Real-World Challenges of Haplo-Identical Hematopoietic Stem Cell Transplant in a Developing Country: A Single Center Experience.

Hematopoietic stem cell transplant (HSCT) is potentially, the sole curative option for many malignant and non-malignant hematological disorders. Finding a human leukocyte antigen (HLA) compatible donor remains one of the limiting factors, hampering the utilization of HSCT. However, the introduction of post-transplant cyclophosphamide (PTCy) has improved the outcomes of haploidentical transplants making it a suitable option for patients lacking HLA-compatible donors. We collected data from 44 patients who underwent haplo-identical allogeneic stem cell transplants at the Armed Forces Bone Marrow Transplant Center/National Institute of Blood and Marrow Transplant (AFBMTC/NIBMT) from the year 2015 to 2022. The diseases were divided into three categories, i.e., bone marrow failure (BMF) syndromes, hematological malignancies (HM) and miscellaneous (Misc) groups. Median age at transplant was 18 (01-39) years. Transplant indications included aplastic anemia (AA) in 21 (47.7%) cases, 15 (34.1%) HM, and eight (18.2%) cases falling in the Misc groups. A maximum number of graft failures occurred in the BMF group; primary graft failure in 07 (33.3%) cases and secondary graft failure in four (19%) cases, (p-value < 0.05). Acute graft versus host disease (aGVHD) grade II-IV occurred in nine (20.5%) cases while chronic graft versus host disease (cGVHD) occurred in 10 (22.7%) cases. Cytomegalovirus (CMV) reactivation was seen in 31 (70.5%) cases. Maximum CMV reactivation was seen in HM group 13 (86.6%) cases, (p-value < 0.05) as compared to BMF (71.4%) and Misc groups (37.5%). Post-transplant cyclophosphamide (PTCy) based regimens, early neutrophil engraftment, and patients with GVHD had better survival outcomes (p-value < 0.05) overall survival (OS), and relapse-free survival (RFS). and GVHD-free relapse-free survival (GFRS) were significantly better in cases with early neutrophil engraftment. OS of the study cohort was 50% while disease-free survival (DFS) and GFRS were 45.5% and 36.4%, respectively.

Comparison of Turbidimetric Inhibition Immunoassay, High-Performance Liquid Chromatography, and Capillary Electrophoresis Methods for Glycated Hemoglobin Determination.

OBJECTIVE: The purpose of this study was to compare the performances of and evaluate the agreement among glycated hemoglobin values analyzed by using National Glycohemoglobin Standardization Program-certified and International Federation of Clinical Chemistry-standardized analyzers. THIS CROSS-SECTIONAL STUDY WAS CONDUCTED AT THE: Armed Forces Institute of Pathology, Department of Chemical Pathology from March 2019 to May 2019. METHODS: Glycated hemoglobin (HbA1c) was measured in the blood specimens from 100 patients on an ADVIA 1800 by a turbidimetric inhibitory immunoassay (TINIA), Sebia instrument by electrophoresis, and Bio-Rad Variant II Turbo system by high-performance liquid chromatography (HPLC). Quantitative variables were calculated as the mean ±â€…standard deviation (SD). Precision and method comparisons were carried out according to Clinical and Laboratory Standards Institute recommendations. The results obtained from each analyzer were compared by correlation analysis. Method comparison was done by linear regression and Bland-Altman plots using the SPSS software version 24. RESULTS: The mean ±â€…SD HbA1c values from TINIA, electrophoresis, and HPLC were 7.188% ±â€…1.89%, 7.164% ±â€…1.866%, and 7.160% ±â€…1.85%, respectively. The between-run coefficients of variation for TINIA, electrophoresis, and HPLC were 0.64%, 0.61%, and 0.60%, respectively. All 3 showed good correlation (TINIA, R2 = .994, P = .00; electrophoresis, R2 = .992, P = 0.00; and HPLC, R2 = .994, P = 0.00). CONCLUSION: The good clinical agreements of HbA1c and strong correlations between analyzers indicate that these analyzers can be used interchangeably.

Efficacy of Antimicrobials Against Multidrug-Resistant Acinetobacter baumannii from Patients in a Tertiary Care Hospital.

Introduction: In just two decades Acinetobacter baumannii has attained considerable importance, evolving from an insignificant organism to a leading pathogen especially in intensive care unit settings globally. Treatment options are already very limited and have almost run out due to the rapid emergence of antimicrobial resistance. Evaluation of antimicrobials that are currently in use to determine their effectiveness against multidrug-resistant (MDR) strains and developing newer options is of utmost importance. We thus set out to determine the efficacy of routinely used antibiotics against MDR A. baumannii. Materials and Methods: This was a cross-sectional study conducted at the Department of Microbiology, Army Medical College, National University of Medical Sciences (Rawalpindi, Pakistan) from December 2015 to June 2016. The organisms were identified on the basis of colony morphology, gram staining, catalase, oxidase, motility test, and API (analytical profile index) 20NE. The organisms were considered to be MDR when the isolate was found to be resistant to at least one agent in more than three antimicrobial groups. Antibiotic sensitivity was determined using the modified Kirby-Bauer disc diffusion method according to Clinical Laboratory Standards Institute (CLSI) guidelines. Results: The 77 isolates were found to have good sensitivity to tigecycline (94.8%) and minocycline (80.5%). Most of the isolates were resistant to other routinely used antibiotics. Conclusion: A few antibiotics, tigecycline and minocycline, are still effective against these MDR A. baumannii. We need to remain up to date regarding the efficacy of antibiotics to effectively treat patients with these MDR bacteria.

Triglycerides-to-HDLC Ratio as a Marker of Cardiac Disease and Vascular Risk Factors in Adults.

OBJECTIVE: To find out correlation of triglycerides-to-HDL cholesterol ratio in elders with cardiac risk factors like obesity, diabetes, and hypertension. STUDY DESIGN: Observational cross-sectional study. PLACE AND DURATION OF STUDY: Department of Chemical Pathology and Endocrinology, Combined Military Hospital, Rawalpindi, from January to June 2018. METHODOLOGY: Inclusion standards were participants aged 20-59 years .Patients with comorbidity and chronic illness were excluded from the study. A planned standardised homogeneous survey was conducted as a pilot study. Social, economic and physical variables like age, gender, marital status and presence of diseases, all were taken into consideration. To check association among cardio metabolic risk factors like diabetes, obesity, hypertension, and TG/HDL-C ratio, Chi-square test was computed for all cardio metabolic risk factors. RESULTS: Overall 350 participants were studied after attainment of authorisation from Ethical Review Board of Combined Military Hospital, Rawalpindi, in which 268 (76.6%) were women; whereas, 82 (23.4%) were men with mean age of 37 ± 11.64 years. There was strong association of TG/HDL ratio with BMI, HOMA-IR, WBISI, visceral fats, smooth muscle mass, HDL, LDL, and triglycerides with p <0.04, p <0.001, p <0.01, and p <0.001, respectively. CONCLUSION: TG/HDLC ratio can be considered as a potential biomarker for the early prediction of cardiometablic risk factors.

Hypertension associated risk factors in Pakistan: A multifactorial case-control study.

OBJECTIVE: To shed light on the association of age, smoking, educational status, family history, diabetes and kidney diseases with hypertension. METHODS: The case-control study was conducted at three different medical centres of Rawalpindi, Pakistan, from December 2016 to July 2017. Data from 549 hypertensive cases and 1451 normotensive controls was collected using a detailed questionnaire and through personal interviews by adopting nonprobability consecutive sampling technique. Overall 2000 adult individuals, both males and females excluding pregnant women, were the part of this study. Those with blood pressure ≥140/90mmHg and taking anti-hypertensive treatment were designated as the cases, while the rest were taken as normotensive controls. Blood pressure was measured by a physician. Multivariate logistics regression analysis was used to estimate the association of various different risk factors with hypertension. All the analysis was performed using software R 3.4.2 and SPSS 24. RESULTS: Of the 2,000 subjects, 549(27.45%) were hypertensive cases and 1451(72.55%) were normotensive controls. Mean age of the cases was 43.32}9.7 years and it was 31.8}10.1 years among the normotensives. Higher age, smoking, lower educational status, presence of kidney diseases, diabetes and family history of hypertension were significantly associated with hypertension (p<0.01 each). CONCLUSIONS: In Pakistani population, age, smoking, illiteracy, kidney diseases, diabetes and family history were found to be associated with hypertension.

Growth Hormone and ACTH Deficiency in a Diabetic Adult.

Adult growth hormone deficiency (AGHD) syndrome has a constellation of features, like impaired cognitive function, altered body composition, poor quality of life and various metabolic changes. Most of its features resemble signs of aging as growth hormone (GH) secretion decreases with age. Hypothalamic-pituitary-adrenal (HPA) axis should be thoroughly investigated in this disease as patients with AGHD are at risk of life-threatening consequences due to partial or complete ACTH deficiency, especially in stressful conditions. GH deficiency has also been related to diabetes or glucose intolerance. It is relatively underdiagnosed problem in adults and requires a thorough workup including dynamic function tests like insulin tolerance test (ITT), which has been termed as the gold standard for the diagnosis of patients with ACTH deficiency.

Frequency of Primary Hyperaldosteronism in Young Hypertensives in a Tertiary Care Setting of Rawalpindi.

OBJECTIVE: To determine the frequency of primary hyperaldosteronism in young hypertensives in hospital settings of Rawalpindi. STUDY DESIGN: Cross-sectional study. PLACE AND DURATION OF STUDY: Department of Chemical Pathology and Endocrinology, Armed Forces Institute of Pathology (AFIP), Rawalpindi, from June 2016 to May 2017. METHODOLOGY: Two hundred and fifty patients with hypertension (blood pressure of more than 140/90 mm Hg) of both genders, with age between 17-40 years were recruited in the study. Patients on anti-hypertensive medications, renal function derangement, pregnant females and those labelled with secondary hypertension were excluded. Blood samples were taken for the analyses of plasma renin, aldosterone, electrolytes, and blood gases. Parametric quantitative variables were presented as mean + SD. RESULTS: Eight cases, out of a total 80 subjects fulfilling the inclusion criteria, were diagnosed with primary hyperaldosteronism and 72 with essential hypertension. Mean age of patients having primary hyperaldosteronism was 29.25 +7.1 years. The mean diastolic blood pressure of all patients was 90.3 +6.5 mm of Hg, while mean systolic blood pressure was 142.7 +10.5 mm of Hg. CONCLUSION: Frequency of primary hyperaldosteronism was found to be 10%, emphasising on the fact that it is not very uncommon in young hypertensives.

Determination of reference intervals of thyroid markers during pregnancy in Urban area of District Rawalpindi Pakistan.

OBJECTIVE: To determine the reference values for thyroid stimulating hormone, free tetra-iodothyronine and total tri-iodothyronine for healthy pregnant women. METHODS: This cross sectional study was conducted at the Armed Forces Institute of Pathology, Rawalpindi, Pakistan, from January 2016 to June 2017. Pregnant women with normal, single intrauterine, uncomplicated pregnancy were recruited from the local population. Blood sample was taken to analyse thyroid stimulating hormone, free tetra-iodothyronine and total tri-iodothyronine using chemiluminescence immunoassay. For thyroid hormone levels during each trimester 5th and 95th percentiles were calculated as reference intervals. Data was analysed using SPSS 24. RESULTS: Out of 384 subjects, 188(48.95%) were in their first trimester and 196(51.04 %) females were in their second trimester. There were 109(57.97%) primigravida in the first trimester and 137(69.9%) in the second trimester. Mean age of subjects presenting in the first and second trimester was 25.37±3.78 years and 26.54±4.65 years respectively. Reference intervals for those in the first trimester for thyroid stimulating hormone was 0.05-2.8uIU/ml, for free tetra-iodothyronine14.4-22.7pmol/l and total tri-iodothyronine1.5-3.3nmol/l. For those in second trimester the corresponding values were 0.16-3.3 uIU/ml, 14.2-24.6.0 pmol/l and 1.6-3.1nmol/l. CONCLUSIONS: Laboratories should adopt trimester-specific reference intervals for thyroid function tests in pregnancy..

Acrophobia in a Young Girl with Parathyroid Hormone Resistance (Pseudohypoparathyroidism).

Pseudohypoparathyroidism (PHP) is an extremely rare group of disorders. It is a spectrum of disorders caused by end organ resistance to parathyroid hormone (PTH) and is represented by impaired signalling that activates cAMP dependent pathways via alpha subunit of G-protein (GS). It is characterised by hypocalcemia, hyperphosphatemia, raised PTH levels due to insensitivity to biological activity of PTH, and normal renal function tests. We describe a case of 10-year girl who presented with fear of falling down from heights. Her laboratory evaluation and skeletal survey showed evidence of PHP along with features of Albright's hereditary osteodystrophy (AHO) pointing towards the diagnosis of PHP type 1a.

Spectrum of renin angiotensin aldosterone system disorders in young hypertensives.

OBJECTIVE: To analyse the spectrum of renin angiotensin aldosterone system disorders in young hypertensive patients in hospital settings. METHODS: This cross-sectional study was conducted at the Department of Chemical Pathology and Endocrinology, Armed Forces Institute of Pathology, Rawalpindi, Pakistan, from January to December, 2016. It comprised hypertensive subjects aged 17-40 years of either gender presenting in the outpatient department. All subjects were having blood pressure more than 140/90mmHg and were not on any anti-hypertensive medicine. Blood sample was taken from each patient to analyse arterial blood gases, plasma renin, serum aldosterone and electrolytes. Association of qualitative variables like age, systolic and diastolic blood pressure with essential hypertension and primary hyperaldosteronism was explored. RESULTS: Of the 80 patients, 72(90%) were diagnosed with essential hypertension and 8(10%) with primary hyperaldosteronism. None of the patients had Liddle syndrome, apparent mineralocorticoid excess or Gordon syndrome. Mean age of patients having essential hypertension was 30.97±7.1 years, whereas, for those with primary hyperaldosteronism it was 29.25±7.1 years. Systolic blood pressure was significantly higher (p = 0.000) among all patients. No statistically significant association was found between age, systolic and diastolic blood pressure (p<0.05). CONCLUSIONS: Primary hyperaldosteronism as compared to other renin angiotensin aldosterone system disorders was found to be the leading cause of hypertension in young population.

In Vitro Efficacy of Doripenem against Pseudomonas aeruginosa and Acinetobacter baumannii by E-Test.

OBJECTIVE: To assess the in vitro efficacy of doripenem against Pseudomonas aeruginosa and Acinetobacter baumannii using Epsilometer strips. STUDY DESIGN: Cross-sectional study. PLACE AND DURATION OF STUDY: Department of Microbiology, Army Medical College, Rawalpindi and National University of Sciences and Technology, Islamabad, from May 2014 to September 2014. METHODOLOGY: A total of 60 isolates of Acinetobacter baumannii and Pseudomonas aeruginosa collected from various clinical samples received from Military Hospital were included in the study. The specimens were inoculated onto blood, MacConkey and chocolate agars. The isolates were identified using Gram staining, motility, catalase test, oxidase test and API 20NE (Biomeriux, France). Organisms identified as Acinetobacter baumannii and Pseudomonas aeruginosa were included in the study. Bacterial suspensions equivalent to 0.5 McFarland turbidity standard of the isolates were prepared and applied on Mueller Hinton agar. Epsilometer strip was placed in the center of the plate and incubated for 18-24 hours. Minimum Inhibitory Concentration (MIC) was taken to be the point where the epsilon intersected the E-strip. MIC of all the isolates was noted. RESULTS: For Pseudomonas aeruginosa isolates, MIC(50) was 12 µg/mL and MIC(90) was 32 µg/mL. For Acinetobacter baumannii MIC(50) and MIC(90) was 32 µg/mL. CONCLUSION: Doripenem is no more effective against Pseudomonas aeruginosa and Acinetobacter baumannii in our setting.