Comparison of survival outcomes between Expanded Criteria Donor and Standard Criteria Donor kidney transplant recipients: a systematic review and meta‐analysis

In 2002, the United Network for Organ Sharing proposed increasing the pool of donor kidneys to include Expanded Criteria Donor (ECD). Outside the USA, the ECD definition remains the one used without questioning whether such a graft allocation criterion is valid worldwide. We performed a meta‐analysis to quantify the differences between ECD and Standard Criteria Donor (SCD) transplants. We paid particular attention to select studies in which the methodology was appropriate and we took into consideration the geographical area. Thirty‐two publications were included. Only five studies, all from the USA, reported confounder‐adjusted hazard ratios comparing the survival outcomes between ECD and SCD kidney transplant recipients. These five studies confirmed that ECD recipients seemed to have poorer prognosis. From 29 studies reporting appropriate survival curves, we estimated the 5‐year pooled nonadjusted survivals for ECD and SCD recipients. The relative differences between the two groups were lower in Europe than in North America, particularly for death‐censored graft failure. It is of primary importance to propose appropriate studies for external validation of the ECD criteria in non‐US kidney transplant recipients.     

Local delivery of mutant CCL2 protein‐reduced orthopaedic implant wear particle‐induced osteolysis and inflammation in vivo

Total joint replacement (TJR) has been widely used as a standard treatment for late‐stage arthritis. One challenge for long‐term efficacy of TJR is the generation of ultra‐high molecular weight polyethylene wear particles from the implant surface that activates an inflammatory cascade which may lead to bone loss, prosthetic loosening and eventual failure of the procedure. Here, we investigate the efficacy of local administration of mutant CCL2 proteins, such as 7ND, on reducing wear particle‐induced inflammation and osteolysis in vivo using a mouse calvarial model. Mice were treated with local injection of 7ND or phosphate buffered saline (PBS) every other day for up to 14 days. Wear particle‐induced osteolysis and the effects of 7ND treatment were evaluated using micro‐CT, histology, and immunofluorescence staining. Compared with the PBS control, 7ND treatment significantly decreased wear particle‐induced osteolysis, which led to a higher bone volume fraction and bone mineral density. Furthermore, immunofluorescence staining showed 7ND treatment decreased the number of recruited inflammatory cells and osteoclasts. Together, our results support the feasibility of local delivery of 7ND for mitigating wear particle‐induced inflammation and osteolysis, which may offer a promising strategy for extending the life time of TJRs. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:58–64, 2016.     

FDG uptake at the bronchial stump after curative lobectomy for non-small cell lung cancer

Purpose

Focal areas of FDG uptake may occur at the bronchial stump following curative lobectomy for non-small-cell lung carcinoma (NSCLC), even in the absence of suspicious CT changes. The purpose of our study was to investigate the significance of such PET/CT findings.

Methods

FDG-PET/CT scans performed in 54 patients after lobectomy for NSCLC were reviewed. The presence of focal areas of FDG uptake at the bronchial stump, associated CT abnormalities, SUVmax, and normalized SUV (SUVnorm = SUVmax/mean liver SUV) were recorded. Final diagnosis was based on biopsy or imaging follow-up.

Results

Focal areas of FDG uptake at the bronchial stump were detected in 30 patients (56 %). Mean SUVmax was 4.0?±?1.9 (range; 2.2–12.1) and mean SUVnorm was 1.8?±?0.8 (range; 0.9–4.5). Biopsy showed recurrence in two patients. In these patients, SUVnorm was respectively 4.4 and 4.5 (with SUVmax of 8.8 and 12.1), whereas SUVnorm was lower than 4.0 in those without recurrence, with mean SUVnorm of 1.6?±?0.5 (range; 0.9–3.4) and mean SUVmax of 3.6?±?0.9 (range; 2.2–5.8). The CT component of the PET/CT revealed ill-defined peribronchial soft tissue opacity only in both patients with recurrence.

Conclusion

FDG uptake at the bronchial stump is a frequent finding after pulmonary lobectomy. Moderate levels of FDG uptake (i.e., SUVnorm?<?4.0) without corresponding abnormal CT findings might be a dual criterion for diagnosing benign post-surgical changes.

     

Morbidity and Mortality After Gastrectomy: Identification of Modifiable Risk Factors

Background

Morbidity after gastrectomy remains high. The potentially modifiable risk factors have not been well described. This study considers a series of potentially modifiable patient-specific and perioperative characteristics that could be considered to reduce morbidity and mortality after gastrectomy.

Methods

This retrospective cohort study includes adults in the ACS NSQIP PUF dataset who underwent gastrectomy between 2011 and 2013. Sequential multivariable models were used to estimate effects of clinical covariates on study outcomes including morbidity, mortality, readmission, and reoperation.

Results

Three thousand six hundred and seventy-eight patients underwent gastrectomy. A majority of patients had distal gastrectomy (N?=?2,799, 76.1 %) and had resection for malignancy (N?=?2,316, 63.0 %). Seven hundred and ninety-eight patients (21.7 %) experienced a major complication. Reoperation was required in 290 patients (7.9 %). Thirty-day mortality was 5.2 %. Age (OR?=?1.01, 95 % CI?=?1.01–1.02, p?=?0.001), preoperative malnutrition (OR?=?1.65, 95 % CI?=?1.35–2.02, p?<?0.001), total gastrectomy (OR?=?1.63, 95 % CI?=?1.31–2.03, p?<?0.001), benign indication for resection (OR?=?1.60, 95 % CI?=?1.29–1.97, p?<?0.001), blood transfusion (OR?=?2.57, 95 % CI?=?2.10–3.13, p?<?0.001), and intraoperative placement of a feeding tubes (OR?=?1.28, 95 % CI?=?1.00–1.62, p?=?0.047) were independently associated with increased risk of morbidity. Association between tobacco use and morbidity was statistically marginal (OR?=?1.23, 95 % CI?=?0.99–1.53, p?=?0.064). All-cause postoperative morbidity had significant associations with reoperation, readmission, and mortality (all p?<?0.001).

Conclusions

Mitigation of perioperative risk factors including smoking and malnutrition as well as identified operative considerations may improve outcomes after gastrectomy. Postoperative morbidity has the strongest association with other measures of poor outcome: reoperation, readmission, and mortality.

     

Acute systemic inflammation induces central mitochondrial damage and mnesic deficit in adult Swiss mice

The aim of this study was to investigate how the brain is affected during systemic inflammation. For this purpose, Swiss mice were challenged with a single intraperitoneal dose of lipopolysaccharide (LPS; 250microg/mouse) to mimic aspects of systemic infection. Spatial learning in Y-maze test demonstrated a differential learning profile during the training test between control and LPS-treated mice, with an alteration in the latter group. We show that systemic LPS-induced inflammation and oxidative injury as assessed by reactive oxygen species (ROS) and nitrites/nitrates (NOx) production associated with reduced glutathione (GSH) depletion, cyclooxygenase-2 (COX-2) expression, and lipid peroxidation. LPS also induced a loss in mitochondrial integrity as shown by a significant decrease in membrane potential and impairment in mitochondrial redox activity. Thus, peripheral inflammation by producing brain inflammation and oxidative injury causes mnesic deficits. It remains to determine whether such events can induce neuronal dysfunction/degeneration and, with time, lead to cholinergic deficiency, amyloid deposits and cognitive impairments as they occur in Alzheimer's disease.     

Transitional carcinoma of the ureter with osseous metaplasia of the stroma: a case report

Transitional cell carcinoma with osseous metaplasia of the stroma is a rare variant of urothelial carcinoma which must be distinguished from sarcomatoid carcinoma. We report here a further observation of this tumor variant, in a very unusual location, the ureter, in order to underline the radiological and pathological characteristics useful for the correct diagnosis, and to point out the problems of differential diagnosis. The diagnosis was made in an 85-year-old patient, presenting with chronic right lombalgias. Imaging studies showed a calcified thickening of the right ureter, associated with a major dilatation of the right excretory cavities and a parenchymal atrophy of the right kidney. A right nephro-ureterectomy was performed. Macroscopical examination showed an ossified, ill-limited tumor, measuring 4 cm in diameter, infiltrating the right ureteral wall. At histological examination, the lesion was identified as a high grade transitional cell carcinoma with extensive osseous metaplasia of the stroma. There was no evidence for a sarcomatous component (absence of mesenchymal cell proliferation, absence of mitosis in stromal cells). An early locoregional recurrence was observed three months after surgery. Our case report underlines the radiological and histological features of a rare variant of transitional cell carcinoma, which may be diagnosed by pre-operative imaging studies and which must be distinguished from a highly aggressive sarcomatoid carcinoma.     

Induction of tau pathology by intracerebral infusion of amyloid-beta -containing brain extract and by amyloid-beta deposition in APP x Tau transgenic mice

Alzheimer's disease presents morphologically with senile plaques, primarily made of extracellular amyloid-beta (A beta) deposits, and neurofibrillary lesions, which consist of intracellular aggregates of hyperphosphorylated tau protein. To study the in vivo induction of tau pathology, dilute brain extracts from aged A beta-depositing APP23 transgenic mice were intracerebrally infused in young B6/P301L tau transgenic mice. Six months after the infusion, tau pathology was induced in the injected hippocampus but also in brain regions well beyond the injection sites such as the entorhinal cortex and amygdala, areas with neuronal projection to the injection site. No or only modest tau induction was observed when brain extracts from aged nontransgenic control mice and aged tau-depositing B6/P301L transgenic mice were infused. To further study A beta-induced tau lesions B6/P301L tau transgenic mice were crossed with APP23 mice. Although A beta deposition in double-transgenic mice did not differ from single APP23 transgenic mice, double-transgenic mice revealed increased tau pathology compared to single B6/P301L tau transgenic mice predominately in areas with high A beta plaque load. The present results suggest that both extract-derived A beta species and deposited fibrillary A beta can induce the formation of tau neurofibrillary pathology. The observation that infused A beta can trigger the tau pathology in the absence of A beta deposits provides an explanation for the discrepancy between the neuroanatomical location of A beta deposits and the development and spreading of tau lesions in Alzheimer's disease brain.     

Differential capacity of T cell priming in naive donors of promiscuous CD4+ T cell epitopes of HCV NS3 and Core proteins

To understand the inter-individual and virus-independent variability of CD4+ T cell responses to HCV components, we evaluated the effect on these responses of HLA II molecules in uninfected healthy donors. Using HLA II-specific binding assays, we identified, in the Core and NS3 proteins, 21 long fragments and 24 15-mer peptides that bound to four to eight of the most preponderant HLA II molecules. We then evaluated the priming capacity of eight long promiscuous peptides in 12 HLA-unrelated healthy donors. The NS3 1250-1264 peptide primed T cells in all the naive donors, while five others were stimulating in at least half of the individuals. We also report sequences that bind to multiple HLA II molecules but are weakly immunogenic. We therefore conclude that (i) broad HLA II specificity is only a prerequisite for a peptide to be stimulating in multiple individuals, and (ii) promiscuous peptides widely differ in their capacity to prime CD4+ T cells from uninfected healthy donors. We suggest that these priming differences result from inter-individual variations in the peptide-specific T cell repertoire. Interestingly, five of the most immunogenic peptides we identified correspond to frequently targeted T cell epitopes in infected patients.     

Prise en charge d’un patient adulte atteint de mucoviscidose

The authors describe the case report of a patient with cystic fibrosis. The nutritional management is discussed during the different stages of disease treatment and progression.