and 34% of global colorectal cancer, respectively. Further analysis showed that low whole grain intake remained the leading cause of cancer death and DALY rate, followed by milk and calcium. Diets that were low in whole grains, milk, and calcium accounted for 81.61% of deaths and 81.64% of DALYs. Deaths and DALYs of dietary factors related to colorectal cancer grew by half from 1990 to 2019. All ASRs remained higher for men than women. Asia carried the highest colorectal cancer burden attributed to dietary risks, especially for East Asia [age-standardized death rate (ASDR): EAPC = 1.15, 95% CI:0.88–1.42; DALY: EAPC = 1.08, 95% CI:0.82–1.34]. The heavy burden also existed in high-middle and middle socio-demographic index (SDI) quintiles. China has always had the highest deaths and DALYs of colorectal cancer attributable to dietary risks, followed by the USA, India, and Japan.Conclusions: Large variations existed in the dietary risk-related colorectal cancer burdens among sexes, regions, and countries. More targeted interventions to address modifiable dietary risk factors would save 32% of deaths and 34% of DALYs for colorectal cancer.

Aflibercept is a human recombinant fusion protein with antiangiogenic effects that functions as a decoy receptor to bind vascular endothelial growth factor A. Proteinuria is one of its major adverse effects with a substantial variation in the incidence rate, and the overall risk of proteinuria has not been systematically studied. We performed a meta-analysis of published clinical trials to quantify the incidence and relative risk of proteinuria in cancer patients treated with aflibercept.The electronic databases were searched, including PubMed, Embase, Cochrane databases, and ASCO (American Society of Clinical Oncology) abstracts. Eligible studies were phase II and III prospective clinical trials of cancer patients treated with aflibercept with toxicity data on proteinuria. Overall incidence rates, relative risk (RR), and 95% confidence intervals (CI) were calculated using fixed or random effects models depending on the heterogeneity of the included studies.A total of 4,596 patients with a variety of solid tumors from 16 prospective clinical trials were included for the meta-analysis. The overall incidences of all-grade and high-grade proteinuria in cancer patients were 33.9% (95% CI: 27.3-42.1%) and 7.9% (95% CI: 6.1-10.2%). The relative risks of proteinuria of aflibercept compared to control were increased for all-grade (RR = 1.41, 95% CI: 1.13-1.77) and high-grade (RR = 6.18, 95% CI: 3.78-10.12) proteinuria. The risk of developing all-grade and high-grade proteinuria with aflibercept was substantially higher than that of bevacizumab (all-grade: RR 1.85, 95% CI: 1.63-2.11; high-grade: RR 2.37, 95% CI: 1.84-3.05).Aflibercept is associated with an increased risk of developing proteinuria. Appropriate monitoring and treatment is strongly recommended to prevent potential renal damage. Future studies are still needed to investigate the risk reduction and possible use of aflibercept in cancer patients.

Background and purpose Cortical superficial siderosis (cSS) and cerebral microbleed (CMB) have distinct effects on intracerebral haemorrhage (ICH). We aim to investigate the combined effect of cSS and CMB on outcomes after ICH.Methods Based on a single-centre stroke registry database, patients with spontaneous ICH who had CT scan within 48 hours after ictus and MRI subsequently were identified. Eligible patients were divided into four groups (cSS-CMB−, cSS-CMB+, cSS+CMB−, cSS+CMB+) according to cSS and CMB on susceptibility-weighted image of MRI. Primary outcomes were haematoma volume on admission and unfavourable outcome defined as modified Rankin Scale scores ≥3 at 3 months. Secondary outcomes were all-cause death, recurrence of stroke and ICH during follow-up (median follow-up 2.0 years, IQR 1.0–3.0 years).Results A total of 673 patients were identified from 1044 patients with spontaneous ICH. 131 (19.5%) had cSS and 468 (69.5%) had CMB. Patients with cSS+CMB+ had the highest rate of poor outcome at 3 months, as well as all-cause death, recurrent stroke and ICH during follow-up. In cSS− patients, CMB was associated with smaller haematoma (β −0.13; 95% CI −0.22 to −0.03; p=0.009), but it still increased risks of recurrent ICH (OR 4.6; 95% CI 1.3 to 15.6; p=0.015) and stroke (OR 2.0; 95% CI 1.0 to 4.0; p=0.049). These effects of CMB became unremarkable in the context of cSS+.Conclusions Patients with different combinations of cSS and CMB have distinct patterns of short-term and long-term outcomes. Although CMB is related to restrained haematoma, it does not improve long-term outcomes.Trial registration number NCT04803292.