Association of Multiple Plasma Biomarker Concentrations with Progression of Prevalent Diabetic Kidney Disease: Findings from the Chronic Renal Insufficiency Cohort (CRIC) Study

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The association of early postoperative desaturation in the operating theatre with hospital discharge to a skilled nursing or long-term care facility

It is unclear which criteria should be used to define readiness for tracheal extubation in the operating theatre. We studied the effects of desaturation in the operating theatre immediately after tracheal extubation on long-term outcomes. Performing a pre-specified, retrospective analysis of 71,025 cases involving previously independent adults undergoing non-cardiac surgery, we evaluated the association between desaturation events (oxygen saturation < 90%) within 10 min of tracheal extubation and adverse discharge (to a skilled nursing facility or long-term care facility). A total of 404 (12.3%) cases with, and 5035 (7.4%) cases without, early postoperative desaturation had an adverse discharge. Early postoperative desaturation was associated with higher odds of being discharged to a nursing facility (adjusted odds ratio 1.36 (95%CI 1.20–1.54); p < 0.001). Increased duration of desaturation augmented the effect (p for trend < 0.001). Desaturation was associated with a higher risk of respiratory, renal and cardiovascular complications as well as increased duration of hospital stay, postoperative intensive care unit admission frequency and cost. Several modifiable factors were associated with desaturation including: high intra-operative long-acting opioid administration; high neostigmine dose; high intra-operative inspired oxygen concentration; and low oxygen delivery immediately before tracheal extubation. There was substantial provider variability between anaesthetists in the incidence of postoperative desaturation unexplained by patient- and procedure-related factors. Early postoperative desaturation is a potentially preventable complication associated with a higher risk of adverse discharge disposition. Anaesthetists may consider developing guidelines to define tracheal extubation readiness that contain postoperative desaturation as an adverse outcome after tracheal extubation.     

Cell-free DNA in the surveillance of heart transplant rejection

BackgroundCirculating cell-free deoxyribonucleic acid (cfDNA) is promptly materializing as a highly useful tool for the surveillance of solid-organ transplant rejection. Donor-specific fraction (DF) cfDNA is a potential marker of selective donor organ injury. It is emerging as a promising analytical target in the near future. The aim of this systematic review is to throw light on the importance of cfDNA and future perspective in detecting acute rejection in heart transplantation.MethodsAn exhaustive search was carried out for this review article on the basis of literature available including scientific databases of PubMed, Embase, and ClinicalTrials.gov. The search engines were systematically explored using the search terms “cell free DNA,” “Heart transplant,” and “Rejection” from inception until August 2020, and narrative analysis was accomplished. Majority of the studies described endomyocardial biopsy-proven acute rejection as reference standard.ResultsAfter initial screening of 331 articles, 11 studies were included and discussed in detail in the present review article. Majority of the studies showed prospective designs. A firm correlation was noted between acute rejection (identified on endomyocardial biopsy) and cfDNA levels by most of the studies.ConclusionscfDNA is a promising tool to replace repeated biopsies to detect rejection. The development in the area of digital droplet polymerase chain reaction and massive parallel sequencing, along with the overall reduction in cost of sequencing with its automation, has helped establish its role in the transplant population.     

The Metabolic Syndrome and Microvascular Complications in a Murine Model of Type 2 Diabetes

To define the components of the metabolic syndrome that contribute to diabetic polyneuropathy (DPN) in type 2 diabetes mellitus (T2DM), we treated the BKS db/db mouse, an established murine model of T2DM and the metabolic syndrome, with the thiazolidinedione class drug pioglitazone. Pioglitazone treatment of BKS db/db mice produced a significant weight gain, restored glycemic control, and normalized measures of serum oxidative stress and triglycerides but had no effect on LDLs or total cholesterol. Moreover, although pioglitazone treatment normalized renal function, it had no effect on measures of large myelinated nerve fibers, specifically sural or sciatic nerve conduction velocities, but significantly improved measures of small unmyelinated nerve fiber architecture and function. Analyses of gene expression arrays of large myelinated sciatic nerves from pioglitazone-treated animals revealed an unanticipated increase in genes related to adipogenesis, adipokine signaling, and lipoprotein signaling, which likely contributed to the blunted therapeutic response. Similar analyses of dorsal root ganglion neurons revealed a salutary effect of pioglitazone on pathways related to defense and cytokine production. These data suggest differential susceptibility of small and large nerve fibers to specific metabolic impairments associated with T2DM and provide the basis for discussion of new treatment paradigms for individuals with T2DM and DPN.