Hematology Commons^™

Opioid Medication Use And Blood Dna Methylation: Epigenome-Wide Association Meta-Analysis, Mikyeong Lee, Roby Joehanes, Daniel L. Mccartney, Minjung Kho, Anke Hüls, Annah B. Wyss, Chunyu Liu, Rosie M. Walker, Sharon L.R. Kardia, Thomas S. Wingo, Adam Burkholder, Jiantao Ma, Archie Campbell, Aliza P. Wingo, Tianxiao Huan, Sinjini Sikdar, Amena Keshawarz, David A. Bennett, Jennifer A. Smith, Kathryn L. Evans, Daniel Levy, Stephanie J. London

Mathematics & Statistics Faculty Publications

Aim: To identify differential methylation related to prescribed opioid use. Methods: This study examined whether blood DNA methylation, measured using Illumina arrays, differs by recent opioid medication use in four population-based cohorts. We meta-analyzed results (282 users; 10,560 nonusers) using inverse-variance weighting. Results: Differential methylation (false discovery rate <0.05) was observed at six CpGs annotated to the following genes: KIAA0226, CPLX2, TDRP, RNF38, TTC23 and GPR179. Integrative epigenomic analyses linked implicated loci to regulatory elements in blood and/or brain. Additionally, 74 CpGs were differentially methylated in males or females. Methylation at significant CpGs correlated with gene expression in blood and/or brain. Conclusion: This study identified DNA …

Platelet Micrornas Inhibit Primary Tumor Growth Via Broad Modulation Of Tumor Cell Mrna Expression In Ectopic Pancreatic Cancer In Mice, Jeremy G.T. Wurtzel, Sophia Lazar, Sonali Sikder, Kathy Q Cai, Igor Astsaturov, Andrew S Weyrich, Jesse W Rowley, Lawrence E. Goldfinger

Department of Medicine Faculty Papers

We investigated the contributions of platelet microRNAs (miRNAs) to the rate of growth and regulation of gene expression in primary ectopic tumors using mouse models. We previously identified an inhibitory role for platelets in solid tumor growth, mediated by tumor infiltration of platelet microvesicles (microparticles) which are enriched in platelet-derived miRNAs. To investigate the specific roles of platelet miRNAs in tumor growth models, we implanted pancreatic ductal adenocarcinoma cells as a bolus into mice with megakaryocyte-/platelet-specific depletion of mature miRNAs. We observed an ~50% increase in the rate of growth of ectopic primary tumors in these mice compared to controls …

Recombinant Human Proteoglycan 4 Regulates Phagocytic Activation Of Monocytes And Reduces Il-1Β Secretion By Urate Crystal Stimulated Gout Pbmcs, Sandy Elsayed, Gregory D. Jay, Ralph Cabezas, Marwa Qadri, Tannin A. Schmidt, Khaled A. Elsaid

Pharmacy Faculty Articles and Research

Objectives

To compare phagocytic activities of monocytes in peripheral blood mononuclear cells (PBMCs) from acute gout patients and normal subjects, examine monosodium urate monohydrate (MSU) crystal-induced IL-1β secretion ± recombinant human proteoglycan 4 (rhPRG4) or interleukin-1 receptor antagonist (IL-1RA), and study the anti-inflammatory mechanism of rhPRG4 in MSU stimulated monocytes.

Methods

Acute gout PBMCs were collected from patients in the Emergency Department and normal PBMCs were obtained from a commercial source. Monocytes in PBMCs were identified by flow cytometry. PBMCs were primed with Pam3CSK4 (1μg/mL) for 24h and phagocytic activation of monocytes was determined using fluorescently labeled latex beads. MSU …

Inhibition Of Nadph Oxidase Blocks Netosis And Reduces Thrombosis In Heparin-Induced Thrombocytopenia, Halina H L Leung, Jose Perdomo, Zohra Ahmadi, Feng Yan, Steven E. Mckenzie, Beng H Chong

Department of Medicine Faculty Papers

Heparin-induced thrombocytopenia (HIT) is associated with severe and potentially lethal thrombotic complications. NETosis was recently shown to be an important driver of thrombosis in HIT. We investigated the role of reactive oxygen species (ROS) and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 2 (NOX2) and their contributions to thrombus development in HIT. We showed that neutrophil activation by HIT immune complexes induced ROS-dependent NETosis. Analysis of thrombi formed in a microfluidics system showed ROS production in both platelets and neutrophils, and abundant neutrophil extracellular traps (NETs) and ROS distributed throughout the clot. Neutrophil-targeted ROS inhibition was sufficient to block HIT-induced NETosis …

Practical Considerations Of Dissolved Oxygen Levels For Platelet Function Under Hypoxia, Branden Kusanto, Andrew Gordon, Leigh Naylor-Adamson, Lloyd Atkinson, Charlie Coupland, Zoe Booth, Yusra Ahmed, Isabel M Pires, Graeme J Stasiuk, Roger Sturmey, Simon D J Calaminus, Mònica Arman

Faculty, Staff and Student Publications

Investigating human platelet function in low-oxygen environments is important in multiple settings, including hypobaric hypoxia (e.g., high altitude), sea level hypoxia-related disease, and thrombus stability. These studies often involve drawing blood from which platelets are isolated and analysed at atmospheric conditions or re-exposed to low oxygen levels in hypoxia chambers before testing. However, it remains unknown how the in vitro handling of the samples itself changes their dissolved oxygen concentration, which might affect platelet function and experimental results. Here, we prepared healthy donor platelet-rich plasma and washed platelet (WP) suspensions and exposed them to 2% oxygen. We found that the …

Thrombosis With Thrombocytopenia Syndrome After Administration Of Azd1222 Or Ad26.Cov2.S Vaccine For Covid-19: A Systematic Review, Usama Waqar, Shaheer Ahmed, Syed M H Ali Gardezi, Muhammad Sarmad Tahir, Zain Ul Abidin, Ali Hussain, Natasha Bahadur Ali, Syed Faisal Mahmood

Medical College Documents

Background: Cases of thrombosis with thrombocytopenia syndrome (TTS) have been reported following vaccination with AZD1222 or Ad26.COV2.S. This review aimed to explore the pathophysiology, epidemiology, diagnosis, management, and prognosis of TTS.
Methods: A systematic review was conducted to identify evidence on TTS till 4th September 2021. Case reports and series reporting patient-level data were included. Descriptive statistics were reported and compared across patients with different sexes, age groups, vaccines, types of thrombosis, and outcomes.
Findings: Sixty-two studies reporting 160 cases were included from 16 countries. Patients were predominantly females with a median age of 42.50 (22) years. AZD1222 was administered …

Central Line Associated Bloodstream Infection Caused By Kodamaea Ohmeri In A Young Child, Amier Haidar, Farhana Khaja, Brian Simms, Amr Issam Elgehiny, Tracy Omoegbele, Nikita Khetan

Faculty, Staff and Student Publications

INTRODUCTION:

CASE REPORT: The patient is a 5-year-old male with a history of short gut syndrome, and total parenteral nutrition (TPN) dependence who presented to the emergency room with a two-day history of productive-cough, rhinorrhea, and fever. Antibiotic therapy was initiated with cefepime and vancomycin for suspected CLABSI. However, within the first twenty-four hours of his admission, his initial blood culture from his central venous catheter became positive for yeast so fluconazole was added due to suspicion of candidemia. During his admission, his initial central line and peripheral blood culture were later speciated as

CONCLUSIONS: This case report further acknowledges …

Vte And Anticoagulation In Menstruating Women, Ida Micaily, Bethany T. Samuelson Bannow

Department of Medicine Faculty Papers

Women of childbearing potential have a high prevalence of venous thromboembolism (VTE) due to high estrogen states, such as pregnancy and the use of estrogen-containing contraceptives. Abnormal uterine bleeding (AUB) affects up to two-thirds of menstruating women on anticoagulation (AC), and can severely impair a woman's quality of life. Rates of heavy menstrual bleeding (HMB) and other forms of AUB including inter-menstrual and postmenopausal bleeding are consistently underreported in the original clinical trials utilizing AC. VTE can occur at any time in a woman's life, and the aim of this review article is to discuss the current landscape of literature …

Predicting Risk Factors For Thromboembolic Complications In Patients With Sickle Cell Anaemia - Lessons Learned For Prophylaxis, Salam Alkindi, Anwaar R Al-Ghadani, Samah R Al-Zeheimi, Said Y Alkindi, Naglaa Fawaz, Samir K. Ballas, Anil V Pathare

Cardeza Foundation for Hematologic Research

Objective: To assess the clinical and laboratory predictors of venous thromboembolism (VTE) in patients with sickle cell anaemia (SCA) and its relationship to morbidity and mortality.

Methods: This retrospective case-control study analysed data from patients with SCA that experienced VTE compared with matched control patients with SCA but no VTE (2:1 ratio).

Results: A total of 102 patients with SCA were enrolled (68 cases with VTE and 34 controls). Amongst the 68 cases (median age, 29.5 years), 26 (38.2%) presented with isolated pulmonary embolism (PE). A higher prevalence of splenectomy (73.5% versus 35.3%) was observed in the cases compared with …

Editorial: Thrombotic Microangiopathies, Diagnostic And Therapeutic Advances, Robert W. Maitta, Hollie M. Reeves

Faculty Scholarship

Thrombotic microangiopathies (TMAs) as a disease group represent a diagnostic and clinical challenge to practitioners. Presentations, which at times have overlapping symptomatology or have undetermined etiologies, emphasize the need for a constant reassessment of what is known about this disease group in order to determine not only how to best treat patients but also to develop targeted approaches to test for a given etiology. Likewise, in those instances when excluding diagnoses is the only available option, timely adjustment of therapy due to lack of therapeutic response needs to be achieved in the most efficient way. It is with this in …

Outcomes Of Patients With Double/Triple Expressor Diffuse Large B-Cell Lymphoma (Dlbcl) Treated With R-Da-Epoch/R-Chop: A Single-Center Experience, Kanta Devi, Mohammad Usman Shaikh, Natasha Bahadur Ali, Salman Adil, Maria Khan, Salman Muhammad Soomar

Section of Haematology/Oncology

In Pakistan 76.4% of all NHLs to be diagnosed as DLBCLs. The survival of R-CHOP is better compared to the DA-REPOCH treatment regimen. A prospective follow-up study was conducted with 113 patients to study the outcomes of treatment. Multivariable cox-proportional hazard model was used to estimate the hazard ratios in patients receiving these treatment regimens considering p-value ≤0.05 significant. The survival rate among double/triple expressor lymphoma patients received R-DA-EPOCH was 82.8%, and 83.3% received R-CHOP. For double/triple expressor lymphoma patients received R-DA-EPOCH. The findings of our study demonstrated that the survival rate in both R-CHOP and R-DA-EPOCH is mostly …

Colchicine, Covid-19 And Hematological Parameters: A Meta-Analysis, Musharraf Sarwar, Zahid Ali, Mahnoor Fatima, Zouina Sarfraz, Azza Sarfraz, Ivan Cherrez-Ojeda

Department of Paediatrics and Child Health

Introduction: Colchicine has the potential in reducing patient morbidity and mortality in COVID-19 infection owing to its anti-inflammatory properties. This study aims to determine the efficacy of colchicine in optimizing inflammatory hematological biomarker levels among COVID-19 patients.
Methods: In accordance to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 statement guidelines, a systematic search was conducted using the following keywords: Colchicine, covid*, SARS-CoV-2, anti-inflammatory, trials, clinical, hematological, laboratory. Databases were searched from December 2019 until August 26, 2021: MEDLINE/PubMed, Web of Science, Cochrane, Scopus, and EMBASE. Other sources were located through ClinicalTrials.Gov, manually searching SAGE, Science Direct, Elsevier, …

Blood Transfusions Increase The Risk For Venous Thromboembolism Events Following Total Joint Arthroplasty, Noam Shohat, Leanne Ludwick, Graham S Goh, Matthew Sherman, Joseph Paladino, Javad Parvizi

Rothman Institute Papers

The association between blood transfusions and thromboembolic events (VTE) following total joint arthroplasty (TJA) remains debatable. Using contemporary institutional data, this study aimed to determine whether blood transfusions increase the risk of VTE following primary and revision TJA. This was a single institution, retrospective cohort study. The clinical records of all patients (n = 34,824) undergoing primary and revision TJA between 2009 and 2020 were reviewed. Demographic variables, co-morbidities, type of chemoprophylaxis and intraoperative factors such as use of tranexamic acid were collected. Clinical notes, hospital orders, and discharge summaries were reviewed to determine if a patient received a blood …

A Phase Ib Dose Escalation Trial Of Ro4929097 (A Γ-Secretase Inhibitor) In Combination With Exemestane In Patients With Er + Metastatic Breast Cancer (Mbc), Julie A. Means-Powell, Ingrid A. Mayer, Roohi Ismail-Khan, Luis Del Valle, Debra Tonetti, Vandana G. Abramson, Melinda S. Sanders, Richard M. Lush, Claudia Sorrentino, Samarpan Majumder, Lucio Miele

School of Medicine Faculty Publications

Preclinical studies: have demonstrated a complex cross-talk between Notch and estrogen signaling in ERα-positive breast cancer. Gamma-secretase inhibitors (GSIs) are investigational agents that block the cleavage and activation of Notch receptors. In animal models of endocrine-resistant breast cancer, combinations of tamoxifen and GSIs produce additive or synergistic efficacy, while decreasing the intestinal toxicity of GSIs. However, results of a clinical trial of a GSI-endocrine therapy combination in the metastatic setting have not been published to date, nor had the safety of such combinations been investigated with longer term treatment. We conducted a phase 1b dose escalation trial (NCT01149356) of GSI …

Strategic Priorities For Hematopoietic Stem Cell Transplantation In The Emro Region, Syed Osman Ahmed, Riad El Fakih, Alaa Elhaddad, Amir Ali Hamidieh, Abdulghani Altbakhi, Qamar-Un-Nisa Chaudhry, Ali Bazarbachi, Salman Adil, Murtadha Al-Khabori, Tarek Ben Othman

Section of Haematology/Oncology

The World Health Organization-designated Eastern Mediterranean region (EMRO) consists of 22 countries in North Africa and Western Asia with a collective population of over 679 million. The area comprises some of the wealthiest countries per capita income and some of the poorest. The population structure is also unique and contrasts with western countries, with a much younger population. The region sits in the heart of the thalassemia belt. Many countries have a significant prevalence of sickle cell disease, and cancer is on the rise in the region. Therefore, the strategic priorities for the growth and development of hematopoietic stem cell …

A Novel Combination Chemotherapy Targeting Extramedullary Disease In Multiple Myeloma Following First-Line Treatment Failure, Ruaa M. Elteriefi, Nourelhuda Abbas Hamed, Omar Nasser Rahal, Faisal Musa

Conference Presentation Abstracts

Introduction:

Multiple Myeloma (MM), a plasma cell neoplasm that resides in the bone marrow’s intramedullary space.

Extramedullary disease (EMD) occurs when plasma cells extend through the bone cortex or via hematogenous spread to different organs.

This case of EMD of MM didn’t respond to the first line RVD regimen per NCCN guidelines which includes Lenalidomide (Revlimid), Bortezomib (Velcade), and Dexamethasone (Decadron). Therefore, new combination chemotherapy including Daratumumab, and Carfilzomib was initiated with excellent response.

Case description:

62-year-old female presenting to the oncologist for progressive right hip pain for 4 weeks. Initial hip x-ray and bone scan suspected malignancy. MRI showed …

Role Of Gut Microbiome In Covid-19: An Insight Into Pathogenesis And Therapeutic Potential, Ikram Hussain, Gabriel Liu Yuan Cher, Muhammad Abbas Abid, Muhammad Bilal Abid

Department of Pathology and Laboratory Medicine

Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), resulted in an unprecedented global crisis. Although primarily a respiratory illness, dysregulated immune responses may lead to multi-organ dysfunction. Prior data showed that the resident microbial communities of gastrointestinal and respiratory tracts act as modulators of local and systemic inflammatory activity (the gut-lung axis). Evolving evidence now signals an alteration in the gut microbiome, brought upon either by cytokines from the infected respiratory tract or from direct infection of the gut, or both. Dysbiosis leads to a "leaky gut". The intestinal permeability then allows access to …

A Prospective Observational Study Of Antihemophilic Factor (Recombinant) Prophylaxis Related To Physical Activity Levels In Patients With Hemophilia A In The United States (Space), Barbara A. Konkle, Doris V. Quon, Leslie Raffini, Michael Recht, Vlad C. Radulescu, Shannon L. Carpenter, Amy L. Dunn, Mei Lu, Maureen Watt

Pediatrics Faculty Publications

Introduction: High collision-risk physical activity can increase bleeding risk in people with hemophilia A, as can increasing the time between factor VIII (FVIII) administration and physical activity. FVIII prophylaxis may be tailored to planned activities to prevent activity-related bleeding.

Aim: To explore the relationship between physical activity levels, FVIII infusion timing, and occurrence of bleeding in patients with severe/moderately severe hemophilia A without FVIII inhibitors receiving antihemophilic factor (recombinant) (rAHF; ADVATE^®; Baxalta US Inc., a Takeda company, Lexington, MA, USA).

Methods: SPACE was a 6-month, prospective, multicenter, observational outcomes study (NCT02190149). Enrolled patients received an eDiary application and …

Type 1 Cryoglobulinemia Secondary To Primary Plasma Cell Leukemia, Antonio Faieta, Khatoon Tawhida

Conference Presentation Abstracts

Primary plasma cell leukemia (pPCL) is a rare and aggressive form of plasma cell dyscrasia that comprises 1% of the plasma cell dyscrasias. Even more rare is its association with type 1 cryoglobulinemia which management can be challenging. A 63-year-old African American male with no past medical history presented with severe burning pain in his legs, necrotizing rash, constitutional symptoms and severe acute kidney injury (AKI). HIV, hepatitis B and C were negative. Serum electrophoresis revealed an M-spike of 5.67, IgG of 7000, free lambda of 152.10 with a K/L of 0 and cryoglobulin of 81%. CT revealed extensive lytic …

Diagnosis And Management Of Diffuse Large B-Cell Lymphoma: Society Of Medical Oncology, Pakistan Society Of Hematology, And Pakistan Society Of Clinical Oncology Joint Clinical Practice Guideline, Raheel Iftikhar, Muhammad Ayaz Mir, Munira Moosajee, Kamran Rashid, Syed Waqas Bokhari, Ahmed Nadeem Abbasi, Tahir Sultan Shamsi, Mohammad Usman Shaikh, Natasha Bahadur Ali, Salman Adil

Section of Haematology/Oncology

Diffuse large B-cell lymphoma (DLBCL) is the commonest non-Hodgkin lymphoma encountered by hematopathologists and oncologists. Management guidelines for DLBCL are developed and published by countries with high income and do not cater for practical challenges faced in resource-constrained settings. This report by a multidisciplinary panel of experts from Pakistan is on behalf of three major national cancer societies: Society of Medical Oncology Pakistan, Pakistan Society of Hematology, and Pakistan Society of Clinical Oncology. The aim is to develop a practical and standardized guideline for managing DLBCL in Pakistan, keeping in view local challenges, which are similar across most of the …