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.

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.

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.

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.

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.

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.

Histopathological factors help to predict lymph node metastases more efficiently than extra-nodal recurrences in submucosa invading pT1 colorectal cancer.

The therapeutic management of patients with endoscopic resection of colorectal cancer invading the submucosa (i.e. pT1 CRC) depends on the balance between the risk of cancer relapse and the risk of surgery-related morbidity and mortality. The aim of our study was to report on the histopathological risk factors predicting lymph node metastases and recurrences in an exhaustive case series comprising every pT1 CRC (of adenocarcinoma subtype only) diagnosed in Finistère (France) during 5-years. For 312 patients with at least 46 months follow-up included in the digestive cancers registry database, histopathological factors required for risk stratification in pT1 CRC were reviewed. Patients were treated by endoscopic resection only (51 cases), surgery only (138 cases), endoscopic resection followed by surgery (102 cases) or transanal resection (21 cases). Lymph node metastases were diagnosed in 19 patients whereas 15 patients had an extra-nodal recurrence (7 local recurrences only, 4 distant metastases only and 4 combining local and distant recurrences). Four patients with distant metastases died of their cancer. Poor tumor differentiation, vascular invasion and high grade tumor budding on HES slides were notably identified as strong risk-factors of lymph node metastases but the prediction of extra-nodal recurrences (local, distant and sometimes fatal) was less obvious, albeit it was more frequent in patients treated by transanal resection than with other treatment strategies. Beyond good performances in predicting lymph node metastases and guiding therapeutic decision in patients with pT1 CRC, our study points that extra-nodal recurrence of cancer is more difficult to predict and requires further investigations.

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.

Asbestos-related lung cancers: A retrospective clinical and pathological study.

Exposure to asbestos results in serious risks of developing mesothelioma and lung cancer. The link between asbestos exposure and lung carcinoma is well established. Nevertheless, precise histopathological data are poorly considered when investigating the asbestos-cancer link in a compensatory approach. In the present study, we aim to describe the features of individuals with compensated lung cancer who were referred to an occupational disease center, regarding occupational exposure to asbestos, smoking history and pathological data. We led a retrospective study of compensated ARLC cases seen in our occupational disease center between 2003 and 2013. A total of 146 men were included (mean age at diagnosis, 63.2 years) of whom approximately 90% were heavy current or former smokers (mean value, 30.4 packs/year). The major industries associated with the lung cancer cases were shipbuilding (69.9%), and building construction (7.5%) in this harbor region. The results of the present study showed that lung upper lobe was most prevalent (61.6%) and an excess of adenocarcinoma was found (45.9%), followed by squamous cell carcinoma (38.4%) as well as thoracic sarcomas (2.1%). Neoplasm was not histologically proven in 6.8% of the cases. Subsequent pathology examinations also reclassified 2 tumors as metastases from esophageal and laryngeal origins. In conclusion, smoking prevention should be encouraged in asbestos-exposed workers as reflected by the number of smokers with asbestos-related lung cancer. Thus, histological data should be considered further to evaluate the potent relationship between asbestos exposure and lung malignancy, especially in a compensatory approach.

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.

Severe Health-Related Quality of Life Impairment in Active Primary Sjögren's Syndrome and Patient-Reported Outcomes: Data From a Large Therapeutic Trial.

OBJECTIVE: To identify the principal determinants of health-related quality of life (HRQOL) impairment in patients with active primary Sjögren's syndrome (SS) participating in a large therapeutic trial, Tolerance and Efficacy of Rituximab in Primary Sjögren's Syndrome (TEARS). METHODS: At the inclusion visit for the TEARS trial, 120 patients with active primary SS completed the Short Form 36 health survey (SF-36), a validated HRQOL assessment tool. Univariate then multivariate linear regression analyses were used to assess associations linking SF-36 physical and mental components to demographic data, patient-reported outcomes (symptom intensity assessments for dryness, pain, and fatigue, including the European League Against Rheumatism [EULAR] Sjögren's Syndrome Patient Reported Index [ESSPRI]), objective measures of dryness and autoimmunity, and physician evaluation of systemic activity (using the EULAR Sjögren's Syndrome Disease Activity Index [ESSDAI]). RESULTS: SF-36 scores indicated marked HRQOL impairments in our population with active primary SS. Approximately one-third of the patients had low, moderate, and high systemic activity according to the ESSDAI. ESSPRI and ESSDAI scores were moderately but significantly correlated. The factors most strongly associated with HRQOL impairment were patient-reported symptoms, best assessed using the ESSPRI, with pain and ocular dryness intensity showing independent associations with HRQOL. Conversely, systemic activity level was not associated with HRQOL impairment in multivariate analyses, even in the patient subset with ESSDAI values indicating moderate-to-high systemic activity. CONCLUSION: The cardinal symptoms of primary SS (dryness, pain, and fatigue, best assessed using the ESSPRI) are stronger predictors of HRQOL impairment than systemic involvement (assessed by the ESSDAI) and should be used as end points in future therapeutic trials focusing on patients' well-being. New consensual and data-driven response criteria are needed for primary SS studies.

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.

Duplication of the V3 domain in hepatitis C virus (1b) NS5A protein: Clonal analysis and physicochemical properties related to hepatocellular carcinoma occurrence.

BACKGROUND: Hepatitis C virus non-structural protein 5A is known to play a role in development of hepatocellular carcinoma (HCC) via interactions with host cell pathways. OBJECTIVES: Hepatitis C virus genotype 1b strains presenting a wide insertion of 31 amino acids in the non-structural protein 5A V3 domain (V3 DI) were studied to determine whether this V3-like additional domain (V3 DII) was associated with HCC occurrence. STUDY DESIGN: Seventy-four patients' sera were screened for V3 DII presence regarding clinical status. RESULTS: Three strains with duplicated V3 were detected among patients with progression to HCC (n=28), two strains among patients with liver cirrhosis (Ci, n=27) and none among patients with chronic hepatitis (Chr, n=19). Phylogenetic trees built from V3 DI and V3 DII sequences indicated that the latter clustered separately. In between-group clonal analysis, V3 DII sequences from the HCC group were found to be more distant from HCV-J than V3 DI sequences (p<0.0001). Between-group comparisons showed significant differences in genetic distances from HCV-J, in HCC V3 DI and HCC V3 DII compared to Ci V3 DI and Ci V3 DII sequences (p<0.0001). HCC V3 DII domain and its junction with V3 DI exhibited higher Shannon entropy values and enrichment in disorder-promoting residues. CONCLUSIONS: Taken together, our results suggest that V3 DII evolution may differ in strains associated with HCC occurrence. The presence of an intrinsically "disordered" V3 duplicate may alter the NS5A protein network. Further investigations are necessary to elucidate the potential impact of V3 duplication in the context of carcinogenesis.