Efficacy and safety of anti-PD-1/PD-L1-based dual immunotherapies versus PD-1/PD-L1 inhibitor alone in patients with advanced solid tumor: a systematic review and meta-analysis.

INTRODUCTION: Numerous randomized controlled trials (RCTs) have investigated PD-1/PD-L1 inhibitor-based combination therapies. The debate surrounding the potential additive clinical benefits of combination of two immune-oncology (IO) therapies for cancer patients persists. METHODS: Both published and grey sources of randomized clinical trials that compared anti-PD-1/PD-L1-based immunotherapy combinations with monotherapy in patients with advanced or metastatic solid tumors were encompassed. The primary outcome was progression-free survival (PFS), and secondary outcomes included objective response rate (ORR), overall survival (OS) and treatment-related adverse events (TRAEs). RESULTS: Our analysis encompassed 31 studies comprising 10,341 patients, which covered 12 distinct immune-oncology combination regimens. Across all patients, the immunotherapy combinations exhibited the capability to enhance the ORR (OR = 1.23 [95% CI 1.13-1.34]) and extend PFS (HR = 0.91 [95% CI 0.87-0.95]). However, the observed enhancement in OS (HR = 0.96 [95% CI 0.91-1.01]) was of no significance. Greater benefits in terms of PFS (HR = 0.82 [95% CI 0.72 to 0.93]) and OS (HR = 0.85 [95% CI 0.73 to 0.99]) may be particularly pronounced in cases where PD-L1 expression is negative. Notably, despite a heightened risk of any-grade TRAEs (OR = 1.72 [95% CI 1.40-2.11]) and grade greater than or equal to 3 TRAEs (OR = 2.01 [95% CI 1.67-2.43]), toxicity was generally manageable. CONCLUSIONS: This study suggests that incorporating an additional immunotherapy agent with PD-1/PD-L1 inhibitors can elevate the response rate and reduce the risk of disease progression, all while maintaining manageable toxicity. However, there remains a challenge in translating these primary clinical benefits into extended overall survival.

Discharge Against Medical Advice After Hospitalization for Sepsis: Predictors, 30-Day Readmissions, and Outcomes.

BACKGROUND: Sepsis is a leading cause of death worldwide. However, little has been known concerning the status of discharge against medical advice (DAMA) in sepsis patients. OBJECTIVE: To identify factors associated with DAMA, evaluate the association of DAMA with 30-day unplanned readmission and readmitted outcomes after sepsis hospitalization. METHODS: Using the National Readmission Database, we identified sepsis patients who discharged routinely or DAMA in 2017. Multivariable models were used to identify factors related to DAMA, evaluate the association between DAMA and readmission, and elucidate the relationship between DAMA and outcomes in patients readmitted within 30 days. RESULTS: Among 1,012,650 sepsis cases, patients with DAMA accounted for 3.88% (n = 39,308). The unplanned 30-day readmission rates in patients who discharged home and DAMA were 13.08% and 27.21%, respectively. Predictors of DAMA in sepsis included Medicaid, diabetes, smoking, drug abuse, alcohol abuse, and psychoses. DAMA was statistically significantly associated with 30-day (odds ratio [OR] 2.18, 95% confidence interval [CI] 2.09-2.28), 60-day (OR 1.98, 95% CI 1.90-2.06), and 90-day (OR 1.88, 95% CI 1.81-1.96) readmission. DAMA is also associated with higher mortality in patients readmitted within 30 days (OR 1.38, 95% CI 1.17-1.63), whereas there were no statistically significant differences in length of stay and costs between patients who discharged home or DAMA. CONCLUSIONS: DAMA occurs in nearly 3.88% of sepsis patients and is linked to higher readmission and mortality. Those at high risk of DAMA should be early identified to motivate intervention to avoid premature discharges and associated adverse outcomes.

Host stimulator of interferon genes is essential for the efficacy of anti-programmed cell death protein 1 inhibitors in non-small cell lung cancer.

The stimulator of interferon genes (STING) pathway is important for anticancer immune responses. However, the relative contributions of host and tumour STING in anti-programmed cell death protein 1 (anti-PD-1) inhibitor responses in non-small cell lung cancer (NSCLC) are unknown. STING expression in tumour and blood was associated with anti-PD-1 therapy in NSCLC patients; Moreover, loss of PD-1 inhibitor therapeutic potency was demonstrated in STING KO (knock out) splenocytes and STING KO mice. STING knock-down in tumour cells had no effect. STING on CD8+ T cells and host cells, not tumour cells, correlated with clinical effect of anti-PD-1 therapy in NSCLC patients. Finally, adoptive transfer of CD8+ T cells restored PD-1 inhibitor anticancer effects. STING in host cells but not in tumour cells mediates anti-PD-1 inhibitor responses in cancer immunotherapy and could be used to select advantageous NSCLC patients from immunotherapy.

Immune checkpoint inhibitors alone vs immune checkpoint inhibitors-combined chemotherapy for NSCLC patients with high PD-L1 expression: a network meta-analysis.

BACKGROUND: We indirectly compared the effects of immune checkpoint inhibitors alone (ICI) and ICI-combined chemotherapy (chemo-ICI) in patients with non-small cell lung cancer who had high programmed death-ligand 1 (PD-L1) expression (defined as tumour proportion score ≥50% or TC3/IC3) through network meta-analyses. METHODS: Through literature searches, we shortlisted 22 randomised controlled trials encompassing 4289 patients, with objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) set as the primary outcomes. The dichotomous data for ORR and hazard ratios (HRs) and their 95% confidence intervals (CIs) for OS and PFS were extracted. RESULTS: We found that chemo-ICI had significantly improved ORR (OR 1.7, 95% CI 1.1-2.5) and PFS (HR 0.59, 95% CI: 0.48-0.74) relative to ICI. Although no significant difference in OS was observed, the analyses revealed that the chemo-ICI patients tended to undergo fewer progression events than ICI patients (HR 0.82, 95% CI 0.6-1.1). In subgroup analysis, the non-squamous, PD-1 inhibitor and first-line treatment cohorts exhibited significant differences in ORR and PFS, but not in OS. However, in the squamous, PD-L1 inhibitor, and previously treated cohorts, PFS, OS and ORR were not different between chemo-ICI and ICI patients. CONCLUSIONS: In conclusion, for non-squamous NSCLC patients, accepting PD-1 as the first-line treatment may be a relatively better option.

Worse Outcomes After Readmission to a Different Hospital After Sepsis: A Nationwide Cohort Study.

BACKGROUND: In the United States, sepsis accounts for 13% of the total hospital expenses and > 50% of hospital deaths. Moreover, people with sepsis are more likely to be readmitted. OBJECTIVE: The aim of this study was to assess the prevalence and outcomes of different hospital readmissions (DHRs) in patients with sepsis, and the factors associated with DHR. METHODS: We used data from the Nationwide Readmissions Database of the United States in 2017 to identify patients admitted for sepsis. Multivariable logistic regression analysis was used to evaluate the factors associated with DHR; five models were constructed to elucidate the relationship between DHR and in-hospital outcomes. RESULTS: In 2017, 85,120 (21.97%) of all patients with sepsis readmitted within 30 days in the United States were readmitted to a different hospital. The most common reason for readmission was infection irrespective of hospital status. Compared with the patients with sepsis who were readmitted to the same hospital, DHR was associated with higher hospitalization costs ($2264; 95% CI $1755-$2772; p < 0.001), longer length of stay (0.58 days; 95% CI 0.44-0.71 days; p < 0.001), and higher risk of in-hospital mortality (odds ratio 1.63; 95% CI 1.55-1.72; p < 0.001). CONCLUSIONS: DHR occurred in one-fifth of patients with sepsis in the United States. Our findings suggest that patients readmitted to a different hospital within 30 days may experience higher in-hospital mortality, longer length of stay, and higher hospitalization costs. Future studies need to examine whether continuity of care can improve the prognosis of patients with sepsis.

Chronic Thrombocytopenia and In-Hospital Outcomes After Primary Total Hip and Knee Arthroplasty.

BACKGROUND: There is a lack of data on the influence of chronic thrombocytopenia (cTCP) on clinical outcomes following primary total hip arthroplasty (THA) and total knee arthroplasty (TKA). Limited studies mainly focused on postoperative heparin-induced TCP from single centers with small sample sizes. This study aims to describe the characteristics, trend, and outcomes of cTCP in patients undergoing THA and TKA from a nationally reprehensive perspective. METHODS: We identified THA and TKA patients with and without cTCP from the 2005 to 2015 Nationwide Inpatient Sample. Annual percent changes were calculated to reflect cTCP trends. Multivariable regression and propensity score analyses were conducted to investigate the association of cTCP and mortality, preoperative complications, cost as well as length of stay. RESULTS: In total, 578,278 and 1,237,331 patients underwent primary THA and TKA, respectively. Proportion of cTCP annually increased by 6.95% in THA and 6.66% in TKA. Patients with cTCP were associated with higher risk of medical (odds ratio [OR] 2.00, 95% confidence interval [CI] 1.89-2.11) and surgical complications (OR 2.72, 95% CI 2.55-2.90) in THA, and higher risk of mortality (OR 1.68, 95% CI 1.22-2.31), medical (OR 1.94, 95% CI 1.85-2.03) and surgical complications (OR 2.55, 95% CI 2.38-2.73) in TKA. Additionally, higher cost and longer length of stay were observed in patients with cTCP for both surgical procedures. CONCLUSION: Patients with cTCP had higher risk of mortality for TKA, more perioperative complications for both TKA and THA. Further studies are warranted to improve the preoperative management and to prevent worse outcomes associated with cTCP.

Discharge Against Medical Advice in Acute Ischemic Stroke: the Risk of 30-Day Unplanned Readmission.

BACKGROUND: Discharge against medical advice may be associated with more readmissions. OBJECTIVE: To evaluate DAMA in patients with acute ischemic stroke (AIS) and identify the relationship between DAMA and 30-day unplanned readmissions. DESIGN: A retrospective cohort study. PARTICIPANTS: The National Readmission Database was used to identify inpatients with a primary diagnosis of AIS who were either discharged home or DAMA between 2010 and 2017 in the USA. MEASURES: Demographic features, hospital type, comorbidities, stroke risk factors, severity indices, and treatments were compared between patients discharged routinely and DAMA. Multivariable logistic regression was used to evaluate predictors of DAMA, and a double robust inverse probability of treatment weighting method was used to assess the association between DAMA and 30-day unplanned readmissions. KEY RESULTS: Overall, 1,335,484 patients with AIS were included, of whom 2.09% (n = 27,892) were DAMA. The prevalence of DAMA in AIS patients increased from 1.65 in 2010 to 2.57% in 2017. The rates of 30-day unplanned readmissions for DAMA and non-DAMA patients were 16.81% and 7.78%, respectively. Patients with drug abuse, alcohol abuse, smoking, prior stroke, psychoses, and intravenous thrombolysis had greater odds of DAMA. DAMA was associated with all-cause readmissions (OR, 2.04; 95% CI, 2.01-2.07) and remained a strong predictor for transient ischemic attack/stroke-specific and cardiac-specific causes of readmissions. CONCLUSIONS: Although the DAMA rate is low in AIS patients, DAMA is a risk factor for all-cause and recurrent stroke-specific readmissions. Future studies are needed to address issues around compliance and engagement with health care to reduce DAMA.

Temporary Trend, Characteristics and Clinical Outcomes of Acute Pancreatitis Patients Infected with Human Immunodeficiency Virus.

BACKGROUND: Compared to general population, human immunodeficiency virus (HIV) infection may increase frequency of acute pancreatitis (AP); however, evidence regarding effects of HIV infection on AP-related outcomes is limited and controversial. AIMS: We aim to investigate the temporary trend, characteristics and clinical outcomes of AP infected with HIV. METHODS: We reviewed data from the 2003-2014 National Inpatient Sample to identify patients with a primary diagnosis of AP. The primary outcomes (in-hospital mortality, acute respiratory failure, acute kidney injury, and prolonged length of stay [LOS]) and secondary outcomes (gastrointestinal hemorrhage, sepsis and total cost) were compared between patients with and without HIV infection using univariate, multivariable and propensity score matching analyses. RESULTS: Of 594,106 patients diagnosed with AP, 6775 (1.14%) had HIV infection. Patients with HIV were more likely to be younger, black, male, less likely to be gallstone-related and had lower rate of interventions. Multivariable analyses based on multiple imputation revealed that HIV infection was associated with higher risk of mortality (odds ratio [OR]: 1.74; 95% confidence interval [CI] 1.34-2.25), acute kidney injury (OR: 1.13; 95% CI 1.19-1.44), prolonged LOS (OR: 1.26; 95% CI 1.15-1.37) and 6% higher cost. There were no differences in sepsis, gastrointestinal bleeding, and respiratory failure between groups. CONCLUSIONS: HIV infection is associated with adverse outcomes including increased mortality, acute kidney injury and more healthcare utilization in AP patients. More assertive management strategies like early intravenous fluid resuscitation in HIV patients hospitalized with AP to prevent acute kidney injury may be helpful to improve clinical outcomes.

Prior bariatric surgery and perioperative cardiovascular outcomes following noncardiac surgery in patients with type 2 diabetes mellitus: hint from National Inpatient Sample Database.

BACKGROUND: Both diabetes and obesity are risk factors for perioperative major adverse events. This study aims to evaluate the association between prior bariatric surgery (prior-BS) and perioperative cardiovascular outcomes following noncardiac surgery in patients with type 2 diabetes mellitus (T2DM). METHODS: We used the National Inpatient Sample Database to identify T2DM patients undergoing major noncardiac surgery from 2006 to 2014. The primary outcome was major perioperative adverse cardiovascular and cerebrovascular events (MACCEs), which include death, acute myocardial infarction and acute ischaemic stroke. In-hospital outcomes between patients with prior BS and morbid obesity were compared using unadjusted logistic, multivariable logistic and propensity score matching analyses. RESULTS: A weighted of 1,526,820 patients diagnosed with T2DM who underwent noncardiac surgery were included. The rates of both prior BS and morbid obesity significantly increased during the study period (P < 0.0001). Patients with prior BS were younger, were more likely to be female, and had lower rates of cardiovascular risk factors but had higher rates of smoking, alcohol abuse, anaemia, prior venous thromboembolism and prior percutaneous coronary intervention. The incidence of MACCEs was 1.01% and 3.25% in patients with prior BS and morbid obesity, respectively. After multivariable adjustment, we found that prior BS was associated with a reduced risk of MACCEs (odds ratio [OR] = 0.71; 95% confidence interval [CI] 0.62-0.81), death (OR = 0.64, 95% CI 0.52-0.78), acute kidney injury (OR = 0.66, 95% CI 0.62-0.70) and acute respiratory failure (OR: 0.46; 95% CI 0.42-0.50). CONCLUSIONS: Prior bariatric surgery in T2DM patients undergoing noncardiac surgery is associated with a lower risk of MACCEs. Prospective studies are needed to verify the benefits of bariatric surgery in patients undergoing noncardiac surgery.

Atrial fibrillation in hospitalized patients with end-stage liver disease: temporal trends in prevalence and outcomes.

BACKGROUND & AIMS: End-stage liver disease (ESLD) happens due to the development and progression of chronic liver disease. This study aims to investigate the temporal trend, patient characteristics and outcomes of atrial fibrillation (AF) in hospitalized ESLD patients across the United States. METHODS: Nationwide Inpatient Sample from 2003 to 2014 was utilized to retrospectively study the weighted prevalence of AF in hospitalized ESLD patients. Multivariable regression models were used to assess the association between AF with clinical factors, in-hospital mortality, length of stay (LOS) and cost. RESULTS: 639 345 hospitalizations associated with ESLD were identified, of which 47 710 (7.48%) were diagnosed with AF. The prevalence of AF increased from 5.73% in 2003 to 9.75% in 2014 in ESLD and varied by age, race, income, insurance type and hospital characteristics. Factors associated with AF included advancing age, male, white race, high income and urban teaching hospital. AF presence was associated with significant higher in-hospital mortality (odds ratio, 1.40; 95% confidence interval, 1.35-1.45), 21% longer LOS and 22% higher cost. In addition, a significant decreasing trend in in-hospital mortality was observed (from 16.70% to 10.63% in patients with AF and from 10.74% to 7.50% in patients without AF). CONCLUSIONS: The prevalence of AF in hospitalized ESLD patients has continued to increase from 2003 through 2014. AF is associated with poor prognosis and higher health resource utilization. Innovative anticoagulation strategies through improved collaboration between cardiologists and hepatologists are required for better management of hospitalized ESLD patients comorbid with AF.

Does dietary intake of selenium protect against cancer? A systematic review and meta-analysis of population-based prospective studies.

Current evidence on selenium and its effects on cancer is conflicting. This study aimed at assessing the association between dietary intake of selenium and incidence of cancers by performing systematic review and meta-analysis of population-based prospective studies. We systematically searched for articles in Medline (Ovid), Embase, Web of Science (Thomson Reuters), China National Knowledge Infrastructure, Wanfang Database and VIP Chinese Scientific Journals. Analysis was performed in Stata version 14.2. Of the 2,564 articles obtained from the databases, 39 met our inclusion criteria, 37 were included in the final analysis. Selenium at recommended daily allowance levels of ≥55 µg/day decreased the risk of cancer [relative risk (RR) = 0.94, 95% confidence interval (CI): 0.90-0.98]. A protective effect was found in men at levels ≥55 µg/day (RR = 0.97, 95% CI: 0.94-0.99). Extra selenium intake from supplements was protective at levels ≥55 µg/day (RR = 0.89, 95% CI: 0.82-0.97). There was an inverse relationship (p value = 0.020) between selenium intake and overall cancer risk after adjusting for age, body mass index, and smoking but there was no evidence of nonlinear relationship (p value = 0.261). The findings in this study suggest that selenium is protective against cancer however the effects vary with different cancers.

Dynamic statistical model for predicting the risk of death among older Chinese people, using longitudinal repeated measures of the frailty index: a prospective cohort study.

BACKGROUND: Frailty is a common characteristic of older people with the ageing process. We aimed to develop and validate a dynamic statistical prediction model to calculate the risk of death in people aged ≥65 years, using a longitudinal frailty index (FI). METHODS: One training dataset and three validation datasets from the Chinese Longitudinal Healthy Longevity Survey (CLHLS) were used in our study. The training dataset and validation datasets 1 to 3 included data from 9,748, 7,459, 9,093 and 6,368 individuals, respectively. We used 35 health deficits to construct the FI and a longitudinal FI based on repeated measurement of FI at every wave of the CLHLS. A joint model was used to build a dynamic prediction model considering both baseline covariates and the longitudinal FI. Areas under time-dependent receiver operating characteristic curves (AUCs) and calibration curves were employed to assess the predictive performance of the model. RESULTS: A linear mixed-effects model used time, sex, residence (city, town, or rural), living alone, smoking and alcohol consumption to calculate a subject-specific longitudinal FI. The dynamic prediction model was built using the longitudinal FI, age, residence, sex and an FI-age interaction term. The AUCs ranged from 0.64 to 0.84, and both the AUCs and the calibration curves showed good predictive ability. CONCLUSIONS: We developed a dynamic prediction model that was able to update predictions of the risk of death as updated measurements of FI became available. This model could be used to estimate the risk of death in individuals aged >65 years.

Comparison and trend of perioperative outcomes between robot-assisted radical prostatectomy and open radical prostatectomy: nationwide inpatient sample 2009-2014.

PURPOSE: To make a further evaluation of perioperative outcomes between the robot-assisted radical prostatectomy (RARP) and open radical prostatectomy (ORP), we conducted a comparison and trend analysis by using the Nationwide Inpatient Sample (NIS) from 2009 to 2014. MATERIALS AND METHODS: Adult prostate cancer patients with radical prostatectomy were abstracted from the NIS. RARP and ORP were identified according to the International Classification of Diseases, 9th Revision, Clinical Modification procedure codes. The perioperative outcomes included blood transfusion, intraoperative and postoperative complications, prolonged length of stay (pLOS), and in-hospital mortality. Propensity score matching method and multivariable logistic regression model were performed to adjust for the pre-defined covariates. The annual percent change (APC) was used to detect the change trend of rates for outcomes. RESULTS: A total of 77.054 patients were included in our study. According to the results of propensity score matching analyses, RARP outperformed ORP in blood transfusion (1.96% vs. 9.40%), intraoperative complication (0.73% vs. 1.25%), overall postoperative complications (8.87% vs. 11.97%), and pLOS (13.39% vs. 36.70%). We also found that there was a significant decreasing tendency of incidence in blood transfusion (APC=-9.81), intraoperative complication (APC=-12.84), and miscellaneous surgical complications (APC=-14.09) for the RARP group. The results of multivariable analyses were almost consistent with those of propensity score matching analyses. CONCLUSIONS: The RARP approach has lower incidence rates of perioperative complications than the ORP approach, and there is a potential decreasing tendency of complication incidence rates for the RARP.

Significant Nationwide Variability in the Costs and Hospital Mortality Rates of Autologous Stem Cell Transplantation for Multiple Myeloma: An Analysis of the Nationwide Inpatient Sample Database.

Autologous hematopoietic stem cell transplantation (AHCT) is the standard of care for eligible patients with multiple myeloma (MM). In this study, we explored disparities in hospital cost and in-hospital mortality among patients with MM who underwent AHCT. Data were obtained from the Nationwide Inpatient Sample database for 2005 to 2014. International Classification of Diseases, Ninth Edition, Clinical Modification diagnosis and procedure codes were used to identify patients. Hospitals were divided into quintiles according to the weighted volume of AHCTs performed in patients with MM. Multiple imputation with chained equation was used for missing data. Linear trend analysis of age- and sex-adjusted mortality, as well as inflation-adjusted hospital cost, was performed. Univariate regression screening followed by stepwise multivariate regression was performed for dependent variables, including mortality and inflation-adjusted hospital cost. Identified significant predictors underwent sensitivity analyses. Overall age- and sex-adjusted mortality rates and inflation-adjusted hospital costs decreased between 2005 and 2014; however, tremendous nationwide variability exists. Patients who underwent AHCT at very-low-volume hospitals (Q1) had significantly higher in-hospital mortality. Both geographic location and hospital type had impacted age- and sex-adjusted mortality rates and inflation-adjusted hospital costs. Despite an overall improvement in mortality and decreased cost of AHCT for patients with MM, nationwide variability in care exists. Further study is needed to identify correctable factors that contribute to the identified correlation.

Dietary fiber intake and reduced risk of ovarian cancer: a meta-analysis.

BACKGROUND: Epidemiological studies regarding the association between dietary fiber intake and ovarian cancer risk are still inconsistent. We aimed to review the available evidence and conduct a dose-response meta-analysis to investigate the relationship between dietary fiber intake and ovarian cancer risk. METHODS: Relevant studies were identified by searching PubMed, EMBASE, and the Cochrane Library databases before August 2017. Studies that reported relative risk (RR) estimates with 95% confidence intervals (CIs) for the association between dietary fiber intake and risk of ovarian cancer were included. Random-effects models were used to combine the estimated effects extracted from individual study. RESULTS: Thirteen studies, with a total of 5777 ovarian cancer cases and 142,189 participants, met the inclusion criteria. The pooled multivariable RRs of ovarian cancer for the highest vs. the lowest category of dietary fiber intake was 0.78 (95% CI: 0.70, 0.88) with no evidence of heterogeneity (I2 = 4.20%, P = 0.40). Our dose-response analysis also showed a significant inverse association between dietary fiber intake and ovarian cancer risk (an increment of 10 g/day; combined RR: 0.88; 95% CI: 0.82, 0.93). There was no evidence for a nonlinear association (P for nonlinearity = 0.83). CONCLUSIONS: This meta-analysis suggests a significant inverse dose-response association between dietary fiber intake and ovarian cancer risk. Further studies with prospective design that take account of more potential confounders are warranted to confirm this association.

Pentraxin-3 in Thrombolytic Therapy for Acute Ischemic Stroke: No Relation with Curative Effect and Prognosis.

BACKGROUND Pentraxin-3 (PTX3) is considered a high quality inflammatory marker of the severity and prognosis of several diseases, however, the value of PTX3 in thrombolytic therapy for acute ischemic stroke remains unclear and PTX3 is still controversial in evaluating the prognosis of stroke patients. In this study, we investigated the association of PTX3 with thrombolytic therapy in patients with acute ischemic stroke. MATERIAL AND METHODS Forty-seven stroke patients who received thrombolytic therapy within 4.5 hours after symptom onset were enrolled consecutively between July 2016 and June 2017. All the patients underwent multiphase CTA (computerized tomography angiography) or CT perfusion before thrombolysis with no indication for endovascular treatment. Initial and 24 hours of National Institute of Health Stroke Scale (NIHSS) scores and serum PTX3 level, stroke risk factors and predictors, and mRS (modified Rankin scale) at 3 months were collected prospectively. Predictors of thrombolytic therapy effect and long-term prognosis were investigated by univariate and multivariate logistic regression. RESULTS The 24 hour NIHSS score and the treatment time was associated with symptom improvement, while the PTX3 level had no association with neurological improvement and prognosis in stroke patients receiving thrombolytic therapy. CONCLUSIONS PTX3 is not suitable to serve as an indicator of thrombolytic efficacy and had no association with long-term prognosis in stroke patients receiving thrombolytic therapy.

Dose-response relationship between dietary magnesium intake, serum magnesium concentration and risk of hypertension: a systematic review and meta-analysis of prospective cohort studies.

BACKGROUND: The findings of prospective cohort studies are inconsistent regarding the association between dietary magnesium intake and serum magnesium concentration and the risk of hypertension. We aimed to review the evidence from prospective cohort studies and perform a dose-response meta-analysis to investigate the relationship between dietary magnesium intake and serum magnesium concentrations and the risk of hypertension. METHODS: We searched systematically PubMed, EMBASE and the Cochrane Library databases from October 1951 through June 2016. Prospective cohort studies reporting effect estimates with 95% confidence intervals (CIs) for hypertension in more than two categories of dietary magnesium intake and/or serum magnesium concentrations were included. Random-effects models were used to combine the estimated effects. RESULTS: Nine articles (six on dietary magnesium intake, two on serum magnesium concentration and one on both) of ten cohort studies, including 20,119 cases of hypertension and 180,566 participates, were eligible for inclusion in the meta-analysis. We found an inverse association between dietary magnesium intake and the risk of hypertension [relative risk (RR) = 0.92; 95% CI: 0.86, 0.98] comparing the highest intake group with the lowest. A 100 mg/day increment in magnesium intake was associated with a 5% reduction in the risk of hypertension (RR = 0.95; 95% CI: 0.90, 1.00). The association of serum magnesium concentration with the risk of hypertension was marginally significant (RR = 0.91; 95% CI: 0.80, 1.02). CONCLUSIONS: Current evidence supports the inverse dose-response relationship between dietary magnesium intake and the risk of hypertension. However, the evidence about the relationship between serum magnesium concentration and hypertension is limited.

The role of methylprednisolone in severe COVID-19 patients: a meta-analysis.

Background: The purpose of this study is to assess the effectiveness of methylprednisolone in severe COVID-19. Methods: PubMed, the Cochrane Library and Web of Science were searched for literatures comparing methylprednisolone and control treatment in severe COVID-19 patients. Statistical pooling was reported as risk ratio (RR) with corresponding 95% confidence interval (CI). The outcomes of interest in the literature survey were mortality and adverse events. Results: A total of 13 studies were included, including 3,138 patients with severe COVID-19, of which 1,634 patients were treated with methylprednisolone and 1,504 patients were treated with control treatment. Five of the 13 studies reported severe adverse events. Our meta-analysis indicates that methylprednisolone treatment in COVID-19 patients is associated with a significant reduction in mortality (RR 0.62, 95% CI 0.46-0.85, p = 0.003) compared to control treatment, without an increased risk of adverse events (RR 1.20, 95% CI 0.92-1.56, p = 0.17). Moreover, high-dose methylprednisolone treatment (RR 0.57; 95% CI 0.40-0.82, p = 0.003) and short-course methylprednisolone treatment (RR 0.54; 95% CI 0.38-0.89, p = 0.01) found to significantly reduce mortality. Additionally, it was found that younger severe COVID-19 patients (RR 0.40; 95% CI 0.20-0.80, p = 0.01) had better outcomes to methylprednisolone than older patients. Conclusion: Methylprednisolone was correlated with lower mortality compared with control treatment in severe COVID-19 patients without increasing serious adverse reactions. Furthermore, high-doses and short-term of methylprednisolone treatment were linked with better younger COVID-19 reported higher benefit from methylprednisolone than older COVID-19 patients.

Identifying patients who benefit more from perioperative immunotherapy combinations for resectable non-small cell lung cancer based on clinical and molecular characteristics: a meta-analysis of randomized clinical trials.

PURPOSE: This study aims to identify patient subgroups who benefit more from perioperative immunotherapy combined with chemotherapy (IO-CT) based on clinical and molecular characteristics in resectable non-small cell lung cancer (NSCLC). METHODS: Randomized controlled trials (RCTs) on perioperative IO-CT were searched. Beneficial differences of IO-CT regimens across different patient subgroups were assessed by pooling trial-specific ratios in event-free survival (EFS), overall survival (OS), pathological complete response (pCR), and major pathological response (MPR). RESULTS: Six studies (n = 3003) involving five IO-CT regimens were included. Compared to CT alone, all IO-CT regimens significantly improved EFS, OS, MPR, and pCR, but increased toxicity. Toripa-chemo showed the best EFS and nivo-chemo showed the best OS. Patients with PD-L1 ≥ 1% had more EFS benefits compared to those with PD-L1 < 1% (HR [hazard ratio]: 1.55, 95% CI 1.17-2.04). Squamous NSCLC patients had significantly more pCR and MPR benefits than non-squamous NSCLC patients (pCR: OR [odds ratio] 0.68, 95% CI 0.49-0.95; MPR: OR 0.61, 95% CI 0.45-0.82). Former smokers had significantly higher pCR benefits than non-smokers (OR: 2.18; 95% CI 1.21-3.92). Additionally, OS benefit was significantly higher in patients < 65 years compared to those ≥ 65 years (HR ratio: 0.59, 95% CI 0.36-0.95). For MPR, males benefited significantly more from IO-CT compared to females (OR: 1.69, 95% CI 1.18-2.42). CONCLUSION: Perioperative IO-CT is more effective but more toxic than CT alone in resectable NSCLC. Patients with PD-L1 ≥ 1%, squamous NSCLC, a history of smoking, age < 65 years and male gender may experience greater benefits from perioperative IO-CT.