Background Previous analyses of The Society of Thoracic Surgeons (STS) Adult Cardiac Surgery Database have demonstrated a reduction over time of risk-adjusted operative mortality after coronary ...artery bypass grafting. The STS Congenital Heart Surgery Database (STS CHSD) was queried to assess multiinstitutional trends over time in discharge mortality and postoperative length of stay (PLOS). Methods Since 2009, operations in the STS CHSD have been classified according to STAT (The Society of Thoracic Surgeons—European Association for Cardio-Thoracic Surgery) Congenital Heart Surgery Mortality Categories. The five STAT Mortality Categories were chosen to be optimal with respect to minimizing variation within categories and maximizing variation between categories. For this study, all index cardiac operations from 1998 to 2014, inclusive, were grouped by STAT Mortality Category (exclusions: patent ductus arteriosus ligation in patients weighing less than or equal to 2.5 kg and operations that could not be assigned to a STAT Mortality Category). End points were discharge mortality and PLOS in survivors for the entire period and for 4-year epochs. The Cochran-Armitage trend test was used to test the null hypothesis that the mortality was the same across epochs, by STAT Mortality Category. Results The analysis encompassed 202,895 index operations at 118 centers. The number of centers participating in STS CHSD increased in each epoch. Overall discharge mortality was 3.4% (6,959 of 202,895) for 1998 to 2014 and 3.1% (2,308 of 75,337) for 2011 to 2014. Statistically significant improvement in discharge mortality was seen in STAT Mortality Categories 2, 3, 4, and 5 ( p values for STAT Mortality Categories 1 through 5 are 0.060, <0.001, 0.015, <0.001, and <0.001, respectively). PLOS in survivors was relatively unchanged over the same time intervals. Sensitivity analyses reveal that the finding of declining risk-stratified rates of discharge mortality over time is not simply attributable to the addition of more centers to the cohort over time. Conclusions This 16-year analysis of STS CHSD reveals declining discharge mortality over time, especially for more complex operations.
Abstract Background Asthmatic inflammation is dominated either by eosinophil and/or neutrophil accumulation in airways. Disposal of these inflammatory cells is the key to disease control. ...Eosinophilic airway inflammation is responsive to corticosteroid treatment, while neutrophilic inflammation is resistant and increases the burden of global health care. Corticosteroid resistant neutrophilic asthma remains mechanistically poorly understood and requires novel effective therapeutic strategies. Objective We thought to explore the underlying mechanisms of airway inflammation persistence as well as corticosteroid resistance, and to investigate a new strategy of effective treatment against corticosteroid-insensitive neutrophilic asthma. Methods Mouse models of either eosinophils-dominated or neutrophils-dominated airway inflammation were used in this study to test corticosteroid sensitivity in vivo and in vitro . We also used vav-Bcl-2 transgenic mice to confirm the importance of granulocytes apoptosis in the clearance of airway inflammation. Finally, Bcl-2 inhibitors ABT-737 or ABT-199 –were tested for their therapeutic effects against eosinophilic or neutrophilic airway inflammation and airway hyperresponsiveness. Results Overexpression of Bcl-2 protein was found to be responsible for persistence of granulocytes in bronchoalveolar lavage fluid following allergic challenge. This was important as allergen-induced airway inflammation aggravated and persisted in vav-Bcl-2 transgenic mice, where nucleated hematopoietic cells were over-expressed with Bcl-2 and resistant to apoptosis. Bcl-2 inhibitors, ABT-737 or ABT-199, play efficient roles in alleviation of either eosinophilic or corticosteroid resistant-neutrophilic airway inflammation, by inducing apoptosis of immune cell, such as eosinophils, neutrophils, Th2, Th17 and dendritic cells. Moreover, these inhibitors were found to be more efficient than steroid to induce granulocytes apoptosis ex vivo from severe asthma patients. Conclusion Apoptosis of inflammatory cells is essential for the clearance of allergen-induced airway inflammation. Bcl-2 inhibitors ABT-737 or ABT-199 may be promising drugs for the treatment against airway inflammation, especially for corticosteroid-insensitive neutrophilic airway inflammation.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
To investigate the current situation of neonatal care resources (NCR), newborn mortality rates (NMR), regional differences and existing challenges in China.
By using a self-designed questionnaire ...form and the cross-sectional method, we conducted a survey of all hospitals equipped with neonatal facilities in China from March 2019 to March 2020 with respect to the level and nature of these hospitals, the number of newborn beds and NICU beds, the number of neonatal pediatricians, and the development of therapeutic techniques. The data about the newborn births and deaths were retrieved from the annual statistics of the health commissions of the related provinces, autonomous regions and municipalities.
Included in this nationwide survey were 3,020 hospitals from all 22 provinces, 5 autonomous regions and 4 municipalities directly under the Central Government of Mainland China, with a 100% response rate. They included 1,183 (39.2%) level-3 (L3) hospitals, 1629 (53.9%) L-2 hospitals and 208 (6.9%) L-1 hospitals. Geographically, 848 (31.4%) hospitals were distributed in Central China, 983 (32.5%) hospitals in East China, and 1,089 (36.1%) in West China. The 3,020 included hospitals were altogether equipped with 75,679 newborn beds, with a median of 20 (2-350) beds, of which 2,286 hospitals (75.7%) were equipped with neonatal intensive care units (NICU), totaling 28,076 NICU beds with a median of 5 (1-160) beds. There were altogether 27,698 neonatal pediatricians in these hospitals, with an overall doctor-bed ratio of 0.366. There were 48.18 newborn beds and 17.87 NICU beds per 10,000 new births in China. In East, Central and West China, the number of neonatal beds, NICU beds, neonatal pediatricians, and attending pediatricians or pediatricians with higher professional titles per 10,000 newborns was 42.57, 48.64 and 55.67; 17.07, 18.66 and 18.17; 16.26, 16.51 and 20.81; and 10.69, 10.81 and 11.29, respectively. However, when the population and area are taken into consideration and according to the health resources density index (HRDI), the number of newborn beds, NICU beds and neonatal pediatricians in West China was significantly lower than that in Central and East China. In addition, only 10.64% of the neonatal pediatricians in West China possessed the Master or higher degrees, vs. 31.7% in East China and 20.14% in Central China. On the contrary, the number of neonatal pediatricians with a lower than Bachelor degree in West China was significantly higher than that in Central and East China (13.28% vs. 7.36% and 4.28%). Technically, the application rate of continuous positive airway pressure (CPAP) and conventional mechanical ventilation (CMV) in L-1 hospitals of West China was lower than that in Central and East China. According to the statistics in 2018, the newborn mortality rate (NMR) in West China was significantly higher than that in Central and East China.
China has already possessed relatively good resources for neonatal care and treatment, which is the primary reason for the rapid decrease in the NMR in China. However, there are still substantial regional differences. The density of health resources, the level of technical development and educational background of neonatal pediatricians in West China still lag behind those in other regions of China and need to be further improved and upgraded.
This research work was funded by National Natural Science Foundation of China (81671504) and United Nations International Children's Emergency Fund (CHINA-UNICEF501MCH).
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From 2003 to 2005, standardised 5-year cancer survival in China was much lower than in developed countries and varied substantially by geographical area. Monitoring population-level cancer survival ...is crucial to the understanding of the overall effectiveness of cancer care. We therefore aimed to investigate survival statistics for people with cancer in China between 2003 and 2015.
We used population-based data from 17 cancer registries in China. Data for the study population was submitted by the end of July 31, 2016, with follow-up data on vital status obtained on Dec 31, 2015. We used anonymised, individual cancer registration records of patients (aged 0–99 years) diagnosed with primary, invasive cancers from 2003 to 2013. Patients eligible for inclusion had data for demographic characteristics, date of diagnosis, anatomical site, morphology, behaviour code, vital status, and last date of contact. We analysed 5-year relative survival by sex, age, and geographical area, for all cancers combined and 26 different cancer types, between 2003 and 2015. We stratified survival estimates by calendar period (2003–05, 2006–08, 2009–11, and 2012–15).
There were 678 842 records of patients with invasive cancer who were diagnosed between 2003 and 2013. Of these records, 659 732 (97·2%) were eligible for inclusion in the final analyses. From 2003–05 to 2012–15, age-standardised 5-year relative survival increased substantially for all cancers combined, for both male and female patients, from 30·9% (95% CI 30·6–31·2) to 40·5% (40·3–40·7). Age-standardised 5-year relative survival also increased for most cancer types, including cancers of the uterus (average change per calendar period 5·5% 95% CI 2·5–8·5), thyroid (5·4% 3·2–7·6), cervix (4·5% 2·9–6·2), and bone (3·2% 2·1–4·4). In 2012–15, age-standardised 5-year survival for all patients with cancer was higher in urban areas (46·7%, 95% CI 46·5–47·0) than in rural areas (33·6%, 33·3–33·9), except for patients with oesophageal or cervical cancer; but improvements in survival were greater for patients residing in rural areas than in urban areas. Relative survival decreased with increasing age. The increasing trends in survival were consistent with the upward trends of medical expenditure of the country during the period studied.
There was a marked overall increase in cancer survival from 2003 to 2015 in the population covered by these cancer registries in China, possibly reflecting advances in the quality of cancer care in these areas. The survival gap between urban and rural areas narrowed over time, although geographical differences in cancer survival remained. Insight into these trends will help prioritise areas that need increased cancer care.
National Key R&D Program of China, PUMC Youth Fund and the Fundamental Research Funds for the Central Universities, and Major State Basic Innovation Program of the Chinese Academy of Medical Sciences.
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Objectives This study tested whether interleukin (IL)-17A is involved in the pathogenesis of mouse myocardial ischemia/reperfusion (I/R) injury and investigated the mechanisms. Background ...Inflammatory processes play a major role in myocardial I/R injury. We recently identified IL-17A as an important cytokine in inflammatory cardiovascular diseases such as atherosclerosis and viral myocarditis. However, its role in myocardial I/R injury remains unknown. Methods The involvement of IL-17A was assessed in functional assays in mouse myocardial I/R injury by neutralization/repletion or genetic deficiency of IL-17A, and its mechanism on cardiomyocyte apoptosis and neutrophil infiltration were further studied in vivo and in vitro. Results Interleukin-17A was elevated after murine left coronary artery ligation and reperfusion. Intracellular cytokine staining revealed that γδT lymphocytes but not CD4+ helper T cells were a major source of IL-17A. Anti–IL-17A monoclonal antibody treatment or IL-17A knockout markedly ameliorated I/R injury, as demonstrated by reduced infarct size, reduced cardiac troponin T levels, and improved cardiac function. This improvement was associated with a reduction in cardiomyocyte apoptosis and neutrophil infiltration. In contrast, repletion of exogenous IL-17A induced the opposite effect. In vitro study showed that IL-17A mediated cardiomyocyte apoptosis through regulating the Bax/Bcl-2 ratio, induced CXC chemokine-mediated neutrophil migration and promoted neutrophil-endothelial cell adherence through induction of endothelial cell E-selectin and inter-cellular adhesion molecule-1 expression. Conclusions IL-17A mainly produced by γδT cells plays a pathogenic role in myocardial I/R injury by inducing cardiomyocyte apoptosis and neutrophil infiltration.
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Background Mitral valve (MV) repair is performed with less frequency than MV replacement in older persons, with referral often delayed until symptoms are severe. Surgical practice in this population ...remains inconsistent in the absence of national MV repair outcomes. The goal of this study was to assess durability and longitudinal outcomes after isolated primary MV repair in patients aged 65 years or more. Methods We linked clinical data from The Society of Thoracic Surgeons adult cardiac surgery database (STS) to longitudinal claims data from the Centers for Medicare and Medicaid Services (CMS). Between January 1991 and December 2007, we identified 14,604 isolated nonemergent primary MV repair operations in STS-CMS data. These were longitudinally examined for mortality, mitral reoperation, and readmissions for heart failure, bleeding, and stroke. Predictors of 5-year death after MV repair were identified using Cox proportional hazard modeling. Results The study cohort had a mean age of 73.3 ± 5.5 years, ejection fraction 54.0% ± 12.9%; 55.8% (8,148 of 14,604) were female; and 8.4% (1,233 of 14,604) were non-Caucasian. Operative mortality was 2.59% (378 of 14,604). Mean follow-up was 5.9 ± 3.9 years (range, 1.0 to 18.0). Survival during follow-up was 74.9% (10,934 of 14,604). The number of observed events for mitral reoperation, heart failure, bleeding, and stroke were 552 of 14,604 (3.7%), 2,681 of 14,604 (18.4%), 1,051 of 14,604 (7.2%), and 1,131 of 14,604 (7.7%), respectively. The 10-year Kaplan-Meier event rates for mitral reoperation, heart failure, bleeding, and stroke were 6.2%, 30.1%, 15.3%, and 16.4%, respectively. The 10-year actuarial survival of 57.4% was equivalent to the matched US population. Conclusions Utilizing linked STS and CMS databases, we demonstrate that MV repair is a safe and durable long-term option for older patients. Survival restored to the normal population suggests repair may suppress the longitudinal impact of mitral regurgitation in the elderly and that the practice of delayed referral should be reevaluated. These data provide a contemporary longitudinal benchmark of MV repair outcomes.
Background Nasal polyps (NPs) are characterized by eosinophilic inflammation, which is generally considered sensitive to corticosteroid treatment. Objectives We evaluated levels of neutrophilia in ...NPs and investigated whether increased neutrophilia in polyp tissue affected the response to corticosteroid treatment. Methods We studied 3 independent cross-sectional groups of patients with NPs. Levels of infiltration by different types of inflammatory cells were determined by using immunohistochemical analyses and compared with those seen in control nasal tissues from subjects without NPs. Levels of inflammatory mediators were measured by using real-time PCR, ELISA, and FlowCytomix analyses. Patients with NPs received oral corticosteroid therapy (30 mg of prednisone once daily for 7 days); clinical parameters of efficacy were associated with NP phenotypes. Results Among patients with NPs, 76.5% had an eosinophilic phenotype, 46.0% had a neutrophilic phenotype, and 35.8% had a mixed phenotype (indicated by double staining). Overall, patients' symptoms improved after corticosteroid treatment; numbers of eosinophils and levels of their mediators (IL-4 and IL-5), but not numbers of neutrophils or levels of their mediators (IL-8 and interferon-inducible protein 10), were reduced ( P < .05). After corticosteroid treatment, patients with the nonneutrophilic phenotype (neutrophil negative) had significantly greater reductions in bilateral polyp size scores, nasal congestion scores, total nasal symptom scores, and nasal resistance than patients with the neutrophilic phenotype (neutrophil positive, P < .05). Conclusions There are different phenotypes of NPs based on the type of immune cell infiltrate and cytokines produced (eosinophilic or neutrophilic). Patients with the neutrophilic phenotype have less response to treatment with corticosteroids based on symptom scores.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Background Failure to rescue (FTR) is increasingly recognized as an important quality indicator in surgery. The Society of Thoracic Surgeons National Database was used to develop FTR metrics and a ...predictive FTR model for coronary artery bypass grafting (CABG). Methods The study included 604,154 patients undergoing isolated CABG at 1,105 centers from January 2010 to January 2014. FTR was defined as death after four complications: stroke, renal failure, reoperation, and prolonged ventilation. FTR was determined for each complication and a composite of the four complications. A statistical model to predict FTR was developed. Results FTR rates were 22.3% for renal failure, 16.4% for stroke, 12.4% for reoperation, 12.1% for prolonged ventilation, and 10.5% for the composite. Mortality increased with multiple complications and with specific combinations of complications. The multivariate risk model for prediction of FTR demonstrated a C index of 0.792 and was well calibrated, with a 1.0% average difference between observed/expected (O/E) FTR rates. With centers grouped into mortality terciles, complication rates increased modestly (11.4% to 15.7%), but FTR rates more than doubled (6.8% to 13.9%) from the lowest to highest terciles. Centers in the lowest complication rate tercile had an FTR O/E of 1.14, whereas centers in the highest complication rate tercile had an FTR O/E of 0.91. Conclusions CABG mortality rates vary directly with FTR, but complication rates have little relation to death. FTR rates derived from The Society of Thoracic Surgeons data can serve as national benchmarks. Predicted FTR rates may facilitate patient counseling, and FTR O/E ratios have promise as valuable quality metrics.
Summary Background Nusinersen is a 2′- O -methoxyethyl phosphorothioate-modified antisense drug being developed to treat spinal muscular atrophy. Nusinersen is specifically designed to alter splicing ...of SMN2 pre-mRNA and thus increase the amount of functional survival motor neuron (SMN) protein that is deficient in patients with spinal muscular atrophy. Methods This open-label, phase 2, escalating dose clinical study assessed the safety and tolerability, pharmacokinetics, and clinical efficacy of multiple intrathecal doses of nusinersen (6 mg and 12 mg dose equivalents) in patients with infantile-onset spinal muscular atrophy. Eligible participants were of either gender aged between 3 weeks and 7 months old with onset of spinal muscular atrophy symptoms between 3 weeks and 6 months, who had SMN1 homozygous gene deletion or mutation. Safety assessments included adverse events, physical and neurological examinations, vital signs, clinical laboratory tests, cerebrospinal fluid laboratory tests, and electrocardiographs. Clinical efficacy assessments included event free survival, and change from baseline of two assessments of motor function: the motor milestones portion of the Hammersmith Infant Neurological Exam—Part 2 (HINE-2) and the Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND) motor function test, and compound motor action potentials. Autopsy tissue was analysed for target engagement, drug concentrations, and pharmacological activity. HINE-2, CHOP-INTEND, and compound motor action potential were compared between baseline and last visit using the Wilcoxon signed-rank test. Age at death or permanent ventilation was compared with natural history using the log-rank test. The study is registered at ClinicalTrials.gov , number NCT01839656. Findings 20 participants were enrolled between May 3, 2013, and July 9, 2014, and assessed through to an interim analysis done on Jan 26, 2016. All participants experienced adverse events, with 77 serious adverse events reported in 16 participants, all considered by study investigators not related or unlikely related to the study drug. In the 12 mg dose group, incremental achievements of motor milestones (p<0·0001), improvements in CHOP-INTEND motor function scores (p=0·0013), and increased compound muscle action potential amplitude of the ulnar nerve (p=0·0103) and peroneal nerve (p<0·0001), compared with baseline, were observed. Median age at death or permanent ventilation was not reached and the Kaplan-Meier survival curve diverged from a published natural history case series (p=0·0014). Analysis of autopsy tissue from patients exposed to nusinersen showed drug uptake into motor neurons throughout the spinal cord and neurons and other cell types in the brainstem and other brain regions, exposure at therapeutic concentrations, and increased SMN2 mRNA exon 7 inclusion and SMN protein concentrations in the spinal cord. Interpretation Administration of multiple intrathecal doses of nusinersen showed acceptable safety and tolerability, pharmacology consistent with its intended mechanism of action, and encouraging clinical efficacy. Results informed the design of an ongoing, sham-controlled, phase 3 clinical study of nusinersen in infantile-onset spinal muscular atrophy. Funding Ionis Pharmaceuticals, Inc and Biogen.
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Prompt identification of patients suspected to have COVID-19 is crucial for disease control. We aimed to develop a deep learning algorithm on the basis of chest CT for rapid triaging in fever ...clinics.
We trained a U-Net-based model on unenhanced chest CT scans obtained from 2447 patients admitted to Tongji Hospital (Wuhan, China) between Feb 1, 2020, and March 3, 2020 (1647 patients with RT-PCR-confirmed COVID-19 and 800 patients without COVID-19) to segment lung opacities and alert cases with COVID-19 imaging manifestations. The ability of artificial intelligence (AI) to triage patients suspected to have COVID-19 was assessed in a large external validation set, which included 2120 retrospectively collected consecutive cases from three fever clinics inside and outside the epidemic centre of Wuhan (Tianyou Hospital Wuhan, China; area of high COVID-19 prevalence, Xianning Central Hospital Xianning, China; area of medium COVID-19 prevalence, and The Second Xiangya Hospital Changsha, China; area of low COVID-19 prevalence) between Jan 22, 2020, and Feb 14, 2020. To validate the sensitivity of the algorithm in a larger sample of patients with COVID-19, we also included 761 chest CT scans from 722 patients with RT-PCR-confirmed COVID-19 treated in a makeshift hospital (Guanggu Fangcang Hospital, Wuhan, China) between Feb 21, 2020, and March 6, 2020. Additionally, the accuracy of AI was compared with a radiologist panel for the identification of lesion burden increase on pairs of CT scans obtained from 100 patients with COVID-19.
In the external validation set, using radiological reports as the reference standard, AI-aided triage achieved an area under the curve of 0·953 (95% CI 0·949–0·959), with a sensitivity of 0·923 (95% CI 0·914–0·932), specificity of 0·851 (0·842–0·860), a positive predictive value of 0·790 (0·777–0·803), and a negative predictive value of 0·948 (0·941–0·954). AI took a median of 0·55 min (IQR: 0·43–0·63) to flag a positive case, whereas radiologists took a median of 16·21 min (11·67–25·71) to draft a report and 23·06 min (15·67–39·20) to release a report. With regard to the identification of increases in lesion burden, AI achieved a sensitivity of 0·962 (95% CI 0·947–1·000) and a specificity of 0·875 (95 %CI 0·833–0·923). The agreement between AI and the radiologist panel was high (Cohen's kappa coefficient 0·839, 95% CI 0·718–0·940).
A deep learning algorithm for triaging patients with suspected COVID-19 at fever clinics was developed and externally validated. Given its high accuracy across populations with varied COVID-19 prevalence, integration of this system into the standard clinical workflow could expedite identification of chest CT scans with imaging indications of COVID-19.
Special Project for Emergency of the Science and Technology Department of Hubei Province, China.
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