Immunotherapy medications that target programmed death 1 protein (PD-1) and programmed death-ligand 1 (PD-L1), such as nivolumab, pembrolizumab, and atezolizumab, are currently used in the first- or ...second-line treatment of non-small cell lung cancers, among other indications. However, these agents are associated with immune-related side effects, the most common of which are endocrinopathies, colitis, hepatitis, and interstitial pneumonitis. In contrast, coronary toxicities are rarely reported and remain poorly understood. Here, we describe the case of a patient who developed an acute coronary syndrome when treated with nivolumab as second-line therapy for metastatic pulmonary adenocarcinoma. A review of the literature, the French pharmacovigilance registry, and the World Health Organization pharmacovigilance database led to the identification of four cases of patients with coronary manifestations attributable to anti-PD1 immunotherapy (with no reported cases of patients undergoing anti-PD-L1 immunotherapy), which we describe herein. The potential mechanisms causing adverse coronary reactions to this type of therapy, which is used to treat lung cancer as well as other solid and hematological neoplastic diseases, are also discussed.
Immunotherapy is becoming a standard of care for many cancers. Immune-checkpoint inhibitors (ICI) can generate immune-related adverse events. Interstitial lung disease (ILD) has been identified as a ...rare but potentially severe event.Between December 2015 and April 2016, we conducted a retrospective study in centres experienced in ICI use. We report the main features of ICI-ILD with a focus on clinical presentation, radiological patterns and therapeutic strategies.We identified 64 (3.5%) out of 1826 cancer patients with ICI-ILD. Patients mainly received programmed cell death-1 inhibitors. ILD usually occurred in males, and former or current smokers, with a median age of 59 years. We observed 65.6% grade 2/3 severity, 9.4% grade 4 severity and 9.4% fatal ILD. The median (range) time from initiation of immunotherapy to ILD was 2.3 (0.2-27.4) months. Onset tended to occur earlier in lung cancer
melanoma: median 2.1 and 5.2 months, respectively (p=0.02). Ground-glass opacities (81.3%) were the predominant lesions, followed by consolidations (53.1%). Organising pneumonia (23.4%) and hypersensitivity pneumonitis (15.6%) were the most common patterns. Overall survival at 6 months was 58.1% (95% CI 37.7-73.8%).ICI-ILD often occurs early and displays suggestive radiological features. As there is no clearly identified risk factor, oncologists need to diagnose and adequately treat this adverse event.
Immunotherapy is becoming a standard of care for many cancers. Immune-checkpoint inhibitors (ICI) can generate immune-related adverse events. Interstitial lung disease (ILD) has been identified as a ...rare but potentially severe event.Between December 2015 and April 2016, we conducted a retrospective study in centres experienced in ICI use. We report the main features of ICI–ILD with a focus on clinical presentation, radiological patterns and therapeutic strategies.We identified 64 (3.5%) out of 1826 cancer patients with ICI–ILD. Patients mainly received programmed cell death-1 inhibitors. ILD usually occurred in males, and former or current smokers, with a median age of 59 years. We observed 65.6% grade 2/3 severity, 9.4% grade 4 severity and 9.4% fatal ILD. The median (range) time from initiation of immunotherapy to ILD was 2.3 (0.2−27.4) months. Onset tended to occur earlier in lung cancer versus melanoma: median 2.1 and 5.2 months, respectively (p=0.02). Ground-glass opacities (81.3%) were the predominant lesions, followed by consolidations (53.1%). Organising pneumonia (23.4%) and hypersensitivity pneumonitis (15.6%) were the most common patterns. Overall survival at 6 months was 58.1% (95% CI 37.7–73.8%).ICI–ILD often occurs early and displays suggestive radiological features. As there is no clearly identified risk factor, oncologists need to diagnose and adequately treat this adverse event.
Introduction
L-group histiocytosis (Erdheim-Chester disease (ECD) and Langerhans-cell histiocytosis (LCH)) are multi-system diseases characterized by histiocyte infiltration in several organs. These ...histiocytes frequently harbor activating somatic mutations of the MAP Kinase pathway. Many of these mutations are frequently associated with a specific phenotype: BRAF V600Emutated ECD patients have more frequently cardiac and vascular involvements, MAP2K1 mutated ECD patients may exhibit overt Rosai-Dorfman Disease (RDD) component, and ALK-mutated patients have a high prevalence of neurological involvement. Our objective was to describe characteristics of patients with histiocytosis and a particular BRAF-deletion mutation.
Methods
We performed a retrospective multi-center study. Patients were identified through the Histiocytosis national referral center pathology laboratory in Ambroise-Paré Hospital (Boulogne-Billancourt) in which all suspected diagnosis of histiocytosis samples are sent for proofreading and sequencing. Samples are sequenced with a specific panel next generation sequencing. We identified patients with BRAFdel mutations and contacted the centers for clinical, morphological, and biological datas.
Results
Twenty-four patients with a BRAFdel mutation were identified. Data were available for 18 of them. Most patients (n=17) had LCH (one with an ECD component) and one had an ECD. Median age at diagnosis was 50 years (IQR 35-78). The most frequent manifestations were hepatic (n=8, 44%) and vulvar (8/10 female gender patients, 80%). Other manifestations were cystic interstitial lung disease (n=6), lytic bone lesions (n=7), diabetes insipidus (n=6), panhypopituitarism (n=3), pachymeningitis (n=2), long bone osteosclerosis (n=1), perirenal infiltration (n=1), salivary gland infiltration (n=1) and digestive track infiltration (n=1). Hepatic manifestation was sclerosing cholangitis in all patients, and 5/6 patients had histiocytic infiltration in liver biopsy. All patients with sclerosing cholangitis had biological cholestasis, elevated aminotransferases, and hyperbilirubinemia. No patient had cirrhosis. Hepatic MRI, when performed, always showed cholangitis (5/5). PET-scan showed liver abnormalities in 4/6 patients (heterogenous liver uptake or uptake in biliary ducts). First line treatments included vinblastine (n=5), aracytine (n=1), methotrexate (n=1), cladribine (n=1) and cobimetinib (n=1). Nine patients did not receive any treatment. Two patients received cobimetinib, that resulted in partial remission and stable disease at 6 months. After a median follow-up of 43 (IQR 11-315 months), one patient had died from unknown cause.
Conclusion
BRAF-deletion mutations in histiocytoses are associated with a specific LCH pattern with high prevalence of hepatic and vulvar involvements. These manifestations should be carefully screened in these patients.
OBJECTIVEThe gene mutations responsible for ABCA3 protein deficiency are involved in respiratory distress of the newborn and much more rarely in adult interstitial lung diseases (ILD). An adult ...patient homozygous for a complex allele encompassing the p.Ala1027Pro likely pathogenic mutation and the p.Gly974Asp variation was followed for a late-onset and fibrotic ILD. The evolution was marked by progressive clinical and functional degradation despite corticosteroid pulses. The patient, who was first registered on the list for lung transplantation, was improved quickly and persistently for at least 6.5 years with hydroxychloroquine treatment, allowing removal from the transplant list.
Since the latest 2017 French guidelines, knowledge about idiopathic pulmonary fibrosis has evolved considerably.
Practical guidelines were drafted on the initiative of the Coordinating Reference ...Center for Rare Pulmonary Diseases, led by the French Language Pulmonology Society (SPLF), by a coordinating group, a writing group, and a review group, with the involvement of the entire OrphaLung network, pulmonologists practicing in various settings, radiologists, pathologists, a general practitioner, a health manager, and a patient association. The method followed the "Clinical Practice Guidelines" process of the French National Authority for Health (HAS), including an online vote using a Likert scale.
After a literature review, 54 guidelines were formulated, improved, and then validated by the working groups. These guidelines addressed multiple aspects of the disease: epidemiology, diagnostic procedures, quality criteria and interpretation of chest CT scans, lung biopsy indication and procedures, etiological workup, methods and indications for family screening and genetic testing, assessment of the functional impairment and prognosis, indication and use of antifibrotic agents, lung transplantation, management of symptoms, comorbidities and complications, treatment of chronic respiratory failure, diagnosis and management of acute exacerbations of fibrosis.
These evidence-based guidelines are intended to guide the diagnosis and practical management of idiopathic pulmonary fibrosis.
Background: Since the latest 2017 French guidelines, knowledge about idiopathic pulmonary fibrosis has evolved considerably.Methods: Practical guidelines were drafted on the initiative of the ...Coordinating Reference Center for Rare Pulmonary Diseases, led by the French Language Pulmonology Society (SPLF), by a coordinating group, a writing group, and a review group, with the involvement of the entire OrphaLung network, pulmonologists practicing in various settings, radiologists, pathologists, a general practitioner, a health manager, and a patient association. The method followed the "Clinical Practice Guidelines" process of the French National Authority for Health (HAS), including an online vote using a Likert scale.Results: After a literature review, 54 guidelines were formulated, improved, and then validated by the working groups. These guidelines addressed multiple aspects of the disease: epidemiology, diagnostic procedures, quality criteria and interpretation of chest CT scans, lung biopsy indication and procedures, etiological workup, methods and indications for family screening and genetic testing, assessment of the functional impairment and prognosis, indication and use of antifibrotic agents, lung transplantation, management of symptoms, comorbidities and complications, treatment of chronic respiratory failure, diagnosis and management of acute exacerbations of fibrosis.Conclusion: These evidence-based guidelines are intended to guide the diagnosis and practical management of idiopathic pulmonary fibrosis
Alzheimer diseases and related disorders (ADRD) remain a major public health issue. The progression of the disease is dominated by behavioral and psychological symptoms of dementia (BPSD) which are ...frequent and burdensome for caregivers. The aim of our survey was to study how the general practionner managed these behavioral disturbances (particularly agitation and aggressiveness) in community living patients with ADRD and support of their main caregivers. We based our study on a medical survey sent to all general practitioners (GP) practicing in four districts in Marseille near from a secure unit. Ninety five out of 260 answered to the survey and 57 had already been exposed to patients' behavioral decompensation. For these BPSD management, atypical neuroleptics and benzodiazepines were mostly prescribed, and according to the literature and guidelines. Half of the GP's recognized the weak effectiveness of this strategy. Almost all of them are interested in having a document summarizing the main strategy to be set up or a possibility to call a specialized mobile team with doctors and professionals caregivers. A few dedicated consultations were devoted to informal caregivers whereas GP were aware of negative effects of these decompensations on them. This study point out difficulties for GP to provide appropriate management for their patients with ADRD living at home and for their informal caregivers, particularly during acute behavioral disturbance, despite their practical knowledges.
Introduction
Pompe disease is caused by a rare biallelic mutation in the
GAA
gene resulting in acid α-glucosidase deficiency and glycogen accumulation.
Aim
We analyzed hospital admissions associated ...with the administration of Myozyme®, utilizing the French hospital discharge database, known in France as the
Programme de Médicalisation des Systèmes d'Information
(PMSI), which comprehensively captures all hospital activity within the country.
Methods
In this observational study, we examined hospitalization records from April 4, 2012, to December 31, 2019, within the PMSI database, focusing on admissions where Myozyme® was administered. We particularly investigated the incidence of critical care admissions and adverse events (AEs) related to Myozyme®.
Results
From 2012 to 2019, approximately 26,714 hospital stays involving Myozyme® administration were recorded for 239 patients. Most (96.6%) of these were outpatient stays, with only 3.2% in critical care. Furthermore, hospitalizations without critical care needs increased from 96% in 2012 to 99% in 2019. Of the patients receiving at least one infusion, 997 critical care admissions were recorded, with 781 (78.3%) occurring concurrent with or the day after the Myozyme® treatment without directly correlating to adverse effects of enzyme therapy.
Conclusions
The analysis of the French hospital discharge database indicated that Myozyme® was associated with a low incidence of AEs and complications in a hospital context, supporting the consideration of its safe use in home-infusion settings.
Background
To describe the clinical, pathological, and molecular characteristics of late‐onset (LO) dysferlinopathy patients.
Methods
Retrospective series of patients with LO dysferlinopathy, defined ...by an age at onset of symptoms ≥30 years, from neuromuscular centers in France and the International Clinical Outcome Study for dysferlinopathy (COS). Patients with early‐onset (EO) dysferlinopathy (<30 years) were randomly selected from the COS study as a control group, and the North Star Assessment for Dysferlinopathy (NSAD) and Activity Limitation (ACTIVLIM) scores were used to assess functionality. Muscle biopsies obtained from 11 LO and 11 EO patients were revisited.
Results
Forty‐eight patients with LO dysferlinopathy were included (28 females). Median age at onset of symptoms was 37 (range 30–57) years and most patients showed a limb‐girdle (n = 26) or distal (n = 10) phenotype. However, compared with EO dysferlinopathy patients (n = 48), LO patients more frequently showed atypical phenotypes (7 vs. 1; p = 0.014), including camptocormia, lower creatine kinase levels (2855 vs. 4394 U/L; p = 0.01), and higher NSAD (p = 0.008) and ACTIVLIM scores (p = 0.016). Loss of ambulation in LO patients tended to occur later (23 ± 4.4 years after disease onset vs. 16.3 ± 6.8 years; p = 0.064). Muscle biopsy of LO patients more frequently showed an atypical pattern (unspecific myopathic changes) as well as significantly less necrosis regeneration and inflammation. Although LO patients more frequently showed missense variants (39.8% vs. 23.9%; p = 0.021), no differences in dysferlin protein expression were found on Western blot.
Conclusions
Late‐onset dysferlinopathy patients show a higher frequency of atypical presentations, are less severely affected, and show milder dystrophic changes in muscle biopsy.
Late‐onset dysferlinopathy patients show a higher frequency of atypical presentations, including camptocormia, and are less severely affected compared with early‐onset patients. Furthermore, they present less necrosis and inflammation in muscle biopsy.
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