Basic Findings of Incidence of Breast Cancer in Allied Hospital Faisalabad, Pakistan: A Retrospective Study.

Background: Breast cancer is the most common malignancy among women worldwide. We aimed to know the past trends of age-specific breast cancer incidence rates in Faisalabad city. Methods: A retrospective study was designed at Allied Hospital Faisalabad (AHF), Pakistan from 2014-2018. Overall, 12742 cancer patients presented throughout these years, out of which 3390 were breast cancer cases. Descriptive statistics were computed and the results were presented as counts and percentage for categorical variables. Means and standard errors were computed for the continuous variables. For testing the association among categorical variables, a chi-square test of independence was used and the p-values less than 0.05 are reported as significant. Results: 84.70% patients were diagnosed with invasive breast carcinoma and 15.30% were all other types reported in the Allied Hospital Faisalabad. The incidence of breast cancer was outrageous in the 40-49 year-old age group (1021 patients, 30.12%) and the mean age is 45 in all years. An increase of 34.86% was observed from 2014 to 2018. The comprehensive four-year data (2015 to 2018) were further analyzed for histology, surgery, staging and grading pattern as 2014 files data was insufficient to discuss. The stage III and grade III were most common throughout the years from 2015 to 2018 with 33.9% and 55.71% respectively. Conclusion: Breast cancer is diagnosed more commonly in women than in any other type of cancers in Faisalabad city. There is a need to upgrade the existing hospital facilities to make the women diagnose the cancer at an earlier stage.

Evaluation of hypomagnesaemia in diabetic patients with nephropathy in a reference clinical laboratory: A comparative cross sectional study.

Serum Magnesium plays a significant role in different diabetic complications. This comparative cross sectional study was conducted to evaluate serum magnesium levels in patients with Type 2 Diabetes Mellitus (T2DM) with and without nephropathy. A total of 182 diabetic patients (91 with nephropathy and 91 without nephropathy) were included. Odds ratio were calculated and Mann Whitney U test was used to compare quantitative variables; p<0.05 was considered significant. The results showed that 64/91 (70.3%) patients with nephropathy had hypomagnesaemia as compared to 21/91 (23.07%) patients without nephropathy. The risk of hypomagnesaemia was higher in patients with nephropathy than without nephropathy (Odds ratio 2.7 vs 0.34). Median magnesium levels (1.73 mg/dl) were lower in patients with nephropathy as compared to patients without nephropathy (2.09 mg/dl), p<0.01. It is concluded that magnesium levels were significantly lower in patients with diabetic nephropathy as compared to without nephropathy.

Etiological study of short stature in children and role of insulin like growth factor-1 and insulin like growth factor binding protein-3 as screening markers for growth hormone deficiency.

OBJECTIVE: To determine aetiological factors in children with short stature, and to evaluate the role of insulin like growth factor-1 and insulin like growth factor binding protein-3 as screening markers for growth hormone deficiency. METHODS: The cross-sectional study was conducted at the Department of Chemical Pathology and Endocrinology, Armed Forces Institute of Pathology, Rawalpindi, Pakistan, from August 2020 to July 2021, and comprised children with short stature. Evaluation protocol included complete history and examination, baseline laboratory investigations, X-ray for bone age and karyotyping. Growth hormone status was assessed using growth hormone stimulation tests, and serum insulin like growth factor-1 and insulin like growth factor binding protein-3 levels were also assessed. Data was analysed using SPSS 25. RESULTS: Of the 649 children, 422(65.9%) were boys and 227(34.9%) were girls. The overall median age was 11 years (interquartile range: 11 years). Of the total, 116(17.9%) children had growth hormone deficiency. Familial short stature was present in 130(20%) children and constitutional delay in growth and puberty in 104(16.1%). There was no significant difference in levels of serum insulin like growth factor-1 and insulin like growth factor binding protein-3 in children who had growth hormone deficiency and those who had other causes of short stature (p>0.05). CONCLUSIONS: Physiological variants of short stature were found to be more common in the population followed by growth hormone deficiency. Serum insulin like growth factor-1 and insulin like growth factor binding protein-3 levels alone should not be used to screen children with short stature for growth hormone deficiency.

A Rare Case of Propionic Acidemia in a Six Months Female Child.

Propionic Acidemia (PA) is a rare metabolic disorder caused by the defect in enzyme (propionyl-coenzyme A (CoA) carboxylase) leading to the abnormal accumulation of metabolites of branched-chain amino acid catabolism in blood and urine. We describe the first ever diagnosed case in our setup of early onset PA in a 06 months old baby girl who presented with the complaints of decreased feed intake, lethargy, vomiting, failure to thrive, and intermittent seizures. The basic laboratory investigations showed pancytopenia along with high anion gap metabolic acidosis, urine dipstick positive for ketones, and hyperammonemia. Plasma amino acid analysis by ion exchange chromatography (IEC) showed elevated plasma glycine and lysine levels. Finally, urine organic acid analysis by gas chromatography-mass spectrometry (GCMS) showed marked elevation of 3-hydroxy propionate, methyl citrate, and 3-hydroxy, 2 methylbutyric acid with moderate rise in 3-hydroxy butyric acid without an elevation of methylmalonate in urine, thus giving the diagnosis of PA. Key Words: Propionic acidemia, Propionyl-CoA Carboxylase deficiency, Gas chromatography-mass spectrometry.

Assessment of National External Quality Assurance Programme of Pakistan as a tool for improving quality of lab results among participating laboratories.

OBJECTIVE: To assess the impact of the National External Quality Assessment Programme of Pakistan NEQAPP in improving the quality of laboratory results among the participating laboratories. METHODS: The cross-sectional observational study was conducted from July to December 2020 at the Department of Chemical Pathology and Endocrinology, Armed Forces Institute of Pathology, Rawalpindi, Pakistan, in association with the National Quality Assurance Programme of Pakistan. A survey questionnaire was developed and sent to the participating laboratories via email. Frequencies of their responses were calculated and data was analysed using SPSS 21. RESULTS: Of the 150 laboratories approached, 145(96.6%) responded. Among them, 140 (96.6%) laboratories were satisfied by the information provided on the programme's portal, 123(84.8%s) were pleased with the responsiveness of the programme manager, 140(96.6%) reported quality of services had improved after participation in the programme, 129(89%) indicated that the clinician's confidence had enhanced, and 122(84%) said the participation in the programme had improved the credibility of their respective of laboratories. CONCLUSIONS: The National External Quality Assessment Programme of Pakistan was found to have significantly contributed in improving the quality of laboratory results among the participating laboratories.

A case of congenital methaemoglobinaemia with secondary polycythemia.

Haemoglobin contains iron in a ferrous form. When the iron is oxidized, it is called Methaemoglobin (MetHb). MetHb leads to tissue hypoxia, cyanosis, and secondary polycythemia. Methaemoglobinaemia is acquired or congenital. In this case, a 22-years-old male patient presented with cyanosis, headache, and lack of concentration. Cyanosis was present since birth. His previous investigations showed polycythemia. He was misdiagnosed on multiple occasions and was undergoing venesections for polycythemia. On evaluation at a private clinic, an Oxygen saturation gap was noted between the results of the pulse oximeter and arterial blood gas analyzer. This raised suspicion on the presence of MetHb. He was referred to Armed Forces Institute of Pathology, Rawalpindi for further workup.The sample obtained for MetHb was chocolate brown in colour. Analysis was done via co-oximetry. A high level of MetHb (45.6%) was obtained. All other radiological and haematological investigations were in the normal range. On the basis of history, clinical presentation, and investigations, he was diagnosed as a case of congenital methaemoglobinaemia with secondary polycythemia.

Association of Trace Metals in Patients with Schizophrenia.

OBJECTIVE: To compare the serum concentrations of copper, iron and zinc in schizophrenic patients with healthy individuals. STUDY DESIGN: Cross-sectional comparison study. PLACE AND DURATION OF STUDY: Department of Chemical Pathology and Endocrinology, Armed Forces Institute of Pathology (AFIP), Rawalpindi, Pakistan. The study was conducted from July to December 2020. METHODOLOGY: Among 115 participants in the study, schizophrenic patients and healthy subjects were 35 and 80, respectively. Copper and zinc were measured by using atomic absorption spectrophotometry. Serum Iron measurement was done on ADVIA 1800 chemistry auto analyser. Comparison of these trace metals among patients with schizophrenia and healthy subjects, by using Mann-Whitney U-test and correlation with the duration of disease, was analysed by the application of Spearman's correlation. RESULTS: Males accounted for 25 (71.4%) and females were 10 (28.6%) in diseased group; while in healthy subjects, males accounted for 54 (67.5%) and females 26 (32.5%). Copper, iron and zinc levels were noted to be significantly reduced in schizophrenic patients, when compared with healthy subjects (p <0.001). CONCLUSION: This study could offer an additional clue in the diagnosis and possible role of trace metals in pathophysiology and progression of many psychiatric illnesses, particularly schizophrenia. Key Words: Psychiatric illness, Schizophrenia, Trace metals.

Establishing biotinidase reference interval: A foundation stone for newborn screening of biotinidase deficiency in Pakistan.

OBJECTIVE: To determine the reference interval of biotinidase activity in healthy neonates. METHODS: The cross-sectional study was conducted at the Department of Chemical Pathology and Endocrinology, Armed Forces Institute of Pathology, Rawalpindi, Pakistan, from May to November 2019, and comprised blood samples collected from healthy neonates aged 2-6 days. The samples were collected on filter paper and analysed on genetic screening processor based on dissociation-enhanced lanthanide flouroimmunoassay. Data was analysed using SPSS 21. RESULTS: Of the 120 dried blood spot specimens, 81(67.5%) were from male babies and 39(32.5%) from female babies. Reference interval for biotinidase activity, based on 2.5th and 97.5th percentiles, was from 3.0 to 11.0 nmol/ml/min. CONCLUSIONS: Screening of newborns for biotinidase deficiency is crucial to prevent irreversible neurological damage.

Procalcitonin as a biomarker of bacterial infection in critically ill patients admitted with suspected Sepsis in Intensive Care Unit of a tertiary care hospital.

OBJECTIVE: To compare the diagnostic accuracy of procalcitonin (PCT), C- reactive protein (CRP), total leukocyte count (TLC) and lactate in critically ill patients admitted with suspicion of sepsis. METHODS: It was a cross sectional study conducted at the department of Chemical Pathology and Endocrinology AFIP, Rawalpindi, in collaboration with Medical and surgical intensive care units (ICU) of CMH Rawalpindi from January 2019 to December 2019. A total of 126 patients of both genders with age above 18 years and fulfilling the inclusion criteria of systemic inflammatory response syndrome (SIRS) were inducted in the study. RESULTS: Out of 126 patients 82 (65%) patients have positive blood culture results. Male predominance was noted in patients with positive blood culture. Out of 82 patients with positive blood culture results 69(84%) patients have positive PCT results as well whereas 13(15%) patients with positive blood culture results have negative PCT values. 57(69%) patients had Gram negative bacterial infection and 25(30%) patients had Gram positive bacterial infection. Significant difference was noted between the medians of PCT in blood culture positive and blood culture negative group (p value< 0.05) whereas no significant difference was found between medians of CRP, TLC and lactate between blood culture positive and blood culture negative patients (p value > 0.05). ROC curve analysis of PCT, CRP and TLC were done, keeping blood culture as reference standard, PCT showed largest area under the curve (AUC) and clearly outperformed TLC and CRP. PCT showed AUC of 0.781 as compared to CRP and TLC, which was 0.568 and 0.617 respectively. PCT showed sensitivity of 93.9%, specificity of 47.7%, positive predictive value (PPV) of 77% and negative predictive value (NPV) of 80.8%. CONCLUSION: Higher NPV makes it a reliable marker for screening out sepsis in suspected cases.

Effect of Temperature and Preservative on Neo-ethanol Formation in Postmortem Whole Blood Samples.

OBJECTIVE: To determine the association of temperature, time duration, and preservatives with ethanol neo-genesis in postmortem whole blood samples. STUDY DESIGN: Observational cross-sectional study. PLACE AND DURATION OF STUDY: Department of Chemical Pathology and Toxicology, Armed Forces Institute of Pathology, Rawalpindi, in collaboration with Combined Military Hospital, Rawalpindi from August 2020 to January 2021. METHODOLOGY: Whole blood samples were obtained from cardiac chamber of an autopsy case with aseptic measures and were drawn into six tubes (3 x EDTA tubes and 3 x NaF tubes). These six tubes were stored at 4˚C, 25˚C, and 37˚C. All samples were analysed along with internal standard, on head space gas-chromatography on Day-0, Day-07, Day-14, Day-21, and Day-28 of sampling. RESULTS: A total of 60 samples out of 10 autopsies, were analysed. Blood alcohol concentrations of all samples were negative on 1st day (Day-0) of analysis. Samples stored at 4˚C did not produce any ethanol at any day of analysis, regardless of preservatives used. Neo-ethanol levels of blood samples stored in EDTA preservative were significantly raised (p <0.001) as compared to samples stored in NaF preservative. Samples stored at 37˚C showed significant increase in neo-ethanol concentration (p <0.001) in comparison with samples stored at 4˚C and 25˚C. Neo-ethanol levels increased with duration of storage till 14th day of analysis. CONCLUSION: Sodium fluoride (NaF) should be used as preservative to avoid ethanol neo-genesis during storage and transportation of blood samples for alcohol analysis. Cold chain maintenance is of pivotal importance to exclude false positive blood alcohol results. Key Words: Neo-ethanol, Neo-genesis, Ethylenediaminetetra acetic acid (EDTA), Sodium fluoride (NaF).

Diagnostic Accuracy of Markers of Insulin Resistance (HOMA-IR) and Insulin Sensitivity (QUICKI) in Gestational Diabetes.

OBJECTIVES: To determine the diagnostic accuracy of HOMA-IR, and QUICKI in diagnosing gestational diabetes mellitus (GDM) considering oral glucose tolerance test (OGTT) as gold standard. STUDY DESIGN: Cross-sectional analytical study. PLACE AND DURATION OF STUDY: Department of Chemical Pathology, Armed Forces Institute of Pathology, Rawalpindi from September 2020 to February 2021. METHODOLOGY: Pregnant women with gestational age between 24 to 28 weeks, who reported to Endocrine Clinic of AFIP for OGTT, were included in the study. OGTT was performed by following ADA guidelines. Sample for fasting insulin was collected along with first fasting sample of OGTT. HOMA-IR and QUICKI were calculated simultaneously. Percentage was used for qualitative variable while median (IQR 25th-75th) was applied for quantitative variables. OGTT was used as gold standard for calculation of diagnostic accuracy of HOMA-IR and QUICKI. RESULTS: Out of 182 patients, 74 (40.6%) were found to have GDM on OGTT while 108 (59.4%) had normal OGTT. Women with GDM (n=74) had median values of fasting insulin 15.9 (IQR 11.2-17.77), HOMA-IR 3.5 (IQR 2.6-4.1) and QUICKI 0.31 (IQR 0.30-0.33) as compared to median values of fasting insulin 8.0 (IQR 5.9-10.3), HOMA-IR 1.60 (IQR 1.12-2.03) and QUICKI 0.35 (IQR 0.34-0.37) in patients (n=108) with normal response to OGTT, (p <0.001). On logistic regression analysis, there was a strong association of HOMA-IR and QUICKI with gestational diabetes mellitus (p <0.001, accuracy 84.6%). HOMA-IR at cutoff of ≤2 had 94.5% sensitivity, 72.2% specificity, 70% PPV, 95.1% NPV, and 81.31% overall diagnostic accuracy with 0.913 AUC. QUICKI at cutoff of 0.34 had 86.4% sensitivity, 83.3% specificity, 78.0% PPV, 90.0% NPV, and 84.61% overall diagnostic accuracy with 0.905 AUC. CONCLUSION: Fasting insulin and HOMA-IR were significantly higher while QUICKI was lower in patients of GDM as compared to non-GDM pregnant patients at 24 to 28 weeks of gestation. Being more convenient for patients, it has the potential to be used as screening tool for gestational diabetes. Key Words: HOMA IR, QUICKI, Gestational diabetes mellitus, Insulin.

Multiple Carboxylase Deficiency Organic Acidemia as a Cause of Infantile Seizures.

Multiple carboxylase deficiency organic Acidemia is a rare inherited metabolic disorder. It is autosomal recessive disorder of two types: Holocarboxylase deficiency and Biotinidase deficiency. It is the metabolic disorder resulting from deficiency of biotin as a co-enzyme or reduced activity of biotin-dependent carboxylases (propionyl CoA carboxylase, and 3-methylcrotonyl CoA carboxylase and pyruvate carboxylase). A case of two months' female child is reported, who presented with recurrent infantile seizures and skin rash since birth; and biochemically with metabolic acidosis, hyper-ammonemia (on and off) since birth with multiple hospitalization. She had past history of jaundice. One sibling's death at 2nd day of life due to similar complaints. Initial presentation of raised ammonia and lactate levels were the first indication to this organic academia, which was later proven by increased peak levels of various organic acids on urine organic acid analysis by gas chromatography-mass spectrometry. Key Words: Multiple carboxylase deficiency, Holocarboxylase synthetase deficiency, Biotinidase deficiency.