Gut microbiota profiling in injection drug users with and without HIV-1 infection in Puerto Rico.

Introduction: The full extent of interactions between human immunodeficiency virus (HIV) infection, injection drug use, and the human microbiome is unclear. In this study, we examined the microbiomes of HIV-positive and HIV-negative individuals, both drug-injecting and non-injecting, to identify bacterial community changes in response to HIV and drug use. We utilized a well-established cohort of people who inject drugs in Puerto Rico, a region with historically high levels of injection drug use and an HIV incidence rate disproportionately associated with drug use.

Switching Residues: A Platform for the Synthesis of Fidaxomicin Antibiotics.

Peripheral modification is often the main approach to optimize natural products for improved biological activity or desired physicochemical properties. This procedure inevitably increases molecular weight, often accompanied by undesired increased lipophilicity. Removing structural elements from natural products is not always tolerated.

Re-programming by a six-factor-secretome in the patient tumor ecosystem during nutrient stress and drug response.

Cancer cells need nutrients to grow and proliferate. During nutrient stress in the microenvironment, it is unclear or cancer cells can adopt alternative resources to re-wire and survive in patients. We discovered a 6-factor-secretome remarkably sustains a critical cell mass during nutrient stress in a pediatric embryonal brain tumor, atypical teratoid rhabdoid tumor (ATRT).

DA-R-EPOCH May Mitigate the Adverse Prognostic Implication of the Diagnosis-to-Treatment Interval (DTI) in Large B-Cell Lymphomas.

Background: Short diagnosis-to-treatment interval (DTI) is associated with high-risk disease and poor survival in diffuse large B-cell lymphoma (DLBCL). There is a paucity of literature on DTI and survival in DLBCL treated with first-line DA-R-EPOCH. We hypothesized that rapid initiation of DA-R-EPOCH in aggressive and high-risk DLBCL mitigates the adverse prognostic implication of short DTI.

Discontinuation of maintenance therapy in multiple myeloma guided by multimodal measurable residual disease negativity (MRD2STOP).

MRD2STOP is a pragmatic trial evaluating maintenance therapy cessation guided by measurable residual disease (MRD) negativity in multiple myeloma (MM). Eligible patients had previous MRD < 10, received ≥1 year of maintenance, and were prospectively confirmed to have undetectable disease by positron emission tomography, bone marrow (BM) flow cytometry (limit of detection [LoD] 10), and BM clonoSEQ (LoD 10). BM aspirates enriched for CD138 cells were analyzed by clonoSEQ to achieve MRD 10 sensitivity.

SOHO State of the Art Updates and Next Questions | Measuring Patient-Reported Outcomes (PROs) and Treatment Tolerability in Patients With Hematologic Malignancies.

There has been a rapid expansion of novel therapeutics for hematologic malignancies, including monoclonal antibodies, small molecules, and cellular therapies, which confer different treatment-related toxicities and symptomatic adverse events (AEs) than traditional cytotoxic chemotherapies. Given that patients with blood cancers are living longer with these newer treatments, with some therapies requiring indefinite or time-intensive administration, consideration of patient-reported tolerability and effects on health-related quality of life (HRQoL) are increasingly relevant. Historically, clinical trials have focused on the efficacy and safety of therapies.

Cognitive Intraindividual variability in injection drug use among Hispanic residents of Puerto Rico.

Despite a high prevalence of injection drug use (IDU) in Puerto Rico, little is known about how it affects neuropsychological functioning in this population. Investigations of intra-individual variability (IIV) have alluded to its utility as a potential indicator of neural decline. The purpose of this study was to characterize IIV among Hispanic residents of Puerto Rico who engage in IDU.

Gynecological Laparoscopic Surgeries under Spinal Anesthesia: Benefits and Challenges.

Objective: This prospective study investigated the feasibility of performing laparoscopic pelvic surgery under spinal anesthesia and analyzed the intraoperative side effects, like pain, nausea, and vomitus, of 915 patients.

Methods: The implementation and performance of laparoscopic surgery under local anesthesia on 915 patients (out of a total of 3212 who underwent laparoscopic pelvic surgery under spinal anesthesia) were analyzed in relation to BMI (body mass index), obesity, pain during surgery, amount of intraperitoneal mmHg CO gas pressure, and surgical complications.

Results: BMI > 30, intra-abdominal adhesions, increased duration of the operation, bleeding, and increased intraperitoneal CO pressure were statistically significant as the main causes of pain during laparoscopic surgery under spinal anesthesia.

Final analysis of a phase II trial of daratumumab, carfilzomib, lenalidomide, and dexamethasone in newly diagnosed multiple myeloma without transplant.

We evaluated the efficacy and safety of 24 cycles of Dara in combination with carfilzomib (K), lenalidomide (R), and dexamethasone (d) without autologous stem cell transplant (ASCT) in newly diagnosed multiple myeloma (NDMM) irrespective of ASCT eligibility in a single-arm, phase II study. The primary endpoint was the rate of stringent complete response (sCR) and/or measurable residual disease (MRD) < 10 by next-generation sequencing (NGS) at the end of cycle 8 (C8). MRD was also assessed on peripheral blood samples using both the EXENT system and liquid chromatography-mass spectrometry (LC-MS).

Phase I Trial of GD2.CART Cells Augmented With Constitutive Interleukin-7 Receptor for Treatment of High-Grade Pediatric CNS Tumors.

Purpose: T cells modified with chimeric antigen receptors (CARTs) have demonstrated efficacy for hematologic malignancies; however, benefit for patients with CNS tumors has been limited. To enhance T cell activity against GD2+ CNS malignancies, we modified GD2-directed CART cells (GD2.CARTs) with a constitutively active interleukin (IL)-7 receptor (C7R-GD2.

The CNS relapse in T-cell lymphoma index predicts CNS relapse in patients with T- and NK-cell lymphomas.

Little is known about risk factors for central nervous system (CNS) relapse in mature T-cell and natural killer cell neoplasms (MTNKNs). We aimed to describe the clinical epidemiology of CNS relapse in patients with MTNKN and developed the CNS relapse In T-cell lymphoma Index (CITI) to predict patients at the highest risk of CNS relapse. We reviewed data from 135 patients with MTNKN and CNS relapse from 19 North American institutions.

Long-term combination therapy with metformin and oxymetholone in a Fanconi anemia mouse model.

Fanconi anemia (FA) is a disease caused by defective deoxyribonucleic acid (DNA) repair that manifests as bone marrow failure, cancer predisposition, and developmental defects. We previously reported that monotherapy with either metformin (MET) or oxymetholone (OXM) improved peripheral blood (PB) counts and the number and functionality of bone marrow hematopoietic stem progenitor cells (HSPCs) number in Fancd2 mice. To evaluate whether the combination treatment of these drugs has a synergistic effect to prevent bone marrow failure in FA, we treated cohorts of Fancd2 mice and wildtype controls with either MET alone, OXM alone, MET+OXM, or placebo diet from age 3 weeks to 18 months.

Ex vivo gene editing and cell therapy for hereditary tyrosinemia type 1.

Background: We previously demonstrated the successful use of in vivo CRISPR gene editing to delete 4-hydroxyphenylpyruvate dioxygenase (HPD) to rescue mice deficient in fumarylacetoacetate hydrolase (FAH), a disorder known as hereditary tyrosinemia type 1 (HT1). The aim of this study was to develop an ex vivo gene-editing protocol and apply it as a cell therapy for HT1.

Methods: We isolated hepatocytes from wild-type (C57BL/6J) and Fah-/- mice and then used an optimized electroporation protocol to deliver Hpd-targeting CRISPR-Cas9 ribonucleoproteins into hepatocytes.

Autologous HER2-specific CAR T cells after lymphodepletion for advanced sarcoma: a phase 1 trial.

In this prospective, interventional phase 1 study for individuals with advanced sarcoma, we infused autologous HER2-specific chimeric antigen receptor T cells (HER2 CAR T cells) after lymphodepletion with fludarabine (Flu) ± cyclophosphamide (Cy): 1 × 10 T cells per m after Flu (cohort A) or Flu/Cy (cohort B) and 1 × 10 CAR T cells per m after Flu/Cy (cohort C). The primary outcome was assessment of safety of one dose of HER2 CAR T cells after lymphodepletion. Determination of antitumor responses was the secondary outcome.

International Prognostic Score for Nodular Lymphocyte-Predominant Hodgkin Lymphoma.

Purpose: Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare cancer, and large international cooperative efforts are needed to evaluate the significance of clinical risk factors and immunoarchitectural patterns (IAPs) for all stages of pediatric and adult patients with NLPHL.

Methods: Thirty-eight institutions participated in the Global nLPHL One Working Group retrospective study of NLPHL cases from 1992 to 2021. We measured progression-free survival (PFS), overall survival (OS), transformation rate, and lymphoma-specific death rate.

Synaptic and dendritic architecture of different types of hippocampal somatostatin interneurons.

GABAergic inhibitory neurons fundamentally shape the activity and plasticity of cortical circuits. A major subset of these neurons contains somatostatin (SOM); these cells play crucial roles in neuroplasticity, learning, and memory in many brain areas including the hippocampus, and are implicated in several neuropsychiatric diseases and neurodegenerative disorders. Two main types of SOM-containing cells in area CA1 of the hippocampus are oriens-lacunosum-moleculare (OLM) cells and hippocampo-septal (HS) cells.

Computer tomography measurements of the airway and thoracic cavity do not provide support for bronchial conformation as a predisposing factor of left cranial lung lobe torsion in pugs.

The objective of this retrospective clinical study was to determine if airway or thoracic cavity measurements in pugs, particularly the left cranial lung lobe, were significantly different from brachycephalic and mesocephalic control. Thoracic computed tomographic studies of 10 pugs, French bulldogs (FB), and Jack Russell Terriers (JRT) were analyzed. Thoracic height: width ratio (H:W), cross-sectional areas of the left mainstem bronchus (CSA LMB), left cranial lung lobe bronchus (CSA LCrBr), left caudal lung lobe bronchus (CSA LCauBr), CSA LCrBr relative to length (CSA LCrBr/length) and CSA LCauBr/length were measured and adjusted to body weight (/kg).

Histopathologic and immunophenotypic characterization of patient-derived pediatric malignant hepatocellular tumor xenografts (PDXs).

Advances in targeted therapies for pediatric hepatocellular tumors have been limited due to a paucity of clinically relevant models. Establishment and validation of intrahepatic patient-derived xenograft (PDX) models would help bridging this gap. The aim of this study is to compare the histomorphologic and immunophenotypic fidelity of patient tumors and their corresponding intrahepatic PDX models.

Mini review: Asymmetric Müllerian duct development in the chicken embryo.

Müllerian ducts are paired embryonic tubes that give rise to the female reproductive tract. In humans, the Müllerian ducts differentiate into the Fallopian tubes, uterus and upper portion of the vagina. In birds and reptiles, the Müllerian ducts develop into homologous structures, the oviducts.

Mixed-Methods Study of End-of-Life Experiences of Patients With Hematologic Malignancies in Social Hospice Residential Home Care Settings.

Purpose: Hospice is underutilized by patients with hematologic malignancies (HM), and when patients are referred, they are typically more ill, hospitalized, and with shorter length of stay (LOS) than patients with solid tumors (ST), limiting research about home hospice care experiences of patients with HM. In this mixed-methods study, we examined the hospice experiences of patients with HM who died at residential care homes (RCHs), home-based settings in which volunteer caregivers and hospice staff provide end-of-life (EOL) care under the social hospice model.

Methods: We queried a registry of 535 hospice patients who died at RCHs between 2005 and 2020 that included quantitative medication administration data as well as qualitative data from hospice intake forms and written volunteer caregiver narratives.

Vesicle condensation induced by synapsin: condensate size, geometry, and vesicle shape deformations.

We study the formation of vesicle condensates induced by the protein synapsin, as a cell-free model system mimicking vesicle pool formation in the synapse. The system can be considered as an example of liquid-liquid phase separation (LLPS) in biomolecular fluids, where one phase is a complex fluid itself consisting of vesicles and a protein network. We address the pertinent question why the LLPS is self-limiting and stops at a certain size, i.

A novel treatment strategy utilizing panobinostat for high-risk and treatment-refractory hepatoblastoma.

Background & Aims: Patients with metastatic, treatment-refractory, and relapsed hepatoblastoma (HB) have survival rates of less than 50% due to limited treatment options. To develop new therapeutic strategies for these patients, our laboratory has developed a preclinical testing pipeline. Given that histone deacetylase (HDAC) inhibition has been proposed for HB, we hypothesized that we could find an effective combination treatment strategy utilizing HDAC inhibition.