Mortality related to coagulase-negative staphylococcal bacteremia in febrile neutropenia: A cohort study

BACKGROUND:

Coagulase-negative staphylococci (CoNS) are currently the most common isolates recovered from the blood of patients with cancer and febrile neutropenia (FN).

OBJECTIVES:

To assess the mortality associated with bloodstream infections (BSIs) caused by CoNS in cancer patients with FN.

METHODS:

A prospective cohort study was conducted in a single tertiary hospital from October 2009 to August 2011. Follow-ups were performed on all of the adult patients who were admitted to the hematology ward with cancer and FN. Bacteremia caused by CoNS was defined as two positive results of two independent cultures. Twenty-eight days after the onset of FN, the mortality rates of the patients with BSIs caused by CoNS were compared with those of patients with BSIs caused by other pathogens.

RESULTS:

A total of 169 subjects were evaluated. During the study period, 78 patients with BSIs were documented. Twenty-three BSIs (29.4%) were a result of CoNS. CoNS-induced bacteremia resulted in lower 28-day mortality compared with bacteremia caused by other pathogens (4.3% versus 32.7%; log-rank P=0.009). In a Cox proportional hazards regression analysis, BSIs caused by CoNS were independently associated with lower mortality (HR 0.09 [95% CI 0.01 to 0.74]).

CONCLUSIONS:

In adult patients with cancer and FN, BSIs caused by CoNS were associated with lower mortality compared with BSIs caused by other pathogens.     

Blocking IL-21 signaling ameliorates xenogeneic GVHD induced by human lymphocytes

In rodent graft-versus-host disease (GVHD) models, anti-IL-21 neutralizing mAb treatment ameliorates lethality and is associated with decreases in Th1 cytokine production and gastrointestinal tract injury. GVHD prevention was dependent on the in vivo generation of donor-inducible regulatory T cells (Tregs). To determine whether the IL-21 pathway might be targeted for GVHD prevention, skin and colon samples obtained from patients with no GVHD or grade 2 to 4 GVHD were analyzed for IL-21 protein expression. By immunohistochemistry staining, IL-21 protein-producing cells were present in all gastrointestinal tract samples and 54% of skin samples obtained from GVHD patients but not GVHD-free controls. In a human xenogeneic GVHD model, human IL-21-secreting cells were present in the colon of GVHD recipients and were associated with elevated serum IL-21 levels. A neutralizing anti-human IL-21 mAb given prophylactically significantly reduced GVHD-associated weight loss and mortality, resulting in a concomitant increase in Tregs and a decrease in T cells secreting IFN-γ or granzyme B. Based on these findings, anti-IL-21 mAb could be considered for GVHD prevention in the clinic.     

Training charter in epilepsy surgery added competence

The present Training Charter in Epilepsy Surgery Added Competence constitutes the third stage of a program initiated by the European Society for Stereotactic and Functional Neurosurgery (ESSFN) and substantiated in close collaboration with the Union Européennedes Médecins Spécialists (UEMS) and the European Association of Neurosurgical Societies (EANS). This program aims to raise the standards of clinical practice by guiding education and quality control concepts. The particular sections of this Charter include: definitions and standards of added competence training, relations of the Epilepsy Unit with the Neurosurgical Department, duration of epilepsy surgery fellowship, institution and training program director requirements, operative totals for epilepsy surgery, educational program, individual requirements, and evaluation and qualification of the trainees. The specification of all these requirements is expected to improve harmonisation and quality of epilepsy surgery practice across Europe, and enhance the clinical activity and the scientific productivity of existing neurosurgical centres.     

Reoperative Surgery After Repair of Postcholecystectomy Bile Duct Injuries: Is it Worthwhile?

Background

Repeat repair of bile duct injuries (BDIs) after cholecystectomy is technically challenging, and its success remains uncertain. We retrospectively evaluated the short- and long-term outcomes of patients requiring reoperative surgery for BDI at a major referral center for hepatobiliary surgery.

Methods

Between January 1991 and May 2011, we performed surgical BDI repairs in 46 patients. Among them, 22 patients had undergone a previous surgical repair elsewhere (group 1), and 24 patients had no previous repair (group 2). We compared the early and late outcomes in the two groups.

Results

The patients in group 1 were younger (48.6 vs. 54.8 years, p = 0.0001) and were referred after a longer interval (>1 month) from BDI (72.7 vs. 41.7 %, p = 0.042). Intraoperative diagnosis of BDI (59.1 vs. 12.5 %, p = 0.001), ongoing cholangitis (45.4 vs. 12.5 %; p = 0.02), and delay of repair after referral to our institution (116 ± 34 days vs. 23 ± 9 days; p = 0.001) were significantly more frequent in group 1 than in group 2. No significant differences were found for postoperative mortality, morbidity, or length of stay between the groups. Patients with associated vascular injuries had a higher postoperative morbidity rate (p = 0.01) and associated hepatectomy rate (p = 0.045). After a mean follow-up of 96.6 ± 9.7 months (range 5–237.2 months, median 96 months), the rate of recurrent cholangitis (6.5 %) was comparable in the two groups.

Conclusions

This study demonstrates that short- and long-term outcomes after surgical repair of BDI are comparable regardless of whether the patient requires reoperative surgery for a failed primary repair. Associated vascular injuries increase postoperative morbidity and the need for liver resection.     

PTH‐enhanced structural allograft healing is associated with decreased angiopoietin‐2–mediated arteriogenesis,mast cell accumulation,and fibrosis

Recombinant parathyroid hormone (rPTH) therapy has been evaluated for skeletal repair in animal studies and clinical trials based on its known anabolic effects, but its effects on angiogenesis and fibrosis remain poorly understood. We examined the effects of rPTH therapy on blood vessel formation and osseous integration in a murine femoral allograft model, which caused a significant increase in small vessel numbers, and decreased large vessel formation (p < 0.05). Histology showed that rPTH also reduced fibrosis around the allografts to similar levels observed in live autografts, and decreased mast cells at the graft‐host junction. Similar effects on vasculogenesis and fibrosis were observed in femoral allografts from Col1caPTHR transgenic mice. Gene expression profiling revealed rPTH‐induced angiopoietin‐1 (8‐fold), while decreasing angiopoietin‐2 (70‐fold) at day 7 of allograft healing. Finally, we show anti‐angiopoietin‐2 peptibody (L1‐10) treatment mimics rPTH effects on angiogenesis and fibrosis. Collectively, these findings show that intermittent rPTH treatment enhances structural allograft healing by two processes: (1) anabolic effects on new bone formation via small vessel angiogenesis, and (2) inhibition of angiopoietin‐2–mediated arteriogenesis. The latter effect may function as a vascular sieve to limit mast cell access to the site of tissue repair, which decreases fibrosis around and between the fractured ends of bone. Thus, rPTH therapy may be generalizable to all forms of tissue repair that suffer from limited biointegration and excessive fibrosis. © 2013 American Society for Bone and Mineral Research.     

Developing a quality by design approach to model tablet dissolution testing: an industrial case study

Abstract

This study applied the concept of Quality by Design (QbD) to tablet dissolution. Its goal was to propose a quality control strategy to model dissolution testing of solid oral dose products according to International Conference on Harmonization guidelines. The methodology involved the following three steps: (1) a risk analysis to identify the material- and process-related parameters impacting the critical quality attributes of dissolution testing, (2) an experimental design to evaluate the influence of design factors (attributes and parameters selected by risk analysis) on dissolution testing, and (3) an investigation of the relationship between design factors and dissolution profiles. Results show that (a) in the case studied, the two parameters impacting dissolution kinetics are active pharmaceutical ingredient particle size distributions and tablet hardness and (b) these two parameters could be monitored with PAT tools to predict dissolution profiles. Moreover, based on the results obtained, modeling dissolution is possible. The practicality and effectiveness of the QbD approach were demonstrated through this industrial case study. Implementing such an approach systematically in industrial pharmaceutical production would reduce the need for tablet dissolution testing.