Early antibiotic treatment for severe acute necrotizing pancreatitis: a randomized, double-blind, placebo-controlled study

BACKGROUND & AIMS: In patients with severe, necrotizing pancreatitis, it is common to administer early, broad-spectrum antibiotics, often a carbapenem, in the hope of reducing the incidence of pancreatic and peripancreatic infections, although the benefits of doing so have not been proved. METHODS: A multicenter, prospective, double-blind, placebo-controlled randomized study set in 32 centers within North America and Europe. Participants: One hundred patients with clinically severe, confirmed necrotizing pancreatitis: 50 received meropenem and 50 received placebo. Interventions: Meropenem (1 g intravenously every 8 hours) or placebo within 5 days of the onset of symptoms for 7 to 21 days. Main Outcome Measures: Primary endpoint: development of pancreatic or peripancreatic infection within 42 days following randomization. Other endpoints: time between onset of pancreatitis and the development of pancreatic or peripancreatic infection; all-cause mortality; requirement for surgical intervention; development of nonpancreatic infections within 42 days following randomization. RESULTS: Pancreatic or peripancreatic infections developed in 18% (9 of 50) of patients in the meropenem group compared with 12% (6 of 50) in the placebo group (P = 0.401). Overall mortality rate was 20% (10 of 50) in the meropenem group and 18% (9 of 50) in the placebo group (P = 0.799). Surgical intervention was required in 26% (13 of 50) and 20% (10 of 50) of the meropenem and placebo groups, respectively (P = 0.476). CONCLUSIONS: This study demonstrated no statistically significant difference between the treatment groups for pancreatic or peripancreatic infection, mortality, or requirement for surgical intervention, and did not support early prophylactic antimicrobial use in patients with severe acute necrotizing pancreatitis.     

A Systematic Review of the Predictive Value of 18FDG-PET in Esophageal and Esophagogastric Junction Cancer After Neoadjuvant Chemoradiation on the Survival Outcome Stratification

Purpose

We studied the predictive value of [¹⁸?F]fluorodeoxyglucose-positron emission tomography (¹⁸FDG-PET) for assessing disease-free (DFS) and overall survival (OS) in esophageal and esophagogastric junction cancer.

Materials and methods

A literature search (PUBMED/MEDLINE, EMBASE, Cochrane) was performed to identify full papers with ¹⁸FDG-PET and survival data, using indexing terms and free text words. Studies with >10 patients with locally advanced esophageal cancer, presenting sequential or at least one post-adjuvant treatment ¹⁸FDG-PET data and Kaplan–Meier survival curves with >6 months median follow-up period were included. We performed a meta-analysis for DFS and OS using the hazard ratio (HRs) as outcome measure. Sources of heterogeneity study were also explored.

Results

We identified 26 eligible studies including a total of 1,544 patients (average age 62 years, 82 % males). The TNM distribution was as follows: stage I 7 %, II 24 %, III 53 % and IV 15 %. The pooled HRs for complete metabolic response versus no response were 0.51 for OS (95 % CI, 0.4–0.64; P?<?0.00001) and 0.47 for DFS (95 % CI, 0.38–0.57; P?<?0.00001), respectively. No statistical heterogeneity was present. To explore sources of clinical heterogeneity, we also realised subgroup and regression analyses. Taken into account the moderate correlation between OS and DFS (ρ?=?0.54), we used joint bivariate random regression model. These analyses did not show a statistically significant impact of study characteristics and PET modalities on the pooled outcome estimates.

Conclusion

Despite methodological and clinical heterogeneity, metabolic response on ¹⁸FDG-PET is a significant predictor of long-term survival data.     

Islet of Langerhans isolation from pediatric and juvenile donor pancreases

Islet grafts isolated from young donors allow superior functional outcomes but are often associated with poor islet isolation yields. The objective of this study was to comparatively analyze the outcomes of islet isolation between young and older donors. We retrospectively analyzed 564 pancreas isolations performed at our institution. Isolation outcomes were compared between donors aged ≤20 years (n = 42, YD) and >20 years (n = 522, OD). Isolation procedure was identical in both groups. Prepurification percentage of embedded islets was higher in YD (44.3 ± 22.7% vs. 24.9 ± 20.9%, P < 0.001). This led to a lower recovery rate in YD (48% vs. 76%, P = 0.002) and hence lower postpurification IEQ/g pancreas in YD (2 412 ± 1 789 IEQ/g vs. 3 194 ± 1 892 IEQ/g, P = 0.01). Final yield was 180 982 ± 128 073 IEQ in YD and 244 167 ± 134 137 IEQ in OD, (P = 0.006). In vitro function was markedly, albeit nonsignificantly, higher in YD (SI: 4.5 ± 5.1 vs. 3.0 ± 5.7, P = 0.350). Proportion of transplanted preparations was similar in both groups, 38% (16/42) in YD vs. 43% (224/522) in OD, P = 0.628. In spite of isolation and purification difficulties, pancreases from young donors allowed similar islet transplantation rates as older donors. Efforts should be directed at improving islet extraction in these donors to realize their full potential for islet transplantation.     

End-stage renal failure and cardiac mortality after heart transplantation

BACKGROUND: Coronary artery disease (CAD) is the leading cause of mortality after the first year of heart transplantation. End-stage renal failure (ESRF) is more frequent because of long-term survival. Impact of ESRF on cardiac mortality in heart transplant patients is unappreciated. The hypothesis of accelerated CAD in uremic patients has been suggested. METHODS: In Pitié La Salpêtrière hospital, 1211 heart transplants have been performed between 1982 and 2001. Thirty-three patients have reached ESRF. A case-control study was performed to identify risk factors responsible for ESRF and to appreciate the impact of ESRF on cardiac mortality. RESULTS: In cases at 6 months, serum creatinine tended to be higher (159 +/- 31 micromol/L vs. 141 +/- 44 micromol/L, p = 0.06) and cyclosporine (CSA) dosage (mg/kg) was significantly lower (5.4 +/- 1.8 mg/kg vs. 7.7 +/- 2.7 mg/ kg, p = 0.002). Mean triglyceride level after transplantation until dialysis was significantly lower in cases (2.18 +/- 0.82 mmol/L vs. 1.48 +/- 0.62 mmol/L, p = 0.002). In cases and controls, cardiac mortality was responsible for 67% (10 of 15) and 38% (three of eight) of all deaths, respectively. High triglyceride level (> or = 2 mmol/L) was associated with cardiac mortality [p < 0.03, hazard ratio (HR) = 3.89]. Kaplan Meier cardiac free survival rates were significantly lower in cases than in controls (p < 0.03). CONCLUSION: These data suggest that CSA nephrotoxicity could result from individually determined susceptibility and that hypertriglyceridemia may have a negative impact on renal function and cardiac mortality. The risk of cardiac mortality is increased in heart transplant patients with ESRF. The hypothesis of accelerated atherosclerosis in ESRF patients after heart transplantation leading to higher cardiac mortality incidence needs further study.     

Late incidence and determinants of stroke after aortic and mitral valve replacement

Background

Stroke is a devastating complication in patients with prosthetic valves, but characterization of its late occurrence from a large cohort is lacking.

Methods

Three thousand one hundred eighty-nine adult patients who underwent a total of 3,576 operations for left-heart valve replacement were managed with contemporary anticoagulation guidelines and prospectively followed in a dedicated clinic. Total follow-up was 20,096 patient years. Bootstrapped survival analysis was used to determine the impact of patient and valve related factors on the incidence of stroke.

Results

Most strokes were embolic. Linearized embolic stroke rates were 1.3% ± 0.2% per year for aortic bioprostheses, 1.4% ± 0.2% per year for aortic mechanical valves, 1.3% ± 0.3% per year for mitral bioprostheses, and 2.3% ± 0.4% per year for mitral mechanical valves (p = 0.002, vs other implant types). Age more than 75 years, female gender, and smoking were independent risk factors after aortic and mitral valve replacement. Atrial fibrillation, coronary disease, and tilting-disc mechanical prostheses were independent predictors of embolic stroke after aortic valve replacement. Preoperative left ventricular (LV) dysfunction was an independent risk factor in patients with mitral prostheses. Primary operative indication, diabetes, redo status, or the presence of two prosthetic valves were not associated with an increased hazard. The addition of acetyl salicylic or dipyridamole to warfarin anticoagulation did not significantly lower embolic stroke risk in patients with mechanical prostheses.

Conclusions

Approximately 20% of patients with valve prostheses have an embolic stroke by 15 years after valve replacement. Some risk factors such as the avoidance of smoking, mitral mechanical prostheses, aortic tilting-disc valves, and proceeding to mitral surgery before LV dysfunction occurs are potentially modifiable.     

Robotic aortic valve replacement: case report

We have developed a technique that enables robotic aortic valve replacement with port access via a small right anterior thoracotomy and minimally invasive aortic cross clamping. The procedure is performed under video guidance with all the annular sutures placed with the robot. In the case we report, the patient's postoperative course was extremely simple and pain was minimal. We believe that this is the first reported aortic valve replacement using robotic technology and that it opens a new field of application for robotic assisted surgery.     

Inter-observer variation in the diagnosis of coronal articular fracture lines in the lunate facet of the distal radius

Background

Several studies support the use of CT for diagnosing coronal fractures of the distal radius but the inter-observer reliability of these observations is less well studied. We tested the null hypothesis that radiographs alone and the combination of radiographs and two-dimensional computed tomography scans (2DCT) have the same inter-observer variation for the diagnosis of coronal articular fracture lines in the distal radius.

Methods

Using a web-based survey, 63 surgeons were randomized to evaluate 16 fractures of the distal radius on radiographs alone or radiographs and 2DCT for the presence or absence of a coronal fracture line of the lunate facet and, if present, the stability of the fracture. The kappa multirater measure was calculated to estimate agreement between observers.

Results

The inter-observer variation in diagnosis of a coronal fracture line was fair with both radiographs and 2DCT, as was the diagnosis of instability of the volar lunate facet fracture when present.

Conclusion

Two-dimensional computed tomography does not improve observer agreement on the diagnosis of coronal plane articular fracture lines in the lunate facet of the distal radius.     

Prognostic Value of BRAF V600 Mutations in Melanoma Patients After Resection of Metastatic Lymph Nodes

Purpose

BRAF ^V600 mutations are frequent in melanomas, and BRAF^V600-targeted therapy have dramatic, but often transitory, efficacy in stage IV patients. Prognosis of patients with American Joint Committee on Cancer (AJCC) stage III melanoma is heterogeneous. We aimed to determine the overall survival (OS) of stage III patients with a nodal deposit of ??2?mm according to BRAF ^V600 mutations and other previously reported prognostic criteria.

Methods

This retrospective study included 105 consecutive patients with stage III cutaneous melanomas. Most patients underwent a prospective follow-up. BRAF ^V600 mutations were detected by sequencing and pyrosequencing of DNA in samples containing >60?% melanoma cells.

Results

BRAF mutations (p.V600E and p.V600K in 83 and 14?% of cases, respectively) were detected in 40?% of the patients. For patients with and without BRAF mutations, death occurred in 83.3 and 60.3?%, with a median OS of 1.4 and 2.8?years, respectively. Patient age, primary melanoma ulceration, number of invaded lymph nodes, AJCC staging at study entry, and BRAF status were linked to OS in the univariate analysis. The only characteristics associated with OS in the multivariate analysis were number of invaded lymph nodes (P?=?0.005, hazard ratio 2.2, 95?% confidence interval 1.3?C3.9) and BRAF status (P?=?0.005, hazard ratio 1.9, 95?% confidence interval 1.2?C3.1).

Conclusions

BRAF ^V600 status could be used to stage melanoma patients with nodal deposits. Our results may also help to plan adjuvant trials in these patients, for whom the low tumor load may induce longer efficacy of BRAF-targeted therapies.