French National Protocol for genetic of amyotrophic lateral sclerosis.

Relationships between genes and amyotrophic lateral sclerosis (ALS) have been widely accepted since the first studies highlighting pathogenic mutations in the SOD1 gene 30years ago. Over the last three decades, scientific literature has clearly highlighted the central role played by genetic factors in the disease, in both clinics and pathophysiology, as well as in therapeutics. This implies that health professionals who care for patients with ALS are increasingly faced with patients and relatives eager to have answers to questions related to the role of genetic factors in the occurrence of the disease and the risk for their relatives to develop ALS. In order to address these public health issues, the French ALS network FILSLAN proposed to the Haute Autorité de santé (HAS) the drafting of a French National Protocol (PNDS) on ALS genetics. This PNDS was developed according to the "method for developing a national diagnosis and care protocol for rare diseases" published by the HAS in 2012 (methodological guide for PNDS available on the HAS website: http://www.has-sante.fr/). This document aims to provide the most recent data on the role of genes in ALS and to detail the implications for diagnosis and care.

Effects of food-based interventions in the management of chemoradiotherapy-induced nausea and vomiting: a systematic review.

BACKGROUND: Cancer treatment-related nausea and vomiting continue to be common and distressing symptoms for patients, despite improvements in antiemetics. Dietary modifications could potentially improve this symptom experience. Clinicians frequently provide dietary advice to patients, although the evidence base of such suggestions or recommendations is not clear. PURPOSE: This systematic review aimed to examine the current literature on food interventions associated with improvements in cancer treatment-related nausea and vomiting. METHODS: Eight electronic databases were searched with a specific search term strategy covering trials without time or language limitations. Eligible studies focused on a food substance, defined as any nutritious substance that people eat or drink to maintain life and well-being. Trials in children and adults during chemotherapy or radiotherapy were included. Cochrane risk of bias tool was used to assess trial quality and GRADE was used to assess the certainty in the effect of each outcome. RESULTS: Seventeen trials were included, 3 focusing on children and 14 on adults. Two trials included patients receiving radiation. Ten out of 17 trials (59%) had a high risk of bias. Strongest evidence with highest certainty was found for dietary counseling to meet macronutrient requirements in reducing incidence of radiotherapy-related nausea and vomiting in adults (n=2 studies; n=124 participants; GRADE level: moderate). There was also moderate certainty in the beneficial effect of protein supplementation on nausea and vomiting incidence in adults during radiotherapy (n=2 studies; n=124 participants; GRADE level: moderate). A significant positive effect on CINV incidence and/or severity in adults was also found for dietary counseling to meet macronutrient requirements during chemotherapy, a peppermint drink, scaly wood mushroom, chamomile, protein with ginger, and a colorless odorless diet (GRADE level: low to very low). CONCLUSIONS: The review identified food-based approaches that could improve the nausea and vomiting experience in patients with cancer and provide guidance to clinicians. However, confidence in these findings was low and studies were heterogeneous and mostly of low quality, requiring further investigation before stronger recommendations can be made. Future research is needed to confirm efficacy and safety. TRIAL REGISTRATION: PROSPERO CRD42022341154.

Synergistic use of bioactive agents for the management of different skin conditions: an overview of biological activities.

Recently, many plant-derived bioactive agents have been included in dermo-cosmetics formulations. This leads to an extensive portfolio of innovative products with an expanded range of benefits, including anti-aging, antioxidant, hydrating and depigmenting. Although different technologies drawing on science and nature are used to create these high-performing molecules, there remains some debate about the mechanism of action of the natural bioactive ingredients within dermo-cosmetics. This review recapitulates the main biological mechanisms underlying the activity of natural active ingredients, with a specific focus on their synergistic use for the management of common, yet quite specific, skin conditions. A total of 28 plant-derived bioactives were selected from the Givaudan Active Beauty (Argenteuil, France) portfolio, a multinational company specializing in innovative natural actives research. An extensive literature review about their biological activity was conducted by a PubMed search using different keywords. No language or publication date restrictions were used. Givaudan Active Beauty data on file were also considered. The bioactive ingredients were described according to the pathogenetic mechanisms underlying 10 common skin conditions that dermo-cosmetics may address. Literature data have shown that plant-derived bioactives are involved in a wide range of biological mechanisms showing anti-inflammatory, antioxidant, and moisturizing properties, along with skin barrier protection and collagen synthesis activities. As a result, different combinations of bioactives within dermo-cosmetics can be defined to counteract simultaneously the different pathogenetic mechanisms underlying different skin conditions. Available literature supports the synergistic use of plant-derived bioactive agents within dermo-cosmetics as a viable and safe option for managing the most common skin conditions.

Gallbladder cancer during pregnancy treated with surgery and adjuvant gemcitabine: A case report and review of the literature.

Background: Gallbladder cancer (GBC) represents the most common biliary tract cancer. Prognosis remains poor with 5-year overall survival rates less than 5% in advanced stages. GBCs are diagnosed more frequently in women, supposedly due to endocrine factors. Case: A 35-year-old woman, diagnosed with a non-metastatic GBC in the 22nd week of gestation, underwent a complete surgical resection 5 weeks later. Adjuvant gemcitabine was administered without complications, temporarily discontinued in the 32nd week to allow childbirth. The patient was disease-free for more than 3 years with ongoing remission at the last visit in July 2022. During the follow-up period, the child had no developmental, cognitive, or other health issues. Conclusion: Malignant tumors occur in about 0.1% of pregnant women, many are treated with chemotherapy. In oncology, the need to deliver optimal treatment in these patients represents a major concern. Both surgery and adjuvant chemotherapy of locally advanced GBC can be performed safely, with certain considerations, in the second trimester of pregnancy.

Impact of disease-modifying treatments on humoral response after COVID-19 vaccination: A mirror of the response after SARS-CoV-2 infection.

OBJECTIVE: To analyze the humoral response after COVID-19 vaccination in patients with multiple sclerosis (MS) according to disease-modifying treatments (DMTs) and in comparison with the humoral response after SARS-CoV-2 infection. METHODS: We included 28 MS patients with serological results after COVID-19 vaccination (Pfizer-BioNTech or Moderna ARNm) and 61 MS patients with serological results after COVID-19 (COVID-19 group) among patients followed up at the MS Center of Strasbourg, France, between January and April 2021. The primary endpoint was the IgG index according to DMTs (anti-CD20 mAb, sphingosine 1-phosphate receptor [S1PR] modulator and other treatments) and COVID-19 vaccine or COVID-19 groups. RESULTS: In the vaccinated MS patients, the median IgG index was lower in patients treated with anti-CD20 mAb and in patients treated with S1PR modulator compared to patients receiving other or no DMTs (4.80 [1.58-28.6], 16.5 [16.3-48.5], 1116 [434-1747] and 1272 [658-1886], respectively, P<0.001). Similar results were found for MS patients after COVID-19. CONCLUSIONS: Patients with MS and treated with S1PR modulators or anti-CD20 mAb had a reduced humoral response after COVID-19 vaccine.

Deployment of the consultation-liaison model in adult and child-adolescent psychiatry and its impact on improving mental health treatment.

BACKGROUND: Little information exists on the perceptions of psychiatrists regarding the implementation and various impacts of the consultation-liaison model. This model has been used in Quebec (Canada) through the function of specialist respondent-psychiatrists (SRP) since 2009. This study assessed the main activities, barriers or facilitators, and impact of SRP in adult and child-adolescent psychiatry on the capacity of service providers in primary care and youth centers to treat patients with mental health disorders (MHD). METHODS: Data included 126 self-administered questionnaires from SRP and semi-structured interviews from 48 SRP managers. Mixed methods were used, with qualitative findings from managers complementing the SRP survey. Comparative analyses of SRP responses in adult versus child-adolescent psychiatry were also conducted. RESULTS: Psychiatrists dedicated a median 24.12 h/month to the SRP function, mainly involving case discussions with primary care teams or youth centers. They were confident about the level of support they provided and satisfied with their influence in clinical decision-making, but less satisfied with the support provided by their organizations. SRP evaluated their impacts on clinical practice as moderate, particularly among general practitioners (GP). SRP working in child-adolescent psychiatry were more comfortable, motivated, and positive about their overall performance and impact than in adult psychiatry. Organizational barriers (e.g. team instability) were most prevalent, followed by system-level factors (e.g. network size and complexity, lack of resources, model inflexibility) and individual factors (e.g. GP reluctance to treat patients with MHD). Organizational facilitators included support from family medicine group directors, collaboration with university family medicine groups and coordination by liaison nurses; at the system level, pre-existing relationships and working in the same institution; while individual-level facilitators included SRP personality and strong organizational support. CONCLUSION: Quebec SRP were implemented sparingly in family medicine groups and youth centers, while SRP viewed their overall impact as moderate. Results were more positive in child-adolescent psychiatry than in adult psychiatry. Increased support for the SRP function, adapting the model to GP in need of more direct support, and resolving key system issues may improve SRP effectiveness in terms of team stability, coordination among providers, access to MH services and readiness to implement innovations.

Alternative use of BRAF inhibitors in patients with metastatic melanoma unable to swallow pills.

INTRODUCTION: BRAF and MEK inhibitors have been approved for use in metastatic melanoma therapies. All of them are administered as oral capsules or pills. We report two cases treated applying an alternative method of vemurafenib or debrafenib-trametinib administration in patients unable to swallow. CASE REPORT: The first case involved a 38-year-old man who was referred to a dermatologist for dysphagia and anorexia. After a computerized tomography (CT) scan it was concluded that the dysphagia was due to compression by mediastinal metastasis in a context of metastatic BRAF mutant melanoma. The second case involved a 35-year-old man who was diagnosed in March 2017 with melanoma of the back of the hand. Several months later a positron emission tomography (PET)/CT scan was performed. It revealed multiple disseminated metastasis.Management & Outcome: The first patient presented total dysphagia and was unable to swallow pills. It was decided to dissolve vemurafenib in order to facilitate administration. Dysphagia was improved 48 hours later, and oral feeding was reintroduced. Due to severe tablet phobia, the second patient was unable to swallow pills. Dabrafenib capsules were emptied and trametinib pills were grinded. One month later, we noted improved health associated with reduction of the metastases. DISCUSSION: Our study highlights the possibility of crushing or dissolving BRAF and MEK inhibitors in metastatic melanoma patients for whom it is impossible to swallow pills, eliciting a response and achieving significant if temporary clinical benefit.

Parkinsonian gait in elderly people: Significance of the threshold value of two and more falls per year.

OBJECTIVES: Parkinsonism in the elderly presents a major risk factor for recurrent falls (2 and more falls per year), which is associated with increased morbidity. The main objective was to investigate explanatory variables relating to the risk of being recurrent fallers (RF) in persons with parkinsonian gait. METHODS: Seventy-nine among 172 eligible persons were enrolled in this prospective study, the findings of which were analyzed at 12 months. Motor and non-motor features, as well as follow-up interviews to identify falls, loss of ability to walk, fluctuating cognition, traumatic falls, all-cause hospitalizations and deaths were collated and results compared between non RF (zero and one fall per year) and RF. Bayesian model averaging was used to predict the probability of patients being RF from their medical history as well as from cognitive assessment, gait velocity, vision and posture. RESULTS: N=79, 0.58 men, 50% had Parkinson's disease, 14% other neurodegenerative parkinsonian syndrome, 23% vascular parkinsonism and 13% Lewy body disease, 58% were RF. Median age 81.2 years and median MMSE 25/30. A history of falls and of hallucinations, median odds ratio respectively 9.06 (CI 2.34-38.22), 4.21 (CI 1.04-18.67) were associated with the highest odds ratios along with fluctuating cognition and abnormal posture. Two or more falls a year was a relevant threshold to distinguish a population with a high risk of comorbidity. CONCLUSION: The whole history of falls, hallucinations and fluctuating cognition can be considered predictive of recurrent falls in elderly people with parkinsonian gait and provide a tracking tool for patient management.

Identification and measurement of cervical spinal cord atrophy in neuromyelitis optica spectrum disorders (NMOSD) and correlation with clinical characteristics and cervical spinal cord MRI data.

INTRODUCTION: The spinal cord is one of the two main targets of neuromyelitis optica (NMO). The aim of this study was to highlight cervical spinal cord atrophy in NMO patients as compared to controls and to assess correlations between atrophy and clinical characteristics and cervical spinal cord MRI data. METHODS: This prospective study investigated 15 patients with a diagnosis of NMOSD and 15 healthy controls. The whole cervical spinal cord was explored by MRI. The cross-sectional area (CSA) was estimate at every level of cup. This measurement was then averaged on the whole cervical spinal cord, providing a single measurement for every subject, denoted as mean CSA. RESULTS: Mean CSA was 68.5 mm2 in the population of NMO patients and 72.8 mm2 in the population of healthy subjects. NMO patients had significantly smaller cervical spinal cord area than healthy controls (T test=0.009). Cervical spinal cord atrophy was associated with clinical signs of medullary involvement (T test=0.0006). There was a tendency toward a relation between cervical spinal cord atrophy and the Expanded Disability Status Scale (EDSS) (T test=0.07). This correlation seems statistically significant (T test<0.05) at the level of the upper cervical spinal cord (C2-C3) CONCLUSION: This study provides the first evidence of cervical spinal cord atrophy in NMOSD by studying the entire cervical spinal cord. Upper cervical spinal cord atrophy was substantially correlated to clinical disability and seems more involved in the development of clinical disability in NMOSD patients in comparison to the lower cervical spinal cord.

Anomalia de artéria coronária e prescrição de prática esportiva: nove casos de coronária anômala em atletas / Coronary artery anomaly and sports prescription: nine cases of anomalous coronary artery in athletes

INTRODUÇÃO: As anomalias da artéria coronária (AAC) são descritas como a segunda causa de morte súbita em atletas jovens nos Estados Unidos e Europa. São classificada mais comumente em anomalias de trajeto (TR) ou origem, tais como: coronária originada do tronco pulmonar e coronária direita ou esquerda com origem no seio coronariano oposto. As formas hemodinamicamente significantes, que oferecem maior risco, são aquelas com TR interarterial (TI) ou de origem da artéria pulmonar. A pesquisa de isquemia (IQ) é crucial nesses pacientes, sua fisiopatologia inclui a dilatação dos vasos adjacentes, formação de ângulo agudo no TR da artéria, espasmos dos vasos anômalos e TR intramural proximal ao vaso, sendo que episódios recorrentes de IQ podem gerar substrato arritmogênico. A maioria dos pacientes é assintomática ou apresenta sintomas inespecíficos, o que torna o diagnóstico um desafio. Eletrocardiograma, teste ergométrico e ecocardiograma possuem limitações, sendo o padrão ouro a angiotomografia coronariana contrastada. Tanto o aconselhamento médico para liberação de exercícios físicos quanto a decisão clinica ou cirúrgica ainda necessitam de evidências científicas mais robustas. O objetivo deste trabalho é apresentar casos de AAC em pacientes ativos para análise de métodos diagnósticos, conduta quanto a prescrição de exercício, intervenção e prognóstico. MÉTODOS: Foram revisados e comparados os prontuários de nove pacientes acompanhados em serviço de referência em cardiologia do estado de São Paulo no setor de cardiologia do esporte. RESULTADOS: a idade variou entre 16 e 60 anos, sendo todos do sexo masculino e praticantes de atividade física, apenas três a nível profissional. Apenas dois apresentavam algum sintoma previamente ao diagnóstico. Em seis casos a coronária percorria TI, a maioria destes apresentava alterações isquêmicas. Nos casos com IQ suspeita ou confirmada, a prática de exercício foi suspensa, dois pacientes foram submetidos à cirurgia sendo liberados após o procedimento. CONCLUSÃO: a melhor conduta frente à AAC ainda necessita de estudo, a suspensão da atividade física visa a prevenção da morte súbita, já que os sintomas quando presentes são mais frequentes ao esforço, contudo o mecanismo do evento ainda é incerto. A conduta cirúrgica, como revascularização ou endoprótese, apesar de feita nos casos de TI ou evidência de IQ, ainda tem benefício controverso na mortalidade.

Measurement of interfacial area from NMR time dependent diffusion and relaxation measurements.

The interfacial area between two immiscible phases in porous media is an important parameter for describing and predicting 2 phase flow. Although present in several models, experimental investigations are sparse due to the lack of appropriate measurement techniques. We propose two NMR techniques for the measurement of oil-water interfacial area: (i) a time dependent NMR diffusion technique applicable in static conditions, similar to those used for the measurement of the solid specific surface of a porous media, and (ii) a fast relaxation technique applicable in dynamic conditions while flowing, based on an interfacial relaxation mechanism induced by the inclusion of paramagnetic salts in the water phase. For dodecane relaxing on doped water, we found an oil interfacial relaxivity of 1.8µm/s, large enough to permit the measurement of specific interfacial surface as small as 1000cm2/cm3. We demonstrate both NMR techniques in drainage followed by imbibition, in a model porous media with a narrow pore size distribution. While flowing, we observe that the interfacial area is larger in imbibition than in drainage, implying a different organization of the oil phase. In a carbonate sample with a wide pore size distribution, we evidence the gradual invasion of the smallest pores as the oil-water pressure difference is increased.

Enzymatic Mechanisms Involved in Evasion of Fungi to the Oxidative Stress: Focus on Scedosporium apiospermum.

The airways of patients with cystic fibrosis (CF) are frequently colonized by various filamentous fungi, mainly Aspergillus fumigatus and Scedosporium species. To establish within the respiratory tract and cause an infection, these opportunistic fungi express pathogenic factors allowing adherence to the host tissues, uptake of extracellular iron, or evasion to the host immune response. During the colonization process, inhaled conidia and the subsequent hyphae are exposed to reactive oxygen species (ROS) and reactive nitrogen species (RNS) released by phagocytic cells, which cause in the fungal cells an oxidative stress and a nitrosative stress, respectively. To cope with these constraints, fungal pathogens have developed various mechanisms that protect the fungus against ROS and RNS, including enzymatic antioxidant systems. In this review, we summarize the different works performed on ROS- and RNS-detoxifying enzymes in fungi commonly encountered in the airways of CF patients and highlight their role in pathogenesis of the airway colonization or respiratory infections. The potential of these enzymes as serodiagnostic tools is also emphasized. In addition, taking advantage of the recent availability of the whole genome sequence of S. apiospermum, we identified the various genes encoding ROS- and RNS-detoxifying enzymes, which pave the way for future investigations on the role of these enzymes in pathogenesis of these emerging species since they may constitute new therapeutics targets.

Comparing ataxias with oculomotor apraxia: a multimodal study of AOA1, AOA2 and AT focusing on video-oculography and alpha-fetoprotein.

Whether the recessive ataxias, Ataxia with oculomotor apraxia type 1 (AOA1) and 2 (AOA2) and Ataxia telangiectasia (AT), can be distinguished by video-oculography and alpha-fetoprotein level remains unknown. We compared 40 patients with AOA1, AOA2 and AT, consecutively referred between 2008 and 2015 with 17 healthy subjects. Video-oculography revealed constant impairments in patients such as cerebellar signs, altered fixation, impaired pursuit, hypometric saccades and abnormal antisaccades. Horizontal saccade latencies could be highly increased reflecting oculomotor apraxia in one third of patients. Specific distinctive alpha-fetoprotein thresholds were determined for AOA1 (7-15 µg/L), AOA2 (15-65 µg/L) and AT (>65 µg/L). Early age onset, severe walking disability, movement disorders, sensori-motor neuropathy and cerebellar atrophy were all shared. In conclusion, alpha-fetoprotein level seems to permit a distinction while video-oculography does not and therefore is not mandatory, even if an appropriate oculomotor examination remains crucial. Our findings are that AOA1, AOA2 and AT form a particular group characterized by ataxia with complex oculomotor disturbances and elevated AFP for which the final diagnosis is relying on genetic analysis. These findings could guide genetic analysis, assist reverse-phenotyping and provide background for the interpretation of the numerous variants of unknown significance provided by next-generation sequencing.

Deciphering the causes of sporadic late-onset cerebellar ataxias: a prospective study with implications for diagnostic work.

The management of sporadic late-onset cerebellar ataxias represents a very heterogeneous group of patients and remains a challenge for neurologist in clinical practice. We aimed at describing the different causes of sporadic late-onset cerebellar ataxias that were diagnosed following standardized, exhaustive investigations and the population characteristics according to the aetiologies as well as at evaluating the relevance of these investigations. All patients consecutively referred to our centre due to sporadic, progressive cerebellar ataxia occurring after 40 years of age were included in the prospective, observational study. 80 patients were included over a 2 year period. A diagnosis was established for 52 patients (65%) corresponding to 18 distinct causes, the most frequent being cerebellar variant of multiple system atrophy (n = 29). The second most frequent cause was inherited diseases (including spinocerebellar ataxias, late-onset Friedreich's disease, SLC20A2 mutations, FXTAS, MELAS, and other mitochondrial diseases) (n = 9), followed by immune-mediated or other acquired causes. The group of patient without diagnosis showed a slower worsening of ataxia (p < 0.05) than patients with multiple system atrophy. Patients with later age at onset experienced faster progression of ataxia (p = 0.001) and more frequently parkinsonism (p < 0.05) than patients with earlier onset. Brain MRI, DaT scan, genetic analysis and to some extent muscle biopsy, thoracic-abdominal-pelvic tomodensitometry, and cerebrospinal fluid analysis were the most relevant investigations to explore sporadic late-onset cerebellar ataxia. Sporadic late-onset cerebellar ataxias should be exhaustively investigated to identify the underlying causes that are numerous, including inherited causes, but dominated by multiple system atrophy.

[Nerve transfer between the intercostal nerves and the motor component of the musculocutaneous nerve. Anatomical study of feasibility]. / Transfert nerveux entre les nerfs intercostaux et la composante motrice du nerf musculocutané. Étude anatomique de faisabilité.

INTRODUCTION: The intercostal nerves (ICN) transfer to the musculocutaneous nerve (MCN) can restore elbow flexion in complete brachial plexus palsy. The last cases our service dealt with, allowed our staff to observe two different situations. In the 2 first patients, we were able to proceed with an intraneurodissection of the MCN motor component up to the axillary cavity level, while on the third case such dissection could not be performed as high. The aim of this work is to assess the feasibility of a transfer on the MCN's motor component. MATERIAL AND METHODOLOGY: We conducted a series of 5 cadaver dissections of the MCN and ICN on the anatomy laboratory. Using magnifying loupes to perform an intraneurodissection, we were able to split the motor and sensory fibers as they stood out. It would help motor recuperation avoiding directional error on sensitive component. RESULTS: The ICN can be sutured on the motor component of the MCN, provided the dissection is very minutious. DISCUSSION: The intraneurodissection of the MCN up to the axillary cavity level is possible as the interfascicular exchanges are scarce there. Publications already refer to the possibility of a nerve transfer between the ICN and the motor component of the MCN. Therefore, our researches suggest that such a procedure can be considered for routine procedures. CONCLUSION: The neurotization is one of the latest breakthroughs in terms of brachial plexus surgery. We are hopeful that anatomical researches could lead to optimization possibilities.

Escherichia coli Probiotic Strain ED1a in Pigs Has a Limited Impact on the Gut Carriage of Extended-Spectrum-ß-Lactamase-Producing E. coli.

Four trials were conducted to evaluate the impact of Escherichia coli probiotic strain ED1a administration to pigs on the gut carriage or survival in manure of extended-spectrum-ß-lactamase-producing E. coli Groups of pigs were orally inoculated with strain E. coli M63 carrying the blaCTX-M-1 gene (n = 84) or used as a control (n = 26). In the first two trials, 24 of 40 E. coli M63-inoculated pigs were given E. coli ED1a orally for 6 days starting 8 days after oral inoculation. In the third trial, 10 E. coli M63-inoculated pigs were given either E. coli ED1a or probiotic E. coli Nissle 1917 for 5 days. In the fourth trial, E. coli ED1a was given to a sow and its 12 piglets, and these 12 piglets plus 12 piglets that had not received E. coli ED1a were then inoculated with E. coli M63. Fecal shedding of cefotaxime-resistant Enterobacteriaceae (CTX-RE) was studied by culture, and blaCTX-M-1 genes were quantified by PCR. The persistence of CTX-RE in manure samples from inoculated pigs or manure samples inoculated in vitro with E. coli M63 with or without probiotics was studied. The results showed that E. coli M63 and ED1a were good gut colonizers. The reduction in the level of fecal excretion of CTX-RE in E. coli ED1a-treated pigs compared to that in nontreated pigs was usually less than 1 log10 CFU and was mainly observed during the probiotic administration period. The results obtained with E. coli Nissle 1917 did not differ significantly from those obtained with E. coli ED1a. CTX-RE survival did not differ significantly in manure samples with or without probiotic treatment. In conclusion, under our experimental conditions, E. coli ED1a and E. coli Nissle 1917 could not durably prevent CTX-RE colonization of the pig gut.