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.     

High-frequency sonography and color Doppler in the management of pigmented skin lesions

We aimed to evaluate high-frequency sonography (HFS) coupled with color Doppler in the management of pigmented skin lesions (PSL). HFS examination was performed in 111 patients with 130 PSL. A color Doppler study was conducted in 107 lesions, to assess intralesional vascularization. Imaging findings were compared with histologic diagnosis. In the case of melanoma, sonographic and histologic maximum thickness measurements were compared. HFS showed 114 of the 130 lesions. Among the detected lesions, HFS alone provided 100% sensitivity and 100% specificity in the distinction of melanoma/nevi from other lesions, and 100% sensitivity and 32% specificity in the distinction of melanomas from nonmelanoma lesions. Sonographic and histologic measurement of melanoma thickness strongly correlated (r > 0.96, p < 0.001). Color Doppler detection of intralesional vessels had a 100% specificity and 34% sensitivity in the distinction of melanomas from other PSL. HFS coupled with color Doppler is a simple, reliable tool for PSL management.     

The incidence of trochlear dysplasia in anterior cruciate ligament tears

Purpose

The purpose of the present epidemiologic study is to record the radiographic presence of trochlear dysplasia and patella alta in patients who undergo anterior cruciate ligament (ACL) reconstruction as a potential underlying factor for post-operative anterior knee pain (AKP).

Methods

All consecutive cases of skeletally-mature ACL-deficient knees that would undergo ACL reconstruction in three different hospitals were prospectively included during a six-month period. Inclusion criteria were acute and sub-acute ACL injury with no previous ipsilateral knee operation. Patients with chronic ACL tears, prior-to-ACL-injury history of patellar instability or other PF disorders were excluded from the study.

Results

A total of 299 knees were included (mean age 32 ± ten years). Forty-four (14.7 %) knees had a positive ‘crossing sign’ in the lateral X-rays and 255 (85.3 %) had no sign of trochlear dysplasia (p < 0.01). Among the cases with trochlear dysplasia, 41 (93 %) had type A trochlear dysplasia with the presence only of the ‘crossing sign’ and three (7 %) had type C trochlear dysplasia. Patellar height results included a mean Caton-Deschamps index of 1.0 ± 0.14 (0.5–1.4). Twenty (6.6 %) knees had an index of less than 0.8, and two (0.6 %) knees had an index less than 0.6. In contrast, 15 (5.0 %) knees had an abnormal value of more than 1.2, indicating patella alta.

Conclusions

The most important finding of the study is the increased prevalence of trochlear dysplasia and patella alta in patients with ACL injury, when compared to the incidence of trochlear dysplasia and patella alta in the general population in the literature. This finding could sound as an alert of a possible additional risk factor for post-operative anterior knee pain after ACL reconstruction.     

Impact of preoperative immunonutrition on morbidity following cystectomy for bladder cancer: a case–control pilot study

Purpose

To compare postoperative complications in patients with or without preoperative immunonutrition before cystectomy.

Methods

A prospective, multicenter, pilot, case–control study was conducted during 6 months. Patients with 7-day preoperative immunonutrition were prospectively included and compared with a retrospective, matched control group without immunonutrition. Early complication rates and the length of hospital stay were analyzed. The bilateral type I error was <0.05; the power was 90 %. Thirty patients in each group were required.

Results

Thirty patients were included in each group, on a comparable basis. In the immunonutrition group, fewer postoperative complications (40 vs. 76.7 %; p = 0.008), less paralytic ileus at D7 (6.6 vs. 33.3 %; p = 0.02), fewer infections (23.3 vs. 60 %; p = 0.008), and in particular less pyelonephritis (16.7 vs. 46.7 %; p = 0.03) occurred. Clavien’s grades for complications were higher in the control group (p = 0.04). Mortality, pulmonary embolism, anastomotic fistulae, and wound dehiscence were similar between two groups. The length of stay was reduced by 3 days in the immunonutrition group.

Conclusions

In this pilot case–control study, immunonutrition is associated with a decrease in postoperative complications, urinary tract infections, Clavien’s grade for complications, and paralytic ileus in patients undergoing cystectomy for bladder cancer. Prospective randomized placebo control studies are needed to confirm these promising results.     

Cardiovascular Morbidity Associated with Gonadotropin Releasing Hormone Agonists and an Antagonist

Background

Androgen deprivation therapy (ADT) is associated with increased cardiovascular morbidity.

Objective

To determine whether cardiovascular morbidity differs following initiation of gonadotropin-releasing hormone (GnRH) agonists compared with an antagonist.

Design, setting, and participants

Pooled data from six phase 3 prospective randomized trials that recruited 2328 men between 2005 and 2012 to compare the efficacy of GnRH agonists against an antagonist. Men recruited had pathologically confirmed prostate cancer, an Eastern Cooperative Oncology Group score <2, a minimum life expectancy of 12 mo, and were naïve to ADT. Men were excluded if they had a prolonged baseline QT/corrected QT interval, other risk factors for heart failure, hypokalemia or a family history of long QT syndrome, or had another cancer diagnosed within 5 yr.

Intervention

Men were randomized to receive a GnRH agonist or an antagonist for either 3–7 mo (n = 642) or 12 mo (n = 1686). Treatment groups were balanced for common baseline characteristics.

Outcome measurements and statistical analysis

Event analysis was based on death from any cause or cardiac events. Data documenting adverse experiences were classified based on the Medical Dictionary for Regulatory Activities. The following conditions defined a cardiac event: arterial embolic or thrombotic events, hemorrhagic or ischemic cerebrovascular conditions, myocardial infarction, and other ischemic heart disease. Kaplan-Meier curves and log-rank tests were used to compare time to a cardiovascular event or death.

Results and limitations

Among men with preexisting cardiovascular disease, the risk of cardiac events within 1 yr of initiating therapy was significantly lower among men treated with a GnRH antagonist compared with GnRH agonists (hazard ratio: 0.44; 95% confidence interval, 0.26–0.74; p = 0.002). Since our analysis is post hoc, our findings should only be interpreted as hypothesis generating.

Conclusions

GnRH antagonists appear to halve the number of cardiac events experienced by men with preexisting cardiovascular disease during the first year of ADT when compared to GnRH agonists.