Clinical impact and cost-consequence analysis of ePlex® blood culture identification panels for the rapid diagnosis of bloodstream infections: a single-center randomized controlled trial.

To assess clinical impact and perform cost-consequence analysis of the broadest multiplex PCR panels available for the rapid diagnosis of bloodstream infections (BSI). Single-center, randomized controlled trial conducted from June 2019 to February 2021 at a French University hospital with an institutional antimicrobial stewardship program. Primary endpoint was the percentage of patients with optimized antimicrobial treatment 12 h after transmission of positivity and Gram stain results from the first positive BC. This percentage was significantly higher in the multiplex PCR (mPCR) group (90/105 = 85.7% %, CI95% [77.5 ; 91.8] vs. 68/107 = 63.6%, CI95% [53.7 ; 72.6]; p < 10- 3) at interim analysis, resulting in the early termination of the study after the inclusion of 309 patients. For patients not optimized at baseline, the median time to obtain an optimized therapy was much shorter in the mPCR group than in the control group (6.9 h, IQR [2.9; 17.8] vs. 26.4 h, IQR [3.4; 47.5]; p = 0.001). Early optimization of antibiotic therapy resulted in a non-statistically significant decrease in mortality from 12.4 to 8.8% (p = 0.306), with a trend towards a shorter median length of stay (18 vs. 20 days; p = 0.064) and a non-significant reduction in the average cost per patient of €3,065 (p = 0.15). mPCR identified all the bacteria present in 88% of the samples. Despite its higher laboratory cost, the use of multiplex PCR for BSI diagnosis leads to early-optimised therapy, seems cost-effective and could reduce mortality and length of stay. Their impact could probably be improved if implemented 24/7.

[Constrictive pericarditis and disseminated nocardiosis]. / Péricardite constrictive et la nocardiose disséminée.

Human nocardiosis usually involves the respiratory tract or the skin but may disseminate to virtually any organ, it occurs in immunocompromised hosts as well as individuals with no apparent predisposition. Involvement of the pericardium is uncommon, having been reported infrequently in the past, but mandates a special management. This report describes the first case in Europe of a patient with chronic constrictive pericarditis from nocardia brasiliens, successfully treated with pericardiectomy and appropriate antibiotic therapy.

[Systematic preoperative SARS-CoV-2 screening by chest CT before urological surgery]. / Dépistage préopératoire systématique du SARS-CoV-2 par scanner thoracique avant chirurgie urologique.

Due to COVID-19 outbreak, the Belgian Association of Urology recommended limiting non-emergency surgical care. The aim of this study was to analyze if a preoperative screening for COVID-19 was key to select optimal operative candidates and its impact on surgical outcomes. MATERIAL AND METHODS: we present a retrospective analysis of all consecutive patients who underwent oncological high-risk and emergency urological surgeries in a Belgium tertiary center from March 30 to April 30, 2020. The screening protocol was based on clinical assessment and chest-CT to identify COVID-19-positive patients. RESULTS: a total of 32 patients underwent elective oncologic (n = 17; 53 %) and emergency (n = 15; 47 %) operations. Screening by chest-CT revealed three cases of COVID-19 (9 %) having led to postpone two interventions. The third positive COVID-19 patient died of respiratory complications after bladder perforation urgent procedure. Two patients developed compatible post-operatively symptoms with one positive chest-CT but no positive RT-PCR and successful recovery. Adapted safety measures were followed to mitigate in-hospital transmission. CONCLUSION: this report suggests feasibility and efficacy of systematic, preoperative screening for COVID-19 by chest computed tomography only. This strategy could allow to perform the majority of scheduled high-risk oncologic interventions safely for both the patients and the surgical staff.

Avec l'épidémie de COVID-19, l'Association Belge d'Urologie a recommandé de limiter les soins chirurgicaux non urgents. Le but de cette étude était d'analyser si un dépistage préopératoire de la COVID-19 était essentiel pour sélectionner les candidats opératoires optimaux et son impact sur les résultats chirurgicaux. Matériel et méthodes : nous présentons une analyse rétrospective des patients qui ont subi des chirurgies urologiques oncologiques à haut risque et d'urgence dans un centre tertiaire belge du 30 mars au 30 avril 2020. Le protocole de dépistage était une évaluation clinique plus CT thoracique pour identifier les patients COVID-19 positifs. Résultats : 32 patients ont bénéficié d'opérations oncologiques (n = 17; 53 %) et urgentes (n = 15; 47 %). Le dépistage par CT thoracique a révélé trois cas de COVID-19 (9 %) conduisant à deux reports de la chirurgie. Le troisième est décédé de complications respiratoires après procédure urgente pour perforation vésicale. Deux patients ont développé des symptômes postopératoires compatibles avec la COVID-19. Un CT thoracique était suspect, les RT-PCR négatives et les récupérations favorables. Des mesures de sécurité ont été instaurées pour atténuer la transmission intra-hospitalière. Conclusion : nous rapportons la faisabilité et l'efficacité du dépistage systématique préopératoire de la COVID-19 uniquement par CT thoracique. Cette stratégie pourrait permettre d'effectuer la majorité des interventions oncologiques à haut risque en toute sécurité pour les patients et le personnel chirurgical.

When residents work less, they feel better: Lessons learned from an unprecedent context of lockdown.

INTRODUCTION: With the COVID-19 outbreak activities of urology departments have been limited to non-deferrable procedures impacting the daily program of residents in urology. We assessed the psychological impact of the lockdown on Belgian residents in urology and their resounding on the quality of the training. MATERIAL AND METHODS: A self-administered anonymous questionnaire assessing the risk of burnout in a pandemic situation and its impact on the quality of the training was e-mailed to the members of the European Society of Residents in Urology of Belgium (ESRU-B). We used the Copenhagen Burnout Inventory score which assesses the different dimensions of burnout (personal (CBIP), professional (CBIPro), relational (CBIR)). Several questions evaluating impact on residents' health and apprehension of the future were included. The survey lasted for 5 days. Comparison of parameters before and during the coronavirus crisis was made using paired samples t-test or Chi2 test were. RESULTS: Fifty percent (62/126) of the ESRU-B members replied to the questionnaire. If 93% of the responders reported a negative impact on the quality of their practical training (CI95=[0.07-1.10]; P=0.83), 56% and 61.7% reported a positive impact of the crisis on their life and on their theoretical training respectively. Burnout risk scores were significantly reduced (P<0.001) for each dimension 7.26 to 3.40 (CBIP), 9.02 to 4.35 (CBIPro) and 4.42 to 3.03 (CBIR) respectively. CONCLUSION: Despite a negative impact on the daily work quality, the decrease in activity induced by the lockdown did not have a negative psychological impact on Belgian residents in urology but stress the opportunity to review the current training system to be better balanced between practice and theoretical formation.

A drop does not fall in a straight line: a rationale for the width of stalagmites.

Drops loaded in calcium ions detach from stalactites and impact the underlying stalagmites, thereby allowing these latter to grow through calcite precipitation. Nevertheless, little is known about the influence of the drop free fall and splash dynamics on stalagmite shape and width. Through high-speed imaging of impacting drops on stalagmites from several caves, we observed that the impact point position of the drops is scattered, sometimes over several centimetres. We show that this dispersal has no external cause and must, therefore, be self-induced. Using a Langevin-like equation, we then propose a prediction of the impact point dispersal as a function of the falling height travelled by the drops. We finally show that measured stalagmite widths are correlated to the dispersal in the impact point position of the drop.

High airborne level of Aspergillus fumigatus and presence of azole-resistant TR34/L98H isolates in the home of a cystic fibrosis patient harbouring chronic colonisation with azole-resistant H285Y A. fumigatus.

Azole-resistant Aspergillus fumigatus (ARAF) has been reported in the domestic environment of patients at risk for aspergillosis. Here, we assessed the mother's and father's homes of an 18-year-old cystic fibrosis patient harbouring chronic colonisation with H285Y CYP51A azole-resistant isolate, in order to explore the link between environmental exposure and ARAF infection. In one dwelling, a very high overall contamination level was found (710-7.240 CFU/m3), with a predominance of A. fumigatus (640-6.490 CFU/m3), and ARAF showing the TR34/L98H mutation was isolated. Mycological follow-up of the patient showed the persistence of H285Y isolates, but no acquisition of TR34/L98H isolates was observed. This could be due to the low proportion of TR34/L98H isolates (<3%), or the establishment of preventative measures and dwelling remediation taken after the environmental investigation. Our data underlines the value of an environmental assessment to establish preventative measures and limit the risk of A. fumigatus exposure and ARAF acquisition.

Food allergy phenotypes: The key to personalized therapy.

Food allergies (FAs) are of increasing public health concern and are characterized by a large spectrum of diseases. Their diversity is well known for immunologic pathways (IgE, non-IgE-mediated FAs) and natural history. Many other factors and patient characteristics are involved including type of food, exposure route, allergic comorbidities, gender, racial and ethnic backgrounds, cofactors and health conditions. Food allergen components and sensitization profiles are also involved in FA phenotypes. A new approach to chronic disorders based on the identification of phenotypes through extensive knowledge of all the complex components is also applicable to FAs and could lead towards integrative care management. Diagnostic biomarkers for FAs are emerging which also contribute to better care modalities. The aim of this article was to highlight current knowledge regarding the phenotypic diversity of FA. This review will focus on IgE-mediated FAs and how identifying phenotypes may help to better understand the pathophysiological complexity, improve diagnosis and lead to personalized treatment strategies.

Constitutional mismatch repair deficiency syndrome: clinical description in a French cohort.

BACKGROUND: Constitutional mismatch repair deficiency (CMMRD) syndrome is a childhood cancer predisposition syndrome involving biallelic germline mutations of MMR genes, poorly recognised by clinicians so far. METHODS: Retrospective review of all 31 patients with CMMRD diagnosed in French genetics laboratories in order to describe the characteristics, treatment and outcome of the malignancies and biological diagnostic data. RESULTS: 67 tumours were diagnosed in 31 patients, 25 (37%) Lynch syndrome-associated malignancies, 22 (33%) brain tumours, 17 (25%) haematological malignancies and 3 (5%) sarcomas. The median age of onset of the first tumour was 6.9 years (1.2-33.5). Overall, 22 patients died, 9 (41%) due to the primary tumour. Median survival after the diagnosis of the primary tumour was 27 months (0.26-213.2). Failure rate seemed to be higher than expected especially for T-cell non-Hodgkin's lymphoma (progression/relapse in 6/12 patients). A familial history of Lynch syndrome was identified in 6/23 families, and consanguinity in 9/23 families. PMS2 mutations (n=18) were more frequent than other mutations (MSH6 (n=6), MLH1 (n=4) and MSH2 (n=3)). CONCLUSIONS: In conclusion, this unselected series of patients confirms the extreme severity of this syndrome with a high mortality rate mostly related to multiple childhood cancers, and highlights the need for its early detection in order to adapt treatment and surveillance.

[Indications for prophylactic hysterectomy]. / Hystérectomie prophylactique : quelle indication ?

Endometrial cancer is the most common gynecologic cancer in France with an incidence in France in 2010, of 6560 new cases and 1900 deaths secondary to endometrial cancer. The main risk factors are age, hyperoestrogenic factors and hereditary syndroms. Prophylactic hysterectomy could prevent endometrial cancer in case of risk factors such as genetic syndroms. Actually, only Lynch syndrome is a validate indication and should be discussed in patients older than 40-45 years. Prophylactic hysterectomy does not seem a reasonable option to patients carrying BRCA 1 or 2 mutation.

Evaluation of a new panel of six mononucleotide repeat markers for the detection of DNA mismatch repair-deficient tumours.

BACKGROUND: Microsatellite instability (MSI) is a molecular phenotype due to defective DNA mismatch repair (MMR) system. It is used to predict outcome of colorectal tumours and to screen tumours for Lynch syndrome (LS). A pentaplex panel composed of five mononucleotide markers has been largely recommended for determination of the MSI status. However, its sensitivity may be taken in default in occasional situations. The aim of the study was to optimise this panel for the detection of MSI. METHODS: We developed an assay allowing co-amplification of six mononucleotide repeat markers (BAT25, BAT26, BAT40, NR21, NR22, NR27) and one polymorphic dinucleotide marker (D3S1260) in a single reaction. Performances of the new panel were evaluated on a cohort of patients suspected of LS. RESULTS: We demonstrate that our assay is technically as easy to use as the pentaplex assay. The hexaplex panel shows similar performances for the identification of colorectal and non-MSH6-deficient tumours. On the other hand, the hexaplex panel has higher sensitivity for the identification of MSH6-deficient tumours (94.7% vs 84.2%) and MMR-deficient tumours other than colorectal cancer (92.9% vs 85.7%). CONCLUSION: The hexaplex panel could thus be an attractive alternative to the pentaplex panel for the identification of patients with LS.

[Family impact of FXTAS diagnosis: genetic counseling for at-risk relatives]. / Conséquences familiales du diagnostic de FXTAS: le conseil génétique aux apparentés à risque.

INTRODUCTION: Fragile X associated Tremor/Ataxia Syndrome (FXTAS) is related to premutation expansions of the FMR1 gene, including 55 to 200 CGG repeats, whereas full expansions, over 200 repeats, cause Fragile X mental retardation. FXTAS is observed in about one-third of men with premutation, generally in their 1950s and over, and less commonly in women. It is characterized by action tremor, ataxia, cognitive, parkinsonism, behavioral difficulties, autonomic dysfunction and peripheral neuropathy. Brain magnetic resonance imaging (MRI) often shows symmetric increases in T2-weighted signal intensity in the middle cerebellar peduncles. The diagnosis of FXTAS in a patient raises important family issues. CASE REPORT: A 47-year-old male patient complained of an abnormal hearing sensation and dizziness for several months. Neurological examination was normal. Brain MRI showed the common signal intensity in middle cerebellar peduncles and bilateral punctual increases in T2-weighted signal intensity in the cerebral white matter. Genetic analysis showed 87CGG repeats, in favor of a possible FXTAS. At the time of diagnosis, fragile X syndrome was subsequently suspected and confirmed in his 10-month-old grandson. DISCUSSION: Due to X-linked inheritance and to the specific related mutational mechanism, the diagnosis of FXTAS in a patient raises major issues for relatives over several generations, including males and females, who should be considered as obligate or potential premutation carriers. Premutated females are not only at risk of transmitting a full mutation to their children but also of developing Fragile X related premature ovarian failure (FXPOI) that may influence their choices in family planning. CONCLUSION: The diagnosis of FXATS in a patient should induce delivery of extensive information and genetic counseling for potential carrier relatives.