Allosensitization in bridge to transplant Novacor left ventricular assist device patients: analysis of long-term outcomes with regard to acute rejection and chronic allograft vasculopathy

BACKGROUND: The true relevance of allosensitization in patients benefiting from left ventricular assist device (LVAD) as bridge to transplant (BTT) is still debated. Available registry data referred to numerous devices precluding LVAD-specific analysis. Therefore, we studied all patients with Novacor LVAD prior to transplantation. METHODS: From 1985 to 2006, 37 Novacor LVADs were implanted as BTT, with 30 patients surviving to transplantation (81%). Post-LVAD sensitization was determined for anti-HLA-class I and class II IgGs. Study endpoints were overall survival and/or graft loss, > or =3A cellular rejection and chronic allograft vasculopathy (CAV). The results from LVAD patients were compared to non-LVAD primary heart transplant recipients (n=318). RESULTS: After LVAD insertion, 5 out of 27 patients available for analysis developed anti-HLA antibodies (18.5%). The mean anti-HLA titer after Novacor LVAD implantation was 14% [SD 31]. Actuarial 5- and 10-year patient/graft survival for LVAD and non-LVAD transplant recipients were 73% and 55%, and 70% and 55%, respectively (p=NS). Overall prevalence of rejection > or =3A was 23.3 % (LVAD group) and 18.9% (non-LVAD group) (p=NS). At follow-up, the respective incidence of CAV was 8% (LVAD group) and 32.4% (non-LVAD group) (p<0.01). However, mean follow-up was significantly different for LVAD and non-LVAD patients, 46 vs 90 months (p<0.001). CONCLUSION: In this study, allosensitization occurred infrequently after Novacor LVAD implantation. Secondly, analysis of outcome variables shows that Novacor-LVAD BTT patients can anticipate similar survival to non-LVAD patients, thus minimizing the impact of allosensitization after LVAD implantation.     

Iatrogenic Injury of the Intrathoracic Esophagus Sustained During a Gastric Banding Procedure

The wide diffusion of laparoscopic adjustable gastric banding as a common surgical procedure for the treatment of morbidly obese patients can be attributed not only to the easy surgical technique, the ability to caliber the stoma, and the potential for reversibility, but also to the fact that this procedure is associated with a low rate of immediate postoperative complications compared to other more complex bariatric procedures. Herein reported is the case of a 63-year-old morbidly obese woman who sustained an iatrogenic injury of the intrathoracic esophagus during a laparoscopic adjustable gastric banding procedure. The putative mechanism of this previously unreported complication of laparoscopic adjustable gastric banding and the therapeutic options are discussed. The patient was initially treated with left pleural cavity drainage, antibiotics and the placement of an endoscopic silicone covered stent to cover the esophageal tear. Nine days later she underwent surgery through left thoracotomy due to the persistence of the esophageal leak. Esophageal perforation is a potentially life- threatening complication that may occur during a laparoscopic gastric banding procedure. The conservative treatment with an endoscopic stent should be reserved to patients with no signs of progressive systemic inflammation and include the drainage of the pleural cavity and the mediastinum, the endoscopic lavage and debridement. Standard surgical treatment with direct repair should not be retarded in case of persistence of the leak.     

Hepatic Arterial Infusion of Oxaliplatin and Intravenous LV5FU2 in Unresectable Liver Metastases from Colorectal Cancer after Systemic Chemotherapy Failure

Background We have previously shown promising activity of hepatic arterial infusion (HAI) oxaliplatin combined with intravenous (IV) 5-fluorouracil (5-FU) and leucovorin (LV) as first-line chemotherapy in patients with colorectal liver metastases (CRLM) (intent-to-treat [ITT] objective response rate [ORR], 64%; secondary resection rate, 18%; overall survival [OS], 27 months). Whether this regimen could be beneficial after systemic chemotherapy failure is unknown. Methods Patients with unresectable CRLM and history of systemic chemotherapy failure were treated bimonthly with HAI oxaliplatin (100 mg/m² 2 hours) combined with IV LV and IV bolus and infusional 5FU (modified LV5FU2 regimen). Results Forty-four consecutive patients (median age 56 years; median number of prior systemic chemotherapy regimens, 2 range 1–5) were included, of whom 43 (98%) had previously received oxaliplatin (n = 34), irinotecan (n = 37), or both (n = 28). Patients received a median of nine cycles of HAI oxaliplatin and IV modified LV5FU2 (range 0–25). Toxicity included grade 3–4 neutropenia (43%), grade 2–3 neuropathy (43%), and grade 3–4 abdominal pain (14%). We observed 24 partial ORs (62%) among the 39 assessable patients (ITT ORR, 55%; 95% CI, 40–69%), including 17, 12, and 12 patients who had failed to respond to prior systemic chemotherapy with FOLFIRI, FOLFOX, or both, respectively. Tumor response allowed further R0 surgical resection (n = 7) or radiofrequency ablation (n = 1) of initially unresectable CRLM in eight patients (18%). Median progression-free survival and OS were 7 and 16 months, respectively. Conclusions HAI oxaliplatin and IV LV5FU2 is feasible, safe, and shows promising activity after systemic chemotherapy failure, allowing surgical resection of initially unresectable CRLM in 18% of patients.     

Randomised clinical trial of Hydrofiber dressing with silver versus povidone-iodine gauze in the management of open surgical and traumatic wounds

This prospective, randomised clinical trial compared pain, comfort, exudate management, wound healing and safety with Hydrofiber dressing with ionic silver (Hydrofiber Ag dressing) and with povidone-iodine gauze for the treatment of open surgical and traumatic wounds. Patients were treated with Hydrofiber Ag dressing or povidone-iodine gauze for up to 2 weeks. Pain severity was measured with a 10-cm visual analogue scale (VAS). Other parameters were assessed clinically with various scales. Pain VAS scores decreased during dressing removal in both groups, and decreased while the dressing was in place in the Hydrofiber Ag dressing group (n = 35) but not in the povidone-iodine gauze group (n = 32). Pain VAS scores were similar between treatment groups. At final evaluation, Hydrofiber Ag dressing was significantly better than povidone-iodine gauze for overall ability to manage pain (P < 0.001), overall comfort (P < or = 0.001), wound trauma on dressing removal (P = 0.001), exudate handling (P < 0.001) and ease of use (P < or = 0.001). Rates of complete healing at study completion were 23% for Hydrofiber Ag dressing and 9% for povidone-iodine gauze (P = ns). No adverse events were reported with Hydrofiber Ag dressing; one subject discontinued povidone-iodine gauze due to adverse skin reaction. Hydrofiber Ag dressing supported wound healing and reduced overall pain compared with povidone-iodine gauze in the treatment of open surgical wounds requiring an antimicrobial dressing.     

Cross-sectional study of pain and disability at knee replacement surgery for osteoarthritis in 299 patients

ObjectiveTo evaluate pain and disability at the time of knee replacement surgery for osteoarthritis.MethodsIn this multicenter cross-sectional study, 299 patients at 12 orthopedic surgery centers in Lyon, France were evaluated on the day before knee replacement surgery. Pain severity was assessed on a visual analog scale (VAS) and function using the Lequesne index and the Western Ontario McMaster Universities Osteoarthritis Index (WOMAC).ResultsThere were 207 women and 92 men with a mean age of 73 years. Mean (±SD) VAS pain score upon walking was 55.8 ± 24 mm. Compared to patients with very severe disability (Lequesne index > 12), those with mild-to-severe disability (Lequesne index ≤ 12) were more likely to be older than 70 years (odds ratio [OR], 2.85; 95% confidence interval [95%CI], 1.25–5) and male (OR, 2.5; 95%CI, 1.3–5); they were less likely to have a body mass index > 27 kg/m² (OR, 2.2; 95%CI, 1.3–3.3) and to engage in sporting activities (OR, 3.3; 95%CI, 1.4–10).ConclusionPatients about to undergo knee replacement surgery had high levels of pain and disability, with little variation across centers. Nevertheless, the severity of pain and disability may depend in part on age, gender, body mass index, and sporting activities, which probably influence the decision to perform knee replacement surgery.     

Multicenter assessment of ultrasound of the spermatic cord in children with acute scrotum

PURPOSE: Intravaginal or extravaginal spermatic cord torsion is a diagnostic challenge for the surgeon and radiologist. Color Doppler sonography can be inaccurate, leading to dangerous false-negative results. To date, no single reliable test has been able to provide 100% diagnostic accuracy. The direct visualization of the twisted cord during emergency high resolution ultrasonography has been proposed to avoid systematic and abusive surgical exploration. The aim of this multicenter study was to assess the validity and reproducibility of high resolution ultrasonography based management of acute scrotum in children. MATERIALS AND METHODS: A total of 919 patients from 11 European university hospitals underwent color Doppler sonography and high resolution ultrasonography for acute scrotum between 1992 and 2005. The spermatic cord was studied along its complete length to detect a spiral twist. The surgical findings were correlated with the preoperative results. RESULTS: A total of 208 patients had spermatic cord torsion proved at surgery. Intratesticular vascularization was absent in the affected testis in only 158 cases (76%). In contrast, high resolution ultrasonography detected the twist as a snail shell-shaped mass, measuring 7 to 33 mm, in 199 patients (96%). High resolution ultrasonography revealed a linear cord for all other causes of acute scrotum (711 patients) with a specificity of 99%. The radiologist training level was the best predictive factor of high resolution ultrasonography reliability (p <0.05). CONCLUSIONS: High resolution ultrasonography based management of acute scrotum is reliable and reproducible. Thanks to its high sensitivity and specificity for the diagnosis of spermatic cord torsion, high resolution ultrasonography can significantly improve the management of acute scrotum in children.     

Individualized Mycophenolate Mofetil Dosing Based on Drug Exposure Significantly Improves Patient Outcomes After Renal Transplantation

Efficacy and safety of mycophenolate mofetil (MMF) may be optimized with individualized doses based on therapeutic monitoring of its active metabolite, mycophenolic acid (MPA). In this 12-month study, 137 renal allograft recipients from 11 French centers receiving basiliximab, cyclosporine A, MMF and corticosteroids were randomized to receive either concentration-controlled doses or fixed-dose MMF. A novel Bayesian estimator of MPA AUC based on three-point sampling was used to individualize doses on posttransplant days 7 and 14 and months 1, 3 and 6. The primary endpoint was treatment failure (death, graft loss, acute rejection and MMF discontinuation). Data from 65 patients/group were analyzed. At month 12, the concentration-controlled group had fewer treatment failures (p = 0.03) and acute rejection episodes (p = 0.01) with no differences in adverse event frequency. The MMF dose was higher in the concentration-controlled group at day 14 (p < 0.0001), month 1 (p < 0.0001) and month 3 (p < 0.01), as were median AUCs on day 14 (33.7 vs. 27.1 mg*h/L; p = 0.0001) and at month 1 (45.0 vs. 30.9 mg*h/L; p < 0.0001). Therapeutic MPA monitoring using a limited sampling strategy can reduce the risk of treatment failure and acute rejection in renal allograft recipients 12 months posttransplant with no increase in adverse events.     

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.