Associations between body mass index and all-cause mortality: A systematic review and meta-analysis

Fasting insulin and c-reactive protein confound the association between mortality and body mass index. An increase in fat mass may mediate the associations between hyperinsulinemia, hyperinflammation, and mortality. The objective of this study was to describe the “average” associations between body mass index and the risk of mortality and to explore how adjusting for fasting insulin and markers of inflammation might modify the association of BMI with mortality. MEDLINE and EMBASE were searched for studies published in 2020. Studies with adult participants where BMI and vital status was assessed were included. BMI was required to be categorized into groups or parametrized as non-first order polynomials or splines. All-cause mortality was regressed against mean BMI squared within seven broad clinical populations. Study was modeled as a random intercept. β coefficients and 95% confidence intervals are reported along with estimates of mortality risk by BMIs of 20, 30, and 40 kg/m². Bubble plots with regression lines are drawn, showing the associations between mortality and BMI. Splines results were summarized. There were 154 included studies with 6,685,979 participants. Only five (3.2%) studies adjusted for a marker of inflammation, and no studies adjusted for fasting insulin. There were significant associations between higher BMIs and lower mortality risk in cardiovascular (unadjusted β −0.829 [95% CI −1.313, −0.345] and adjusted β −0.746 [95% CI −1.471, −0.021]), Covid-19 (unadjusted β −0.333 [95% CI −0.650, −0.015]), critically ill (adjusted β −0.550 [95% CI −1.091, −0.010]), and surgical (unadjusted β −0.415 [95% CI −0.824, −0.006]) populations. The associations for general, cancer, and non-communicable disease populations were not significant. Heterogeneity was very large (I² ≥ 97%). The role of obesity as a driver of excess mortality should be critically re-examined, in parallel with increased efforts to determine the harms of hyperinsulinemia and chronic inflammation.     

Chronic kidney disease and postoperative mortality: a systematic review and meta-analysis

Whether renal dysfunction is an important factor in postoperative risk assessment has been difficult to prove. In an attempt to provide more compelling evidence, we conducted a systematic review comparing the risk of death and cardiac events in patients with and without chronic kidney disease who underwent elective noncardiac surgery. From electronic databases, web search engines, and bibliographies, 31 cohort studies were selected, evaluating postoperative outcomes in patients with chronic kidney disease. These patients had higher risks of postoperative death and cardiovascular events compared to those with preserved renal function. The pooled incidence of postoperative death was significantly less in those with preserved renal function than in those patients with chronic kidney disease. Meta-regression showed a graded relationship between disease severity and postoperative death. In adjusted analysis, chronic kidney disease had a similar strength of association with postoperative death as diabetes, stroke, and coronary disease. Our review identifies chronic kidney disease as an independent risk factor for postoperative death and cardiovascular events after elective, noncardiac surgery.     

Effect of chlorhexidine digluconate on different cell types: a molecular and ultrastructural investigation.

Although several studies have shown that chlorhexidine digluconate (CHX) has bactericidal activity against periodontal pathogens and exerts toxic effects on periodontal tissues, few have been directed to evaluate the mechanisms underlying its adverse effects on these tissues. Therefore, the aim of the present study was to investigate the in vitro cytotoxicity of CHX on cells that could represent common targets for its action in the surgical procedures for the treatment of periodontitis and peri-implantitis and to elucidate its mechanisms of action. Osteoblastic, endothelial and fibroblastic cell lines were exposed to various concentrations of CHX for different times and assayed for cell viability and cell death. Also analysis of mitochondrial membrane potential, intracellular Ca2+ mobilization and reactive oxygen species (ROS) generation were done in parallel, to correlate CHX-induced cell damage with alterations in key parameters of cell homeostasis. CHX affected cell viability in a dose and time-dependent manners, particularly in osteoblasts. Its toxic effect consisted in the induction of apoptotic and autophagic/necrotic cell deaths and involved disturbance of mitochondrial function, intracellular Ca2+ increase and oxidative stress. These data suggest that CHX is highly cytotoxic in vitro and invite to a more cautioned use of the antiseptic in the oral surgical procedures.     

Community‐Based Premarital Prevention: Clergy and Lay Leaders on the Front Lines*

This study reports on the results of the dissemination of an empirically‐based, premarital education program within religious organizations. The following major results are discussed with respect to premarital prevention: (a) Clergy and lay leaders were as effective in the short run as our university staff; (b) couples taking the more skills‐oriented intervention showed advantages over couples receiving naturally occurring services on interaction quality; and (c) couples reported that the communication skills components of premarital education were the most helpful.     

Development of Diabetes Mellitus Following Kidney Transplantation: A Canadian Experience

The onset of diabetes mellitus following kidney transplantation or post-transplant diabetes mellitus (PTDM) is now recognized as being an increasingly common complication that is associated with poor graft and patient survival. The incidence and clinical correlates of PTDM in a Canadian kidney transplant population has not been examined and may vary based on differences in demographics (i.e. race). Furthermore, little information exists on the association of variables such as cumulative dose of corticosteroids and trough calcineurin inhibitor levels and PTDM. We examined all recipients of a kidney transplant in our center between 1995 and 2001 and found an overall PTDM rate of 9.8%. Five clinical factors were independently associated with PTDM: older recipient age, deceased donor, hepatitis C antibody status, rejection episode and use of tacrolimus (vs. cyclosporine). Furthermore, cumulative corticosteroid dose and calcineurin inhibitor trough level were not associated with PTDM. This study demonstrates that in a Canadian kidney transplant population that there is a significant risk of PTDM following kidney transplantation, and it is therefore advisable to minimize this risk.     

Effect of frequent nocturnal hemodialysis vs conventional hemodialysis on left ventricular mass and quality of life: a randomized controlled trial

Context  Morbidity and mortality rates in hemodialysis patients remain excessive. Alterations in the delivery of dialysis may lead to improved patient outcomes. Objective  To compare the effects of frequent nocturnal hemodialysis vs conventional hemodialysis on change in left ventricular mass and health-related quality of life over 6 months. Design, Setting, and Participants  A 2-group, parallel, randomized controlled trial conducted at 2 Canadian university centers between August 2004 and December 2006. A total of 52 patients undergoing hemodialysis were recruited. Intervention  Participants were randomly assigned in a 1:1 ratio to receive nocturnal hemodialysis 6 times weekly or conventional hemodialysis 3 times weekly. Main Outcome Measures  The primary outcome was change in left ventricular mass, as measured by cardiovascular magnetic resonance imaging. The secondary outcomes were patient-reported quality of life, blood pressure, mineral metabolism, and use of medications. Results  Frequent nocturnal hemodialysis significantly improved the primary outcome (mean left ventricular mass difference between groups, 15.3 g, 95% confidence interval [CI], 1.0 to 29.6 g; P = .04). Frequent nocturnal hemodialysis did not significantly improve quality of life (difference of change in EuroQol 5-D index from baseline, 0.05; 95% CI, –0.07 to 0.17; P = .43). However, frequent nocturnal hemodialysis was associated with clinically and statistically significant improvements in selected kidney-specific domains of quality of life (P = .01 for effects of kidney disease and P = .02 for burden of kidney disease). Frequent nocturnal hemodialysis was also associated with improvements in systolic blood pressure (P = .01 after adjustment) and mineral metabolism, including a reduction in or discontinuation of antihypertensive medications (16/26 patients in the nocturnal hemodialysis group vs 3/25 patients in the conventional hemodialysis group; P < .001) and oral phosphate binders (19/26 patients in the nocturnal hemodialysis group vs 3/25 patients in the conventional dialysis group; P < .001). No benefit in anemia management was seen with nocturnal hemodialysis. Conclusion  This preliminary study revealed that, compared with conventional hemodialysis (3 times weekly), frequent nocturnal hemodialysis improved left ventricular mass, reduced the need for blood pressure medications, improved some measures of mineral metabolism, and improved selected measures of quality of life. Trial Registration  isrctn.org Identifier: ISRCTN25858715      

Amino acid changes in the amino terminus of the Na,K-adenosine triphosphatase alpha-2 subunit associated to familial and sporadic hemiplegic migraine

Familial hemiplegic migraine (FHM) is a rare subtype of migraine with aura inherited with an autosomal dominant pattern. Here, we report the genetic analysis of four families and one sporadic case with hemiplegic migraine (HM) in whom we searched for mutations in the three genes associated with the disease CACNA1A, ATP1A2 and SCN1A. Two novel amino acid changes p.Arg65Trp and p.Tyr9Asn, in the Na,K-adenosine triphosphatase (ATPase) alpha-2 subunit encoded by the ATP1A2 gene, were found in one FHM family and in the sporadic case, respectively. These mutations are peculiar for their location in the extreme N-terminus, an uncommon mutation target in this protein. Low frequency of migraine attacks in all our mutant patients with low complexity of the associated aura symptoms in the sporadic case is also observed. Besides the two novel mutations, the data here reported confirm the involvement of ATP1A2 gene in the sporadic form of HM, while the negative results on the other families tested for all genes known in HM strengthen the hypothesis of the existence of at least another locus involved in FHM.