Pakistan Journal of Pathology 2018-03-05T18:18:01+00:00 Lt Col Asif Ali Memon Open Journal Systems CAR T CELLS – GET OWN CELLS TO TREAT CANCERS 2018-03-05T18:17:55+00:00 Muhammad Mukarram Bashir <p>Recently, sitting in my TV lounge, I watched a footage on BBC: a living drug for childhood blood cancers, has an 87% cure rate, comes with a price tag of $475,000 per patient, and has been approved by FDA. The drug consists of patient’s OWN T cells, armed <em>in vitro</em> to attack and kill the cancer cells after being infused back to the same patient.</p><p>As a student of Immunology, reading passages on passive immunity, I always wondered how adoptive transfer of cells could be a worthwhile medium of passive immunity…neutrophils have such a short life in circulation and foreign lymphocytes would be readily attacked and eliminated by the host immune system. Just another theoretical mess to irritate students. But, here we are, with amazing possibilities!</p><p>Classical treatments for cancers remind us of surgery, chemotherapy, and radiation therapy. In the last two decades, targeted therapies like <a href="">imatinib (Gleevec®)</a> and <a href="">trastuzumab (Herceptin®)</a>—drugs that target cancer cells—have established themselves as standard treatments for some cancers. Now, the world is likely to witness the miracle of <a href="">immunotherapy</a>—therapies that tap the power of a patient’s immune system to attack tumours—as the “fifth pillar” of cancer treatment.</p><p>A rapidly emerging immunotherapy approach called adoptive cell transfer (ACT), collecting and using patients’ own immune cells to treat their cancer can employ various theoretical means but, thus far, the one that has advanced the furthest in clinical development is CAR (Chimeric Antigen Receptor) T-cell therapy. Initially used for advanced blood cancers, the treatment offers great hope for both children and adults when all other treatments had stopped working. Last year, Food and Drug Administration (FDA) approved two CAR T-cell therapies, one for the treatment of children with <a href="">acute lymphoblastic leukemia</a> (ALL) and the other for adults with advanced lymphomas.</p><p>As its name implies, the backbone of CAR T-cell therapy is <a href=";version=Patient&amp;language=English">T cells</a>, which are often called the workhorses of the immune system because of their critical role in orchestrating the immune response and killing cells infected by pathogens. The therapy requires drawing blood from patients and separating out the T cells. Next, using a disarmed virus, the T cells are genetically engineered to produce receptors on their surface called chimeric antigen receptors, or CARs. These receptors are synthetic molecules, don’t exist naturally and allow the T cells to recognize and attach to a specific protein, or <a href=";version=Patient&amp;language=English">antigen</a>, on tumour cells. The CAR T cell therapies target an antigen found on B cells called CD19.  Once the collected T cells have been engineered to express the antigen-specific CAR, they are “expanded” in the laboratory into the hundreds of millions. The final step is the infusion of the CAR T cells into the patient (which is preceded by a “lymphodepleting” chemotherapy regimen). If all goes as planned, the engineered cells further multiply in the patient’s body and, with guidance from their engineered receptor, recognize and kill cancer cells that harbour the antigen on their surfaces.</p><p>The progress made with CAR T-cell therapy in children with ALL has been fantastic and the results in lymphoma to date have been termed incredibly successful. There are cohorts of patients, who would have been considered terminal, but are now in durable and meaningful remissions with good quality of life for up to 5 years,</p><p>CAR T-cell therapy can cause several worrisome, and sometimes fatal, side effects. One of the most frequent is <a href=";version=Patient&amp;language=English">cytokine release syndrome</a> (CRS). T cells release cytokines, chemical messengers that help to stimulate and direct the immune response. A rapid and massive release of cytokines into the bloodstream can lead to dangerously high fevers and precipitous drops in blood pressure. In many patients, CRS can be managed with standard supportive therapies, including steroids. In more serious cases of CRS, blockade of IL-6 is the key to treatment.</p><p>Another potential side effect of CAR T-cell therapy—an off-target effect—is a mass die off of B cells, known as B-cell aplasia. Normal B cells are also often killed by the infused CAR T cells. To compensate, many patients must receive immunoglobulin therapy, which provides them with the necessary antibodies to fight off infections.</p><p>One might wonder: what is next! Imagined and real future developments include preparing CAR T cells not from the actual patients but from healthy donors. These ready-made cells would be available immediately like other drugs and don’t have to be actually prepared for individual patients. Other novel methods are <em>in vivo</em> preparation of CAR T cells (inside the body) by nanotechnology, making cells with “off switches” to minimize the side effects and using gene editing technology to precisely engineer the T cells.</p><p>The potential and the possibilities are endless and magical but human desires and imagination, the driving force for all possibilities to take form, far exceed everything, as Ghalib said it so well:</p><p align="center">ہے  کہاں تمنّا  کا  دوسر ا قدم  یا  رب</p><p align="center">ہم نے دشتِ امکاں کو ایک نقشِ پا پایا</p>Where will the next step of desire be, O Lord,<br /> I/ we found the whole desert of possibility to be just one footprint. 2018-03-05T18:17:55+00:00 ##submission.copyrightStatement## FREQUENCY OF ABO AND Rh BLOOD GROUP AMONG THE HEALTHY BLOOD DONORS, A SINGLE CENTRE STUDY 2018-03-05T18:17:56+00:00 Muhammad Arif Sadiq Rizwan Yusuf Aamir Hussain Asma Bilal <p><strong>Objective:</strong>  To determine the frequency of ABO and Rh blood groups among the healthy blood donors. <br /> <strong>Study Design:</strong> Cross sectional study.</p><p><strong>Place and Duration of study:</strong> This was carried out at Pakistan Air Force (PAF) Hospital Islamabad from January 2015 to April 2017.</p><p><strong>Materials and Methods:</strong> The blood donors were recruited from Islamabad and surroundings. A detailed medical history and examination was carried out by medical officer. All donors were provided questionnaire and consent Proforma. The blood donors negative for previous history of viral hepatitis and other contraindications for blood donation were included in study. Blood group of each donor was confirmed by using ABO Antisera and Rhesus monoclonal Antisera of Biolaboratories by tube method. </p><p><strong>Results:</strong> A total of 2185 healthy blood donors were enrolled. Male were predominant population among the blood donors with a ratio of 45:1. Majority of the blood donors were in the third decade of their life. The most common ABO blood group was B whereas Rh positive was most common among Rh blood group system.<br /> <strong>Conclusion:</strong> The blood group B was most frequent blood group among the healthy blood donors. Whereas, AB was found to be least frequent. Among the Rh blood group system, Rh positive was found to be more frequent as compared to Rh negative.</p><strong>Keywords:</strong> Blood donors, ABO, Rh, Blood group 2018-03-05T18:17:56+00:00 ##submission.copyrightStatement## EMPIRICAL USE OF ANTIBIOTICS FOR SORE THROAT – HOW RATIONAL IS IT? 2018-03-05T18:17:56+00:00 Rifat Nadeem Ahmad Sajida Naseem Mahwish Majid Bhatti Haider Ghazanfar Zainab Ali Khan <p><strong>Objective:</strong> To determine the frequency of Group A Streptococci culture positive cases among sore throat patients who were prescribed antibiotics</p><p><strong>Study Design:</strong> Cross-sectional study.</p><p><strong>Place and Duration of study:</strong> This study was conducted at Shifa College of Medicine, Islamabad and outpatient departments of two tertiary care hospitals of Islamabad from August to November 2015.</p><p><strong>Materials and Methods:</strong> Throat swab cultures were done in cases prescribed empirical antibiotics for sore throat. All data regarding the physicians and patients, presenting complaints, clinical findings and prescriptions was recorded on a structured questionnaire. Frequencies and percentages were calculated for each variable in the questionnaire.</p><p><strong>Results:</strong> A total of 151 adult patients, who presented with sore throat were enrolled for the study. Inflammation of posterior pharyngeal wall/tonsils was observed in 132 (87%) patients, while exudate was seen in 40 (27%) cases. Tonsils were enlarged in 9 (6%) cases, follicular tonsillitis was observed in 3 (2%) and cervical lymphadenopathy was present in 2 (1.3%) patients. All patients were prescribed empirical antibiotics. Among them, 55 (36.4%) received levofloxacin, 29 (19.2%) azithromycin, 25 (16.6%) amoxicillin/clavulanate potassium or a combination of these with a cephalosporin (27.8%). Group A Streptococci were isolated from throat swabs of only 3 (2%) patients.</p><p><strong>Conclusion:</strong> Empirical prescription of antibiotics for sore throat in most cases is unjustified and the practice should be discouraged.</p><strong>Keywords:</strong> Pharyngitis, Antibiotics, Clinical practice patterns, Inappropriate prescribing. 2018-03-05T18:17:56+00:00 ##submission.copyrightStatement## ANALYSIS OF CEREBROSPINAL FLUID ANALYTES IN BACTERIAL AND TUBERCULOUS MENINGITIS 2018-03-05T18:17:57+00:00 Noreen Samad Sadia Jabeen Iqra Zulfiqar <p><strong>Objective:</strong>  Meningitis is the severe and lethal infection spread worldwide. The most common forms of meningitis are viral and bacterial meningitis caused by Neisseria meningitides and other species. Tuberculous meningitis (TBM) is the most mortal form of <em>Mycobacterium tuberculosis </em>infection, which has a high rate of neurological complications and sequelae. The best method for diagnosis of meningitis is cerebrospinal fluid analysis (CSF). The purpose of present study is to determine the CSF examination (glucose and protein levels) of subjects with bacterial meningitis (BM) and TBM and their comparison with healthy individuals.</p><p><strong>Study Design:</strong> Cohort Study.</p><p><strong>Place and Duration of study:</strong> The study was conducted in Children Medical Complex Hospital Multan, during February 2016 to June 2016.</p><p><strong>Materials and Methods:</strong> The data of 75 children (25 of TBM, 25 of BM and 25 of normal) with age &lt;5 years was collected. The analysis of CSF protein and glucose levels was done by standard methods. The data was statistically analyzed by using SPSS software (version 20).</p><p><strong>Results:</strong> Results showed that levels of glucose in CSF were decreased in BM and TBM than normal individuals, whereas, in TBM glucose levels were more decreased than BM. On the other hand, the levels of protein were high in both diseases bacterial meningitis and TBM than normal individuals.</p><p><strong>Conclusion:</strong> It is concluded that, poverty, sneezing, coughing, low nutritional quality of meals and unhygienic conditions are responsible for meningitis. Earlier diagnosis can might prevent the disease but severe form of this disease need effective antibiotic treatment. Vaccination also plays an efficient role in prevention of meningitis.</p><strong>Keywords:</strong> Meningitis, BM, TBM, CSF analysis, Glucose, Protein 2018-03-05T18:17:57+00:00 ##submission.copyrightStatement## ETIOLOGICAL SPECTRUM OF PANCYTOPENIA USING BONE MARROW ASPIRATION AND BIOPSY 2018-03-05T18:17:58+00:00 Muhammad Ihtesham Khan Syeda Hina Fatima Neelam Ahmad <p><strong>Objective:</strong> The objective of this study was to analyse the etiology of pancytopenia in our setup using bone marrow biopsy, thus highlighting the diagnostic importance of bone marrow biopsy examination and helping to develop an approach in management of this condition.</p><p><strong>Study design: </strong>Cross sectional descriptive study.<strong></strong></p><p><strong>Place and duration of the study:</strong>  Khyber Teaching Hospital, Peshawar, from 1.1.2016 to 31.12.2016.<strong></strong></p><p><strong>Materials &amp; Methods</strong>: The 79 patients of all ages and both gender referred for bone marrow biopsy having pancytopenia were included in the study. Hemoglobin level below 10gm/dL, white cell count of less than 4x10<sup>9</sup>/L and platelet count below 150x10<sup>9</sup> were taken as the criteria for pancytopenia. Pancytopenia was reported by automated cell counter. Low platelet count was confirmed by peripheral blood film examination. Bone marrow aspiration and biopsy were done. The findings were recorded in proforma and results were drawn accordingly.</p><p><strong>Results</strong>: During the study period, about 79 patients fulfilled the criteria for pancytopenia. About 3 patients had diluted bone marrow aspirate which was unfit for making final diagnosis that’s why they were excluded. Remaining 76 patients with pancytopenia were included in the study. Age of study subjects ranged from 1 to 65 years (mean age 31 years ± 16.3 SD). 41(54%) males, and 35 (46%) females, male to female ratio of 1.2: 1. Among 76 cases, the commonest non-malignant etiology for pancytopenia on bone marrow examination was megaloblastic anemia, which was seen in 16(21%) cases. Commonest malignant etiology was acute leukemia which was seen in 10.6% cases (i.e. 5.3 % Acute myeloid leukemia and 5.3% Acute lymphoblastic leukemia), and mononuclear infiltration (seen in 10.5 % cases). Myelodysplasia and myelofibrosis were seen in 3 (3.9%) cases. Chronic lymphocytic leukemia, Gaucher’s disease, mixed deficiency anemia and Niemann pick disease were seen in 2 (2.6%) cases each. Anemia of chronic disorder, Malaria, hemolytic anemia, multiple myeloma, visceral leishmaniasis, and hemophagocytic lymphohistiocytosis were seen in 1 (1.3%) case of pancytopenia.</p><p><strong>Conclusion:</strong> Megaloblastic anemia was the commonest, non-malignant cause, while acute leukemia was the commonest, malignant cause of pancytopenia. It was through the bone marrow aspiration biopsy examination that such a wide spectrum of diagnoses was made in patients presenting with the single finding of pancytopenia. Hence, bone marrow aspiration biopsy is useful diagnostic tools in evaluating pancytopenia.</p><strong>Keywords</strong>:  Pancytopenia, Bone marrow, Megaloblastic anemia. 2018-03-05T18:17:58+00:00 ##submission.copyrightStatement## NASAL CARRIAGE OF METHICILLIN RESISTANT STAPHYLOCOCCUS AUREUS AMONG TERTIARY CARE HOSPITAL EMPLOYEES IN A NON-OUTBREAK SETTING 2018-03-05T18:17:59+00:00 Amina Asif Iffat Javed Sohaila Mushtaq Saeed Anwar <p><strong>Objective:  </strong>To estimate the frequency of methicillin resistant <em>Staphylococcus aureus</em> (MRSA) nasal carriage in employees of a tertiary care hospital.<strong></strong></p><p><strong>Study design:</strong> Descriptive cross-sectional study<strong></strong></p><p><strong>Place and Duration of Study:  </strong>This descriptive cross-sectional study was carried out in Lahore General Hospital, Lahore during October, 2015 – January 2016.The samples were processed according to standard operating procedures at Microbiological laboratory of Post Graduate Medical Institute, Lahore. <strong></strong></p><p><strong>Materials and Methods:  </strong>Nasal swabs were collected from three hundred and eighty healthcare personnel working in various clinical wards of Lahore General Hospital, Lahore.  Preliminary identification of <em>Staphylococcus aureus</em> was done by observing colony morphology and mannitol fermentation on mannitol salt agar, Gram stain and catalase test. Further biochemical test, DNase, was applied for the confirmation of the organism. The phenotypic resistance to methicillin was determined using Cefoxitin disk 30 µg according to CLSI guidelines. <strong></strong></p><p><strong>Results:</strong>  Out of 380 nasal samples, 89 (23.42%) cultures yielded the growth of <em>S. aureus</em> out of which 31 (34.83%) were MRSA. The overall frequency of MRSA among all the HCWs was 8.15%. The MRSA carriage was more in males (9.7%). Age group of 50 years and above had the highest number of carriers (12.34%). The working category most affected was the paramedic staff (12.50%).  The highest number of MRSA carrier HCWs were working in the Pediatrics department (15.15%).<strong></strong></p><p><strong>Conclusion:</strong> The results of our study emphasize the need for the formulation of effective infection control policies within the healthcare setups<strong></strong></p><strong>Keywords: </strong><em>Staphylococcus aureus</em><strong>, </strong>MRSA, Nasal carriage, Hospital employees/ healthcare workers 2018-03-05T18:17:59+00:00 ##submission.copyrightStatement## ZIKA VIRUS, AN EMERGING THREAT: EVALUATION OF AWARENESS AMONG MEDICAL STUDENTS AND HEALTH CARE WORKERS IN A PUBLIC-SECTOR UNIVERSITY 2018-03-05T18:17:59+00:00 Tooba Ali Yameenah Farrukh Fauzia Imtiaz Mukkarum Ali Arif Ali <p><strong>Objective:  </strong>To find out awareness of Zika virus among medical students and health care workers.<strong></strong></p><p><strong>Study design: </strong>Cross sectional survey.<strong></strong></p><p><strong>Place and Duration of Study: </strong>A cross sectional survey was conducted in a Public Sector Medical College of Karachi to evaluate and compare knowledge between medical students, house officers and residents, during the period of May-Dec 2016. <strong></strong></p><p><strong>Materials and Methods: </strong>Questionnaire was designed to assess participant’s knowledge, attitude and approach towards this disease. The sample size was calculated by open epi online software giving a value of 587. The sampling technique used in this survey is nonrandom purposive type. The data was entered and analyzed on SPSS-version 16.0 using Chi-Square test and unpaired T-test. Interpretation was done using x and p values. Mean knowledge score for every group was then calculated to ascertain the level of existing knowledge.<strong></strong></p><p><strong>Results:</strong> Total of 587 participants consented to fill the questionnaire in the study, out of which 523 questionnaires were completely responded to. The response rate is 89%. Among them 71% were females and 29% were male.  62.3% of the participants were aware about the threat of zika virus, with the most common source of information (51.5%) being internet.<strong></strong></p><p><strong>Conclusion:</strong> The healthcare professionals have the awareness about the zika virus. On evaluation, a remarkably sound level of knowledge was ascertained among Residents, House Officers and medical students. However further awareness about disease control and diagnosis is of vital importance. <strong></strong></p><strong>Keywords: </strong>Zika virus, Awareness medical students, Health care workers. 2018-03-05T18:17:59+00:00 ##submission.copyrightStatement## ANTI-M ANTIBODY IN A NULLIPAROUS NEVER TRANSFUSED WOMAN – A CASE REPORT 2018-03-05T18:18:00+00:00 Rozina Ghani Maqbool Alam Muhammad Sajid Yazdani Muhammad Ali Rathore <p>Anti-M antibodies are mostly IgM, less commonly mixture of IgM and IgG and rarely solely of IgG type. The naturally occurring Anti-M is usually inactive at 37°C making it insignificant clinically. In less common cases the antibody is active at 37°C making it clinically significant due to its ability to cause haemolytic transfusion reactions (HTR) and haemolytic disease of fetus and newborn (HDFN). We report a case of naturally occurring Anti-M antibody active at 22°C and 37°C as well, detected incidentally in a nulliparous never transfused woman. This clinically significant antibody caused discrepancy in blood grouping also. M antigen negative red cells are required for transfusion in such cases and its presence creates a potential risk of HDFN in future pregnancies.</p><p><strong>Keywords: </strong>Anti-M antibody, Red cell alloantibody, Naturally occurring anti-M.<strong></strong></p> 2018-03-05T18:18:00+00:00 ##submission.copyrightStatement##