The Effect of the Pre-Transplant Disease Status on the Outcome for Recipients of T-Cell Depleted Allogeneic Haematopoietic Stem Cell Transplants for Large B Cell Lymphomas.

Objectives: Deauville scores (DS) from PET/CT imaging are increasingly being used to direct response-adjusted treatment strategies in lymphoma, including large B cell lymphomas (LBCL). We aimed to investigate the outcome of allogeneic haematopoietic stem cell transplantation (alloHSCT) in LBCL and the role played by pre-transplant disease status, as determined by DS.

Methods: We performed a retrospective, observational study of adults treated with a T-cell depleted alloHSCT for de novo DLBCL or high-grade transformation.

Over-the-Counter Anti-inflammatory Supplements for Adjunctive Rheumatoid Arthritis Therapy: A Comprehensive Narrative Review.

Rheumatoid arthritis (RA), a prevalent chronic disease, poses significant treatment challenges, including side effects and high costs of conventional therapies. This heightens interest in natural, over-the-counter (OTC) anti-inflammatory supplements as potential adjunctive treatments. Given their roles in mitigating inflammation and oxidative stress, key factors in RA pathogenesis, these supplements could offer valuable therapeutic adjunctive.

TIF1γ and SMAD4 regulation in colorectal cancer: impact on cell proliferation and liver metastasis.

We investigated the effects of transcriptional intermediary factor 1γ (TIF1γ) and SMAD4 on the proliferation and liver metastasis of colorectal cancer (CRC) cells through knockdown of TIF1γ and/or SMAD4 and knockdown of TIF1γ and/or restoration of SMAD4 expression. Furthermore, we examined TIF1γ and SMAD4 expression in human primary CRC and corresponding liver metastatic CRC specimens. TIF1γ promoted but SMAD4 inhibited the proliferation of CRC cells by competitively binding to activated SMAD2/SMAD3 complexes and then reversely regulating c-Myc, p21, p27, and cyclinA2 levels.

Allogeneic hematopoietic stem cell transplantation outcome in oldest known surviving patients with Wiskott-Aldrich syndrome.

Regardless of their age, adult patients with Wiskott-Aldrich syndrome should be considered for hematopoietic stem cell transplantation if clinically indicated.

The Human GP130 Cytokine Receptor and Its Expression-an Atlas and Functional Taxonomy of Genetic Variants.

Genetic variants in IL6ST encoding the shared cytokine receptor for the IL-6 cytokine family GP130 have been associated with a diverse number of clinical phenotypes and disorders. We provide a molecular classification for 59 reported rare IL6ST pathogenic or likely pathogenic variants and additional polymorphisms. Based on loss- or gain-of-function, cytokine selectivity, mono- and biallelic associations, and variable cellular mosaicism, we grade six classes of IL6ST variants and explore the potential for additional variants.

MEDICAL OUTREACH AND IMPROVED ACCESS TO SPECIALIST SERVICES FOR THE RURAL COMMUNITY OF BAUCHI STATE, NIGERIA: THE REQUIREMENTS FOR SUSTAINABILITY.

Introduction: The West African College of Physicians (Nigeria) conducted its Annual General and Scientific Meeting (AGSM) in Bauchi State, Nigeria on 11th-15th of July, 2023. The theme of the AGM is HEALTH-RELATED SDGs IN NIGERIA: THE PROGRESS SO FAR. The sub- themes included challenges of health care in the face of Disaster and the menace of brain drain on health care manpower and medical education.

Selectivity, efficacy and safety of JAKinibs: new evidence for a still evolving story.

Fundamental insight gained over the last decades led to the discovery of cytokines as pivotal drivers of inflammatory diseases such as rheumatoid arthritis, psoriasis/psoriasis arthritis, inflammatory bowel diseases, atopic dermatitis and spondylarthritis. A deeper understanding of the pro-inflammatory and anti-inflammatory effects of various cytokines has prompted new cytokine-targeting therapies, which revolutionised the treatment options in the last years for patients with inflammatory disorders. Disease-associated immune responses typically involve a complex interplay of multiple cytokines.

CAR-T cells, the first pharmaceutical cell therapy.

The success of genetically engineered adoptive cell therapies in haematological malignancy in the second decade of the 21st century has surprised both immunologists and oncologists. It challenges much of our understanding of the role of personalised medicine, the divide between cell products and pharmaceutical drugs and the limitations of the immune system to clear cancer. Furthermore, many challenges remain, the therapy is both expensive, hazardous and largely restricted to lymphoproliferative disease.

Protein kinases: drug targets for immunological disorders.

Protein kinases play a major role in cellular activation processes, including signal transduction by diverse immunoreceptors. Given their roles in cell growth and death and in the production of inflammatory mediators, targeting kinases has proven to be an effective treatment strategy, initially as anticancer therapies, but shortly thereafter in immune-mediated diseases. Herein, we provide an overview of the status of small molecule inhibitors specifically generated to target protein kinases relevant to immune cell function, with an emphasis on those approved for the treatment of immune-mediated diseases.

FrangiPANe, a tool for creating a panreference using left behind reads.

We present here FrangiPANe, a pipeline developed to build panreference using short reads through a map-then-assemble strategy. Applying it to 248 African rice genomes using an improved CG14 reference genome, we identified an average of 8 Mb of new sequences and 5290 new contigs per individual. In total, 1.

Genomic diagnosis and care co-ordination for monogenic inflammatory bowel disease in children and adults: consensus guideline on behalf of the British Society of Gastroenterology and British Society of Paediatric Gastroenterology, Hepatology and Nutrition.

Genomic medicine enables the identification of patients with rare or ultra-rare monogenic forms of inflammatory bowel disease (IBD) and supports clinical decision making. Patients with monogenic IBD frequently experience extremely early onset of treatment-refractory disease, with complex extraintestinal disease typical of immunodeficiency. Since more than 100 monogenic disorders can present with IBD, new genetic disorders and variants are being discovered every year, and as phenotypic expression of the gene defects is variable, adaptive genomic technologies are required.

Multispectral intraoperative imaging for the detection of the hemodynamic response to interictal epileptiform discharges.

Interictal epileptiform discharges (IEDs) are brief neuronal discharges occurring between seizures in patients with epilepsy. The characterization of the hemodynamic response function (HRF) specific to IEDs could increase the accuracy of other functional imaging techniques to localize epileptiform activity, including functional near-infrared spectroscopy and functional magnetic resonance imaging. This study evaluated the possibility of using an intraoperative multispectral imaging system combined with electrocorticography (ECoG) to measure the average HRF associated with IEDs in eight patients.

A central role for STAT5 in the transcriptional programing of T helper cell metabolism.

Activated lymphocytes adapt their metabolism to meet the energetic and biosynthetic demands imposed by rapid growth and proliferation. Common gamma chain (cγ) family cytokines are central to these processes, but the role of downstream signal transducer and activator of transcription 5 (STAT5) signaling, which is engaged by all cγ members, is poorly understood. Using genome-, transcriptome-, and metabolome-wide analyses, we demonstrate that STAT5 is a master regulator of energy and amino acid metabolism in CD4 T helper cells.

Allogeneic stem cell transplantation compared to conservative management in adults with inborn errors of immunity.

Allogeneic hematopoietic stem cell transplantation (alloSCT) is curative for severe inborn errors of immunity (IEIs), with recent data suggesting alloSCT in adulthood is safe and effective in selected patients. However, questions remain regarding the indications for and optimal timing of transplant. We retrospectively compared outcomes of transplanted vs matched nontransplanted adults with severe IEIs.

Characterization of Selective and Potent JAK1 Inhibitors Intended for the Inhaled Treatment of Asthma.

Purpose: Janus kinase 1 (JAK1) is implicated in multiple inflammatory pathways that are critical for the pathogenesis of asthma, including the interleukin (IL)-4, IL-5, IL-13, and thymic stromal lymphopoietin cytokine signaling pathways, which have previously been targeted to treat allergic asthma. Here, we describe the development of AZD0449 and AZD4604, two novel and highly selective JAK1 inhibitors with promising properties for inhalation.

Methods: The effects of AZD0449 and AZD4604 in JAK1 signaling pathways were assessed by measuring phosphorylation of signal transducer and activator of transcription (STAT) proteins and chemokine release using immunoassays of whole blood from healthy human volunteers and rats.

Inhibition of acylglycerol kinase sensitizes DLBCL to venetoclax via upregulation of FOXO1-mediated BCL-2 expression.

Despite of the paradigm change on the treatments of acute myeloid leukemia (AML) and chronic lymphocytic leukemia (CLL) by venetoclax, it has been less successful in the treatment of diffuse large B-cell lymphoma (DLBCL). Here, we explored whether acylglycerol kinase regulates the sensitivity of DLBCLs to venetoclax and its mechanism in both cell lines and preclinical animal models. The expression of AGK and sensitivity to venetoclax of seven DLBCL cell lines were determined.

Transcription factor EB coordinates environmental cues to regulate T regulatory cells' mitochondrial fitness and function.

T regulatory (Treg) cells are essential for self-tolerance whereas they are detrimental for dampening the host anti-tumor immunity. How Treg cells adapt to environmental signals to orchestrate their homeostasis and functions remains poorly understood. Here, we identified that transcription factor EB (TFEB) is induced by host nutrition deprivation or interleukin (IL)-2 in CD4 T cells.

Pembrolizumab for the treatment of progressive multifocal leukoencephalopathy following anti-CD19 CAR-T therapy: a case report.

Progressive multifocal leukoencephalopathy (PML) is an opportunistic brain infection with few treatment options and poor survival when reversal of the underlying immune dysfunction is not achievable. JC polyomavirus reactivation resulting in PML can rarely complicate chimeric antigen receptor T-cell (CAR-T) therapy. We describe successful treatment of PML with Programmed death-1 (PD-1) blockade using pembrolizumab, 4 months following axicabtagene ciloleucel.

Retrospective, Landmark Analysis of Long-term Adult Morbidity Following Allogeneic HSCT for Inborn Errors of Immunity in Infancy and Childhood.

Purpose: Allogeneic hematopoietic stem cell transplant (HSCT) remains the treatment of choice for patients with inborn errors of immunity (IEI). There is little published medical outcome data assessing late medical complications following transition to adult care. We sought to document event-free survival (EFS) in transplanted IEI patients reaching adulthood and describe common late-onset medical complications and factors influencing EFS.