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Inherited Bleeding Disorders-Experience Of A Not-For-Profit Organization In Pakistan, Shabneez Hussain, Shahida Baloch, Azra Parvin, Akbar Najmuddin, Farhana Musheer, Mubashra Junaid, Rab Nawaz Memon, Fareeda Bhanbhro, Hayat Ullah, Bushra Moiz 2018 Fatimid Foundation, Karachi, Pakistan

Inherited Bleeding Disorders-Experience Of A Not-For-Profit Organization In Pakistan, Shabneez Hussain, Shahida Baloch, Azra Parvin, Akbar Najmuddin, Farhana Musheer, Mubashra Junaid, Rab Nawaz Memon, Fareeda Bhanbhro, Hayat Ullah, Bushra Moiz

Department of Pathology and Laboratory Medicine

Patient registry is a powerful tool for planning health care and setting groundwork for research. This survey reports a detailed registry of inherited bleeding disorders (IBD) and their management at a not-for-profit organization in a developing country to form the basis for planning development and research. We reviewed medical records of patients with IBD from 8 hemophilia treatment centers of Fatimid Foundation located in various cities. Information collected included sociodemographic data, diagnostic tests, severity of hemophilia A and B, number of bleeding episodes per year, site and frequency of hemarthrosis, and seropositivity for viral diseases. We analyzed 1497 patients from ...


Resistome Of Carbapenem- And Colistin-Resistant Klebsiella Pneumoniae Clinical Isolates, Sara Lomonaco, Matthew A. Crawford, Christine Lascols, Ruth E. Timme, Kevin Anderson, David R. Hodge, Debra J. Fisher, Segaran P. Pillai, Stephen A. Morse, Erum Khan 2018 U.S. Food & Drug Administration

Resistome Of Carbapenem- And Colistin-Resistant Klebsiella Pneumoniae Clinical Isolates, Sara Lomonaco, Matthew A. Crawford, Christine Lascols, Ruth E. Timme, Kevin Anderson, David R. Hodge, Debra J. Fisher, Segaran P. Pillai, Stephen A. Morse, Erum Khan

Department of Pathology and Laboratory Medicine

The emergence and dissemination of carbapenemases, bacterial enzymes able to inactivate most β-lactam antibiotics, in Enterobacteriaceae is of increasing concern. The concurrent spread of resistance against colistin, an antibiotic of last resort, further compounds this challenge further. Whole-genome sequencing (WGS) can play a significant role in the rapid and accurate detection/characterization of existing and emergent resistance determinants, an essential aspect of public health surveillance and response activities to combat the spread of antimicrobial resistant bacteria. In the current study, WGS data was used to characterize the genomic content of antimicrobial resistance genes, including those encoding carbapenemases, in 10 multidrug-resistant ...


Recurrent Hotspot Mutations In Hras Q61 And Pi3k-Akt Pathway Genes As Drivers Of Breast Adenomyoepitheliomas., Felipe C. Geyer, Anqi Li, Anastasios D. Papanastasiou, Alison Smith, Pier Selenica, Kathleen A. Burke, Marcia Edelweiss, Huei-Chi Wen, Salvatore Piscuoglio, Anne M. Schultheis, Luciano G. Martelotto, Fresia Pareja, Rahul Kumar, Alissa Brandes, Dan Fan, Thais Basili, Arnaud Da Cruz Paula, John R. Lozada, Pedro Blecua, Simone Muenst, Achim A. Jungbluth, Maria P. Foschini, Hannah Y. Wen, Edi Brogi, Juan P. Palazzo, Brian P. Rubin, Charlotte K.Y. Ng, Larry Norton, Zsuzsanna Varga, Ian O. Ellis, Emad A. Rakha, Sarat Chandarlapaty, Britta Weigelt, Jorge S. Reis-Filho 2018 Memorial Sloan Kettering Cancer Center; Instituto Israelita de Ensino e Pesquisa; Instituto Do Cancer Do Estado de São Paulo

Recurrent Hotspot Mutations In Hras Q61 And Pi3k-Akt Pathway Genes As Drivers Of Breast Adenomyoepitheliomas., Felipe C. Geyer, Anqi Li, Anastasios D. Papanastasiou, Alison Smith, Pier Selenica, Kathleen A. Burke, Marcia Edelweiss, Huei-Chi Wen, Salvatore Piscuoglio, Anne M. Schultheis, Luciano G. Martelotto, Fresia Pareja, Rahul Kumar, Alissa Brandes, Dan Fan, Thais Basili, Arnaud Da Cruz Paula, John R. Lozada, Pedro Blecua, Simone Muenst, Achim A. Jungbluth, Maria P. Foschini, Hannah Y. Wen, Edi Brogi, Juan P. Palazzo, Brian P. Rubin, Charlotte K.Y. Ng, Larry Norton, Zsuzsanna Varga, Ian O. Ellis, Emad A. Rakha, Sarat Chandarlapaty, Britta Weigelt, Jorge S. Reis-Filho

Department of Pathology, Anatomy and Cell Biology Faculty Papers

Adenomyoepithelioma of the breast is a rare tumor characterized by epithelial-myoepithelial differentiation, whose genetic underpinning is largely unknown. Here we show through whole-exome and targeted massively parallel sequencing analysis that whilst estrogen receptor (ER)-positive adenomyoepitheliomas display PIK3CA or AKT1 activating mutations, ER-negative adenomyoepitheliomas harbor highly recurrent codon Q61 HRAS hotspot mutations, which co-occur with PIK3CA or PIK3R1 mutations. In two- and three-dimensional cell culture models, forced expression of HRAS


Dystrophic Calcifications Point The Way-Unusual And Early Diagnostic Clue Of Conradi-Hünermann-Happle Syndrome, Kenneth Yu, Alexander T. Reid, Stephanie J T Chen, Rajiv M. Patel, Steven M. Donn, Johann E. Gudjonsson, Lori Lowe 2018 University of Iowa

Dystrophic Calcifications Point The Way-Unusual And Early Diagnostic Clue Of Conradi-Hünermann-Happle Syndrome, Kenneth Yu, Alexander T. Reid, Stephanie J T Chen, Rajiv M. Patel, Steven M. Donn, Johann E. Gudjonsson, Lori Lowe

Stead Family Department of Pediatrics Publications

No abstract provided.


No Risk Reduction For Plasmodium Vivax Malaria In Sickle Cell Disease, Bushra Moiz, Ayesha Majeed Memon 2018 Aga Khan University

No Risk Reduction For Plasmodium Vivax Malaria In Sickle Cell Disease, Bushra Moiz, Ayesha Majeed Memon

Department of Pathology and Laboratory Medicine

Hemoglobin S is known to protect against uncomplicated Plasmodium falciparum malaria. However, there is paucity of the literature regarding interaction of HbS and other malaria species. Usually, P. vivax malaria is a relapsing condition, and without radical cure with primaquine, recurrence may be observed even with hemoglobin S.


Extending The Phenotypic Spectrum Of Sengers Syndrome: Congenital Lactic Acidosis With Synthetic Liver Dysfunction., David B Beck, Kristina Cusmano-Ozog, Nickie Andescavage, Eyby Leon 2018 George Washington University

Extending The Phenotypic Spectrum Of Sengers Syndrome: Congenital Lactic Acidosis With Synthetic Liver Dysfunction., David B Beck, Kristina Cusmano-Ozog, Nickie Andescavage, Eyby Leon

Pathology Faculty Publications

Sengers syndrome is a rare autosomal recessive mitochondrial disease characterized by lactic acidosis, hypertrophic cardiomyopathy and bilateral cataracts. We present here a case of neonatal demise, within the first day of life, who initially presented with severe lactic acidosis, with evidence of both chorioamnionitis and cardiogenic shock. Initial metabolic labs demonstrated a severe lactic acidosis prompting genetic testing which revealed a homozygous pathogenic variant for Sengers syndrome in


The Path Report Volume 1 Issue 4, Pathology Department, New York Medical College 2018 Touro College and University System

The Path Report Volume 1 Issue 4, Pathology Department, New York Medical College

Newsletters & Newspapers

No abstract provided.


Stromal Trim28-Associated Signaling Pathway Modulation Within The Colorectal Cancer Microenvironment., Sean Fitzgerald, Virginia Espina, Lance Liotta, Katherine M. Sheehan, Anthony O'Grady, Robert Cummins, Richard O'Kennedy, Elaine W. Kay, Gregor S. Kijanka 2018 Dublin City University

Stromal Trim28-Associated Signaling Pathway Modulation Within The Colorectal Cancer Microenvironment., Sean Fitzgerald, Virginia Espina, Lance Liotta, Katherine M. Sheehan, Anthony O'Grady, Robert Cummins, Richard O'Kennedy, Elaine W. Kay, Gregor S. Kijanka

Pathology Articles

Background: Stromal gene expression patterns predict patient outcomes in colorectal cancer. TRIM28 is a transcriptional co-repressor that regulates an abundance of genes through the KRAB domain family of transcription factors. We have previously shown that stromal expression of TRIM28 is a marker of disease relapse and poor survival in colorectal cancer. Here, we perform differential epithelium-stroma proteomic network analyses to characterize signaling pathways associated with TRIM28 within the tumor microenvironment.

Methods: Reverse phase protein arrays were generated from laser capture micro-dissected carcinoma and stromal cells from fresh frozen colorectal cancer tissues. Phosphorylation and total protein levels were measured for 30 ...


Onyx Use In Extracranial Pathologies - A Retrospective Case Review, Faezeh Razjouyan, Rishi Sood, Alex Cho, Anthony Venbrux, Shawn Sarin 2018 George Washington University

Onyx Use In Extracranial Pathologies - A Retrospective Case Review, Faezeh Razjouyan, Rishi Sood, Alex Cho, Anthony Venbrux, Shawn Sarin

GW Research Days 2016 - Present

Purpose:

Onyx is an embolic agent currently FDA approved for neurointerventional procedures such as in the treatment of aneurysms and arteriovenous malformations. Despite its limited indications, the agent's off-label use in the treatment of extracranial pathologies continues to increase. To date, there has not been a single-center study demonstrating a large number of cases demonstrating safe and effective peripheral embolization with Onyx.

Materials:

We performed a retrospective review of all cases that used Onyx between October 2010 and July 2016 at a single tertiary care academic university urban hospital. Institutional review board approval was appropriately obtained. Initial case selection ...


Adequacy Of Platelet Counting By Automated Haematology Analyzers: An Insight On Current Methodologies, Muhammad Shariq Shaikh, Noor Rahman Khan, Zeeshan Ansar Ahmed 2018 Aga Khan University

Adequacy Of Platelet Counting By Automated Haematology Analyzers: An Insight On Current Methodologies, Muhammad Shariq Shaikh, Noor Rahman Khan, Zeeshan Ansar Ahmed

Department of Pathology and Laboratory Medicine

No abstract provided.


The Role Of Reactive Astrocitose In The Chronological Evolution Of Traumatic Brain Injury, Roxana M. Duncea-Borca, Vladimir Belis, Mihnea Costescu, Relu G. Calota, Reka Kutasi, Cosmin A. Moldovan 2018 Forensic Medicine of Teleorman County, Department of Forensic Medicine

The Role Of Reactive Astrocitose In The Chronological Evolution Of Traumatic Brain Injury, Roxana M. Duncea-Borca, Vladimir Belis, Mihnea Costescu, Relu G. Calota, Reka Kutasi, Cosmin A. Moldovan

Journal of Mind and Medical Sciences

Introduction and objectives. This study aims to investigate whether the cerebral modifications of posttraumatic reactive astrocitose can be considered an objective criterion for determining the age of traumatic cranio-cerebral lesions.

Materials and methods. The present study consists of a series of 23 medico-legal cases that underwent autopsy inTeleormanCounty(Romania) Department of Forensic Medicine during 2007–2016, with full immune-histochemical microscopic examination using GFAP staining. The study consists of two groups, a series of 13 cases with cranio-cerebral trauma with different posttraumatic survival periods and 9 cases as a control group.

Results and discussions. We discovered GFAP+ reactive astrocytes even when ...


Histopathology Report On Colon Cancer Specimens; Measuring Surgical Quality, An Increasing Stress For Surgeons, Stefan Morarasu, Tudor Frunza, Karina Bilavschi, Ana Maria Patrascu, Sorinel Lunca, Gabriel Dimofte 2018 Regional Institute of Oncology, Department of Surgical Oncology, Grigore T Popa University of Medicine and Pharmacy

Histopathology Report On Colon Cancer Specimens; Measuring Surgical Quality, An Increasing Stress For Surgeons, Stefan Morarasu, Tudor Frunza, Karina Bilavschi, Ana Maria Patrascu, Sorinel Lunca, Gabriel Dimofte

Journal of Mind and Medical Sciences

Introduction. Improving the quality of surgical resections by evaluating surgical specimens is probably the most important feedback a surgeon can receive. Moreover, prognosis of patients with colon cancer is based on achieving appropriate resection margins and assessment of lymph node status. For these reasons we aim to provide a retrospective analysis on colon cancer specimens operated by a single surgical team.

Materials and Methods. 88 patients operated between 2013 and 2016 were included in the study. Data were gathered prospectively and assessed by multivariate analysis for the main variables (age, gender, tumor staging, specimen length, distance to closest resection margin ...


Pathogen Recognition By Cd4 Effectors Drives Key Effector And Most Memory Cell Generation Against Respiratory Virus, Priyadharshini Devarajan, Michael C. Jones, Olivia Kugler-Umana, Allen M. Vong, Jingya Xia, Susan L. Swain 2018 University of Massachusetts Medical School

Pathogen Recognition By Cd4 Effectors Drives Key Effector And Most Memory Cell Generation Against Respiratory Virus, Priyadharshini Devarajan, Michael C. Jones, Olivia Kugler-Umana, Allen M. Vong, Jingya Xia, Susan L. Swain

Open Access Articles

Although much is known about the mechanisms by which pathogen recognition drives the initiation of T cell responses, including those to respiratory viruses, the role of pathogen recognition in fate decisions of T cells once they have become effectors remains poorly defined. Here, we review our recent studies that suggest that the generation of CD4 T cell memory is determined by recognition of virus at an effector "checkpoint." We propose this is also true of more highly differentiated tissue-restricted effector cells, including cytotoxic "ThCTL" in the site of infection and TFH in secondary lymphoid organs. We point out that ThCTL ...


Spsnet: Subpopulation-Sensitive Network-Based Analysis Of Heterogeneous Gene Expression Data., Abha Belorkar, Rajanikanth Vadigepalli, Limsoon Wong 2018 Thomas Jefferson University; National University of Singapore

Spsnet: Subpopulation-Sensitive Network-Based Analysis Of Heterogeneous Gene Expression Data., Abha Belorkar, Rajanikanth Vadigepalli, Limsoon Wong

Department of Pathology, Anatomy and Cell Biology Faculty Papers

BACKGROUND: Transcriptomic datasets often contain undeclared heterogeneity arising from biological variation such as diversity of disease subtypes, treatment subgroups, time-series gene expression, nested experimental conditions, as well as technical variation due to batch effects, platform differences in integrated meta-analyses, etc. However, current analysis approaches are primarily designed to handle comparisons between experimental conditions represented by homogeneous samples, thus precluding the discovery of underlying subphenotypes. Unsupervised methods for subtype identification are typically based on individual gene level analysis, which often result in irreproducible gene signatures for potential subtypes. Emerging methods to study heterogeneity have been largely developed in the context of ...


Sex-Dependent Effects Of Developmental Lead Exposure On The Brain, Garima Singh, Vikrant Singh, Marissa Sobolewski, Deborah A. Cory-Slechta, Jay S. Schneider 2018 Thomas Jefferson University

Sex-Dependent Effects Of Developmental Lead Exposure On The Brain, Garima Singh, Vikrant Singh, Marissa Sobolewski, Deborah A. Cory-Slechta, Jay S. Schneider

Department of Pathology, Anatomy and Cell Biology Faculty Papers

The role of sex as an effect modifier of developmental lead (Pb) exposure has until recently received little attention. Lead exposure in early life can affect brain development with persisting influences on cognitive and behavioral functioning, as well as, elevated risks for developing a variety of diseases and disorders in later life. Although both sexes are affected by Pb exposure, the incidence, manifestation, and severity of outcomes appears to differ in males and females. Results from epidemiologic and animal studies indicate significant effect modification by sex, however, the results are not consistent across studies. Unfortunately, only a limited number of ...


Integrating Tuberculosis And Antimicrobial Resistance Control Programmes, Rumina Hasan, Sadia Shakoor, Johanna Hanefeld, Mishal Khan 2018 Aga Khan University

Integrating Tuberculosis And Antimicrobial Resistance Control Programmes, Rumina Hasan, Sadia Shakoor, Johanna Hanefeld, Mishal Khan

Department of Pathology and Laboratory Medicine

Many low- and middle-income countries facing high levels of antimicrobial resistance, and the associated morbidity from ineffective treatment, also have a high burden of tuberculosis. Over recent decades many countries have developed effective laboratory and information systems for tuberculosis control. In this paper we describe how existing tuberculosis laboratory systems can be expanded to accommodate antimicrobial resistance functions. We show how such expansion in services may benefit tuberculosis case-finding and laboratory capacity through integration of laboratory services. We further summarize the synergies between high-level strategies on tuberculosis and antimicrobial resistance control. These provide a potential platform for the integration of ...


Cold Agglutinins In Peripheral Blood With Atypical Cells With An Owl-Eye Appearance In Bone Trephine, Ayesha Majeed Memon, Farheen Karim 2018 Aga Khan University

Cold Agglutinins In Peripheral Blood With Atypical Cells With An Owl-Eye Appearance In Bone Trephine, Ayesha Majeed Memon, Farheen Karim

Department of Pathology and Laboratory Medicine

Autoimmune hemolytic anemia (AIHA) is a form of hemolytic anemia in which red cells lysis occurs due to presence of an autoantibody. Association of AIHA is well known with lymphoproliferative disorders, especially with non-Hodgkin's lymphoma. However, AIHA in association with Hodgkin's lymphoma is seen occasionally. Of the AIHA associated with Hodgkin's lymphoma, most are of warm type or mixed type. Cold AIHA, as seen in our case, is very rare in Hodgkin's lymphoma.


Identification Of Herpes Zoster-Associated Temporal Arteritis Among Cases Of Giant Cell Arteritis, Erin M. Buckingham, Maria A. Foley, Charles Grose, Nasreen A. Syed, Morton E. Smith, Todd P. Margolis, Matthew J. Thurtell, Randy Kardon 2018 University of Iowa

Identification Of Herpes Zoster-Associated Temporal Arteritis Among Cases Of Giant Cell Arteritis, Erin M. Buckingham, Maria A. Foley, Charles Grose, Nasreen A. Syed, Morton E. Smith, Todd P. Margolis, Matthew J. Thurtell, Randy Kardon

Stead Family Department of Pediatrics Publications

PURPOSE: To examine whether herpes zoster antigen (also called varicella-zoster virus antigen) was detectable in temporal artery biopsies taken from individuals with giant cell arteritis (GCA).

DESIGN: Retrospective comparative case series.

METHODS: Sections of formalin-fixed paraffin-embedded temporal arteries were examined first by hematoxylin-eosin (H&E) staining to establish the diagnosis of GCA. Adjacent sections of the same biopsy were then examined by immunohistochemistry, using 2 different monoclonal antibodies against a major antigen of varicella-zoster virus called gE. Pathologic specimens were obtained from patients cared for at the University of Iowa and Washington University in St. Louis ophthalmology clinics.

RESULTS: The ...


Human West Nile Virus Disease Outbreak In Pakistan, 2015–2016, E. Khan, Kelli L. Barr, Joveria Farooqi, Dhani Prakoso, Alizae Abbas, Zain Y. Khan, Shanze Ashi, Kehkashan Imtiaz, Z Aziz, Faisal Malik 2018 Aga Khan University

Human West Nile Virus Disease Outbreak In Pakistan, 2015–2016, E. Khan, Kelli L. Barr, Joveria Farooqi, Dhani Prakoso, Alizae Abbas, Zain Y. Khan, Shanze Ashi, Kehkashan Imtiaz, Z Aziz, Faisal Malik

Department of Pathology and Laboratory Medicine

Like most of the world, Pakistan has seen an increase in mosquito-transmitted diseases in recent years. The magnitude and distribution of these diseases are poorly understood as Pakistan does not have a nation-wide system for reporting disease. A cross-sectional study to determine which flaviviruses were causing of arboviral disease in Pakistan was instituted. West Nile virus (WNV) is a cause of seasonal fever with neurotropic findings in countries that share borders with Pakistan. Here, we describe the active and persistent circulation of WNV in humans in the southern region of Pakistan. This is the first report of WNV causing neurological ...


Emergence Of An Extensively Drug-Resistant Salmonella Enterica Serovar Typhi Clone Harboring A Promiscuous Plasmid Encoding Resistance To Fluoroquinolones And Third-Generation Cephalosporins, Rumina Hasan, Sadia Shakoor, Farah Naz Farid, Dania Khalid Saeed, Ghazala Shaheen, Shahida Qureshi, Mohammad Tahir Yousafzai, Muhammad Khalid Salim, Zahra Hasan, Elizabeth J. Klemma, Andrew J. Page, Kim Judge, Vanessa K. Wong, Timothy J. Dallman, Satheesh Nair, Stephen Baker, Gordon Dougan 2018 Agha Khan University

Emergence Of An Extensively Drug-Resistant Salmonella Enterica Serovar Typhi Clone Harboring A Promiscuous Plasmid Encoding Resistance To Fluoroquinolones And Third-Generation Cephalosporins, Rumina Hasan, Sadia Shakoor, Farah Naz Farid, Dania Khalid Saeed, Ghazala Shaheen, Shahida Qureshi, Mohammad Tahir Yousafzai, Muhammad Khalid Salim, Zahra Hasan, Elizabeth J. Klemma, Andrew J. Page, Kim Judge, Vanessa K. Wong, Timothy J. Dallman, Satheesh Nair, Stephen Baker, Gordon Dougan

Department of Pathology and Laboratory Medicine

Antibiotic resistance is a major problem in Salmonella enterica serovar Typhi, the causative agent of typhoid. Multidrug-resistant (MDR) isolates are prevalent in parts of Asia and Africa and are often associated with the dominant H58 haplotype. Reduced susceptibility to fluoroquinolones is also widespread, and sporadic cases of resistance to third-generation cephalosporins or azithromycin have also been reported. Here, we report the first large-scale emergence and spread of a novel S. Typhi clone harboring resistance to three first-line drugs (chloramphenicol, ampicillin, and trimethoprim-sulfamethoxazole) as well as fluoroquinolones and third-generation cephalosporins in Sindh, Pakistan, which we classify as extensively drug resistant (XDR ...


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