Prognostic Factors Associated with Clinical and Economic Outcomes of Appendectomies in Children: A Multilevel Analysis in a National Retrospective Cohort Study

World Journal of Surgery - Acute appendicitis is the most common acute surgical abdominal pathology in children, and it has a large impact on morbidity and the costs incurred by health care...     

Novel isomannide-based peptide mimetics containing a tartaric acid backbone as serine protease inhibitors

Hepatitis C viral infection is a cause of chronic liver disease, and current therapies are only effective in 50 % of patients. Serine proteases, which are present in both hepatitis C virus (HCV) and the dengue virus, are the most studied class of proteolytic enzymes and are the primary targets for drug development in this field. In this paper, we describe the synthesis of a novel class of isomannide-based peptide mimetic compounds based on a tartaric acid backbone. Our data showed that substitutions at position 168 (D168A) and 170 (V170A) conferred low-level resistance against compound 5a3, whereas substitutions at position 155 (R155K) and 156 (A156V) conferred no resistance. These data suggest that even though compound 5a3 is a noncompetitive inhibitor; it is able to interact with important residues located near the catalytic site. In addition, this novel compound class exhibits potent antiviral activity against variants carrying resistance mutations to boceprevir and telaprevir. Our docking studies showed important interactions, including hydrogen bonds and a π–π interaction, between compound 5a3 and residues of the allosteric site of NS3/4A. Biological and theoretical results indicate that 5a3 is a promising lead compound for the development of new drugs targeting HCV infection.     

Stroke Volume Response to Liver Graft Reperfusion Stress in Cirrhotic Patients

Introduction

In patients with advanced cirrhosis, stressful stimuli may reveal a silent reduced cardiac performance. During liver transplantation (LT), graft reperfusion strongly stresses the heart and may unmask latent myocardial dysfunction.

Aim

The objective of this study was to assess heart response to acutely increased preload after liver graft reperfusion and correlate this response with preoperative data and outcome.

Methods

Preoperative clinical, echocardiographic, and hemodynamic data, and patient outcome were retrospectively recorded for 235 liver recipients who had no known cardiac disease. Myocardial dysfunction was defined as less than 10 % increase of stroke volume after graft reperfusion (non-responder).

Results

We found 84 (35.7 %) non-responder patients. The non-responders showed higher Model for end-stage liver disease scores (p = 0.046), left atrial diameter (LAD) (p = 0.040), hepatic vein pressure gradient (p = 0.055), and hyperdynamic state than responders. The percentages of patients with hyponatremia (p = 0.048) and alcohol etiology (p = 0.025) were also higher among non-responders. Independent predictors of inadequate cardiac response in the multivariate analysis were low preoperative systemic vascular resistance (SVRI) [odds ratio (OR) 3.09, 95 % CI 1.15–4.82; p = 0.027] and enlargement of LAD (OR 2.08, 95 % CI 1.49–2.74; p = 0.044). Non-response was associated with higher rates of early cardiovascular events [hazard ratio (HR) 2.84, 95 % CI 1.09–4.22; p = 0.039] and higher length of intensive care unit stay (p = 0.038). No differences were found in 1-year survival rates.

Conclusions

Latent cardiac dysfunction among LT recipients, considered to be abnormal stroke volume response to unclamping of portal vein, is very prevalent. SVRI and LAD were independent predictors of inadequate responses. This condition deserves special attention since it may aggravate the early postoperative course of LT.     

Management of Early-stage Esophageal Neoplasia (MESEN) Consensus

Background

Treatment of esophageal adenocarcinoma often involves surgical resection. Newer technologies in interventional endoscopy have led to a substantial paradigm shift in the management of early-stage neoplasia in Barrett’s esophagus comprising high-grade dysplasia (HGD), intramucosal carcinoma, and, in some cases, submucosal carcinoma. However, there has been no consensus regarding the indications for esophageal preservation in these cases. In this work, consensus guidelines were established for the management of early-stage esophageal neoplasia considering clinically relevant aspects (age, comorbidities, and social environment) in each scenario.

Methods

Seventeen experts were invited to participate based on their background and clinical expertise at high-volume centers. A questionnaire was created that included four clinical scenarios covering a wide range of situations within HGD and/or early esophageal neoplasia, particularly where controversies are likely to exist. Each of the clinical scenarios was open to discussion subdivided by patient age (20, 50, and 80 s). For each clinical scenario an expert was chosen to defend that position. Each defense triggered a subsequent discussion during a consensus meeting. Conclusions of that discussion together with an accompanying literature analysis allowed experts to confirm or change their original choices and served as the basis for the recommendations stated in this article.

Results

There was 100 % consensus supporting esophageal preservation in patients with HGD, independent of patient age or Barrett’s length. In patients with T1a adenocarcinoma, consensus for preservation was not reached (65 %) for young and middle-aged individuals but was supported for elderly patients (100 %). For T1b adenocarcinoma, consensus was reached for surgical resection (90 %), leaving organ preservation for patients with very low risk of nodal invasion or poor surgical candidates.

Conclusion

Advances in endoscopic imaging and therapy allow for organ preservation in most settings of early-stage neoplasia of the esophagus, provided that the patient understands the implications of this decision.     

Impact of dutasteride on nocturia in men with lower urinary tract symptoms suggestive of benign prostatic hyperplasia (LUTS/BPH): a pooled analysis of three phase III studies

Purpose

To assess the impact of dutasteride compared with placebo on nocturia in men with lower urinary tract symptoms suggestive of benign prostatic hyperplasia, using pooled data from dutasteride phase III studies.

Methods

Nocturia was assessed using Question 7 of the International Prostate Symptom Score questionnaire. Efficacy measures included: mean change in nocturia at 24 months; proportion of patients with improvement/worsening in nocturia; nocturnal voiding frequency at baseline and study end, overall and by baseline subgroups; and nocturnal voiding frequency <2 at study end in patients with baseline score ≥2.

Results

In total, 4,321 patients with a mean age of 66 years were evaluated. From month 12 onwards, mean nocturia improvements were significantly superior with dutasteride than with placebo (p ≤ 0.05). Reduction in nocturia was significantly better with dutasteride than with placebo across all baseline subgroups tested (p ≤ 0.05). Also at month 24, dutasteride therapy resulted in a greater proportion of subjects with nocturia improvement compared with placebo (p ≤ 0.05), with the largest treatment group differences in subjects with a baseline nocturia score of 2 or 3. Among patients with significant nocturia at baseline (score ≥2), significantly more subjects with dutasteride versus placebo had a score <2 at month 24 (26 vs. 19 %, p < 0.001).

Conclusions

After 24 months of treatment, dutasteride treatment provided significantly greater improvements in nocturia, and less worsening, compared with placebo, primarily in subjects with two or three nocturia episodes per night. Studies specifically designed to assess nocturia are required to prospectively confirm these findings.     

Effects of Vancomycin,Cefazolin and Test Conditions on the Wear Behavior of Bone Cement

Antibiotic cement has been recommended in the treatment of prosthetic infections. The purpose of this study was to investigate the mechanical behavioral changes in cement loaded with two antibiotics, vancomycin and cefazolin, in dry and liquid medium. Six groups and four study conditions were established according to the doses of antibiotic used and the ageing (immersion in phosphate buffered saline) of the samples. Properties evaluated were friction coefficient and wear. Samples in dry medium showed higher wears than in liquid. Antibiotic selection did not influence wear properties tested in dry conditions, however, in liquid medium, there were higher frictional coefficients and wear for cefazolin loaded cement after one week and for vancomycin and cefazolin after one month. The results suggest that antibiotic cements behave differently in liquid and that the molecular characteristics of antibiotics are essential for determining this influence.