Pathology Commons^™

Dissemination And Spread Of New Delhi Metallo-Beta-Lactamase-1 Superbugs In Hospital Settings, Erum Khan, Seema Irfan, Binish Arif Sultan, Amna Nasir, Rumina Hasan

Department of Pathology and Laboratory Medicine

Objective:
To find out frequency of isolation of carbapenem-resistant enterobacteriaceae and the predominantly responsible metallo-beta-lactamasegene in a hospital setting.
Methods:
The descriptive, cross-sectional study was conducted from May 2009 to June 2012 at the Aga Khan University Hospital, Karachi, and comprised non-duplicate clinical carbapenem-resistant enterobacteriaceae isolates obtained from different collection units across Pakistan. Kirby-Bauer disk diffusion screening of carbapenem-resistant enterobacteriaceae was confirmed by minimum inhibitory concentration using E-test. Polymerase chain reaction assay was performed to detect blaKPC, blaNDM-1, blaIMP, and blaVIM genes. In addition variable number tandem repeat typing was performed on selected cluster of New Delhi metallo-beta-lactamase-1- positive …

Human Herpesvirus Multiplex Ddpcr Detection In Brain Tissue From Low- And High-Grade Astrocytoma Cases And Controls., Cheng-Te Major Lin, Emily C Leibovitch, M Isabel Almira-Suarez, Steven Jacobson

Pathology Faculty Publications

BACKGROUND: Glioblastoma (GBM) is a fatal CNS malignancy, representing 50 % of all gliomas with approximately 12-18 months survival time after initial diagnosis. Recently, the human herpesvirus cytomegalovirus (CMV) has been suggested to have an oncogenic role, yet this association remains controversial. In addition, human herpesvirus 6 (HHV-6) and Epstein-Barr virus (EBV) have also been associated with low-grade gliomas, but few studies have examined HHV-6 and EBV in glioblastomas. Droplet digital PCR (ddPCR) is a highly precise diagnostic tool that enables the absolute quantification of target DNA. This study examines the association between multiple human herpesviruses and astrocytomas.

METHODS: This …

Mir-27a And Mir-27b Regulate Autophagic Clearance Of Damaged Mitochondria By Targeting Pten-Induced Putative Kinase 1 (Pink1), Jaekwang Kim, Fabienne C. Fiesel, Krystal C. Belmonte, Roman Hudec, Wang-Xia Wang, Chaeyoung Kim, Peter T. Nelson, Wolfdieter Springer, Jungsu Kim

Pathology and Laboratory Medicine Faculty Publications

Background: Loss-of-function mutations in PINK1 and PARKIN are the most common causes of autosomal recessive Parkinson’s disease (PD). PINK1 is a mitochondrial serine/threonine kinase that plays a critical role in mitophagy, a selective autophagic clearance of damaged mitochondria. Accumulating evidence suggests mitochondrial dysfunction is one of central mechanisms underlying PD pathogenesis. Therefore, identifying regulatory mechanisms of PINK1 expression may provide novel therapeutic opportunities for PD. Although post-translational stabilization of PINK1 upon mitochondrial damage has been extensively studied, little is known about the regulation mechanism of PINK1 at the transcriptional or translational levels.

Results: Here, we demonstrated that microRNA-27a (miR-27a) and …

The Genetic Landscape Of Dural Marginal Zone Lymphomas, Karthik A. Ganapathi, Vaidehi Jobanputra, Fabio Iwamoto, Pallavi Khattar, Elaine S. Jaffe, Mahesh M. Mansukhani, Govind Bhagat

NYMC Faculty Publications

The dura is a rare site of involvement by marginal zone lymphoma (MZL) and the biology of dural MZL is not well understood. We performed genome-wide DNA copy number and targeted mutational analysis of 14 dural MZL to determine the genetic landscape of this entity. Monoallelic and biallelic inactivation of TNFAIP3 by mutation (n=5) or loss (n=1) was observed in 6/9 (67%) dural MZL exhibiting plasmacytic differentiation, including 3 IgG4+ cases. In contrast, activating NOTCH2 mutations were detected in 4/5 (80%) dural MZL displaying variable monocytoid morphology. Inactivating TBL1XR1 mutations were identified in all NOTCH2 mutated cases. Recurrent mutations in …

Multisite Evaluation Of Cepheid Xpert Carba-R Assay For Detection Of Carbapenemase-Producing Organisms In Rectal Swabs., M Tato, P Ruiz-Garbajosa, R Humphries, J Hindler, J Veltman, H Wang, R Cantón

NYMC Student Publications

Rapid identification of patients who are colonized with carbapenemase-producing organisms (CPO) is included in multiple national guidelines for containment of these organisms. In a multisite study, we evaluated the performance of the Cepheid Xpert Carba-R assay, a qualitative diagnostic test that was designed for the rapid detection and differentiation of the blaKPC, blaNDM, blaVIM, blaOXA-48, and blaIMP-1 genes from rectal swab specimens. A double rectal swab set was collected from 383 patients admitted at four institutions (2 in the United States, 1 in the United Kingdom, 1 in Spain). One swab was used for reference culture (MacConkey broth containing 1 …

A Rare Case Of The Upper Extremity Diffuse Large B-Cell Lymphoma Mimicking Soft Tissue Sarcoma In An Elderly Patient, Aleksandra Mamorska-Dyga, Faisal Ronny, Carmelo Puccio, Humayun Islam, Delong Liu

NYMC Faculty Publications

Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma, with about 30% of new cases presenting with extranodal disease. Lesions originating from soft tissues of the upper extremities are extremely rare and may mimic other malignancies like sarcoma. We present a case of an elderly patient with right upper extremity (RUE) mass which was proven to be DLBCL instead of sarcoma. We emphasize the increasing need for investigating new therapeutic options for patients of extreme age and/or with underlying heart disease.

Data Correlations Between Gender, Cytomegalovirus Infection And T Cells, Nk Cells, And Soluble Immune Mediators In Elderly Humans, Ahmad Al-Attar, Steven R. Presnell, Charlotte A. Peterson, D. Travis Thomas, Charles T. Lutz

Pathology and Laboratory Medicine Faculty Publications

We describe a cohort of 50 elderly subjects, age at least 70 years. We present gender-specific findings in T lymphocyte markers and soluble immune mediators. We show the correlation between cytomegalovirus infection status with CD56^dim NK cell responses to a variety of stimuli and with CD56^bright/CD56^dim NK cell ratio. We also present the correlation of retinol binding protein (RBP)−4 plasma levels with NK cell responses and we explore the relationship between gender and adiponectin, 25(OH)D (vitamin D), and RBP4 in affecting CD56^dim NK cell responses. These data are discussed in Al-Attar et al. (2016)

Histological And Molecular Analysis Of A Progressive Diffuse Intrinsic Pontine Glioma And Synchronous Metastatic Lesions: A Case Report., Javad Nazarian, Gary E Mason, Cheng Ying Ho, Eshini Panditharatna, Madhuri Kambhampati, Louis Gilbert Vezina, Roger J. Packer, Eugene I Hwang

Genomics and Precision Medicine Faculty Publications

There is no curative treatment for patients with diffuse intrinsic pontine glioma (DIPG). However, with the recent availability of biopsy and autopsy tissue, new data regarding the biologic behavior of this tumor have emerged, allowing greater molecular characterization and leading to investigations which may result in improved therapeutic options. Treatment strategies must address both primary disease sites as well as any metastatic deposits, which may be variably sensitive to a particular approach.In this case report, we present a patient with DIPG treated with irradiation and serial investigational agents. The clinical, pathological and molecular phenotypes of both the progressive primary tumor …

Mrsa Causing Infections In Hospitals In Greater Metropolitan New York: Major Shift In The Dominant Clonal Type Between 1996 And 2014, Maria Pardos De La Gandara, Judith Berger, David Burstein, Phyllis Della-Latta, Guiqing Wang, Alexander Tomasz

NYMC Faculty Publications

A surveillance study in 1996 identified the USA100 clone (ST5/SCCmecII)-also known as the "New York/Japan" clone-as the most prevalent MRSA causing infections in 12 New York City hospitals. Here we update the epidemiology of MRSA in seven of the same hospitals eighteen years later in 2013/14. Most of the current MRSA isolates (78 of 121) belonged to the MRSA clone USA300 (CC8/SCCmecIV) but the USA100 clone-dominant in the 1996 survey-still remained the second most frequent MRSA (25 of the 121 isolates) causing 32% of blood stream infections. The USA300 clone was most common in skin and soft tissue infections (SSTIs) …

Low Level Phosphorylation Of Histone H2ax On Serine 139 (Gammah2ax) Is Not Associated With Dna Double-Strand Breaks, Paulina Rybak, Agnieszka Hoang, Lukasz Bujnowicz, Tytus Bernas, Zbigniew Darzynkiewicz, Jerzy Dobrucki

NYMC Faculty Publications

Phosphorylation of histone H2AX on serine 139 (γH2AX) is an early step in cellular response to a DNA double-strand break (DSB). γH2AX foci are generally regarded as markers of DSBs. A growing body of evidence demonstrates, however, that while induction of DSBs always brings about phosphorylation of histone H2AX, the reverse is not true - the presence of γH2AX foci should not be considered an unequivocal marker of DNA double-strand breaks. We studied DNA damage induced in A549 human lung adenocarcinoma cells by topoisomerase type I and II inhibitors (0.2 μM camptothecin, 10 μM etoposide or 0.2 μM mitoxantrone for …

Glomus Tumor Of Trachea In An Adult Male, Sidra Arshad, Zubair Ahmad, Nasir Ud Din

Department of Pathology and Laboratory Medicine

Glomus tumors most commonly occur in distal extremities, particularly in the subungual region. The origin of these tumors is modified smooth muscle cells of glomus bodies. Trachea is one of the rare sites where normal glomus bodies may be sparse or absent, so occurrence of glomus tumor in trachea is very rare. Only 30 cases have been reported in the literature so far. In this case report, the authors describe a very rare and in fact first case of glomus tumor of trachea in a 45-year male Pakistani patient.

Diagnostic Accuracy Of Anti-Endomysial Antibody In Celiac Disease, Arslaan Javaeed, Walayat Shah, Saaniya Khan Gauri, Rizwan Akhtar

Department of Pathology and Laboratory Medicine

The objective of the study was to determine the diagnostic accuracy of anti-EMA antibody in comparison to histopathological findings in patients suspected of CD. This cross-sectional study was conducted at Gastroenterology Department, Fatima Memorial Hospital, Lahore, from March to October 2014. One hundred and twenty-one patients aged between 5 - 60 years of either gender were recruited in the study. Every patient went through serological testing and biopsy specimens were obtained from second part of the duodenum. Histopathological evaluation was done according to the Modified Marsh classification. The overall sensitivity of anti-EMAcame out to be 85.7% which varied with the …

Cerebral Aspergillosis And Pulmonary Tuberculosis In A Child With Chronic Granulomatous Disease, Muhammad Waqas, Sidra Zafar, Tooba Rehman, Muhammed Riyaz, Muhammad Ehsan Bari, Romana Idress

Section of Neurosurgery

Background: Chronic granulomatous disease (CGD) is an immune disorder that affects phagocytes. It is characterized by recurrent or persistent bacterial and fungal infections. Reports of tuberculosis (TB) in patients with CGD are rare. In developing countries, where TB is endemic, possibility of other chronic infections is often overlooked by physicians.
Case description: We report the case of a 4-year-old boy who had recurrent respiratory infections and episodes of headache. He was put on antituberculosis (ATT) drugs without microbiological or pathological evidence 2 months prior to presentation. The child did not improve and was brought to our hospital where a computed …

Induction Process Of Trainees In Pathology Residency, Imran Siddiqui, Natasha Bahadur Ali

Department of Pathology and Laboratory Medicine

This article describes the evolution of the induction process of pathology residency at The Aga Khan University hospital. The Department of Postgraduate Medical Education was established in 1985. The induction process is an exhaustive exercise that includes an admission test held simultaneously in Karachi, Hyderabad, Lahore, and Rawalpindi, followed by an interview of the shortlisted candidates. The pathology residency program was started 25 years ago and since then the induction process has undergone major changes with the course of time.

How Diet Intervention Via Modulation Of Dna Damage Response Through Micrornas May Have An Effect On Cancer Prevention And Aging, An In Silico Study, Felicia Carotenuto, Maria C. Albertini, Dario Coletti, Alessandra Vilmercati, Luigi Campanella, Zbigniew Darzynkiewicz, Laura Teodori

NYMC Faculty Publications

The DNA damage response (DDR) is a molecular mechanism that cells have evolved to sense DNA damage (DD) to promote DNA repair, or to lead to apoptosis, or cellular senescence if the damage is too extensive. Recent evidence indicates that microRNAs (miRs) play a critical role in the regulation of DDR. Dietary bioactive compounds through miRs may affect activity of numerous genes. Among the most studied bioactive compounds modulating expression of miRs are epi-gallocatechin-3-gallate, curcumin, resveratrol and n3-polyunsaturated fatty acids. To compare the impact of these dietary compounds on DD/DDR network modulation, we performed a literature search and an in …

Recurrent Mutations Of T-Cell Receptor And Co-Stimulatory Signaling Proteins In Peripheral T-Cell Lymphomas, Joseph Rohr

Theses & Dissertations

Peripheral T-cell lymphomas (PTCLs) comprise a heterogeneous group of mature T-cell neoplasms with a poor prognosis. Recently, mutations in TET2 and other epigenetic modifiers as well as RHOA have been identified in these diseases, particularly in angioimmunoblastic T-cell lymphoma (AITL). CD28 is the major co-stimulatory receptor in T-cells which, upon binding ligand, induces sustained T-cell proliferation and cytokine production when combined with T-cell receptor stimulation, through many signaling molecules including VAV1. This thesis identifies recurrent mutations in CD28 in PTCLs, as well as mutations in VAV1. Two residues of CD28 – D124 and T195 – were recurrently mutated in 11.3% …

Assessment Of Wt1 Expression As A Marker Of Treatment Outcome In Karyotype Normal Acute Myeloid Leukemia Patients In Pakistan, Zeeshan Ansar Ahmed, Muhammad Shariq Shaikh, Tariq Moatter

Department of Pathology and Laboratory Medicine

Currently, there is an effort to predict relapse by follow-up monitoring of MRD and subsequently to begin the treatment of the patients during their clinical and hematological remission prior to overt hematological relapse. Expression of WT1 in AM Lis known to be independently associated with significant inferior response to therapy and short survival outcome. Follow-up monitoring of WT1 gene expression during or after therapy would be a valuable predictive marker for early recurrence or relapse of AMLdisease. This pilot study evaluated newly diagnosed and post-induction or consolidation chemotherapy of AMLpatients who were registered with the Oncology Clinics of the Aga …

Adenoid Cystic Carcinoma Of Breast: Clinicopathologic Study Of Seven Cases, Raabia Nizamuddin, Nasir Ud Din, Romana Idress, Naila Kayani

Department of Pathology and Laboratory Medicine

Adenoid cystic carcinoma (ACC) of the breast is a rare type of tumor. Our objective was to determine the clinicopathologic features of breast ACC. We reviewed slides of breast ACC reported during 12 years. Seven cases were identified. Age ranged from 38 to 59 years (mean = 47 years). Mean tumor size was 2.3 cm (range 1.2 to 4 cm). Histologically, dominant cribriform pattern was seen in 4 cases, solid in 2 and tubular in one case. Mitotic figures ranged from 2 to 22/10 HPFs. Grades I and II were seen in 3 cases each while 1 was grade III. …

Cll Metabolism Is Regulated By Prognostic Factors, Modulated By Stroma And Abrogated By Pi3k Inhibition, Hima Vangapandu

Dissertations and Theses (Open Access)

Metabolism of chronic lymphocytic leukemia (CLL), a disease characterized by the relentless accumulation of mature B cells has been little explored. Bone marrow stromal cells provide a survival benefit to CLL cells, in part through PI3K/AKT pathway. Compared with proliferative B-cell lines, metabolic fluxes of oxygen and lactate were low in quiescent malignant B lymphocytes from CLL patients. Glycolysis (extracellular acidification rate, ECAR) was consistently low in CLL samples, but oxygen consumption (OCR) varied considerably. Higher OCR was associated with poor prognostic factors such as ZAP 70 positivity, unmutated IgVH, high β2M levels, and higher Rai stage. Co-culture with the …

Isolation Frequency And Susceptibility Pattern Of Non-O1 And Non-O139 Vibrio Cholerae In A Tertiary Health Care Laboratory, 1999-2012, S Irfan, N Fasih, N K. Ghanchi, Erum Khan

Department of Pathology and Laboratory Medicine

In the past decade the importance of non-O1 and non-O139 strains of Vibrio cholerae has been highlighted globally. This study aimed to evaluate the frequency and antimicrobial susceptibility profile of non-O1 and non-O139 V. cholerae in Pakistan. Data of stool specimens yielding growth of non-O1 and non-O139 V. cholerae isolated at a national referral laboratory from 1999 to 2012 were retrospectively analysed and evaluated for resistance to ampicillin, tetracycline, chloramphenicol, co-trimoxazole and ofloxacin. A total of 95 800 stool samples submitted over 1999-2012 yielded 3668 strains of V. cholerae, of which 6% were non-O1 and non-O139 V. cholerae. A high …