Do pregnancies reduce iron overload in HFE hemochromatosis women? results from an observational prospective study.

BACKGROUND: HFE hemochromatosis is an inborn error of iron metabolism linked to a defect in the regulation of hepcidin synthesis. This autosomal recessive disease typically manifests later in women than men. Although it is commonly stated that pregnancy is, with menses, one of the factors that offsets iron accumulation in women, no epidemiological study has yet supported this hypothesis. The aim of our study was to evaluate the influence of pregnancy on expression of the predominant HFE p.[Cys282Tyr];[Cys282Tyr] genotype. METHODS: One hundred and forty p.Cys282Tyr homozygous women enrolled in a phlebotomy program between 2004 and 2011 at a blood centre in western Brittany (France) were included in the study. After checking whether the disease expression was delayed in women than in men in our study, the association between pregnancy and iron overload was assessed using multivariable regression analysis. RESULTS: Our study confirms that women with HFE hemochromatosis were diagnosed later than men cared for during the same period (52.6 vs. 47.4 y., P < 0.001). Compared to no pregnancy, having at least one pregnancy was not associated with lower iron markers. In contrast, the amount of iron removed by phlebotomies appeared significantly higher in women who had at least one pregnancy (eß = 1.50, P = 0.047). This relationship disappeared after adjustment for confounding factors (eß = 1.35, P = 0.088). CONCLUSIONS: Our study shows that pregnancy status has no impact on iron markers level, and is not in favour of pregnancy being a protective factor in progressive iron accumulation. Our results are consistent with recent experimental data suggesting that the difference in disease expression observed between men and women may be explained by other factors such as hormones.

PKD2-Related Autosomal Dominant Polycystic Kidney Disease: Prevalence, Clinical Presentation, Mutation Spectrum, and Prognosis.

BACKGROUND: PKD2-related autosomal dominant polycystic kidney disease (ADPKD) is widely acknowledged to be of milder severity than PKD1-related disease, but population-based studies depicting the exact burden of the disease are lacking. We aimed to revisit PKD2 prevalence, clinical presentation, mutation spectrum, and prognosis through the Genkyst cohort. STUDY DESIGN: Case series, January 2010 to March 2016. SETTINGS & PARTICIPANTS: Genkyst study participants are individuals older than 18 years from 22 nephrology centers from western France with a diagnosis of ADPKD based on Pei criteria or at least 10 bilateral kidney cysts in the absence of a familial history. Publicly available whole-exome sequencing data from the ExAC database were used to provide an estimate of the genetic prevalence of the disease. OUTCOMES: Molecular analysis of PKD1 and PKD2 genes. Renal survival, age- and sex-adjusted estimated glomerular filtration rate. RESULTS: The Genkyst cohort included 293 patients with PKD2 mutations (203 pedigrees). PKD2 patients with a nephrology follow-up corresponded to 0.63 (95% CI, 0.54-0.72)/10,000 in Brittany, while PKD2 genetic prevalence was calculated at 1.64 (95% CI, 1.10-3.51)/10,000 inhabitants in the European population. Median age at diagnosis was 42 years. Flank pain was reported in 38.9%; macroscopic hematuria, in 31.1%; and cyst infections, in 15.3% of patients. At age 60 years, the cumulative probability of end-stage renal disease (ESRD) was 9.8% (95% CI, 5.2%-14.4%), whereas the probability of hypertension was 75.2% (95% CI, 68.5%-81.9%). Although there was no sex influence on renal survival, men had lower kidney function than women. Nontruncating mutations (n=36) were associated with higher age-adjusted estimated glomerular filtration rates. Among the 18 patients with more severe outcomes (ESRD before age 60), 44% had associated conditions or nephropathies likely to account for the early progression to ESRD. LIMITATIONS: Younger patients and patients presenting with milder forms of PKD2-related disease may not be diagnosed or referred to nephrology centers. CONCLUSIONS: Patients with PKD2-related ADPKD typically present with mild disease. In case of accelerated degradation of kidney function, a concomitant nephropathy should be ruled out.

Chronic subdural haematomas in elderly population. Neurosurgical aspects and focus on the single-burr hole technique performed under assisted local anaesthesia.

OBJECTIVE: Chronic subdural haematomas (CSDH) is a common pathology that usually affects the elderly population. The incidence of CSDH has recently been increasing with the expansion of the aging population. The objective of our study was to evaluate the outcome following surgical drainage of CSDH in elderly patients. MATERIALS AND METHODS: We performed a retrospective analysis of 455 consecutive patients with CSDHs over a 5-year period. Among them, all 121 patients older than 80-year old were included in the study. Clinical status, comorbidities, type of surgical technique and outcome were analyzed. Outcome at last follow-up was measured using the Markwalder grading score and the Glasgow outcome scale. RESULTS: Patients ranged from 80- to 94-year old with a median age of 84 years (range 80-94). Ninety-eight percent of patients were surgically treated by a small burr hole under assisted local anaesthesia. About 69.2% of patients improved post-operatively. The mortality rate was 6.8%. CONCLUSION: CSDH is a common pathology in the elderly population. Patients with CSDHs often have comorbodities that need to be considered in deciding whether surgical treatment is indicated. When surgery is elected, small craniostomy techniques performed under assisted local anesthesia is safe and should be favored in this frail population.

Measures to improve microbial quality surveillance of gastrointestinal endoscopes.

BACKGROUND AND STUDY AIM: Infectious outbreaks associated with the use of gastrointestinal endoscopes have increased in line with the spread of highly resistant bacteria. The aim of this study was to determine the measures required to improve microbial quality surveillance of gastrointestinal endoscopes. METHODS: We reviewed the results of all microbiological surveillance testing of gastrointestinal endoscopes and automatic endoscope reprocessors (AERs) performed at Brest Teaching Hospital from 1 January 2008 to 1 June 2015. We analyzed the influence of the time of incubation on the rate of positive results using the Kaplan - Meier method. We also studied risk factors for gastrointestinal endoscope contamination using a multivariable logistic regression model. RESULTS: Over the study period, 1100 microbiological tests of gastrointestinal endoscopes (n = 762) and AERs (n = 338) were performed. A total of 264 endoscope tests (34.6 %) showed a level of contamination higher than the target. After 2 days of incubation, contamination was apparent in only 55.5 % of the endoscopes that were later shown to be contaminated (95 % confidence interval [CI] 49.2 - 61.8). Multivariable analysis showed that the use of storage cabinets for heat-sensitive endoscopes significantly reduced the risk of endoscope contamination (odds ratio [OR] 0.23, 95 %CI 0.09 - 0.54; P  < 0.001) and that the use of endoscopes older than 4 years significantly increased this risk (OR ≥ 6 vs. < 2 years 2.92, 95 %CI 1.63 - 5.24; P < 0.001). CONCLUSIONS: Microbiological culture technique, mainly incubation duration, strongly influenced the results of endoscope sampling. Samples should be cultured for more than 2 days to improve the detection of contaminated endoscopes. Particular attention should be paid to endoscopes older than 2 years and to those that are not stored in storage cabinets for heat-sensitive endoscopes.

Type of PKD1 mutation influences renal outcome in ADPKD.

Autosomal dominant polycystic kidney disease (ADPKD) is heterogeneous with regard to genic and allelic heterogeneity, as well as phenotypic variability. The genotype-phenotype relationship in ADPKD is not completely understood. Here, we studied 741 patients with ADPKD from 519 pedigrees in the Genkyst cohort and confirmed that renal survival associated with PKD2 mutations was approximately 20 years longer than that associated with PKD1 mutations. The median age at onset of ESRD was 58 years for PKD1 carriers and 79 years for PKD2 carriers. Regarding the allelic effect on phenotype, in contrast to previous studies, we found that the type of PKD1 mutation, but not its position, correlated strongly with renal survival. The median age at onset of ESRD was 55 years for carriers of a truncating mutation and 67 years for carriers of a nontruncating mutation. This observation allows the integration of genic and allelic effects into a single scheme, which may have prognostic value.

[Breast cancer in Finistère, France: epidemiological description and tendencies over a 10-year period (2000-2009) according to pathology data]. / Épidémiologie des cancers du sein dans le Finistère entre 2000 et 2009 à partir d'une base de données anatomopathologiques.

UNLABELLED: The aim of this study was the description of breast carcinoma over a 10-year period according to pathology data. METHOD: Descriptive epidemiological study based on data collection of pathological code ADICAP (injury, organ, and applied technical), histological, hormonal, node and administrative data. From January 1st 2000 to December 31st 2009, 6186 women living in Finistère have had a diagnosis of invasive breast carcinoma. The incidence rate involved from 125 per 100,000 women to 136 in 2009. Average age to the first diagnosis was 61.4 ± 13.6; class of age with the more important incidence rate was for the 50-74 years old. The different histological subtypes varied over the period (P<0.0001). Tumour's size was notified for more than 75% in the whole period of the study. The average size evolved significantly over the period (P<0.0001 from 23.5mm [± 18.4] in 2000 to 21.02 [± 16.2] in 2009, particularly after 2003 [P<0.0002]). The grade status (SBR, MSBR and Elston Ellis) showed a trend to the gravity decrease over the period (respectively P=0.03 [r(2)=-0,04]; P<0.0001 [r(2)=-0.10]; P<0.0001 [r(2)=-0.08]). CONCLUSION: Our results confirm the interest of pathology database for the description of invasive breast cancer.

Does Decreased Diffusing Capacity of the Lungs for Carbon Monoxide Constitute a Risk of Decompression Sickness in Occupational Divers?

Long-term alterations of pulmonary function (mainly decreased airway conductance and capacity of the lungs to diffuse carbon monoxide (DLCO)) have been described after hyperbaric exposures. However, whether these alterations convey a higher risk for divers' safety has never been investigated before. The purpose of the present pilot study was to assess whether decreased DLCO is associated with modifications of the physiological response to diving. In this case-control observational study, 15 "fit-to-dive" occupational divers were split into two groups according to their DLCO measurements compared to references values, either normal (control) or reduced (DLCO group). After a standardized 20 m/40 min dive in a sea water pool, the peak-flow, vascular gas emboli (VGE) grade, micro-circulatory reactivity, inflammatory biomarkers, thrombotic factors, and plasmatic aldosterone concentration were assessed at different times post-dive. Although VGE were recorded in all divers, no cases of decompression sickness (DCS) occurred. Compared to the control, the latency to VGE peak was increased in the DLCO group (60 vs. 30 min) along with a higher maximal VGE grade (p < 0.0001). P-selectin was higher in the DLCO group, both pre- and post-dive. The plasmatic aldosterone concentration was significantly decreased in the control group (-30.4 ± 24.6%) but not in the DLCO group. Apart from a state of hypocoagulability in all divers, other measured parameters remained unchanged. Our results suggest that divers with decreased DLCO might have a higher risk of DCS. Further studies are required to confirm these preliminary results.

A cluster of Pneumocystis infections among renal transplant recipients: molecular evidence of colonized patients as potential infectious sources of Pneumocystis jirovecii.

BACKGROUND: Eighteen renal transplant recipients (RTRs) developed Pneumocystis jirovecii infections at the renal transplantation unit of Brest University Hospital (Brest, Brittany, France) from May 2008 through April 2010, whereas no cases of P. jirovecii infection had been diagnosed in this unit since 2002. This outbreak was investigated by identifying P. jirovecii types and analyzing patient encounters. METHODS: The identification of P. jirovecii internal transcribed spacer (ITS) types was performed on P. jirovecii isolates from the 18 RTRs (12 patients with Pneumocystis pneumonia [PCP], 6 colonized patients), 22 unlinked control patients (18 patients with PCP, 4 colonized patients), and 69 patients (34 patients with PCP, 35 colonized patients) with contemporaneously diagnosed P. jirovecii infections in the Brest geographic area. A transmission map was drawn up. Its analysis was combined with the results of P. jirovecii typing. RESULTS: P. jirovecii ITS type identification was successful in 14 of 18 RTRs, 15 of 22 control patients, and 48 of the 69 patients. Type Eg was the most frequent type in the 3 patient groups. However, its frequency was significantly higher in the first patient group than in the 2 other groups (P < .05 and P < .01, respectively). Fourteen encounters between RTRs who harbored an identical type were observed. Ten patients were considered as possible index patients, of whom 3 were colonized by the fungus, and 7 presented PCP. CONCLUSIONS: The results provide to our knowledge the first data on the role of colonized patients as potential sources of P. jirovecii in a context of nosocomial acquisition of the fungus.

La surveillance microbiologique des endoscopes comme élément d'assurance qualité au Centre hospitalier territorial de Nouvelle-Calédonie entre 2012 et 2020.

CONTEXTE: Les endoscopes souples sont des appareils complexes non autoclavables qui doivent subir une désinfection de haut niveau. La présence de souillures et de biofilms peut être à l'origine d'infection et favoriser la diffusion de résistances aux antibiotiques. La surveillance microbiologique des endoscopes est recommandée en France mais reste controversée au niveau international. L'objectif de cette étude est d'évaluer l'apport de cette surveillance comme élément d'assurance qualité en Nouvelle Calédonie. Méthode. Nous avons revu l'ensemble des contrôles microbiologiques effectué sur les endoscopes souples entre le 1er janvier 2012 et le 31 décembre 2020 au Centre hospitalier territorial (CHT) de Nouvelle-Calédonie. Nous avons évalué le taux de contamination et identifié les principaux microorganismes isolés. Résultats. Six-cent-cinq contrôles microbiologiques d'endoscopes ont été analysés. Au total, 87 prélèvements (14,4 %) n'atteignaient pas le niveau cible. Le taux de non-conformité variait de 25,0 % à 4,5 % en fonction des années. Les cholédoscopes et les échoendoscopes étaient les appareils (p = 0,0035) les plus contaminés. Les principaux microorganismes identifiés étaient des bactéries gram positives comme les staphylocoques à coagulase négative (n = 122) et Micrococcus sp (n = 97), et des bactéries gram négatives dont Moraxella sp (n = 31) et des Pseudomonas (n = 17). CONCLUSION: Cette étude a permis d'évaluer l'efficacité de la désinfection des endoscopes souples utilisés au CHT. Le taux global de contamination (14,4 %) est conforme aux chiffres publiés dans différentes études. Cette surveillance permet d'identifier des écarts dans le processus de désinfection et d'apporter les mesures correctives qui garantissent la sécurité des patients.

Both microbiological surveillance and audit of procedures improve reprocessing of flexible bronchoscopes and patient safety.

BACKGROUND: Microbiological surveillance of bronchoscopes and automatic endoscope reprocessors (AERs)/washer disinfectors as a quality control measure is controversial. Experts also are divided on the infection risks associated with bronchoscopic procedures. OBJECTIVE: We evaluated the impact of routine microbiological surveillance and audits of cleaning/disinfection practices on contamination rates of reprocessed bronchoscopes. DESIGN: Audits were conducted of reprocessing procedures and microbiological surveillance on all flexible bronchoscopes used from January 2007 to June 2020 at a teaching hospital in France. Contamination rates per year were calculated and analyzed using a Poisson regression model. The risk factors for microbiological contamination were analyzed using a multivariable logistical regression model. RESULTS: In total, 478 microbiological tests were conducted on 91 different bronchoscopes and 57 on AERs. The rate of bronchoscope contamination significantly decreased between 2007 and 2020, varying from 30.2 to 0% (P < .0001). Multivariate analysis confirmed that retesting after a previous contaminated test was significantly associated with higher risk of bronchoscope contamination (OR, 2.58; P = .015). This finding was explained by the persistence of microorganisms in bronchoscopes despite repeated disinfections. However, the risk of persistent contamination was not associated with the age of the bronchoscope. CONCLUSIONS: Our results confirm that bronchoscopes can remain contaminated despite repeated reprocessing. Routine microbial testing of bronchoscopes for quality assurance and audit of decontamination and disinfection procedures can improve the reprocessing of bronchoscopes and minimize the rate of persistent contamination.

Prevention and control of highly antibiotic-resistant bacteria in a Pacific territory: Feedback from New Caledonia between 2004 and 2020.

OBJECTIVE: Carbapenemase-producing Enterobacteriaceae (CRE) and Enterococcus faecium resistant to vancomycin (VRE) constitute major threats to public health worldwide. The Pacific area is concerned and has implemented strategies to control antimicrobial resistance (AMR). However, accurate epidemiological data are rarely reported. Our study aimed to present the strategies applied to prevent and control the spread of highly resistant bacteria in the Pacific territory of New Caledonia. PATIENTS AND METHODS: Cohort prospective study of all cases of highly resistant bacteria (HRB) isolated in New Caledonia from September 2004 to December 2020. Evaluation of the impact of the infection control measures implemented in healthcare settings: screening strategy, cohorting unit, IT tools and control of antibiotic prescriptions. RESULTS: A total of 346 patients with HRB were identified. Most of them (63.0%) were infected or colonized by VRE (n=218) and 128 by CRE. While the number of CREs significantly increased from 2013 to 2020 (P<0.0001), control procedures have limited their dissemination. Most patients were colonized by IMP-4-CRE (n=124/128). The incidence density of VRE significantly decreased from 38.52 for 100,000 hospitalisation-days in 2015 to 4.19 for 100,000 hospitalisation-days in 2019 due to systematic screening of patients before sanitary repatriation from Australia and cohorting implementation. The risk of VRE diffusion is now well under control. CONCLUSIONS: Our study confirms that it is possible to control the spread of AMR in a circumscribed territory by means of a global control strategy involving screening, cohorting unit, IT tools and antibiotic prescription controls.

Evaluation of posaconazole antifungal prophylaxis in reducing the incidence of invasive aspergillosis in patients with acute myeloid leukemia.

PURPOSE OF THE STUDY: Invasive aspergillosis (IA) is the most prevalent invasive fungal disease (IFD) in neutropenic patients. Environment is the main source of Aspergillus spores aerosolization especially during building construction. International guidelines recommend mechanical protection during hospital building works; otherwise the use of antifungal prophylaxis is not clearly indicated. Our objective was to determine the efficacy of antifungal prophylaxis by posaconazole on IA incidence in acute myeloid leukemia population and to analyse the benefit of this prophylaxis and HEPA-filters during hospital buildings works. PATIENTS AND METHODS: We included patients treated for acute myeloid leukemia at Brest teaching hospital from January 2009 to December 2015. We compared incidence of IA in the group treated by posaconazole from 2012 to 2015 to the incidence of IA in the first group who did not receive antifungal prophylaxis (from 2009 to 2011). The one-year overall survival was also analyzed using the Kaplan-Meier method. RESULTS: 245 patients were enrolled including 151 treated with posaconazole. 23 IA were diagnosed between 2009 and 2011 (without antifungal prophylaxis), then 31 between 2012 and 2015 (with posaconazole) without statistical difference between the incidence densities (0.34 per 100 hospitalization-days vs. 0.30 per 100 hospitalization-days, p = 0.71). Incidence density of IA increased during building works (2.40 per 100 hospitalization-days vs. 0.28 per 100 hospitalization-days, p < 0.0001). The incidence density of IA significantly decreased during construction periods when posaconazole prophylaxis was used (1.59 per 100 hospitalization-days vs. 4.87 per 100 hospitalization-days p < 0.0001). CONCLUSION: Our study suggests, for the first time, the interest of antifungal prophylaxis in addition to HEPA filtration in prevention of IA during hospital building works.

A training program for fibromyalgia management: A 5-year pilot study.

We studied the effects of a specific cardio training program lasting 5 years on pain and quality of life in fibromyalgia patients. METHOD: An observational longitudinal pilot study was conducted in 138 fibromyalgia women. Fibromyalgia women recruited were asked to carry out three sessions per week, each lasting 45 min, of moderate-intensity continuous training (64%-75% Maximal Heart rate [HRmax]). During the first year, the patients progressively increased their training intensity. During the last 2 years, the patients were asked to associate moderate-intensity continuous training and high-intensity interval training (85%-90% HRmax). Pain on a visual analog scale, anxiety and depression state on the Hospital Anxiety and Depression Scale, impact of fibromyalgia on daily life using the Fibromyalgia Impact Questionnaire, heart rate and sleep quality (visual analog scale) were assessed at baseline and each year for 5 years. RESULTS: Forty-nine patients dropped out in the first year. Depending on their training status, the remaining 89 patients were retrospectively assigned to one of the three groups: Active (moderate-intensity continuous training), Semi-Active (one or two sessions, low-intensity continuous training <60% HRmax) and Passive (non-completion of training), based on their ability to comply with the program. Alleviation of all symptoms (p < 0.0001) was observed in the Active group. Increasing exercise intensity enhanced the effects obtained with moderate-intensity continuous training. Significant change in the Fibromyalgia Impact Questionnaire (p < 0.0001) and depression (Hospital Anxiety and Depression Scale; p < 0.0001), and no significant decrease in pain were noted in the Semi-Active group. No effect of the training was observed in the Passive group. CONCLUSION: The study intervention associated with multidisciplinary care alleviated pain, anxiety and depression, and improved both quality of life and quality of sleep, in fibromyalgia patients.

[The organization and management of health services during mine clearance operations in Finistère]. / Organisation sanitaire lors des opérations de déminage dans le Finistère.

The regional social affairs and health services department (DDASS) of Finistère in France, in cooperation with first-aid workers, the town hall and the police headquarters, have developed and refined a method for medical evacuations of people during mine clearance in the area of Brest. It consists of conducting a census of the population in their place of residence, identifying the hospitalisation needs, and organising their management and care provided by the first-aid workers. Having been applied and put into practice since 2003, this method is reliant on tools created by the regional social affairs and health services department of. It is frequently used and has proven its effectiveness.