Notes

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Major limb amputations are physiologically stressful and subject patients to peri-operative cardiovascular risk. Up to 90% of major lower extremity amputations (LEAMP) are being performed under general anaesthesia, despite regional anaesthesia being an acceptable option in most cases. Obtaining a better understanding of who would benefit from regional vs. Afimoxifene chemical structure general anaesthesia could reduce complications and help establish best evidence based practice. It was hypothesised that patients undergoing LEAMP with regional anaesthesia would have better post-operative outcomes than patients receiving general anaesthesia.

This retrospective cohort study used the U.S. Vascular Quality Initiative lower extremity amputation module to identify patients (≥18 years) who underwent LEAMP from 2013 to 2018. Outcomes included 30 day incidence of major adverse cardiac events (MACE) and all cause mortality. Multivariable logistic regression models were used to compute odds ratios (OR) and 95% confidence intervals (CI). Time to dMP. Further studies are needed to establish best practices in LEAMP procedures.
There was no difference in outcomes between regional or general anaesthesia techniques in patients undergoing LEAMP, despite the regional group having more comorbidities. Regional anaesthesia may be under used for high risk patients undergoing LEAMP. Further studies are needed to establish best practices in LEAMP procedures.
This study evaluated cardiac involvement in patients recovered from coronavirus disease-2019 (COVID-19) using cardiac magnetic resonance (CMR).

Myocardial injury caused by COVID-19 was previously reported in hospitalized patients. It is unknown if there is sustained cardiac involvement after patients' recovery from COVID-19.

Twenty-six patients recovered from COVID-19 who reported cardiac symptoms and underwent CMR examinations were retrospectively included. CMR protocols consisted of conventional sequences (cine, T2-weighted imaging, and late gadolinium enhancement [LGE]) and quantitative mapping sequences (T1, T2, and extracellular volume [ECV] mapping). Edema ratio and LGE were assessed in post-COVID-19 patients. Cardiac function, native T1/T2, and ECV were quantitatively evaluated and compared with controls.

Fifteen patients (58%) had abnormal CMR findings on conventional CMR sequences myocardial edema was found in 14 (54%) patients and LGE was found in 8 (31%) patients. Decreased right ventricle symptoms.
Cardiac involvement was found in a proportion of patients recovered from COVID-19. CMR manifestation included myocardial edema, fibrosis, and impaired right ventricle function. Attention should be paid to the possible myocardial involvement in patients recovered from COVID-19 with cardiac symptoms.Chronic kidney disease (CKD) is associated with greater sympathetic nerve activity but it is unclear if this is a kidney-specific response or due to generalized stimulation of sympathetic nervous system activity. To determine this, we used a rabbit model of CKD in which quantitative comparisons with control rabbits could be made of kidney sympathetic nerve activity and whole-body norepinephrine spillover. Rabbits either had surgery to lesion 5/6th of the cortex of one kidney by electro-lesioning and two weeks later removal of the contralateral kidney, or sham lesioning and sham nephrectomy. After three weeks, the blood pressure was statistically significantly 20% higher in conscious rabbits with CKD compared to rabbits with a sham operation, but their heart rate was similar. Strikingly, kidney nerve activity was 37% greater than in controls, with greater burst height and frequency. Total norepinephrine spillover was statistically significantly lower by 34%, and kidney baroreflex curves were shifted to the right in rabbits with CKD. Plasma creatinine and urine output were elevated by 38% and 131%, respectively, and the glomerular filtration rate was 37% lower than in sham-operated animals (all statistically significant). Kidney gene expression of fibronectin, transforming growth factor-β, monocyte chemotactic protein1, Nox4 and Nox5 was two- to eight-fold greater in rabbits with CKD than in control rabbits. Overall, the glomerular layer lesioning model in conscious rabbits produced a moderate, stable degree of CKD characterized by elevated blood pressure and increased kidney sympathetic nerve activity. Thus, our findings, together with that of a reduction in total norepinephrine spillover, suggest that kidney denervation, rather than generalized sympatholytic treatments, may represent a preferable management for CKD associated hypertension.Allogeneic transplants elicit dynamic T cell responses that are modulated by positive and negative co-stimulatory receptors. Understanding mechanisms that intrinsically modulate the immune responses to transplants is vital to develop rational treatment for rejection. Here, we have investigated the impact of programed cell death-1 (PD-1) protein, a negative co-stimulatory receptor, on the rejection of MHC incompatible kidney transplants in mice. T cells were found to rapidly infiltrate the kidneys of A/J mice transplanted to C57BL/6 mice, which peaked at six days and decline by day 14. The T cells primarily encircled tubules with limited infiltration of the tubular epithelium. Lipocalin 2 (LCN2), a marker of tubular injury, also peaked in the urine at day six and then declined. Notably, flow cytometry demonstrated that most of the T cells expressed PD-1 (over 90% of CD8 and about 75% of CD4 cells) at day six. Administration of blocking antibody to PD-L1, the ligand for PD-1, before day six increased T cell infiltrates and urinary LCN2, causing terminal acute rejection. In contrast, blocking PD-1/PD-L1 interactions after day six caused only a transient increase in urinary LCN2. Depleting CD4 and CD8 T cells virtually eliminated LCN2 in the urine in support of T cells injuring tubules. Thus, our data indicate that PD-1/PD-L1 interactions are not just related to chronic antigenic stimulation of T cells but are critical for the regulation of acute T cell responses to renal transplants.
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