Diagnosis and Management of Kaposi Sarcoma-Associated Herpesvirus Inflammatory Cytokine Syndrome in Resource-Constrained Settings: A Case Report and an Adapted Case Definition.

Kaposi sarcoma-associated herpes virus (KSHV), also known as human herpes virus 8 (HHV-8), is the primary etiologic cause of Kaposi sarcoma (KS) and KSHV Inflammatory Cytokine Syndrome (KICS). Patients with KICS demonstrate symptoms of systemic inflammation, high KSHV viral load, elevation of inflammatory markers, and increased mortality. Management requires rapid diagnosis, treatment of underlying HIV, direct treatment of KS, and addressing the hyperimmune response.

Disseminated histoplasmosis from western Mexico-rethinking our geographic distribution of endemic fungal species: a case report and review of literature.

Background: Histoplasma is a fungal pathogen found in many parts of the world. In North America, its distribution is traditionally thought to be endemic to the Ohio and Mississippi River valleys. Development of histoplasmosis after Histoplasma exposure is related to degree of inoculum exposure and susceptibility, for example, immunocompromised status.

Genetic Manipulation and Extended Culture of Human Germinal Center B Cells to Model Lymphomagenesis.

The germinal center (GC) is the stage of B cell differentiation that gives rise to a majority of B cell lymphomas. Here, we present an experimental coculture system for the ex vivo expansion and genetic manipulation of human GC B cells purified from discarded tonsil tissue. This system can be used to investigate the impact of defined genetic alterations, either individually or in combination, upon the growth and survival of human GC B cells in vitro.

Subtle Sonographic Signs of Disseminated Tuberculosis: A Case Report and Narrative Literature Review.

Miliary tuberculosis is a form of disseminated tuberculosis that can be difficult to detect when the classic pattern is absent on chest radiograph and advanced cross-sectional imaging is not readily available. While the focused assessment with sonography for HIV-associated tuberculosis (FASH) protocol for extrapulmonary tuberculosis emphasizes easy-to-teach findings, experienced sonographers may detect additional, subtler signs that can aid in diagnosis. We report a case of a 20-year-old man with miliary tuberculosis diagnosed on computed tomography of the chest.

Molecular Determinants of Sensitivity to Polatuzumab Vedotin in Diffuse Large B-Cell Lymphoma.

Polatuzumab vedotin (Pola-V) is an antibody-drug conjugate directed to the CD79B subunit of the B-cell receptor (BCR). When combined with conventional immunochemotherapy, Pola-V improves outcomes in diffuse large B-cell lymphoma (DLBCL). To identify determinants of Pola-V sensitivity, we used CRISPR-Cas9 screening for genes that modulated Pola-V toxicity for lymphomas or the surface expression of its target, CD79B.

Latent Epstein-Barr virus infection collaborates with Myc over-expression in normal human B cells to induce Burkitt-like Lymphomas in mice.

Epstein-Barr virus (EBV) is an important cause of human lymphomas, including Burkitt lymphoma (BL). EBV+ BLs are driven by Myc translocation and have stringent forms of viral latency that do not express either of the two major EBV oncoproteins, EBNA2 (which mimics Notch signaling) and LMP1 (which activates NF-κB signaling). Suppression of Myc-induced apoptosis, often through mutation of the TP53 (p53) gene or inhibition of pro-apoptotic BCL2L11 (BIM) gene expression, is required for development of Myc-driven BLs.

Response to Bruton's tyrosine kinase inhibitors in aggressive lymphomas linked to chronic selective autophagy.

Diffuse large B cell lymphoma (DLBCL) is an aggressive, profoundly heterogeneous cancer, presenting a challenge for precision medicine. Bruton's tyrosine kinase (BTK) inhibitors block B cell receptor (BCR) signaling and are particularly effective in certain molecular subtypes of DLBCL that rely on chronic active BCR signaling to promote oncogenic NF-κB. The MCD genetic subtype, which often acquires mutations in the BCR subunit, CD79B, and in the innate immune adapter, MYD88, typically resists chemotherapy but responds exceptionally to BTK inhibitors.

Patterns of Oncogene Coexpression at Single-Cell Resolution Influence Survival in Lymphoma.

Unlabelled: Cancers often overexpress multiple clinically relevant oncogenes, but it is not known if combinations of oncogenes in cellular subpopulations within a cancer influence clinical outcomes. Using quantitative multispectral imaging of the prognostically relevant oncogenes MYC, BCL2, and BCL6 in diffuse large B-cell lymphoma (DLBCL), we show that the percentage of cells with a unique combination MYC+BCL2+BCL6- (M+2+6-) consistently predicts survival across four independent cohorts (n = 449), an effect not observed with other combinations including M+2+6+. We show that the M+2+6- percentage can be mathematically derived from quantitative measurements of the individual oncogenes and correlates with survival in IHC (n = 316) and gene expression (n = 2,521) datasets.

Striving towards true equity in global health: A checklist for bilateral research partnerships.

Interest in "global health" among schools of medicine, public health, and other health disciplines in high-income countries (HIC) continues to rise. Persistent power imbalances, racism, and maintenance of colonialism/neocolonialism plague global health efforts, including global health scholarship. Scholarly projects conducted in low- and middle-income countries (LMIC) by trainees at these schools in HIC often exacerbate these problems.

Cytokine receptor IL27RA is an NF-κB-responsive gene involved in CD38 upregulation in multiple myeloma.

Multiple myeloma (MM) shows constitutive activation of canonical and noncanonical nuclear factor κB (NF-κB) signaling via genetic mutations or tumor microenvironment (TME) stimulations. A subset of MM cell lines showed dependency for cell growth and survival on the canonical NF-κB transcription factor RELA alone, suggesting a critical role for a RELA-mediated biological program in MM pathogenesis. Here, we determined the RELA-dependent transcriptional program in MM cell lines and found the expression of the cell surface molecules interleukin-27 receptor-α (IL-27Rα) and the adhesion molecule JAM2 to be responsive to RELA at the messenger RNA and protein levels.

Genetic Profiling in Diffuse Large B-Cell Lymphoma: The Promise and the Challenge.

Diffuse large B-cell lymphoma (DLBCL) is the most common non-Hodgkin lymphoma. Over the previous 2 decades, tremendous progress has been made in our understanding of the molecular pathogenesis of DLBCL. However, this biological understanding has not yet been translated into improved first-line therapy.

Plasmodium infection is associated with cross-reactive antibodies to carbohydrate epitopes on the SARS-CoV-2 Spike protein.

Sero-surveillance can monitor and project disease burden and risk. However, SARS-CoV-2 antibody test results can produce false positive results, limiting their efficacy as a sero-surveillance tool. False positive SARS-CoV-2 antibody results are associated with malaria exposure, and understanding this association is essential to interpret sero-surveillance results from malaria-endemic countries.

A 77-Year-Old Woman With Capillary Hypoxia and Perioral Cyanosis.

A 77-year-old woman with asthma, hypothyroidism, irritable bowel syndrome, overactive bladder, and multiple rheumatologic conditions was sent from the clinic to the ED for evaluation of hypoxia. In the clinic, she reported dizziness without shortness of breath and was noted to have perioral cyanosis with an oxygen saturation measured by pulse oximetry (Spo) of 80%. She was given a nonrebreather mask delivering oxygen at 8 L/min, but the Spo remained at 77% to 82%.

Managing relapsed refractory lymphoma with palliative oral chemotherapy: A multicentre retrospective study.

PEP-C (prednisolone, etoposide, procarbazine and cyclophosphamide) is an orally administered daily chemotherapy regimen used with palliative intent in relapsed refractory lymphoma. To our knowledge, no data on PEP-C have been reported since the original group described the regimen. Here we present a multicentre retrospective cohort reporting our use of PEP-C in 92 patients over an 8-year period.

Clinical characteristics of Plasmodium falciparum infection among symptomatic patients presenting to a major urban military hospital in Cameroon.

Background: Urban malaria has received insufficient attention in the literature. The prevalence and clinical characteristics of Plasmodium falciparum infection amongst patients presenting with suspected malaria were investigated at a major urban hospital in Douala, Cameroon with a particular focus on anaemia.

Methods: A cross-sectional, 18-week demographic and clinical survey was conducted of patients presenting to the Emergency Department of Douala Military Hospital with suspected malaria, largely defined by the presence or recent history of fever.

Viral transduction of primary human lymphoma B cells reveals mechanisms of NOTCH-mediated immune escape.

Hotspot mutations in the PEST-domain of NOTCH1 and NOTCH2 are recurrently identified in B cell malignancies. To address how NOTCH-mutations contribute to a dismal prognosis, we have generated isogenic primary human tumor cells from patients with Chronic Lymphocytic Leukemia (CLL) and Mantle Cell Lymphoma (MCL), differing only in their expression of the intracellular domain (ICD) of NOTCH1 or NOTCH2. Our data demonstrate that both NOTCH-paralogs facilitate immune-escape of malignant B cells by up-regulating PD-L1, partly dependent on autocrine interferon-γ signaling.

Immunodeficiency, autoimmunity, and increased risk of B cell malignancy in humans with mutations.

Tumor necrosis factor receptor-associated factor 3 (TRAF3) is a central regulator of immunity. TRAF3 is often somatically mutated in B cell malignancies, but its role in human immunity is not defined. Here, in five unrelated families, we describe an immune dysregulation syndrome of recurrent bacterial infections, autoimmunity, systemic inflammation, B cell lymphoproliferation, and hypergammaglobulinemia.

Diverse mutational landscapes in human lymphocytes.

The lymphocyte genome is prone to many threats, including programmed mutation during differentiation, antigen-driven proliferation and residency in diverse microenvironments. Here, after developing protocols for expansion of single-cell lymphocyte cultures, we sequenced whole genomes from 717 normal naive and memory B and T cells and haematopoietic stem cells. All lymphocyte subsets carried more point mutations and structural variants than haematopoietic stem cells, with higher burdens in memory cells than in naive cells, and with T cells accumulating mutations at a higher rate throughout life.

Longitudinal expression profiling identifies a poor risk subset of patients with ABC-type diffuse large B-cell lymphoma.

Despite the effectiveness of immuno-chemotherapy, 40% of patients with diffuse large B-cell lymphoma (DLBCL) experience relapse or refractory disease. Longitudinal studies have previously focused on the mutational landscape of relapse but fell short of providing a consistent relapse-specific genetic signature. In our study, we have focused attention on the changes in GEP accompanying DLBCL relapse using archival paired diagnostic/relapse specimens from 38 de novo patients with DLBCL.

Cardiac tamponade as the initial presentation of autoimmune polyglandular syndrome Type 2: a case report.

Background: Cardiac tamponade is a rare but serious manifestation of autoimmune polyglandular syndrome Type 2 (APS 2). Patients often present with symptoms of thyroid dysfunction and adrenal insufficiency, but the insidious onset of the disease may lead to delayed diagnosis, which can progress rapidly to haemodynamic instability requiring urgent intervention.

Case Summary: A 39-year-old previously healthy male was admitted with cardiac tamponade complicated by cardiac arrest requiring emergent pericardiocentesis.