Monitoring clonal burden as an alternative to blast count for myelodysplastic neoplasm treatment response.

Accurate assessment of therapy response in myelodysplastic neoplasm (MDS) has been challenging. Directly monitoring mutational disease burden may be useful, but is not currently included in MDS response criteria, and the correlation of mutational burden and traditional response endpoints is not completely understood. Here, we used genome-wide and targeted next-generation sequencing (NGS) to monitor clonal and subclonal molecular disease burden in 452 samples from 32 patients prospectively treated in a clinical trial.

Laparoscopic sleeve gastrectomy to Roux-en-Y gastric bypass conversion versus primary Roux-en-Y gastric bypass: a propensity score matching analysis.

Background: Secondary bariatric surgery rates have increased, accounting for approximately 19% of the total bariatric cases in the last years, most commonly conversion of sleeve gastrectomy to gastric bypass. Using the MBSAQIP, we evaluate the outcomes of this procedure compared to the primary RYGB surgery.

Methods: The new variable, conversion of sleeve gastrectomy to RYGB in the 2020 and 2021 MBSAQIP database was analyzed.

Persistent Molecular Disease in Adult Patients With AML Evaluated With Whole-Exome and Targeted Error-Corrected DNA Sequencing.

Purpose: Persistent molecular disease (PMD) after induction chemotherapy predicts relapse in AML. In this study, we used whole-exome sequencing (WES) and targeted error-corrected sequencing to assess the frequency and mutational patterns of PMD in 30 patients with AML.

Materials And Methods: The study cohort included 30 patients with adult AML younger than 65 years who were uniformly treated with standard induction chemotherapy.

Convergent Clonal Evolution of Signaling Gene Mutations Is a Hallmark of Myelodysplastic Syndrome Progression.

Unlabelled: Progression from myelodysplastic syndromes (MDS) to secondary acute myeloid leukemia (AML) is associated with the acquisition and expansion of subclones. Our understanding of subclone evolution during progression, including the frequency and preferred order of gene mutation acquisition, remains incomplete. Sequencing of 43 paired MDS and secondary AML samples identified at least one signaling gene mutation in 44% of MDS and 60% of secondary AML samples, often below the level of standard sequencing detection.

Improving Antibiotic Stewardship in Acute Appendicitis through Risk-Based Empiric Treatment Selection.

Empiric antimicrobial treatment selection for management of appendicitis is based on patient risk of infection with drug-resistant pathogens. Per Surgical Infection Society (SIS) guidelines, only high-risk patients should receive extended spectrum antibiotics. After observing substantial use of piperacillin-tazobactam at an academic medical center, a quality improvement initiative was developed targeting standardization of antibiotics for uncomplicated appendicitis.

Genome Sequencing as an Alternative to Cytogenetic Analysis in Myeloid Cancers.

Background: Genomic analysis is essential for risk stratification in patients with acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS). Whole-genome sequencing is a potential replacement for conventional cytogenetic and sequencing approaches, but its accuracy, feasibility, and clinical utility have not been demonstrated.

Methods: We used a streamlined whole-genome sequencing approach to obtain genomic profiles for 263 patients with myeloid cancers, including 235 patients who had undergone successful cytogenetic analysis.

Immune Escape of Relapsed AML Cells after Allogeneic Transplantation.

Background: As consolidation therapy for acute myeloid leukemia (AML), allogeneic hematopoietic stem-cell transplantation provides a benefit in part by means of an immune-mediated graft-versus-leukemia effect. We hypothesized that the immune-mediated selective pressure imposed by allogeneic transplantation may cause distinct patterns of tumor evolution in relapsed disease.

Methods: We performed enhanced exome sequencing on paired samples obtained at initial presentation with AML and at relapse from 15 patients who had a relapse after hematopoietic stem-cell transplantation (with transplants from an HLA-matched sibling, HLA-matched unrelated donor, or HLA-mismatched unrelated donor) and from 20 patients who had a relapse after chemotherapy.

Mutation Clearance after Transplantation for Myelodysplastic Syndrome.

Background: Allogeneic hematopoietic stem-cell transplantation is the only curative treatment for patients with myelodysplastic syndrome (MDS). The molecular predictors of disease progression after transplantation are unclear.

Methods: We sequenced bone marrow and skin samples from 90 adults with MDS who underwent allogeneic hematopoietic stem-cell transplantation after a myeloablative or reduced-intensity conditioning regimen.

A case of acute myeloid leukemia with promyelocytic features characterized by expression of a novel - fusion.

Novel fusion in an AML case with promyelocytic features and no evidence of - or X- fusion. Gene fusions involving can initiate AML with promyelocytic morphological features.

Subclones dominate at MDS progression following allogeneic hematopoietic cell transplant.

Allogeneic hematopoietic cell transplantation (alloHCT) is a potentially curative treatment for myelodysplastic syndromes (MDS), but patients who relapse after transplant have poor outcomes. In order to understand the contribution of tumor clonal evolution to disease progression,we applied exome and error-corrected targeted sequencing coupled with copy number analysis to comprehensively define changes in the clonal architecture of MDS in response to therapy using 51 serially acquired tumor samples from 9 patients who progressed after an alloHCT. We show that small subclones before alloHCT can drive progression after alloHCT.

Mutant U2AF1-expressing cells are sensitive to pharmacological modulation of the spliceosome.

Somatic mutations in spliceosome genes are detectable in ∼50% of patients with myelodysplastic syndromes (MDS). We hypothesize that cells harbouring spliceosome gene mutations have increased sensitivity to pharmacological perturbation of the spliceosome. We focus on mutant U2AF1 and utilize sudemycin compounds that modulate pre-mRNA splicing.

TP53 and Decitabine in Acute Myeloid Leukemia and Myelodysplastic Syndromes.

Background: The molecular determinants of clinical responses to decitabine therapy in patients with acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS) are unclear.

Methods: We enrolled 84 adult patients with AML or MDS in a single-institution trial of decitabine to identify somatic mutations and their relationships to clinical responses. Decitabine was administered at a dose of 20 mg per square meter of body-surface area per day for 10 consecutive days in monthly cycles.

Brief Report: The Role of Rare Protein-Coding Variants in Anti-Tumor Necrosis Factor Treatment Response in Rheumatoid Arthritis.

Objective: In many rheumatoid arthritis (RA) patients, disease is controlled with anti-tumor necrosis factor (anti-TNF) biologic therapies. However, in a significant number of patients, the disease fails to respond to anti-TNF therapy. We undertook the present study to examine the hypothesis that rare and low-frequency genetic variants might influence response to anti-TNF treatment.

Dynamic changes in the clonal structure of MDS and AML in response to epigenetic therapy.

Traditional response criteria in myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) are based on bone marrow morphology and may not accurately reflect clonal tumor burden in patients treated with non-cytotoxic chemotherapy. We used next-generation sequencing of serial bone marrow samples to monitor MDS and AML tumor burden during treatment with epigenetic therapy (decitabine and panobinostat). Serial bone marrow samples (and skin as a source of normal DNA) from 25 MDS and AML patients were sequenced (exome or 285 gene panel).

Implant-derived magnesium induces local neuronal production of CGRP to improve bone-fracture healing in rats.

Orthopedic implants containing biodegradable magnesium have been used for fracture repair with considerable efficacy; however, the underlying mechanisms by which these implants improve fracture healing remain elusive. Here we show the formation of abundant new bone at peripheral cortical sites after intramedullary implantation of a pin containing ultrapure magnesium into the intact distal femur in rats. This response was accompanied by substantial increases of neuronal calcitonin gene-related polypeptide-α (CGRP) in both the peripheral cortex of the femur and the ipsilateral dorsal root ganglia (DRG).

An Unusual Case Presentation of the May-Thurner Syndrome.

A 56-year-old woman underwent abdominoplasty with no immediate complications. She had no known bleeding history nor any relevant past surgical history. Adequate preventive measures for venous thromboembolism were performed, including sequential compression devices, good hydration, and early ambulation.

A common founding clone with TP53 and PTEN mutations gives rise to a concurrent germ cell tumor and acute megakaryoblastic leukemia.

We report the findings from a patient who presented with a concurrent mediastinal germ cell tumor (GCT) and acute myeloid leukemia (AML). Bone marrow pathology was consistent with a diagnosis of acute megakaryoblastic leukemia (AML M7), and biopsy of an anterior mediastinal mass was consistent with a nonseminomatous GCT. Prior studies have described associations between hematological malignancies, including AML M7 and nonseminomatous GCTs, and it was recently suggested that a common founding clone initiated both cancers.