Pulmonary fibrosis in patients with autoimmune pulmonary alveolar proteinosis: a retrospective nationwide cohort study.

Background: Autoimmune pulmonary alveolar proteinosis (aPAP) is a rare disease that may progress towards pulmonary fibrosis. Data about fibrosis prevalence and risk factors are lacking.

Methods: In this retrospective multicentre nationwide cohort, we included patients newly diagnosed with aPAP between 2008 and 2018 in France and Belgium.

Therapist-Reported Differences between Teletherapy via Phone and via Videoconferencing.

When therapists provide teletherapy they can choose between teletherapy via phone and teletherapy via videoconferencing, however, little is known about differences between using these two teletherapy formats. We aimed to compare therapists' attitudes, level of professional self-doubt, and experience of the therapeutic relationship in sessions conducted via phone versus via videoconferencing. We administered an online survey to 117 therapists who had experience with sessions both via phone and videoconferencing.

Infections in autoimmune pulmonary alveolar proteinosis: a large retrospective cohort.

Background: Autoimmune pulmonary alveolar proteinosis (aPAP) is a rare disease, predisposing to an increased risk of infection. A complete picture of these infections is lacking.

Research Question: Describe the characteristics and clinical outcomes of patients diagnosed with aPAP, and to identify risk factors associated with opportunistic infections.

Axicabtagene ciloleucel as second-line therapy in large B cell lymphoma ineligible for autologous stem cell transplantation: a phase 2 trial.

Axicabtagene ciloleucel (axi-cel) demonstrated superior efficacy compared to standard of care as second-line therapy in patients with high-risk relapsed/refractory (R/R) large B cell lymphoma (LBCL) considered eligible for autologous stem cell transplantation (ASCT); however, in clinical practice, roughly half of patients with R/R LBCL are deemed unsuitable candidates for ASCT. The efficacy of axi-cel remains to be ascertained in transplant-ineligible patients. ALYCANTE, an open-label, phase 2 study, evaluated axi-cel as a second-line therapy in 62 patients with R/R LBCL who were considered ineligible for ASCT.

Regulatory B Cells Contribute to the Clinical Response After Bone Marrow-Derived Mesenchymal Stromal Cell Infusion in Patients With Systemic Sclerosis.

Mesenchymal stromal cells (MSCs) have recently emerged as an interesting therapeutic approach for patients with progressive systemic sclerosis (SSc), a rare and life-threatening orphan autoimmune disease. Whereas MSC immunomodulatory potential is considered as a central mechanism for their clinical benefit, very few data are available on the impact of MSCs on immune cell subsets in vivo. In the current extended study of a phase I/II clinical trial exploring the injection of a single dose of allogeneic bone marrow-MSCs (alloBM-MSCs) in patients with severe SSc (NCT02213705), we performed a longitudinal in-depth characterization of circulating immune cells in 19 MSC-treated patients, including 14 responders and 5 non-responders.

Lenalidomide triggers T-cell effector functions in vivo in patients with follicular lymphoma.

The immunomodulatory drug lenalidomide is used in patients with follicular lymphoma (FL) with the aim of stimulating T-cell antitumor immune response. However, little is known about the effects of lenalidomide on T-cell biology in vivo in patients with FL. We thus undertook an extensive longitudinal immunologic study, including phenotypic, transcriptomic, and functional analyses, on 44 first-line and 27 relapsed/refractory patients enrolled in the GALEN trial (Obinutuzumab Combined With Lenalidomide for Relapsed or Refractory Follicular B-Cell Lymphoma) to test the efficacy of lenalidomide and obinutuzumab combination in patients with FL.

Pulmonary alveolar proteinosis.

PAP is an ultra-rare disease in which surfactant components, that impair gas exchange, accumulate in the alveolae. There are three types of PAP. The most frequent form, primary PAP, includes autoimmune PAP which accounts for over 90% of all PAP, defined by the presence of circulating anti-GM-CSF antibodies.

Integrated transcriptomic, phenotypic, and functional study reveals tissue-specific immune properties of mesenchymal stromal cells.

Clinical-grade mesenchymal stromal cells (MSCs) can be expanded from bone marrow and adipose tissue to treat inflammatory diseases and degenerative disorders. However, the influence of their tissue of origin on their functional properties, including their immunosuppressive activity, remains unsolved. In this study, we produced paired bone marrow-derived mesenchymal stromal cell (BM-MSC) and adipose-derived stromal cell (ASC) batches from 14 healthy donors.

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PREDICTIVE BIOMARKERS OF RESPONSE TO IMMUNE CHECKPOINT INHIBITORS: PD-1 checkpoint inhibitors are becoming the reference treatment for several types of cancers. Many patients show remarkable efficacy and low toxicity. However, some patients have a better outcome than others with PD-1 checkpoint inhibitors.

An open-label phase 1b study of obinutuzumab plus lenalidomide in relapsed/refractory follicular B-cell lymphoma.

Obinutuzumab is a type II anti-CD20 monoclonal antibody that enhances antibody-dependent cellular cytotoxicity better than rituximab. Given promising results with lenalidomide and rituximab, this phase 1b study assessed the safety and efficacy of lenalidomide combined with obinutuzumab (GALEN). Patients age ≥18 years with relapsed or refractory (R/R) follicular lymphoma (FL) after rituximab-containing therapy received escalating doses (10 [n = 7], 15 [n = 3], 20 [n = 6], and 25 mg [n = 3]) of daily oral lenalidomide on days 1 to 21 of cycle 1 and on days 2 to 22 of cycles 2 to 6 (28-day cycles).

POFA trial study protocol: a multicentre, double-blind, randomised, controlled clinical trial comparing opioid-free versus opioid anaesthesia on postoperative opioid-related adverse events after major or intermediate non-cardiac surgery.

Introduction: Reducing opioid consumption during and after surgery has been recommended for more than 10 years. Opioid-free anaesthesia (OFA) is a multimodal anaesthesia associating hypnotics, NMDA antagonists, local anaesthetics, anti-inflammatory drugs and α-2 agonists. Proofs of the effect of OFA on reducing opioid-related adverse effects after major or intermediate non-cardiac surgery are still scarce.

Rituximab for auto-immune alveolar proteinosis, a real life cohort study.

Background: Whole lung lavage is the current standard therapy for pulmonary alveolar proteinosis (PAP) that is characterized by the alveolar accumulation of surfactant. Rituximab showed promising results in auto-immune PAP (aPAP) related to anti-GM-CSF antibody.

Methods: We aimed to assess efficacy of rituximab in aPAP in real life and all patients with aPAP in France that received rituximab were retrospectively analyzed.

NK cell activation and recovery of NK cell subsets in lymphoma patients after obinutuzumab and lenalidomide treatment.

Obinutuzumab (OBZ) shows stronger antibody-dependent cell cytotoxicity (ADCC) compared to rituximab and improved clinical activity for treating certain CD20 neoplasia. However, the efficacy of monoclonal antibody (mAb) as a monotherapy is limited. Natural Killer (NK) cells are mediators of ADCC.

Regulatory myeloid cells: an underexplored continent in B-cell lymphomas.

In lymphomas arising from the germinal center, prognostic factors are linked to the myeloid compartment. In particular, high circulating monocyte or myeloid-derived suppressor cell counts are associated with poor prognosis for patients with high-grade B-cell lymphomas. Macrophages with an M2 phenotype are enriched within lymphoma tumors.

Brief Report: Proteasomal Indoleamine 2,3-Dioxygenase Degradation Reduces the Immunosuppressive Potential of Clinical Grade-Mesenchymal Stromal Cells Undergoing Replicative Senescence.

Owing to their immunosuppressive properties, mesenchymal stromal cells (MSCs) obtained from bone marrow (BM-MSCs) or adipose tissue (ASCs) are considered a promising tool for cell therapy. However, important issues should be considered to ensure the reproducible production of efficient and safe clinical-grade MSCs. In particular, high expansion rate, associated with progressive senescence, was recently proposed as one of the parameters that could alter MSC functionality.

Liposuction Preserves the Morphological Integrity of the Microvascular Network: Flow Cytometry and Confocal Microscopy Evidence in a Controlled Study.

Background: Liposuction is a very popular technique in plastic surgery that allows for the taking adipose tissue (AT) on large surfaces with little risk of morbidity. Although liposuction was previously shown to preserve large perforator vessels, little is known about the effects of liposuction on the microvasculature network.

Objectives: The aim of this study was to analyze the effect of liposuction on the preservation of microvessels at tissue and cellular levels by flow cytometry and confocal microscopy following abdominoplasty procedure.

Emergence of long-lived autoreactive plasma cells in the spleen of primary warm auto-immune hemolytic anemia patients treated with rituximab.

Primary warm autoimmune hemolytic anemia (wAIHA) is a rare autoimmune disease in which red blood cells are eliminated by IgG autoantibodies. We analyzed the antibody-secreting cells in the spleen and the peripheral blood of wAIHA patients in various contexts of treatment. Plasmablasts were observed in peripheral blood of newly diagnosed wAIHA patients and, accordingly, active germinal center reactions were present in the spleen of patients receiving short-term corticosteroid therapy.

Germinal center reentries of BCL2-overexpressing B cells drive follicular lymphoma progression.

It has recently been demonstrated that memory B cells can reenter and reengage germinal center (GC) reactions, opening the possibility that multi-hit lymphomagenesis gradually occurs throughout life during successive immunological challenges. Here, we investigated this scenario in follicular lymphoma (FL), an indolent GC-derived malignancy. We developed a mouse model that recapitulates the FL hallmark t(14;18) translocation, which results in constitutive activation of antiapoptotic protein B cell lymphoma 2 (BCL2) in a subset of B cells, and applied a combination of molecular and immunofluorescence approaches to track normal and t(14;18)(+) memory B cells in human and BCL2-overexpressing B cells in murine lymphoid tissues.

Effects of a ceramic biomaterial on immune modulatory properties and differentiation potential of human mesenchymal stromal cells of different origin.

The aim of this study was to assess the immune modulatory properties of human mesenchymal stromal cells obtained from bone marrow (BM-MSCs), fat (ASCs), and cord blood (CB-MSCs) in the presence of a hydroxyapatite and tricalcium-phosphate (HA/TCP) biomaterial as a scaffold for MSC delivery. In resting conditions, a short-term culture with HA/TCP did not modulate the anti-apoptotic and suppressive features of the various MSC types toward T, B, and NK cells; in addition, when primed with inflammatory cytokines, MSCs similarly increased their suppressive capacities in the presence or absence of HA/TCP. The long-term culture of BM-MSCs with HA/TCP induced an osteoblast-like phenotype with upregulation of OSTERIX and OSTEOCALCIN, similar to what was obtained with dexamethasone and, to a higher extent, with bone morphogenetic protein 4 (BMP-4) treatment.

Human t(14;18)positive germinal center B cells: a new step in follicular lymphoma pathogenesis?

Follicular lymphoma (FL) is a B-cell neoplasm resulting from the transformation of germinal center (GC) B cells. Although t(14;18) and ectopic B-cell lymphoma 2 (BCL2) expression constitute the genetic hallmark of FL, t(14;18)(pos) B cells bearing genotypic and phenotypic features of FL cells can be found in the blood of most healthy individuals. Nevertheless, the localization of these FL-like cells (FLLCs) in nonmalignant GC-rich tissues and the functional consequences of BCL2 overexpression have not been evaluated thus far.