Benefit of phlebotomy and low-dose aspirin in the prevention of vascular events in patients with EPOR primary familial polycythemia on the island of New Caledonia.

Not available.

Microbiome of Ceca from Broiler Chicken Vaccinated or Not against Coccidiosis and Fed Berry Pomaces.

American cranberry (Vaccinium macrocarpon) and lowbush/wild blueberry (V. angustifolium) pomace are polyphenol-rich products having potentially beneficial effects in broiler chickens. This study investigated the cecal microbiome of broiler-vaccinated or non-vaccinated birds against coccidiosis. Birds in each of the two groups (vaccinated or non-vaccinated) were fed a basal non-supplemented diet (NC), a basal diet supplemented with bacitracin (BAC), American cranberry (CP), and lowbush blueberry (BP) pomace alone or in combination (CP + BP). At 21 days of age, cecal DNA samples were extracted and analyzed using both whole-metagenome shotgun sequencing and targeted-resistome sequencing approaches. Ceca from vaccinated birds showed a lower abundance of Lactobacillus and a higher abundance of Escherichia coli than non-vaccinated birds (p < 0.05). The highest and lowest abundance of L. crispatus and E. coli, respectively, were observed in birds fed CP, BP, and CP + BP compared to those from NC or BAC treatments (p < 0.05). Coccidiosis vaccination affected the abundance of virulence genes (VGs) related to adherence, flagella, iron utilization, and secretion system. Toxin-related genes were observed in vaccinated birds (p < 0.05) in general, with less prevalence in birds fed CP, BP, and CP + BP than NC and BAC (p < 0.05). More than 75 antimicrobial resistance genes (ARGs) detected by the shotgun metagenomics sequencing were impacted by vaccination. Ceca from birds fed CP, BP, and CP + BP showed the lowest (p < 0.05) abundances of ARGs related to multi-drug efflux pumps, modifying/hydrolyzing enzyme and target-mediated mutation, when compared to ceca from birds fed BAC. Targeted metagenomics showed that resistome from BP treatment was distant to other groups for antimicrobials, such as aminoglycosides (p < 0.05). Significant differences in the richness were observed between the vaccinated and non-vaccinated groups for aminoglycosides, ß-lactams, lincosamides, and trimethoprim resistance genes (p < 0.05). Overall, this study demonstrated that dietary berry pomaces and coccidiosis vaccination significantly impacted cecal microbiota, virulome, resistome, and metabolic pathways in broiler chickens.

[Nephropathy associated with monoclonal immunoglobulins: From clonal expansion B to renal toxicity of pathological immunoglobulins]. / Les néphropathies associées aux immunoglobulines monoclonales : de l'expansion clonale B à la toxicité rénale des immunoglobulines pathologiques.

Germinal center regulation pathways are often involved in lymphomagenesis and myelomagenesis. Most of the lymphomas (and multiple myeloma) derive from post-germinal center B-cells that have undergone somatic hypermutation and class switch recombination. Hence, B-cell clonal expansion can be responsible for the presence of a monoclonal component (immunoglobulin) of variable titer which, owing to physicochemical properties, can provoke pathologically defined entities of diseases. These diseases can affect any functional part of the kidney, by multiple mechanisms, either well known or not. The presence of renal deposition is influenced by germinal gene involved, immunoglobulin primary structure, post-translational modifications and microenvironmental interactions. The two ways immunoglobulin can cause kidney toxicity are (i) an excess of production (overcoming catabolism power by proximal tubule epithelial cells) with an excess of free light chains within the distal tubules and a subsequent risk of precipitation due to local physicochemical properties; (ii) by structural characteristics that predispose immunoglobulin to a renal disease (whatever their titer). The purpose of this manuscript is to review literature concerning the pathophysiology of renal toxicities of clonal immunoglobulin, from molecular B-cell expansion mechanisms to immunoglobulin renal toxicity.

Impact of the treatment of chronic myeloid leukaemia by tyrosine-kinase inhibitors on sick leaves refund: a nationwide cohort study.

BACKGROUND: The advent of chronic myeloid leukaemia (CML) tyrosine-kinase inhibitors (TKI) has led to new paradigms including occupational rehabilitation. OBJECTIVES: This study aimed to characterize the impact of CML treatment on sick leaves within the 2 years following diagnosis in working-age patients. METHODS: A cohort of all 18-60-year-old newly diagnosed CML patients initiating a TKI between January 1st 2011 and December 31st 2014 in France was identified in the French National Healthcare database (Système National des Données de Santé [SNDS]). Patients with a sick leave identified in the 24 months after TKI initiation were compared with sex and initiation date matched controls in a nested case-control design. Factors associated with sick leaves were identified through a conditional logistic regression model, providing adjusted odds-ratio (OR) with their 95% confidence interval (CI). RESULTS: Among 646 18-60-year-old patients, 268 were prescribed at least one sick leave in the study period, with 176 (27.2%) having their first sick leave prescribed after TKI initiation. The median number of sick days over the 2-years period was 115 per patient (interquartile range 25.5-384.5). In the nested case-control study (176 cases and 176 matched controls), sick leaves were more likely observed with second generation TKI (OR 4.11 [1.80-9.38]), whereas they were less likely observed in case if social deprivation (OR 0.07 [0.02-0.28]. CONCLUSION: More than 25% of working-age CML patients had at least one sick leave within 2 years of TKI initiation, with a higher impact of second generation TKI, and with a median duration of 115 days.

The swine enteric virome in a commercial production system and its association with neonatal diarrhea.

Swine are an important food source worldwide and producers may not always be aware of the variety of the pathogens infecting their herds, particularly viruses. In this study, 12 enteric viruses were monitored in a total of 181 diarrheic and healthy piglets; namely porcine astrovirus groups 1-5 (poAstV1-5), rotavirus A and C (RVA-RVC), caliciviruses (CaVs), porcine kobuvirus (PoK), hepatitis E virus (HEV), and torque teno sus virus 1 and k2 (TTsuV1-k2). All animals were sampled before 3 weeks of age, and then at 5, 12 and 20 weeks of age. In addition to the 12 targeted viruses, the virome of 12 piglets at 4 different life stages was characterized using a high-throughput sequencing approach. The presence of CaV (sapovirus), poAstV-3 or poAstV-5 was found to be a risk factor for neonatal diarrhea. Co-infections with RVC and poAstV-2, poAstV-3, and poAstV-4 and CaV co-infected with PoK or poAstV-4 were also found to be risk factors for diarrhea in piglets. RVC, PoK, poAstV-3 and poAstV-4 were the most prevalent viruses in piglets below 3 weeks of age. PoAstV-2, poAstV-4, TTsuV1 and TTsuVk2 were found to be the most prevalent viruses infecting piglets of 20 weeks of age. The enteric virome composition varied between healthy and diarrheic piglets. The alpha and beta diversity of the enteric viromes varied from under 3 weeks of age to 20 weeks and was mainly supported by phages. Overall, this study sheds new light on enteric virome dynamics and the virome's relationship with neonatal diarrhea.

Lenalidomide-induced arthritis: A case report and review of literature and pharmacovigilance databases.

INTRODUCTION: Lenalidomide is an immunomodulatory agent with multiple mechanisms of action, and treatment with lenalidomide is associated with adverse events such as thrombosis and abdominal pain; nonetheless, other rarer adverse events do exist, with few knowledge from physicians and pharmacists. For such adverse events, pharmacovigilance databases are of great interest. CASE REPORT: A 71-year-old patient with no rheumatologic history, in complete remission of a mantle-cell lymphoma following rituximab, doxorubicin, vincristine, cyclophosphamide, and prednisone induction, received a maintenance treatment with rituximab and lenalidomide. After each course of lenalidomide and with no other new medication, the patient presented with fever and high inflammatory markers level, and a scapular-belt arthritis. MANAGEMENT AND OUTCOME: The patient was managed with non-steroidal anti-inflammatory drugs and colchicine, with symptomatology and inflammation improvement. After discontinuation of lenalidomide, he had no arthritis relapse; it was then concluded that the patient had a lenalidomide-induced arthritis. We interrogated the national and international (VigiBase®) pharmacovigilance databases and found that arthritis in the context of lenalidomide exposure is a rare finding, with only three reported cases in France; 0.13% of adverse events reported with lenalidomide in the international database VigiBase® were arthritis. DISCUSSION: Our case then reports an uncommon finding, of which both pharmacists and physicians should be aware due to the wide and increasing use of lenalidomide.

Impact of therapeutic management and geriatric evaluation on patient of eighty years and older with diffuse large B-cell lymphoma on survival: A systematic review.

BACKGROUND: Diffuse large B cell lymphoma (DLBCL) is an aggressive disease. The first-line treatment is well defined in young patients; however, in oldest old patients treatment remains unclear. OBJECTIVES: To investigate the impact of therapeutics management and geriatric evaluation on survival in aged patients with DLBCL. METHODS: We performed a systematic review of PubMed and COCHRANE databases of published report on elderly patients (median age 80 and above) with DLBCL, from January 2002 to January 2020. RESULTS: We included 32 studies (6 prospective and 26 retrospective). Patients treated with anthracyclines-containing chemoimmunotherapy had a 2-year overall survival (OS) of 59%-74.3% in prospective studies and 48.1-64.6% in retrospective studies. With less intensive treatment without anthracyclines, 2-year OS was 28%-53%. Without specific treatment, median OS was 2 months. History of falls and severe comorbidities were associated with a decreased survival. CONCLUSIONS: Chemoimmunotherapy with anthracyclines increases survival in selected very elderly patients in comparison with less intensive regimen. Geriatric assessment, in particular altered mobility disorders and severe comorbidities, is predictive of survival and should be associated with the therapeutic decision. More comparative studies are needed to guide the management of frailer patients.

Patterns of Tyrosine Kinase Inhibitor Utilization in Newly Treated Patients With Chronic Myeloid Leukemia: An Exhaustive Population-Based Study in France.

We analyzed demographic characteristics, comorbidities and patterns of treatment with tyrosine kinase inhibitors (TKIs) in a cohort of 3,633 incident cases of chronic myeloid leukemia (CML) identified across France from 1 January 2011 to 31 December 2014. Patients were identified through a specific algorithm in the French Healthcare Data System and were followed up 12 months after inclusion in the cohort. The estimated incidence rate of CML for this period in France was 1.37 per 100,000 person-years (95% Confidence Interval 1.36-1.38) and was higher in men, with a peak at age 75-79 years. At baseline, the median age of the cohort was 60 years (Inter Quartile Range 47-71), the Male/Female ratio was 1.2, and 25% presented with another comorbidity. Imatinib was the first-line TKI for 77.6% of the patients, followed by nilotinib (18.3%) and dasatinib (4.1%). Twelve months after initiation, 86% of the patients remained on the same TKI, 13% switched to another TKI and 1% received subsequently three different TKIs. During the follow-up, 23% discontinued and 52% suspended the TKI. Patients received a mean of 16.7 (Standard Deviation (SD) 9.6) medications over the first year of follow-up, and a mean of 2.7 (SD 2.3) concomitant medications on the day of first TKI prescription: 24.4% of the patients received allopurinol, 6.4% proton pump inhibitors (PPI) and 6.5% antihypertensive agents. When treatment with TKI was initiated, incident CML patients presented with comorbidities and polypharmacy, which merits attention because of the persistent use of these concomitant drugs and the potential increased risk of drug-drug interactions.

Outcomes after first-line immunochemotherapy for primary mediastinal B-cell lymphoma: a LYSA study.

Primary mediastinal B-cell lymphoma (PMBL) is a rare type of aggressive lymphoma typically affecting young female patients. The first-line standard of care remains debated. We performed a large multicenter retrospective study in 25 centers in France and Belgium to describe PMBL patient outcomes after first-line treatment in real-life settings. A total of 313 patients were enrolled and received rituximab (R) plus ACVBP (doxorubicin, cyclophosphamide, vindesine, bleomycin, and prednisone) (n = 180) or CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) delivered every 14 days (R-CHOP14, n = 76) or 21 days (R-CHOP21, n = 57) and consolidation strategies in modalities that varied according to time and institution, mainly guided by positron emission tomography. Consolidation autologous stem cell transplantation was performed for 46 (25.6%), 24 (31.6%), and 1 (1.8%) patient in the R-ACVBP, R-CHOP14, and R-CHOP21 groups, respectively (P < .001); only 17 (5.4%) patients received mediastinal radiotherapy. The end-of-treatment complete metabolic response rates were 86.3%, 86.8%, and 76.6% (P = .23) in the R-ACVBP, R-CHOP14, and R-CHOP21 groups. The median follow-up was 44 months, and the R-ACVBP, R-CHOP14, and R-CHOP21 three-year progression-free survival probabilities were 89.4% (95% confidence interval [CI], 84.8-94.2), 89.4% (95% CI, 82.7-96.6), and 74.7% (95% CI, 64-87.1) (P = .018). A baseline total metabolic tumor volume (TMTV) ≥360 cm3 was associated with a lower progression-free survival (hazard ratio, 2.18; 95% CI, 1.05-4.53). Excess febrile neutropenia (24.4% vs 5.3% vs 5.3%; P < .001) and mucositis (22.8% vs 3.9% vs 1.8%; P < .001) were observed with R-ACVBP compared with the R-CHOP regimens. Patients with PMBL treated with dose-dense immunochemotherapy without radiotherapy have excellent outcomes. R-ACVBP acute toxicity was higher than that of R-CHOP14. Our data confirmed the prognostic importance of baseline TMTV.

Effects of Vaccination Against Coccidiosis on Gut Microbiota and Immunity in Broiler Fed Bacitracin and Berry Pomace.

Feeding practices have been found to influence gut microbiota which play a major role in immunity of poultry. In the present study, changes in cecal microbiota and humoral responses resulting in the 55 ppm bacitracin (BACI), 1% each of cranberry (CP1) and wild blueberry (BP1) pomace alone or in combination (CP+BP) feeding in broiler Cobb 500 vaccinated or not against coccidiosis were investigated. In the non-vaccinated group, no significant treatment effects were observed on performance parameters. Vaccination significantly affected bird's performance parameters particularly during the growing phase from 10 to 20 days of age. In general, the prevalence of coccidiosis and necrotic enteritis (NE) was reduced by vaccination (P < 0.05). BACI-treated birds showed low intestinal lesion scores, and both CP1 and BP1 feed supplementations reduced Eimeria acervulina and Clostridium perfringens incidences similar to BACI. Vaccination induced change in serum enzymes, minerals, and lipid levels in 21-day old birds while, levels of triglyceride (TRIG) and non-esterified fatty acids (NEFA) were higher (P < 0.05) in CP1 treated non-vaccinated group than in the control. The levels of NEFA were lower in BACI- and CP1-fed birds than in the control in non-vaccinated day 28 old birds. The highest levels of all estimated three immunoglobulins (IgY, IgM, and IgA) were found in the vaccinated birds. Metagenomics analysis of the cecal bacterial community in 21-day old birds showed the presence of Firmicutes (90%), Proteobacteria (5%), Actinobacteria (2%), and Bacteroidetes (2%). In the vaccinated group, an effect of BACI was noted on Proteobacteria (P = 0.03). Vaccination and/or dietary treatments influenced the population of Lactobacillaceae, Enterobacteriaceae, Clostridiaceae, and Streptococcaceae which were among the most abundant families. Overall, this study revealed that besides their beneficial effects on performance, alike bacitracin, berry pomaces in poultry feed have profound impacts on the chicken cecal microbiota and blood metabolites that could be influenced by vaccination against coccidiosis.

Brentuximab vedotin in real life, a seven year experience in patients with refractory/relapsed CD30+ T cell lymphoma.

INTRODUCTION: Brentuximab vedotin (Bv) has been approved for the treatment of Refractory/Relapsed (R/R) Anaplastic Large Cell Lymphomas (ALCL) and cutaneous T-Cell Lymphomas, but is also effective in other CD30+ malignancies. We report here the outcomes of patients with various R/R Peripheral T Cell Lymphoma (PTCL) treated with Bv in real life practice. METHOD: This was a retrospective, single-center study based on medical records of patients with R/R PTCL treated either with Bv alone or in combination with chemotherapy. RESULTS: Among 27 patients treated with Bv, neutropenia was the main serious adverse event observed in particular when Bv was used as combination treatment. The complete Response Rates (CRR) was 40.7%; it was significantly improved when Bv was used as combination treatment. The majority of eligible patients (7/10) underwent Stem Cell Transplantation. Median Progression Free Survival (PFS) and Overall Survival (OS) were 5.2 months and 12.5 months respectively. CONCLUSION: Our current study shows that Bv used in combination with chemotherapy provides a high CRR and thereby allows SCT in R/R PTCL. The use of Bv treatments in this setting warrants further investigation.

Impact of a comprehensive geriatric assessment on decision-making in older patients with hematological malignancies.

OBJECTIVE: Hematological treatment decisions in older adults with hematological malignancies are complex. Our objective is to study the impact of a comprehensive geriatric assessment on hematological treatment decision in older patients and the factors associated with change in treatment plan. METHODS: We conducted a cross-sectional analysis of patients aged 65 years and above with hematological malignancies, hospitalized between 2008 and 2019 at the University Cancer Institute of Toulouse. They were assessed by a geriatrician/nurse team using a comprehensive geriatric assessment (CGA). A penalized logistic regression model with elastic net regularization was used to identify factors associated with change in hematological treatment plan. RESULTS: A total of 424 patients were included. Main hematological malignancies were lymphoma (36.1 %), acute myeloid leukemia (26.9 %) and myelodysplastic syndrome (19.8%). Change in hematological treatment plan was suggested after CGA for 92 patients (21.7%). Factors associated with change in treatment plan were functional impairment according to ADL and IADL scale, mobility impairment, the presence of comorbidity defined by the Charlson score >1 and increasing age. CONCLUSION: A CGA has a significant impact on hematological treatment decision in older patients. Functional and mobility impairment, comorbidities and age are predictive factors of change in treatment plan.