Search

Background: Our study aimed to identify inclisiran-related adverse events(AEs) for primary hypercholesterolemia and arteriosclerotic cardiovascular disease(ASCVD) from the US FDA Adverse Event Reporting System (FAERS) database, analyzing its links to AEs in the overall patient population and sex-specific subgroups to improve medication safety., Methods: We analyzed inclisiran-related AEs signals by using statistical methods like Reporting Odds Ratio (ROR), Proportional Reporting Ratios (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-item Gamma-Poisson Shrinker (MGPS)., Results: Analyzing 2,400 AE reports with inclisiran as the primary suspected drug in the FAERS database, we identified 70 AE signals over 13 organ systems using the above four methods. Notable findings were strong signals for systemic diseases and various reactions at the site of administration (ROR 1.49, 95% CI 1.41-1.57), and various musculoskeletal and connective tissue diseases (ROR 4.07, 95% CI 3.83-4.03) in overall and gender-specific populations. Myalgia, a new ADE signal not in the drug insert, was a top signal by intensity and frequency (ROR 14.76, 95% CI 12.84-16.98)., Conclusion: Our study revealed the strongest AE signals associated with inclisiran in both the overall population and gender subgroups, highlighting potential risks in clinical medication use and guiding balanced clinical decision-making.

Objectives: To examine spatial access to sleep health care in the United States and investigate associations with demographic and socioeconomic characteristics, thereby identifying high-risk communities with limited spatial access to sleep health service., Design: A cross-sectional population-based geospatial analysis., Settings and Participants: Residents in US Census tracts across the 48 contiguous states, Alaska, and Hawaii., Methods: The 2020 American Community Survey 5-year estimates, 2010 rural-urban commuting area codes, 2020 Area Deprivation Index, and sleep care provider locations from the National Provider Identifier file were used to assess the spatial access and related demographic/socioeconomic characteristics. Spatial access was measured by spatial access ratio using enhanced 2-step floating catchment area methods. The associations were investigated using logistic regression analysis and multivariate linear regression analysis., Results: A total of 45.8 million residents experienced low spatial access to sleep health care. Spatial access decreased in rural and high Area Deprivation Index areas, and in areas characterized by higher population with uninsured status, vehicle unavailability, internet unavailability, cognitive difficulties, and hearing difficulties. With a 10% increase in the percentage of the racial minority (non-white) population, metropolitan census tracts experienced an increase in spatial access (3.268%), whereas micropolitan (-1.526%) and rural (-4.493%) areas experienced a decrease in spatial access. Similar findings were observed within the ethnic minority (Hispanic or Latino) population., Conclusions and Implications: Disparities exist in spatial access to sleep health care across the United States, especially for disadvantaged individuals. Racial/ethnic minorities exhibit contrasting spatial access patterns in urban and rural areas, with those in rural areas facing more challenges in spatial access to sleep health care., Competing Interests: Disclosures The authors declare no conflicts of interest., (Copyright © 2024 Post-Acute and Long-Term Care Medical Association. Published by Elsevier Inc. All rights reserved.)

Background: Anemia significantly contributes to the global disease burden, with its incidence potentially influenced by the trace metal content within the body., Objective: This study aims to examine the associations between trace metals and anemia risk, with a particular focus on investigating the potential mediating roles of iron status and inflammation in these associations., Methods: Five trace metals (Ni, Co, Mn, Se, and Mo) were examined in 1274 US adults, utilizing data from the National Health and Nutrition Examination Survey (NHANES) 2017-2020. The individual and combined effects of these metals on anemia were assessed using logistic regression, quantile g-computation (QGC), and Bayesian kernel machine regression (BKMR). A sex-stratified analysis was conducted to discern any gender-specific susceptibilities. Additionally, mediation analysis was employed to explore the potential mediating roles of iron status and inflammation in the associations between these metals and anemia., Results: Increased risks of anemia were positively associated with Co and Ni levels but negatively correlated with Se and Mn levels (all with p < 0.05). The trace metal mixture was negatively associated with anemia, with the highest weights of Co and Se in different directions in both the QGC and BKMR models. In the sex-specific analysis, we observed less pronounced protective effects from trace metals in females. Moreover, the mediating proportion of the iron status and inflammation in these relationships ranged from 10.29% to 58.18%., Conclusion: Our findings suggest that the trace element mixture was associated with decreased anemia risk, among which Se was a protective factor while Co was a risk factor, and females were more susceptible. The effects of these trace metals on anemia may be mediated by the iron status and inflammation.

Background: Ethylene oxide (EO) is a volatile compound positively correlated with respiratory and cardiovascular diseases. Currently, evidence suggests that environmental exposure may contribute to depressive symptoms. This study evaluated the correlation between EO exposure and depressive symptoms and investigated whether inflammatory indicators had a mediation effect on this correlation., Methods: Patients were enrolled from the National Health and Nutrition Examination Survey during 2013-2016, and 2,764 (49.67% male and 50.33% female) participants were ultimately included. EO exposure was determined by measuring hemoglobin-EO adduct (Hb-EO) concentration due to its long half-life, which was log 2 -transformed. Depressive symptoms were assessed using the Patient Health Questionnaire-9. Multivariable logistic regression analysis was performed to identify any correlations before and after covariate adjustment. Sensitivity analysis, subgroup analyses, and interaction tests were performed to further evaluate identified correlations. Mediation analysis was conducted to reveal whether specific inflammatory indicators mediated the correlation., Results: A high prevalence of depressive symptoms was observed in quartiles with increased levels of EO exposure, and male individuals exhibiting higher Hb-EO levels than female individuals. A positive correlation was observed between EO exposure and depressive symptoms (odds ratio [OR]: 1.439, 95% confidence interval [CI]: 1.310, 1.581), which remained stable even after covariate adjustment (OR: 1.332, 95% CI: 1.148, 1.545). Interaction tests showed significant effects of sex ( p  < 0.001) and thyroid diseases ( p = 0.048) on this correlation. In the mediation analysis, white blood cell ( p = 0.010) and neutrophil counts ( p = 0.010) exerted a mediating effect, accounting for 13.6 and 11.9%, respectively., Conclusion: Increased exposure to EO is associated with an elevated risk of depressive symptoms, where white blood cell and neutrophil counts exert a significant mediating effect. Further prospective studies are required to investigate the potential link among EO, other environmental pollutants, and human mental health., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Du, Yuan, Guan, Xie and Dong.)

Background: New cancer drugs can be approved by the US Food and Drug Administration (FDA) on the basis of surrogate endpoints while data on overall survival are still incomplete or immature, with too few deaths for meaningful analysis. We aimed to evaluate whether clinical trials with immature survival data generated evidence of overall survival benefit during the period after marketing authorisation, and where that evidence was reported., Methods: In this retrospective analysis, we searched Drugs@FDA to identify cancer drug indications approved between Jan 1, 2001, and Dec 31, 2018, on the basis of immature survival data. We systematically collected publicly available data on postapproval overall survival results in labelling (Drugs@FDA), journal publications (MEDLINE via PubMed), and clinical trial registries (ClinicalTrials.gov). The primary outcome was availability of statistically significant overall survival benefits during the period after marketing authorisation (until March 31, 2023). Additionally, we evaluated the availability and timing of overall survival findings in labelling, journal publications, and ClinicalTrials.gov records., Findings: During the study period, the FDA granted marketing authorisation to 223 cancer drug indications, 95 of which had overall survival as an endpoint. 39 (41%) of these 95 indications had immature survival data. After a minimum of 4·3 years of follow-up during the period after marketing authorisation (and median 8·2 years [IQR 5·3-12·0] since FDA approval), additional survival data from the pivotal trials became available in either revised labelling or publications, or both, for 38 (97%) of 39 indications. Additional data on overall survival showed a statistically significant benefit in 12 (32%) of 38 indications, whereas mature data yielded statistically non-significant overall survival findings for 24 (63%) indications. Statistically significant evidence of overall survival benefit was reported in either labelling or publications a median of 1·5 years (IQR 0·8-2·3) after initial approval. The median time to availability of statistically non-significant overall survival results was 3·3 years (2·2-4·5). The availability of overall survival results on ClinicalTrials.gov varied considerably., Interpretation: Fewer than a third of indications approved with immature survival data showed a statistically significant overall survival benefit after approval. Notable inconsistencies in timing and availability of information after approval across different sources emphasise the need for better reporting standards., Funding: None., Competing Interests: Declaration of interests HN reported receiving grants from Commonwealth Fund, Health Foundation, National Institute for Health and Care Research, and UK Research and Innovation, and personal fees from Pharmaceutical Group of the European Union, WHO, and The BMJ (serving as an adviser). AKW reported receiving grants from the American Cancer Society. SW reported receiving grants from Arnold Ventures. XG reported receiving an award from the National Natural Science Foundation of China. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: The National Quality Forum has endorsed at least 12 lymph node yield (LNY) as a surgical quality indicator in colorectal cancer (CRC), but the prognostic value of adequate lymphadenectomy has rarely been investigated for CRC patients with distant metastatic disease., Methods: A total of 4575 CRC patients with synchronous liver metastasis who underwent primary tumor resection were identified from a Chinese registry and the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2017. The Kaplan-Meier methods and Cox regression models were performed to assess the correlations between LNY and 3-year cancer-specific survival (CSS). Propensity score matching were used to confirmed the survival comparison between patients with less than 12 and of at least 12 LNY., Results: The retrieval of at least 12 LNY was identified in most CRC patients (SEER database, 3380/3899, 86.7%; Chinese cohort, 565/676, 83.6%). In both the SEER database and the Chinese cohort, the patients with LNY ≥12 was significantly associated with better CSS compared with patients with LNY <12 before and after propensity score matching, with all P -value less than 0.05. After controlling for the confounders, multivariate analysis demonstrated that LNY was also an independent prognostic factor for patients with distant metastasis in both cohorts. In subgroup analysis, the CSS benefit for patients with LNY ≥12 was observed across most of the subgroups., Conclusions: Clinical feasibility of the 12-node threshold as a guideline quality metric of cancer care for CRC patients is necessary, and an oncologically adequate lymphadenectomy is still a critical component of high-quality surgical standard in CRC patients with distant metastases., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Purpose: This study performed an analysis of clinicopathological characteristics, surgical treatment strategy, and survival for CRC patients with LM between China and the USA., Methods: The CRC patients with simultaneous LM were identified from the Surveillance, Epidemiology, and End Results (SEER) registry and the Chinese National Cancer Center (CNCC) database from 2010 to 2017. We assessed 3-year cancer-specific survival (CSS) according to surgical treatment strategy and time period., Results: Differences in patient age, gender, primary tumor location, tumor grade, tumor histology, and tumor stage were observed between the USA and China. Compared to the USA, a larger proportion of patients in China underwent both primary site resection (PSR) and hepatic resection (HR) (35.1% vs 15.6%, P < 0.001), and fewer patients underwent only PSR in China (29.1% vs 45.1%, P < 0.001). From 2010 to 2017, the proportion of patient who underwent both PSR and HR has increased from 13.9% to 17.4% in the USA and from 25.4% to 39.4% in China. The 3-year CSS were increasing over time in both the USA and China. The 3-year CSS of patients receiving HR and PSR were significantly higher than those receiving only PSR and patients treated with no surgery in the USA and China. There were no significant differences of 3-year CSS between the USA and China after adjustment (P = 0.237)., Conclusions: Despite the distinctions of tumor characteristics and surgical strategy in patients with LM between the USA and China, increased adoption of HR has contributed to the profound improvements of survival during recent decade., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Golidocitinib is an orally available, potent and highly selective JAK (Janus kinase)-1 inhibitor of JAK/STAT3 signaling under clinical development for the treatment of cancer and autoimmune diseases. The objectives of the two reported studies were to investigate the pharmacokinetics (PK), safety, and tolerability of golidocitinib in healthy Chinese participants as compared to those healthy Western participants, as well as the food effect exploration., Methods: Two phase I studies (JACKPOT2 and JACKPOT3) were conducted in USA and China, respectively. In JACKPOT2 study, participants were randomized into placebo or golidocitinib arm in single-ascending dose cohorts (5 - 150 mg) and multiple-ascending dose cohorts (25 - 100 mg, once daily) for 14 days. In the food effect cohort, golidocitinib (50 mg) was administrated shortly after a high-fat meal (fed conditions) as compared to under fasting conditions. In JACKPOT3 study conducted in China, participants were randomized to placebo or golidocitinib arm in single-ascending dose cohorts (25 - 150 mg)., Results: Exposure of golidocitinib generally increased in a dose-proportional manner across a dose range of 5 mg to 150 mg (single dose) and 25 mg to 100 mg (once daily). High-fat food did not alter the PK of golidocitinib with statistical significance. Low plasma clearance and extensive volume of distribution characterizes PK of golidoctinib, and long half-life across the dose levels supported once daily dosing. The inter-ethnic difference in primary PK parameters was evaluated. The result suggested slightly higher peak plasma concentrations (C max ) but comparable area under the plasma concentration-time curve (AUC) was observed in Asian (Chinese) subjects as compared to Caucasian and/or Black subjects, while it was not considered clinically relevant. Golidocitinib was well tolerated without Common Terminology Criteria for Adverse Events (CTCAE) grade 3 or higher drug-related treatment emergent adverse events (TEAE) reported., Conclusion: No noticeable inter-ethnic difference was observed among Asian, Black, and Caucasian healthy subjects in anticipation of the favorable PK properties of golidocitinib. The effect of food on the bioavailability of golidocitinib was minor following a single oral administration of 50 mg. These data guided to use the same dose and regimen for multinational clinical development., Clinical Trial Registrations: https://clinicaltrials.gov/ct2/show/NCT03728023?term=NCT03728023&draw=2&rank=1, identifier (NCT03728023); http://www.chinadrugtrials.org.cn/clinicaltrials.searchlistdetail.dhtml, identifier (CTR20191011)., Competing Interests: KC, ZY, YZ, ZL, XD and DL were employed by Dizal Pharmaceuticals. The authors declare that the studies (JACKPOT2 and JACKPOT3) received funding from Dizal Pharmaceuticals. The funder had the following involvement in the studies: the study design, interpretation of data, manuscript draft and review for both JACKPOT2 and JACKPOT3 studies., (Copyright © 2023 Chen, Guan, Yang, Zhou, Liu, Deng, Liu, Hu and Chen.)

Objective: To evaluate practices among first-trimester surgical abortion facilities and providers in Canada in 2012 and examine the characteristics of the surgical abortion work force., Design: Self-administered paper or electronic survey adapted from a survey previously fielded in the United States., Setting: Canada., Participants: Facility administrators and physicians., Main Outcomes Measures: Descriptive statistics on reported first-trimester surgical abortion practice and provider demographic characteristics., Results: Eighty-three percent of identified facilities (78 of 94) and 178 physicians responded. Of the respondents, 99% of facilities and 96% of physicians provided first-trimester surgical abortions. Responding facilities provided 68,154 first-trimester surgical abortions in 2012. This represented 96% of their reported total (combined medical and surgical) first-trimester abortions. More than half (55%) of responding facilities were community based, while 45% were hospital affiliated. Most physician providers were female (68%) and were family doctors (59%). Preoperatively, 96% of physicians routinely used ultrasound and 89% gave perioperative antibiotics. Almost half (48%) used manual vacuum aspiration, but less than 35% did so beyond 9 weeks after the last menstrual period. At most facilities, most procedures were performed under combined local anesthesia and intravenous sedation (73%); only 7% indicated deep sedation or general anesthesia were used exclusively. Postoperatively, 81% of physicians performed immediate tissue examination and 96% offered postabortion contraception on the same day as the abortion. Other assessed outcomes included medication regimens and cervical preparation, with a high degree of consistency among facilities and physicians., Conclusion: First-trimester surgical abortion providers are mostly family physicians and most are female. Practices across Canada were mostly uniform and followed evidence-based guidelines. Uptake of the most recent Canadian practice guidelines may help further standardize patient care and improve routine perioperative antibiotic use and immediate tissue examination., (Copyright © 2023 the College of Family Physicians of Canada.)

Background: Pancreatic cancer (PC) is a highly malignant tumor of the digestive system. The number of elderly patients with PC is increasing, and older age is related to a worse prognosis. Accurate prognostication is crucial in treatment decisions made for people diagnosed with PC. However, an accurate predictive model for the prognosis of these patients is still lacking. We aimed to construct nomograms for predicting the overall survival (OS) of elderly patients with PC., Methods: Patients with PC, older than 65 years old from 2010 to 2015 in the Surveillance, Epidemiology, and End Results database, were selected and randomly divided into training cohort ( n = 4,586) and validation cohort ( n = 1,966). Data of patients in 2016-2018 ( n = 1,761) were used for external validation. Univariable and forward stepwise multivariable Cox analysis was used to determine the independent prognostic factors. We used significant variables in the training set to construct nomograms predicting prognosis. The performance of the models was evaluated for their discrimination and calibration power based on the concordance index (C-index), calibration curve, and the decision curve analysis (DCA)., Results: Age, insurance, grade, surgery, radiation, chemotherapy, T, N, and American Joint Commission on Cancer were independent predictors for OS and thus were included in our nomogram. In the training cohort and validation cohort, the C-indices of our nomogram were 0.725 (95%CI: 0.715-0.735) and 0.711 (95%CI: 0.695-0.727), respectively. The 1-, 3-, and 5-year areas under receiver operating characteristic curves showed similar results. The calibration curves showed a high consensus between observations and predictions. In the external validation cohort, C-index (0.797, 95%CI: 0.778-0.816) and calibration curves also revealed high consistency between observations and predictions. The nomogram-related DCA curves showed better clinical utility compared to tumor-node-metastasis staging. In addition, we have developed an online prediction tool for OS., Conclusions: A web-based prediction model for OS in elderly patients with PC was constructed and validated, which may be useful for prognostic assessment, treatment strategy selection, and follow-up management of these patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhong, Liao, Peng, Cao, Liu, Liu, Qiu, Guan, Zhang, Liu and Peng.)

Different from less developed countries, 80% of children with cancers in the United States are cured. Traditional chemotherapy drugs are the mainstay of therapies; new targeted medications have become available recently. Using publicly available data, we created a database of cancer drugs with paediatric malignancy indications approved by 31 October 2020 in China and the United States. We compared numbers, type, indications and listing on the World Health Organization Model List of Essential Medicines for Children (WHO EMLc) between the two countries, assessed the correlation between paediatric indications and cancer incidences, and described evidence supporting approvals of targeted medications in the two settings. Our study showed that by 31 October 2020, 31 and 39 cancer drugs available in China and the United States were approved for use in children, corresponding to 137 and 102 paediatric cancer indications, respectively. About half of these drugs (17 in China and 18 in the United States) were listed on the WHO EMLc. The correlation between indications and burden of disease was higher in the United States (r = 0.68) than China (r = 0.59). More traditional chemotherapy drugs were approved in China (n = 27) than the United States (n = 19). Of 20 targeted childhood anticancer medicines approved in the United States, mainly on the basis of single arm trials (27/32 indications, 84.4%), only four were approved for paediatric indications in China, at a median of 2.8 years after US Food and Drug Administration approval. A harmonised, evidence-based regulatory framework is needed to ensure approvals of needed, safe and efficacious childhood cancer drugs across the world., (© 2021 UICC.)

Background: The newly described ABCD-10 (age, bicarbonate, cancer, dialysis, 10% body surface area [BSA]) is a 5-item mortality prediction model for patients with Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN). It was developed in the United States, has at present been externally tested only in the United States, Spain, and Singapore, and remains to be validated in resource-restricted settings. We sought to compare the accuracy of ABCD-10 and Score of Toxic Epidermal Necrolysis (SCORTEN) in predicting in-hospital mortality in a cohort from central China. Due to disease progression affecting the accuracy of the prediction model during hospitalization, for example, higher predictive accuracy of SCORTEN based on parameters collected on day 3 of hospitalization, we also assessed the overall predictive value of ABCD-10 on days 1 and 3, respectively., Methods: A retrospective study was performed over a 10-year period (2010-2020) from 3 medical institutions in Wuhan. The performance of predictive models was assessed by both discrimination and calibration. Receiver-operating characteristic (ROC) curves, Hosmer-Lemeshow goodness-of-fit tests and calibration plots were used to evaluate the model discrimination and calibration., Results: Of 84 included patients, 11 (13.1%) did not survive. The discrimination power of ABCD-10 was not significantly different from that of SCORTEN (area under the curve: day 1, p > 0.05; day 3, p > 0.05). Although the calibration of ABCD-10 was good, it was inferior to SCORTEN as it underestimated total mortality (Hosmer-Lemeshow goodness-of-fit test: day 1, p = 0.17 vs. p = 0.63; day 3, p = 0.35 vs. p = 0.93). Besides, the performance of ABCD-10 was slightly better on day 3 relative to day 1. During hospitalization, bacteremia developed in 21 (25.0%) patients, which was associated with a higher risk of death in our cohort (odds ratio, 22.88; 95% CI, 4.38-119.40; p < 0.001)., Conclusion: ABCD-10 showed acceptable overall performance, but revealed mortality underestimation and was inferior to the performance of SCORTEN. In consistence with SCORTEN, ABCD-10 was a better model when using values collected at day 3 of hospitalization relative to day 1., (© 2021 S. Karger AG, Basel.)

Importance: Radiotherapy is a common treatment for rectal cancer, yet the risk of second gynecological malignant neoplasms (SGMNs) in patients with rectal cancer undergoing radiotherapy have not been adequately studied., Objective: To investigate the association between radiotherapy and the risk of individual types of SGMN in patients with rectal cancer and assess survival outcomes., Design, Setting, and Participants: A large population-based cohort study was designed to identify the risk of SGMNs in patients with rectal cancer diagnosed from January 1973 to December 2015. The statistical analysis was conducted from September 2019 to April 2020. The study was based on the 9 cancer registries of Surveillance, Epidemiology, and End Results database. A total of 20 142 female patients with rectal cancer in localized and regional stage were included., Exposure: Receipt of neoadjuvant radiotherapy for rectal cancer., Main Outcomes and Measures: The development of an SGMN defined as any type of GMN occurring more than 5 years after the diagnosis of rectal cancer. The cumulative incidence of SGMNs was estimated by Fine-Gray competing risk regression. Poisson regression was used to evaluate the radiotherapy-associated risk for SGMNs in patients undergoing radiotherapy vs patients not undergoing radiotherapy. The Kaplan-Meier method was used to assess the survival outcomes of patients with SGMNs., Results: Of 20 142 patients, 16 802 patients (83.4%) were White and the median age was 65 years (interquartile range, 54-74 years). A total of 5310 (34.3%) patients were treated with surgery and radiotherapy, and 14 832 (65.7%) patients were treated with surgery alone. The cumulative incidence of SGMNs during 30 years of follow-up was 4.53% among patients who received radiotherapy and 1.53% among patients who did not. In competing risk regression analysis, undergoing radiotherapy was associated with a higher risk of developing cancer of the uterine corpus (adjusted hazard ratio, 3.06; 95% CI, 2.14-4.37; P < .001) and ovarian cancer (adjusted hazard ratio, 2.08; 95% CI, 1.22-3.56; P = .007) compared with those who did not receive radiotherapy. The dynamic radiotherapy-associated risks (RR) for cancer of the uterine corpus significantly increased with increasing age at rectal cancer diagnosis (aged 20-49 years: adjusted RR, 0.79; 95% CI, 0.35-1.79; P = .57; aged 50-69 years: adjusted RR, 3.74; 95% CI, 2.63-5.32; P < .001; aged ≥70 years: adjusted RR, 5.13; 95% CI, 2.64-9.97; P < .001) and decreased with increasing latency since rectal cancer diagnosis (60-119 months: adjusted RR, 3.22; 95% CI, 2.12-4.87; P < .001; 120-239 months: adjusted RR, 2.72; 95% CI, 1.75-4.24; P < .001; 240-360 months: adjusted RR, 1.95; 95% CI, 0.67-5.66; P = .22), but the dynamic RR for ovarian cancer increased with increasing latency since rectal cancer diagnosis (60-119 months: adjusted RR, 0.70; 95% CI, 0.26-1.89; P = .48; 120-239 months: adjusted RR, 2.26; 95% CI, 1.09-4.70; P = .03; 240-360 months: adjusted RR, 11.84; 95% CI, 2.18-64.33; P = .004). The 10-year overall survival among patients with radiotherapy-associated cancer of the uterine corpus was significantly lower than that among matched patients with primary cancer of the uterine corpus (21.5% vs 33.6%; P = .01)., Conclusions and Relevance: Radiotherapy for rectal cancer was associated with an increased risk of cancer of the uterine corpus and ovarian cancer. Special attention should be paid to reduce radiotherapy-associated SGMNs and improve their prognosis.

Background: The early detection of synchronous bone metastasis (BM) in newly diagnosed colorectal cancer (CRC) affects its initial management and prognosis. A clinical model to individually predict the risk of developing BM would be attractive in current clinical practice., Methods: A total of 55,869 CRC patients were identified from Surveillance, Epidemiology, and End Results (SEER) database, of whom 317 patients were diagnosed with synchronous BM. Risk factors for BM in CRC patients was identified using multivariable logistic regression. A weighted scoring system was built with beta-coefficients (P < 0.05). A random sample of 75% of the CRC patients was used to establish the risk model, and the remaining 25% was used to validate its accuracy of this model. The performance of risk model was estimated by receiver operating curve (ROC) analysis., Results: The risk model consisted of 8 risk factors including rectal cancer, poorly-undifferentiation, signet-ring cell carcinoma, CEA positive, lymph node metastasis, brain metastasis, liver metastasis and lung metastasis. The areas under the receiver operating curve (AUROC) were 0.903 and 0.889 in the development and validation cohort. Patients with scores from 0 to 4 points had about 0.1% risk of developing BM, and the risk increased to about 30% in patients with scores ≥15 points., Conclusions: This clinical risk model is accurate enough to identify the CRC patients with high risk of synchronous BM and to further provide more individualized clinical decision.

Background: Intravenous thrombolysis with recombinant tissue plasminogen activator (rtPA) is an effective treatment of acute ischemic stroke (AIS). The safety of intravenous rtPA in patients with thrombocytopenia is unclear. This study sought to evaluate the impact of thrombocytopenia on in-hospital outcomes in patients with AIS who received intravenous thrombolysis., Methods: This was a retrospective study using the 2012-2014 National Inpatient Sample (20% stratified sample of US hospitals). The study identified adult patients admitted with AIS who received intravenous rtPA during hospitalization. The identified admissions were stratified into 2 cohorts based on the presence or absence of thrombocytopenia. Multilevel, multivariate regression analysis and propensity matching were performed to evaluate in-hospital mortality, length of stay, and in-hospital complications., Results: Of 101,527 patients admitted for AIS and received intravenous rtPA from 2012 to 2014, 3,520 (3.47%) had thrombocytopenia. In-hospital mortality was 10.8 vs. 6.9% in patients with and without thrombocytopenia in original data, p < 0.001. In-hospital length of stay was significantly higher in the thrombocytopenia group (5.9 vs. 8.2 days, p < 0.001). The differences were significant in both the multivariate regression model and the propensity score matching model. Patients with thrombocytopenia also had a statistically higher incidence of intracranial hemorrhage, postprocedural bleeding, blood transfusion, tracheotomy, and mechanical ventilation., Conclusion: Thrombocytopenia is associated with higher in-hospital mortality, longer length of stay, a higher incidence of intracranial hemorrhage, postprocedural bleeding, and mechanical ventilation in stroke patients who received intravenous rtPA., (© 2019 S. Karger AG, Basel.)

Large reductions of sulfur and nitrogen oxide emissions in the United States have led to considerable improvements in air quality, though recent analyses in the Southeastern United States have shown little response of aerosol pH to these reductions. This study examines the effects of reduced emissions on the trend of aerosol acidity in fine particulate matter (PM 2.5 ), at a nationwide scale, using ambient concentration data from three monitoring networks-the Ammonia Monitoring Network (AMoN), the Clean Air Status and Trends network (CASTNET) and the Southeastern Aerosol Research and Characterization Network (SEARCH), in conjunction with thermodynamic (ISORROPIA-II) and chemical transport (CMAQ) model results. Sulfate and ammonium experienced similar and significant decreases with little change in pH, neutralization ratio ( f = [NH 4 + ]/2[SO 4 2- ] + [NO 3 - ]), or nitrate. Oak Grove, MS was the only SEARCH site showing statistically significant pH changes in the Southeast region where small increases in pH (0.003-0.09 pH units/year) were observed. Of the five regions characterized using CASTNET/AMoN data, only California exhibited a statistically significant, albeit small pH increase of +0.04 pH units/year. Furthermore, statistically insignificant (α = 0.05) changes in ammonia were observed in response to emission and PM 2.5 speciation changes. CMAQ simulation results had similar responses, showing steady ammonia levels and generally low pH, with little change from 2001 to 2011.

Invasive Asian bighead and silver carp (Hypophthalmichthys nobilis and H. molitrix) pose a substantial threat to North American aquatic ecosystems. Recently, environmental DNA (eDNA), genetic material shed by organisms into their environment that can be detected by non-invasive sampling strategies and genetic assays, has gained recognition as a tool for tracking the invasion front of these species toward the Great Lakes. The goal of this study was to develop new species-specific conventional PCR (cPCR) and quantitative (qPCR) markers for detection of these species in North American surface waters. We first generated complete mitochondrial genome sequences from 33 bighead and 29 silver carp individuals collected throughout their introduced range. These sequences were aligned with those from other common and closely related fish species from the Illinois River watershed to identify and design new species-specific markers for the detection of bighead and silver carp DNA in environmental water samples. We then tested these genetic markers in the laboratory for species-specificity and sensitivity. Newly developed markers performed well in field trials, did not have any false positive detections, and many markers had much higher detection rates and sensitivity compared to the markers currently used in eDNA surveillance programs. We also explored the use of multiple genetic markers to determine whether it would improve detection rates, results of which showed that using multiple highly sensitive markers should maximize detection rates in environmental samples. The new markers developed in this study greatly expand the number of species-specific genetic markers available to track the invasion front of bighead and silver carp and will improve the resolution of these assays. Additionally, the use of the qPCR markers developed in this study may reduce sample processing time and cost of eDNA monitoring for these species.

We compared the severity of pediatric inflammatory bowel disease in South Asians with Whites in the US. South Asians more commonly presented with poor weight gain, developed fistulas, and received treatment with antibiotics, methotrexate, adalimumab, and steroids. South Asians appear to have a more complicated presentation and course of pediatric inflammatory bowel disease., (Copyright © 2013 Mosby, Inc. All rights reserved.)