The effect of climate change on avian offspring production: A global meta-analysis

Climate change affects timing of reproduction in many bird species, but few studies have investigated its influence on annual reproductive output. Here, we assess changes in the annual production of young by female breeders in 201 populations of 104 bird species (N = 745,962 clutches) covering all continents between 1970 and 2019. Overall, average offspring production has declined in recent decades, but considerable differences were found among species and populations. A total of 56.7% of populations showed a declining trend in offspring production (significant in 17.4%), whereas 43.3% exhibited an increase (significant in 10.4%). The results show that climatic changes affect offspring production through compounded effects on ecological and life history traits of species. Migratory and larger-bodied species experienced reduced offspring production with increasing temperatures during the chick-rearing period, whereas smaller-bodied, sedentary species tended to produce more offspring. Likewise, multi-brooded species showed increased breeding success with increasing temperatures, whereas rising temperatures were unrelated to repro- ductive success in single-brooded species. Our study suggests that rapid declines in size of bird populations reported by many studies from different parts of the world are driven only to a small degree by changes in the production of young

The Spectrum of Chronic CD8 T-Cell Expansions: Clinical Features in 14 Patients

International audienceChronic CD8 + T-cell expansions can result in parotid gland swelling and other organ infiltration in HIV-infected patients, or in persistent cytopenias. We report 14 patients with a CD8 + T-cell expansion to better characterize the clinical spectrum of this ill-defined entity. Patients (9 women/5 men) were 65 year-old (range, 25–74). Six patients had $1 symptomatic organ infiltration, and 9 had$1 cytopenia with a CD8 + (.50% of total lymphocyte count) and/or a CD8 + /CD57 + (.30% of total lymphocyte count) T-cell expansion for at least 3 months. One patient had both manifestations. A STAT3 mutation, consistent with the diagnosis of large granular lymphocyte leukemia, was found in 2 patients with cytopenia. Organ infiltration involved lymph nodes, the liver, the colon, the kidneys, the skin and the central nervous system. Three patients had a HIV infection for 8 years (range, 0.5–20 years). Two non-HIV patients with hypogammaglobulinemia had been treated with a B-cell depleting monoclonal antibody (rituximab) for a lymphoma. One patient had a myelodysplastic syndrome with colon infiltration and agranulocytosis. The outcome was favorable with efficient antiretroviral therapy and steroids in HIV-infected patients and intravenous immunoglobulins in 2/3 non-HIV patients. Six patients had an agranulocytosis of favorable outcome with granulocyte-colony stimulating factor only (3 cases), cyclophosphamide, methotrexate and cyclosporine A, or no treatment (1 case each). Three patients had a pure red cell aplasia, of favorable outcome in 2 cases with methotrexate and cyclosporine A; one patient was unresponsive. Chronic CD8 + T-cell expansions with organ infiltration in immunocompromised patients may involve other organs than parotid glands; they are non clonal and of favorable outcome after correction of the immune deficiency and/or steroids. In patients with bone marrow infiltration and unexplained cytopenia, CD8 + T-cell expansions can be clonal or not; their identification suggests that cytopenias are immune-mediated. Our results extend the clinical spectrum of chronic CD8 + T-cell expansions

Agranulocytosis and PRCA-associated CD8⁺ T-cell expansion.

<p>Clinical features. F: female. M: male. Allo-SCT: allogeneic hematopoietic stem cell transplantation. AML: acute myeloblastic leukemia. HCV: hepatitis C virus. ANCA: anti-neutrophil cytoplasm antibodies. BM: bone marrow. ANC: absolute neutrophil count. <i>E. coli</i>: <i>Escherichia coli</i>. MTX: methotrexate. CsA: cyclosporine A. MMF: mycofenolate mofetil. G-CSF: granulocyte-colony stimulating factor. rEPO: recombinant erythropoietin. IVIG: intravenous immunoglobulins. RBC: red blood cells. FU: follow-up.</p

Agranulocytosis and PRCA-associated CD8⁺ T-cell expansion.

<p>Biological features.</p><p>*performed from PBL immunophenotyping. PBL: peripheral blood lymphocytes. LGL: large granular lymphocytes. BM: bone marrow. TCR: T-cell receptor. ANC: absolute neutrophil count. Hb: hemoglobin. STAT: <u>S</u>ignal <u>T</u>ransducer and <u>A</u>ctivator of <u>T</u>ranscription. SH2: Src homology-2. WT: wild type. NA: not available.</p

CD8⁺ T-cell expansion with tissue infiltration in the context of HIV infection.

<p>Clinical features. M: male. HIV: human immunodeficiency virus. HBV: hepatitis B virus. HCV: hepatitis C virus. HHV8: human herpes virus 8. DILS: diffuse infiltration of CD8⁺ T-cell lymphocytes syndrome. NRH: nodular regenerative hyperplasia. ART: antiretroviral therapy. FU: follow-up.</p

CD4⁺/CD8⁺ ratio in infiltrated organs.

<p>*CD4⁺/CD8⁺ ratio was 0/141.</p

CD8⁺ T-cell expansion with tissue infiltration without HIV infection.

<p>Clinical features. F: female. FCR: Fludarabine, cyclophosphamide and rituximab. CSF: cerebrospinal fluid. NRH: nodular regenative hyperplasia. IVIG: intravenous immunoglobulins. FU: follow-up.</p

CD4⁺/CD8⁺ ratio in infiltrated organs in patients with agranulocytosis and PRCA-associated CD8⁺ T-cell expansion.

<p>CD4⁺/CD8⁺ ratio in infiltrated organs in patients with agranulocytosis and PRCA-associated CD8⁺ T-cell expansion.</p

Anti-CD19 CAR T-Cell Therapy for Patients with Richter Syndrome: A Lysa Study from the Descar-T Registry

International audienceBackground Richter syndrome (RS) refers to the onset of aggressive lymphoma, mostly diffuse large B-cell lymphoma (DLBCL), in patients with chronic lymphocytic leukemia (CLL). The outcome of RS patients is usually very poor with short survival (typically 2. Tocilizumab was administered to 9 (75%) patients. Five (42%) patients had ICANS, 3 (25%) with grade > 3. Regarding hematotoxicity, 6 (50%) patients presented with grade > 2 thrombocytopenia, 5 (42%) with grade > 2 anemia, and 7 with (58%) grade > 2 neutropenia. One case of macrophage activation syndrome was reported. Three patients were admitted to intensive care. A total of 5 (42%) patients had infections. After a median follow-up of 1.6 months (range, 0-23), 8 (67%) patients were alive, 4 (33%) patients died (2 from CRS and 2 from disease progression).Conclusions CD19-directed CAR T-cell therapy showed high response rates in our series of heavily pretreated RS patients. Frequency of CAR T-cell-specific adverse events was in the range of what is observed in de novo DLBCL while severity appeared higher (Schuster et al., NEJM 2019; Neelapu et al., NEJM 2017). Larger cohort with longer follow-up and prospective trials are warranted to confirm these observations

Anti-CD19 CAR T-Cell Therapy for Patients with Richter Syndrome: A Lysa Study from the Descar-T Registry

International audienceBackground Richter syndrome (RS) refers to the onset of aggressive lymphoma, mostly diffuse large B-cell lymphoma (DLBCL), in patients with chronic lymphocytic leukemia (CLL). The outcome of RS patients is usually very poor with short survival (typically 2. Tocilizumab was administered to 9 (75%) patients. Five (42%) patients had ICANS, 3 (25%) with grade > 3. Regarding hematotoxicity, 6 (50%) patients presented with grade > 2 thrombocytopenia, 5 (42%) with grade > 2 anemia, and 7 with (58%) grade > 2 neutropenia. One case of macrophage activation syndrome was reported. Three patients were admitted to intensive care. A total of 5 (42%) patients had infections. After a median follow-up of 1.6 months (range, 0-23), 8 (67%) patients were alive, 4 (33%) patients died (2 from CRS and 2 from disease progression).Conclusions CD19-directed CAR T-cell therapy showed high response rates in our series of heavily pretreated RS patients. Frequency of CAR T-cell-specific adverse events was in the range of what is observed in de novo DLBCL while severity appeared higher (Schuster et al., NEJM 2019; Neelapu et al., NEJM 2017). Larger cohort with longer follow-up and prospective trials are warranted to confirm these observations