[Allogeneic hematopoietic stem cell transplantation and treatment with CAR-T cells - identification of psycho-social vulnerability factors: Guidelines from the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC)]. / Allogreffe de cellules souches hématopoïétiques et traitement par CAR-T cells ­ repérage des facteurs de vulnérabilité psycho-sociale : recommandations de la Société francophone de greffe de moelle et de thérapie cellulaire (SFGM-TC).

Allogeneic hematopoietic stem cell transplantation (HCT) and CAR-T cells therapy are treatments with curative aim for certain hematological malignancies, refractory or relapse. Nevertheless, they carry the risk of morbidity and mortality and may have a significant psychosocial impact, particularly for HCT. It is therefore necessary to identify psychological difficulties and social problems, as well as the patient's resources, and those of his entourage, in order to improve his overall management. The objective of this evaluation is not to pose contraindications to treatments, but to adapt the personalized care project. This identification must be carried out early on in the pre-HCT assessment journey to enable the implementation of appropriate actions by the various care providers. Based on a review of the literature, we designed a psychosocial data collection grid that can be initiated in pre-transplant and updated by accompanying the patient at each stage of follow-up (discharge from hospital, day-hospital follow-up, D100 evaluation). This grid is divided into 3 axes: socio-family context, psychological and somatic aspects. This tool allows the traceability of the interventions of different professionals and is a support for multidisciplinary exchanges.

Screening for psychosocial risks among physicians in a pediatric hospital.

Over the past decades, productivity practices at hospital resulted in staff overload and burnout. Prompted by physicians' complaints, this study assessed the level of psychosocial risk among senior pediatricians in a university hospital. The survey used the checklist of Quebec's National Institute of Public Health that comprises two six-indicator parts: "Context" and "Key Components" of the Organization. The psychosocial risk level was evaluated by a physician-psychologist duo during interviews of homogeneous groups of workers. The indicators were scored, tabulated, and discussed. The survey led to a substantial qualitative and quantitative clarification of physicians' working conditions, claims, and needs. Regarding Context, the staff reported mainly: (a) cumbersome organization and norms vs. limited human resources (lack of stability, incentives, and promotions); (b) absenteeism and presenteeism; (c) reluctance to seek care or advice for fear of discredit; (d) presence of verbal violence; (e) self-imposed harsh returns-to-work; (f) work-life conflicts and difficult mental disconnection from work. Regarding the Key Components, the staff reported mainly: (a) work overload (physical, mental, psychological, and relational/social), continuous stress, and perceived exhaustion; (b) low job satisfaction and insufficient recognition; (c) inconstant support by their superiors; (d) poor job relationships and colleagues' support; (e) occasional participation and lack of real autonomy and/or strategy sharing. The survey succeeded in underlining concerning issues that required the immediate attention of occupational physicians and managers. It proved the method feasible and valuable in the medical context despite a high diversity of staff functions and degrees.

Nutritional management of people living with cystic fibrosis throughout life and disease continuum: Changing times, new challenges.

Cystic fibrosis (CF) is a genetic disease caused by mutations in the gene encoding for the ion channel cystic fibrosis transmembrane conductance regulator (CFTR). The management of CF disease has evolved in recent decades from treating downstream disease manifestations affecting the airways, the lungs and the gastrointestinal system to addressing the CFTR gene defect. The advent of CFTR modulators, which correct the functionality of the defective CFTR, contributes to reshaping the landscape of CF demographics, prognosis and therapies, including nutritional management. A spectrum of clinical manifestations is emerging within the same patient population where undernutrition and nutritional deficiencies coexist with excessive weight gain and metabolic derangements. Such contrasting presentations challenge current practices, require adjustments to traditional approaches, and involve more individualised interventions. This narrative review examines the current state of knowledge on the nutritional management of people living with cystic fibrosis from early life to adulthood in the era of CFTR modulation.

Time trend in surgical indications and outcomes in ulcerative colitis-A two decades in-depth retrospective analysis.

BACKGROUND: Recent data regarding the impact of biologics and new surgical techniques on the indications and outcomes of colectomy for ulcerative colitis (UC) are limited. AIMS: The present study aimed at determining the trend of colectomy in UC by comparing colectomy indications and outcomes between 2000 and 2010 and 2011-2020. METHODS: This observational retrospective study was conducted in two tertiary hospitals, including consecutive patients who underwent colectomy between 2000 and 2020. All data concerning UC history, treatment and surgeries were collected. RESULTS: Among the 286 patients included, 87 underwent colectomy in 2001-2010 and 199 in 2011-2020. Patients' characteristics were similar between groups, except for prior biologic exposure (50.6 % vs. 74.9%; p<0.001). The indications of colectomy significantly decreased for refractory UC (50.6 % vs. 37.7%; p = 0.042), but were similar for acute severe UC (36.8 % vs. 42.2%; p = 0.390) and (pre)neoplastic lesions (12.6 % vs. 20.1%; p = 0.130). A widespread use of laparoscopy (47.7 % vs. 81.4%; p<0.001) was associated with fewer early complications (12.6 % vs. 5.5%; p = 0.038). CONCLUSION: Over the last two decades, the proportion of surgery for refractory UC significantly decreased compared to other surgical indications while surgical outcomes improved despite larger exposure to biologics.

Incidence of commuting accidents among non-physician staff in a large French university hospital centre from 2012 to 2016.

BACKGROUND: Traffic road crashes are the leading cause of fatal crashes at work. The circumstances of work-related road accidents have been a regular focus of study, but there is still a lack of knowledge about commuting accidents. OBJECTIVE: The aims of this study were to estimate the overall incidence of commuting accidents for non-physician professionals in a major French university hospital, by gender and different professional categories, and to assess its evolution over a 5-year period. METHODS: A descriptive analysis was performed on 390 commuting accidents from 2012 to 2016 extracted from the university hospital's occupational health service. Incidences of commuting accidents were calculated according to gender, occupational categories, and years. Crude relative risk (RR) for the association of commuting accidents with gender, occupational categories, and year of the accident was also estimated using log-binomial regressions. RESULTS: The annual incidence ranged from 354 to 581 accidents per 100,000 employees. Compared with administrative staff, the relative risk (RR) for commuting accidents for service agents was 1.6 (95% confidence interval (CI): 1.1-2.4) and for auxiliary nurses and childcare assistants was 1.3 (95% CI: 1.0-1.9). Nursing executives had a non-significantly lower RR of 0.6 (95% CI: 0.3-1.5). CONCLUSION: The increased risk observed for the auxiliary nurses and childcare assistants and for the service agents may be related in part to the fatigue caused by work schedules, long commuting distances, physical work, and psychological burden.

Underreporting of occupational blood and body fluid exposure in French university hospitals in 2017.

BACKGROUND: Occupational blood and body fluid exposures (OBBFEs) are one of the biological risks run by health professionals, especially in hospitals. OBJECTIVE: The objectives of this study were to assess the occurrence and reporting of occupational blood and body fluid exposures (OBBFEs) in university hospital medical staff and to investigate factors associated to declared OBBFE and factors associated to reported OBBFE. METHODS: A self-administered questionnaire has been e-mailed to all junior and senior medical staff in four university hospital centers in one administrative region of France in 2017. RESULTS: 292 of the 1,228 respondents declared at least one OBBFE. More than two-thirds (70.2%) were under-reporters and more than half (53.8%) non-reporters. Younger subjects, surgical specialties and other associated work accidents were risk factors for OBBFE. Considering the reporting procedure too complex was a risk factor for underreporting. CONCLUSIONS: Underreporting by hospital medical staff was a persistent phenomenon, with a high rate. The OBBFE reporting procedure needs rethinking.

A Bayesian two-step integrative procedure incorporating prior knowledge for the identification of miRNA-mRNAs involved in hepatocellular carcinoma.

Recent studies have confirmed the role of miRNA regulation of gene expression in oncogenesis for various cancers. In parallel, prior knowledge about relationships between miRNA and mRNA have been accumulated from biological experiments or statistical analyses. Improved identification of disease-associated miRNA-mRNA pairs may be achieved by incorporating prior knowledge into integrative genomic analyses. In this study we focus on 39 patients with hepatocellular carcinoma (HCC) and 25 patients with liver cirrhosis and use a flexible Bayesian two-step integrative method. We found 66 significant miRNA-mRNA pairs, several of which contain molecules that have previously been identified as potential biomarkers. These results demonstrate the utility of the proposed approach in providing a better understanding of relationships between different biological levels, thereby giving insights into the biological mechanisms underlying the diseases, while providing a better selection of biomarkers that may serve as diagnostic, prognostic, or therapeutic biomarker candidates.

COVID-19 clusters in a teaching hospital during the second wave of the SARS-CoV-2 pandemic in France: A descriptive study and lessons learned for waves to come.

A total of 92 coronavirus disease 2019 clusters involving 1,156 individuals (729 patients and 427 healthcare workers) occurred in Lyon University Hospital between September 1, 2020 and March 31, 2021, mostly on medical and geriatric wards. The number of clusters was closely correlated to the trend in coronavirus disease 2019 community incidence over time; in-hospital clusters did not persist when community incidence decreased. Recommended preventive measures were not fully applicable due to specific ward-associated determinants and patient characteristics.

Exposure of paediatric healthcare personnel to nitrous oxide in paediatric care units.

Nitrous oxide (N2O) was found responsible for genetic and reproductive toxicities, whereas it is widely used in paediatric care units where most healthcare providers are women of childbearing age. This motivated investigating occupational overexposure and overexposure factors in several paediatric hospital units. A cross-sectional study was carried out in seven healthcare units. On each of 34 healthcare providers, air samples were extracted (portable pumps and Tedlar® bags) and N2O quantified (gas chromatography, pulsed discharge ionization detection, and infrared spectrometry). The data allowed calculating mean instantaneous exposures. The mean instantaneous exposure was: i) four times higher in closed vs. open treatment rooms; ii) two times higher in case of use vs. non-use of N2O; iii) significantly higher in junior vs. senior healthcare providers (by 12%); and, iv) higher during presumably short vs. presumably long procedures (by 20%). Overexposures to N2O were mainly seen in the emergency unit and in day hospitals for thoracic/abdominal diseases and nephrology. Overexposures were frequent during short-duration procedures; among 88 N2O measurements, 77 (87.5%) exceeded the 200 ppm threshold over 15 minutes. The overexposures call for dedicated treatment rooms (with adequate equipment and ventilation), more efficient anaesthetic practices, appropriate training, and regular checks.

Glycated Hemoglobin as a First-line Screening Test for Cystic Fibrosis‒Related Diabetes and Impaired Glucose Tolerance in Children With Cystic Fibrosis: A Validation Study.

OBJECTIVES: Our aims in this study were to document the screening rate for cystic fibrosis‒related diabetes (CFRD) in children followed at a cystic fibrosis (CF) clinic in Canada and to evaluate the accuracy of various glycated hemoglobin (A1C) cutoffs to screen for CFRD and impaired glucose tolerance (IGT) in a pediatric CF population. METHODS: The CFRD screening rate was calculated over a follow-up period of up to 8 years among children who attended the CF clinic between 1993 and 2018. Test performance of A1C at various thresholds ranging from 5.5% to 6.2% was compared with the oral glucose tolerance test (OGTT) as the reference method. Children with CF aged ≥10 years with an OGTT performed within 120 days of A1C measurement were included in the analysis. RESULTS: The overall CFRD screening rate was 53.0%. A total of 256 children were included for the A1C performance analysis, of whom 8.6% had an OGTT-confirmed CFRD diagnosis. An A1C threshold of 5.8% demonstrated an optimal balance between sensitivity (90.9%) and specificity (60.7%) for CFRD screening, leading to a potential reduction of 56.3% of the annual required OGTTs. A1C demonstrated poor accuracy for identifying children with IGT. CONCLUSIONS: An A1C threshold ≥5.8% allows for identification of children requiring further CFRD investigations, which may reduce the clinical burden of children with CF without compromising the ability of early CFRD diagnosis.

In silico QTL mapping in an oil palm breeding program reveals a quantitative and complex genetic resistance to Ganoderma boninense.

Basal stem rot caused by Ganoderma boninense is the major threat to oil palm cultivation in Southeast Asia, which accounts for 80% of palm oil production worldwide, and this disease is increasing in Africa. The use of resistant planting material as part of an integrated pest management of this disease is one sustainable solution. However, breeding for Ganoderma resistance requires long-term and costly research, which could greatly benefit from marker-assisted selection (MAS). In this study, we evaluated the effectiveness of an in silico genetic mapping approach that took advantage of extensive data recorded in an ongoing breeding program. A pedigree-based QTL mapping approach applied to more than 10 years' worth of data collected during pre-nursery tests revealed the quantitative nature of Ganoderma resistance and identified underlying loci segregating in genetic diversity that is directly relevant for the breeding program supporting the study. To assess the consistency of QTL effects between pre-nursery and field environments, information was collected on the disease status of the genitors planted in genealogical gardens and modeled with pre-nursery-based QTL genotypes. In the field, individuals were less likely to be infected with Ganoderma when they carried more favorable alleles at the pre-nursery QTL. Our results pave the way for a MAS of Ganoderma resistant and high yielding planting material, and the provided proof-of-concept of this efficient and cost-effective approach could motivate similar studies based on diverse breeding programs. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-021-01246-9.

Abnormal glucose tolerance in a pediatric cystic fibrosis cohort: Trends in clinical outcomes and associated factors in the preceding years.

BACKGROUND AND AIMS: Deterioration of anthropometric and lung function parameters was shown to precede the onset of cystic fibrosis-related diabetes (CFRD) in adults. In children, studies have been conducted in small cohorts with relatively short observation period. Study objectives were to document the longitudinal trends of anthropometric, pulmonary, nutritional and metabolic parameters from cystic fibrosis (CF) diagnosis to the ascertainment of abnormal glucose tolerance and identify parameters associated with the incidence of such abnormalities in a pediatric CF cohort. METHODS AND RESULTS: Retrospective cohort study of 281 children with CF. Longitudinal trends of anthropometric, lung function, nutritional and metabolic data were generated from CF diagnosis to the ascertainment of abnormal glucose tolerance defined as the presence of either impaired glucose tolerance (IGT), unconfirmed CFRD or CFRD. Cox models and Kaplan-Meier curves were used to identify factors associated with developing abnormal glucose tolerance. Forty-five percent of cohort had normal glucose tolerance (NGT), 27% IGT, 10% unconfirmed CFRD and 18% CFRD. Children who developed CFRD displayed lower height z-scores from a very early age. Conversely, HbA1c levels began to rise closer to CFRD ascertainment. Height z-scores (HR: 0.45; CI 95% [0.29-0.69]) and HbA1c (HR: 2.43; CI 95% [1.86-3.18]) in years preceding ascertainment were associated with the risk of developing CFRD. CONCLUSION: Children who developed CFRD display distinctive trends for height z-scores from a very early age, whereas HbA1c appears as a marker of established glucose metabolism derangements.

Incidence of Asymptomatic and Symptomatic Influenza Among Healthcare Workers: A Multicenter Prospective Cohort Study.

BACKGROUND: Influenza is an important cause of viral hospital-acquired infection involving patients, healthcare workers (HCW), and visitors. The frequency of asymptomatic influenza among HCW with possible subsequent transmission is poorly described. The objective is to determine the cumulative incidence of asymptomatic, paucisymptomatic, and symptomatic influenza among HCW. METHOD: A multicenter prospective cohort study was done in 5 French university hospitals, including 289 HCW during the 2016-2017 influenza season. HCW had 3 physical examinations (time [T] 0, before epidemic onset; T.1, before epidemic peak; T.2, T.3, after epidemic peak). A blood sample was taken each time for influenza serology and a nasal swab was collected at T1 and T2 for influenza detection by polymerase chain reaction (PCR). Positive influenza was defined as either a positive influenza PCR, and/or virus-specific seroconversion against influenza A, the only circulating virus, with no vaccination record during follow-up. Symptoms were self-reported daily between T1 and T2. Cumulative incidence of influenza was stratified by clinical presentation per 100 HCW. RESULTS: Of the 289 HCW included, 278 (96%) completed the entire follow-up. Overall, 62 HCW had evidence of influenza of whom 46.8% were asymptomatic, 41.9% were paucisymptomatic, and 11.3% were symptomatic. Cumulative influenza incidence was 22.3% (95% confidence interval [CI]: 17.4%-27.2%). Cumulative incidence of asymptomatic influenza was 5.8% (95% CI: 3.3%-9.2%), 13.7% (95% CI: 9.9%-18.2%) for paucisymptomatic influenza, and 2.9% (95% CI: 1.3%-5.5%) for symptomatic influenza. CONCLUSIONS: Asymptomatic and paucisymptomatic influenza were frequent among HCW, representing 47% and 42% of the influenza burden, respectively. These findings highlight the importance of systematic implementation of infection control measures among HCW regardless of respiratory symptoms from preventing nosocomial transmission of influenza. CLINICAL TRIALS REGISTRATION: NCT02868658.

Commuting Accidents among Non-Physician Staff of a Large University Hospital Center from 2012 to 2016: A Case-Control Study.

Road risks (commuting and on-duty accidents) have been responsible for 44% of work-related fatalities compensated by the French system of Social Security in 2012 and still represented 37% in 2018. Our objective was to assess risk factors for commuting accidents among the non-physician staff in a French university hospital. We conducted a case-control study of commuting accidents from 2012 to 2016. Cases were identified and controls were randomly selected from the hospital's personnel file with matches by year of the accident, gender and age. Risk factors were assessed using conditional logistic regression analysis. An increased risk was observed for 2 × 8 hour shifts, crude OR = 1.40 (95% CI = 1.05-1.86) compared to daytime schedules, but not confirmed in the multiple model. Being a duty officer and not working the day before the accident were associated with increased risk of accidents with adjusted OR = 1.9 (95% CI = 1.1; 3.3) and OR = 1.5, (95% CI = 1.1; 2.1), respectively. The risk increased as the distance between home and work increased, such as adjusted OR = 2.2 (95% CI = 1.4; 3.4) for a distance of >3.6 to 9 km, OR = 2.6, (95% CI = 1.7; 4.0) for a distance of >9 km to 19 km, and OR = 4.2, (95% CI = 2.8; 6.2) for >19 km vs. <3.6 km. The distance between home and work, not working the day before the accident, and certain categories of personnel were related to commuting accidents.

[Multiparametric biochemical analysis revealing an increase of homocysteinemia and NT-proBNP in hypertensive patients living in Bamako (Mali)]. / Analyse biochimique multi-paramétrique révélant une augmentation de l'homocystéinémie et du NT-ProBNP chez les patients hypertendus à Bamako (Mali).

INTRODUCTION: Arterial hypertension is a major public health problem in sub-Saharan Africa due to its high frequency and to the cardiovascular risk that it entails. The purpose of this study was to assess the prevalence of clinical and biological risk factors of hypertension in Bamako (Mali). METHODS: We conducted a case-control study, stratified in function of the sex, of 72 participants including 36 patients with hypertension and 36 controls. Twenty-two plasma biochemical parameters have been measured and analyzed using univariate and multivariate tests. RESULTS: Hyperhomocysteinemia was found in 55.6% of women (p = 0.03) and 100% of men (p = 0.007) with hypertension. High NT-proBNP was also found in 16.7% of women (VIP > 1 in multivariate model) and of men with hypertension (p = 0.00006). A good multivariate predictive model (OPLS-DA) was only obtained in women with high blood pressure, with Q2cum = 0.73, attesting severe sexual dimorphism associated with arterial hypertension. This model involved eight parameters whose plasma concentration was modified (homocysteine, NT-proBNP, potassium, urea, blood glucose, sodium, chlorine and total proteins). CONCLUSION: We registered a significant association between hyperhomocysteinemia and arterial hypertension. Therefore, the assay of homocysteine associated with good management would decrease the risk of cardiovascular diseases while improving the quality of life of hypertensive patients.

Early care of N-acetyl glutamate synthase (NAGS) deficiency in three infants from an inbred family.

N-acetyl glutamate synthase (NAGS) deficiency is the rarest urea cycle defect presenting as neonatal onset life-threatening hyperammonemia. We report here a family history of severe NAGS deficiency: after the index-case with severe hyperammonemia, one patient benefited from antenatal diagnosis, and from primary care at birth, another one was diagnosed at 2-days and immediately treated with carbaglumic-acid. Finally, we report excellent tolerance to long-term carbaglumic-acid treatment, with no side effects, and healthy neurological and psychomotor development.

Environmental and trophic determinism of fruit abscission and outlook with climate change in tropical regions.

Fruit abscission facilitates the optimal conditions and timing of seed dispersal. Environmental regulation of tropical fruit abscission has received little attention, even though climate change may have its strongest impacts in tropical regions. In this study, oil palm fruit abscission was monitored during multiple years in the Benin Republic to take advantage of the climatic seasonality and the continuous fruit production by this species. An innovative multivariable statistical method was used to identify the best predictors of fruit abscission among a set of climate and ecophysiological variables, and the stage of inflorescence and fruit bunch development when the variables are perceived. The effects of climate scenarios on fruit abscission were then predicted based on the calibrated model. We found complex regulation takes place at specific stages of inflorescence and bunch development, even long before the fruit abscission zone is competent to execute abscission. Among the predictors selected, temperature variations during inflorescence and fruit bunch development are major determinants of the fruit abscission process. Furthermore, the timing of ripe fruit drop is determined by temperature in combination with the trophic status. Finally, climate simulations revealed that the abscission process is robust and is more affected by seasonal variations than by extreme scenarios. Our investigations highlighted the central function of the abscission zone as the sensor of environmental signals during reproductive development. Coupling ecophysiological and statistical modeling was an efficient approach to disentangle this complex environmental regulation.

Hatching Induction of Cyst Nematodes in Bare Soils Drenched With Root Exudates Under Controlled Conditions.

Cyst nematodes account for substantial annual yield losses in crop production worldwide. Concerns over environmental and health issues due to the use of chemical nematicides mean alternative sustainable and integrated solutions are urgently required. Hatch induction of encysted eggs in the absence of host plants, i.e., 'suicide-hatching,' could be a sustainable alternative in reducing population densities of cyst nematodes in infested soils. Here we examined in situ hatching of encysted eggs of Globodera pallida, Heterodera carotae, and Heterodera schachtii at varying soil depths, following exogenous applications of host root exudates in repeated glasshouse experiments. Cysts were retrieved 30 or 43 days post-incubation depending on the nematode species and assessed for hatching rates relative to the initial number of viable eggs per cyst. Hatching of the potato cyst nematode G. pallida depended on both soil moisture and effective exposure to root exudates, and to a lesser extent on exudate concentration. The carrot cyst nematode H. carotae had over 75% hatched induced by root exudate irrespective of the concentration, with better hatch induction at 20 cm as compared with 10 cm soil depth. Hatching of the beet cyst nematode H. schachtii largely depended on the soil moisture level at constant temperature, rather than the type or concentration of root exudates applied. As a conclusion, exogenously applied host root exudates may play a major role in inducing in situ hatch of encysted eggs of potato and carrot cyst nematodes in the absence of host plant under favorable soil temperature/moisture conditions. To improve such strategy, the characterization of chemical profiles of the root exudate composition and field validation are currently ongoing.