René Ecochard

Relationship between haemagglutination-inhibiting antibody titres and clinical protection against influenza: development and application of a bayesian random-effects model

BackgroundAntibodies directed against haemagglutinin, measured by the haemagglutination inhibition (HI) assay are essential to protective immunity against influenza infection. An HI titre of 1:40 is generally accepted to correspond to a 50% reduction in the risk of contracting influenza in a susceptible population, but limited attempts have been made to further quantify the association between HI titre and protective efficacy.MethodsWe present a model, using a meta-analytical approach, that estimates the level of clinical protection against influenza at any HI titre level. Source data were derived from a systematic literature review that identified 15 studies, representing a total of 5899 adult subjects and 1304 influenza cases with interval-censored information on HI titre. The parameters of the relationship between HI titre and clinical protection were estimated using Bayesian inference with a consideration of random effects and censorship in the available information.ResultsA significant and positive relationship between HI titre and clinical protection against influenza was observed in all tested models. This relationship was found to be similar irrespective of the type of viral strain (A or B) and the vaccination status of the individuals.ConclusionAlthough limitations in the data used should not be overlooked, the relationship derived in this analysis provides a means to predict the efficacy of inactivated influenza vaccines when only immunogenicity data are available. This relationship can also be useful for comparing the efficacy of different influenza vaccines based on their immunological profile.

Ten-Year Survival Results of a Randomized Trial of Irradiation of Internal Mammary Nodes After Mastectomy

PURPOSE To evaluate the efficacy of irradiation of internal mammary nodes (IMN) on 10-year overall survival in breast cancer patients after mastectomy. METHODS AND PATIENTS This multicenter phase 3 study enrolled patients with positive axillary nodes (pN+) or central/medial tumors with or without pN+. Other inclusion criteria were age <75 and a Karnofsky index ≥70. All patients received postoperative irradiation of the chest wall and supraclavicular nodes and were randomly assigned to receive IMN irradiation or not. Randomization was stratified by tumor location (medial/central or lateral), axillary lymph node status, and adjuvant therapy (chemotherapy vs no chemotherapy). The prescribed dose of irradiation to the target volumes was 50 Gy or equivalent. The first 5 intercostal spaces were included in the IMN target volume, and two-thirds of the dose (31.5 Gy) was given by electrons. The primary outcome was overall survival at 10 years. Disease-free survival and toxicity were secondary outcomes. RESULTS T total of 1334 patients were analyzed after a median follow-up of 11.3 years among the survivors. No benefit of IMN irradiation on the overall survival could be demonstrated: the 10-year overall survival was 59.3% in the IMN-nonirradiated group versus 62.6% in the IMN-irradiated group (P=.8). According to stratification factors, we defined 6 subgroups (medial/central or lateral tumor, pN0 [only for medial/central] or pN+, and chemotherapy or not). In all these subgroups, IMN irradiation did not significantly improve overall survival. CONCLUSIONS In patients treated with 2-dimensional techniques, we failed to demonstrate a survival benefit for IMN irradiation. This study cannot rule out a moderate benefit, especially with more modern, conformal techniques applied to a higher risk population.

Effect of Age, Gender, and Diabetes on Excess Death in End-Stage Renal Failure

Life expectancy is short in elderly individuals with end-stage renal failure (ESRF). This study aimed to compare mortality in patients with ESRF versus the general population (GP) to assess the evolution of excess mortality by age, gender, nephropathy, and dialysis modality after first dialysis. All incident adult dialysis patients from January 1,1999, to December 31, 2003, who lived in Rhône-Alpes Region (France) were included and followed up to death or December 31, 2005. Standardized mortality ratios (SMR) in comparison with GP were computed in the first to the fifth years after first dialysis. In the whole cohort (3025 incident patients), SMR decreased during these 5 yr from 7.4 to 5.2 (P = 0.002). In the 18- to 44-, 45- to 64-, 65- to 74-, 75- to 84-, and > or =85-yr-old groups, SMR decreased from 26.7 to 6.2 (P = 0.01), from 12.8 to 8.1 (P = 0.03), from 8.6 to 5.6 (P = 0.051), from 7.1 to 4.5 (P = 0.02), and from 3.5 to 1.2 (P = 0.14), respectively. Among age categories, differences were significant in the first 3 yr (P < 0.05). SMR were higher 1.5-fold in women than in men in the first 4 yr (P < 0.05). In patients with diabetic nephropathy (DN), SMR increased during the first 3 yr (P = 0.045) and were higher than in patients without DN in the second, third, and fourth years (P < 0.05). SMR were higher in the peritoneal dialysis than in the hemodialysis group in the fourth year (P < 0.01). Patients with ESRF have a high excess mortality compared with the GP. Older patients with ESRF experienced less excess mortality. ESRF cancels out womens survival advantage noted in the GP. SMR evolution in patients with DN was different from that in patients without DN.

Genome-Wide Comparison between IL-17A- and IL-17F-Induced Effects in Human Rheumatoid Arthritis Synoviocytes

IL-17A is implicated in rheumatoid arthritis (RA) pathogenesis; however, the contribution of IL-17F remains to be clarified. Using microarrays and gene-specific expression assays, we compared the regulatory effects of IL-17A and IL-17F alone or in combination with TNF-α on RA synoviocytes. IL-17A and IL-17F expression was studied in osteoarthritis and RA synovium by immunohistochemistry. The comparison between the IL-17A and IL-17F stimulatory effect on RA synoviocytes was assessed at the protein level by ELISA and at the mRNA level by microarrays and real-time RT-PCR. TNFRII expression was studied by real-time RT-PCR and immunofluorescence, and neutralizing Ab was used to analyze its contribution to CCL20 secretion. IL-17A and IL-17F were detected in plasma cell-like cells from RA but not osteoarthritis synovium. In microarrays, IL-17A and IL-17F alone had similar regulatory effects, IL-17F being quantitatively less active. Both cytokines induced a similar expression pattern in the presence of TNF-α. Based on a cooperation index, 130 and 203 genes were synergistically induced by IL-17A or IL-17F plus TNF-α, respectively. Among these, the new target genes CXCR4, LPL, and IL-32 were validated by real-time RT-PCR. IL-17A and IL-17F up-regulated TNFRII expression, but had no effects on TNFRI, IL-17RA or IL-17RC. TNFRII blockade inhibited the synergistic induction of CCL20 by IL-17A or IL-17F and TNF-α. IL-17A and IL-17F are both expressed in RA synovium. In the presence of TNF-α, they induced a similar expression pattern in RA synoviocytes. Accordingly, IL-17F appears as a target in Th17-mediated diseases such as RA.

Surveillance of Duodenal Adenomas in Familial Adenomatous Polyposis Reveals High Cumulative Risk of Advanced Disease

PURPOSE The development of high-grade dysplasia (HGD) on duodenal or jejunal adenomas and of late-stage (stage IV) duodenal polyposis are major clinical events for familial adenomatous polyposis (FAP) patients. Our aim was to determine their respective frequency, risk factors, and cumulative risk. PATIENTS AND METHODS A prospective, optimized, endoscopic surveillance protocol was applied to 58 FAP patients in a university hospital. The number, size, and histology of duodenojejunal polyps were assessed, and the Spigelmans score was calculated at each endoscopy. Cox regression and linear regression analysis were used to determine risk factors for HGD development and the cumulative risk of stage IV duodenal polyposis, respectively. RESULTS During a median (+/- standard deviation) follow-up of 47.9 +/- 15.6 months, 35 patients with at least two consecutive examinations had 107 duodenojejunal examinations. The Spigelmans score increased in 21 patients (60.0%), and HGD developed in 12 patients (34.2%). High initial Spigelmans score (> 7 points), but not age or APC mutation site, was a risk factor for HGD development. Estimated cumulative risk of developing stage IV duodenal polyposis was of 42.9% at age 60 (95% CI, 35.7% to 50.0%) and 50.0% at age 70 (95% CI, 42.9% to 57.1%). CONCLUSION This prospective series shows a higher duodenal polyposis progression rate and cumulative risk of late-stage (stage IV) duodenal polyposis in FAP patients compared with previous series. These results suggest that current modalities for surveillance and management of these patients need revision.

Chronological aspects of ultrasonic, hormonal, and other indirect indices of ovulation

Objective To improve prediction of ovulation in normal cycles.

Cannabis use correlates with schizotypal personality traits in healthy students

The literature suggests that cannabis use and schizotypal traits both constitute risk factors for the later development of schizophrenia. However, their interrelationships remain to be evaluated. The present study examined the association between cannabis use and schizotypal traits in 232 healthy students who ranged in age from 18 to 25 years. All the students had completed the Schizotypal Personality Questionnaire and four of the Chapman Psychosis Proneness Scales: the Magical Ideation Scale; the Perceptual Aberration Scale; the Revised Physical Anhedonia Scale; and the Revised Social Anhedonia Scale. Subjects were divided into three groups according to cannabis use typology: those who had never used cannabis, those who were past or occasional users, and those who were regular users. Higher scores on the Schizotypal Personality Questionnaire and the Magical Ideation Scale characterized the regular and past or occasional users compared with those who had never used cannabis. The co-occurrence of cannabis use and schizotypal traits appeared to be independent of anxiety and depression dimensions. These data suggest that cannabis use and schizotypal traits have to be jointly considered in further longitudinal studies of schizophrenia risk factors.

Chronic Rejection Triggers the Development of an Aggressive Intragraft Immune Response through Recapitulation of Lymphoid Organogenesis

The unwarranted persistence of the immunoinflammatory process turns this critical component of the body’s natural defenses into a destructive mechanism, which is involved in a wide range of diseases, including chronic rejection. Performing a comprehensive analysis of human kidney grafts explanted because of terminal chronic rejection, we observed that the inflammatory infiltrate becomes organized into an ectopic lymphoid tissue, which harbors the maturation of a local humoral immune response. Interestingly, intragraft humoral immune response appeared uncoupled from the systemic response because the repertoires of locally produced and circulating alloantibodies only minimally overlapped. The organization of the immune effectors within adult human inflamed tissues recapitulates the biological program recently identified in murine embryos during the ontogeny of secondary lymphoid organs. When this recapitulation was incomplete, intragraft B cell maturation was impeded, limiting the aggressiveness of the local humoral response. Identification of the molecular checkpoints critical for completion of the lymphoid neogenesis program should help develop innovative therapeutic strategies to fight chronic inflammation.

Planned vaginal delivery versus elective caesarean section in singleton term breech presentation: a study of 1116 cases.

OBJECTIVE To compare neonatal and maternal morbidity and mortality between planned vaginal delivery and elective cesarean section for singleton term breech presentation. STUDY DESIGN We studied retrospectively all deliveries of singleton breech presentations at term in the public Hospitals of Lyon between 1 January 1991 and 31 December 1995. To take only the effect of delivery on the fetus into account, we eliminated high risk pregnancies and fetal malformations. Fetal parameters were corrected perinatal mortality, Apgar score<7 at 1 and 5 min, umbilical cord arterial pH<7.15, neurological disorders, trauma and need for neonatal intensive care. Maternal parameters were mild, moderate and severe complications. RESULTS Of the 1116 breech presentations, 702 (62.9%) underwent an elective caesarean section and 414 (37.1%) a planned vaginal delivery. In the latter group, 342 (30.6%) had a vaginal delivery and 72 (6.5%) a non-elective caesarean section. Infants for whom the vaginal route was planned were at higher risk of mortality and morbidity. There were 2 deaths in this group and none in the elective caesarean section group and all fetal parameters were poorer: more Apgar<7 at 5 min (RR: relative risk=3.05; 1.03-9.05), arterial pH<7.15 (RR=1.64; 1.11-2.43), intubations (RR=7.35; 2.10-25.6), neurological disorders, trauma (RR=4.24; 1.66-10.8), transfer to intensive care units (RR=3.23; 1.57-6.64). The overall maternal morbidity was lower in the planned vaginal delivery group (RR=0.65; 0.44-0.94) but this was only because of less mild complications. The moderate and severe complications were the same in the two groups (RR=0.97; 0.59-1.57). CONCLUSIONS Planned vaginal delivery in singleton term breech presentation increases the risk of death and of neonatal complications. Elective caesarean section increases the risk of only mild maternal complications. For these reasons, elective caesarean section should be preferred for singleton term breech presentations.

Performance of creatinine-based equations compared in older patients.

BACKGROUND The current equations for estimating glomerular filtration rate (GFR) have limited precision in older people. The Berlin Initiative Study (BIS-1) equation has recently been developed to improve the precision and accuracy of GFR estimation in older people, over the previous simplified Modification of Diet in Renal Disease (MDRD) Study and the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations. METHODS The study included 224 white patients aged >70 years who had simultaneous measurements of plasma creatinine and renal clearance of inulin. Creatinine assays used an enzymatic method with calibrators defined by isotope dilution mass spectrometry. The performance of BIS-1, MDRD and CKD-EPI equations in estimating GFR were compared. RESULTS BIS-1 was the most accurate: the percentage of GFR estimates that fell within the range of measured GFR ± 30% (P30) was 75.56% vs. 70.67% with MDRD and 72% with CKD-EPI. BIS-1 had the lowest median bias: (interquartile range) (4.1 (11.4) vs 5.8 (12.7) and 5.4 (12.8) respectively) the highest precision (the SD of the estimated GFR minus measured GFR differences was 9.21 vs 12.78 and 10.83 mL/min/1.73 m² respectively) and the highest concordance correlation coefficient (CCC) (0.82 vs. 0.74 and 0.79 respectively, p<0.05). However, in chronic kidney disease (CKD) stages 4 and 5, the CKD-EPI equation had the highest P30, the lowest median bias and the highest CCC: it was more accurate than the BIS-1 equation. CONCLUSION Among the 3 creatinine-based equations compared, BIS-1 was the most reliable for assessing renal function in older white patients, especially in those with CKD stages 1 to 3.