Clinical Laboratory Research Articles

Internal quality control in a clinical biochemistry laboratory: Management of non-conformities on the general chemistry automate DXC800

Internal quality control in a clinical biochemistry laboratory: Management of non-conformities on the general chemistry automate DXC800

The Value of Nailfold Capillaroscopy in the Classification and Differential Diagnosis of Raynaud's Phenomenon in Rheumatology.

Among instrumental techniques, nailfold capillaroscopy plays a leading role in the assessment of Raynaud's phenomenon (RP) patients because it is the only method that provides opportunities for morphological assessment of capillaroscopic findings in the nailfold area, with proven diagnostic and prognostic significance in rheumatology. The discussion about updating the classification of RP in rheumatology is interesting given the current understanding of capillaroscopic findings in rheumatic diseases and improvements in immunological diagnostics. The presence of dilation of the "true" capillary diameters in primary RP could be observed. There are some cases of primary RP where the capillaroscopic pattern is completely normal and there are no dilated capillaries present, which could be related to the duration and severity of the symptoms. It is possible that longer duration and greater severity are associated with the appearance of capillary dilations, but more research is needed to confirm it. Rarely, pathological capillaroscpic features of microangiopathy could be observed in RP patients in whom clinical, laboratory and immunological findings are compatible with the diagnosis "primary RP". These cases should be defined as "suspected secondary RP" and require closer follow-up for the assessment of symptom evolution. Abnormal "scleroderma" type capillaroscopic pattern has been established as a new classification criterion for systemic sclerosis (SSc) in 2013. Similar changes ("scleroderma-like" pattern) could be observed in other rheumatic diseases, i.e., undifferentiated connective tissue disease (UCTD), systemic lupus erythematosus, dermatomyositis, rheumatoid arthritis, including without evidence of overlap with scleroderma. The appearance of such microvascular abnormalities at disease presentation is less well studied in diseases different from SSc. However, "scleroderma-like" microangiopathy has also been reported as an initial sign in some systemic rheumatic diseases, such as UCTD and systemic lupus erythematosus. Thus, interpretation of capillaroscopic findings is performed in overall context, including clinical findings and laboratory and immunological test results.

Intraprostatic Injection of Tranexamic Acid Decrease Blood Loss During Monopolar Transurethral Resection of the Prostate: A Randomized Controlled Clinical Trial

ObjectiveTo assess the role of intraprostatic injection of tranexamic acid (TXA) in reducing blood loss during transurethral resection of the prostate (TURP). MethodsWe conducted a randomized, controlled, double-blind trial involving 60 patients with benign prostatic hyperplasia (BPH) aged 50–85 years, undergoing monopolar TURP. Patients' prostatic weights ranged from 50 to 80 grams. They were divided equally into two groups: Group I received an intraprostatic injection of 1 gram of TXA (Cyklokapron) dissolved in 50 ml of 0.9% saline at multiple sites, while Group II (control) received a 60 ml saline injection. Comprehensive clinical assessments and standard laboratory tests, including screenings for TXA hypersensitivity, were performed for all patients. ResultsGroup I exhibited significantly lower intraoperative blood loss and hemoglobin concentration in irrigation fluid immediately post-surgery and at the 6-hour postoperative mark compared to Group II (P < 0.05). Coagulation parameters—activated partial thromboplastin time (APTT), prothrombin time (PT), fibrinogen level (FB), and thrombin clotting time (TT)—showed no significant differences between the groups preoperatively or at 6 and 24 hours postoperatively. No thromboembolic events or other complications were reported in either group. ConclusionThe intraprostatic injection of TXA during monopolar TURP is safe, with minimal adverse effects, and effectively reduces blood loss.

Liver Involvement is Associated with Higher Risk of Rapidly Progressive Interstitial Lung Disease and Mortality in Anti-Melanoma Differentiation-Associated Gene 5 Antibody- Positive Dermatomyositis.

This study aimed to assess liver involvement and investigate its correlation with rapidly progressive interstitial lung disease (RP-ILD) and mortality in anti-melanoma differentiation-associated gene 5 antibody-positive (anti-MDA5 positive) DM patients. This retrospective study included 159 patients diagnosed with anti-MDA5 positive DM or anti-synthetase syndrome (ASyS). Clinical features and laboratory findings were compared between patients with anti-MDA5 positive DM and patients with ASyS. In the anti-MDA5 positive DM cohort, clinical features and laboratory findings between patients with liver involvement and without liver involvement were further compared. The effects of liver involvement on the overall survival (OS) and development of RP-ILD were also analyzed using Kaplan-Meier method and Cox regression analysis. Levels of serum aspartate aminotransferase (AST), alanine transaminase (ALT), γ-glutamyl transferase (γGT) and alkaline phosphatase (ALP) were all significantly higher in patients with anti-MDA5 positive DM than those in patients with ASyS. In our cohort of anti-MDA5 positive DM patents, 31 patients (34.4%) were complicated with liver involvement. Survival analysis revealed that serum ferritin >1030.0 ng/mL (p<0.001), ALT >103.0 U/l (p<0.001), AST >49.0 U/l (p<0.001), γGT >82.0 U/l (p<0.001), ALP >133.0 U/l (p<0.001), lactate dehydrogenase (LDH)>474.0 U/l (p<0.001), plasma albumin (ALB) <35.7 g/l (p<0.001) and direct bilirubin (DBIL) >2.80 μmol/l (p=0.002) predicted poor prognosis. The incidence of RP-ILD increased remarkably in patients with liver involvement compared to patients without liver involvement (58.1% vs 22.0%, p=0.001). Multivariate analysis revealed that elevated serum ALT level was an independent risk factor for mortality (HR 6.0, 95% CI 2.3, 16.2, p<0.001) and RP-ILD (HR 5.9, 95% CI 2.2, 15.9, p<0.001) in anti-MDA5 positive DM patents. Liver involvement is common in patients with anti-MDA5 positive DM. Elevated serum ALT level was an independent risk factor for RP-ILD and mortality in patients with anti-MDA5 positive DM.

AKIMLpred: An interpretable machine learning model for predicting acute kidney injury within seven days in critically ill patients based on a prospective cohort study

BackgroundEarly recognition and timely intervention for AKI in critically ill patients were crucial to reduce morbidity and mortality. This study aimed to use biomarkers to construct a optimal machine learning model for early prediction of AKI in critically ill patients within seven days. MethodsThe prospective cohort study enrolled 929 patients altogether who were admitted in ICU including 680 patients in training set (Jiefang Campus) and 249 patients in external testing set (Binjiang Campus). After performing strict inclusion and exclusion criteria, 421 patients were selected in training set for constructing predictive model and 167 patients were selected in external testing for evaluating the predictive performance of resulting model. Urine and blood samples were collected for kidney injury associated biomarkers detection. Baseline clinical information and laboratory data of the study participants were collected. We determined the average prediction efficiency of six machine learning models through 10-fold cross validation. ResultsIn total, 78 variables were collected when admission in ICU and 43 variables were statistically significant between AKI and non-AKI cohort. Then, 35 variables were selected as independent features for AKI by univariate logistic regression. Spearman correlation analysis was used to remove two highly correlated variables. Three ranking methods were used to explore the influence of 33 variables for further determining the best combination of variables. The gini importance ranking method was found to be applicable for variables filtering. The predictive performance of AKIMLpred which constructed by the XGBoost algorithm was the best among six machine learning models. When the AKIMLpred included the nine features (NGAL, IGFBP7, sCysC, CAF22, KIM-1, NT-proBNP, IL-6, IL-18 and L-FABP) with the highest influence ranking, its model had the best prediction performance, with an AUC of 0.881 and an accuracy of 0.815 in training set, similarly, with an AUC of 0.889 and an accuracy of 0.846 in validation set. Moreover, the performace was slightly outperformed in testing set with an AUC of 0.902 and an accuracy of 0.846. The SHAP algorithm was used to interpret the prediction results of AKIMLpred. The web-calculator of AKIMLpred was shown for predicting AKI with more convenient(https://www.xsmartanalysis.com/model/list/predict/model/html?mid=8065&symbol=11gk693982SU6AE1ms21). AKIMLpred was better than the optimal model built with only routine tests for predicting AKI in critically ill patients within 7 days. ConclusionThe model AKIMLpred constructed by the XGBoost algorithm with selecting the nine most influential biomarkers in the gini importance ranking method had the best performance in predicting AKI in critically ill patients within 7 days. This data-driven predictive model will help clinicians to make quick and accurate diagnosis.

HaNDL Syndrome: The Innocent Lymphocytic Pleocytosis.

HaNDL syndrome is a transient and rare condition that presents with neurological deficit and headache accompanied by lymphocytosis on cerebrospinal fluid (CSF) analysis. It is usually characterized by spontaneous recovery without neurological sequelae. This is a benign condition, which has not yet been adequately defined and includes many diseases in the differential diagnosis. We indicated 2 different cases that applied with acute neurological findings. Two patients who were admitted to our hospital with transient neurological deficits and headaches were evaluated. There was no significant pathology in cranial imaging and EEG reports. Lymphocytic pleocytosis was observed in CSF. Patients were followed up with attacks but were discharged without deficits. We diagnosed the patients with HaNDL syndrome with clinical features, imaging, and laboratory findings. HaNDL is an underdiagnosed syndrome and it should be considered especially for young patients with headaches is prominent without a risk factor for ischemia, recurrent episodes with neurological symptoms, CSF pleocytosis, and normal imaging findings.Therefore, we wanted to raise awareness for the existence of this rare disease which is a waste of time by performing unnecessary tests and therapies during the diagnosis period.

Prognostic Value of Inflammatory Cytokines in Predicting Hospital Readmissions in Heart Failure with Preserved Ejection Fraction.

The aim of this study was to explore the relationship between inflammatory cytokines and the risk of heart failure (HF) readmission in patients with heart failure with preserved ejection fraction (HFpEF). We enrolled 429 patients with HFpEF admitted to the cardiology department in our hospital from January 2020 to July 2022. The patients were divided into the readmission or non-readmission groups according to whether they were readmitted for heart failure within 1 year of discharge. The clinical features and laboratory date of the subjects were collected and analyzed. Multivariate cox regression analysis was used to identify predictors of HF readmission. In addition, receiver operating characteristic (ROC) curves were used to determine the prognostic value of each factor. The levels of IL-1β, IL-6, IL-10, IL-17, TNF-α, NT-proBNP, heart rate, total cholesterol and NYHA class were significantly higher in the readmission group than in the non-readmission group (p < 0.05). IL-1β, IL-6, IL-17, TNF-α, NT-proBNP, heart rate and NYHA class were identified as independent predictors of HF readmission. Inflammatory markers, including IL-1β, IL-6, IL-17 and TNF-α were related to the HF readmission in patients with HFpEF.

Relationship between Triglyceride-Glucose Index and Disease Activity and Subclinical Atherosclerosis in Rheumatoid Arthritis.

In rheumatoid arthritis (RA), insulin resistance (IR) is related to inflammatory markers, disease activity, and progression of atherosclerotic changes. Triglyceride-glucose (TyG) index is a relatively new indicator of IR. The present study aimed to investigate the relationship between TyG index, disease activity and subclinical atherosclerosis (SCA) in RA patients. The present case-control study included 100 RA patients and 50 age- and sex-matched healthy controls. All participants were subjected to careful history taking through clinical examination and standard laboratory assessment. The TyG index was calculated as TyG index = ln (Fasting triglyceride (mg/dL) × fasting glucose (mg/dL))/2. Carotid intima-media thickness (CIMT) measurement was done using B-mode ultrasound. Patients had significantly higher TyG index as compared to controls. Patients with high disease activity had significantly higher frequency of extraarticular manifestations (39.6% versus 51.6%, p = 0.028), higher Larsen score (3.8 ± 1.3 versus 2.8 ± 1.2, p < 0.001), higher anti-cyclic citrullinated peptide (anti-CCP) levels (median (IQR): 243.1 (205.0-408.0) U/ml versus 99.0 (78.0-332.5), p < 0.001), higher TyG index (4.8 ± 0.22 versus 4.67 ± 0.24, p = 0.006), and higher CIMT (0.87 ± 0.22 versus 0.77 ± 0.17 mm, p = 0.018). Patients with SCA had higher BMI (34.6 ± 6.2 versus 30.5 ± 5.3 Kg/m2, p < 0.001), higher Larsen score (3.7 ± 1.4 versus 3.1 ± 1.3, p = 0.028) and higher TyG index (4.89 ± 0.23 versus 4.64 ± 0.19, p < 0.001). Binary logistic regression analysis identified patients' age (OR (95% CI): 0.94 (0.89-0.99), p = 0.018), Larsen score (OR (95% CI): 1.93 (1.32-2.82), p = <0.001), anti-CCP (OR (95%): 1.04 (1.02-1.07), p = 0.032), and TyG index (OR (95% CI): 22.67 (2.14-240.4), p = 0.01) as significant predictors of high disease activity in multivariate analysis. IR estimated by the TyG index is related to disease activity and SCA in RA patients.

Implementation of a quality risk management approch in a clinical mycobacteriology laboratory

Implementation of a quality risk management approch in a clinical mycobacteriology laboratory

Development and validation of a nomogram for pneumonia risk in burn patients with inhalation injury: a multicenter retrospective cohort study.

Burn patients with inhalation injury are at higher risk of developing pneumonia, and yet there is no reliable tool for the assessment of the risk for such patients at admission. This study aims to establish a predictive model for pneumonia risk for burn patients with inhalation injury based on clinical findings and laboratory tests. This retrospective study enrolled 546 burn patients with inhalation injury. They were grouped into a training cohort and a validation cohort. The least absolute shrinkage and selection operator (LASSO) regression analysis and binary logistic regression analysis were utilized to identify risk factors for pneumonia. Based on the factors, a nomogram for predicting pneumonia in burn patients with inhalation injury was constructed. Areas under the receiver operating characteristic curves (AUC), calibration plots, and decision curve analysis (DCA) were used to evaluate the efficiency of the nomogram in both the training and validation cohorts. The training cohort included 432 patients, and the validation cohort included 114 patients, with a total of 225 (41.2%) patients experiencing pneumonia. Inhalation injury, tracheal intubation/tracheostomy, low serum albumin, and high blood glucose were independent risk factors for pneumonia in burn patients with inhalation injury and they were further used to build the nomogram. The AUC of the nomogram in the training and validation cohorts were 0.938 (95% CI: 0.917-0.960) and 0.966 (95% CI: 0.931-1), respectively. The calibration curve for probability of pneumonia showed optimal agreement between the prediction by nomogram and the actual observation, and the DCA indicated that the constructed nomogram conferred high clinical net benefit. This nomogram can accurately predict the risk of developing pneumonia for burn patients with inhalation injury, and help professionals to identify high-risk patients at an early stage as well as to make informed clinical decisions.

Inferring fungal growth rates from optical density data.

Quantifying fungal growth underpins our ability to effectively treat severe fungal infections. Current methods quantify fungal growth rates from time-course morphology-specific data, such as hyphal length data. However, automated large-scale collection of such data lies beyond the scope of most clinical microbiology laboratories. In this paper, we propose a mathematical model of fungal growth to estimate morphology-specific growth rates from easy-to-collect, but indirect, optical density (OD600) data of Aspergillus fumigatus growth (filamentous fungus). Our method accounts for OD600 being an indirect measure by explicitly including the relationship between the indirect OD600 measurements and the calibrating true fungal growth in the model. Therefore, the method does not require de novo generation of calibration data. Our model outperformed reference models at fitting to and predicting OD600 growth curves and overcame observed discrepancies between morphology-specific rates inferred from OD600 versus directly measured data in reference models that did not include calibration.

Application of the six sigma approach in the clinical biochemistry laboratory

Application of the six sigma approach in the clinical biochemistry laboratory

Fluid overload in critically ill children: A narrative review

Fluid overload (FO) is a common and challenging complication encountered among critically ill children admitted to pediatric intensive care unit (PICU), posing significant risks for morbidity and mortality. The pathophysiology of FO involves disruptions in fluid balance, exacerbated by underlying medical conditions, critical illness, and therapeutic interventions. Assessment of fluid status relies on a combination of clinical evaluation, laboratory tests, and imaging studies, with a focus on early detection and intervention to prevent complications. Management strategies for FO in the PICU encompass both preventive and therapeutic approaches. Prevention involves judicious fluid resuscitation, dynamic fluid assessment, advanced hemodynamic monitoring, careful monitoring of fluid input and output, early recognition of at-risk patients, and individualized approach. Therapeutic interventions may include diuretic therapy, optimization of hemodynamic support, and renal replacement therapy tailored to individual patient needs. Challenges in managing FO in PICU include balancing the need for adequate tissue perfusion with the risk of exacerbating FO and preventing complications such as electrolyte disturbances and organ dysfunction. Multidisciplinary collaboration, evidence-based practices, and continuous monitoring are essential for successful fluid management in critically ill children. This review aims to provide a comprehensive overview of the current understanding and management strategies for FO among critically ill children.

Internal quality control in a clinical biochemistry laboratory: Management of non-conformities on the general chemistry automate DxC800

Internal quality control in a clinical biochemistry laboratory: Management of non-conformities on the general chemistry automate DxC800

Pediatric cardiomyopathy illustrates the importance of reinterpreting the significance of genetic variants

BackgroundClinical genetic testing is increasingly being utilized to establish a molecular diagnosis to help manage children with cardiomyopathy and to assess the risk of cardiomyopathy among family members. However, as evidence and guidelines evolve, variant classification can change with the potential to impact counseling and family screening. ObjectivesThe main purpose of this study was to investigate whether variants in cardiomyopathy genes previously interpreted by clinical genetic testing laboratories would be reclassified under current guidelines for the interpretation of sequence variants. MethodsIn 211 children enrolled in the Pediatric Cardiomyopathy Registry, we compared the results of previous clinical genetic testing with the results of research testing in 37 cardiomyopathy genes. ResultsThe mean time difference between initial testing and reinterpretation was 7 years. Using the 2015 American College of Medical Genetics and Genomics guidelines for the interpretation of sequence variants, we found that 18 % of the tested population had a change in variant classification. Ninety-two percent of the initial classifications were performed before the publication of the guidelines, with 82 % of reclassifications resulting in a variant downgrade. Most of these were changes from the pathogenic or likely pathogenic category to a variant of uncertain significance. Reclassification frequency was similar across types of cardiomyopathy. ConclusionOur results highlight that a portion of variants get downgraded, and periodic reinterpretation of genetic testing results is necessary for all types of cardiomyopathy—particularly for variant interpretations prior to 2015. Importantly, variant reclassification has potential impact on the clinical management of at-risk patients.

Changes in blood biochemical parameters in highly productive cows with ketosis.

Biochemical blood testing is the main diagnostic indicator of the clinical condition of highly productive animals and a method of determining changes in metabolic disorders. This study focuses on metabolic changes (ketosis), which are of the utmost importance in the assessment of the health status of animals, as well as differences in intergroup characteristics. The main focus of this study is to demonstrate the influence of subclinical ketosis in highly productive cows on changes in biochemical blood parameters during different physiological periods to further prevent this disease, adjust feeding rations, and prevent premature culling of animals. This study aimed to evaluate and establish changes in the biochemical status dynamics of highly productive cows with metabolic disorders in an industrial livestock complex. Blood samples were systematically collected from highly productive cows of the Simmental breed (n = 60) and served as the primary material for subsequent analyses. Each methodological step was designed to ensure evaluation of the metabolic changes associated with post-calving adjustments in highly productive dairy cows. This study employed a comprehensive approach integrating clinical assessments, laboratory analyses, biochemical evaluations, instrumental measurements, and statistical analyses. A biochemical blood test showed that the number of ketone bodies in the experimental group exceeded the norm, varied depending on the physiological state of the animals, and ranged from 0.89 to 1.45 mmol/L. At 10 days after calving, the highest indicator was 1.45 ± 0.05 mmol/L. This indicator was 1.05 mmol/L higher than that in the control group and exceeded the norm by 0.95. Excess ketone bodies in the blood of animals led to accumulation in urine and milk, indicating a disturbance in metabolic processes in the body and a decrease in the quality of animal husbandry products. The sample size and the focus on a single breed from one geographical location may limit the generalizability of the findings. Further research should explore the mechanistic bases of ketosis development, potentially integrating genomic and proteomic approaches to understand the genetic predispositions and molecular pathways involved.

Clinical presentation and outcome of enteric fever in adult patients with cancer: a perspective from Pakistan.

Introduction. Enteric fever is a significant health concern in endemic countries. While extensive research has been conducted to understand its presentation and outcomes in non-cancer patients, limited data exist on its impact on cancer patients. This descriptive study aims to investigate the clinical presentation and outcome in cancer patients. Methodology. This retrospective observational study analysed 90 adult cancer patients from a single centre in Pakistan from January 2017 to December 2022. Inclusion criteria involved documented blood culture infections with Salmonella typhi or paratyphi A, B, or C. We examined clinical presentation, laboratory parameters, antimicrobial resistance, complications, and outcomes. Additionally, we explored the effects of chemotherapy, comorbidities, type of malignancy, and patient age on complications and mortality. Results. Salmonella typhi was the most prevalent organism (72.2 %), followed by Salmonella paratyphi A (22.2 %) and B (5.5 %). Variably-resistant isolates constituted 51.5 %, multi-drug resistant (MDR) isolates accounted for 20 %, extensively drug-resistant (XDR) for 14.4 % and ESBL-producers for 15.5 %, of all enteric fever infections. Enteric fever-associated complications were observed in 21.1 % of cases. Chemotherapy in the preceding month did not affect mortality, nor did age, gender, or malignancy type. However, comorbidities were statistically significant for mortality (p-value 0.03). A total of 8.8 % of patients required ICU care, and the all-cause 30 day mortality rate was 13.3 % Conclusion. Enteric fever remains prevalent in our geographical region. Unlike non-typhoidal Salmonella (NTS), enteric fever does not behave differently in an immunocompromised population, including cancer patients.

Clinical variables influencing the severity of diabetes ketoacidosis.

To evaluate clinical indicators in order to examine the intensity of diabetes ketoacidosis (DKA) episodes in children and adolescents diagnosed with type 1 diabetes mellitus (T1DM). Data from 156 T1DM patients aged 6 months to 14 years, who presented with DKA to the emergency room, were retrospectively reviewed from 2018 to 2022. Data on demographic characteristics, economic status, initial clinical presentation, glycemic control, DKA severity, and laboratory evaluations were also collected. Diabetes ketoacidosis episodes were more prevalent among male patients during the middle childhood age group. Notably, these episodes displayed seasonal patterns. The severity was found to be inversely associated with economic status and positively correlated with early adolescence. Newly diagnosed T1DM patients constituted 52.9%, with a statistically significant connection observed between severe DKA and this subgroup. Furthermore, there was a significant escalation in poor glycemic control with episode severity. Prolonged episode duration also exhibited a statistically significant association with more severity. Gastrointestinal symptoms were commonly reported during the presentation. Moreover, several clinical signs and symptoms, including decreased consciousness, reduced activity, drowsiness, Kussmaul breathing, shortness of breath, vomiting, tachycardia, and severe dehydration, were significantly correlated with the severity of DKA (p<0.05). Hypernatremia was more frequent among children with severe DKA. Diabetes ketoacidosis was observed to occur more frequently among males in middle childhood with seasonal variations. Furthermore, the severity of DKA was associated with lower economic status, early adolescence, and the presence of hypernatremia.

Detection accuracy and clinical applications of DP-TOF mass spectrometry.

Matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) is currently used in clinical microbiology laboratories. This study aimed to determine whether dual-polarity time-of-flight mass spectrometry (DP-TOF MS) could be applied to clinical nucleotide detection. This prospective study included 40 healthy individuals and 110 patients diagnosed with cardiovascular diseases. We used DP-TOF MS and Sanger sequencing to evaluate 17 loci across 11 genes associated with cardiovascular drug responses. In addition, we used DP-TOF MS to test 998 retrospectively collected clinical DNA samples with known results. A, T, and G nucleotide detection by DP-TOF MS and Sanger sequencing revealed 100% concordance, whereas the C nucleotide concordance was 99.86%. Genotyping based on the results of the two methods showed 99.96% concordance. Regarding clinical applications, DP-TOF MS yielded a 99.91% concordance rate for known loci. The minimum detection limit for DNA was 0.4 ng; the inter-assay and intra-assay precision rates were both 100%. Anti-interference analysis showed that aerosol contamination greater than 1013 copies/µL in the laboratory environment could influence the results of DP-TOF MS. The DP-TOF MS platform displayed good detection performance, as demonstrated by its 99.96% concordance rate with Sanger sequencing. Thus, it may be applied to clinical nucleotide detection.

Application of DMAIC methodology to reduce pre-analytical errors in a tertiary hospital clinical chemistry laboratory in India

Application of DMAIC methodology to reduce pre-analytical errors in a tertiary hospital clinical chemistry laboratory in India