“En bloc” resection of sacral chordomas by combined anterior and posterior surgical approach: a monocentric retrospective review about 29 cases

Purpose

“En bloc” resection of sacral chordomas (SC) with wide margins is statistically linked with a decrease of local recurrence (LR). Nevertheless, surgery potentially leads to complications and neurological deficits. The effectiveness of radiotherapy (RT) and chemotherapy (CT) remains controversial. The aim of the study was to evaluate the margins of tumor resection, the morbidity of “En bloc” resection of SC by combined anterior and posterior surgical approach and to look for predictive factors on survival and LR.

Methods

We performed sacrococcygectomy by surgical combined approach in 29 SC between 1985 and 2012. We analyzed overall survival and survival to LR with survival analysis using Kaplan–Meier method. Complications and morbidity were reported.

Results

The mean follow-up was of 77.9 months (0–241 months). We found 18 (62.1 %) postoperative infections and 7 (24.1 %) wound dehiscences. Eighteen patients had tumor wide margins (62.1 %), 6 marginal (20.7 %) and 4 intralesional (13.8 %). Seven patients had a LR (24.1 %). OS rate was 84.4 % at 5 and 10 years, survival rate with LR was 64 and 56 %, respectively, after 5 and 10 years. Quality of margins (p = 0.106), tumor volume (p = 0.103), postoperative RT (p = 0.245) and postoperative local infection (p = 0.754) did not have effect on LR.

Conclusion

“En bloc” resection by combined surgical approach seems to be a relevant alternative especially for SC invading the high sacrum above S3. Nevertheless, it yet remains the problem of postoperative infection. Systematic Adjuvant RT might allow better control on LR in association with surgery.     

Diagnostic markers of postoperative morbidity after laparoscopic Roux-en-Y gastric bypass for obesity

Purpose

The main objective of this study was to detect subacute complications that can arise from laparoscopic Roux-en-Y gastric bypass and take a rational approach to manage these complications.

Methods

A prospective observational study was performed from November 2010 to December 2012. All patients undergoing gastric bypass surgery for morbid obesity were included in this study. Patients with complications before day 5 were excluded from the study. Clinical and laboratory data (C-reactive protein, leukocyte count) at postoperative day 5, 30-day morbidity, were recorded. The diagnostic value of C-reactive protein (CRP) and leukocytes were determined by the area under the curve (AUC) of the receiver operating characteristic (ROC) curve.

Results

One hundred and twenty-six patients were included. The overall incidence of 30-day morbidity was 8.7 %, and anastomotic leakage rate was 3.2 %. C-reactive protein at postoperative day 5 was a good predictor of complications (AUC was 0.862 (95 % CI [0.76; 0.96]; p?<?0.001) and anastomotic leakage (AUC was 0.863 (95 % CI [0.66; 1]; p?=?0.014). A CRP cutoff level of 136 mg/l at postoperative day 5 yielded a specificity of 95.5 % and a sensitivity of 57.1 % for the detection of postoperative complications. The negative predictive value was 94.6 %. A CRP level of 136 mg/l at day 5 was significantly associated with postoperative morbidity.

Conclusions

C-reactive protein dosage at postoperative day 5 is a relevant predictor of postoperative complications permitting to select patients at risk. Radiological examination and close monitoring could be restricted to patients with CRP level exceeding 136 mg/l.     

Description of a large measles epidemic in Democratic Republic of Congo, 2010–2013

Background

Although measles mortality has declined dramatically in Sub-Saharan Africa, measles remains a major public health problem in countries like the Democratic Republic of Congo (DRC). Here, we describe the large measles epidemic that occurred in the Democratic Republic of Congo between 2010 and 2013 using data from the national surveillance system as well as vaccine coverage surveys to provide a snapshot of the epidemiology of measles in DRC.

Methods

Standardized national surveillance data were used to describe measles cases from 2010 to 2013. Attack rates and case fatality ratios were calculated and the temporal and spatial evolution of the epidemic described. Data on laboratory confirmation and vaccination coverage surveys as a part of routine program monitoring are also presented.

Findings

Between week 1 of 2010 and week 45 of 2013, a total of 294,455 cases and 5,045 deaths were reported. The cumulative attack rate (AR) was 0.4%. The Case Fatality Ratio (CFR) was 1.7% among cases reported in health structures through national surveillance. A total of 186,178 cases (63%) were under 5 years old, representing an estimated AR of 1.4% in this age group. Following the first mass vaccination campaigns, weekly reported cases decreased by 21.5%. Results of post-vaccination campaign coverage surveys indicated sub-optimal (under 95%) vaccination coverage among children surveyed.

Conclusions

The data reported here highlight the need to seek additional means to reinforce routine immunization as well as ensure the timely implementation of Supplementary Immunization Activities to prevent large and repeated measles epidemics in DRC. Although reactive campaigns were conducted in response to the epidemic, strategies to ensure that children are vaccinated in the routine system remains the foundation of measles control.

     

DDX3Y encodes a class I MHC-restricted H-Y antigen that is expressed in leukemic stem cells

The Y chromosome encodes male-specific minor histocompatibility (H-Y) antigens that stimulate T- and B-lymphocyte responses after sex-mismatched allogeneic hematopoietic cell transplantation (HCT). A CD8(+) cytotoxic T lymphocyte (CTL) clone that recognizes a novel HLA-B*2705-restricted H-Y antigen encoded by the DDX3Y gene was isolated from a male who had received a hematopoietic cell graft from his human leukocyte antigen (HLA)-identical sister. The antigenic peptide is a decamer that differs from the homologous DDX3X-encoded peptide at 4 positions. Expression of DDX3Y and of the H-Y epitope that it encodes was examined by quantitative polymerase chain reaction (PCR) and by CTL recognition assays. Expression of DDX3Y is detected in all myeloid and lymphoid leukemic cells that carry an intact Y chromosome. Moreover, the DDX3Y-encoded H-Y epitope is presented on the surface of both myeloid and lymphoid leukemic cells from male HLA-B*2705(+) patients. DDX3Y-specific CTLs prevent engraftment of human acute leukemia in nonobese diabetic/severe combined immune deficient mice, demonstrating that the DDX3Y-encoded H-Y antigen is also expressed in leukemic stem cells. These results demonstrate that CD8(+) T-cell responses against DDX3Y have the potential to contribute to graft-versus-leukemia (GVL) activity after female into male allogeneic HCT. This study is registered at http://clinicaltrials.gov as NCT00107354.     

Lack of evidence for reduced plasma apo B48 catabolism in patients with heterozygous familial hypercholesterolemia carrying the same null LDL receptor gene mutation

Increasing evidence suggests that remnants of chylomicrons and very low density lipoprotein (VLDL) also known as triglyceride-rich lipoproteins (TRL) are directly related to the pathogenesis of atherosclerosis. While studies in animals suggest that low density lipoprotein (LDL) receptor deficiency delays clearance of chylomicron remnants, human data supporting this hypothesis are conflicting. The objective of this study was to compare the fractional catabolic rate (FCR) and production rate (PR) of TRL apolipoprotein B48, the principal structural protein of intestinally derived chylomicron remnants, between familial hypercholesterolemic (FH) heterozygotes and non-FH controls. This was achieved by examining the kinetics of TRL apo B48 labelled with a stable isotope (L-(5,5,5-D3)leucine) in five normolipidemic males (age: 24.7 +/- 1.3 years; body mass index (BMI): 23.9 +/- 1.4 kg/m2) and six genetically defined FH heterozygous males (age: 29.7 +/- 9.9 years; (BMI): 22.0 +/- 4.3 kg/m2) carrying the same null LDL receptor gene mutation. All participants were apo E3 homozygotes. During the kinetic study, the subjects consumed 1/30 of their daily food intake every 30 min over a 15 h period. No significant difference was observed between FH heterozygotes and controls for FCR of TRL apo B48 (7.9 +/- 2.1 versus 7.9 +/- 2.6 pools per day, P = 0.99) while the TRL apo B48 pool size (10.5 +/- 5.4 versus 5.7 +/- 2.4 mg, P = 0.03) and PR (1.1 +/- 0.3 versus 0.6 +/- 0.3 mg kg(-1) per day, P = 0.02) were significantly higher among FH than in controls. In conclusion, this study shows no evidence for reduced plasma apo B48 catabolism in patients with heterozygous FH carrying the same null LDL receptor gene mutation and suggests that the plasma levels of intestinally derived TRL are elevated in FH due to an increased production rate.     

Tumor necrosis factor receptor family costimulation increases regulatory T-cell activation and function via NF-κB

Several drugs targeting members of the TNF superfamily or TNF receptor superfamily (TNFRSF) are widely used in medicine or are currently being tested in therapeutic trials. However, their mechanism of action remains poorly understood. Here, we explored the effects of TNFRSF co-stimulation on murine Foxp3⁺ regulatory T cell (Treg) biology, as they are pivotal modulators of immune responses. We show that engagement of TNFR2, 4-1BB, GITR, and DR3, but not OX40, increases Treg proliferation and survival. Triggering these TNFRSF in Tregs induces similar changes in gene expression patterns, suggesting that they engage common signal transduction pathways. Among them, we identified a major role of canonical NF-κB. Importantly, TNFRSF co-stimulation improves the ability of Tregs to suppress colitis. Our data demonstrate that stimulation of discrete TNFRSF members enhances Treg activation and function through a shared mechanism. Consequently, therapeutic effects of drugs targeting TNFRSF or their ligands may be mediated by their effect on Tregs.     

Rapid Determination of the Chemical Composition of Ethylene/Butadiene Copolymers Using FTIR Spectroscopy and Chemometrics

Fourier transform infrared spectroscopy by attenuated total reflection (ATR‐FTIR), combined with the partial least square (PLS) method provides a fast characterization of ethylene/butadiene copolymers' intricate composition. The PLS regression method is constructed to quantify ethylene, 1,2‐butadiene (vinyl), trans‐1,4‐butadiene, and 1,2‐cyclohexane units in the copolymer. These rings are formed by intramolecular cyclization during polymerization. The performance of PLS models is evaluated by comparing the result obtained by ¹³C NMR and the model for three unknown samples. It is shown that the proposed method allows to accurately estimate the chemical composition of ethylene/butadiene copolymers in a much shorter time than NMR.     

Basal asynchrony and resynchronization with biventricular pacing predict long-term improvement of LV function in heart failure patients

Biventricular pacing (BiV) is emerging for patients with dilated cardiomyopathy (DCM) and asynchrony. We measured basal asynchrony and early resynchronization by radionuclide angioscintigraphy (RNA) in order to predict long-term evolution of ventricular function after BiV. Thirty-four patients (NYHA Class III-IV,65.4 +/- 11 years) with large QRS(179 +/- 18 ms)were implanted with BiV and studied by RNA before (D0), at day 8 (D8), and during follow-up(20 +/- 7 months). We calculated left and right ejection fractions, the interventricular dyssynchrony (TRVLV), and the apicobasal dyssynchrony (Tab). LVEF improved from 20.2 +/- 8.1%(D0) to27.1%+/- 12.6%(follow-up,P < 0.003 vs D0) and RVEF from 28.6%+/- 13%(D0) to 34.3 +/- 11.5%(follow-up,P < 0.03 vs D0). Inter- (DeltaTRVLV) and intraventricular resynchronization was immediate and remained stable: TRVLV decreased from 68.3 +/- 38 ms(D0) to 13.4 +/- 48.5 ms(D8) and1.8 +/- 39.2 ms(follow-up,P < 0.0001 vs D0); and Tab from 45.8 +/- 64.1 msto-18 +/- 68(D8) and-28.3 +/- 53.6 ms(follow-up,P < 0.0001 vs D0). Early inter- and intraventricular resynchronization (DeltaTab) at D8 were related to late LVEF and RVEF improvement. Together, an LVEF > 15% and a significant interventricular dyssynchrony (TRVLV > 60 ms) at D0 have a sensitivity of 79% and a positive predictive value of 83% to predict an improvement of LVEF superior to 5% at follow-up. In DCM patients, BiV resynchronizes ventricles early and in the long-term, while RVEF and LVEF improve progressively. Patients with large electromechanical dyssynchrony benefit most from BiV.