Routine Chemistry Research Articles

Artificial Intelligence–Assisted Electrocardiography for Early Diagnosis of Thyrotoxic Periodic Paralysis

ContextThyrotoxic periodic paralysis (TPP) characterized by acute weakness, hypokalemia, and hyperthyroidism is a medical emergency with a great challenge in early diagnosis since most TPP patients do not have overt symptoms.ObjectiveThis work aims to assess artificial intelligence (AI)-assisted electrocardiography (ECG) combined with routine laboratory data in the early diagnosis of TPP.MethodsA deep learning model (DLM) based on ECG12Net, an 82-layer convolutional neural network, was constructed to detect hypokalemia and hyperthyroidism. The development cohort consisted of 39 ECGs from patients with TPP and 502 ECGs of hypokalemic controls; the validation cohort consisted of 11 ECGs of TPP patients and 36 ECGs of non-TPP individuals with weakness. The AI-ECG–based TPP diagnostic process was then consecutively evaluated in 22 male patients with TTP-like features.ResultsIn the validation cohort, the DLM-based ECG system detected all cases of hypokalemia in TPP patients with a mean absolute error of 0.26 mEq/L and diagnosed TPP with an area under curve (AUC) of approximately 80%, surpassing the best standard ECG parameter (AUC = 0.7285 for the QR interval). Combining the AI predictions with the estimated glomerular filtration rate and serum chloride boosted the diagnostic accuracy of the algorithm to AUC 0.986. In the prospective study, the integrated AI and routine laboratory diagnostic system had a PPV of 100% and F-measure of 87.5%.ConclusionAn AI-ECG system reliably identifies hypokalemia in patients with paralysis, and integration with routine blood chemistries provides valuable decision support for the early diagnosis of TPP.

Correlation among Hemolysis Biomarkers in Pediatric Patients Undergoing Extracorporeal Membrane Oxygenation

Hemolysis is a common complication associated with mortality on extracorporeal membrane oxygenation (ECMO). Plasma-free hemoglobin (PFH) is the most commonly used biomarker reported for hemolysis on ECMO. This test is not readily available at all institutions, and other more readily available tests may indicate hemolysis nearly as well or as well as PFH. The purpose of this study was to study the correlation of other biomarkers of hemolysis to PFH on ECMO. All patients younger than 21 years placed on ECMO in a quaternary children's hospital between January 2013 and December 2016 were included in the study; biomarkers (urine hemoglobin [U-Hb], PFH, lactate dehydrogenase [LDH], aspartate aminotransferase [AST], gross hemolysis, and red cell distribution width (RDW)) were collected from the medical record. Descriptive statistics and repeated bivariate analyses were determined using SPSS 22.0. The median age on day 0 of ECMO was 29 days (.08 years) (IQR: 2; 319 days (.005; .875 years)). The median weight was 3.9 kg (IQR: 2.8; 8.6), and the median total duration of the ECMO run was 10.48 days (IQR: 4.25; 14), with 82% of all the patients being on venoarterial ECMO. There was no correlation between hematuria on urinalysis and the level of PFH (p= .338). There was a statistically significant positive correlation between PFH and the following respective biomarkers: gross hemolysis on the routine chemistry studies (p< .01, Rho = .439), AST (p< .01, Rho = .439), RDW (p< .01, Rho = .190), LDH (p< .01, Rho = .584), and AST (when associated elevated alanine transaminase (ALT) levels were censored) (p< .01, Rho = .552). U-Hb correlated poorly with PFH. The serum biomarkers AST (in the absence of ALT elevation) and LDH can be useful surrogates for PFH to quantify hemolysis on ECMO in pediatric patients.

Correlation among Hemolysis Biomarkers in Pediatric Patients Undergoing Extracorporeal Membrane Oxygenation.

Hemolysis is a common complication associated with mortality on extracorporeal membrane oxygenation (ECMO). Plasma-free hemoglobin (PFH) is the most commonly used biomarker reported for hemolysis on ECMO. This test is not readily available at all institutions, and other more readily available tests may indicate hemolysis nearly as well or as well as PFH. The purpose of this study was to study the correlation of other biomarkers of hemolysis to PFH on ECMO. All patients younger than 21 years placed on ECMO in a quaternary children's hospital between January 2013 and December 2016 were included in the study; biomarkers (urine hemoglobin [U-Hb], PFH, lactate dehydrogenase [LDH], aspartate aminotransferase [AST], gross hemolysis, and red cell distribution width (RDW)) were collected from the medical record. Descriptive statistics and repeated bivariate analyses were determined using SPSS 22.0. The median age on day 0 of ECMO was 29 days (.08 years) (IQR: 2; 319 days (.005; .875 years)). The median weight was 3.9 kg (IQR: 2.8; 8.6), and the median total duration of the ECMO run was 10.48 days (IQR: 4.25; 14), with 82% of all the patients being on venoarterial ECMO. There was no correlation between hematuria on urinalysis and the level of PFH (p = .338). There was a statistically significant positive correlation between PFH and the following respective biomarkers: gross hemolysis on the routine chemistry studies (p < .01, Rho = .439), AST (p < .01, Rho = .439), RDW (p < .01, Rho = .190), LDH (p < .01, Rho = .584), and AST (when associated elevated alanine transaminase (ALT) levels were censored) (p < .01, Rho = .552). U-Hb correlated poorly with PFH. The serum biomarkers AST (in the absence of ALT elevation) and LDH can be useful surrogates for PFH to quantify hemolysis on ECMO in pediatric patients.

Comparative evaluation of blood collection tubes for clinical chemistry analysis

BackgroundRoutine chemistry testing is typically performed using serum or plasma to assess a patient’s clinical status. At our institution, serum is the specimen type used. To reduce processing times, evaluation of plasma-based and rapid serum gel separator tubes was performed. MethodsWe compared the results of routine chemistry analytes collected in serum gel separator tubes (SST), plasma gel separator tubes (PST), rapid serum gel separator tubes (RST), and plasma tubes without gel separators (DGT). Result concordance was assessed at baseline (immediate testing after processing) and up to one week of refrigerated storage. Other parameters assessed were the susceptibility to hemolysis and lipemia interference, and changes in results after re-centrifugation. Percent changes were compared against the SST and evaluated according to established bias thresholds. ResultsTotal protein and potassium results at baseline in plasma-based tubes had percent changes from the SST that exceeded acceptability thresholds. Stability was significantly shortened for glucose, potassium, aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) when collected in the PST as compared to the SST. The RST was the least susceptible to hemolysis and lipemia interferents. Re-centrifugation affected the serum-based analysis of potassium. ConclusionsPlasma may reduce processing time at the expense of shortened sample stability and may require specimen source-specific reference intervals for potassium and total protein. The RST provides an alternate option to reduce processing time, while maintaining storage stability.

The Hidden Cost of Hemolyzed Blood Samples in the Emergency Department.

On average, patients with hemolyzed potassium samples spend about 1 h longer in the emergency department (ED), regardless of acuity level or disposition. We aimed to quantify the direct expenses associated with poor-quality preanalytic blood samples collected in the ED. We created a simple table with a range of direct expenses (i.e., costs) and rates of hemolyzed sample draws, allowing for identification of potential high-level cost-of-care impact analysis. We included a range of costs informed by review of literature on the topic. Those costs range from $600 to $3000 per bed-hour. This amount was inflation adjusted from 1996 to 2020 (1.68 × [direct cost per visit] × [100000 visits per year/365 days/24 h]). We provided a range of hemolysis incidence based on previously reported data. We showed that for an ED with 100000 annual visits, a 40% draw rate for routine chemistries (including potassium), and a 10% hemolysis incidence, the direct cost impact of hemolysis waste is approximately $4 million/year as a result of the 1 h of added length of stay on average for a patient with a hemolyzed blood sample. This amount represents an annualized estimated cost of caring for a patient in the ED with an avoidable extended length of stay. The financial burden of poor-quality blood samples can be estimated using cost per bed-hour and rate of sample failure. Similar methodology may identify additional QC issues with previously invisible financial implications.

Routine Postoperative Chemistry Panels Are Not Necessary for Most Total Joint Arthroplasty Patients.

The routine use of traditional chemistry-7 (chem-7) laboratory tests following total joint arthroplasty (TJA) has been called into question with the advent of short-stay procedures. Our objective was to determine the incidence, risk factors, and clinical interventions associated with inpatient abnormal routine postoperative chem-7 panels. From 2015 to 2017, 3,162 patients underwent a total of 3,721 TJA procedures, including primary total hip arthroplasty (THA) (n = 1,939; 52.1%) or primary total knee arthroplasty (TKA) (n = 1,782; 47.9%). Patients underwent routine preoperative and postoperative chem-7 testing. Clinical interventions were identified. With use of mixed-effects multivariate logistic regression, potential risk factors for abnormal chemistry panel values (including preoperative chem-7 results, type of surgery, age, sex, race, comorbidities, American Society of Anesthesiologists [ASA] score, and medications) were analyzed. The rates of abnormal preoperative laboratory results were 3.4% for sodium (Na+), 7.4% for potassium (K+), 15.8% for blood urea nitrogen (BUN), and 26.4% for creatinine (Cr). The incidence of abnormal postoperative results was low for K+ (9.7%) and higher for Na+ (25.6%), BUN (55.6%), and Cr (27.9%). Preoperative abnormal laboratory results were a significant predictor of a postoperative abnormality for Na+ (odds ratio [OR] = 2.15; 95% confidence interval [CI] = 1.82 to 2.54), K+ (OR = 4.22; 95% CI = 3.03 to 5.88), and Cr (OR = 3.00; 95% CI = 2.45 to 3.68). Bilateral TJA was associated with increased odds of abnormal postoperative Na+ (OR = 1.56; 95% CI = 1.44 to 1.68). Renal disease was associated with increased odds of abnormal postoperative Cr (OR = 15.21; 95% CI = 5.67 to 40.77). Patients taking loop diuretics had increased odds of abnormal postoperative K+ (OR = 2.10; 95% CI = 1.42 to 3.11) and Cr (OR = 2.28; 95% CI = 1.56 to 3.33). Regarding intervention, 6.7% of hypokalemic patients received potassium chloride (KCl) fluid/tablets. Forty percent of hyponatremic patients received sodium chloride (NaCl) fluid/tablets. The electrolyte-related medicine consultation rate was 0.3% (13 of 3,721). On the basis of our findings, we recommend postoperative chem-7 testing for patients with an abnormal preoperative laboratory result (Na+, K+, BUN, Cr), preexisting renal disease, bilateral TJA, and prescribed angiotensin-converting enzyme inhibitors (ACE), angiotensin II receptor blockers (ARB), and diuretics. Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Report of Three Bengali Cases with Hemoglobin E Variant in Najran

INTRODUCTION: Differential diagnosis of hemoglobin (Hb) variants eluting in the A2 window on high-performance liquid chromatography (HPLC) is of particular importance. Of particular importance is Hb E, which is the most common and the most significant variant. The aim of this study was to study a rare variant infrequently seen in our countries during the routine work. METHODS: Sixteen Bengali workers at Najran University Hospital, Saudi Arabia, came to the laboratory for routine investigation. CBC, routine blood chemistry, and Hb separation by HPLC were performed. RESULTS: Three cases out of 16 showed an abnormal Hb peaked on the A2 window on HPLC consistent with the diagnosis of Hb E. Two of them had Hb E of 29.1% of each. The third case had Hb E around 86%. In addition, one case was consistent with β thalassemia trait had increased Hb A2 of 5.7%. Five cases were borderline. CONCLUSION: HbE could be adequately differentiated from other Hb variants eluting in the A2 window on HPLC by the percentage of the variant, its retention time, the mild clinical presentation, and the ethnic origin of the patient.

THE EFFECTS OF CARDIAC REHABILITATION ON HYPERTENSIVE BURDEN AND ARTERIAL STIFFNESS IN HYPERTENSIVE PATIENTS. A RANDOMIZED CROSSOVER STUDY

Objective: To investigate the effect of continuous versus intermittent exercise on hypertensive burden as well as the correlation of pulse wave velocity (PWV) with various parameters of CPX testing. Design and method: A randomized crossover study that will enroll 150 hypertensive patients. Patients will be randomized on continuous or intermittent exercise program for three months, then will follow a month of wash out period and the patients will be cross over from continuous to intermittent and vice versa for another three months of exercise. In all subjects, routine blood chemistry, including SUA determination, echocardiographic examination, office and 24 h ambulatory blood pressure (BP) as well as 24 h ambulatory PWV and central (BP) measurement as well as CPX testing will be performed in all study stages. Results: We present the preliminary results of 32 hypertensive patients (mean age 65.1 ± 11.3 years). A negative correlation was found between PWV and Peak VO2 (r = -0.540, p = 0.002), (r = -0.508, p = 0.045) at baseline and after 3 months of exercise. Peak VO2 was inversely correlated with PWV (r = -0.512, p = 0.003) and positive with diastolic BP (r = 0.469, p = 0.008), but not with systolic BP levels (p = ns). Eighteen patients until now have completed the 3 months of exercise. PWV, systolic and diastolic BP levels were decreased while Peak VO2 levels were increased between baseline and after 3 months of exercise but with no statistically significant differences. Specifically, the mean baseline PWV was 9.26 (±1.60) m/sec and the final PWV was 9.23 (±1.60) m/sec (p = 0.769). The mean of systolic and diastolic BP 127.59 (±7.94)/ 78.12 (±8.57) and 124.59 (±7.57)/ 77.24 (±8.57) mmHg for baseline and after three months of exercise (p = ns). The mean of Peak VO2 levels were 21.63 (±4.61) and 22.24 (±3.97) ml/kg/min for baseline and after three months of exercise (p = 0.394). It has to be mentioned however that in 6 patients (33%) the antihypertensive drug regiment was reduced. Conclusions: PWV was significantly correlated with functional capacity levels irrespectively of the levels of systolic BP. Cardiac rehabilitation may decrease BP levels or the number of antihypertensive drugs.

Prevalence of non-alcoholic fatty liver disease among patients with non-diabetic chronic kidney disease detected by transient elastography.

Non-alcoholic fatty liver disease (NAFLD) shares a close relationship with cardiovascular morbidity and mortality. The purpose of this study is to evaluate the frequency of NAFLD in the patients with non-diabetic chronic kidney disease (CKD). This cross-sectional study included 80 patients with non-diabetic CKD, of which, 50 patients were on hemodialysis (HD) and 30 patients had CKD stage G3-5 not on dialysis. These patients were randomly selected from Ain Shams University Hospitals, Cairo, Egypt. Patients with diabetes mellitus, obesity, alcohol intake, viral hepatitis, or drug-induced liver steatosis were excluded from this study. Importantly, the controlled attenuation parameter (CAP) (dB/m) of liver steatosis (S0-S3) and liver stiffness/fibrosis measurement (F0-F4) were measured using transient elastography (Fibroscan®). Other evaluations included complete blood count, routine blood chemistry, and C-reactive protein (CRP) titer. In total, 45 (56.25%) (30 males, 15 females) out of total 80 studied patients were reported to have NAFLD. There were 29 patients with end-stage renal disease who were on regular HD and 16 patients with pre-dialysis CKD G3-5. The mean CAP values of hepatic steatosis in the patients with CKD on dialysis and patients with pre-dialysis CKD were 265.41 ± 52.73 and 259 ± 44.8dB/m, respectively. A significant association between the severity of hepatic steatosis degree with decreased glomerular filtration rate and increased CKD stage was observed in this study. The degree of liver stiffness was significantly related to an increased hepatic steatosis grade. A significant positive correlation was found between the degree of NAFLD and serum levels of alanine aminotransferase, aspartate transaminase, total cholesterol, triglycerides, low-density lipoprotein, and CRP titer (P < 0.05). Importantly, NAFLD was significantly associated with an evident history of cardiovascular disease (CVD) among the studied patients. A high frequency of NAFLD (56%) was observed among the patients with non-diabetic CKD on hemodialysis and patients with pre-dialysis CKD. NAFLD may be associated with an increased liver stiffness grade and CVD among those patients.

Routine Blood Chemistry Predicts Functional Recovery After Traumatic Spinal Cord Injury: A Post Hoc Analysis

Background Spinal cord injury (SCI) leads to various degrees of lifelong functional deficits. Most individuals with incomplete SCI experience a certain degree of functional recovery, especially within the first-year postinjury. However, this is difficult to predict, and surrogate biomarkers are urgently needed. Objective We aimed to (1) determine if routine blood chemistry parameters are related to neurological recovery after SCI, (2) evaluate if such parameters could predict functional recovery, and (3) establish cutoff values that could inform clinical decision-making. Methods We performed a post hoc analysis of routine blood chemistry parameters in patients with traumatic SCI (n = 676). Blood samples were collected between 24 and 72 hours as well as at 1, 2, 4, 8, and 52 weeks postinjury. Linear mixed models, regression analysis, and unbiased recursive partitioning (URP) of blood chemistry data were used to relate to and predict walking recovery 1 year postinjury. Results The temporal profile of platelet counts and serum levels of albumin, alkaline phosphatase, and creatinine differentiated patients who recovered walking from those who remained wheelchair bound. The 4 blood chemistry parameters from the sample collection 8 weeks postinjury predicted functional recovery observed 1 year after incomplete SCI. Finally, URP defined a cutoff for serum albumin at 3.7 g/dL, which in combination with baseline injury severity differentiates individuals who regain ambulation from those not able to walk. Specifically, about 80% of those with albumin >3.7 g/dL recovered walking. Conclusions Routine blood chemistry data from the postacute phase, together with baseline injury severity, predict functional outcome after incomplete SCI.

Nasal manifestations in patients with chronic renal failure on hemodialysis

Background Patients with end-stagerenal disease (ESRD) on regular hemodialysis (HD) show various otolaryngological manifestations owing to uremic toxins and electrolyte imbalance. Previous studies have reported epistaxis as the most common ENT manifestations of ESRD on HD as explained by bleeding tendency related to uremia or HD itself. Nasal crustation, septal perforation, and olfactory dysfunction were also observed in HD patients. Objective To evaluate the frequency of different nasal manifestations among nondiabetic prevalent HD patients. Patients and methods A cross-sectional study was conducted in Ain Shams University Hospital from March 2019 till September 2019. It included 68 eligible nondiabetic patients with ESRD on regular HD more than 6 m. All patients were subjected to full history and clinical examination. CT nose and sinus was done only if indicated. Complete blood count and routine chemistry (blood urea nitrogen, serum creatinine, urea reduction ratio, calcium, phosphorus, parathyroid hormone, and iron profile) were done. Results Most patients did not give a past history of epistaxis (94.1%). Overall, 44.1% of the patients experienced dry nasal mucosa and pale inferior turbinates, and 10.3% of the patients had congested nasal mucosa. Crustations were founded in 7.4% of the patients, although they were found in nearly double percentage in nasal septum (14.7%). The nasal septum deviation and ulceration were found in 2.9% each. Only one (1.5%) patient had nasal septum perforation. The mean level of hemoglobin (g/dl) concentration was 10.4 (range, 6.8–15 g/dl). Conclusion Modern adequate HD techniques have reduced epistaxis in patients with ESRD. The most common ENT manifestations were dry nasal mucosa and pale inferior nasal turbinate and to a lesser extent crustations on both nasal septum and inferior nasal turbinate.

Synthetic Cannabinomimetics: A Brief History and the Challenges They Pose for the Forensic Chemist

Since the first detection of synthetic cannabinomimetics in herbal smoking blends in 2008 the clandestine production of these compounds, based on seizure data, increased in number every year until ~2012. In recent years there has been a decline in synthetic cannabinomimetic production both in number and diversity. The synthetic details of the first generation cannabinoids were documented in the scientific and medical literature making production comparatively simple. Subsequent generations of synthetic cannabinoids involved more complex but still very practicable synthetic chemistry. This resulted in a period of rapid growth in synthetic cannabinoids creating a health crisis and problems for forensic chemists faced with many substances for which no certified reference materials existed. Routine forensic chemistry laboratories were well practiced at identifying known drugs using chromatographic–mass spectrometric techniques and comparison to reference materials. However as synthetic cannabinomimetics, often referred to in the literature as synthetic cannabinoids, appeared in large numbers, few laboratories were equipped with the nuclear magnetic resonance (NMR) spectrometers and high resolution mass spectrometers (HRMS) required for identification of unknown substances. These developments also challenged public prosecutors for opinions from forensic experts as to the legality or otherwise of these novel drugs.

Real-world study on the effectiveness and safety of basal insulin IDegLira in type 2 diabetic patients previously treated with multi-injective insulin therapy.

Achieving glycemic target is paramount to control diabetes mellitus (DM) and reduce micro-vascular and macro-vascular complications. Despite the mostly recent-developed drugs, most patients still show an above desired glycated hemoglobin (HbA1c) level due to DM complex pathophysiology, therapeutic and dietary compliance and clinical inertia in introducing or intensifying insulin therapy. To support the promising results of clinical trials on the effectiveness and safety of the degludec/liraglutide combination (IDegLira) in type 2 DM patients with C-peptide values >1 ng/ml who were previously treated with basal-bolus multiple daily-dose insulin injections. This observational, prospective and non-randomized trial enrolled type 2 DM patients referred to our outpatient clinic between January 2019 and December 2019, who were shifted from multiple daily-dose insulin injection therapy to degludec/liraglutide combination as per the physician's decision. The main assessment was HbA1c variation at 6 months from baseline. Secondary assessments included variation in fasting glycemia, routine anthropometric assessments, blood chemistry, blood pressure and patients' quality of life (measured by the Diabetes Treatment Satisfaction Questionnaire [DTSQ]), from baseline to 6 months. HbA1c (8.4 vs. 7.4%; p<0.0001) and body weight (94.1 vs. 93 kg; p<0.0001) were significantly lower after 6 months for patients on the degludec/liraglutide combination. A similar trend was observed in fasting glycemia levels (159 vs. 125 mg/dl; p<0.0001). An improved glycemic control was achieved with degludec/liraglutide despite a reduction in total daily insulin units (42 U at 6 months vs. 22 U at baseline; p<0.0001). In addition, higher scores in the DTSQ were registered after 6 months on degludec/liraglutide (mean score: 27 vs. 20; p<0.0001). The combination therapy also proved more convenient than basal-bolus therapy in terms of costs, with an average per-patient cost difference of €-0.41±0.59/die (p<0.0001). These real-world findings show that degludec/liraglutide seems to be more effective than basal-bolus insulin in achieving glycemic control, allowing cost sustainability and improving patient satisfaction.

Disorders of Calcium Metabolism: Hypocalcemia and Hypercalcemia.

Calcium (Ca+2) is a divalent cation that plays a critical role in numerous body functions such as skeletal mineralization, signal transduction, nerve conduction, muscle contraction, and blood coagulation. Ca+2 metabolism is linked to magnesium (Mg+2) and phosphate metabolism. Ca+2 homeostasis is dependent on intestinal absorption, bone turnover, and renal reabsorption. The hormonal regulators of these processes are the parathyroid hormone (PTH), calcitriol {1,25-dihydroxyvitamin D [1,25(OH)2D]}, and serum ionized Ca+2. Cloning of the Ca+2-sensing receptor (CaSR) has greatly advanced the understanding of Ca+2 metabolism. Disorders of Ca+2 metabolism are easily recognized because Ca+2 is included in routine chemistry panels. Measurement of ionized Ca+2 is the preferred way to ascertain the diagnosis of hypocalcemia and hypercalcemia.

Diagnostic yield from routine metabolic screening tests in evaluation of global developmental delay and intellectual disability

The aim of this retrospective review was to evaluate the diagnostic yield from these first-tier tests in the 7 years before (2006 to 2012) and after (2013 to 2019) implementation at the community paediatrician level. Prior and postimplementation diagnostic yield of an IEM from first-tier metabolic testing was 9 out of 986 (0.91%) and 11 out of 4,345 children (0.25%), respectively. Disorders of creatine metabolism and organic acidurias were the most frequently established diagnoses in both time periods. No diagnoses were established through acylcarnitine copper/ceruloplasmin, lactate, or ammonia testing. Twenty out of 24 patients had specific neurological or other red flag signs in addition to GDD/ID. Four boys diagnosed with an x-linked creatine transporter defect (CTD) had speech-language delay as the most prominent finding. The expansion of first-tier metabolic testing to community-based paediatricians in BC did not yield an increase in IEM diagnoses. A modified first-tier test panel should be offered to patients with GDD/ID, neurologic, and/or red flag signs. Urine creatine testing in boys with speech-language delay warrants consideration to detect CTD.

Analysis of performance of clinical biochemistry laboratory using Sigma metrics and Quality Goal Index

BackgroundUnreliable and ingenuine results issued by clinical laboratories have serious consequences for the patients. Sigma metrics is a standardized tool for Quality assessment for test performance in a laboratory. ObjectiveTo evaluate the performance of routine biochemistry laboratory at MMIMSR, Mullana in terms of Sigma metrics and Quality Goal Index. Material and methodsThis cross sectional study evaluated performance of 14 routine chemistry parameters using retrospective Internal Quality Control data of two levels on Siemens Dimension Rxl from Feb to Jul 2019 for CV% and EQAS reports from CMC, Vellore for Bias%. Sigma metrics was calculated using total allowable error targets as per CLIA and Biological Variability database guidelines. ResultsFor level-2 IQC; TG, Chol, ALP showed excellent performance with σ ​> ​6 while σ ​< ​3 was observed for AST, Total Protein, Glucose, BUN and ALT using CLIA guidelines while in IQC Level-3 poor performers were only BUN and ALT with Ca, TG and Chol showing σ ​> ​6. Further by using Biological Variability data guidelines; 10 parameters of IQC Level-2 and 5 of IQC level-3 were poor performers with σ ​< ​3. ConclusionSigma metrics is an excellent tool for performance analysis of tests performed in a clinical laboratory. Lack of precision in terms of CV% was seen for majority of the poor performers. Total allowable error targets using Biological Variability data revealed σ ​< ​3 for 10 parameters while using CLIA guidelines σ ​< ​3 was seen for only 5 parameters of IQC level-2.

Case report: Pitt-Hopkins like syndrome with CNTNAP2 mutation

BackgroundPitt-Hopkins syndrome (PHS) is a rare cause of severe intellectual disability, seizures, language impairment, and peculiar facial dysmorphism. It is caused by a mutation in transcription factor 4 (TCF4). Through molecular karyotyping and mutational analysis, a study identified recessive defects in two genes, contactin associated protein like 2 (CNTNAP2) and Neurexin I (NRXN1), in patients with similar presentations of Pitt-Hopkins syndrome and called Pitt-Hopkins-like syndrome (Zweier et al., J Med Genet 80: 994-1001, 2007).We present the first case report of a child in Iraq with Pitt-Hopkins-like syndrome that was referred to the Welfare Children’s Hospital/Medical City of Baghdad because of her intellectual disability.Case presentationThe patient was 4-year-old female child who presented with psychomotor delay and language impairment. She had frequent attacks of the respiratory tract and eye infections. Ophthalmologic examination revealed left-sided esotropia and severe myopia. Routine hematologic, serologic, and chemistry tests were within normal ranges. EEG revealed diffuse theta slowing and diffuse beta activity. The audiological test was normal. NCS and EMG showed normal results. Echo study, chest X-ray, and abdominal/pelvic ultrasound revealed normal findings. Brain MRI showed mild bilateral frontal-temporal atrophy. Whole-exome sequencing (WES) revealed a homozygous stop mutation in CNTNAP2 with a heterozygous state in both parents.ConclusionIntellectual disability may result from different types of abnormal cellular processes and with widening the use of molecular gene analysis in cases of intellectual disability, underdiagnosed cases of Pitt-Hopkins and Pitt-Hopkins-like syndromes may be uncovered.

Validation of the newly FDA-approved Buhlmann fCal Turbo assay for measurement of fecal calprotectin in a pediatric population

ObjectivesInflammatory bowel disease (IBD) is an increasingly prevalent disorder marked by chronic intestinal inflammation. Fecal calprotectin has emerged as a useful biomarker for differential diagnostics and monitoring IBD activity. We validated the newly FDA-approved fCal Turbo fecal calprotectin assay in our pediatric hospital. Design and methodsThe performance of the fCal Turbo assay was assessed on the Vitros 5600 analyzer (Ortho Clinical Diagnostics, USA), including limit of quantitation, linearity, precision, and interference studies. Method comparison was performed with 20 fecal samples with the Buhlmann fCal ELISA, and reference range verification was performed with 33 fecal samples. ResultsThe fCal Turbo assay on the Vitros 5600 was linear between 33.1 and 14,182.5 ​μg/g, with dilution studies extending the range to 33.1–22,000 ​μg/g, Reproducibility of the assay met acceptability criteria, with intra-assay CV of 0.3–3.2% and inter-assay CV of 5.2–8.9%. Interference studies identified acceptable thresholds for protein, bilirubin, and lipids. We verified a reference range of 33.1–60 ​μg/g in our patient population. Deming regression identified acceptable correlation with minor positive bias (2.7%) between the fCal Turbo and fCal ELISA methods. ConclusionsThe fCal Turbo assay performs well on the Vitros 5600 analyzer in our patient population, with the assay being easy to use in our routine chemistry workflow. We anticipate that the fCal Turbo assay will be useful as a rapid screening method for differential diagnostics and disease monitoring of IBD in our patient population.

Bariatric surgery and LDL cholesterol (BASALTO) trial study protocol: randomised controlled study evaluating the effect of gastric bypass versus sleeve gastrectomy on high LDL cholesterol

IntroductionObservational studies have shown gastric bypass to be superior to sleeve gastrectomy in terms of low-density lipoprotein (LDL) cholesterol improvement. If these results are confirmed in randomised controlled trials, presurgical...

Establishing hemolysis and lipemia acceptance thresholds for clinical chemistry tests

BackgroundA key component of laboratory medicine is the evaluation of specimen suitability for downstream analytical testing. Accurate identification and characterization of the impact of interferents on clinical chemistry analytes is important for patient care. To empirically assess the influence of hemolysis and lipemia on clinical chemistry tests analyzed on a Roche cobas® c701 system, we evaluated serum pools spiked with increasing concentrations of hemolysate and Intralipid®. MethodsUsing an interferent acceptance threshold of within ± 10% of the non-hemolyzed or non-lipemic results, 31 routine chemistry analytes were evaluated. ResultsThe majority of analytes were determined to have the same or very similar acceptability thresholds as those listed in the vendor package insert. However, several analytes resulted in new thresholds that deviated from manufacturer recommendations (9 higher and 2 lower for lipemia, 7 higher and 6 lower for hemolysis). Samples with high enzyme activities (LDH, ALT, AST, ALP, and CK) were observed to tolerate higher levels of hemolysis, and tiered hemolysis thresholds were established for these enzymes. Independent evaluation of indices is recommended to enable thoughtful implementation of specimen quality criteria and to provide guidance to laboratorians and providers on the nature of these interferences.