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RATIONALE: On the occasion of the General stage meeting of Internal Medicine, the National College of Internal Medicine Teachers (CEMI) conducted a survey on teaching activity among all French university hospital (HU) internal medicine specialists. METHOD: The survey was carried out in September 2023 by sending an email to 101 hospital practitioners university professors (PU-PH) and 18 hospital practitioners assistant professors (MCU-PH) of internal medicine in subsection 53-01 of the National council of universities (CNU), as well as to the 11 HU internists working in immunology (subsection 47-01) or therapeutics (subsection 48-04). RESULTS: Seventy-three HUs (56.1%) responded to the survey, including 65 PU-PH, 7 MCU-PH and 1 university hospital practitioner (PHU). Internal medicine HUs participate in faculty teaching: 80% are responsible for teaching, 30% are responsible for the year or cycle or lead committees and 40% have had or have an elected mandate at the faculty or at university. Internal medicine HU are involved in the teaching of semiology during the first cycle of medical studies, but also in pharmaceutical sciences, dentistry, midwifery and in paramedical training. They are very invested in the implementation of the second cycle reform and 80% are involved in the preparation of Objective Structured Clinical Examinations (ECOS), mainly as examiners (90%). They also participate in teaching using simulation (60%), teaching advanced practice nurses (IPA) (25%), and writing CEMI books (75%). For ECOS, 90% participate as examiners, 60% participate in teaching using simulation, 25% are involved in teaching advanced practice nurses (IPA), 75% participated in the writing of CEMI works. Eight (12%) internal medicine HUs co-facilitate training with patients and 26 (38%) participate in master's courses at the Faculty of Sciences. Finally, 94% are affiliated with a research unit and 48% supervise university theses students. CONCLUSION: Internal medicine universities teachers have a strong educational commitment, particularly in semiology and in the reform of the second cycle of medical studies with ECOS and simulation.
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BACKGROUND: Simulation-based education in healthcare encompasses a wide array of modalities aimed at providing realistic clinical experiences supported by meticulously designed scenarios. The French-speaking Society for Simulation in Healthcare (SoFraSimS) has developed guidelines to assist educators in the design of scenarios for manikin- or simulated participant- based immersive simulation and procedural simulation, the three mainly used modalities. METHODS: After establishing a French-speaking group of experts within the SoFraSimS network, we performed an extensive literature review with theory-informed practices and personal experiences. We used this approach identify the essential criteria for practice-based scenario design within the three simulation modalities. RESULTS: We present three comprehensive templates for creating innovative scenarios and simulation sessions, each tailored to the specific characteristics of a simulation modality. The SoFraSimS templates include five sections distributed between the three modalities. The first section contextualizes the scenario by describing the practicalities of the setting, the instructors and learners, and its connection to the educational program. The second section outlines the learning objectives. The third lists all the elements necessary during the preparation phase, describing the educational method used for procedural simulation (such as demonstration, discovery, mastery learning, and deliberate practice). The fourth section addresses the simulation phase, detailing the behaviors the instructor aims to analyze, the embedded triggers, and the anticipated impact on simulation proceedings (natural feedback). This ensures maximum control over the learning experience. Finally, the fifth section compiles elements for post-simulation modifications to enhance future iterations. CONCLUSION: We trust that these guidelines will prove valuable to educators seeking to implement simulation-based education and contribute to the standardization of scenarios for healthcare students and professionals. This standardization aims to facilitate communication, comparison of practices and collaboration across different learning and healthcare institutions.
'What this article adds'1. The SoFraSimS provides guidelines to facilitate the development of simulation-based activities.2. These guidelines are theory-informed as well as evidence and experience-based.3. A detailed approach to writing a complete activity or scenario for procedural and immersive simulation including manikins or simulated participants is provided (the 'SoFraSimS templates').4. This work aims at standardizing practices and exchanging scenarios between simulation centers.
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Maniquíes , Entrenamiento Simulado , Humanos , Francia , Competencia Clínica , Guías como Asunto , Educación Médica/métodosRESUMEN
Asplenic patients are at high risk of serious infectious or thrombotic complications, especially when they are not adequately informed of the risk and not closely followed. Ladhani et al. on behalf of the British Society for Haematology propose updated guidelines for managing these patients. Healthcare professionals need to improve infection prevention in patients with hypofunctional or absent spleen through better identification and immunisation using established national registries. Commentary on: Ladhani et al. Prevention and treatment of infection in patients with absent or hypofunctional spleen: A British Society for Haematology guideline. Br J Haematol 2024;204:1672-1686.
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Guías de Práctica Clínica como Asunto , Sistema de Registros , Humanos , Esplenectomía , Sociedades Médicas/normas , Reino Unido , Bazo , Hematología/normasRESUMEN
BACKGROUND: Infliximab is currently recommended as a third-line treatment for refractory sarcoidosis. Data in function of clinical phenotype are currently lacking. We evaluated patients' characteristics and responses to infliximab according to their GenPhenReSa cluster. METHODS: We evaluated clinical and biological characteristics of patients diagnosed with sarcoidosis who received infliximab between September 2008 and April 2019 at our centre. RESULTS: Fifty-five patients (median disease duration, 87 months) received infliximab: 48 (87%) as a second- or third-line treatment, and 7 (13%) as a first-line treatment. After a median duration of 12 months, 24 (45%) and 14 (25%) patients achieved complete and partial responses, respectively, together with a significant decrease in the number of affected organs and tapering of steroid doses. All patients with neurosarcoidosis (OR 17), 90% in group 2 (ocular-cardiac-cutaneous-CNS, OR 7.4), and approximately two-thirds of those in groups 1 (abdominal organs), 4 (pulmonary-lympho-nodal), and 5 (extrapulmonary), achieved a response, whereas patients in group 3 (musculoskeletal-cutaneous) had a treatment-failure OR of 9. Infliximab could be stopped after complete remission was achieved in 7 patients: 4 relapsed after a median of 6 months. Overall, 36% of patients experienced serious adverse events, mainly infections, which led to treatment cessation in 29% of patients and caused two deaths. CONCLUSIONS: Other than patients with musculoskeletal-cutaneous involvement (group 3), infliximab led to a good response for patients with CNS (group 2) and liver (group 1) organ-predominant sarcoidosis. However, it led to serious infections and merely suspended sarcoidosis, so further research on factors predictive of relapse is needed.
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Sarcoidosis , Humanos , Infliximab/efectos adversos , Estudios Retrospectivos , Resultado del Tratamiento , Sarcoidosis/diagnóstico , Sarcoidosis/tratamiento farmacológico , FenotipoRESUMEN
OBJECTIVES: Antisynthetase syndrome (ASyS) is a rare autoimmune disease. We aimed to determine clinical, biological, radiological, and evolutive profiles of ASyS patients with anti-PL7 or anti-PL12 autoantibodies. METHODS: We performed a retrospective study that included adults with overt positivity for anti-PL7/anti-PL12 autoantibodies and at least one Connors' criterion. RESULTS: Among 72 patients, 69% were women, 29 had anti-PL7 and 43 anti-PL12 autoantibodies, median age was 60.3 years, and median follow-up period was 52.2 months. At diagnosis, 76% of patients had interstitial lung disease, 61% had arthritis, 39% myositis, 25% Raynaud's phenomenon, 18% mechanic's hands, and 17% had fever. The most frequent pattern on initial chest computed tomography was non-specific interstitial pneumonia and 67% had fibrosis at last follow-up. During follow-up, 12 patients had pericardial effusion (18%), 19 had pulmonary hypertension (29%), 9 (12.5%) had neoplasms, and 14 (19%) died. Sixty-seven patients (93%) received at least one steroid or immunosuppressive drug. Patients with anti-PL12 autoantibodies were younger (p=0.01) and more frequently exhibited anti-SSA autoantibodies (p=0.01); patients with anti-PL7 autoantibodies had more severe weakness and higher maximum creatine kinase levels (p=0.03 and 0.04, respectively). Initial severe dyspnoea was more common in patients from the West Indies (p=0.009), with lower predicted values of forced vital capacity, forced expiratory volume in 1s, and total lung capacity (p=0.01, p=0.02, p=0.01, respectively) contributing to a more severe 'respiratory' initial presentation. CONCLUSIONS: The high mortality and significant numbers of cardiovascular events, neoplasms and lung fibrosis in anti-PL7/12 patients justify close monitoring and question addition of antifibrotic drugs.
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Autoanticuerpos , Miositis , Adulto , Humanos , Femenino , Persona de Mediana Edad , Masculino , Estudios Retrospectivos , Miositis/diagnóstico , Región del CaribeRESUMEN
BACKGROUND: Thrombocytopenia occurs in 60% of patients with myelodysplastic syndromes (MDS), increasing the risk of life-threatening haemorrhage in this population of mainly old patients with comorbidities. However, data are scare regarding immune thrombocytopenia (ITP) secondary to MDS. AIM: We analyzed the utility of indium-111 platelet scintigraphy (IPS) to better characterize the mechanisms of thrombocytopenia in 21 adult patients with MDS. METHODS: Adult patients with a definite diagnosis of MDS according to the international criteria who underwent IPS between 2009 and 2018 because of an increased bleeding risk were retrospectively selected. Autologous 111Indium platelet labelling was performed with a technique similar to that described previously using a standardized method. RESULTS: Platelet lifespan ≤ 6 days identified patients with peripheral platelet destruction. Taking into account the response to ITP-directed therapies after IPS, the sensitivity, specificity, and positive and negative predictive values of IPS were 100%, 84.6%, 80%, and 100%, respectively. CONCLUSION: We show that IPS can be a useful tool to identify the mechanism and guide treatment of a chronic thrombocytopenia increasing the bleeding risk in patients with MDS.
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Combining drugs could be an effective option for treating multirefractory ITP, that is, patients not responding to rituximab, thrombopoietin receptor agonists (TPO-RA) and splenectomy. We conducted a retrospective, multicenter, observational study including multirefractory ITP patients who received a combination of a TPO-RA and an immunosuppressive drug. We included 39 patients (67% women, median age 59 years [range 21-96]), with a median ITP duration of 57 months [3-393] and a median platelet count at initiation of 10 × 109 /L [1-35]. The combination regimen was given for a median duration of 12 months [1-103] and included eltrombopag (51%) or romiplostim (49%), associated with mycophenolate mofetil (54%), azathioprine (36%), cyclophosphamide (5%), cyclosporin (3%) or everolimus (3%). Overall, 30 patients (77%) achieved at least a response (platelet count ≥30 × 109 /L and at least doubling baseline during at least 3 months), including 24 complete responses (platelet count >100 × 109 /L during at least 3 months) with a median time to response of 30 days [7-270] and a median duration of response of 15 months [4-63]. Severe adverse event related to ITP treatment was observed in 31%. In conclusion, this study confirms that some patients with multirefractory ITP can achieve long lasting response with this combination.
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Púrpura Trombocitopénica Idiopática , Humanos , Adulto , Femenino , Adulto Joven , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Masculino , Púrpura Trombocitopénica Idiopática/tratamiento farmacológico , Púrpura Trombocitopénica Idiopática/inducido químicamente , Receptores de Trombopoyetina/agonistas , Estudios Retrospectivos , Recuento de Plaquetas , Rituximab/efectos adversos , Receptores Fc/uso terapéutico , Trombopoyetina/efectos adversos , Benzoatos/uso terapéutico , Hidrazinas/efectos adversos , Proteínas Recombinantes de Fusión/efectos adversosRESUMEN
The emergence of rituximab biosimilars offers the prospect of significant savings to the healthcare system. However, these drugs have never been evaluated for treating immune thrombocytopenia (ITP). This was an observational, matched study. We included adults who received a rituximab biosimilar for ITP. Each rituximab-naïve biosimilar patient was matched with two controls from the historic ITP-ritux registry. For non-naïve patients, we compared the response to the biosimilar with that observed with the reference product. Response status was defined according to international criteria. We included 107 patients; 55 receiving Rixathon™ and 52 Truxima™. Three months after the first infusion of rituximab biosimilars, the overall response rate was 47/74 (63.5%) versus 76/142 (53.5%) for the matched controls receiving the reference product (p = .13). The 3-month overall response rate was 76.5% for Rixathon™ versus 51.5% for the matched control group (p = .01) and 21/40 (52.5%) for Truxima™ versus 41/74 (55.4%) for the matched controls (p = .81). For non-naïve patients, the response pattern was similar to that observed previously with the reference product. Safety was analogous to that observed with the reference product. Rituximab biosimilars seemed safe and effective for ITP treatment.
What is the context? Immune thrombocytopenia (ITP) is an autoimmune disease defined by a low platelet count without any other cause of thrombocytopenia. Patients with ITP may experience severe bleedings.Rituximab, a biotechnological therapy, is a valid second-line treatment option for ITP.Biotechnological therapies are expensive. Because the patent expiratory date of the reference product of Rituximab expired, highly similar drugs called biosimilars have been developed and used in ITP treatment without any direct evaluation in this particular disease.What is new? In this study, we evaluate the efficacy and safety of rituximab biosimilars versus the reference product for treating adult ITPWe included adults who received a rituximab biosimilar for ITP. Each rituximab-naïve biosimilar patient was matched with two controls from a historic registry that included ITP patients treated by the reference product. For non-naïve patients, we compared the response to the biosimilar with that observed with the reference product.For naïve and non-naïve patients, the response pattern was similar to that observed previously with the reference product. Safety was analogous to that observed with the reference product.What is the impact? This study provides further evidence that rituximab biosimilars are safe and effective for immune thrombocytopenia treatment.
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Biosimilares Farmacéuticos , Púrpura Trombocitopénica Idiopática , Trombocitopenia , Adulto , Humanos , Rituximab/uso terapéutico , Biosimilares Farmacéuticos/uso terapéutico , Púrpura Trombocitopénica Idiopática/tratamiento farmacológico , Trombocitopenia/tratamiento farmacológicoRESUMEN
Insulin amyloidosis is a rare form of localized amyloidosis due to insulin aggregation into subcutaneous amyloid fibrils. We describe the case of a 55 years old male with insulin-requiring type 1 diabetes presenting with two non-inflammatory intra-dermal nodules associated with local lymph node enlargement. Diagnosis was confirmed by Congo red coloration of the amyloid deposit and insulin protein identification on mass spectrometry. Insulin amyloidosis is a potential complication of repeated subcutaneous insulin injections. The main risk factor is the intrinsic characteristic of the insulin used. Insulin amyloidosis leads to systemic metabolic consequences such as chronic hyperglycemia or unpredictable hypoglycemia, as well as unesthetic cutaneous lumps or abscesses. Standard-of-care is yet to be defined but mainly rely on therapeutical education of insulin injections, while surgical excision is reported to improve glycemic control in some patients.
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Immune thrombocytopenia (ITP) is defined by a low platelet count that can trigger potentially life-threatening haemorrhages. Three-quarters of adult patients exhibit persistent or chronic disease and require second-line treatments. Among these, rituximab, an anti-CD20 antibody, has yielded valuable results, with global responses in 60% of patients at 6 months and complete responses in 30% at 5 years. Factors predictive of response to ITP therapy would help physicians choose optimal treatments. We retrospectively analysed clinical courses, biological markers and blood lymphocyte subset numbers of 72 patients on rituximab to treat persistent/chronic ITP followed-up in our department between 2007 and 2021, divided into three groups according to the platelet count at 6 months: complete, partial or no response. Among all studied parameters, a low number of CD3- CD16+ CD56+ circulating NK cells was associated with the complete response to rituximab. We also found that, after rituximab therapy, complete responders exhibited increased NK and decreased activated CD8+ T cell percentages. These results emphasize that the role played by NK cells in ITP remains incompletely known but that factors predictive of response to rituximab can be easily derived using blood lymphocyte subset data.
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Púrpura Trombocitopénica Idiopática , Trombocitopenia , Humanos , Adulto , Rituximab/uso terapéutico , Púrpura Trombocitopénica Idiopática/tratamiento farmacológico , Estudios Retrospectivos , Células Asesinas NaturalesRESUMEN
Background: JAK2 V617F and Calreticulin (CALR) mutations are the most frequent molecular causes of Phi-negative myeloproliferative neoplasms (MPN). Patients with CALR mutations are at lower risk of thrombosis than patients with JAK2 V617F. We hypothesized that CALR-mutated blood platelets would have platelet function defects that might explain why these patients are at lower risk of thrombosis. Objectives: Our main objective was to explore and compare platelet function depending on the MPN molecular marker. Methods: We analyzed platelet function in 16 patients with MPN with CALR mutations and 17 patients with JAK2 V617F mutation and compared them with healthy controls. None of these patients was taking antiplatelet therapy. We performed an extensive analysis of platelet function and measured plasmatic soluble P-selectin and CD40L levels. Results: We observed significant defects in platelet aggregation, surface glycoprotein expression, fibrinogen binding, and granule content in platelets from patients with MPN compared with that in controls. Moreover, soluble CD40L and P-selectin levels were elevated in patients with MPN compared with that in controls, suggesting an in vivo platelet preactivation. Comparison of platelet function between patients with CALR and JAK2 V617F MPN revealed only minor differences in platelets from patients with CALR. However, these results need to be interpreted within the context of absence of an inflammatory environment that could impact platelet function during MPN. Conclusions: These results do not support the hypothesis that calreticulin-mutated platelets have platelet function defects that could explain the lower thrombotic risk of patients with CALR.
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Sustained response off treatment (SROT) after thrombopoietin receptor agonist (TPO-RA) discontinuation has been reported in immune thrombocytopenia (ITP). This prospective multicenter interventional study enrolled adults with persistent or chronic primary ITP and complete response (CR) on TPO-RAs. The primary end point was the proportion of patients achieving SROT (platelet count >30 × 109/L and no bleeding) at week 24 (W24) with no other ITP-specific medications. Secondary end points included the proportion of sustained CR off-treatment (SCROT, platelet count >100 × 109/L and no bleeding) and SROT at W52, bleeding events, and pattern of response to a new course of TPO-RAs. We included 48 patients with a median age of 58.5 years; 30 of 48 had chronic ITP at TPO-RA initiation. In the intention-to-treat analysis, 27 of 48 achieved SROT, 15 of 48 achieved SCROT at W24; 25 of 48 achieved SROT, and 14 of 48 achieved SCROT at W52. No severe bleeding episode occurred in patients who relapsed. Among patients rechallenged with TPO-RA, 11 of 12 achieved CR. We found no significant clinical predictors of SROT at W24. Single-cell RNA sequencing revealed enrichment of a tumor necrosis factor α signaling via NF-κB signature in CD8+ T cells of patients with no sustained response after TPO-RA discontinuation, which was further confirmed by a significant overexpression of CD69 on CD8+ T cells at baseline in these patients as compared with those achieving SCROT/SROT. Our results strongly support a strategy based on progressive tapering and discontinuation of TPO-RAs for patients with chronic ITP who achieved a stable CR on treatment. This trial was registered at www.clinicaltrials.gov as #NCT03119974.
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Púrpura Trombocitopénica Idiopática , Trombocitopenia , Adulto , Humanos , Persona de Mediana Edad , Estudios Prospectivos , Púrpura Trombocitopénica Idiopática/tratamiento farmacológico , Recuento de Plaquetas , Trombocitopenia/tratamiento farmacológico , Autoinmunidad , Trombopoyetina/uso terapéutico , Proteínas Recombinantes de Fusión/uso terapéutico , Receptores Fc/uso terapéutico , Hidrazinas/uso terapéuticoRESUMEN
Introduction: Coronavirus disease 2019 (COVID-19) can cause life-threatening acute respiratory distress syndrome (ARDS). Recent data suggest a role for neutrophil extracellular traps (NETs) in COVID-19-related lung damage partly due to microthrombus formation. Besides, pulmonary embolism (PE) is frequent in severe COVID-19 patients, suggesting that immunothrombosis could also be responsible for increased PE occurrence in these patients. Here, we evaluate whether plasma levels of NET markers measured shorty after admission of hospitalized COVID-19 patients are associated with clinical outcomes in terms of clinical worsening, survival, and PE occurrence. Patients and Methods: Ninety-six hospitalized COVID-19 patients were included, 50 with ARDS (severe disease) and 46 with moderate disease. We collected plasma early after admission and measured 3 NET markers: total DNA, myeloperoxidase (MPO)-DNA complexes, and citrullinated histone H3. Comparisons between survivors and non-survivors and patients developing PE and those not developing PE were assessed by Mann-Whitney test. Results: Analysis in the whole population of hospitalized COVID-19 patients revealed increased circulating biomarkers of NETs in patients who will die from COVID-19 and in patients who will subsequently develop PE. Restriction of our analysis in the most severe patients, i.e., the ones who enter the hospital for COVID-19-related ARDS, confirmed the link between NET biomarker levels and survival but not PE occurrence. Conclusion: Our results strongly reinforce the hypothesis that NETosis is an attractive therapeutic target to prevent COVID-19 progression but that it does not seem to be linked to PE occurrence in patients hospitalized with COVID-19.
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COVID-19 , Trampas Extracelulares , Embolia Pulmonar , Síndrome de Dificultad Respiratoria , Biomarcadores , COVID-19/complicaciones , Humanos , Embolia Pulmonar/etiología , Síndrome de Dificultad Respiratoria/etiologíaRESUMEN
BACKGROUND: Acquired von Willebrand syndrome (AVWS) is frequent in patients with myeloproliferative neoplasms (MPNs). For von Willebrand factor (VWF) functional evaluation, ristocetin cofactor activity by aggregometry (VWF:RCo) is considered the gold standard but has limitations, and automated activity measurement has been developed such as the HemosIL VWF:RCo Werfen with particle agglutination (VWF:GPIbR). OBJECTIVES: To evaluate the performance of VWF:GPIbR with HemosIL VWF:RCo Werfen (VWF:GPIbR) versus VWF:RCo in patients with thrombocytosis in the context of MPNs (T-MPNs) and in patients with secondary thrombocytosis (ST). METHODS: MPN patients with thrombocytosis >450 G/L (T-MPNs) were compared with patients with ST due to inflammation or iron deficiency. VWF activity (VWF:Act) was analyzed using VWF:RCo or VWF:GPIbR. VWF analysis was completed by analysis of VWF multimers and VWF collagen binding (CB) assay (VWF:CB). RESULTS: A total of 33 T-MPNs and 18 ST patients were included. Compared with aggregometry, evaluation of VWF:Act by VWF:GPIbR led to lower values in T-MPN patients, but also in ST patients. Interestingly, although the VWF:RCo/VWF:Ag ratio did not reveal differences between T-MPNs and ST patients, the VWF:GPIbR/VWF:Ag ratio analysis allowed us to suspect AVWS only in T-MPN patients. Using the distribution of VWF multimer analysis and VWF:CB, we here demonstrated that VWF:GPIbR allows AVWS diagnosis in nine T-MPNs as opposed to aggregometry. CONCLUSION: Evaluation of VWF:Act using VWF:GPIbR has a greater sensitivity compared with aggregometry to detect AVWS in T-MPN patients.
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Neoplasias , Trombocitosis , Enfermedades de von Willebrand , Colágeno/metabolismo , Humanos , Enfermedades de von Willebrand/diagnóstico , Factor de von Willebrand/metabolismoRESUMEN
Thrombotic microangiopathy (TMA) gathers consumptive thrombocytopenia, mechanical haemolytic anemia, and organ damage. Hemolytic uremic syndromes (HUS) are historically classified as primary or secondary to another disease once thrombotic thrombocytopenic purpura (TTP), Shiga-toxin HUS, and cobalamin C-related HUS have been ruled out. Complement genetics studies reinforced the link between complement dysregulation and primary HUS, contributing to reclassifying some pregnancy- and/or post-partum-associated HUS and to revealing complement involvement in severe and/or refractory hypertensive emergencies. By contrast, no firm evidence allows a plausible association to be drawn between complement dysregulation and Shiga-toxin HUS or other secondary HUS. Nevertheless, rare complement gene variants are prevalent in healthy individuals, thus providing an indication that an investigation into complement dysregulation should be carefully balanced and that the results should be cautiously interpreted with the help of a trained geneticist. Several authors have suggested reclassifying HUS in two entities, regardless of they are complement-mediated or not, since the use of eculizumab, an anti-C5 antibody, dramatically lowers the proportion of patients who die or suffer from end-stage renal disease within the year following diagnosis. Safety and the ideal timing of eculizumab discontinuation is currently under investigation, and the long-term consequences of HUS should be closely monitored over time once patients exit emergency departments.