Abstract 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.
Abstract Background The intermediate-term impact of acute kidney injury (AKI) in patients after major gastrointestinal and liver surgery has not been well characterized. This study aimed to evaluate the 1-year mortality rate and renal outcomes associated with postoperative AKI in a national prospective cohort. Methods This prospective multicentre, observational cohort with 1-year postoperative follow-up included adults undergoing major gastrointestinal and liver surgery across the UK and Ireland between 23 September and 18 November 2015. AKI was defined according to Kidney Disease Improving Global Outcomes (KDIGO) criteria. The primary outcome was death at 1-year after surgery, and the secondary outcome was Major Adverse Kidney Events (MAKE-365). Cox proportionate and multilevel logistic regression were used to account for case mix. Results Of 5745 patients across 173 centres, 1-year follow-up data was completed for 3504 patients (62.2 per cent, 126 centres), with attrition largely explained by centre non-participation (63.1 per cent). Some 13.6 per cent (475 of 3504) patients developed AKI by 7 days after surgery (stage 1: 9.2 per cent; stage 2/3: 4.3 per cent). At 1 year, 10.8 per cent (378 patients) experienced a MAKE-365 endpoint (303 patients had died, 61 had renal replacement therapy and 78 had renal dysfunction). Patients who experienced AKI by 7 days after surgery had a higher hazard of death at 1 year for KDIGO stage 1 (hazard ratio 1.50 (95 per cent c.i. 1.08 to 2.08), P = 0.016) and KDIGO stage 2/3 (hazard ratio 2.96 (95 per cent c.i. 2.02 to 4.33), P < 0.001). Both KDIGO stage 1 (odds ratio 2.09 (95 per cent c.i. 1.50 to 2.92), P < 0.001) and stage 2/3 (odds ratio 9.26 (95 per cent c.i. 6.31 to 13.59), P < 0.001) AKI were independently associated with MAKE-365. Conclusion AKI events within 7 days after gastrointestinal or liver surgery are associated with significantly worse survival and renal outcomes at 1 year.
The morbidity of radical cystectomy remains high. A multidisciplinary approach utilizing hospitalist comanagement may improve outcomes. It is unclear what factors should be considered to determine which patients might benefit from this approach. We sought to determine if there are differences between the perceived need for co-management between urologists and hospitalists. Preoperative variables were analyzed to determine which factors might be associated with need for comanagement.A case-based survey was emailed to urologists and hospitalists at 3 academic institutions to investigate perceptions regarding need for inpatient medical comanagement of fictitious patients following cystectomy. Decisions were rated based on patient comorbidities, age, race, sex, cancer stage, neoadjuvant therapy, alcohol intake, performance status, and English literacy. A Wilcoxon rank sum test assessed each question for differences. A Mantel-Haenszel chi-square test was used to assess whether the proportion of respondents who advocated for comanagement increased as Charlson comorbidity score increased.The most significant determinant of need for postoperative comanagement was patients' comorbidities. Urologists and hospitalists did not differ significantly in beliefs regarding need for comanagement.The most important determining factor for comanagement was presence of comorbidities. Further studies are needed to evaluate the impact of this multidisciplinary approach.
Purpose: Descemet stripping endothelial keratoplasty (DSEK), currently the most common procedure for managing corneal endothelial dysfunction, may be repeated following DSEK failure from a variety of causes. This multicenter study reports the risk factors and outcomes of repeat DSEK. Methods: This was an institutional review board-approved multicenter retrospective chart review of patients who underwent repeat DSEK. Twelve surgeons from 5 Midwest academic centers and 3 private practice groups participated. The Eversight Eye Bank provided clinical indication and donor graft data. We also assessed the role of the learning curve by comparing cohorts from the first and second 5-year periods. Results: A total of 121 eyes from 121 patients who underwent repeat DSEK were identified. The average age of the patients was 70 ± 12 years. The most common indication for repeat DSEK was late endothelial graft failure without rejection (58%, N = 63). Average preoperative and 12-month postoperative repeat DSEK corrected distance visual acuities were 20/694 and 20/89, respectively. Visual acuity outcomes, endothelial cell density, and cell loss did not significantly vary between the 2 cohorts. Initial graft rebubble rates for the first and second cohorts were 51% and 25%. The presence of glaucoma, prior glaucoma surgery, or a history of penetrating (full thickness) keratoplasty did not significantly affect visual outcomes. The median, mean, and range of intraocular pressures before repeat DSEK were 15.0, 15.7, and 6 to 37 mm Hg, respectively. Patients with higher intraocular pressures before repeat DSEK had improved postoperative corrected distance visual acuities. Conclusions: Repeating DSEK improves vision following failed or decompensated DSEK surgery. Higher preoperative repeat DSEK IOPs were associated with improved visual outcomes, and initial graft rebubble rates, which decreased over time, were likely due to surgeon experience.
Hepatitis C (HCV) is a deleterious virus that can be cured with new, highly effective anti-viral treatments, yet more than 185 million individuals worldwide remain HCV positive (with the vast majority un-diagnosed or untreated). Of importance, HCV is a leading cause of chronic liver disease and liver cancer, especially in Sub-Saharan Africa (SSA) where the prevalence remains high but uncertain due to little population-based evidence of the epidemic. We aimed to synthesize available data to calculate and highlight the HCV disease burden in SSA.Weighted random-effects generalized linear mixed models were used to estimate prevalence by risk cohort, African region (Southern, Eastern, Western, and Central Africa), type of assay used, publication year, and whether the estimate included children. A pooled prevalence estimate was also calculated. Multi-variable analyses were limited to cohort and region specific prevalence estimates in the adult population due to limited studies including children. Prevalence estimates were additionally weighted using the known adult population size within each region.We included more than 10 years of data. Almost half of the studies on HCV prevalence in SSA were from the Western region (49 %), and over half of all studies were from either blood donor (25 %) or general population cohorts (31 %). In uni-variable analyses, prevalence was lowest in Southern Africa (0.72 %), followed by Eastern Africa at 3.00 %, Western Africa at 4.14 %, and Central Africa at 7.82 %. Blood donors consistently had the lowest prevalence (1.78 %), followed by pregnant women (2.51 %), individuals with comorbid HIV (3.57 %), individuals from the general population (5.41 %), those with a chronic illness (7.99 %), and those at high risk for infection (10.18 %). After adjusting for the population size in each region, the overall adult prevalence of HCV in SSA rose from 3.82 to 3.94 %.This meta-analysis offers a timely update to the HCV disease burden in SSA and offers additional evidence of the burgeoning epidemic. The study highlights the need to account for type of cohort and region variation when describing the HCV epidemic in SSA, the need for more studies that include children, as well as the need to factor in such variations when planning public health interventions.
e22255 Background: Metabolic syndrome (MetS) has been known to be associated with HCC; however, the biomarkers of this syndrome have not been adequately profiled. Adipokine expression profile alterations in MetS and signaling of these biomarkers may have a role in the pathogenesis of HCC. Methods: To measure markers of MetS in the presence of HCC, the Biochip Array technology (Randox-Co. Antrim, UK) was used. This chip is capable of measuring C Peptide, ferritin, IL6, resistin, insulin, TNFa, IL1a, leptin, and PAI-1 in a single blood sample. Blood samples of 31 patients with HCC and 25 healthy controls were collected under IRB approval. The HCC patients were subdivided according to treatment experienced (n = 13) or non-treated (n = 18). The non-treated HCC group was divided into two groups based a diagnosis of Diabetes Mellitus (DM); diabetic (n = 6) and not diabetic (n = 12). Correlation analysis between tumor size and expression of MetS biomarkers were performed. Data is compiled as median [IQR]. Results: The HCC patients exhibited significant increase in some of the biomarkers: ferritin 268 ng/mL [120-366] p < .0001, IL6 5.96 pg/mL [2-26] p < .0001, resistin 4.74 ng/mL [3.3-6.7] p < .0001, TNFa 8.7 pg/mL [6-10] p < .0001, IL-1a 0.49 pg/mL [0.38-0.7] p = .041 and PAI-1 8.44 ng/mL [4.7-13] p < .0001. Insulin, C peptide and leptin did not show any changes. When the HCC patients were stratified in to treated and non-treated, no difference were noted in biomarker profile except ferritin which was higher in treated group than non-treated 366.7 [269-436] vs 185.2 [101-299] p = .005. When non-treated HCC patients were stratified in DM and non-DM groups, no difference was noted in biomarker profiles. In HCC patients increased levels of resistin was correlated with IL-6 (p = .049) and IL-1a (p < .0001). Also in these patients, PAI-1 level was correlated with TNF-alpha (p = .0005). PAI-1 was the only a-marker which correlated with tumor size (r = 0.42; p = .017). Conclusions: The observed increased levels of IL-6, ferritin, TNF alpha, IL-1a, resistin and PAI-1 support the co-existence of ongoing inflammatory, fibrinolytic and metabolic derangement processes in HCC. Targeting these biomarkers may provide additional approaches for the adjunctive management of HCC.
Dedifferentiated chondrosarcoma is a rare malignancy with reported 5-year overall survival rates ranging from 7% to 24%. The purpose of this investigation is to determine the overall survival of dedifferentiated chondrosarcoma in a modern patient series and how it is impacted by patient demographics, tumor characteristics, and surgical treatment factors.This is a retrospective review of the Surveillance, Epidemiology, and End Results (SEER) database from 2001 to 2011. Kaplan Meier analyses were used for overall and disease-specific survival. Univariable and multivariable cox regression models were used to identify prognostic factors.Five year overall- and disease-specific survival was 18% (95% CI: 12-26%) and 28% (95% CI: 18-37%), respectively. Individuals with extremity tumors had a worse prognosis than individuals with a primary tumor in the chest wall or axial skeleton (HR 0.20, 95% CI: 0.07-0.56; P = 0.002 and HR 0.60, 95% CI: 0.36-0.99; P = 0.04, respectively). Patients with AJCC stage III or IV disease (HR 2.51, 95% CI: 1.50-4.20; P = 0.001), tumors larger than 8 cm (HR 2.17, 95% CI: 1.11-4.27; P = 0.046), metastatic disease at diagnosis (HR 3.25, 95% CI: 1.98-5.33; P < 0.001), and those treated without surgical resection (amputation: HR 0.43, 95% CI 0.23-0.80; P = 0.01; limb salvage/non-amputation resection: HR 0.41, 95% CI: 0.24-0.69; P = 0.001) had a significant increase in risk of mortality.The overall prognosis of dedifferentiated chondrosarcoma is poor with a 5-year overall survival of 18%. Patients with a primary tumor located in the chest wall had a better prognosis. Tumors larger than 8 cm, presence of metastases at diagnosis, and treatment without surgical resection were significant predictors of mortality.
1 We characterized the mechanisms in vascular smooth muscle cells (VSMCs) that produce asynchronous, wave-like Ca2+ oscillations in response to phenylephrine (PE). Confocal imaging was used to observe [Ca2+]i in individual VSMCs of intact inferior vena cava (IVC) from rabbits. 2 It was found that the Ca2+ waves were initiated by Ca2+ release from the sarcoplasmic reticulum (SR) via inositol 1,4,5-trisphosphate-sensitive SR Ca2+ release channels (IP3R channels) and that refilling of the SR Ca2+ store through the sarcoplasmic-endoplasmic reticulum Ca2+-ATPase (SERCA) was required for maintained generation of the repetitive Ca2+ waves. 3 Blockade of L-type voltage-gated Ca2+ channels (L-type VGCCs) with nifedipine reduced the frequency of PE-stimulated [Ca2+]i oscillations, while additional blockade of receptor-operated channels/store-operated channels (ROCs/SOCs) with SKF96365 abolished the remaining oscillations. Parallel force measurements showed that nifedipine inhibited PE-induced tonic contraction by 27% while SKF96365 abolished it. This indicates that stimulated Ca2+ entry refills the SR to support the recurrent waves of SR Ca2+ release and that both L-type VGCCs and ROCs/SOCs contribute to this process. 4 Application of the Na+-Ca2+ exchanger (NCX) inhibitors 2′,4′-dichlorobenzamil (forward- and reverse-mode inhibitor) and KB-R7943 (reverse-mode inhibitor) completely abolished the nifedipine-resistant component of [Ca2+]i oscillations and markedly reduced PE-induced tone. 5 Thus, we conclude that each Ca2+ wave depends on initial SR Ca2+ release via IP3R channels followed by SR Ca2+ refilling through SERCA. Na+ entry through ROCs/SOCs facilitates Ca2+ entry through the NCX operating in the reverse mode, which refills the SR and maintains PE-induced [Ca2+]i oscillations. In addition some Ca2+ entry through L-type VGCCs and ROCs/SOCs serves to modulate the frequency of the oscillations and the magnitude of force development.
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