Right Ventricular Response to Acute Hypoxia Exposure: A Systematic Review

Background: Acute hypoxia exposure is associated with an elevation of pulmonary artery pressure (PAP), resulting in an increased hemodynamic load on the right ventricle (RV). In addition, hypoxia may exert direct effects on the RV. However, the RV responses to such challenges are not fully characterized. The aim of this systematic review was to describe the effects of acute hypoxia on the RV in healthy lowland adults.Methods: We systematically reviewed PubMed and Web of Science and article references from 2005 until May 2021 for prospective studies evaluating echocardiographic RV function and morphology in healthy lowland adults at sea level and upon exposure to simulated altitude or high-altitude.Results: We included 37 studies in this systematic review, 12 of which used simulated altitude and 25 were conducted in high-altitude field conditions. Eligible studies reported at least one of the RV variables, which were all based on transthoracic echocardiography assessing RV systolic and diastolic function and RV morphology. The design of these studies significantly differed in terms of mode of ascent to high-altitude, altitude level, duration of high-altitude stay, and timing of measurements. In the majority of the studies, echocardiographic examinations were performed within the first 10 days of high-altitude induction. Studies also differed widely by selectively reporting only a part of multiple RV parameters. Despite consistent increase in PAP documented in all studies, reports on the changes of RV function and morphology greatly differed between studies.Conclusion: This systematic review revealed that the study reports on the effects of acute hypoxia on the RV are controversial and inconclusive. This may be the result of significantly different study designs, non-compliance with international guidelines on RV function assessment and limited statistical power due to small sample sizes. Moreover, the potential impact of other factors such as gender, age, ethnicity, physical activity, mode of ascent and environmental factors such as temperature and humidity on RV responses to hypoxia remained unexplored. Thus, this comprehensive overview will promote reproducible research with improved study designs and methods for the future large-scale prospective studies, which eventually may provide important insights into the RV response to acute hypoxia exposure.

Efficacy and Safety of Autologous Stem-Cell Transplantation as Part of First-Line Treatment for Newly Diagnosed Primary Central Nervous System Lymphoma: A Systematic Review and Meta-Analysis

ObjectiveThe reviewed literature supports a treatment regimen for primary central nervous system lymphoma (PCNSL) that includes induction chemotherapy, followed by one consolidation therapy. High-dose chemotherapy supported by autologous stem-cell transplantation (ASCT) is the most studied option, but its effects are controversial. The aim of this study was to evaluate the efficacy and safety of ASCT for newly diagnosed PCNSL by means of a meta-analysis.MethodsThe PubMed, Embase, and Cochrane Library databases were systematically searched for studies published until May 20, 2021. Included studies were prospective studies of patients with newly diagnosed PCNSL treated with ASCT. The pooled rates and 95% confidence intervals (CIs) were determined for all outcomes. Subgroup analysis was conducted to compare the relative risk (RR) with 95% CIs for the complete remission (CR) rate and the hazard ratios (HRs) with 95% CIs for progression-free survival (PFS) and overall survival (OS).ResultsThirteen prospective studies including 348 patients were analyzed. The pooled CR rate, overall response rate, and relapse rate were 80% (95% CI, 71–88%, I2 = 67.06%, p = 0.00), 95% (95% CI, 87–100%, I2 = 73.65%, p= 0.00), and 19% (95% CI, 15–24%, I2 = 76.18%, p = 0.00), respectively. The pooled 2- and 5-year PFS and OS rates were 74% (95% CI, 68–80%, I2 = 3.90%), 65% (95% CI, 51–77%, I2 = 74.61%), 80% (95% CI, 72–88%, I2 = 57.54%), and 69% (95% CI, 53–83%, I2 = 83.89%), respectively. Hematological toxicity and infections were more common adverse events above grade 3. The pooled treatment-related mortality was 3% (95% CI, 1–6%, I2 = 28.18%, p = 0.16). In the group analysis of ASCT compared with whole-brain radiotherapy, there were no significant differences in the CR rate (RR, 1.00, 95% CI, 0.88–1.14, p = 0.971), relapse rate (RR, 0.44, 95% CI, 0.06–3.10, p = 0.408), PFS (HR, 1.28, 95% CI, 0.81–2.01, p = 0.29), or OS (HR, 1.62, 95% CI, 0.97–2.69, p = 0.06). Cognitive functions were preserved or improved after ASCT.ConclusionsASCT is a feasible approach for consolidation with good tolerability for newly diagnosed PCNSL patients. High-quality randomized controlled trials are still needed to confirm the effects of ASCT.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42021268422.

Dose-Response Association Between Bilirubin and Cardiovascular Disease: A Systematic Review and Meta-analysis

The association between bilirubin (BIL) and cardiovascular disease (CVD) remains controversial. We performed a meta-analysis of prospective studies to evaluate this association in the general population. We searched PubMed, EMBASE, Web of Science, Cochrane, and Scopus databases through to September 2021. The Newcastle-Ottawa Quality Assessment Scale was used to assess study quality. The pooled effect estimate was calculated by the fixed-effect model or random-effect model. We included 12 prospective studies (368 567 participants). The pooled risk ratio of CVD for the lowest vs highest groups of BIL levels was .75 (95% CI: .58-.97) with high heterogeneity (I2 = 87.5%, P < .001). Similar associations were observed for coronary heart disease and stroke. We further performed a “dose-response” meta-analysis, and a significant U-shaped relationship between circulating (most values were serum bilirubin, but a few were plasma bilirubin) BIL and CVD ( P < .01) was observed. The lowest risk of CVD events was observed in participants with a BIL of 17-20 µmol/L in serum and/or plasma. In conclusion, there was a U-shaped dose-response relationship between BIL and CVD, especially for men. Further studies are needed to confirm our findings and identify the mechanisms involved as well as any prognostic or therapeutic potential.

Prognosis of Upfront Surgery for Pancreatic Cancer: A Systematic Review and Meta-Analysis of Prospective Studies

BackgroundThe rate of patients with pancreatic ductal adenocarcinoma (PDAC) receiving neoadjuvant chemotherapy is increasing, but upfront resection is still offered to most patients with resectable or borderline resectable disease. Encouraging data reported in adjuvant chemotherapy trials prompts surgeons towards upfront surgery, but such trials are subject to a significant selection bias. This systematic review aims to summarize available high-quality evidence regarding survival of patients treated with upfront surgery for PDAC.MethodsPubmed, Cochrane, and Web of Science Databases were interrogated for prospective studies published between 2000 and 2021 that included at least a cohort of patients treated with upfront surgery for resectable or borderline resectable PDAC. The Cochrane Collaboration’s risk-of-bias tool for randomized trials (RoB-2) was used to assess risk of bias in all randomized studies. Patient weighted median overall survival (OS) and disease-free survival (DFS) were calculated.ResultsOverall, 8,341 abstracts were screened, 17 reports were reviewed in full text, and finally 5 articles and 1 conference abstract underwent data extraction. Included studies were published between 2014 and 2021. All studies were RCTs comparing different neoadjuvant treatment strategies to upfront surgery. Three studies included only resectable PDAC patients, two studies recruited patients with resectable and borderline resectable disease, and one study selected only borderline resectable patients. A total of 439 patients were included in the upfront resection cohorts of the 6 studies, ranging between 20 to 180 patients per study. The weighted median OS after upfront surgery was 18.8 (95% CI 12.4 – 20.6) months. Median DFS was 9 (95% CI 1.6 – 12.5) months. Resection rate was 74.5% (range 65-90%). Adjuvant treatment was initiated in 68% (range 43-77%) of resected patients.ConclusionsHigh-quality data for PDAC patients undergoing upfront surgery is scarce. Meta-analysis from the included studies showed a significantly shorter OS and DFS compared to recently published studies focusing on adjuvant combination chemotherapy, suggesting that the latter may overestimate survival due to the exclusion of most patients scheduled for upfront surgery.

The Decision-Making Process for Palliative Sedation for Patients with Advanced Cancer–Analysis from a Systematic Review of Prospective Studies

Background. The involvement of patients in decision making about their healthcare plans is being emphasized. In the context of palliative sedation, it is unclear how these decisions are made and who are involved in. The aim of the study is to understand how this decision-making is taken. Method. Information from a systematic review on clinical aspects of palliative sedation prospective studies were included. PubMed, CINAHL, Cochrane, MEDLINE, and EMBASE were searched (January 2014–December 2019). Data extraction and analysis regarded: (a) When and by whom the decision-making process is initiated; (b) patient involvement; (c) family involvement and (d) healthcare involvement. Results. Data about decision making were reported in 8/10 included articles. Palliative sedation was reported in 1137 patients (only 16 of them were non-cancer). Palliative sedation was introduced by the palliative care team during the disease process, at admission, or when patients experienced refractory symptoms. Only two studies explicitly mentioned the involvement of patients in decision making. Co-decision between families and the regular health care professionals was usual, and the health care professionals involved had been working in palliative care services. Conclusion. Patient participation in decision making appeared to be compromised by limited physical or cognitive capacity and family participation is described. The possibility of palliative sedation should be discussed earlier in the disease process.

The impact of clinical and population strategies on coronary heart disease mortality: an assessment of Rose’s big idea

Background Coronary heart disease (CHD), the leading cause of death worldwide, has declined in many affluent countries but it continues to rise in industrializing countries. Objective To quantify the relative contribution of the clinical and population strategies to the decline in CHD mortality in affluent countries. Design Meta-analysis of cross-sectional and prospective studies. Data sources PubMed and Web of Science from January 1, 1970 to December 31, 2019. Method We combined and analyzed data from 22 cross-sectional and prospective studies, representing 500 million people, to quantify the relative decline in CHD mortality attributable to the clinical strategy and population strategy. Result The population strategy accounted for 48% (range = 19 to 73%) of the decline in CHD deaths and the clinical strategy accounted for 42% (range = 25 to 56%), with moderate inconsistency of results across studies. Conclusion Since 1970, a larger fraction of the decline in CHD deaths in industrialized countries was attributable to reduction in CHD risk factors than medical care. Population strategies, which are more cost-effective than clinical strategies, are under-utilized.

Asymptomatic Scalp Carriage among Household Contacts of Children Affected by Tinea Capitis: A Prospective Study in the Metropolitan Area of Brussels, Belgium

<b><i>Introduction:</i></b> Tinea capitis (TC) is a superficial fungal infection affecting the scalp. The existence of asymptomatic carriers (ACs) could represent a potential reservoir responsible of (re)contamination and failure of treatment. No prospective studies on ACs in household contacts of TC patients in Europe have been published to date. <b><i>Objectives:</i></b> The aim of this study was to assess the prevalence of ACs in a cohort of household contacts of children who were diagnosed with TC in the metropolitan area of Bruxelles, Belgium. <b><i>Methods:</i></b> This prospective observational study was conducted from October 2015 to April 2016 at the Dermatology Department of the University Hospitals Brugmann, Saint-Pierre, Queen Fabiola Children Hospital. <b><i>Results:</i></b> Ninety-nine cases of TC from 95 different family circles were included. The main infectious agent identified was <i>Microsporum audouinii</i> in 53 cases. The mean age of TC patients was 5.8 years. Male/female ratio was 2.8. Eighty-one household contacts of TC patients were enrolled in the study. Two cases of ACs (5%) were identified. <b><i>Conclusions:</i></b> <i>M. audouinii</i> was the most common pathogen identified. The prevalence of ACs we report is on average higher compared to other European large cities. Larger prospective studies including all close contacts of affected patients are required in order to establish guidelines regarding identification and management of ACs.

Modifiable Risk Factors for Incident Dementia and Cognitive Impairment: An Umbrella Review of Evidence

Dementia and cognitive impairment can be attributed to both genetic and modifiable risk factors. Recently, considerable evidence emerged and urgently require standardized evaluation. To address it, we conducted an umbrella review of prospective studies regarding the associations of dementia and cognitive impairment with modifiable factors to evaluate the strength and validity of the existing evidence. We searched PubMed, Embase, CINAHL and Cochrane Database of Systematic Reviews to identify relevant systematic reviews and meta-analyses of prospective studies. Mendelian randomization studies were reviewed to assess the causality for these associations. For each association, we analyzed the summary effect size, 95% confidence interval, 95% prediction interval, heterogeneity, small study effect and excess significance bias. Based on these estimates, the evidence was graded into levels of convincing, highly suggestive, suggestive, or weak. In total, 12015 articles were identified, of which 118 eligible studies yielded 243 unique associations. Convincing evidence was found for associations of dementia and cognitive impairment with early-life education, midlife to late-life plasma glucose, body mass index, atrial fibrillation, benzodiazepine use, and gait speed. Suggestive to highly suggestive evidence was found for associations of dementia and cognitive impairment with midlife to late-life blood pressure, homocysteine, cerebrovascular diseases, hearing impairment, respiratory illness, anemia, smoking, alcohol consumption, diet, sleep, physical activity and social engagement. Among convincing evidence, Mendelian randomization studies verified genetic predicted causal relationships for education and plasma glucose with Alzheimer's disease. Modifiable factors identified in this study, especially those with high-level evidence, should be considered in dementia prevention. Trial registration: PROSPERO CRD42020195729.