Glycogen storage diseases-time to flip the outdated diagnostic approach centered on liver biopsy with the molecular testing

The glycogen storage diseases (GSDs) are a group of inherited metabolic disorders that result from a defect in any one of several enzymes required for either glycogen synthesis or glycogen degradation. The traditional diagnostic approach is based on the invasive hepatic or muscle biopsies, which are neither cost effective nor convenient. Molecular (gene testing) has emerged over the course of past few years as a robust alternative diagnostic tool, which not only confirms the diagnosis of GSDs but also clearly differentiates the types of GSDs allowing the initiation of the type-specific appropriate treatment for the particular type of GSDs. The aim of this update is to highlight the limitations of undertaking a liver biopsy for the diagnosis of GSDs; and to further describe the pros of the molecular testing for better patient centered care

Trend analysis of lab tests requisitions of COVID-19 prognostic biomarkers at a clinical chemistry reference laboratory-an observational study

Background: Biochemical parameters, such as C-reactive protein (C-RP), Procalcitonin (PCT), Lactate dehydrogenase (LDH) and Ferritin are associated with COVID-19 severity and prognosis. This trend analysis of COVID-19 prognostic biomarker requisitions is aimed at providing a reflection of the clinical practices adopted amidst the peak of the pandemic. This knowledge of the prognostic biomarkers utilized, will further aid to classify patients based on their risk, for optimal resource allocation and improve outcomes.Material & methods: This cross-sectional study was conducted at the clinical chemistry laboratory at the Aga Khan University Hospital (AKUH), Karachi Pakistan. A team consisting of two clinical chemistry consultants reviewed the COVID-19 prognostic biomarkers tests performance data from March to July 2020 using the integrated laboratory information management system (ILMS). The test statistics of March to July 2020 when COVID-19 cases were on the rise in the country were compared with those of the same months from 2019. The changes in the test groups were expressed in percentages. Microsoft Excel for windows 2019 was used for data analysis.Results: The total specimens received for testing in 2020 (n = 574,092) showed a percent decline of approximately (-) 33% compared to 2019 (n = 858,756). Contrary to the overall decline in volumes an upward surge was noted for the prognostic biomarkers. From March to July, the highest percent change was noted for LDH (+155.1%), followed by PCT (+66.7.1%), C-RP (+26.5%) and Ferritin (+22.1%) in 2020 compared to the same time frame in 2019. The highest percent change was noted in June.Conclusion: During the COVID 19 pandemic, a significant increase in utilization of laboratory services was seen for COVID-19 prognostic markers

Is it T3 thyrotoxicosis? A case of falsely elevated tri-iodothyronine (T3) levels leading to a diagnosis of multiple myeloma

We are presenting a case of falsely elevated T3 levels in a patient due to interference from monoclonal immunoglobulins. A 56-year-old, clinically euthyroid man referred to the endocrinology clinic of the Aga Khan university, Karachi Pakistan, for possible T3 thyrotoxicosis after thyroid function tests revealed total T3 \u3e12.32 nmol/L (reference range 0.6-2.79), normal TSH, and total T4 level. There was a mismatch in clinical and laboratory parameters and preliminary laboratory results were suggestive of thyroid binding globulin abnormalities. Further evaluation in this context unmasked multiple myeloma. The presence of monoclonal immunoglobulins can lead to assay interference and spurious results. To the best of our knowledge, this is the second case defining the cause of falsely elevated T3 levels, due to assay interferences with binding of T3 only to monoclonal immunoglobulins

Impact of COVID-19 on laboratory professionals-A descriptive cross sectional survey at a clinical chemistry laboratory in a developing country

Background: The lab professionals at one end are at increased risk of contracting the infection while on the other end have to deal with the various challenges during the Coronavirus Disease 2019 (COVID-19) outbreak. This survey was undertaken to analyze the lab professionals\u27 perspectives, in terms of the challenges, financial implications, fears, motivation and satisfaction from organizational processes and policies adopted, amid the COVID-19 crisis.Material & methods: The study utilized a cross-sectional survey design. The survey was administered online via the google docs survey tool from medical laboratory professionals (n = 64) serving at the section of Clinical Chemistry, department of Pathology and Laboratory Medicine, the Aga Khan University (AKU), Pakistan from June 4th to 14th 2020. A team consisting of three Clinical Chemistry consultants serving as faculty at the section, designed the survey questionnaire. The responses were recorded on a five-point Likert Scale (1 = strongly disagree, 2 = disagree, 3 = neutral, 4 = agree and 5 = strongly agree). The statistical analysis was performed using the Microsoft Excel 2013. Frequency and percentages were calculated for gender, experience and designation while descriptive results based on the responses were also recorded.Results: The response rate was 78% (n = 50). 60% responded that the current lifestyle adopted during the pandemic was not better than the traditional one. The fear of employment termination and financial challenges were being faced by 42% and 78% respondents respectively. The quality of family life was improved in 54% cases while 96% were of the view that their social activities at work have suffered. Whereas, 22% were not satisfied by the measures taking by the management during the outbreak.Conclusion: The findings of this survey provide laboratorians\u27 perspective, in times of such crisis and provides us certain lessons to prepare for such unpredicted situations in future

Alternative approaches for the treatment of Asthma and COPD: Focus on Cell-based therapies, Epigenetics, and Gene silencing approaches

Despite many organized health initiatives and critically acclaimed guidelines for proper management of asthma therapy, there is still a large population of severe asthmatics having an uncontrolled disease. Severe persistent asthma, characterized by chronic airway inflammation, increased eosinophils and serum IgE is currently managed by using inhaled corticosteroids. It is quite challenging to get the best treatment guidelines for bronchial asthma in severe asthmatics, particularly in the presence of steroid resistance and the non-responsiveness to β-agonists. For that purpose, other methodologies are required to reverse the uncontrolled airway remodeling in steroid-resistant severe asthma. These advanced alternative approaches should be able to treat asthma symptoms and to improve the inflammatory conditions underlying characteristic pathological features of asthma. The current review focuses and summarizes the alternative approaches used in severe asthma patients. Agents targeting inflammatory cytokines, phosphodiesterase inhibitors, antibodies, oligonucleotides, stem cells, and target drug delivery using gene silencing, offer promise in treating severe asthma.Keywords: Asthma; COPD; Therapies; Epigenetics; Gene silencin

Evaluation of \u27CKD-EPI Pakistan\u27 equation for estimated glomerular filtration rate (eGFR): a comparison of eGFR prediction equations in Pakistani population

Objective: To evaluate the results of 24-hour urinary creatinine clearance (CrCl) with estimated glomerular filtration rate (eGFR) using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), CKD-EPI Pakistan (CKD-EPI Pak), Cockcroft Gault (CG) and 4-variable Modification of Diet in Renal Disease (MDRD) equations.Study Design: Descriptive, cross-sectional study.Place and Duration of Study: Section of Clinical Chemistry, Department of Pathology and Laboratory Medicine, The Aga Khan University, Karachi, from June to October 2013. Methodology: Laboratory data of subjects ≥18 years ordering 24-hour urinary CrCl from June to October 2013 was retrieved. Statistical comparison of eGFR using CKD-EPI, CKD-EPI Pak, CG and MDRD with the timed urine collection CrCl was done using regression analysis. Result: The mean age of the group (n=670) was 51.3 ±15.4 years with a median of 53 (IQR:22.3) years, 55.7% being males. Median BMI of males and females was 26.98 kg/m2(IQR: 7.09) and 26.16 kg/m2(IQR: 6.97), respectively. Mean GFR using 24-hour creatinine clearance was 57.1 ±35.9 ml/min/1.73m2 with a median of 51 ml/min/1.73m2. Urinary creatinine clearance showed strong correlation with CG, MDRD, CKD-EPI and CKD-EPI Pak, showing r=0.78, r=0.79, r=0.82, and r=0.82, respectively. Sensitivity was highest for the CKD-EPI Pakistan (84.7%). Similarly, CKD-EPI Pakistan equation showed the highest agreement (88.7%) with CrCl compared to the other formulae. Conclusion: The CKD-EPI Pak equation is more accurate and precise than the CG, CKD-EPI and MDRD in estimating GFR in Pakistani population

Performance evaluation of cardiac troponin I assay: A comparison between the point-of-care testing radiometer AQT90 FLEX and the central laboratory siemens advia centaur analyzer

Background: To validate the point of care testing (POCT) Trop-I analyzer and compare it with a central laboratory-based chemiluminescence immunoassay, in order to evaluate its performance for use in critical care areas. Moreover, for clinical decision-making, it is imperative to know the extent to which patient stratification will differ based on the analytic method being used. In particular, the aim of this study was to evaluate the analytical performance of the point-of-care analyzer and demonstrate the agreement with the central laboratory measurements in patients presenting to the emergency department (ED) with chest pain and suspected acute coronary syndrome (ACS).Methods: This cross-sectional study was performed at the section of chemical pathology, department of pathology and laboratory medicine, the Aga Khan University (AKU), Karachi, from October to November 2017. Samples from patients and the quality control material of Trop-I were analyzed for imprecision, linearity, and method comparison on Advia Centaur (Siemens Diagnostics, CA, USA), and the AQT90 FLEX analyzer (Radiometer Medical ApS, Brønshøj, Denmark) with photometric detection at the section of chemical pathology, AKU. Statistical analysis was done using Microsoft Excel (Microsoft Corporation, Washington, United States) and EP Evaluator version 10.3.0.556 (Data Innovations, LLC, VT, US). Quantitative variables were represented in terms of mean ± SD. For precision, the computed SD was compared with allowable random error. Furthermore, Cohen’s kappa was applied to observe the agreement between the two methods.Results: The Trop-I Precision study on the POCT analyzer showed a coefficient of variation (CV) of 2.4% using a pooled patient sample with a mean Trop-I of 2.15 ± 0.05 ng/ml. Three standards ranging from 0.034 to 1.316 ng/ml were run in triplicate to verify accuracy and linearity. The allowable systematic error (SEa) was 10.0%. The maximum deviation for a mean recovery from 100% was 4.1%. All three of the mean recoveries were accurate and within the allowable error limits. The results were linear with slope 1.04, intercept 0.0. On a method comparison, Trop-I showed good agreement, yielding a kappa value of 0.95.Conclusion: This study has validated the performance of a POCT Trop-I assay against a central laboratory immunoassay and found acceptable results. POCT assays for cTnI should be implanted in emergency settings to ensure the fast triage of patients with chest pain, as well as timely diagnosis

Is COVID-19 impacting cancer screening in Pakistan? An observational study of cancer screening test requests during the pandemic

Background: The purpose of this study is to assess how the COVID-19 pandemic affected cancer screening at a large tertiary care setting in the city of Karachi, the third largest city in the world, and to identify if there has been any decrease in cancer screening during the ongoing pandemic.Methods: A retrospective observational study was conducted at the clinical chemistry laboratory at the Department of Pathology & Laboratory Medicine, Aga Khan University Hospital (AKUH), Karachi Pakistan. Data for test volumes was extracted from the Integrated Laboratory Management System (ILMS) for the following tumor markers: CA19 Carbohydrate Antigen 19-9 (CA 19-9), Calcitonin, Prostate Specific Antigen (PSA), from 2017 to 2020. Data from January 1st, 2017 till December 31st, 2019 was recorded and compared with the test volume data from January 1st, 2020 till December 31st, 2020. Number of tests performed in the prior 3 years were compared with tests performed in 2020, specifically looking at changes during the lockdown period in 2020 (1st March - 9 th April) and compared with the same period in preceding years.Results: During the four-year period, a total of 6,530 tests were performed for CA19-9, 893 for Calcitonin, and 54,769 for PSA. Year 2019 recorded the highest volume for all 3 tests with test volumes increasing continuously from 2017 to 2019. Number of tests performed decreased throughout the year 2020 for Calcitonin and PSA, whereas volume of tests for CA19-9 only reduced during the lockdown period while increased in the non-lockdown period as compared to previous years. Highest percent decline during the 2020 lockdown period was seen for Calcitonin (-62.5%), followed by PSA (-51.8%) and CA19-9 (-19%).Conclusion: In conclusion, the amount of CA19-9, Calcitonin, and PSA tests performed in Karachi, Pakistan has drastically reduced due to the lockdown that was mandated due to the COVID-19 outbreak. It is crucial that despite an imposed lockdown, regular cancer screening must continue

Indirect determination of serum creatinine reference intervals in a Pakistani pediatric population using big data analytics

Background: The indirect methods of reference intervals (RI) establishment based on data mining are utilized to overcome the ethical, practical challenges and the cost associated with the conventional direct approach.Aim: To generate RIs for serum creatinine in children and adolescents using an indirect statistical tool.Methods: Data mining of the laboratory information system was performed for serum creatinine analyzed from birth to 17 years for both genders. The timeline was set at six years from January 2013 to December 2018. Microsoft Excel 2010 and an indirect algorithm developed by the German Society of Clinical Chemistry and Laboratory Medicine\u27s Working Group on Guide Limits were used for the data analysis.Results: Data were extracted from 96104 samples and after excluding multiple samples for the same individual, we calculated RIs for 21920 males and 14846 females, with stratification into six discrete age groups.Conclusion: Serum creatinine dynamics varied significantly across gender and age groups

Osteoporosis and its perspective in Pakistan: A review of evidence and issues for addressing fragility fractures

Despite major advances in osteoporosis diagnosis and treatment, low rates of investigating and treating osteoporosis in patients with fragility fracture are reported in Pakistan. Cost of therapies, time and cost of resources for diagnosis, concerns about medications and lack of clarity regarding the onus of responsibility to undertake this care, are some of the barriers to osteoporosis identification and treatment. Data from our part of the world on osteoporosis as well as on fragility fractures is sparse. This review addresses the current screening and diagnostic strategies for osteoporosis and reviews the existing literature to highlight the issues prevalent in our society on this major public health problem