Smoking-Associated Carcinogen-Induced Inflammation Promotes Lung Carcinogenesis via IRAK4 Activation.

Purpose: Even though smoking is associated with lung cancer, the exact molecular pathways that link carcinogens with inflammation and oncogenic transformation are not well elucidated. Two major carcinogens in cigarette smoke, nicotine-derived nitrosamine ketone, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), and benzo(α)pyrene (BaP), have not been tested in models that mimic inhaled exposure for prolonged periods of time.

Experimental Design: Mouse models were used for intratracheal delivery of NNK and BaP (NB) for 18 months.

Understanding the Continuum between High-Risk Myelodysplastic Syndrome and Acute Myeloid Leukemia.

Myelodysplastic syndrome (MDS) is a clonal hematopoietic neoplasm characterized by bone marrow dysplasia, failure of hematopoiesis and variable risk of progression to acute myeloid leukemia (AML). Recent large-scale studies have demonstrated that distinct molecular abnormalities detected at earlier stages of MDS alter disease biology and predict progression to AML. Consistently, various studies analyzing these diseases at the single-cell level have identified specific patterns of progression strongly associated with genomic alterations.

Lower Limb Paralysis as Initial Presentation of Arterial Embolism Secondary to Heparin-Induced Thrombocytopenia after Hip Fracture - a Case Report.

Prophylactic anticoagulation (AC) with low molecular weight heparins (LMWHs) following hip fracture has reduced the incidence of severe thromboembolic events. However, heparin-induced thrombocytopenia (HIT) remains a serious complication in these patients. We report an unusual case of thrombosis due to severe HIT in a 75-year-old female patient following intramedullary nailing for a hip fracture.

Outcomes of Refractory Cytomegalovirus Infection in the First Year after Allogeneic Hematopoietic Cell Transplantation.

Outcomes of refractory (Rf) cytomegalovirus (CMV) infection (CMVi) after hematopoietic cell transplantation (HCT) are poor owing to limited treatment options and treatment related toxicities. Maribavir, an orally bioavailable CMV antiviral, was recently approved for treatment of Rf-CMVi. Real-world studies quantifying the burden of Rf-CMVi prior to maribavir provide a benchmark for evaluating the net value of novel treatments.

Impact of Letermovir Primary Cytomegalovirus Prophylaxis on 1-Year Mortality After Allogeneic Hematopoietic Cell Transplantation: A Retrospective Cohort Study.

Background: Cytomegalovirus (CMV)-seropositive (R+) hematopoietic cell transplant (HCT) recipients have a survival disparity compared with CMV-seronegative recipient/donor (R-D-) pairs. We hypothesized that primary letermovir prophylaxis (LET) may abrogate this disparity. We investigated the relationship between LET and mortality at 1 year post-HCT.

Increased Incidence of Thrombosis in a Cohort of Cancer Patients with COVID-19.

Background: Increased rates of thromboembolism (TE) have been reported in patients with COVID-19, even without prior predisposition to thrombosis. Cancer patients are already predisposed to a hypercoagulable state. This study was designed to assess the TE incidence in COVID-19+ patients with active cancer and its impact on survival.

Clinical Trials Assessing Hypomethylating Agents Combined with Other Therapies: Causes for Failure and Potential Solutions.

Purpose: Azacitidine and decitabine are hypomethylating agents (HMA), that is, both inhibit and deplete DNA methyltransferase 1 (DNMT1). HMAs are standard single-agent therapies for myelodysplastic syndromes and acute myelogenous leukemias. Several attempts to improve outcomes by combining HMAs with investigational agents, excepting with the BCL2-inhibitor venetoclax, have failed in randomized clinical trial (RCT) evaluations.

Normal anatomy, variants and factors associated with the cervical vagus nerve topography: a high-resolution ultrasound study.

Purpose: To describe the cervical vagus nerve (CVN) topography at the thyroid lobe (TL) level using high-resolution ultrasound and to investigate the possible association with anthropometric data, TL size, and thyroid disease.

Methods: We prospectively examined 550 CVNs in 275 (205 female, 70 male) individuals with normal thyroid (53/275, 19.3%), multinodular disease (167/275, 60.

The Use of Point-of-Care Ultrasound (POCUS) in the Diagnosis of Deep Vein Thrombosis.

Acute lower extremity proximal deep venous thrombosis (DVT) requires accurate diagnosis and treatment in order to prevent embolization and other complications. Point-of-care ultrasound (POCUS), a clinician performed, and clinician interpreted bedside ultrasound examination has been increasingly used for DVT evaluation mainly in the urgent and critical care setting, but also in the ambulatory clinics and the medical wards. Studies have demonstrated that POCUS has excellent diagnostic accuracy for acute proximal DVT when performed by well-trained users.

Diabetes is associated with increased risk for in-hospital mortality in patients with COVID-19: a systematic review and meta-analysis comprising 18,506 patients.

Purpose: Infectious diseases are more frequent and can be associated with worse outcomes in patients with diabetes. The aim of this study was to systematically review and conduct a meta-analysis of the available observational studies reporting the effect of diabetes on mortality among hospitalized patients with COVID-19.

Methods: The Medline, Embase, Google Scholar, and medRxiv databases were reviewed for identification of eligible studies.

Impact of Preemptive Therapy for Cytomegalovirus on Hospitalizations and Cost after Hematopoietic Stem Cell Transplantation.

Cytomegalovirus (CMV) viremia occurs in 40% to 80% of CMV-seropositive (R+) recipients of allogeneic hematopoietic cell transplantation (HCT). The preemptive therapy (PET) strategy has reduced the risk of CMV end-organ disease (EOD) and associated mortality but may lead to substantial healthcare resource utilization (HCRU) and costs. Real-world data on the economic impact of PET is relevant for the evaluation of alternative strategies for CMV management.

Adenovirus Viral Kinetics and Mortality in Ex Vivo T Cell-Depleted Hematopoietic Cell Transplant Recipients With Adenovirus Infection From a Single Center.

Background: We report on predictors of adenovirus (ADV) viremia and correlation of ADV viral kinetics with mortality in ex vivo T-cell depleted (TCD) hematopoietic cell transplant (HCT).

Methods: T cell-depleted HCT recipients from January 1, 2012 through September 30, 2018 were prospectively monitored for ADV in the plasma through Day (D) +100 posttransplant or for 16 weeks after the onset of ADV viremia. Adenovirus viremia was defined as ≥2 consecutive viral loads (VLs) ≥1000 copies/mL through D +100.

Impact of Preemptive Therapy for Cytomegalovirus on Toxicities after Allogeneic Hematopoietic Cell Transplantation in Clinical Practice: A Retrospective Single-Center Cohort Study.

(Val)ganciclovir (vGCV) or foscarnet (FCN) as preemptive therapy (PET) for cytomegalovirus (CMV) after allogeneic hematopoietic cell transplantation (HCT) is associated with myelosuppression and nephrotoxicity, respectively. We analyzed a cohort of CMV-seropositive (R) HCT recipients managed preemptively at a single center. The objectives of our study were to (1) quantify the frequencies of neutropenia and acute kidney injury (AKI) through day +100 (D100) post-HCT and at PET discontinuation and (2) assess the impact of PET on neutropenia and AKI in multivariate models.

Liver findings in patients with Carney complex, germline PRKAR1A pathogenic variants, and link to cardiac myxomas.

This study aimed to evaluate liver involvement in patients with Carney complex (CNC) based on a large cohort and to analyze any germline PRKAR1A genotype-phenotype association of liver disease. The study included 83 patients with CNC, followed between 1995 and 2018 at a tertiary research center. We reviewed liver images, recorded types and number of lesions and analyzed per genotype: all patients were sequenced for the PRKAR1A gene.

Impact of advanced glycation end products (AGEs) signaling in coronary artery disease.

Coronary artery disease remains the leading cause of mortality in adult diabetic population with however, a high predominance also in non-diabetic subjects. In search of common molecular mechanisms and metabolic by-products with potential pathogenic role, increased advanced glycation end products (AGEs) present a critical biomarker for CAD development in both cases. Interaction of AGEs with their transmembrane cell receptor, RAGE in endothelial and smooth muscle cells as well as in platelets, activates intracellular signaling that leads to endothelial injury, modulation of vascular smooth muscle cell function and altered platelet activity.

Critical Role of IL-8 Targeting in Gliomas.

Background: Glioma is a heterogeneous, highly complicated central nervous system (CNS) tumor with uncertain mechanism of initiation and progression, resulting in an unfavorable outcome. An extended network of cytokines is recognized as a major regulator of glioma pathogenesis, either promoting or inhibiting glioma progression based on their type and specificity. Interleukin-8 (IL-8) has been revealed as a critical regulator of CNS function and development with participation in many CNS disorders including gliomas.

Failure to Thrive in the Context of Carney Complex.

Background/aims: Carney complex (CNC) is a rare syndrome associated with multiple tumors and several other unique manifestations. We describe the clinical, genetic, and laboratory findings in a cohort of patients with CNC and failure to thrive (FTT).

Methods: A retrospective case series of pediatric patients with CNC presenting with FTT.