[The causes of splenic infarction: An almost systematic review of the literature]. / Les causes des infarctus spléniques : une revue quasi systématique de la littérature.

INTRODUCTION: Splenic infarction is a rare event in clinical practice, diagnosed by CT scan. There are many causes. They often determine the treatment given. However, there is no consensus on etiological investigations. METHODS: We present here an almost systematic review of the literature, based on data available on Pubmed from 1991 to 2022. Using the keywords "splenic infarct", from 1893 references, 11 cohort studies and 867 clinical cases were included in this review. Articles written in languages using alphabets other than Latin were excluded. RESULTS AND CONCLUSIONS: Analysis of these various studies has enabled us to draw up a list that is intended to be as exhaustive as possible of the causes of splenic infarction. The most frequent are emboligenic heart disease, hematological malignancies, solid neoplasia and certain infections. The descriptions available in the literature were mainly based on isolated clinical cases, not always making it possible to establish a causal link with the disease described, especially as around 20% of reported cases of splenic infarction were asymptomatic and potentially of incidental discovery. Based on the findings of this literature review, we propose a protocol for the etiological assessment of splenic infarcts.

The culture of doubt: Do medical students really experience clinical uncertainty when they should?

Uncertainty is a fundamental aspect of medical practice, necessitating incorporation into undergraduate medical training. The integrative model of uncertainty tolerance (UT) developed by Hillen and Han serves as a comprehensive framework for exploring clinical uncertainty. While studies have extensively examined UT dimensions, including sources, responses, and moderators, the factors influencing the perception of uncertainty stimuli remain underexplored. However, students' ability to perceive uncertainty and their approach to uncertain stimuli play a crucial role in enabling them to develop adaptive responses to uncertainty, necessary for their comfort in these situations. Defining uncertainty as a metacognitive state suggests significant variability in its perception among individuals and within an individual over time. Moreover, several studies have demonstrated the substantial influence of various individual and contextual factors on how individuals perceive and respond to uncertainty. In this paper, the authors present multiple hypotheses to address the question of whether students genuinely perceive uncertainty stimuli when they should. The authors argue that students' personal relationship with their knowledge is essential in their ability to identify clinical uncertainty, particularly concerning the limits of medical knowledge. Therefore, they propose that an academic culture fostering doubt, through exposing students to a variety of perspectives, would enhance their ability to identify uncertainty zones in a clinical situation at an early stage. Drawing on Dewey's situational theory, the authors emphasize the importance of better understanding, in a work setting, the influence of contextual and situational characteristics on individual perceptions of uncertainty. In line with this idea, ethnographic studies would offer valuable insights into identifying the relationship between the students, their work environment, and their perception of clinical uncertainty.

Systemic sclerosis, silica exposure and cellular therapies: The sand in the gears?

Systemic sclerosis (SSc) is a chronic orphan autoimmune disease with the highest mortality rate among rheumatic diseases. SSc-related interstitial-lung disease (ILD) remains among the leading causes of SSc-related mortality with still few therapeutic effective strategies. In patients with crystallin silica exposure, SSc is recognized as an occupational disease according to the French social security system (Table 25A of the general insurance regimen). Lympho-ablative or myeloablative immunosuppression followed by autologous hematopoietic stem-cell transplantation (aHSCT) is the only therapeutic approach with demonstrated efficacy, improved survival with disease modifying effects on SSc-fibrotic manifestations (skin disease and ILD) and quality of life. A documented past and/or present occupational silica exposure, with extensive exposure and/or silica-related ILD and/or with persistent silica content in the broncho-alveolar lavage fluid are contra-indications to aHSCT in SSc patients, due to the risk of silica-related malignancy or of SSc relapse. This article aims to discuss alternative options in SSc patients with a history of silica exposure, and how innovative cellular therapies (mesenchymal stromal cells, CAR cells) could represent new therapeutic options for these patients.

Drug development and novel therapeutics to ensure a personalized approach in the treatment of systemic sclerosis.

INTRODUCTION: Systemic sclerosis (SSc) is a systemic disease encompassing autoimmunity, vasculopathy, and fibrosis. SSc is still burdened by high mortality and morbidity rates. Recent advances in understanding the pathogenesis of SSc have identified novel potential therapeutic targets. Several clinical trials have been subsequently designed to evaluate the efficacy of a number of new drugs. The aim of this review is to provide clinicians with useful information about these novel molecules. AREA COVERED: In this narrative review, we summarize the available evidence regarding the most promising targeted therapies currently under investigation for the treatment of SSc. These medications include kinase inhibitors, B-cell depleting agents, and interleukin inhibitors. EXPERT OPINION: Over the next five years, several new, targeted drugs will be introduced in clinical practice for the treatment of SSc. Such pharmacological agents will expand the existing pharmacopoeia and enable a more personalized and effective approach to patients with SSc. Thus, it will not only possible to target a specific disease domain, but also different stages of the disease.

[Tolerating uncertainty: Towards a competence-based approach]. / Faire de la tolérance à l'incertitude une compétence médicale.

Uncertainty in inherent to every aspects of medical practice. As the concept of uncertainty in healthcare is still to explore, deciphering the determinants and the roots of this uncertainty would benefit from the insights of various disciplines, such as epistemology, sociology, mathematics, or philosophy. The urgent need to improve physician's ability to cope with uncertainty, has been recently highlighted by the COVID-19 pandemic. Besides, the concept of uncertainty tolerance has been proposed, and could serve as a relevant basis for approaching uncertainty, in medical education. Thus, we propose at first to discuss the uncertainty tolerance framework from Hillen et al. Then, from an educational perspective, we outline some avenues regarding how uncertainty tolerance could be thought, in a competence-based approach, and discuss several educational activities, which have proven efficient in promoting uncertainty tolerance among medical practitioners abroad.

[Systemic sclerosis-related interstitial lung disease: Diagnostic and therapeutic strategy in the light of recent clinical trials]. / Pneumopathie interstitielle diffuse associée à la sclérodermie systémique : prise en charge diagnostique et thérapeutique à la lumière des essais thérapeutiques récents.

Systemic sclerosis (SSc) is an autoimmune disease associated to fibrotic manifestations. Interstitial lung disease (SSc-ILD), one of the main fibrotic features of SSc, is the first cause of SSc-related death. The management of SSc-ILD has recently benefited from the results of key randomised controlled trials. French authorities have approved Nintedanib for the treatment of SSc-ILD, and tocilizumab has recently been approved by the Food and Drug Administration (FDA) in the United-States (US). These recent approvals challenge the management of this fibrotic manifestation of SSc. This narrative literature review, at the crossroad of internal medicine and pulmonology, discusses what could be an up-to date approach, in terms of diagnostic and therapeutic strategies for SSc-ILD, in the light of the results from recent clinical trials.

[Hypersensitivity Pneumonitis: An update]. / Mise au point : pneumopathies d'hypersensibilité.

Hypersensitivity Pneumonitis (HP) is a common immune-mediated interstitial lung disease (ILD) induced by repeated exposure to environmental antigens in susceptible individuals. The most commonly known forms are bird fancier's disease and farmer's lung. However, the antigens involved are widely diverse. Therefore, the list of causes of HP is frequently expanding. HP seems to be under-diagnosed owing to its highly heterogeneous presentation in both the non-fibrotic and fibrotic subtypes and could represent up to 15% of all ILDs encountered in clinical practice. However, the recognition of HP cases is essential to ensure appropriate therapy for the patient. Home health care workers' intervention is sometimes critical in this context. In case of confirmed exposure, the diagnosis could be considered with high confidence if the high-resolution computed tomography (HR-CT) shows a typical HP pattern associated with a lymphocytosis over 30% in the broncho-alveolar lavage (BAL). In all other situations, the patients should undergo further investigations and additional histopathological sampling should be considered and submitted to a multidisciplinary team discussion. After diagnosis, antigenic eviction is the rule whenever possible. Corticosteroid treatment is the first-line medical treatment for severe forms and aims to prevent the development of fibrosis. Anti-fibrotic therapy is now an option for patients with progressive ILD and failure of immunomodulatory/immunosuppressive therapies.

[Illnesses unrelated to systemic sclerosis (IUSS) diagnosed throughout the patient's follow-up in a referral center: A cohort of 200 patients]. / Affections non-directement attribuables à la sclérodermie systémique (ANDAS) diagnostiquées au cours du suivi dans un centre de compétence: à propos d'une cohorte de 200 patients.

INTRODUCTION: Our work aimed to investigate the illnesses unrelated to systemic sclerosis (IUSS), diagnosed among patients with systemic sclerosis (SSc) throughout their follow-up in a referral tertiary care center. METHODS: All the patients with SSc followed in the Internal Medicine Department of the University Hospital between October, 2014 and December, 2015, were included. We specifically reviewed the medical records of the patients who exhibited IUSS, defined as an illness that could not be considered as a typical clinical manifestation or as a usual complication of the disease. RESULTS: Two hundred patients were included, and 38 IUSS were diagnosed among 31 SSc patients, over a 4 years median follow-up period. These diagnoses included vascular diseases (26%), heart diseases (21%), neoplasia (8%), infectious diseases (6%), autoimmune diseases (5%), endocrinopathies (5%), and others (24%). The median follow-up time before IUSS diagnosis was two years. Seventeen (45%) of these diagnoses were considered in patients showing suggestive clinical signs. A specific therapy was delivered in 25 cases (66%). Group comparisons revealed that dyslipidemia was more frequent in patients with IUSS (OR = 2.6 [1.1-1.5]; p = 0.014), while no differences were found for the other characteristics. Especially, no association between auto-antibodies specificity and the occurrence of IUSS was found. CONCLUSION: This study focused on IUSS in SSc patients and highlights the need for a polyvalent clinical approach all along the follow up of SSc patients.

[Screening for pulmonary arterial hypertension in patients with systemic sclerosis: Comparison of DETECT algorithm to decisions of a multidisciplinary team, in a competence centre]. / Dépistage de l'hypertension artérielle pulmonaire au cours de la sclérodermie systémique : comparaison de l'algorithme DETECT à une discussion pluridisciplinaire en centre de compétence.

INTRODUCTION: Pulmonary arterial hypertension (PAH) is a severe complication of systemic sclerosis and detecting PAH efficiently remains challenging. The DETECT study has offered in 2013 a composite screening tool for PAH. The objective of our study was to compare the indication of right heart catheterisation (RHC) as suggested by the DETECT algorithm with the decisions of a multidisciplinary team. METHODS: This prospective monocentric non-interventional study consecutively included systemic sclerosis patients when data required to apply DETECT algorithm were available. We evaluate the number of RHC as requested by this algorithm and confronted it with the indications of RHC suggested by a multidisciplinary group blinded for the result of DETECT algorithm. RESULTS: In total, 117 systemic sclerosis patients were included. When DETECT algorithm was applied to all patients, RHC was suggested by this algorithm for 70 patients, whereas only 15 indications were required by the multidisciplinary group; among those patients only 7 had PAH. When DETECT algorithm was applied only to the 42 patients with DLCO<60% and disease duration of more than 3 years, RHC was suggested for 31 patients whereas only 13 were indicated by the multidisciplinary group; among those patients only 7 had PAH. CONCLUSION: The DETECT algorithm is able to efficiently detect all PAH patients finally diagnosed by our multidisciplinary team. However, it increases by 3 the number of RHC that should be performed.

[Hereditary thrombophilia testing and its therapeutic impact on venous thromboembolism disease: Results from a retrospective single-center study of 162 patients]. / La recherche de thrombophilie héréditaire et son impact thérapeutique dans la maladie thromboembolique veineuse : résultats d'une étude monocentrique rétrospective sur 162 patients.

INTRODUCTION: Venous thromboembolic disease is a multifactorial, frequently recurrent pathology, whose treatment is based on anticoagulation. As part of the etiological investigation, screening for an inherited thrombophilia is framed by French guidelines published in 2009. The aim of the study is to assess the contribution of inherited thrombophilias testing in common practice. METHOD: This is a retrospective single-center observational study. Over a period of a year, all records of patients who were screened for a hereditary thrombophilia were analyzed. The conformity of the indication of hereditary thrombophilia workup in balance with the guidelines, its completeness and therapeutic impact were studied. RESULTS: Of the 494 records analyzed, 225 were related to venous thromboembolism. Among them, there were 162 pulmonary embolisms or deep vein thrombosis of the lower limbs. In this subgroup, 57 % of records complied with guidelines and 69 % were complete. Thirty-four thrombophilias were highlighted: 4 protein S deficiencies, 1 protein C deficiency, 4 combined deficiencies, 17 factor V Leiden mutations and 8 factor II G20210A mutations. For one patient, hereditary thrombophilia diagnosis had profoundly changed the curative therapeutic approach. CONCLUSION: Adherence to French guidelines remains limited. In clinical practice, diagnosis of hereditary thrombophilia has little impact on the curative therapeutic approach in venous thromboembolic disease.

Vemurafenib-induced eccrine squamous syringometaplasia.

We report herein a patient treated with vemurafenib for a stage IV melanoma who developed an eruption related to eccrine squamous syringometaplasia (ESS). This entity is a well-described side effect of cytostatic therapies used for malignant neoplasia and is clinically characterized by a symmetric cutaneous eruption composed of papules and vesicles preferentially located on fold and intertriginous areas. It is histologically defined by a squamous metaplasia of eccrine ductal epithelium. ESS represents another skin eruption to be added to the list of cutaneous adverse events associated with vemurafenib, a selective BRAF inhibitor used to treat patients with metastatic melanoma harboring the V600E mutation. The discussion focuses on the pathogenesis of ESS secondary to vemurafenib and on alternative diagnoses.

Gestational age-related reference values for amniotic fluid organic acids.

BACKGROUND: Normative data for amniotic fluid (AF) levels of organic acids at different gestational ages are lacking. They can provide a useful framework to investigate the accuracy of prenatal diagnosis for organic acidemias. METHODS: We report on the concentration of 21 organic acids in AF obtained by gas chromatography/mass spectrometry between the 12th and 34th weeks of gestation from 92 pregnancies that were not at risk for organic acidurias. RESULTS: We infer normal reference values that can be compared with 134 pregnancies at risk for several metabolic conditions, that is, propionic acidemia, methylmalonic acidemia (methylmalonyl-CoA mutase deficiency or defects in cobalamin metabolism), 4-hydroxybutyric acidemia, glutaric acidemia and pyroglutamic acidemia. CONCLUSION: Most of the metabolites tested did not show conspicuous variations across gestational ages in normal fetuses, with ranges that were consistently similar to available reference values from pooled samples in previous reports. With rare exceptions, knowledge of pathological versus normal values for relevant metabolites leads to clear-cut differentiation of affected versus unaffected fetuses. Nevertheless, it is strongly recommended that mutational analysis and/or additional biochemical approaches complement organic acid analysis for an adequate diagnostic workup.

Prenatal diagnosis of some metabolic diseases using early amniotic fluid samples: report of a 15 years, experience.

BACKGROUND: In the present study, we report the results of 132 prenatal diagnoses performed on chorionic villi and cell-free amniotic fluid obtained simultaneously at 12-13 weeks of gestation. In addition, we report the result of 59 prenatal diagnoses performed at 12-13th week using amniotic fluid only. METHODS AND RESULTS: A total of one fetal loss (1/191) was observed when a sample of amniotic fluid was obtained at around 12-13 weeks, whereas three losses (3/82) were observed after midtrimester amniocentesis. We attribute this finding to the fact that only a very small volume of amniotic fluid was sampled using a very small needle. CONCLUSION: From these data it appears that when a couple is facing a high risk of recurrence of some metabolic diseases, the study of chorionic villus and amniotic fluid sampled simultaneously offers a safe and reliable method of early prenatal diagnosis.