Adjuvant/Perioperative Therapy in Pancreatic and Periampullary Cancer

The delivery of postoperative combined modality adjuvant therapy for completely resected pancreatic adenocarcinoma was initially shown to be beneficial based on a prospective, randomized trial published 30 years ago. Since then, oncologists have debated whether chemotherapy alone, chemoradiation, or both are optimal adjuvant therapies following pancreatectomy for pancreatic ductal adenocarcinomas (PDAC). No global consensus has emerged, and there is no one superior modality despite randomized trials in part, to poor trial design, poor patient selection, and poor therapy options itself. We need to have a disciplined approach to the selection of patients for pancreatectomy, pathologic assessment of surgical resection margins, and postoperative (pre-treatment) imaging. In the era of the multidetector CT optimized for pancreatic imaging, tumors of “borderline resectability” have emerged as a distinct subset of PDAC. The attempt to standardize the definition of borderline resectable is a work in progress and modified with time. This distinction (between resectable and borderline resectable) is essential to minimize potentially confounding results of clinical trials. Additionally, preoperative therapy is not only preferred but mandatory in a large population of borderline resectable patients. Ultimately, as we develop more effective systemic therapies for PDAC, proceeding with surgery after a period of induction therapy will be even more compelling especially if there is a clear positive impact on overall survival.     

Impact of the Combination of Daptomycin and Trimethoprim-Sulfamethoxazole on Clinical Outcomes in Methicillin-Resistant Staphylococcus aureus Infections

Complicated Staphylococcus aureus infections, including bacteremia, are often associated with treatment failures, prolonged hospital stays, and the emergence of resistance to primary and even secondary therapies. Daptomycin is commonly used as salvage therapy after vancomycin failure for the treatment of methicillin-resistant S. aureus (MRSA) infections. Unfortunately, the emergence of daptomycin resistance, especially in deep-seated infections, has been reported, prompting the need for alternative or combination therapy. Numerous antibiotic combinations with daptomycin have been investigated clinically and in vitro. Of interest, the combination of daptomycin and trimethoprim-sulfamethoxazole (TMP-SMX) has proved to be rapidly bactericidal in vitro to strains that are both susceptible and nonsusceptible to daptomycin. However, to date, there is limited clinical evidence supporting the use of this combination. This was a multicenter, retrospective case series of patients treated with the combination of daptomycin and TMP-SMX for at least 72 h. The objective of this study was to describe the safety and effectiveness of this regimen in clinical practice. The most commonly stated reason that TMP-SMX was added to daptomycin was persistent bacteremia and/or progressive signs and symptoms of infection. After the initiation of combination therapy, the median time to clearance of bacteremia was 2.5 days. Microbiological eradication was demonstrated in 24 out of 28 patients, and in vitro synergy was demonstrated in 17 of the 17 recovered isolates. Further research with this combination is necessary to describe the optimal role and its impact on patient outcomes.     

Ultra-wide field retinal imaging: A wider clinical perspective

The peripheral retina is affected in a variety of retinal disorders. Traditional fundus cameras capture only a part of the fundus even when montaging techniques are used. Ultra-wide field imaging enables us to delve into the retinal periphery in greater detail. It not only facilitates assessing color images of the fundus, but also fluorescein angiography, indocyanine green angiography, fundus autofluorescence, and red and green free images. In this review, a literature search using the keywords “ultra-widefield imaging”, “widefield imaging”, and “peripheral retinal imaging” in English and non-English languages was done and the relevant articles were included. Ultra-wide field imaging has made new observations in the normal population as well as in eyes with retinal disorders including vascular diseases, degenerative diseases, uveitis, age-related macular degeneration, retinal and choroidal tumors and hereditary retinal dystrophies. This review aims to describe the utility of ultra-wide field imaging in various retinal disorders.     

Nephrectomy for the failed renal allograft in children: predictors and outcomes

Background

There are no guidelines for the removal of a failed renal allograft, and its impact on subsequent dialysis and retransplantation has not yet been described.

Methods

We performed a 10-year review of allograft failure to study the factors that determined an outcome of transplant nephrectomy and choice of subsequent renal replacement therapy in children with or without nephrectomy.

Results

A total of 34 children developed graft failure over the 10-year study period, of whom 18 (53 %) required transplant nephrectomy. The median graft survival was 1.1 (range 0.2–10.6) versus 7.5 (1.5–15.0) years in the nephrectomy and non-nephrectomy groups, respectively (p?=?0.011). Children with graft failure within 1 year of transplantation were four-fold more likely to require transplant nephrectomy than those with graft failure after 1 year (p?=?0.04). Renal biopsy performed at ≤8 weeks prior to graft loss showed Banff grade II acute rejection in 13 of the 18 children who required subsequent nephrectomy versus three of the 13 children who did not need nephrectomy (p?=?0.01). Inflammation (fever, graft tenderness and raised C-reactive protein (CRP) in the 2 weeks preceding graft failure) was seen in 66 % of nephrectomized children, but not in any in the non-nephrectomy group (p?=?0.0003 for CRP between groups). Banff II rejection, an inflammatory response and the time post-transplantation significantly and independently predicted the outcome of nephrectomy (p?=?0.008, R ²?=?67 %). Human leukocyte antigen (HLA) antibody levels after graft failure were higher in the nephrectomy group (p?=?0.0003), but there was no difference between groups in terms of the presence or class of donor-specific antibodies. Of the children with graft failure, 82 % required dialysis (61 % hemodialysis) and 35 % have to date been successfully retransplanted.

Conclusions

Children with Banff II rejection, an inflammatory response and early graft loss are more likely to require transplant nephrectomy. Nephrectomy may be associated with higher circulating HLA antibody levels.     

Loss to follow-up in orthopaedic clinical trials: a systematic review

Purpose

The rate of patients lost to follow-up may contribute to bias in randomized controlled trials (RCTs).

Methods

We systematically reviewed orthopaedic RCTs from 2008 to 2011, including 559 RCTs with 131,836 enrolled subjects. The loss to follow-up rates and minimum follow-up times were recorded for each trial. Orthopaedic subspecialty, country of origin, number of enrolled patients, patient age, follow-up strategy, and funding type were also recorded.

Results

Loss to follow-up was not reported in 111 of these studies (20 %). Mean loss to follow-up was 10.4 %. No orthopaedic subspecialty demonstrated significantly different follow-up rates. Remote follow-up strategies did not reduce the loss to follow-up rate. Studies with a minimum follow-up length of three years showed significantly higher loss to follow-up rates compared with studies with shorter minimum follow-up time (14.8 % versus 9.8 %, p?=?0.01). Studies performed in the United States had a significantly higher rate of loss to follow-up compared with non-United States studies (13.8 % versus 9.4 %; p?=?0.01).

Conclusions

Loss to follow-up rates in published orthopaedic randomized controlled trials is overall relatively low. A substantial portion of publications does not adequately report follow-up data. Studies performed in the United States and studies with longer follow-up periods seem to be at higher risk for loss to follow-up.