An Approach to Re-evaluate the Reference Cutoff of the Parameters of Newborn Screening: An Observational Study.

Background Unless a cutoff level of the parameters of newborn screening (NBS) is defined, a screening test's results would end in high recall rates and apprehensive parents. The study aimed to establish a cutoff level of the healthy term newborns. Materials and methods The study was a retrospective observational data analysis on a cohort of 1158 term newborns who underwent NBS in our institute. The percentile distribution of the NBS parameters was computed and the 99th percentile value was considered the new cutoff. For lower values, such as neonatal glucose 6-phosphate dehydrogenase (nG6PD) and neonatal biotinidase (nBIOT), low percentile values were regarded as new cutoff value. Results Neonatal thyroid stimulating hormone (nTSH), nG6PD, neonatal immunoreactive trypsinogen (nIRT), and nBIOT showed a wide variation in the distribution. Most newborns had neonatal galactose (nGAL), nIRT, and nBIOT values above the median. The 99th percentile value of nTSH was 14.5 mIU/L, and that of neonatal 17-hydroxyprogesterone (n17-OHP) was 43.7 nmol/L. The 1.0th percentile value for nG6PD was decreased to 2.18 IU/gHb. The new cutoff values for nBIOT, nIRT, neonatal phenylketonuria (nPKU) and nGAL were 48.59 U, 95.3 µg/L, 2.3 mg/dL and 15.9 mg/dL. The mean and median nTSH values did not significantly differ (p=0.99) in the first five days of birth. On the contrary, the study population depicted considerably raised levels of n17-OHP on day 3, followed by a sharp decrease (p=0.029). Similarly, nIRT displayed significant differences in the first five days (p=0.017). Conclusion Using the 99th percentile values of the NBS parameters as the new cutoff levels might be beneficial in terms of the recall rates and cost burden.

Inflammatory Markers in Patients With Major Depressive Disorder: A Prospective, Clinic-Based, Cohort Study From India.

Background Patients with major depressive disorder have varying response rates to treatment. Multiple factors such as non-adherence, comorbidity, chronic stressors, and biological factors may be responsible for this variation. Inflammatory (pro and anti) markers have been well studied as a cause for depression, predisposing factors, and a consequence of depression. Among these, interleukins (ILs), interferons, C-reactive protein (CRP), and tumor necrosis factor-alpha (TNF-α) have been studied repeatedly. We conducted a pilot study to assess the levels of these inflammatory markers in patients with major depressive disorder. The specific objectives of this study were to compare and correlate changes in pro- and anti-inflammatory markers throughout different phases of depression, including pretreatment and posttreatment periods, and to evaluate the pattern of pro- and anti-inflammatory markers in patients who experienced remission or showed a positive response to treatment. Methodology This was a prospective, clinic-based, cohort study done for a period of one and a half years. Patients aged 18-65 years with depressive disorder per the International Classification of Diseases Tenth Edition and who scored more than 7 on the Hamilton Depression Rating Scale were included in this study. A total of 81 patients were recruited who were followed up till eight weeks after inclusion. A total of 31 patients completed the eight weeks of follow-up. Levels of IL-10 and TNF-α were assessed at baseline, two weeks, four weeks, and eight weeks of follow-up. Results This study tried to compare the levels of pro- and anti-inflammatory markers across pretreatment and various posttreatment phases of depression. Results showed that the levels of pro-inflammatory cytokine TNF-α increased from baseline till eight weeks of follow-up, and levels of IL-10 decreased from baseline till eight weeks of follow-up. However, these changes were not statistically significant. Conclusions This study supports the hypothesis that inflammatory markers can be trait markers of depression rather than the consequence or result.

Serological Evaluation of Antibody Titers After Vaccination Against COVID-19 in 18-44-Year-Old Individuals at a Tertiary Care Center.

Background The evaluation of the effectiveness of the vaccines (ChAdOx1-nCOV; Covishield and BBV-152; Covaxin) against coronavirus disease 2019 (COVID-19) is necessary to assess their efficacy. Because most antibodies that neutralize the coronavirus are directed against the receptor binding domain within the spike protein of the virus, these antibodies serve as markers for viral neutralizers and, in turn, for vaccine response. The present study aimed to evaluate the anti-neutralizing antibody (receptor binding domain (RBD)) and immunoglobulin G2 (IgG2) titers following the completion of the vaccination schedule (both vaccines) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Methodology In this longitudinal prospective study, conducted in a tertiary care center, 30 sequentially (two doses) vaccinated study participants between the ages of 18 and 44 years were sampled for estimation of anti-RBD antibody titer and IgG2. All statistical analysis was done using SPSS version 20 (IBM Corp., Armonk, NY, USA). P-values less than 0.05 were considered significant. Results There was a statistically significant increase in the neutralizing antibody titer after one month of the second dose (z = -4.597, p < 0.001), while a significant decrease was seen in the IgG2 levels (z = -3.075, p = 0.002). The results showed a significant neutralizing effect of the vaccines being used, with Covishield being more effective than Covaxin. The levels of neutralizing antibodies were independent of all demographic variables such as age, sex, and body mass index. Conclusions This study evaluating the efficacy of the two vaccines, namely, Covishield and Covaxin, is the first of its kind in the state of Chhattisgarh. The results of this study are similar to previous studies conducted in India and outside India, concluding that Covishield is a more effective vaccine.

Effect of the Angiotensin-Converting Enzyme (ACE) (I/D) Polymorphism in COVID-19 Patients and Their Healthy Contacts.

Introduction The quest to understand the pathophysiology behind the deleterious effects of the coronavirus disease 2019 (COVID-19) outbreak took a turn when involvement of the angiotensin converting enzyme (ACE) receptors in different organs, especially the lungs, could explain all the clinical manifestations and adverse events in patients. The I/D polymorphism in the ACE gene, having been attributed in various studies, was also seen to have an effect in this pandemic. Present study aimed to analyze the effect of this I/D mutation in COVID-19 patients and in their healthy contacts. Methods Patients with past history of COVID-19 infection and their healthy contacts were enrolled in the study after obtaining ethical clearance and informed consent. The polymorphism was studied by real-time polymerase chain reaction (PCR). Data was analyzed in SPSS version 20 (IBM Corp., Armonk, NY, USA). p value less than 0.05 was taken as significant. Results The allelic distribution followed the Hardy-Weinberg equilibrium, with the wild 'D' allele being dominant in the population. Between the case and controls, the mutant 'I' allele was observed more in the controls, and the association was statistically significant. Conclusion From the results of the present study, it could be concluded that while the wild 'D' allele led to higher chances of being affected with COVID-19, the polymorphism to 'I' allele was relatively protective in nature.

Association of Methylenetetrahydrofolate Reductase Gene Polymorphism in Mothers With Adverse Clinical Outcomes in Neonates.

BACKGROUND: The presence of polymorphic methylenetetrahydrofolate reductase (MTHFR) in mothers poses a risk for numerous detrimental outcomes in neonates. The present study investigated the association of maternal MTHFR A1298C and C677T single nucleotide polymorphisms (SNPs) with the clinical outcomes in their neonates. MATERIALS AND METHODS: The cross-sectional study included 60 mothers and their neonates. Blood samples from mothers were analyzed for MTHFR A1298C and C677T SNP genotyping by real-time polymerase chain reaction. Clinical details of mothers and neonates were documented. Study groups were stratified based on wild, heterozygous, and mutant genotypes for the respective polymorphisms observed in mothers. Multinomial regression was applied for the association, followed by gene model formulation to estimate the impact of the genetic variants on the outcomes. RESULTS: The frequency percentages of mutant CC1298 and TT677 genotypes were 25% and 8.06%, respectively, and the mutant allele frequencies (MAF) were 42.5% and 22.5%. Percentages of adverse outcomes such as intrauterine growth restriction, sepsis, anomalies, and mortality were higher in neonates born to mothers with homozygous mutant genotypes. Maternal C677T MTHFR SNPs revealed a significant association with neonatal anomalies (p = 0.001). The multiplicative risk model depicted OR (95% CI) for CT vs. CC+TT as 3.0 (95% CI: 0.66-13.7), and for TT vs. CT+CC was 15 (95% CI: 2.01-112.12). The C677T SNP in mothers predicted a dominant model for neonatal death (OR (95% CI): 5.84 (0.57-60.03), p = 0.15), whereas the A1298C reported recessive model for 1298CC mothers (OR (95% CI): 11 (1.05-115.5), p = 0.02). Both the genotypes assumed a recessive model for adverse neonatal outcomes: OR (95%CI) for CC vs. AA+AC was 3.2 (0.79-12.9, p = 0.1), and for TT vs. CC+CT was 5.48 (0.57-175.7, p = 0.2). The risk for sepsis in neonates was nearly six times higher in those born from mothers with homozygous CC1298 and TT677 than in the wild and heterozygous variants. CONCLUSION: Mothers with C677T and A1298C SNPs are highly susceptible to adverse outcomes in their neonates. Hence, screening the SNPs during the antenatal period can purposefully serve as a better predictive marker, following which proper clinical management could be planned.

Altered T-cell profile in sickle cell disease.

Background: Impaired immune status due to altered T-cell response in sickle cell disease (SCD) might provide substantial insight into immune activity in SCD patients. Materials & methods: A total of 30 healthy control, 20 SCD patients in a crisis state and 38 SCD patients in a steady state were evaluated for T-cell subsets. Results: A significant decrease in CD8+ (p = 0.012) and CD8+45RA-197+ (p = 0.015) T-cells were observed among SCD patients. Naive T-cells (45RA+197+; p < 0.01) were elevated and effector (RA-197-) and central memory (RA-197+) T-cells were grossly reduced in the crisis state. Negative regression of naive T-cells with CD8+57+ affirmed immune inactivation. The predictor score reflected 100% sensitivity for predicting the crisis state (area under the curve = 0.851; p < 0.001). Conclusion: Monitoring naive T-cells with predictive scores can help assess the early shift from a steady state to a crisis state.

The sickle-shaped hemoglobin in sickle cell disease (SCD) patients are known to cause frequent episodes of blockage in small vessels. Repeated episodes of blockage result in tissue injury and create a state of chronic inflammation. In response, a series of inflammatory reactions initiate such that the immune response in these patients is quite altered. To understand these changes, this study was conducted to observe alterations in T-cell subtypes and gain substantial insight into immune activity in SCD patients. A total of 30 healthy control, 20 SCD patients in a crisis state and 38 SCD patients in a steady state were evaluated for T-cell subsets. The SCD patient experienced a gross decrease in T-cells with killing ability and memorizing ability for immune responses. The SCD patients in crisis state reported a significant increase in inactivated T-cells but the levels of activated T-cells that can defend and memorize the immune response were quite low. The finding suggested that this group of SCD patients had compromised immune activation that hindered the activation and differentiation of inactivated T-cells to their effector and memory cells. An equation was derived considering all the parameters that were significantly altered to derive a predictive score that showed 100% sensitivity for predicting a crisis state. Hence, it is proposed that monitoring the inactivated T-cell population or predictive score might help clinicians to assess clinical severity at an early stage and initiate appropriate preventive measures.

A pilot study to evaluate the changes in venous blood gas parameters and hypoxia biomarkers in health care workers using different kinds of masks.

Background: The study is aimed to investigate the metabolic alterations and changes in biochemical parameters associated with extended mask. Methods: It was a prospective comparative study conducted on 129 participants comprised of 37 healthy controls and 92 health care workers using different kind of masks like, cloth mask, surgical masks and N95-FFR/PPE. Two samples on day-1 and day-10 were collected for analysis of blood gas parameters, serum hypoxia-inducible factor-α (HIF-α), and erythropoietin (EPO). Results: Oxygen saturation percentage (sO2) of 72.68 (P = 0.033) was significantly low, whereas, Na+ (P = 0.05) and Ca2+ (P < 0.001) were raised in exposed individuals than the healthy controls. The serum HIF-α level of 3.26 ng/mL, was considerable higher in the exposed individuals than controls (P = 0.001). pO2 and sO2 were the lowest and HIF-α and EPO were raised in N95-FFR/PPE of all mask users (P < 0.01). A significant difference was evidenced for pCO2, pH, Na+, Ca2+, and EPO in the exposed group. A positive correlation between the duration of mask use (in hours) with HIF-α (r = 0.247, P = 0.005) and Ca2+ (r = 0.306, P < 0.001) was observed. The major complaints in N95-FFR/PPE users were headache (15.2%) and polydipsia (33.3%). Conclusion: The study findings depicted a significant metabolic alterations in PPE/N95 users which could be due to chronic hypoxic exposure of the tissues.

Processing Validation Metrics of Syva Enzyme-Multiplied Immunoassay Technique (EMIT) Methotrexate Assay for Beckman Coulter System.

BACKGROUND: High-dose methotrexate (HDMTX), defined as a dose greater than 500 mg/m2, is used to treat a variety of cancers; and though safe, it can cause major toxicity. Syva enzyme-multiplied immunoassay technique (EMIT) methotrexate (MTX) assay (Gurgaon, India: Siemens Healthcare Diagnostics Ltd.) uses a homogeneous enzyme immunoassay method. Low-end precision performances are very important for laboratory methods, especially when their results have clinical significance at these levels. METHODOLOGY: A total of 25 replicates (five replicates per run, for five runs) were analyzed for profiling. Precision, accuracy, linearity, limit of blank, limit of detection, and limit of quantification were determined using existing guidelines. Imprecision profile and limit of quantitation (LoQ) at 10% were determined by fitting data with hyperbolic regression. RESULTS: The coefficient of variation percentage (CV%) for low, mid, and high-level internal quality control (IQC) was 1.25%, 3.45%, and 1.55%, respectively. Similarly, estimated bias was -4.58%, -3.54%, -7.21% for each level. The assay linearity was maintained from a range of 0.041-1.993 mmol/L with an R2 of 0.959. The limit of detection was estimated to be 0.07 mmol/L. CONCLUSION: Syva EMIT MTX assay can be precisely and accurately used to measure low levels of serum methotrexate at levels lower than claimed by the manufacturer, aiding in the monitoring of toxicity in patients.

Association of Serum IL-17 and IL-23 Cytokines With Disease Activity and Various Parameters of Rheumatoid Arthritis in Indian Patients.

Introduction Interleukin-23/T helper 17 (IL-23/Th17) axis cytokine has been thought to be a critical pathway for rheumatoid arthritis (RA) disease development and its association with disease severity, joint erosion, and functional outcome. There is a paucity of data on the role of IL-23/Th17 axis cytokines in an Indian RA subset of patients. We aimed to determine the association between serum cytokines (interleukin-17 [IL-17] and [IL-23]) and disease activity as well as with clinical and biochemical parameters of RA patients. Methods In this observational cross-sectional study, 84 consecutive RA cases were recruited after obtaining consent. Serum IL-17 and IL-23 levels were measured by the enzyme-linked immunosorbent assay (ELISA) method. Clinical and laboratory parameters, disease activity score 28-erythocyte sedimentation rate (DAS28-ESR), and Health Assessment Questionnaire-II (HAQ-II) were recorded. Correlation of cytokines with various clinical and biochemical parameters was elicited. Results Only C-reactive protein (CRP) correlated positively with IL-23 (rs = 0.26, p = 0.014) but not the ESR. Both IL-17 and IL-23 levels showed an insignificant, weak positive correlation with the disease activity DAS28 (rs = 0.18, p = 0.097; rs = 0.12, p = 0.259, respectively). Neither IL-17 nor IL-23 levels differed among the disease severity group (p = 0.13, p = 0.215). Only the IL-23 level positively correlated with functional status (HAQ-II) (rs = 0.28, p = 0.009). IL-17 level was higher in advanced RA as compared to early RA (p = 0.028). Both IL-17 and IL-23 levels did not vary within the different subgroups (age, obesity, disease-modifying drugs/steroid/biologics use, and serology status). Conclusion Females had higher IL-23 levels than males. Advanced RA had higher IL-17 levels than early RA. The cytokine levels were not influenced by factors like age, duration of disease, serology status, or drugs. Neither of the cytokines correlated significantly with disease severity. Higher IL-17 levels may have a role in the progression of early non-erosive to chronic erosive arthritis. Higher IL-23 levels may signal a bad functional outcome.

Early Biochemical Markers in Predicting the Clinical Outcome of COVID-19 Patients Admitted in Tertiary Care Hospital.

Introduction An array of routinely accessible serum biomarkers was assessed to explore their overall impact on severity and mortality in coronavirus disease 2019. Materials and Methods A retrospective analysis of 1,233 adults was conducted. The study groups comprised 127 nonsurvivors and 1,106 survivors. Data for demographic details, clinical presentations, and laboratory reports were recorded from the medical record section. The predictors were analyzed for their influence on mortality. Results The mean (+ standard deviation) age of the patients in the nonsurvivor group was 58.8 (13.8) years. The mean age (56.4 years) was highest in severe grade patients. The odds ratio for death was 2.72 times for patients above the age of 40 years. About 46% of nonsurvivors died within 5 days of admission. Males were found to be more prone to death than females by a factor of 1.36. Serum urea depicted highest sensitivity (85%) for nonsurvival at 52.5 mg/dL. Serum albumin (3.23 g/dL), albumin-to-globulin ratio (0.97), and C-reactive protein-to albumin ratio (CAR) (2.08) showed a sensitivity of more than 70% for mortality outcomes. The high hazard ratio (HR) for deceased patients with hyperkalemia was 2.419 (95% confidence interval [CI] = 1.96-2.99; p < 0.001). The risk for nonsurvival was increased with elevated serum creatinine by 15.6% and uric acid by 21.7% ( p < 0.001). The HR for hypoalbuminemia was 0.254 (95% CI: 0.196-0.33; p < 0.001) and CAR was 1.319 (95% CI: 1.246-1.397; p < 0.001). Saturation of oxygen ( p < 0.001), lactate dehydrogenase ( p = 0.006), ferritin ( p = 0.004), hyperuricemia ( p = 0.027), hyperkalemia ( p < 0.001), hypoalbuminemia ( p = 0.002), and high CAR values (0.031) served as potential predictors for mortality. Conclusion Adjusting for all the predictor variables, serum uric acid, potassium, albumin, and CAR values at the time of admission were affirmed as the potential biomarkers for mortality.

First-Trimester Reference Intervals for Thyroid Function Testing among Women Screened at a Tertiary Care Hospital in India.

Objectives Due to differences in the method of assay and population-specific factors, each laboratory needs to establish its own gestation-specific reference intervals (GRIs) for thyroid hormones. Materials and Methods Three-hundred forty-one women with less than 14 weeks gestation were screened at a tertiary care hospital in Chhattisgarh, India. Serum levels of thyroid-stimulating hormone (TSH), free thyroxine (fT4), and thyroid peroxidase antibody (anti-TPO) were measured using an ADVIA Centaur XP immunoassay. GRIs (2.5th and 97.5th percentiles) were determined for TSH and fT4. TSH and fT4 concentrations were converted to multiples of the median (MoM) values. Effect of maternal age, gestational age, and maternal weight was analyzed. Statistical Analysis Quantitative variables were expressed as means and standard deviations (SD), and qualitative variables were expressed as frequencies and percentages. Normality of the data was checked using the Kolmogorov-Smirnov test. Values that were normally distributed were expressed only as means and SD. Those that were not normally distributed were expressed as medians and interquartile range. For all statistical analysis, p < 0.05 was considered as statistically significant. Results First-trimester GRI was 0.245 to 4.971 mIU/L for TSH, 10.2 to 18.9 pmol/L for fT4, and 27.0 to 56.89 kIU/L for anti-TPO. There was no significant difference in the mean serum TSH ( p = 0.920), fT4 ( p = 0.714), or anti-TPO ( p = 0.754) values among women in 4 to 7th week and 7 to 14th week of gestation. The 1st and 99th centile MoMs were 0.03 and 4.09 for TSH and 0.66 and 1.39 for fT4. There was a significant positive correlation between the maternal weight and TSH MoM values ( p = 0.027, r = 0.120). Conclusion These laboratory- and first-trimester-specific GRI for TSH and fT4 shall help in proper diagnosis and treatment of subclinical thyroid dysfunctions. TSH and fT4 MoM values can be used to indicate high or low values in a quantitative manner independent of the reference ranges and may be used by other laboratories.

Influence of laboratory biomarkers on inflammatory indices for assessing severity progression in COVID-19 cases.

Background and Objective: This study explored the role of various laboratory biomarkers on inflammatory indices for predicting disease progression toward severity in COVID-19 patients. Methods: This retrospective study was conducted on 1233 adults confirmed for COVID-19. The participants were grouped undermild, moderate, and severe grade disease. Serum bio-inflammatory index (SBII) and systemic inflammatory index (SII) were calculated and correlated with disease severity. The study variables, including clinical details and laboratory variables, were analyzed for impact on the inflammatory indices and severity status using a sequential multiple regression model to determine the predictors for mortality. Receiver operating characteristics defined the cut-off values for severity. Results: Among the study population, 56.2%, 20.7%, and 23.1% were categorized as mild, moderate, and severe COVID-19 cases. Diabetes with hypertension was the most prevalent comorbid condition. The odds for males to have the severe form of the disease was 1.6 times (95% CI = 1.18-2.18, P = 0.002). The median (inter-quartile-range) of SBII was 549 (387.84-741.34) and SII was 2097.6 (1113.9-4153.73) in severe cases. Serum urea, electrolytes, gamma-glutamyl transferase, red-cell distribution width-to-hematocrit ratio, monocytopenia, and eosinopenia exhibited a significant influence on the SpO2, SBII, and SII. Both SBII (r = -0.582, P < 0.001) and SII (r = -0.52, P < 0.001) strongly correlated inversely with SpO2 values [Figures 3a and 3b]. More than 80% of individuals admitted with severe grade COVID-19 had values of more than 50th percentile of SBII and SII. The sensitivity and specificity of SBII at 343.67 for severity were 81.4% and 70.1%, respectively. SII exhibited 77.2% sensitivity and 70.8% specificity at 998.72. Conclusion: Serial monitoring of the routinely available biomarkers would provide considerable input regarding inflammatory status and severity progression in COVID-19.

Serum testosterone level and semen quality in male patients with sickle cell disease in outpatient department of Chhattisgarh: a case-control study.

INTRODUCTION: Infertility issues in men with sickle cell disease (SCD) have been studied more frequently than those in women. Semen analysis of men with SCD often shows sperm abnormalities in up to 91%. No such study has been conducted in India so far, and Chhattisgarh being a state with a high incidence of male infertility as well as SCD, this study holds significance. OBJECTIVES: 1. To identify whether male patients attending All India Institute of Medical Sciences Outpatient Department with SCD have abnormal testosterone and/or poor semen quality. 2. Counseling of infertile male patients with SCD regarding future childbearing, prognosis, fertility preservation, and management options. METHODS: This study was an age-matched case-control study; 58 participants of age between 18-45 years were assigned in each group. RESULTS: The sperm count was higher in HbSS, while volume and pH were greater in HbAA. However, no significant difference (P>0.05) was found in total motility or progressive motility. A highly significant difference (P<0.001) was observed in pH, sperm count, total motility, and normal morphology. There was a significant difference (P=0.005) in volume. The values of the HbSS subjects were higher than the standard reference values. The values of the HbAA subjects were higher than the standard reference value. However, no significant difference (P>0.05) was found in sperm count or vitality. CONCLUSION: Men in Chhattisgarh with SCD do not suffer from any reproductive disorders such as delayed sexual maturity, low serum testosterone, poor semen quality, or hypogonadism.

A study of apolipoprotein A1(ApoA1) and interleukin-10(IL-10) in diabetes with foot ulcers.

Background: The high morbidity, mortality and associated economic burden have entailed to identifying early biomarker of diabetic foot ulcers (DFU). Pro-inflammatory and anti-inflammatory molecules play a role in the chronic inflammation associated with diabetic foot ulcers (DFU). Aim: This study aims to find the association between ApoA1, IL-10, TNF-α and diabetic foot ulcers, and whether their levels can assess the severity of the disease. Method: Two groups, diabetic mellitus without foot ulcers and diabetes with foot ulcers were recruited for the study. Detailed clinical history was obtained and blood was collected to measure TNF-α , IL-10 and Apo A1. The association between variables was analysed using Pearson correlation test. ROC analysis was used to identify cut-off values of ApoA1, IL-10 and TNF-α in diabetes patients with foot ulcers. Results: The presence of pro-inflammatory parameter, TNF-α , was higher and anti-inflammatory biomarkers, HDL, ApoA1 and IL-10 were lower in patients of DFU than those without foot ulcers (p < 0.001). Increasing age, smoking, retinopathy, eGFR and inflammatory biomarkers like low levels of ApoA1 (p < 0.005) and IL-10 (p < 0.001) significantly contributed to the development of diabetic foot ulcers. ROC curve identified the cut-off for ApoA1 and IL-10 as 89.82mg/dL and 78.80pg/mL respectively. Conclusion: In the light of this study, ApoA1 has the potential to predict DFU. The finding proposes IL-10 (b = -0.37, p < 0.001) could be considered in stratifying DFU as per its severity.

Machine learning algorithm to evaluate risk factors of diabetic foot ulcers and its severity.

Early identification of the risk factors associated with development of diabetic foot ulcer (DFU) can be facilitated using machine learning techniques. The aim of this study is to find out the association of various clinical and biochemical risk factors with DFU and develop a prediction model using different machine learning algorithms. Eighty each of type 2 diabetes mellitus (T2DM) with DFU and (T2DM) without DFU were enrolled for this observational study. Clinical and laboratory data were analysed using different machine learning algorithms: Support vector machines (SVM-Poly K), Naive Bayes (NB), K-nearest neighbour (KNN), random forest (RF) and three ensemble learners: Stacking C, Bagging and AdaBoost for constructing prediction models for discriminating between the two groups (stage I classification) and ulcer type classification (stage II classification). Ensemble learning performed better than individual classifiers in terms of various performance evaluation metrics. New risk factors like ApoA1 and IL-10 for development of DFU in diabetes mellitus were identified. IL-10 along with uric acid could discriminate the grades of ulcers according to its severity. Decision fusion strategy using Stacking C algorithm resulted in enhanced prediction accuracy for both the stages of classification which can be used as a complementary method for computational screening for DFU and its subtypes. Current methodology for T2DM with DFU/T2DM without DFU and ulcer type classification.

Plasma Interleukin-33 Cannot Predict Hip Osteonecrosis in Patients With Sickle Cell Disease: A Case-Control Study.

Background Plasma interleukin-33 (IL-33), a cytokine associated with inflammatory and autoimmune disease, has been described to be significantly raised in osteonecrosis of the femoral head (ONFH) and hence was recommended for use as a marker for ONFH. The concentration of plasma interleukin-33 level has not been estimated in any studies conducted in patients with sickle cell disease (SCD); hence, we investigated the levels of plasma interleukin-33 in patients with sickle cell disease with or without ONFH to assess whether it can be used as a marker for the early detection of ONFH in this disease also. Methods Forty-four consecutive patients with sickle cell disease with osteonecrosis of the femoral head and matched controls without ONFH were evaluated for plasma interleukin-33 levels by enzyme-linked immunosorbent assay (ELISA). All patients were confirmed for sickle cell disease using high-performance liquid chromatography (HPLC). ONFH was diagnosed in patients with sickle cell disease using clinical-radiological findings. Univariate and multivariate analyses were performed using the IL-33 level as the dependent variable. Results Plasma IL-33 levels were comparable in 44 patients with sickle cell disease with osteonecrosis of the femoral head as compared with 24 patients with sickle cell disease without ONFH (2.05 ± 4.57 pg/mL versus 1.50 ± 2.89 pg/mL, p-value = 0.590). There was no significant difference in IL-33 levels in different stages of avascular necrosis (AVN). Conclusions Plasma interleukin-33 levels cannot act as a marker of ONFH as were being considered in idiopathic ONFH or ONFH caused by other causes such as trauma and chronic steroid or alcohol usage.

Information technology-based joint preoperative assessment, risk stratification and its impact on patient management, perioperative outcome, and cost.

BACKGROUND:  Despite negative recommendations, routine preoperative testing practice is nearly universal. Our aim is to bring the healthcare providers on one platform by using information-technology based preanaesthetic assessment and evaluate the routine preoperative testing's impact on patient outcome and cost. METHODS: A prospective, non-randomised study was conducted in a teaching hospital during January 2019-August 2020. A locally developed software and cloud-computing were used as a tool to modify preanaesthesia evaluation. The number of investigations ordered, time taken, cost incurred, were compared with the routine practice. Further data were matched as per surgical invasiveness and the patient's physical status. Appropriate tests compared intergroup differences and p-value <0.05 was considered significant.  Results: Data from 114 patients (58 in routine and 56 in patient and surgery specific) were analysed. Patient and surgery specific investigation led to a reduction in the investigations by 80-90%, hospital visit by 50%, and the total cost by 80%, without increasing the day of surgery cancellation or complications. CONCLUSION: Information technology-based joint preoperative assessment and risk stratification are feasible through locally developed software with minimal cost. It helps in applying patient and surgery specific investigation, reducing the number of tests, hospital visit, and cost, without adversely affecting the perioperative outcome. The application of the modified method will help in cost-effective, yet quality and safe perioperative healthcare delivery. It will also benefit the public from both service and economic perspective.

Importance of Setting Up Reference Intervals and Multiple of Medians (MoM).

I was interested in the article of Kianpour et al. on reference intervals for thyroid hormones during the first trimester of gestation from an area with sufficient iodine level 1. The unavailability of data in this population had triggered this study where 436 pregnant and 444 non-pregnant women were recruited. I appreciate the great effort taken by the authors to recruit such a large population for the study. Following screening as per exclusion criteria 291 pregnant women were eliminated and thus the data of 145 pregnant was included for analysis. However, the article mentions the analysis of samples of 185 patients. The authors have also calculated the multiples of medians (MoM) to unitise different laboratory reports.

Antinuclear Antibody Profiling in Patients of a Tertiary Care Centre in Central India.

The incidence of autoimmune disorders that includes the connective tissue diseases has seen a rise in India in recent times. Antinuclear antibodies, the telltale sign of systemic autoimmune response, thus can be used as a screening tool and also to support the diagnosis of systemic autoimmune disease. The present retrospective cross- sectional analysis aimed to study the antinuclear antibodies profile (patterns and specific antibody reactivity) amongst suspected cases of auto-immune disorders at a tertiary care teaching hospital. The study retrieved and reviewed reports of 644 patients sent for ANA testing by indirect immunofluorescence assay over a period of 1 year by different specialty departments. Positive samples were further processed for anti-ds-DNA antibody and antibodies to extractable nuclear antigen. Data collected was statistically analysed. ANA pattern positivity was observed in 31% of cases and a positive antibody reactivity was seen in 66% of them. Female predominance (82%) was noted in both pattern positivity and antibody reactivity. High levels of pattern positivity and antibody reactivity was found in the young adults (45.9%). Amongst the ANA patterns, the nuclear homogenous pattern was found the commonest. The common antibodies associated with this pattern were anti-dsDNA and U1 Sm/RNP antibodies. A stronger fluorescence intensity on initial screening showed a higher confirmation rate for specific antibodies on immunoassay. High occurrence of positive ANA patterns in autoimmune disorders suggests its utilization as a screening tool for them and would also play an adjuvant to the diagnosis. Early knowledge about future autoimmunity will earn better prognostic achievements through better treatment interventions.

Immuno-inflammatory predictors of disease severity in COVID-19: A systematic review and meta-analysis.

Deregulated immune response and raised inflammation are the cardinal laboratory features in COVID-19 infection reflecting severity of condition. Detection of the markers will help in early diagnosis with timely therapeutic implementation and effective outcome. Observational studies have suggested alteration in these parameters with severity of the condition. This systematic review and meta-analysis was conducted to assess the relevance of the fact. Observational studies from databases were scrutinised and 3669 articles were identified. Further screening, based on the inclusion criteria a total of 19 articles with 3115 participants, were reviewed for meta-analysis using random effects model. Any data in median and interquartile range were converted to mean ± SD. There was a significant rise in total leukocyte count, C-reactive protein, ferritin, IL-6, IL-10, procalcitonin in severe cases but absolute lymphocyte count, CD4+ and CD8+ registered a fall in severe cases in comparison to non-severe group. Immune and inflammatory markers are significantly altered and related to severity of manifestation in COVID-19 infection.