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Articles 661 - 690 of 2441
Full-Text Articles in Medical Specialties
Blackwater Fever And Acute Kidney Injury In Children Hospitalized With An Acute Febrile Illness: Pathophysiology And Prognostic Significance, Andrea Conroy, Michael Hawkes, Aleksandra Leligdowicz, Ivan Mufumba, Michelle Starr, Kathleen Zhong, Sophie Namasopo, Robert Opoka, Chandy John, Kevin C. Kain
Blackwater Fever And Acute Kidney Injury In Children Hospitalized With An Acute Febrile Illness: Pathophysiology And Prognostic Significance, Andrea Conroy, Michael Hawkes, Aleksandra Leligdowicz, Ivan Mufumba, Michelle Starr, Kathleen Zhong, Sophie Namasopo, Robert Opoka, Chandy John, Kevin C. Kain
Paediatrics and Child Health, East Africa
Background: Acute kidney injury (AKI) and blackwater fever (BWF) are related but distinct renal complications of acute febrile illness in East Africa. The pathogenesis and prognostic signifcance of BWF and AKI are not well understood.
Methods: A prospective observational cohort study was conducted to evaluate the association between BWF and AKI in children hospitalized with an acute febrile illness. Secondary objectives were to examine the association of AKI and BWF with (i) host response biomarkers and (ii) mortality. AKI was defned using the Kidney Disease: Improving Global Outcomes criteria and BWF was based on parental report of tea-colored urine. Host …
Idiopathic Pulmonary Fibrosis And Lung Cancer: Future Directions And Challenges, Ahmad Abu Qubo, Jamil Numan, Juan Snijder, Maria Padilla, John H.M. Austin, Kathleen M. Capaccione, Monica Pernia, Jean Bustamante, Timothy O’Connor, Mary M. Salvatore
Idiopathic Pulmonary Fibrosis And Lung Cancer: Future Directions And Challenges, Ahmad Abu Qubo, Jamil Numan, Juan Snijder, Maria Padilla, John H.M. Austin, Kathleen M. Capaccione, Monica Pernia, Jean Bustamante, Timothy O’Connor, Mary M. Salvatore
Einstein Health Papers
Idiopathic pulmonary fibrosis (IPF) is a progressive disease of pulmonary scarring. New treatments slow disease progression and allow pulmonary fibrosis patients to live longer. Persistent pulmonary fibrosis increases a patient’s risk of developing lung cancer. Lung cancer in patients with IPF differs from cancers that develop in the non-fibrotic lung. Peripherally located adenocarcinoma is the most frequent cell type in smokers who develop lung cancer, while squamous cell carcinoma is the most frequent in pulmonary fibrosis. Increased fibroblast foci in IPF are associated with more aggressive cancer behaviour and shorter doubling times. Treatment of lung cancer in fibrosis is challenging …
Randomized Placebo-Controlled Trial Of Oral Tannin Supplementation On Covid-19 Symptoms, Gut Dysbiosis And Cytokine Response, Silvia Molino, Andrea Pisarevsky, Shyam Badu, Qinglong Wu, Fabiana López Mingorance, Patricia Vega, Juan Pablo Stefanolo, Julieta Repetti, Guillermina Ludueña, Pablo Pepa, Juan Ignacio Olmos, Marcelo Rodriguez Fermepin, Tatiana Uehara, Elisa Viciani, Andrea Castagnetti, Tor Savidge, María Marta Piskorz
Randomized Placebo-Controlled Trial Of Oral Tannin Supplementation On Covid-19 Symptoms, Gut Dysbiosis And Cytokine Response, Silvia Molino, Andrea Pisarevsky, Shyam Badu, Qinglong Wu, Fabiana López Mingorance, Patricia Vega, Juan Pablo Stefanolo, Julieta Repetti, Guillermina Ludueña, Pablo Pepa, Juan Ignacio Olmos, Marcelo Rodriguez Fermepin, Tatiana Uehara, Elisa Viciani, Andrea Castagnetti, Tor Savidge, María Marta Piskorz
Faculty, Staff and Students Publications
The clinical study aim was to investigate whether a tannin-based dietary supplementation could improve the efficacy of standard-of-care treatment of hospitalized COVID-19 patients by restoring gut microbiota function. Adverse events and immunomodulation post-tannin supplementation were also investigated. A total of 124 patients receiving standard-of-care treatment were randomized to oral tannin-based supplement or placebo for a total of 14 days. Longitudinal blood and stool samples were collected for cytokine and 16S rDNA microbiome profiling, and results were compared with 53 healthy controls. Although oral tannin supplementation did not result in clinical improvement or significant gut microbiome shifts after 14-days, a reduction …
Effects Of Apical Sodium-Bile Acid Transporter Inhibitor And Obeticholic Acid Co-Treatment In Experimental Non-Alcoholic Steatohepatitis, David J Matye, Xuan Qin, Mohammad Nazmul Hasan, Lijie Gu, Yung-Dai Clayton, Feng Li, Tiangang Li
Effects Of Apical Sodium-Bile Acid Transporter Inhibitor And Obeticholic Acid Co-Treatment In Experimental Non-Alcoholic Steatohepatitis, David J Matye, Xuan Qin, Mohammad Nazmul Hasan, Lijie Gu, Yung-Dai Clayton, Feng Li, Tiangang Li
Faculty, Staff and Students Publications
BACKGROUND AND AIMS: Several bile acids-based monotherapies have been developed for non-alcoholic steatohepatitis (NASH) treatment but clinical trial findings suggest that they do not satisfactorily improve NASH and liver fibrosis in many patients. Recently, we have shown that combining a gut-restricted apical sodium-bile acid transporter (ASBT) inhibitor GSK2330672 (GSK) with adeno-associated virus (AAV)-mediated liver fibroblast growth factor 15 (FGF15) overexpression provides significantly improved efficacy than either single treatment against NASH and liver fibrosis in a high fat, cholesterol, and fructose (HFCFr) diet-induced NASH mouse model. The beneficial effects of the combined treatment can be attributed to the markedly reduced bile …
Study Of The Roles Of Cytochrome P450 (Cyps) In The Metabolism And Cytotoxicity Of Perhexiline, Zhen Ren, Si Chen, Xuan Qin, Feng Li, Lei Guo
Study Of The Roles Of Cytochrome P450 (Cyps) In The Metabolism And Cytotoxicity Of Perhexiline, Zhen Ren, Si Chen, Xuan Qin, Feng Li, Lei Guo
Faculty, Staff and Students Publications
Perhexiline is a prophylactic antianginal agent developed in the 1970s. Although, therapeutically, it remained a success, the concerns of its severe adverse effects including hepatotoxicity caused the restricted use of the drug, and eventually its withdrawal from the market in multiple countries. In the clinical setting, cytochrome P450 (CYP) 2D6 is considered as a possible risk factor for the adverse effects of perhexiline. However, the role of CYP-mediated metabolism in the toxicity of perhexiline, particularly in the intact cells, remains unclear. Using our previously established HepG2 cell lines that individually express 14 CYPs (1A1, 1A2, 1B1, 2A6, 2B6, 2C8, 2C9, …
Amplification Of The Plag-Family Genes-Plagl1 And Plagl2-Is A Key Feature Of The Novel Tumor Type Cns Embryonal Tumor With Plagl Amplification, Michaela-Kristina Keck, Martin Sill, Andrea Wittmann, Piyush Joshi, Damian Stichel, Pengbo Beck, Konstantin Okonechnikow, Philipp Sievers, Annika K. Wefers, Nasir Uddin
Amplification Of The Plag-Family Genes-Plagl1 And Plagl2-Is A Key Feature Of The Novel Tumor Type Cns Embryonal Tumor With Plagl Amplification, Michaela-Kristina Keck, Martin Sill, Andrea Wittmann, Piyush Joshi, Damian Stichel, Pengbo Beck, Konstantin Okonechnikow, Philipp Sievers, Annika K. Wefers, Nasir Uddin
Department of Pathology and Laboratory Medicine
Pediatric central nervous system (CNS) tumors represent the most common cause of cancer-related death in children aged 0-14 years. They differ from their adult counterparts, showing extensive clinical and molecular heterogeneity as well as a challenging histopathological spectrum that often impairs accurate diagnosis. Here, we use DNA methylation-based CNS tumor classification in combination with copy number, RNA-seq, and ChIP-seq analysis to characterize a newly identified CNS tumor type. In addition, we report histology, patient characteristics, and survival data in this tumor type. We describe a biologically distinct pediatric CNS tumor type (n = 31 cases) that is characterized by focal …
Clinical And Molecular Insights Into Gastrointestinal Dysfunction In Myotonic Dystrophy Types 1 & 2, Janel A M Peterson, Thomas A Cooper
Clinical And Molecular Insights Into Gastrointestinal Dysfunction In Myotonic Dystrophy Types 1 & 2, Janel A M Peterson, Thomas A Cooper
Faculty, Staff and Students Publications
Myotonic dystrophy (DM) is a highly variable, multisystemic disorder that clinically affects one in 8000 individuals. While research has predominantly focused on the symptoms and pathological mechanisms affecting striated muscle and brain, DM patient surveys have identified a high prevalence for gastrointestinal (GI) symptoms amongst affected individuals. Clinical studies have identified chronic and progressive dysfunction of the esophagus, stomach, liver and gallbladder, small and large intestine, and rectum and anal sphincters. Despite the high incidence of GI dysmotility in DM, little is known regarding the pathological mechanisms leading to GI dysfunction. In this review, we summarize results from clinical and …
Depletion Of Cd206+ M2-Like Macrophages Induces Fibro-Adipogenic Progenitors Activation And Muscle Regeneration, Allah Nawaz, Muhammad Bilal, Shiho Fujisaka, Tomonobu Kado, Muhammad Rahil Aslam, Saeed Ahmed, Keisuke Okabe, Yoshiko Igarashi, Yoshiyuki Watanabe, Takahide Kuwano, Koichi Tsuneyama, Ayumi Nishimura, Yasuhiro Nishida, Seiji Yamamoto, Masakiyo Sasahara, Johji Imura, Hisashi Mori, Martin M Matzuk, Fujimi Kudo, Ichiro Manabe, Akiyoshi Uezumi, Takashi Nakagawa, Yumiko Oishi, Kazuyuki Tobe
Depletion Of Cd206+ M2-Like Macrophages Induces Fibro-Adipogenic Progenitors Activation And Muscle Regeneration, Allah Nawaz, Muhammad Bilal, Shiho Fujisaka, Tomonobu Kado, Muhammad Rahil Aslam, Saeed Ahmed, Keisuke Okabe, Yoshiko Igarashi, Yoshiyuki Watanabe, Takahide Kuwano, Koichi Tsuneyama, Ayumi Nishimura, Yasuhiro Nishida, Seiji Yamamoto, Masakiyo Sasahara, Johji Imura, Hisashi Mori, Martin M Matzuk, Fujimi Kudo, Ichiro Manabe, Akiyoshi Uezumi, Takashi Nakagawa, Yumiko Oishi, Kazuyuki Tobe
Faculty, Staff and Students Publications
Muscle regeneration requires the coordination of muscle stem cells, mesenchymal fibro-adipogenic progenitors (FAPs), and macrophages. How macrophages regulate the paracrine secretion of FAPs during the recovery process remains elusive. Herein, we systemically investigated the communication between CD206+ M2-like macrophages and FAPs during the recovery process using a transgenic mouse model. Depletion of CD206+ M2-like macrophages or deletion of CD206+ M2-like macrophages-specific TGF-β1 gene induces myogenesis and muscle regeneration. We show that depletion of CD206+ M2-like macrophages activates FAPs and activated FAPs secrete follistatin, a promyogenic factor, thereby boosting the recovery process. Conversely, deletion of the FAP-specific follistatin gene results in …
Drug-Resistant Bacterial Infections: We Need Urgent Action And Investment That Focus On The Weakest Link, Christiane Dolecek, Sadia Shakoor, Buddha Basnyat, Tochi Okwor, Benn Sartorius
Drug-Resistant Bacterial Infections: We Need Urgent Action And Investment That Focus On The Weakest Link, Christiane Dolecek, Sadia Shakoor, Buddha Basnyat, Tochi Okwor, Benn Sartorius
Department of Pathology and Laboratory Medicine
Despite high mortality and morbidity, drug-resistant bacterial infections remain the forgotten pandemic. We argue for strengthening of diagnostics, WASH (water, sanitation, and hygiene) and infection prevention and control to reduce drug-resistant infections, as an integral part of sustainable high-quality health services, particularly in low- and middle-income countries.
Assessment During Covid-19: Quality Assurance Of An Online Open Book Formative Examination For Undergraduate Medical Students, Javeria Rehman, Rahila Ali Mazhar, Azam Afzal, Sara Shakil, Amber Shahmim Sultan, Romana Idress, Syeda Sadia Fatima
Assessment During Covid-19: Quality Assurance Of An Online Open Book Formative Examination For Undergraduate Medical Students, Javeria Rehman, Rahila Ali Mazhar, Azam Afzal, Sara Shakil, Amber Shahmim Sultan, Romana Idress, Syeda Sadia Fatima
Department of Pathology and Laboratory Medicine
Background: The spread of COVID-19 pandemic in early 2020 compelled all the educational activities, including medical education to be shifted from face-to-face interaction to a virtual platform. This shift provided opportunities for exploring online assessment modalities. One such assessment method is an online open book exam which is a unique concept in medical education of Pakistan. Limited information is available in literature regarding open book exam for the basic science subjects. Hence, the objective of the study was to determine the quality of the open book exam administered as a pilot project to the first-year medical students.
Methods: It was …
Human Dectin-1 Deficiency Impairs Macrophage-Mediated Defense Against Phaeohyphomycosis, Rebecca A. Drummond, Jigar V. Desai, Amy P. Hsu, Vasileios Oikonomou, Donald C. Vinh, Joshua A. Acklin, Michael S. Abers, Magdalena A. Walkiewicz, Sarah L. Anzick, Muthulekha Swamydas, Simon Vautier, Mukil Natarajan, Andrew J. Oler, Daisuke Yamanaka, Katrin D. Mayer-Barber, Yoichiro Iwakura, David Bianchi, Brian Driscoll, Ken Hauck, Ahnika Kline, Nicholas S.P. Viall, Christa S. Zerbe, Elise M.N. Ferré, Monica M. Schmitt, Tom Dimaggio, Stefania Pittaluga, John A. Butman, Adrian M. Zelazny, Yvonne R. Shea, Cesar A. Arias, Cameron Ashbaugh, Maryam Mahmood, Zelalem Temesgen, Alexander G. Theofiles, Masayuki Nigo, Varsha Moudgal, Karen C. Bloch, Sean G. Kelly, M. Suzanne Whitworth, Ganesh Rao, Cindy J. Whitener, Neema Mafi, Juan Gea-Banacloche, Lawrence C. Kenyon, William R. Miller, Katia Boggian, Andrea Gilbert, Matthew Sincock, Alexandra F. Freeman, John E. Bennett, Rodrigo Hasbun, Constantinos M. Mikelis, Kyung J. Kwon-Chung, Yasmine Belkaid, Gordon D. Brown, Jean K. Lim, Douglas B. Kuhns, Steven M. Holland, Michail S. Lionakis
Human Dectin-1 Deficiency Impairs Macrophage-Mediated Defense Against Phaeohyphomycosis, Rebecca A. Drummond, Jigar V. Desai, Amy P. Hsu, Vasileios Oikonomou, Donald C. Vinh, Joshua A. Acklin, Michael S. Abers, Magdalena A. Walkiewicz, Sarah L. Anzick, Muthulekha Swamydas, Simon Vautier, Mukil Natarajan, Andrew J. Oler, Daisuke Yamanaka, Katrin D. Mayer-Barber, Yoichiro Iwakura, David Bianchi, Brian Driscoll, Ken Hauck, Ahnika Kline, Nicholas S.P. Viall, Christa S. Zerbe, Elise M.N. Ferré, Monica M. Schmitt, Tom Dimaggio, Stefania Pittaluga, John A. Butman, Adrian M. Zelazny, Yvonne R. Shea, Cesar A. Arias, Cameron Ashbaugh, Maryam Mahmood, Zelalem Temesgen, Alexander G. Theofiles, Masayuki Nigo, Varsha Moudgal, Karen C. Bloch, Sean G. Kelly, M. Suzanne Whitworth, Ganesh Rao, Cindy J. Whitener, Neema Mafi, Juan Gea-Banacloche, Lawrence C. Kenyon, William R. Miller, Katia Boggian, Andrea Gilbert, Matthew Sincock, Alexandra F. Freeman, John E. Bennett, Rodrigo Hasbun, Constantinos M. Mikelis, Kyung J. Kwon-Chung, Yasmine Belkaid, Gordon D. Brown, Jean K. Lim, Douglas B. Kuhns, Steven M. Holland, Michail S. Lionakis
Department of Pathology, Anatomy, and Cell Biology Faculty Papers
Subcutaneous phaeohyphomycosis typically affects immunocompetent individuals following traumatic inoculation. Severe or disseminated infection can occur in CARD9 deficiency or after transplantation, but the mechanisms protecting against phaeohyphomycosis remain unclear. We evaluated a patient with progressive, refractory Corynespora cassiicola phaeohyphomycosis and found that he carried biallelic deleterious mutations in CLEC7A encoding the CARD9-coupled, β-glucan-binding receptor, Dectin-1. The patient's PBMCs failed to produce TNF-α and IL-1β in response to β-glucan and/or C. cassiicola. To confirm the cellular and molecular requirements for immunity against C. cassiicola, we developed a mouse model of this infection. Mouse macrophages required Dectin-1 and CARD9 for IL-1β and …
Exploring Stakeholders' Experiences And Perceptions Regarding Barriers To Effective Surveillance Of Communicable Diseases In A Rural District Of Pakistan: A Qualitative Study, Imran Naeem Abbasi, Sameen Siddiqi, Mmna Rehana Sididiqui, Rumina Hasan
Exploring Stakeholders' Experiences And Perceptions Regarding Barriers To Effective Surveillance Of Communicable Diseases In A Rural District Of Pakistan: A Qualitative Study, Imran Naeem Abbasi, Sameen Siddiqi, Mmna Rehana Sididiqui, Rumina Hasan
Community Health Sciences
Objective: To explore the experiences and perceptions of health system stakeholders of a rural district of Sindh, Pakistan regarding the barriers to effective surveillance of communicable diseases.
Design: This qualitative descriptive exploratory design comprised in-depth interviews. Both inductive and deductive thematic analysis was applied to identify key themes from the data.
Settings: The study was conducted in public sector healthcare facilities and the district health office of the rural district of Thatta, in Sindh province, Pakistan.
Participants: Fifteen healthcare managers and healthcare providers working in the eight public sector primary and secondary healthcare facilities were interviewed using an open-ended in-depth …
Simultaneous Onset Of Haematological Malignancy And Covid: An Epicovideha Survey, Chiara Cattaneo, Jon Salmanton-García, Francesco Marchesi, Shaimaa El-Ashwah, Federico Itri, Barbora Weinbergerová, Maria Gomes Da Silva, Michelina Dargenio, Julio Dávila-Valls, Natasha Ali
Simultaneous Onset Of Haematological Malignancy And Covid: An Epicovideha Survey, Chiara Cattaneo, Jon Salmanton-García, Francesco Marchesi, Shaimaa El-Ashwah, Federico Itri, Barbora Weinbergerová, Maria Gomes Da Silva, Michelina Dargenio, Julio Dávila-Valls, Natasha Ali
Department of Pathology and Laboratory Medicine
Background: The outcome of patients with simultaneous diagnosis of haematological malignancies (HM) and COVID-19 is unknown and there are no specific treatment guidelines.
Methods: We describe the clinical features and outcome of a cohort of 450 patients with simultaneous diagnosis of HM and COVID-19 registered in the EPICOVIDEHA registry between March 2020 to February 2022.
Results: Acute leukaemia and lymphoma were the most frequent HM (35.8% and 35.1%, respectively). Overall, 343 (76.2%) patients received treatment for HM, which was delayed for longer than one month since diagnosis in 57 (16.6%). An overall response rate was observed in 140 (40.8%) patients …
Diagnostic Accuracy Of Artificial Intelligence For Detecting Gastrointestinal Luminal Pathologies: A Systematic Review And Meta-Analysis, Om Parkash, Asra Tus Saleha Siddiqui, Uswa Jiwani, Fahad Rind, Zahra Ali Padhani, Arjumand Rizvi, Zahra Hoodbhoy, Jai K. Das
Diagnostic Accuracy Of Artificial Intelligence For Detecting Gastrointestinal Luminal Pathologies: A Systematic Review And Meta-Analysis, Om Parkash, Asra Tus Saleha Siddiqui, Uswa Jiwani, Fahad Rind, Zahra Ali Padhani, Arjumand Rizvi, Zahra Hoodbhoy, Jai K. Das
Section of Gastroenterology
Background: Artificial Intelligence (AI) holds considerable promise for diagnostics in the field of gastroenterology. This systematic review and meta-analysis aims to assess the diagnostic accuracy of AI models compared with the gold standard of experts and histopathology for the diagnosis of various gastrointestinal (GI) luminal pathologies including polyps, neoplasms, and inflammatory bowel disease.
Methods: We searched PubMed, CINAHL, Wiley Cochrane Library, and Web of Science electronic databases to identify studies assessing the diagnostic performance of AI models for GI luminal pathologies. We extracted binary diagnostic accuracy data and constructed contingency tables to derive the outcomes of interest: sensitivity and specificity. …
Case Report: Autoimmune Anemia And Thrombocytopenia Following Hematopoietic Stem Cell Transplant, Thomas Cochran, Gabor Oroszi, Nancy Terwilliger, Gabe Metzler, Lejla Music Aplenc
Case Report: Autoimmune Anemia And Thrombocytopenia Following Hematopoietic Stem Cell Transplant, Thomas Cochran, Gabor Oroszi, Nancy Terwilliger, Gabe Metzler, Lejla Music Aplenc
Posters
Background: Autoimmune cytopenias (AIC) post hematopoietic stem cell transplant (HSCT) are rare but exceptionally challenging complications. Here, we report anti E, warm autoimmune hemolytic anemia (WAIHA), cold autoantibody, polyagglutination and immune thrombocytopenia in a 5-year-old boy with a history of chronic granulomatous disease, who underwent an ABO incompatible, mismatched (9/10) unrelated HSCT. Study design: Case report. Four months after HSCT, the patient was admitted for fever, fatigue, and decreased appetite. His original blood type was O+ and donor’s blood type B+. Prior to the admission he was transfused with 2 doses of red cells and 2 doses of platelets. On …
Clinicopathologic Features Of Renal Cell Carcinomas Seen At The Aga Khan University Hospital In Kenya, Anderson Mutuiri, Samuel Gakinya
Clinicopathologic Features Of Renal Cell Carcinomas Seen At The Aga Khan University Hospital In Kenya, Anderson Mutuiri, Samuel Gakinya
Pathology, East Africa
Introduction: Kidney cancer accounted for 1. 8% of global cancer deaths according to Globocan 2020 estimates, with most of these being renal cell carcinomas. Lower rates of renal cell carcinoma are reported for Africa and these are expected to change for a combination of reasons. The clinical and morphologic characteristics of renal cell carcinoma seen within Kenya have not been described before. This study aims to partially fill this gap.
Materials and methods: This was a cross-sectional descriptive study examining electronic histopathology reports from the Aga Khan University Hospital Nairobi Laboratory for the period January 2016 to May 2022.
Results: …
Vaginal Microbiota In Women With Spontaneous Preterm Labor Versus Those With Term Labor In Kenya: A Case Control Study, Edgar Gulavi, Fridah Mwendwa, David Atandi, Patricia Okiro, Michael Hall, Robert G. Beiko, Rodney Adam
Vaginal Microbiota In Women With Spontaneous Preterm Labor Versus Those With Term Labor In Kenya: A Case Control Study, Edgar Gulavi, Fridah Mwendwa, David Atandi, Patricia Okiro, Michael Hall, Robert G. Beiko, Rodney Adam
Obstetrics and Gynaecology, East Africa
Background: Preterm birth is a global problem with about 12% of births in sub-Saharan Africa occurring before 37 weeks of gestation. Several studies have explored a potential association between vaginal microbiota and preterm birth, and some have found an association while others have not. We performed a study designed to determine whether there is an association with vaginal microbiota and/or placental microbiota and preterm birth in an African setting.
Methods: Women presenting to the study hospital in labor with a gestational age of 26 to 36 weeks plus six days were prospectively enrolled in a study of the …
Validation Of Atovaquone Plasma Levels By Liquid Chromatography-Tandem Mass Spectrometry For Therapeutic Drug Monitoring In Pediatric Patients, Thomas D Horvath, Izmarie Poventud-Fuentes, Lily Olayinka, Asha James, Sigmund J Haidacher, Kathleen M Hoch, Alexandra M Stevens, Anthony M Haag, Sridevi Devaraj
Validation Of Atovaquone Plasma Levels By Liquid Chromatography-Tandem Mass Spectrometry For Therapeutic Drug Monitoring In Pediatric Patients, Thomas D Horvath, Izmarie Poventud-Fuentes, Lily Olayinka, Asha James, Sigmund J Haidacher, Kathleen M Hoch, Alexandra M Stevens, Anthony M Haag, Sridevi Devaraj
Faculty, Staff and Students Publications
BACKGROUND: Atovaquone has traditionally been used as an antiparasitic and antifungal agent, but recent studies have shown its potential as an anticancer agent. The high variability in atovaquone bioavailability highlights the need for therapeutic drug monitoring, especially in pediatric patients. The goal of our study was to develop and validate the performance of an assay to quantify atovaquone plasma concentrations collected from pediatric cancer patients using LC-MS/MS.
METHODS: Atovaquone was extracted from a 10 µL volume of K
RESULTS: Atovaquone and its deuterated internal standard were analyzed using a gradient chromatographic method that had an overall cycle-time of 7.4 min …
Clinical And Molecular Features Of Pediatric Cancer Patients With Lynch Syndrome, Sarah Scollon, Mohammad K Eldomery, Jacquelyn Reuther, Frank Y Lin, Samara L Potter, Lauren Desrosiers, Kenneth L Mcclain, Valeria Smith, Jack Meng-Fen Su, Rajkumar Venkatramani, Jianhong Hu, Viktoriya Korchina, Neda Zarrin-Khameh, Richard A Gibbs, Donna M Muzny, Christine Eng, Angshumoy Roy, D Williams Parsons, Sharon E Plon
Clinical And Molecular Features Of Pediatric Cancer Patients With Lynch Syndrome, Sarah Scollon, Mohammad K Eldomery, Jacquelyn Reuther, Frank Y Lin, Samara L Potter, Lauren Desrosiers, Kenneth L Mcclain, Valeria Smith, Jack Meng-Fen Su, Rajkumar Venkatramani, Jianhong Hu, Viktoriya Korchina, Neda Zarrin-Khameh, Richard A Gibbs, Donna M Muzny, Christine Eng, Angshumoy Roy, D Williams Parsons, Sharon E Plon
Faculty, Staff and Students Publications
BACKGROUND: The association of childhood cancer with Lynch syndrome is not established compared with the significant pediatric cancer risk in recessive constitutional mismatch repair deficiency syndrome (CMMRD).
PROCEDURE: We describe the clinical features, germline analysis, and tumor genomic profiling of patients with Lynch syndrome among patients enrolled in pediatric cancer genomic studies.
RESULTS: There were six of 773 (0.8%) pediatric patients with solid tumors identified with Lynch syndrome, defined as a germline heterozygous pathogenic variant in one of the mismatch repair (MMR) genes (three with MSH6, two with MLH1, and one with MSH2). Tumor analysis demonstrated evidence for somatic second …
Pleomorphic Dermal Sarcoma: A Clinical And Histopathologic Emulator Of Atypical Fibroxanthoma, But Different Biologic Behavior, Michael Carletti, Daniel A. Nguyen, Peter Malouf, Zachary Ingersoll, Gregory A. Hosler, Stephen E. Weis
Pleomorphic Dermal Sarcoma: A Clinical And Histopathologic Emulator Of Atypical Fibroxanthoma, But Different Biologic Behavior, Michael Carletti, Daniel A. Nguyen, Peter Malouf, Zachary Ingersoll, Gregory A. Hosler, Stephen E. Weis
HCA Healthcare Journal of Medicine
Pleomorphic dermal sarcoma (PDS) can clinically and histopathologically mimic atypical fibroxanthoma (AFX). However, it has a more aggressive clinical course with a higher recurrence rate and metastatic potential. This case presentation aims to report a rapidly-growing, exophytic, 4 cm tumor following a non-diagnostic shave biopsy 2 months prior and to highlight distinctive features between PDS and AFX needed to make the correct diagnosis. Like AFX, PDS occurs on the sun-damaged skin of the elderly, usually on the head and neck. Also, like AFX, PDS histopathologically consists of sheets or fascicles of epithelioid and/or spindle-shaped cells, often with multinucleation, pleomorphism, and …
Spatial Profiling Of The Prostate Cancer Tumor Microenvironment Reveals Multiple Differences In Gene Expression And Correlation With Recurrence Risk, Vinay Kumar, Pavneet Randhawa, Robert Bilodeau, Dan Mercola, Michael Mcclelland, Anshu Agrawal, James Nguyen, Patricia Castro, Michael M Ittmann, Farah Rahmatpanah
Spatial Profiling Of The Prostate Cancer Tumor Microenvironment Reveals Multiple Differences In Gene Expression And Correlation With Recurrence Risk, Vinay Kumar, Pavneet Randhawa, Robert Bilodeau, Dan Mercola, Michael Mcclelland, Anshu Agrawal, James Nguyen, Patricia Castro, Michael M Ittmann, Farah Rahmatpanah
Faculty, Staff and Students Publications
The tumor microenvironment plays a crucial role in both the development and progression of prostate cancer. Furthermore, identifying protein and gene expression differences between different regions is valuable for treatment development. We applied Digital Spatial Profiling multiplex analysis to formalin-fixed paraffin embedded prostatectomy tissue blocks to investigate protein and transcriptome differences between tumor, tumor-adjacent stroma (TAS), CD45+ tumor, and CD45+ TAS tissue. Differential expression of an immunology/oncology protein panel (n = 58) was measured. OX40L and CTLA4 were expressed at higher levels while 22 other proteins, including CD11c, were expressed at lower levels (FDR < 0.2 and p-value < 0.05) in TAS as compared to tumor epithelia. A tissue microarray analysis of 97 patients with 1547 cores found positive correlations between high expression of CD11c and increased time to recurrence in tumor and TAS, and inverse relationships for CTLA4 and OX40L, where higher expression in tumor correlated with lower time to recurrence, but higher time to recurrence in TAS. Spatial transcriptomic analysis using a Cancer Transcriptome Atlas panel (n = 1825 genes) identified 162 genes downregulated and 69 upregulated in TAS versus tumor, 26 downregulated and 6 upregulated in CD45+ TAS versus CD45+ tumor. We utilized CIBERSORTx to estimate the relative immune cell fractions using CD45+ gene expression and found higher average fractions for memory B, naïve B, and T cells in TAS. In summary, the combination of protein expression differences, immune cell fractions, and correlations of protein expression with time to recurrence suggest that closely examining the tumor microenvironment provides valuable data that can improve prognostication and treatment techniques.
Respiratory Virus Surveillance Among Children With Acute Respiratory Illnesses - New Vaccine Surveillance Network, United States, 2016-2021., Ariana Perez, Joana Y. Lively, Aaron Curns, Geoffrey A. Weinberg, Natasha B. Halasa, Mary Allen Staat, Peter G. Szilagyi, Laura S. Stewart, Monica M. Mcneal, Benjamin Clopper, Yingtao Zhou, Brett L. Whitaker, Elizabeth Lemasters, Elizabeth Harker, Janet A. Englund, Eileen J. Klein, Rangaraj Selvarangan, Christopher J. Harrison, Julie A. Boom, Leila C. Sahni, Marian G. Michaels, John V. Williams, Gayle E. Langley, Susan I. Gerber, Angela Campbell, Aron J. Hall, Brian Rha, Meredith Mcmorrow, New Vaccine Surveillance Network Collaborators
Respiratory Virus Surveillance Among Children With Acute Respiratory Illnesses - New Vaccine Surveillance Network, United States, 2016-2021., Ariana Perez, Joana Y. Lively, Aaron Curns, Geoffrey A. Weinberg, Natasha B. Halasa, Mary Allen Staat, Peter G. Szilagyi, Laura S. Stewart, Monica M. Mcneal, Benjamin Clopper, Yingtao Zhou, Brett L. Whitaker, Elizabeth Lemasters, Elizabeth Harker, Janet A. Englund, Eileen J. Klein, Rangaraj Selvarangan, Christopher J. Harrison, Julie A. Boom, Leila C. Sahni, Marian G. Michaels, John V. Williams, Gayle E. Langley, Susan I. Gerber, Angela Campbell, Aron J. Hall, Brian Rha, Meredith Mcmorrow, New Vaccine Surveillance Network Collaborators
Manuscripts, Articles, Book Chapters and Other Papers
The New Vaccine Surveillance Network (NVSN) is a prospective, active, population-based surveillance platform that enrolls children with acute respiratory illnesses (ARIs) at seven pediatric medical centers. ARIs are caused by respiratory viruses including influenza virus, respiratory syncytial virus (RSV), human metapneumovirus (HMPV), human parainfluenza viruses (HPIVs), and most recently SARS-CoV-2 (the virus that causes COVID-19), which result in morbidity among infants and young children (1-6). NVSN estimates the incidence of pathogen-specific pediatric ARIs and collects clinical data (e.g., underlying medical conditions and vaccination status) to assess risk factors for severe disease and calculate influenza and COVID-19 vaccine effectiveness. Current NVSN …
The Association Of Immune And Genomic Biomarkers And Response To Neoadjuvant Chemotherapy In Breast Cancer Patients At Aga Khan University Hospital Nairobi, Catherine Wairimu Mutahi
The Association Of Immune And Genomic Biomarkers And Response To Neoadjuvant Chemotherapy In Breast Cancer Patients At Aga Khan University Hospital Nairobi, Catherine Wairimu Mutahi
Master of Medicine in Anatomic Pathology
Introduction: Breast Cancer (BC) is the most diagnosed cancer among women worldwide and in Kenya. It is a highly heterogeneous disease requiring patient specific treatment and strategies to monitor response to therapy, especially in the neoadjuvant (NAC) setting. Currently, there are no reliable markers in use that can predict response to chemotherapy among patients receiving NAC. Tumour Infiltrating Lymphocytes (TILs) and Cell free DNA (cfDNA) are biomarkers that could possibly bridge this gap. However, limited studies have been carried out on the African population. With the increasing mortality rates attributable to BC in Sub-Saharan Africa, coupled with the growing preference …
Acute Pericarditis And Acute Pleuritis/Empyema Following Submandibular Infection In A Covid-19 Positive Patient - An Autopsy Revealing The Danger Space Of The Neck, Jessica D. Anderson, Seyedalireza Fatemi, Joseph Fullmer, Ping I. Zhang
Acute Pericarditis And Acute Pleuritis/Empyema Following Submandibular Infection In A Covid-19 Positive Patient - An Autopsy Revealing The Danger Space Of The Neck, Jessica D. Anderson, Seyedalireza Fatemi, Joseph Fullmer, Ping I. Zhang
Posters
Acute pericarditis and empyema are life-threatening complications of severe odontogenic infections; reports of these findings from an autopsy perspective are rare. We report an autopsy case demonstrating infection from the mandibular molars to the pericardium and pleura in a patient following Covid-19 infection
Association Of Isolated Colitis With Non-Steroidal Anti-Inflammatory Drugs Usage, Ashbita Pokharel, Wei Li
Association Of Isolated Colitis With Non-Steroidal Anti-Inflammatory Drugs Usage, Ashbita Pokharel, Wei Li
Posters
Non-steroidal anti-inflammatory drugs (NSAIDs) have been known to produce various clinical gastrointestinal side-effects and histopathological changes. It has been reported that NSAIDs usage is associated with isolated colitis in periappendiceal orifice region. This study aims to further evaluate the clinicopathologic features of 16 patients with isolated colitis limited to the cecum or peri-appendiceal orifice region.
Cd30 Expression In Cutaneous B-Cell Lymphomas, Olabisi Afolayan-Oloye, Lili Zhao, Trilokraj Tejasvi, May P. Chan, Paul W. Harms, Douglas R. Fullen, Ryan A. Wilcox, Alexandra C. Hristov
Cd30 Expression In Cutaneous B-Cell Lymphomas, Olabisi Afolayan-Oloye, Lili Zhao, Trilokraj Tejasvi, May P. Chan, Paul W. Harms, Douglas R. Fullen, Ryan A. Wilcox, Alexandra C. Hristov
Posters
CD30 expression has been infrequently described in cutaneous B-cell lymphomas (CBCL). We examined CD30 expression in reactive lymphoid hyperplasia (RLH) and CBCL and correlated expression with clinicopathologic features.
Diagnostic Accuracy Of High-Sensitivity Cardiac Troponin In The Diagnosis Of Acute Myocardial Infarction At The Aga Khan University Hospital Nairobi, Kenya, Assumpta Wanjiru Chege
Diagnostic Accuracy Of High-Sensitivity Cardiac Troponin In The Diagnosis Of Acute Myocardial Infarction At The Aga Khan University Hospital Nairobi, Kenya, Assumpta Wanjiru Chege
Master of Medicine in Clinical Pathology
Methodology: This cross-sectional study was carried out at Aga Khan University Hospital, Nairobi between July 1st 2020 and December 31st 2021. Participants were adults aged 18 years and above presenting to the emergency department with signs and symptoms suggesting an acute myocardial infarction. Patients were identified on the hospital management information system (CARE 2000) using test results for baseline high-sensitivity cardiac troponin I. The final diagnosis as well as secondary clinical data was obtained from both physical and electronic patient medical records. The reference standard for the diagnosis of acute myocardial infarction was taken as the final clinical diagnosis made …
Repeat Tracheal Aspirates In Pediatric Intensive Care Patients: Frequency, Resistance And Antimicrobial Use, Edward Lyon, Jennifer Goldman, Brian Lee, Margaret Campbell, Rangaraj Selvarangan, Elizabeth Monsees
Repeat Tracheal Aspirates In Pediatric Intensive Care Patients: Frequency, Resistance And Antimicrobial Use, Edward Lyon, Jennifer Goldman, Brian Lee, Margaret Campbell, Rangaraj Selvarangan, Elizabeth Monsees
Posters
Background: Tracheal aspirates (TA) are frequently obtained in the pediatric intensive care unit (PICU); however, no data exists on the frequency or clinical management of multiple TA cultures on the same PICU patient. In this study, we describe the frequency of repeat TAs in PICU patients, the emergence of multidrug resistant organisms (MDRO), frequently cultured pathogens of TAs, and associated antibiotic prescribing patterns. Methods: We identified 70 PICU patients between 2018-2019 who met our criteria for retrospective chart review with ≥2 TAs obtained during their hospitalization. The following information was collected: patient demographics, number of TAs per patient, microbiology with …
Emergence Of A Multidrug-Resistant And Virulent Streptococcus Pneumoniae Lineage Mediates Serotype Replacement After Pcv13: An International Whole-Genome Sequencing Study, Stephanie W. Lo, Kate Mellor, Robert Cohen, Alba Redin Alonso, Sophie Belman, Narender Kumar, Paulina A. Hawkins, Rebecca A. Gladstone, Sadia Shakoor, Muhammad Imran Nisar
Emergence Of A Multidrug-Resistant And Virulent Streptococcus Pneumoniae Lineage Mediates Serotype Replacement After Pcv13: An International Whole-Genome Sequencing Study, Stephanie W. Lo, Kate Mellor, Robert Cohen, Alba Redin Alonso, Sophie Belman, Narender Kumar, Paulina A. Hawkins, Rebecca A. Gladstone, Sadia Shakoor, Muhammad Imran Nisar
Department of Pathology and Laboratory Medicine
Background: Serotype 24F is one of the emerging pneumococcal serotypes after the introduction of pneumococcal conjugate vaccine (PCV). We aimed to identify lineages driving the increase of serotype 24F in France and place these findings into a global context.
Methods: Whole-genome sequencing was performed on a collection of serotype 24F pneumococci from asymptomatic colonisation (n=229) and invasive disease (n=190) isolates among individuals younger than 18 years in France, from 2003 to 2018. To provide a global context, we included an additional collection of 24F isolates in the Global Pneumococcal Sequencing (GPS) project database for analysis. A Global Pneumococcal Sequence Cluster …
Increased Eosinophils In The Muscularis Propria Of Appendix May Indicate Early Symptomatic Appendicitis, Ping L. Zhang, Zhenhong Qu
Increased Eosinophils In The Muscularis Propria Of Appendix May Indicate Early Symptomatic Appendicitis, Ping L. Zhang, Zhenhong Qu
Conference Presentation Abstracts
Background: The presence of neutrophils in muscularis propria is known to best correlate with clinical symptoms of acute appendicitis. Eosinophils present in the muscularis propria were noted in cases of acute appendicitis in 2000 (Carr, NJ. Annal of Diagnostic Pathology 2000;4:46–58), but the significance of their presence there has been unclear. The goal of this study was to investigate whether increased eosinophils in muscularis propria could be correlated with early symptoms of patients with clinical diagnosis of symptomatic appendicitis.
Methods: Seventeen patients with clinical diagnosis of acute appendicitis were identified as having acute symptomatology, but the resection specimens displayed a …