Pulmonary hypertension: An important predictor of outcomes in patients undergoing non-cardiac surgery

SummaryObjectivesPerioperative risk associated with pulmonary hypertension (PH) in patients undergoing non-cardiac surgery (NCS) remains poorly defined. We report perioperative outcomes in a large cohort of patients undergoing NCS, comparing those with and without PH.MethodsPatients undergoing NCS at our institution between January 2002 and December 2006, were cross matched with a Right Heart Catheterization (RHC) database for the same period. Patients were excluded if they were <18 years old and if they underwent cardiac surgery prior to NCS or minor procedures using local anesthesia or sedation. Controls were defined as patients who underwent similar NCS with mean pulmonary arterial pressure (MPAP) ≤ 25 mmHg.Results173 patients underwent RHC and NCS during the specified period and were included in the analysis. Of these 96 (55%) had PH. Mean pulmonary arterial pressure (p = 0.001), American Association of Anesthesiology Class (p = 0.02), and chronic renal insufficiency (p = 0.03) were determined as independent risk factors for post-operative morbidity. Patients with PH were more likely to develop congestive heart failure (p < 0.001; OR: 11.9), hemodynamic instability (p < 0.002), sepsis (p < 0.0005), and respiratory failure (p < 0.004). Patients with PH needed longer ventilatory support (p < 0.002), stayed longer in the ICU (p < 0.04), and were more frequently readmitted to the hospital within 30 days (p < 008; OR 2.4).ConclusionsIn addition to the traditionally known risk factors for outcomes after NCS such as coronary artery disease, diabetes mellitus, chronic renal insufficiency, American Society of Anesthesiology class, the presence of underlying PH can have a significant negative impact on perioperative outcomes

Acute Endovascular Reperfusion Therapy in Ischemic Stroke: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

[email protected] Randomized controlled trials (RCTs) of endovascular therapy for acute ischemic stroke have had inconsistent results. We evaluated the efficacy and safety of endovascular therapy in published RCTs. Methods We performed a systematic review of RCTs of endovascular therapy with thrombolytic or mechanical reperfusion compared with interventions without endovascular therapy. Primary outcome was the frequency of good functional outcome (modified Rankin scale (mRS) of 0-2 at 90 days) and secondary outcomes were mortality at 90 days and symptomatic intracranial hemorrhage (sICH). Random-effects meta-analysis was performed and the Cochrane risk of bias assessment was used to evaluate quality of evidence. Results Ten studies involving 1,612 subjects were included. Endovascular therapy was not significantly associated with good functional outcome (Relative Risk [RR] =1.17; 95% CI, 0.97 to 1.42; p=0.10 and Absolute Risk Difference [ARD] =7%; 95%CI -0.1% to 14%; p=0.05); heterogeneity was moderate among studies (I2=30%). Mortality was unchanged with endovascular therapy (RR=0.92; 95 % CI, 0.75 to 1.13; p=0.45) and there was no difference in sICH (RR=1.20; 95 % CI, 0.79 to 1.82; p=0.39). The quality of evidence was low for all outcomes and the recommendation is weak for the use of endovascular therapy as per GRADE methodology. Conclusions Intra-arterial therapy did not show significant increase in good outcomes and no changes in either mortality or sICH in patients with acute ischemic stroke. We need further RCTs with better design and quality to evaluate the true efficacy of endovascular therapy.Revisión por pare

Effects of preeclampsia and eclampsia on maternal metabolic and biochemical outcomes in later life: a systematic review and meta-analysis

Objective: To evaluate the association between preeclampsia (PE) and eclampsia (E) on subsequent metabolic and biochemical outcomes. Methods: Systematic review and meta-analysis of observational studies. We searched five engines until November 2018 for studies evaluating the effects of PE/E on metabolic and biochemical outcomes after delivery. PE was defined as presence of hypertension and proteinuria at >20 weeks of pregnancy; controls did not have PE/E. Primary outcomes were blood pressure (BP), body mass index (BMI), metabolic syndrome (MetS), blood lipids and glucose levels. Random effects models were used for meta-analyses, and effects reported as risk difference (RD) or mean difference (MD) and their 95% confidence interval (CI). Subgroup analyses by time of follow up, publication year, and confounder adjustment were performed. Results: We evaluated 41 cohorts including 3300 PE/E and 13,967 normotensive controls. Women were followed up from 3 months after delivery up to 32 years postpartum. In comparison to controls, PE/E significantly increased systolic BP (MD = 8.3 mmHg, 95%CI 6.8 to 9.7), diastolic BP (MD = 6.8 mmHg, 95%CI 5.6 to 8.0), BMI (MD = 2.0 kg/m2; 95%CI 1.6 to 2.4), waist (MD = 4.3 cm, 95%CI 3.1 to 5.5), waist-to-hip ratio (MD = 0.02, 95%CI 0.01 to 0.03), weight (MD = 5.1 kg, 95%CI 2.2 to 7.9), total cholesterol (MD = 4.6 mg/dL, CI 1.5 to 7.7), LDL (MD = 4.6 mg/dL; 95%CI 0.2 to 8.9), triglycerides (MD = 7.7 mg/dL, 95%CI 3.6 to 11.7), glucose (MD = 2.6 mg/dL, 95%CI 1.2 to 4.0), insulin (MD = 19.1 pmol/L, 95%CI 11.9 to 26.2), HOMA-IR index (MD = 0.7, 95%CI 0.2 to 1.2), C reactive protein (MD = 0.05 mg/dL, 95%CI 0.01 to 0.09), and the risks of hypertension (RD = 0.24, 95%CI 0.15 to 0.33) and MetS (RD = 0.11, 95%CI 0.08 to 0.15). Also, PE/E reduced HDL levels (MD = –2.15 mg/dL, 95%CI –3.46 to −0.85). Heterogeneity of effects was high for most outcomes. Risk of bias was moderate across studies. Subgroup analyses showed similar effects as main analyses. Conclusion: Women who had PE/E have worse metabolic and biochemical profile than those without PE/E in an intermediate to long term follow up period. ©Revisión por pare

Insulin resistance and endometrial cancer risk: A systematic review and meta-analysis

Abstract Aim: It has been suggested that chronic hyperinsulinemia from insulin resistance is involved in the etiology of endometrial cancer (EC). We performed a systematic review and meta-analysis to assess whether insulin resistance is associated with the risk of EC. Methods: We searched PubMed-Medline, Embase, Scopus, and Web of Science for articles published from database inception through 30th September 2014. We included all observational studies evaluating components defining insulin resistance in women with and without EC. Quality of the included studies was assessed by NewcastleeOttawa scale. Randomeffects models and inverse variance method were used to meta-analyze the association between insulin resistance components and EC. Results: Twenty-five studies satisfied our inclusion criteria. Fasting insulin levels (13 studies, n Z 4088) were higher in women with EC (mean difference [MD] 33.94 pmol/L, 95% confi- dence interval [CI] 15.04e52.85, p Z 0.0004). No differences were seen in postmenopausal versus pre- and postmenopausal subgroup analysis. Similarly, non-fasting/fasting C-peptide levels (five studies, n Z 1938) were also higher in women with EC (MD 0.14 nmol/L, 95% CI 0.08e0.21, p < 0.00001). Homeostatic model assessment - insulin resistance (HOMA-IR) values (six studies, n Z 1859) in EC patients were significantly higher than in women without EC (MD 1.13, 95% CI 0.20e2.06, p Z 0.02). There was moderate-to-high heterogeneity among the included studies. Conclusion: Currently available epidemiologic evidence is suggestive of significantly higher risk of EC in women with high fasting insulin, non-fasting/fasting C-peptide and HOMAIR values.Revisión por pare

Efficacy and harms of tocilizumab for the treatment of COVID-19 patients: A systematic review and meta-analysis

Introduction We systematically assessed benefits and harms of tocilizumab (TCZ), which is an antibody blocking IL-6 receptors, in hospitalized COVID-19 patients. Methods Five electronic databases and two preprint webpages were searched until March 4, 2021. Randomized controlled trials (RCTs) and inverse probability treatment weighting (IPTW) cohorts assessing TCZ effects in hospitalized, COVID-19 adult patients were included. Primary outcomes were all-cause mortality, clinical worsening, clinical improvement, need for mechanical ventilation, and adverse events (AE). Inverse variance random-effects meta-analyses were performed with quality of evidence (QoE) evaluated using GRADE methodology. Results Nine RCTs (n = 7,021) and nine IPTW cohorts (n = 7,796) were included. TCZ significantly reduced all-cause mortality in RCTs (RR 0.89, 95%CI 0.81–0.98, p = 0.03; moderate QoE) and non-significantly in cohorts (RR 0.67, 95%CI 0.44–1.02, p = 0.08; very low QoE) vs. control (standard of care [SOC] or placebo). TCZ significantly reduced the need for mechanical ventilation (RR 0.80, 95%CI 0.71–0.90, p = 0.001; moderate QoE) and length of stay (MD -1.92 days, 95%CI -3.46 to -0.38, p = 0.01; low QoE) vs. control in RCTs. There was no significant difference in clinical improvement or worsening between treatments. AEs, severe AEs, bleeding and thrombotic events were similar between arms in RCTs, but there was higher neutropenia risk with TCZ (very low QoE). Subgroup analyses by disease severity or risk of bias (RoB) were consistent with main analyses. Quality of evidence was moderate to very low in both RCTs and cohorts. Conclusions In comparison to SOC or placebo, TCZ reduced all-cause mortality in all studies and reduced mechanical ventilation and length of stay in RCTs in hospitalized COVID-19 patients. Other clinical outcomes were not significantly impacted. TCZ did not have effect on AEs, except a significant increased neutropenia risk in RCTs. TCZ has a potential role in the treatment of hospitalized COVID-19 patients.Revisión por pare

Efficacy and Safety of Colchicine in Post-acute Myocardial Infarction Patients : A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Background: Inflammation plays a key role in atherosclerotic plaque destabilization and adverse cardiac remodeling. Recent evidence has shown a promising role of colchicine in patients with coronary artery disease. We evaluated the efficacy and safety of colchicine in post-acute myocardial infarction (MI) patients. Methods: We searched five electronic databases from inception to January 18, 2021, for randomized controlled trials (RCTs) evaluating colchicine in post-acute MI patients. Primary outcomes were cardiovascular mortality and recurrent MI. Secondary outcomes were all-cause mortality, stroke, urgent coronary revascularization, levels of follow-up high-sensitivity C-reactive protein (hs-CRP), and drug-related adverse events. All meta-analyses used inverse-variance random-effects models. Results: Six RCTs involving 6,005 patients were included. Colchicine did not significantly reduce cardiovascular mortality [risk ratio (RR), 0.91; 95% confidence interval (95% CI), 0.52-1.61; p = 0.64], recurrent MI (RR, 0.87; 95% CI, 0.62-1.22; p = 0.28), all-cause mortality (RR, 1.06; 95% CI, 0.61-1.85; p = 0.78), stroke (RR, 0.28; 95% CI, 0.07-1.09; p = 0.05), urgent coronary revascularization (RR, 0.46; 95% CI, 0.02-8.89; p = 0.19), or decreased levels of follow-up hs-CRP (mean difference, −1.95 mg/L; 95% CI, −12.88 to 8.98; p = 0.61) compared to the control group. There was no increase in any adverse events (RR, 0.97; 95% CI, 0.89-1.07; p = 0.34) or gastrointestinal adverse events (RR, 2.49; 95% CI, 0.48-12.99; p = 0.20). Subgroup analyses by colchicine dose (0.5 vs. 1 mg/day), time of follow-up (30 days) showed no changes in the overall findings. Conclusion: In post-acute MI patients, colchicine does not reduce cardiovascular or all-cause mortality, recurrent MI, or other cardiovascular outcomes. Also, colchicine did not increase drug-related adverse event

Macrophage Migration Inhibitory Factor Secretion Is Induced by Ionizing Radiation and Oxidative Stress in Cancer Cells.

The macrophage migration inhibitory factor (MIF) has been increasingly implicated in cancer development and progression by promoting inflammation, angiogenesis, tumor cell survival and immune suppression. MIF is overexpressed in a variety of solid tumor types in part due to its responsiveness to hypoxia inducible factor (HIF) driven transcriptional activation. MIF secretion, however, is a poorly understood process owing to the fact that MIF is a leaderless polypeptide that follows a non-classical secretory pathway. Better understanding of MIF processing and release could have therapeutic implications. Here, we have discovered that ionizing radiation (IR) and other DNA damaging stresses can induce robust MIF secretion in several cancer cell lines. MIF secretion by IR appears independent of ABCA1, a cholesterol efflux pump that has been implicated previously in MIF secretion. However, MIF secretion is robustly induced by oxidative stress. Importantly, MIF secretion can be observed both in cell culture models as well as in tumors in mice in vivo. Rapid depletion of MIF from tumor cells observed immunohistochemically is coincident with elevated circulating MIF detected in the blood sera of irradiated mice. Given the robust tumor promoting activities of MIF, our results suggest that an innate host response to genotoxic stress may mitigate the beneficial effects of cancer therapy, and that MIF inhibition may improve therapeutic responses

Efficacy of Tunnel Technique (TUN) versus Coronally Advanced Flap (CAF) in the Management of Multiple Gingival Recession Defects: A Meta-Analysis

Objective. We systematically assessed the efficacy of tunnel technique (TUN) vs. coronally advanced flap (CAF) in the management of multiple gingival recession defects in adults. Methods. Five databases were searched until September 2021 for randomized controlled trials (RCTs) assessing TUN vs. CAF; grafts of interest were acellular dermal matrix (ADM) and connective tissue graft (CTG). Primary outcomes were root coverage (RC) and complete root coverage (CRC). Secondary outcomes were clinical attachment level (CAL), keratinized tissue width (KTW), probing depth (PD), and recession coverage (REC). Effect measures were risk ratio (RR) or mean difference (MD) with their confidence intervals (95% CI). Inverse variance methods and random-effects model meta-analyses were used. Subgroup analyses by the type of graft were performed. Quality of evidence was assessed using GRADE methodology. Results. Five RCTs (n = 173) were included, with a follow-up of 6 months for all outcomes. In comparison to CAF, TUN did not significantly reduce CRC (RR 0.65; 95% CI 0.002–176.7; p=0.51) and did not increase RC (MD 0.99%; 95% CI −6.7 to 8.6; p=0.80). In comparison to CAF, TUN showed no significant reduction of secondary outcomes. Subgroup analyses by type of graft showed no differences in comparison to primary analyses for primary and secondary outcomes. Three RCTs had a high risk of bias, and five RCTs had very low quality of evidence for all outcomes. Conclusions. In adults with gingival recessions, TUN had similar primary and secondary outcomes in comparison with CAF. Subgroup analyses by the type of graft did not affect main conclusions. More RCTs with better design are needed to further characterize the effects of TUN vs. CAF in the treatment of multiple gingival recession defects