Light chain amyloidosis

Light chain amyloidosis (AL) is the most common subtype of amyloidosis except wild type tranthyretine amyloidosis and is caused by the deposition of misfolded monoclonal light chains of immunoglobulins produced by a monoclonal B cell, mainly of plasma cell origin. Affected patients may present with amyloidosis alone or in association with other plasma cell or lymphoid dyscrasias (multiple myeloma, Waldenström macroglobulinemia or other B lymphoma). Diagnosis of amyloidosis is histological. Cardiac and renal involvement are the most frequent and present in nearly two thirds of patients as hypertrophic heart disease and/or nephrotic syndrome, respectively. AL amyloidosis is a clonal plasma cell disorder and is treated by chemotherapy dedicated to eradicate the underlying clone. Assessment of the severity of the disease with the Mayo Clinic score is used to guide the choice of treatment. First-line treatment combine bortezomib, cyclophosphamide or melphalan and dexamethasone for severe cases, plus or minus daratumumab, an anti-CD-38 monoclonal antibody, following the excellent results of the ANDROMEDA phase 3 study; mild cases can still benefit from melphalan and dexamethasone

Erythroferrone and hepcidin as mediators between erythropoiesis and iron metabolism during allogeneic hematopoietic stem cell transplant.

Hematopoietic cell transplantation (HCT) brings important alterations in erythropoiesis and iron metabolism. Hepcidin, which regulates iron metabolism, increases in iron overload or inflammation and decreases with iron deficiency or activated erythropoiesis. Erythroferrone (ERFE) is the erythroid regulator of hepcidin. We investigated erythropoiesis and iron metabolism after allogeneic HCT in 70 patients randomized between erythropoietin (EPO) treatment or no EPO, by serially measuring hepcidin, ERFE, CRP (inflammation), soluble transferrin receptor (sTfR, erythropoiesis), serum iron and transferrin saturation (Tsat; iron for erythropoiesis) and ferritin (iron stores). We identified biological and clinical factors associated with serum hepcidin and ERFE levels. Serum ERFE correlated overall with sTfR and reticulocytes and inversely with hepcidin. Erythroferrone paralleled sTfR levels, dropping during conditioning and recovering with engraftment. Inversely, hepcidin peaked after conditioning and decreased during engraftment. Erythroferrone and hepcidin were not significantly different with or without EPO. Multivariate analyses showed that the major determinant of ERFE was erythropoiesis (sTfR, reticulocytes or serum Epo). Pretransplant hepcidin was associated with previous RBC transfusions and ferritin. After transplantation, the major determinants of hepcidin were iron status (ferritin at all time points and Tsat at day 56) and erythropoiesis (sTfR or reticulocytes or ERFE), while the impact of inflammation was less clear and clinical parameters had no detectable influence. Hepcidin remained significantly higher in patients with high compared to low pretransplant ferritin. After allogeneic HCT with or without EPO therapy, significant alterations of hepcidin occur between pretransplant and day 180, in correlation with iron status and inversely with erythroid ERFE

Peri-operative red blood cell transfusion in neonates and infants: NEonate and Children audiT of Anaesthesia pRactice IN Europe: A prospective European multicentre observational study

BACKGROUND: Little is known about current clinical practice concerning peri-operative red blood cell transfusion in neonates and small infants. Guidelines suggest transfusions based on haemoglobin thresholds ranging from 8.5 to 12 g dl-1, distinguishing between children from birth to day 7 (week 1), from day 8 to day 14 (week 2) or from day 15 (≥week 3) onwards. OBJECTIVE: To observe peri-operative red blood cell transfusion practice according to guidelines in relation to patient outcome. DESIGN: A multicentre observational study. SETTING: The NEonate-Children sTudy of Anaesthesia pRactice IN Europe (NECTARINE) trial recruited patients up to 60 weeks' postmenstrual age undergoing anaesthesia for surgical or diagnostic procedures from 165 centres in 31 European countries between March 2016 and January 2017. PATIENTS: The data included 5609 patients undergoing 6542 procedures. Inclusion criteria was a peri-operative red blood cell transfusion. MAIN OUTCOME MEASURES: The primary endpoint was the haemoglobin level triggering a transfusion for neonates in week 1, week 2 and week 3. Secondary endpoints were transfusion volumes, 'delta haemoglobin' (preprocedure - transfusion-triggering) and 30-day and 90-day morbidity and mortality. RESULTS: Peri-operative red blood cell transfusions were recorded during 447 procedures (6.9%). The median haemoglobin levels triggering a transfusion were 9.6 [IQR 8.7 to 10.9] g dl-1 for neonates in week 1, 9.6 [7.7 to 10.4] g dl-1 in week 2 and 8.0 [7.3 to 9.0] g dl-1 in week 3. The median transfusion volume was 17.1 [11.1 to 26.4] ml kg-1 with a median delta haemoglobin of 1.8 [0.0 to 3.6] g dl-1. Thirty-day morbidity was 47.8% with an overall mortality of 11.3%. CONCLUSIONS: Results indicate lower transfusion-triggering haemoglobin thresholds in clinical practice than suggested by current guidelines. The high morbidity and mortality of this NECTARINE sub-cohort calls for investigative action and evidence-based guidelines addressing peri-operative red blood cell transfusions strategies. TRIAL REGISTRATION: ClinicalTrials.gov, identifier: NCT02350348

Anemia in patients with severe chronic obstructive pulmonary disease, a comorbity more common than previously thought

peer reviewedIl est classiquement rapporté qu’une polycythémie survient en réponse à une hypoxémie chez les patients souffrant de BPCO sévère. Néanmoins, certaines données récentes ont souligné la présence d’une anémie dans une proportion non négligeable de cas. Nous avons évalué, dans une étude rétrospective, la prévalence des troubles de l’érythropoïèse au sein d’une cohorte de 100 patients BPCO stables (de stade II à IV selon la classification de GOLD). Une anémie était présente chez 31 % de ces sujets tandis qu’une polycythémie était retrouvée dans 15 % des cas. L’anémie était plus souvent observée dans le sexe masculin. Une corrélation inverse existait entre le taux d’hémoglobine et la CRP (r=-0.56, p < 0.0001). Les BPCO avec anémie avaient été plus souvent hospitalisés pour exacerbation au cours de l’année précédente (p < 0.05). L’anémie est plus fréquente que la polycythémie chez le patient BPCO sévère; elle est associée à une inflammation systémique et à une tendance accrue aux hospitalisations pour exacerbation.Chronic obstructive pulmonary disease (COPD) is traditionally associated with polycythemia which results from chronic hypoxemia. Nevertheless, recent studies have shown that anemia may be more frequent than expected in patients with COPD. In this retrospective study, we investigated the prevalence of hemoglobin disorders in a cohort of 100 patients with stable, moderate to severe COPD (II to IV GOLD classification). We identified 31 % patients with anemia while only 15 % had polycythemia. Anemia was more frequent in male patients. We also demonstrated a negative correlation between hemoglobin and CRP levels (R=-0.56, p < 0.0001). COPD patients with anemia had experienced a higher rate of hospitalizations for exacerbation in the previous year than those with polycythemia (p < 0.05). Anemia is a frequent comorbidity in COPD; it is associated with systemic inflammation and a propensity to hospitalization for exacerbation

Amylose à chaînes légères (AL)

L’amylose à chaînes légères (AL) est le sous-type le plus fréquent d’amylose en dehors des amyloses par dépôts de transthyrétine non mutée (amylose sénile). Elle est caractérisée par des dépôts de chaînes légères monoclonales d’immunoglobulines mal conformées, produites par un clone B, le plus souvent plasmocytaire. Environ 60% des patients ont une immunoglobuline monoclonale isolée (MGUS) et 40% un myélome qui est le plus souvent de stade I ; moins de 10% des patients ont une prolifération plutôt lymphoïde ou lympho plamocytaire associée en général à une IgM. Le diagnostic des différentes amyloses est histologique. Les atteintes cardiaques et rénales sont les plus fréquentes et se présentent sous la forme d’une cardiopathie hypertrophique et/ou d’un syndrome néphrotique. Le traitement de l'amylose AL vise à éradiquer le clone secrétant les chaînes légères amyloïdogènes. L’évaluation de la sévérité de la maladie (selon le score de la Mayo clinic*) permet d’orienter le choix thérapeutique. Le traitement de première intention comprend du bortezomib associé au cyclophosphamide ou au melphalan et à la dexamethasone pour les atteintes sévères, plus ou moins associé au daratumumab, un anticorps monoclonal anti-CD 38 ayant démontré d’excellent résultats dans l’étude de phase 3 ANDROMEDA; pour les cas peu sévères l’association du melphalan et de la dexamethasone est toujours une excellente alternative

Ce n'était pas une myasthénie

peer reviewedUn patient de 49 ans se présente à la consultation en raison d’une dyspnée. Il se dit fatiqué. La mise au point initiale habituellement entreprise en pareilles circonstances se révèle peu contributive. Le tableau se complique par la survenue de symptômes neurologiques

Granulomatosis With Polyangiitis in a Patient on Programmed Death-1 Inhibitor for Advanced Non-small-cell Lung Cancer.

Objectives: To contribute to a precise and thorough knowledge of immune-related adverse events (irAE) induced by immune checkpoint inhibitors (ICI) and to emphasize the importance of this specific form of toxicity in terms of potential predictive value and long-term effects. Materials and Methods: We report the first case of granulomatosis with polyangiitis (GPA) in a patient treated with an anti-Programmed Death protein-1 (PD-1) antibody for advanced non-small-cell lung cancer (NSCLC). Results: After a single dose of this drug the patient showed severe myositis associated with a high anti-PR3 anti-neutrophil cytoplasmic antibody titer. Discontinuation of the anti-PD-1 and introduction of corticoids led to a remission of the irAE. Regarding tumor a partial response was noted. A year later a neutrophilic, sterile pleural exudate and cutaneous lesions appeared with the pathological findings of neutrophilic vasculitis. Retreatment with corticoids induced a new remission of symptoms. It remains unclear whether GPA was preexisting and clinically silent but revealed by the use of ICI or primarily induced by this treatment. Conclusions: irAE are rare when anti-PD-1 antibodies are used in monotherapy. They present with a distinct clinical picture and temporal course and require specific treatment. Patients with irAE usually have a favorable oncological outcome