Incidence and management of malignant digestive endocrine tumours in a well defined French population

BACKGROUND AND AIMS: Little is known about the epidemiology of malignant digestive endocrine tumours. The aim of this study was to report on their incidence and management in a well defined population. METHODS: Data were obtained from the population based Digestive Cancer Registry of Burgundy (France) over a 24 year period. Incidence rates were calculated by sex, age groups, and period of diagnosis. Treatment and stage at diagnosis were also investigated. Prognosis was determined using crude and relative survival rates. A multivariate relative survival analysis was performed. RESULTS: Between 1976 and 1999, 229 cases were recorded. Age standardised incidence rates were 0.76/100,000 for men and 0.50/100,000 for women. They increased over time in both sexes. The resectability rate was 74.1%. Among recorded cases, 26.6% did not extend beyond the organ, 20% had lymph node metastases, and 53.3% had visceral metastases or were unresectable. There was no improvement in the resection rate or in the stage at diagnosis over the study period. The overall relative survival rate was 66.9% at one year, 50.4% at five years, and 40.6% at 10 years. Stage at diagnosis, age at diagnosis, and subsite were independent significant prognostic factors. CONCLUSIONS: Although their incidence is increasing, malignant digestive endocrine tumours remain a rare cancer, representing 1% of digestive cancers. Stage at diagnosis and prognosis at a population level are worse than those reported in hospital series. In the short term, new therapeutic possibilities represent the best way to improve their prognosis.     

Intradermal influenza vaccine administered using a new microinjection system produces superior immunogenicity in elderly adults: a randomized controlled trial

BACKGROUND: Enhanced influenza vaccines are needed to provide improved protection for elderly individuals. The intradermal vaccination route was hypothesized to provide immunogenicity superior to that provided by the intramuscular vaccination route. METHODS: In a multicenter, randomized study, 1107 volunteers >60 years of age received intradermal trivalent inactivated influenza vaccine containing 15 or 21 microg of hemagglutinin per strain or intramuscular control vaccine. Intradermal vaccines used a novel microinjection system designed to ensure easy, convenient, consistent vaccination. The primary end points of the study were the strain-specific hemagglutination inhibition geometric mean titers (GMTs) noted 21 days after vaccination. Groups were compared using noninferiority and superiority analyses. RESULTS: For each strain, the GMTs noted in association with each intradermal vaccine were superior to those noted with the intramuscular control (adjusted P< .0001). Seroprotection rates, seroconversion rates, and mean titer increases were also superior for intradermally administered vaccine in all but one of the analyses undertaken. Systemic reactogenicity was comparable between routes. Local injection site reactions, particularly erythema but not pain, were more commonly associated with intradermal vaccination. CONCLUSIONS: For the first time, the intradermal vaccination route has been used to elicit immune responses significantly superior to those noted in association with the conventional intramuscular vaccination route. This was done using an easy-to-use, reliable microinjection system. This superior response is expected to enhance annual protection against influenza in this vulnerable population. TRIAL REGISTRATION: Clinicaltrials.gov registry number: NCT00296829.     

Safety and efficacy of Hansenula-derived PEGylated-interferon alpha-2a and ribavirin combination in chronic hepatitis C Egyptian children

AIM:To investigate the safety and efficacy of a Hansenula-derived PEGylated(polyethylene glycol)interferon(IFN)-alpha-2a(Reiferon Retard)plus ribavirin customized regimen in treatment-na?ve and previously treated(non-responders and relapsers)Egyptian children with chronic hepatitis C infection.METHODS:Forty-six children with chronic hepatitis C virus(HCV)infection were selected from three tertiary pediatric hepatology centers.Clinical and laboratory evaluations were undertaken.Quantitative polymerase chain reaction(PCR)for HCV-RNA was performed before starting treatment,and again at 4,12,24,48,72wk during treatment and 6 mo after treatment cessation.All patients were assigned to receive a weekly subcutaneous injection of PEG-IFN-alpha-2a plus daily oral ribavirin for 12 wk.Thirty-four patients were treatment-na?ve and 12 had a previous treatment trial.Patients were then divided according to PCR results into two groups.GroupⅠincluded patients who continued treatment on a weekly basis(7-d schedule),while groupⅡincluded patients who continued treatment on a 5-d schedule.Patients from either group who were PCR-negative at week 48,but had at least one PCRpositive test during therapy,were assigned to have an extended treatment course up to 72 wk.The occurrence of adverse effects was assessed during treatment and follow up.The study was registered at www.ClinicalTrials.gov(NCT02027493).RESULTS:Only 11 out of 46(23.9%)patients showed a sustained virological response(SVR),two patients were responders at the end of treatment;however,they were lost to follow up at 6 mo post treatment.Breakthrough was seen in 18(39.1%)patients,one patient(2.17%)showed relapse and 14(30.4%)were non-responders.Male gender,short duration of infection,low viral load,mild activity,and mild fibrosis were the factors related to a better response.On the other hand,patients with high viral load and absence of fibrosis failed to respond to treatment.Before treatment,liver transaminases were elevated.After commencing treatment,they were normalized in all patients at week 4 and were maintained normal in responders till the end of treatment,while they increased again significantly in non-responders(P=0.007 and 0.003 at week 24 and 72 respectively).The 5-d schedule did not affect the response rate(1/17 had SVR).Treatment duration(whether 48 wk or extended course to 72 wk)gave similar response rates(9/36 vs 2/8 respectively;P=0.49).Type of previous treatment(short acting IFN vs PEG-IFN)did not affect the response to retreatment.On the other hand,SVR was significantly higher in previous relapsers than in previous non-responders(P=0.039).Only mild reversible adverse effects were observed and children tolerated the treatment well.CONCLUSION:Reiferon Retard plus ribavirin combined therapy was safe.Our customized regimen did not influence SVR rates.Further trials on larger numbers of patients are warranted.     

Acute Respiratory Distress Syndrome and Risk of AKI among Critically Ill Patients

Background and objectives

Increasing experimental evidence suggests that acute respiratory distress syndrome (ARDS) may promote AKI. The primary objective of this study was to assess ARDS as a risk factor for AKI in critically ill patients.

Design, setting, participants, & measurements

This was an observational study on a prospective database fed by 18 intensive care units (ICUs). Patients with ICU stays >24 hours were enrolled over a 14-year period. ARDS was defined using the Berlin criteria and AKI was defined using the Risk, Injury, Failure, Loss of kidney function, and End-stage kidney disease criteria. Patients with AKI before ARDS onset were excluded.

Results

This study enrolled 8029 patients, including 1879 patients with ARDS. AKI occurred in 31.3% of patients and was more common in patients with ARDS (44.3% versus 27.4% in patients without ARDS; P<0.001). After adjustment for confounders, both mechanical ventilation without ARDS (odds ratio [OR], 4.34; 95% confidence interval [95% CI], 3.71 to 5.10) and ARDS (OR, 11.01; 95% CI, 6.83 to 17.73) were independently associated with AKI. Hospital mortality was 14.2% (n=1140) and was higher in patients with ARDS (27.9% versus 10.0% in patients without ARDS; P<0.001) and in patients with AKI (27.6% versus 8.1% in those without AKI; P<0.001). AKI was associated with higher mortality in patients with ARDS (42.3% versus 20.2%; P<0.001).

Conclusions

ARDS was independently associated with AKI. This study suggests that ARDS should be considered as a risk factor for AKI in critically ill patients.     

Primary biliary cirrhosis and autoimmune hepatitis overlap syndrome: therapeutic features in 5 patients

Autoimmune hepatitis (AIH) and primary biliary cirrhosis (PBC) are two different liver diseases, however diagnosis criteria of these two affections can be found in a same patient. The aim of this study is to relate the clinical, serologic and histologic features of patients presenting the overlap syndrome, AIH-PBC, defined by the presence of at least of two main criteria of each disease and to evaluate their response to therapy. PATIENTS AND METHODS: This was a retrospective study concerning patients presenting overlap syndrome diagnosed between January 1998 and December 2001. These patients had been treated with ursodesoxycholic acid (AUDC) or prednisone and azathioprine or a combination of these three products. Clinical and biological criteria were used to assess response to therapy. RESULTS: Five patients fulfilled the diagnostic criteria of overlap syndrome. All patients were females, the median age was 38 years (range: 19-65 years). Three patients were treated by UDCA, a clinical and biological response was noted in only one patient. Two patients were treated by prednisone and azathioprine without any remission. Three patients were treated by a combination of these three products with a good response in two cases. CONCLUSION: Optimal treatment for overlap AIH-PBC syndrome remains to be determined. Treatment with UDCA or immunosuppressor alone is not efficient. A combination of these drugs should be evaluated in further studies.     

Fast migrating protein, immunochemically related to human factor VIII, studied by crossed immunoelectrophoresis in agarose

S ummary . A fast migrating protein (FMP) was detected by agarose radio-crossed immunoelectrophoresis, in addition to factor VIII antigen (VII:RAg), using antiserum to human factor VIII (FVIII). FMP had partial immunochemical identity with FVIII, migrated as an α-protein, and was distinct from α-2 macroglobulin, fibronectin or IgM. FMP was precipitated by concanavalin A and was separable from the bulk of VII:RAg by ammonium sulphate fractionation. A significant amount of FMP was seen in normal serum ( n = 12), plasma from patients with: (a) disseminated intravascular coagulation ( n = 12) and (b) severe haemophilia A ( n = 6). Trace amounts of FMP were observed in plasma from normal donors ( n = 12), but neither VIII: RAg nor FMP was detectable in the plasma or serum from patients with severe von Willebrand's disease ( n = 3). Freshly prepared cryoprecipitate contained trace amounts of FMP, similar to normal plasma, but increased levels were observed in antihaemophilic factor concentrates prepared for patient use. Significant levels of FMP were also seen in cryoprecipitate after storage at 4°C for 7 d and this generation of FMP was diminished by the addition of protease inhibitors. The presence of significant levels of FMP in situations where proteolytic enzymes may be activated and inhibition of its generation by protease inhibitors, suggest that this protein is produced by proteolytic action of enzyme(s) on the FVIII molecule.     

Dual-source computed tomography coronary angiography: influence of obesity, calcium load, and heart rate on diagnostic accuracy.

AIMS: To prospectively investigate the diagnostic accuracy of dual-source computed tomography coronary angiography (CTCA) to diagnose coronary stenoses in relation to body mass index (BMI), Agatston score (AS), and heart rate (HR) as compared with catheter coronary angiography (CCA). METHODS AND RESULTS: Hundred and fifty consecutive patients (47 female, mean age 62.9 +/- 12.1 years) underwent dual-source CTCA without HR control. Patients were divided into subgroups depending on the median of their BMI (26.0 kg/m2), AS (194), and HR (66 b.p.m.). CCA was considered the standard of reference. Mean BMI was 26.5 +/- 4.2 kg/m2 (range 18.3-39.1 kg/m2), mean AS was 309 +/- 408 (range 0-4387), and HR was 68.5 +/- 12.6 b.p.m. (range 35-102 b.p.m.). Diagnostic image quality was found in 98.1% of all segments (2020/2059). Considering not-evaluative segments at CTCA as false-positive, overall per-patient sensitivity, specificity, positive, and negative predictive value were 96.6%, 86.8%, 82.6%, and 97.5%, respectively. High HR did not deteriorate diagnostic accuracy of CTCA. High BMI and AS were associated with a decrease in per-patient specificity to 84.1% and 77.8%, respectively, while sensitivity and negative predictive value remained high. CONCLUSION: Dual-source CTCA provides high diagnostic accuracy irrespective of the HR and serves as a modality to rule-out coronary artery stenoses even in patients with high BMI and AS.