Despite advances in clinical management, cardiovascular disease remains the leading cause of death in America. While cardiomyocytes retain limited plasticity following maturation, the heart is grossly unable to recover from structural damage. Mesenchymal stem cell (MSC) therapy, through its promise of repair and regeneration of cardiac tissue, represents an exciting avenue of treatment for a range of cardiovascular diseases. MSCs are relatively immunoprivileged, lacking both major histocompatibility II and T-cell co-stimulatory signal expression, and possess the unique ability to home into sites of myocardial damage when delivered systemically. Additionally, they have been shown to provide therapeutic benefit via several distinct mechanisms, the most important of which appears to be the abundant secretion of paracrine factors that promote local regeneration. In light of this, several groups have sought to precondition MSCs, using various molecular and genetic means, in order to enhance viability and growth factor secretion in the heart, following transplantation. Here, we analyze and integrate information from recent MSC studies, focusing on underlying mechanisms of MSC-associated repair in animal models of cardiac disease. Additionally, MSC pretreatment studies are organized here to examine their relative effectiveness and potential for clinical use. Data emerging from ongoing human clinical trials are also evaluated for consistency with animal studies and their therapeutic promise. Finally, we attempt to answer whether cumulative evidence from animal and human studies is suggestive of significant, clinically viable cardiac repair in acute and chronic conditions and explore ways in which future studies can enhance effectiveness of cell-based therapy.
BACKGROUND & AIMS: Colonoscopy within 24 hours (early colonoscopy) is recommended for patients with colonic diverticular bleeding, but it is unclear if this strategy improves postdischarge outcomes. We aimed to determine whether early colonoscopy is associated with decreased risk of rebleeding and hospital re-admission within 30 days. METHODS: We performed a retrospective cohort study using Marketscan (Truven Health Analytics, Inc, Ann Arbor, MI), a nationwide insurance claims database. From January 2004 through September 2015, patients with a primary diagnosis of diverticular bleeding who underwent inpatient colonoscopy were included. We used propensity score matching to account for differences between recipients of early vs delayed colonoscopy. Multivariable logistic regression was performed to determine the association between early colonoscopy and rebleeding or hospital re-admission within 30 days of discharge. RESULTS: In total, 20,010 patients underwent colonoscopy for diverticular bleeding; 11,690 underwent early colonoscopy. After propensity matching, 8320 pairs of patients were analyzed. In the matched analysis, higher proportions of patients who received early colonoscopy underwent additional colonoscopies (73%), compared with patients who did not receive early colonoscopy (4%) (P < .0001), but lower proportions received endoscopic interventions (3% vs 8%; P < .0001). On multivariable analysis, early colonoscopy (odds ratio [OR], 1.34; 95% CI, 1.08-1.66; P [ .007), transfusion requirement (OR, 2.31; 95% CI, 1.88-2.83; P < .0001), and baseline chronic kidney disease (OR, 2.13; 95% CI, 1.49-3.04; P < .0001) were associated with increased risk of rebleeding within 30 days.
Early colonoscopy does not affect 30-day mortality but may allow for earlier endoscopic intervention and decreased transfusion need.
In total, 607 patients were admitted with warfarin-associated LGIB. A total of 403 (66.4%) patients had warfarin held at discharge. Discontinuation of warfarin was associated with an increased 90-day and 6-month mortality on univariate analysis [hazard ratio (HR), 2.07, 95% confidence interval (CI), 1.04-4.58, P=0.04; HR, 1.78, 95% CI, 1.02-3.27, P=0.04]. On multivariate regression adjusting for age, comorbidities, and transfusion requirement, only a higher Charlson Index was associated with increased 90-day mortality (HR, 1.18, 95% CI, 1.07-1.29, P=<0.001). At 6 months, only older age was associated with an increased mortality on multivariate regression (HR, 1.02, 95% CI, 1.00-1.05, P=0.02), with no significantly increased mortality risk with holding warfarin (HR, 1.48, 95% CI, 0.84-2.78, P=0.18) CONCLUSIONS:: There was no association between resumption of warfarin at discharge following hospitalization for LGIB and either 90-day or 6-month mortality on multivariate analysis. Mortality in LGIB was largely driven by age and comorbidities.
Background This study aimed to determine the impact of preoperative exposure to intravenous contrast for CT and the risk of developing postoperative acute kidney injury (AKI) in patients undergoing major gastrointestinal surgery. Methods This prospective, multicentre cohort study included adults undergoing gastrointestinal resection, stoma reversal or liver resection. Both elective and emergency procedures were included. Preoperative exposure to intravenous contrast was defined as exposure to contrast administered for the purposes of CT up to 7 days before surgery. The primary endpoint was the rate of AKI within 7 days. Propensity score‐matched models were adjusted for patient, disease and operative variables. In a sensitivity analysis, a propensity score‐matched model explored the association between preoperative exposure to contrast and AKI in the first 48 h after surgery. Results A total of 5378 patients were included across 173 centres. Overall, 1249 patients (23·2 per cent) received intravenous contrast. The overall rate of AKI within 7 days of surgery was 13·4 per cent (718 of 5378). In the propensity score‐matched model, preoperative exposure to contrast was not associated with AKI within 7 days (odds ratio (OR) 0·95, 95 per cent c.i. 0·73 to 1·21; P = 0·669). The sensitivity analysis showed no association between preoperative contrast administration and AKI within 48 h after operation (OR 1·09, 0·84 to 1·41; P = 0·498). Conclusion There was no association between preoperative intravenous contrast administered for CT up to 7 days before surgery and postoperative AKI. Risk of contrast‐induced nephropathy should not be used as a reason to avoid contrast‐enhanced CT.
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