Multidisciplinary analysis of cancer-related fatigue at the time of diagnosis: preliminary results of the BIOCARE FActory cohort.

PURPOSE: Cancer-related fatigue (CRF) is a common side effect of cancer and cancer treatment that significantly impairs the quality of life and can persist for years after treatment completion. Although fatigue is often associated with cancer treatment, it is also a result of the disease itself, even before intervention. CRF at the time of diagnosis may affect treatment timing or completion and is a consistent predictor of post-treatment fatigue at any time. The mechanisms underlying CRF are multidimensional and not well understood, particularly at the time of diagnosis. METHODS: Sixty-five breast cancer patients at the time of diagnosis were included. The participants completed self-assessment questionnaires about CRF, sleep disturbances, and emotional symptoms and wore an accelerometer to assess levels of spontaneous physical activity and sleep quality. During the experimental session, the participants underwent cognitive, neuromuscular, and exercise metabolism evaluations. RESULTS: Using augmented backward elimination regression, this study found that emotional symptoms and perceived sleep disturbances were the strongest predictors of CRF (adjusted r2 = 0.51). Neuromuscular fatigability and sleep disturbance were also associated with physical dimensions, whereas cognitive performance was associated with cognitive dimensions. CONCLUSION: At the time of diagnosis, emotional and cognitive dimensions are over-represented compared to the general population, and specific subdimensions have specific predictors that support the idea of distinct mechanisms. Evaluating CRF subdimensions and their potential mechanisms at the time of diagnosis would be particularly relevant for identifying high-risk patients and offering them appropriate interventions. TRIAL REGISTRATION: This study was registered at ClinicalTrials.gov (NCT04391543) in May, 2020.

Building a biopsychosocial model of cancer-related fatigue: the BIOCARE FActory cohort study protocol.

BACKGROUND: Cancer-related fatigue (CRF) is the most common side effect of cancer and cancer treatment. CRF prevalence is up to 50% in breast cancer patients and can continue several years after cancer remission. This persistent subjective sense of exhaustion is multifactorial. Numerous parameters have been evidenced to be related to CRF across biological, physical, psychological, social and/or behavioral dimensions. Although CRF has been studied for many years, the majority of previous studies focused on only one dimension, i.e., physical function. Moreover, few studies investigated CRF longitudinally with repeated measures. These are the two main obstacles that limit the understanding of CRF mechanisms. The purpose of this study is to create a biopsychosocial model of CRF with simultaneous and longitudinal anthropometric, clinical, biological, physical, psychological and sociological parameters. METHODS: BIOCARE FActory is a multicentric prospective study that will consist of an 18-month follow-up of 200 women diagnosed with breast cancer. Four visits will be scheduled at diagnosis, after treatments, and 12 and 18 months after diagnosis. The same procedure will be followed for each visit. Each session will be composed of anthropometric data collection, a semi-structured interview, cognitive tests, postural control tests, neuromuscular fatigability tests and a cardiorespiratory fitness test. Clinical and biological data will be collected during medical follow-ups. Participants will also complete questionnaires to assess psychological aspects and quality of life and wear an actigraphy device. Using a structural equation modeling analysis (SEM), collected data will build a biopsychosocial model of CRF, including the physiological, biological, psychological, behavioral and social dimensions of CRF. DISCUSSION: This study aims to highlight the dynamics of CRF and its correlates from diagnosis to post treatment. SEM analysis could examine some relations between potential mechanisms and CRF. Thus, the biopsychosocial model will contribute to a better understanding of CRF and its underlying mechanisms from diagnosis to the aftermaths of cancer and its treatments. TRIAL REGISTRATION: This study is registered at ClinicalTrials.gov ( NCT04391543 ), May 2020.

Impact of music therapy before first-trimester instrumental termination of pregnancy: a randomised controlled trial.

OBJECTIVES: To evaluate the impact of preoperative Music Therapy (MT) on pain in first-trimester termination of pregnancy (TOP) under local anaesthesia. DESIGN: Randomised controlled trial comparing women undergoing a first-trimester TOP under local anaesthesia with or without a preoperative MT session. SETTING: University Hospital of Angers from November 2016 to August 2017. POPULATION: Women who underwent first-trimester TOP under local anaesthesia. METHODS: Women allocated to the MT group underwent a preoperative 20-minute session of MT. MAIN OUTCOME MEASURES: Pain was assessed using a visual analogue scale (VAS) just before the procedure, during the procedure, at the end of the procedure and upon returning to the ward. RESULTS: A total of 159 women were randomised (80 in the MT group, and 79 in the control group). Two women were excluded from the control group and six from the MT group. Therefore, 77 women were analysed in the control group and 74 in the MT group. The intensity of pain was similar in the two groups just before the procedure (VAS 4.0 ± 2.9 versus 3.6 ± 2.5; P = 0.78), during the procedure (VAS 5.3 ± 2.5 versus 4.9 ± 2.9; P = 0.78), at the end of the procedure (VAS 2.7 ± 2.4 versus 2.6 ± 2.4; P = 0.43) and upon returning to the ward (VAS 1.8 ± 2.0 versus 1.5 ± 2.0; P = 0.84). The difference in pain between entering the department and returning to the room after the procedure was similar between the MT and control groups (difference in VAS 0.3 ± 2.5 versus 0.3 ± 2.4; P = 0.92). CONCLUSION: An MT session before a TOP under local anaesthesia procedure resulted in no improvement in patient perception of pain during a first-trimester TOP. TWEETABLE ABSTRACT: Music therapy before first-trimester termination of pregnancy under local anaesthesia did not improve the perception of pain.

Validation of EN ISO method 15216 - Part 1 - Quantification of hepatitis A virus and norovirus in food matrices.

Hepatitis A virus (HAV) and norovirus are important agents of food-borne human viral illness, with common vehicles including bivalve molluscan shellfish, soft fruit and various vegetables. Outbreaks of viral illness due to contamination of the surfaces of foods, or food preparation surfaces by for example infected food handlers are also common. Virus analysis of food matrices can contribute towards risk management for these hazards and a two-part technical specification for determination of Hepatitis A virus and norovirus in food matrices (ISO/TS 15216:2013) was published jointly by the European Committee for Standardisation and the International Organization for Standardization in 2013. As part of the European Mandate No. M381 to validate 15 standards in the field of food microbiology, an international validation study involving 18 laboratories from 11 countries in Europe was conducted between 2012 and 2014. This study aimed to generate method characteristics including limit of detection, limit of quantification, repeatability and reproducibility for ISO 15216 - Part 1, the method for quantification, in seven food matrices. The organization and results of this study, including observations that led to improvements in the standard method are presented here. After its conclusion, the method characteristics generated were added to the revised international standard, ISO 15216-1:2017, published in March 2017.

A pan-European ring trial to validate an International Standard for detection of Vibrio cholerae, Vibrio parahaemolyticus and Vibrio vulnificus in seafoods.

Globally, vibrios represent an important and well-established group of bacterial foodborne pathogens. The European Commission (EC) mandated the Comite de European Normalisation (CEN) to undertake work to provide validation data for 15 methods in microbiology to support EC legislation. As part of this mandated work programme, merging of ISO/TS 21872-1:2007, which specifies a horizontal method for the detection of V. parahaemolyticus and V. cholerae, and ISO/TS 21872-2:2007, a similar horizontal method for the detection of potentially pathogenic vibrios other than V. cholerae and V. parahaemolyticus was proposed. Both parts of ISO/TS 21872 utilized classical culture-based isolation techniques coupled with biochemical confirmation steps. The work also considered simplification of the biochemical confirmation steps. In addition, because of advances in molecular based methods for identification of human pathogenic Vibrio spp. classical and real-time PCR options were also included within the scope of the validation. These considerations formed the basis of a multi-laboratory validation study with the aim of improving the precision of this ISO technical specification and providing a single ISO standard method to enable detection of these important foodborne Vibrio spp.. To achieve this aim, an international validation study involving 13 laboratories from 9 countries in Europe was conducted in 2013. The results of this validation have enabled integration of the two existing technical specifications targeting the detection of the major foodborne Vibrio spp., simplification of the suite of recommended biochemical identification tests and the introduction of molecular procedures that provide both species level identification and discrimination of putatively pathogenic strains of V. parahaemolyticus by the determination of the presence of theromostable direct and direct related haemolysins. The method performance characteristics generated in this have been included in revised international standard, ISO 21872:2017, published in July 2017.

Listeria monocytogenes-associated respiratory infections: a study of 38 consecutive cases.

OBJECTIVES: Listeria monocytogenes (Lm) is a foodborne human pathogen responsible for severe infections, including septicaemia, neurolisteriosis, and maternal-foetal and focal infections. Little is known about Lm-associated respiratory tract or lung infections. METHODS: We conducted a retrospective study of culture-proven cases of Lm pleural infections and pneumonia reported to the French National Reference Centre for Listeria from January 1993 to August 2016. RESULTS: Thirty-eight consecutive patients with pleural infection (n = 32), pneumonia (n = 5), or both (n = 1) were studied; 71% of these were men. Median age was 72 (range 29-90). Two patients presented with concomitant neurolisteriosis. All patients but one reported at least one immunosuppressive condition (97%), with a median number of 2 (range 0-5), including 29% (8/28) with current exposure to immunosuppressive therapy and 50% (17/34) with ongoing neoplasia; 75% (21/28) reported previous pleural or pulmonary disease. Antibiotic therapy mostly consisted in amoxicillin (72%) associated with aminoglycoside in 32%. Chest-tube drainage was performed in 7/19 patients with empyema (37%); 25% of the patients (7/30) required intensive care management. In-hospital mortality reached 35% and occurred after a median time interval of 4 days (range 1-33 days). Three patients had recurrence of empyema (time interval of 1 week to 4 months after treatment completion). Altogether, only 13/31 patients (42%) diagnosed with Lm respiratory infection experienced an uneventful outcome at 2-year follow-up. CONCLUSION: Lm is a rare but severe cause of pneumonia and pleural infection in older immunocompromised patients, requiring prompt diagnosis and adequate management and follow-up.

[Membranous microparticles and respiratory disease]. / Microparticules membranaires et maladies respiratoires.

Microparticles (MP) are plasmic membrane fragments released from cells after physiological stimulation or stress conditions like inflammation or infection. Their production is correlated to the rate of cell apoptosis. All types of cells can produce MP but they are produced mainly by platelets, endothelial cells, and leukocytes. They carry many bio-active molecules on their surface, specific to the parental cell, giving them the ability to be biomarkers and bio-effectors. MP are present in circulating blood, tissues and many biological fluids. Circulating MP levels can change during the course of many diseases. They have been the subject of many studies in the fields of cardiovascular disease and oncology. In the lungs, they are present in circulating blood and in the airways. They seem to have a role in pulmonary homeostasis in physiological situations and also in the expression of several disease processes. In this review of the literature, we were interested in the quantitative and qualitative variations in MP and their impact in airway diseases like chronic obstructive pulmonary disease (COPD) and asthma, pulmonary fibrosis and pulmonary hypertension.

Contamination by Salmonella spp., Campylobacter spp. and Listeria spp. of most popular chicken- and pork-sausages sold in Reunion Island.

One of the most popular meat products of the local "cuisine" is sausage composed with 100% chicken or 100% pork. In this study, we aimed to determine the presence of Salmonella spp., Campylobacter spp. and Listeria spp. in chicken- and pork-sausages, quantify Salmonella spp. population and identify the factors that could be associated with contamination in the outlets. Two hundred and three batches of pork and chicken sausages were randomly collected from 67 local outlets (supermarkets, groceries and butcher shops). Salmonella spp. was detected in 11.8% (95% confidence interval (CI): [10.0; 13.5]) of samples, Campylobacter spp. in 1.5% [0.7; 4.2] and Listeria monocytogenes in 5.9% [4.4; 7.3]. Most probable number of Salmonella spp. varied between 6cfu per gram to 320cfu per gram. Salmonella serotypes isolated from pork and chicken sausages were S. Typhimurium (45.8%), S. London (20.8%), S. Derby (16.7%), S. Newport (8.33%), S. Blockley (4.2%) and S. Weltevreden (4.17%). Using a logistic (mixed-effect) regression model, we found that Salmonella spp. contamination was positively associated with sausages sold in papers or plastic bags and no control of rodents. Chicken sausages were associated with a decreasing risk of Salmonella contamination. Listeria monocytogenes contamination was positively associated with the presence of fresh rodent droppings in the outlet and negatively when the staff was cleaning regularly their hands with soap and water or water only. All the sampled outlets of Reunion Island were not equivalent in terms of food safety measures. Increasing awareness of these traders remains a cornerstone to limit the presence of Salmonella spp. and Listeria spp. in sausages, particularly in a tropical context (high temperature and humidity).

[The role of reflectance confocal microscopy in the diagnosis of secondary syphilis of the vulva and anus: A first case report]. / Apport de la microscopie confocale par réflectance dans le diagnostic de syphilides ano-vulvaires, premier cas relaté.

PATIENTS AND METHODS: Herein we report the case of an 18-year-old pregnant patient presenting with plantar and ano-genital lesions of syphilis, pharyngitis, erythematosus and scalynasolabial intertrigo and angular cheilitis. REFLECTANCE CONFOCAL MICROSCOPY: In vivo reflectance confocal microscopy examination (Vivascope 3000®; Caliber Inc, Rochester, NY, USA, distributed in France by Mavig, Munich) of ano-genital lesions enabled us to identify hyper-reflective elongated rods in the papillary dermis suggesting spirochetes. The diagnosis was confirmed by TPHA and VDRL as well as immunohistological examination. COMMENTS: We identified for the first time rod shaped structures in ano-genital lesions of secondary syphilis, regularly alternating hyper-reflective and non-reflective areas corresponding to helix-shaped treponemes visualized by darkfield microscopy, which may not be confused with other cell structures.

Skin graft secured by VAC (vacuum-assisted closure) therapy in chronic leg ulcers: A controlled randomized study.

INTRODUCTION: Leg ulcers are a common condition. There have been very few studies of combined therapy involving VAC (vacuum-assisted closure) and skin graft. METHODS: We performed a randomized controlled trial of VAC therapy vs. hydrocolloid dressings over 5 days following autologous grafting on chronic leg ulcers. The primary objective was to assess the difference in success (defined as a reduction in wound area of at least 50% at 1 month) between the two dressing methods. Forty-six patients with ulcers present for over one month were included. Following a 7-day hospitalization period, follow-up was performed for 3 months on an outpatient basis. RESULTS: Our study does not demonstrate a statistically significant difference, with a 45.8% success rate in the VAC group vs. 40.9% in the conventional dressing group (P=0.73). In the venous ulcer group, the success rate was 57.9% for VAC vs. 40% for conventional dressings (P=0.3). The difference in favor of VAC in this group was not statistically significant, most likely due to an insufficient number of patients studied. CONCLUSION: Our study does not demonstrate superiority of VAC associated with skin graft over conventional dressings. We observed more complications with VAC (40%) than with conventional dressings (23%) (P=0.06).

Ex vivo confocal microscopy: a new diagnostic technique for mucormycosis.

BACKGROUND: Skin-dedicated ex vivo confocal microscopy (EVCM) has so far mainly been employed to identify cutaneous tumours on freshly excised samples. We present two cases where EVCM has been used to diagnose cutaneous mucormycosis. METHODS: The skin biopsies were evaluated by the skin-dedicated ex vivo confocal microscope VivaScope 2500(®) (MAVIG GmbH, Munich Germany) under both reflectance and fluorescence mode. Conventional direct optical examination on skin scraping and histological examination were later performed. RESULTS: Mucormycetes observed by EVCM presented as hyper-reflective elongated 20 µm in diameter structures with perpendicular ramifications. Fungi were found both under reflectance and fluorescence mode and were better visible with acridine orange under fluorescence EVCM. Conventional direct optical examination on skin scraping and histological examination found the same elongated and branching structures confirming the presence of Mucormycetes. CONCLUSIONS: Ex vivo confocal microscopy has both the advantages of being fast as the direct optical examination, and to be able to show the localisation of the fungi in the tissue like the histological examination. In our cases, EVCM allowed to rapidly confirm the clinical diagnosis of mucormycosis, which is essential for the treatment of this fungal infection. Further studies are needed to compare the performance of EVCM with the findings of conventional histological and mycological examinations.

Clinical usefulness of oral immunoglobulins in lung transplant recipients with norovirus gastroenteritis: a case series.

Viral gastroenteritis causing diarrhea is a common complication observed in lung transplant recipients. Differently from the mild and typically self-limited disease seen in immunocompetent subjects, immunocompromised patients frequently have a more severe course. Norovirus and rotavirus are among the leading causes of severe gastroenteritis in transplant recipients. Specific treatment is unavailable, although good supportive treatment can significantly reduce morbidity. Previous studies have suggested that oral immunoglobulins may be used for the treatment of acute viral gastroenteritis after solid-organ transplantation. Herein, we conducted a retrospective chart review of 12 lung transplant recipients with norovirus-induced gastroenteritis who were treated with oral immunoglobulins for 2 days. Eleven patients were successfully treated, whereas 1 subject was only mildly improved. Four patients had at least 1 recurrence. No significant adverse effects were observed. We conclude that oral immunoglobulins may be clinically useful for lung transplant recipients with norovirus-induced gastroenteritis.

Pregnancy-related listeriosis in France, 1984 to 2011, with a focus on 606 cases from 1999 to 2011.

This study describes trends in the incidence of pregnancy-related listeriosis in France between 1984 and 2011, and presents the major characteristics of 606 cases reported between 1999 and 2011 to the French Institute for Public Health Surveillance through the mandatory notification system. The incidence of pregnancy-related listeriosis decreased by a factor of 12 from 1984 to 2011. This reduction was a result of progressive implementation of specific Listeria monocytogenes control measures in food production. A lower incidence of pregnancy-related listeriosis was observed in regions with a lower prevalence of toxoplasmosis. Given that dietary recommendations in pregnancy target both toxoplasmosis and listeriosis prevention, we suppose that recommendations may have been delivered and followed more frequently in these regions. Cases reported between 1999 and 2011 (n=606) were classified as maternal infections with ongoing pregnancy (n=89, 15%), fetal loss (n=166, 27%), or live-born neonatal listeriosis (n=351, 58%). The majority of live-born neonatal listeriosis cases (n=216, 64%) were preterm births (22­36 weeks of gestation), of whom 14% (n=30) were extremely preterm births (22­27 weeks of gestation). Eighty per cent of mothers reported having eaten high risk food during pregnancy. A better awareness of dietary recommendations in pregnant women is therefore necessary.

Typing and clustering of Yersinia pseudotuberculosis isolates by restriction fragment length polymorphism analysis using insertion sequences.

Yersinia pseudotuberculosis is an enteropathogen that has an animal reservoir and causes human infections, mostly in temperate and cold countries. Most of the methods previously used to subdivide Y. pseudotuberculosis were performed on small numbers of isolates from a specific geographical area. One aim of this study was to evaluate the typing efficiency of restriction fragment length polymorphism of insertion sequence hybridization patterns (IS-RFLP) compared to other typing methods, such as serotyping, ribotyping, and multilocus sequence typing (MLST), on the same set of 80 strains of Y. pseudotuberculosis of global origin. We found that IS100 was not adequate for IS-RFLP but that both IS285 and IS1541 efficiently subtyped Y. pseudotuberculosis. The discriminatory index (DI) of IS1541-RFLP (0.980) was superior to those of IS285-RFLP (0.939), ribotyping (0.944), MLST (0.861), and serotyping (0.857). The combination of the two IS (2IS-RFLP) further increased the DI to 0.998. Thus, IS-RFLP is a powerful tool for the molecular typing of Y. pseudotuberculosis and has the advantage of exhibiting well-resolved banding patterns that allow for a reliable comparison of strains of worldwide origin. The other aim of this study was to assess the clustering power of IS-RFLP. We found that 2IS-RFLP had a remarkable capacity to group strains with similar genotypic and phenotypic markers, thus identifying robust populations within Y. pseudotuberculosis. Our study thus demonstrates that 2IS- and even IS1541-RFLP alone might be valuable tools for the molecular typing of global isolates of Y. pseudotuberculosis and for the analysis of the population structure of this species.

Prevalence, identification by a DNA microarray-based assay of human and food isolates Listeria spp. from Tunisia.

OBJECTIVES: We aimed at evaluating the prevalence of Listeria species isolated from food samples and characterizing food and human cases isolates. MATERIAL AND METHODS: Between 2005 and 2007, one hundred food samples collected in the markets of Tunis were analysed in our study. Five strains of Listeria monocytogenes responsible for human listeriosis isolated in hospital of Tunis were included. Multiplex PCR serogrouping and pulsed field gel electrophoresis (PFGE) applying the enzyme AscI and ApaI were used for the characterization of isolates of L. monocytogenes. We have developed a rapid microarray-based assay to a reliable discrimination of species within the Listeria genus. RESULTS: The prevalence of Listeria spp. in food samples was estimated at 14% by using classical biochemical identification. Two samples were assigned to L. monocytogenes and 12 to L. innocua. DNA microarray allowed unambiguous identification of Listeria species. Our results obtained by microarray-based assay were in accordance with the biochemical identification. The two food L. monocytogenes isolates were assigned to the PCR serogroup IIa (serovar 1/2a). Whereas human L. monocytogenes isolates were of PCR serogroup IVb, (serovars 4b). These isolates present a high similarity in PFGE. Food L. monocytogenes isolates were classified into two different pulsotypes. These pulsotypes were different from that of the five strains responsible for the human cases. CONCLUSION: We confirmed the presence of Listeria spp. in variety of food samples in Tunis. Increased food and clinical surveillance must be taken into consideration in Tunisia to identify putative infections sources.

Inadequate management of pregnancy-associated listeriosis: lessons from four case reports.

Listeria monocytogenes infection during pregnancy can lead to dramatic fetal or neonatal outcomes. No clinical trial has evaluated treatment options, and retrospective studies of cases are therefore important to define optimal regimens. We report four cases of materno-neonatal listeriosis illustrating inadequate antimicrobial therapy management and discuss recommended treatment options.

Early assessment of glucose abnormalities during continuous glucose monitoring associated with lung function impairment in cystic fibrosis patients.

BACKGROUND: Cystic fibrosis-related diabetes (CFRD) is correlated with a decline in lung function. Under certain circumstances, oral glucose tolerance test (OGTT) screening, used to diagnose CFRD, fails to reveal early glucose tolerance abnormalities. In this situation, continuous glucose monitoring (CGM) could be a useful tool for evaluating early abnormalities of glucose tolerance in CF patients. We aimed to study the CGM glucose profile in CF patients with normal OGTT screening results and to evaluate lung function and nutritional status according to the CGM glucose profile. METHODS: We assessed glycemic control, the CGM glucose profile, nutritional status, lung function antibiotic courses and colonization (P. aeruginosa and S. aureus) in CF patients, aged 10 years and over, with normal screening OGTT results (blood glucose at T120 min < 7.8 mmol/l). Two groups were identified according to the max CGM glucose value: Group 1<11 mmol/l and Group 2 ≥ 11 mmol/l. RESULTS: Among the 38 patients with normal OGTT, 12 (31.6%) were in Group 2. Compared to Group 1, Group 2 patients exhibited a significant impairment in lung function: FEV1, 68.2 ± 25.6% vs. 87.3 ± 17%, p = 0.01 and FVC, 86.1% ± 19.4% vs. 99.3% ± 13.4%, p=0.021, as well as a higher rate of colonization by P. aeruginosa: 83.3% vs. 44%, p=0.024. Nevertheless, there were no differences in nutritional status (BMI standard deviation score: p = 0.079; prealbumin: p = 0.364). CONCLUSIONS: CGM reveals early abnormalities of glucose tolerance that remain undiagnosed by OGTT screening and are associated with worse lung function and a higher prevalence of P. aeruginosa colonization in patients with CF. CLINICAL TRIAL REGISTRATION NUMBER: NCT00476281.

Disseminated nocardiosis mimicking exacerbation of pulmonary sarcoidosis.

Nocardiosis is a rare, mixed suppurative and granulomatous, bacterial infection that can affect various organs, but most commonly lungs. Clinical manifestation is usually uncharacteristic; can mimic fungal, parasitic and mycobacterial infections or malignancy. Presentation can be also similar to that of the other granulomatous diseases, among them sarcoidosis. We present an unusual case of disseminated nocardiosis in a patient diagnosed before with sarcoidosis and treated with glucocorticoids. Clinical symptoms initially mimicked exacerbation of pulmonary sarcoidosis. The course of disease was severe.