Presentation and outcome of pediatric lupus nephritis from a large single centre contemporary cohort in Eastern India.

BACKGROUND: We present clinical, biochemical, and histopathological characteristics and treatment outcomes of biopsy proven childhood lupus nephritis (LN) from a low/middle income setting treated in the current era of increased use of Mycophenolate Mofetil (MMF) and biologics. METHODS: Retrospective observational study of children (1-18 years) with biopsy proven LN treated from 01.01.2010 to 31.01.2020. RESULTS: 60 children met our inclusion criteria (80%, n = 48 were females). The median age at diagnosis was 11 (IQR: 9-12) years. The most common extra-renal manifestation was mucocutaneous (n = 54, 90%) and the most common kidney manifestation was edema (n = 50, 83.3%). The median 24-h urinary protein excretion was 1117.8 (IQR: 795.4-1941.7) mg/m2/day with 67% (n = 40) having nephrotic range proteinuria (>1000 mg/m2/day). 75% (n = 45) children had eGFR <90 mL/min/1.73 m2 (median eGFR = 71; IQR: 56-90 mL/min/1.73 m2). Anti-Nuclear Antibody was positive in all, both complement three and four were low in 82% (n = 49) and anti-double stranded DNA antibodies were positive in 63% (n = 38). 85% (n = 51) had proliferative LN with majority being class IV (57%, n = 34). All children received steroids for induction therapy. MMF was given as the sole induction agent in 48% (n = 29) and cyclophosphamide in 27% (n = 16). Rituximab was added in 17% (n = 10) as a rescue agent. Median follow up duration was 50 (IQR: 28-82) months. Six children (10%) died as a result of serious infections and none of them had shown complete response (CR). Out of the 52 children who had a follow up duration of at least 2 years, CR was achieved in 46 children (88%) and partial response (PR) or no response (NR) in three children (6%) each. Although children who were in CR/PR at last follow up had lower proteinuria, higher eGFR, and lower histopathology activity index at onset; low numbers in the NR group precluded us from subjecting them to any statistical correlation tests. 36% (n = 22) of children developed 36 episodes of renal flares with overall incidence of 0.14/person-year. CONCLUSION: Our study on a contemporary cohort of childhood LN highlights the importance of achieving CR and its feasibility.

Vitamin C and E supplementation can ameliorate NaF mediated testicular and spermatozoal DNA damages in adult Wistar rats.

OBJECTIVE: Present study was designed to explore the efficacy of vitamin C and E (VC&VE) against fluoride mediated testicular, epididymal and spermatozoal anomalies. MATERIALS AND METHODS: Thirty two adult Wistar rats were divided into four groups. Group-I was control; Group-II received sodium fluoride (NaF) at 15 mg/kg/day dose; Group-III was provided with VC (200 mg/kg/day) and VE (400 mg/kg/day) plus NaF; Group-IV received only VC&VE. Structural integrity and oxidative stress markers (superoxide dismutase, catalase, malondialdehyde and protein carbonyl) of testis and epididymis were assessed. Spermatozoal parameters (count, motility, viability and hypo-osmotic swelling) were evaluated. Testicular functional maker enzymes (acid phosphatase, alkaline phosphatase and lactate dehydrogenase) were also assessed. Integrity of testicular and spermatozoal DNA was evaluated. Testicular fluoride content was measured. RESULT: Fluoride induced structural changes and alterations of oxidative stress markers were observed in testis and epididymis. Spermatozoal potentials were altered and reduced activities of testicular functional marker enzymes were observed. Fluoride caused testicular and spermatozoal DNA damages. VC&VE supplementation resulted in protection from all fluoride mediated alterations and helped in attenuating testicular fluoride accumulation. CONCLUSION: Antioxidant properties of VC&VE ameliorated fluoride mediated reproductive damages but only supplementation did not exhibit any notable effect compared to control rats.

Fluoride induced testicular toxicities in adult Wistar rats.

Fluoride is essential for the development of teeth and bone but its excessive exposure causes reprotoxic effects. We have studied the graded effects of different doses of sodium fluoride (NaF) on 24 adult Wistar rats which were randomly divided into four groups (n = 6). All the rats were given normal diet prepared in our laboratory. Control (group I) rats were received vehicle only and treated rats (group II, III, and IV) were administered NaF orally at 10, 15, and 20 mg/kg/d doses, respectively, for 30 consecutive days. Gravimetric index of testis was decreased significantly in group III and IV rats but such changes were not observed in the accessory reproductive organs. Marked alterations in number, motility, viability, and plasma membrane functional integrity of caudal spermatozoa were noted in most of the treated groups. Noticeable alterations in testicular histoarchitecture were observed in group III and IV rats. Graded Changes of testicular redox homeostasis were noted by assessment of enzymatic (superoxide dismutase [SOD], catalase, glutathione s-transferase [GST], and glutathione peroxidase [GPx]) and nonenzymatic (malondialdehyde [MDA] and protein carbonyl [PC]) markers. Changes of testicular functional markers (acid phosphatase [ACP], alkaline phosphatase [ALP], and lactate dehydrogenase (LDH) activity) were noted in group III and IV rats. DNA fragmentation assay proved the possibility of DNA damage caused by oxidative stress, as evidenced by prominent trailing pattern of fragmented testicular genomic DNA from group III and IV rats. The study concludes that fluoride-mediated oxidative stress not only impedes the structural and functional facets of testis but also results in testicular DNA damage.

Development and initial validation of a composite disease activity score for systemic juvenile idiopathic arthritis.

OBJECTIVE: To develop a composite disease activity score for systemic JIA (sJIA) and to provide preliminary evidence of its validity. METHODS: The systemic Juvenile Arthritis Disease Activity Score (sJADAS) was constructed by adding to the four items of the original JADAS a fifth item that aimed to quantify the activity of systemic features. Validation analyses were conducted on patients with definite or probable/possible sJIA enrolled at first visit or at the time of a flare, who had active systemic manifestations, which should include fever. Patients were reassessed 2 weeks to 3 months after baseline. Three versions were examined, including ESR, CRP or no acute-phase reactant. RESULTS: A total of 163 patients were included at 30 centres in 10 countries. The sJADAS was found to be feasible and to possess face and content validity, good construct validity, satisfactory internal consistency (Cronbach's alpha 0.64-0.65), fair ability to discriminate between patients with different disease activity states and between those whose parents were satisfied or not satisfied with illness outcome (P < 0.0001 for both), and strong responsiveness to change over time (standardized response mean 2.04-2.58). Overall, these properties were found to be better than those of the original JADAS and of DAS for RA and of Puchot score for adult-onset Still's disease. CONCLUSION: The sJADAS showed good measurement properties and is therefore a valid instrument for the assessment of disease activity in children with sJIA. The performance of the new tool should be further examined in other patient cohorts that are evaluated prospectively.

A comparison of serum IL6 and CRP levels with respect to coronary changes and treatment response in Kawasaki disease patients: a prospective study.

To evaluate serum levels of IL6 in patients with Kawasaki disease and compare it with CRP, and to assess the role of these biomarkers in predicting coronary changes and resistance to the first-line therapy of this disease in a subset of Indian population. A single centre prospective observational study was conducted amongst all Kawasaki disease patients for a period of 18 months from January 2017 at Institute of Child Health, Kolkata. Serum IL6 and CRP were compared at diagnosis and after 48 h of administering IVIG in patients who developed coronary changes with those who did not and also among the responders and non-responders to IVIG, the first-line therapy given to these patients. Out of total 72 patients of KD [mean age of presentation: 24 months, M:F = 1.22:1], 30% (n = 22) had coronary artery involvement (CALs), and 15% (n = 11) were IVIG non-responders. Mean IL6 prior to IVIG in those with CALs was 143.60 pg/ml, which was about three times higher than in those without CALs (mean = 52.90 pg/ml), the difference being significant (p < 0.01). Mean CRP values also were significantly raised in patients with CALs (p < 0.01) whereas post-IVIG levels of mean serum IL6 was found to be 108.15 pg/ml in non-responders which was about 17 times raised than that in the responders (mean IL6 = 6.22),the difference again was statistically significant (p < 0.001).Also, ROC analysis revealed a sensitivity and specificity of 81.0% and 82.0%, respectively, for IL6; 72% and 74%, respectively, for CRP for predicting CALs. This study also shows a sensitivity of 72% and specificity of 68% for IL6 in predicting IVIG resistance whereas that of CRP being 90% sensitive and 36% specific. These results suggest that higher levels of IL-6 and CRP at diagnosis are associated with occurrence of CALs and IVIG resistance in KD patients. Using the cutoff for IL6 and CRP from our study, chances of developing CALs and IVIG resistance can be predicted, which might prevent the development of future complications like aneurysms in such patients.

A Young Child with Eosinophilia, Rash, and Multisystem Illness: Drug Rash, Eosinophilia, and Systemic Symptoms Syndrome After Receipt of Fluoxetine.

Drug rash, eosinophilia, and systemic symptoms (DRESS) syndrome is a severe systemic hypersensitivity reaction that usually occurs within 6 weeks of exposure to the offending drug. Diagnosis is usually straightforward in patients with pyrexia, skin rash, hepatitis, and eosinophilia with a preceding history of exposure to agents often associated with DRESS syndrome, such as aromatic anticonvulsants and sulfa drugs, but diagnosis of DRESS may still be a challenge. We report a 4-year-old child with probable DRESS syndrome complicated by multiple hematologic complications that developed 1 month after exposure to fluoxetine, a drug not known to be associated with such severe reactions.

Co-administration of L-Ascorbic Acid and α-Tocopherol Alleviates Arsenic-Induced Immunotoxicities in the Thymus and Spleen by Dwindling Oxidative Stress-Induced Inflammation.

Herein, we investigated whether L-ascorbic acid (L-AA) and α-tocopherol (α-T) co-administration has the potential to alleviate arsenic-induced immunotoxicities in the thymus, spleen, and circulating leukocytes. Forty-eight adult male Wistar rats were randomly divided into four groups before the treatment: group I (control); group II (sodium arsenite, 3 mg/kg/day/rat); group III (sodium arsenite + L-AA (200 mg/kg/day/rat) and α-T (400 mg/kg/day/rat)); group IV (L-AA and α-T). The result showed that sodium arsenite exposure (consecutive 30 days) caused weight reduction, structural alterations in the thymus and spleen, accompanied by a decrease in thymocyte and splenocyte count. Decreased superoxide dismutase and catalase activity, increased malondialdehyde and protein-carbonyl content, reduced Nrf2 and Bcl2 expression, and increased p-ERK, NF-kß, Bax, and cleaved-caspase-3 expression were also observed in the thymus and spleen of arsenic-exposed rats. Enhanced plasma ACTH and corticosterone, ROS-induced apoptosis of lymphocytes were also observed. L-AA and α-T co-administration has the potential to abrogate the deleterious impact of arsenic on the thymus, spleen, and circulating lymphocytes. Whole transcriptome analysis of leukocytes revealed that arsenic treatment augmented the expression of Itga4, Itgam, and MMP9 genes, which might help in transient migration of the leukocytes through the endothelial cell layer. Co-administration with L-AA and α-T maintained Itga4, Itgam, and MMP9 gene expression within leukocytes at a lower level.

A child with recurrent headache, fever and diffuse meningeal enhancement on MRI.

Juvenile neurolupus presents primarily with neuropsychiatric manifestations which may also be the initial presentation. Such primary neuropsychiatric SLE (NPSLE) events are a consequence either of microvasculopathy and thrombosis, or of autoantibodies and inflammatory mediators. Diagnosis of NPSLE requires the exclusion of other causes, and clinical assessment directs the selection of appropriate investigations. These investigations include measurement of autoantibodies, analysis of cerebrospinal fluid, electrophysiological studies, neuropsychological assessment and neuroimaging to evaluate brain structure and function. In our patient, the disease presented with chronic headache initially diagnosed as migraine, followed by fever and paraparesis. Fundoscopy showed retinal haemorrhages. Investigations revealed anaemia, neutrophilic leucocytosis, thrombocytopenia and raised inflammatory markers (ESR 119 mm/h CRP 58 mg/L) and high globulin. MRI brain showed diffuse meningeal enhancement resembling meningitis but CSF analysis was normal. ANA and dsDNA were positive with low C3, C4. All diffuse meningeal enhancements may not be meningitis and one needs to corroborate all the clinical, biochemical and imaging analyses to come to a diagnosis.

Defining Criteria for Disease Activity States in Systemic Juvenile Idiopathic Arthritis Based on the Systemic Juvenile Arthritis Disease Activity Score.

OBJECTIVE: Our objective was to develop and validate cutoff values in the systemic Juvenile Arthritis Disease Activity Score 10 (sJADAS10) that distinguish the states of inactive disease (ID), minimal disease activity (MDA), moderate disease activity (MoDA), and high disease activity (HDA) in children with systemic juvenile idiopathic arthritis, based on subjective disease state assessment by the treating pediatric rheumatologist. METHODS: The cutoff definition cohort was composed of 400 patients enrolled at 30 pediatric rheumatology centers in 11 countries. Using the subjective physician rating as an external criterion, six methods were applied to identify the cutoffs: mapping, calculation of percentiles of cumulative score distribution, the Youden index, 90% specificity, maximum agreement, and receiver operating characteristic curve analysis. Sixty percent of the patients were assigned to the definition cohort, and 40% were assigned to the validation cohort. Cutoff validation was conducted by assessing discriminative ability. RESULTS: The sJADAS10 cutoffs that separated ID from MDA, MDA from MoDA, and MoDA from HDA were ≤2.9, ≤10, and >20.6, respectively. The cutoffs discriminated strongly among different levels of pain, between patients with and without morning stiffness, and among patients whose parents judged their disease status as remission or persistent activity or flare or were satisfied or not satisfied with current illness outcome. CONCLUSION: The sJADAS cutoffs revealed good metrologic properties in both definition and validation cohorts and are therefore suitable for use in clinical trials and routine practice.

Orange-brown chromonychia, a novel finding in Kawasaki disease.

Kawasaki disease (KD) is one of the commonest vasculitis of childhood, where diagnosis is clinical based on a plethora of signs and symptoms. One of the typical findings is the changes in the extremities including the nail changes. Orange-brown chromonychia is a colour change in the nails which has been observed in some cases of KD. Here, we report a series of 40 patients of KD, where a typical transverse orange-brown discolouration of nails or chromonychia was noted in 29 patients. Though chromonychia is noted in many other rheumatic and nonrheumatic diseases, the typical transverse orange-brown chromonychia observed in KD patients can be included as an additional clinical feature in diagnosis of KD.

Infection-associated haemophagocytic lymphohistiocytosis: a case series using steroids only protocol for management.

Haemophagocytic lymphohistiocytosis (HLH) is a heterogeneous group of clinical syndromes characterised by activation and subsequent uncontrolled non-malignant proliferation of T lymphocytes and macrophages, leading to a cytokine storm that accounts for most of its clinical features such as acute febrile illness, hepatosplenomegaly, multi-organ dysfunction and fulminant pancytopenia-resembling severe sepsis. Here, we present a series of 23 cases of infection-associated HLH diagnosed in our hospital within a time period of last three and half years. Though the presentation and progression of disease was variable, the patients shared some common features like prolonged fever unresponsive to broad spectrum antibiotics, organomegaly and cytopenias. In most of the cases, however, the triggering infectious agent could not be identified. They were treated using a steroid only protocol along with supportive measures and showed an excellent response.

Casein and pea enriched high-protein diet attenuates arsenic provoked apoptosis in testicles of adult rats.

Arsenic toxicity is a major health issue that also threats male reproductive system leading to impairment of fertility. The antioxidant capacity of casein and pea enriched formulated high-protein diet (FHPD) is found to be effective in different toxicity management. The present study was endeavored to investigate the mitigatory aspect of FHPD on arsenic stimulated testicular apoptosis. Adult male rats were maintained on either normal diet as control (Gr I, n = 8) and arsenic (As2O3) treated at a dose of 3 mg/kg/rat/day (Gr II, n = 8) or on isocaloric FHPD as supplemented (Gr III, n = 8) with same dose of arsenic for 30 consecutive days. Testicular histomorphometry, spermatokinetics, testicular functional marker enzymes, serum gonadotrophins, oxidative stress markers, testicular deoxyribonucleic acid (DNA) damage, and apoptosis markers were evaluated to assess the reprotoxicity of arsenic and subsequent protection by FHPD. FHPD protected the histopathological alterations and also restored normal spermatogenesis. Altered enzymatic activities of testicular functional markers like lactate dehydrogenase, γ-glutamyl transferase, acid phosphatase, and alkaline phosphatase were also regularized. FHPD also reinstated the normal level of follicle stimulating hormone (FSH), luteinising hormone (LH), and also normalized the enzymatic activities of testicular glutathione peroxidase and glutathione reductase. Testicular DNA damage was also prevented by FHPD supplementation. Testicular apoptosis marked by the altered messenger ribonucleic acid and protein expression of apoptotic markers like Bax, Bcl-2, caspase 9, and caspase 3 were also attenuated upon FHPD supplementation along with diminution of arsenic accumulation in testicular tissues. FHPD not only mitigated the adverse effects of arsenic induced gonadotoxicity but also helped in sustaining the normal reproductive functions.

Multisystem Inflammatory Syndrome in Children (MIS-C): Comparison of the First and the Second Waves.

This study comparing the different parameters of children suffering from multisystem inflammatory syndrome in children (MIS-C) in Kolkata, India, during the two waves (July, 2020-January, 2021 and April-July, 2021) showed that the second wave had a higher propensity of Kawasaki disease (KD)-like presentation, cardiac affection and pediatric intensive care unit admission, and increased incidence of use of steroids for treatment.

N-Terminal Pro-Brain Natriuretic Peptide Levels in Kawasaki Disease, Sepsis and Other Febrile Illnesses.

OBJECTIVE: To compare the values of N-Terminal Pro-Brain Natriuretic Peptide (NT-proBNP) in acute phase of Kawasaki disease (KD), sepsis and other acute febrile illnesses. METHODS: We conducted a cross-sectional study on 40 KD patients and 40 age- and sex-matched controls with sepsis and other febrile illnesses between January, 2019 and June, 2020. Complete blood count, C-reactive protein (CRP), liver and renal function tests, serum electrolytes, chest X-ray, NT-proBNP level, Bactec blood culture, urine microscopy and culture along with detailed physical examination was done for all cases and control. RESULTS: Mean (SD) values of NT-proBNP levels in acute KD was higher than sepsis/other febrile illnesses (914.9 vs 219 pg/mL; P=0.001). Also, the number of KD patients whose NT-proBNP was elevated were significantly higher compared to controls (70% vs 32.5%; P<0.001). CONCLUSION: NT-proBNP may be useful as a biomarker in the diagnosis of acute phase KD.

Risk factors in IVIG-resistant Kawasaki disease and correlation with Japanese scoring systems - a study from Eastern India.

OBJECTIVES: To assess the risk factors of intravenous immunoglobulin (IVIG)-resistant Kawasaki disease (KD) and to evaluate the performance of the three Japanese risk-scoring systems, namely the Kobayashi, Egami, and Sano scores in predicting IVIG resistance among the Indian patients. METHODS: Prospective observational study on children admitted with KD at Institute of Child Health, Kolkata, over a period of 16 months, from January 2019 to April 2020. The study included 70 KD patients all of whom were treated with IVIG. Clinical parameters, laboratory variables, and risk scores were compared between the IVIG-responsive and the IVIG-resistant groups. RESULTS: A total of 31.4% were IVIG non-responders. Skin rash was found to be significantly associated with IVIG-resistant KD. The IVIG-resistant group had higher total bilirubin, lower albumin, higher CRP levels, and higher ALT and AST levels. High Kobayashi score, high Egami score, and high Sano score were significantly associated with IVIG resistance, individually. Sano score had the highest sensitivity (81.8%) and Kobayashi score had the highest specificity (77.1%) in our cohort. CONCLUSION: The presence of skin rash, high total bilirubin, high CRP, high AST, high ALT, and low albumin were important predictors of IVIG resistance in our population. Among the three scores, Sano score is the most reliable in identifying potential non-responders to IVIG. But Sano score lacked good specificity. Therefore, Indian KD patients may need an exclusive scoring system to predict non-responsiveness to IVIG so that a more aggressive therapy can be instituted at the earliest. Key points • Early prediction of IVIG-resistant KD is necessary to limit cardiac injuries. • Sano score has high sensitivity to predict IVIG resistance in Indian population.

Attenuation of sodium arsenite mediated ovarian DNA damage, follicular atresia, and oxidative injury by combined application of vitamin E and C in post pubertal Wistar rats.

Arsenic being a toxic metalloid ubiquitously persists in environment and causes several health complications including female reproductive anomalies. Epidemiological studies documented birth anomalies due to arsenic exposure. Augmented reactive oxygen species (ROS) generation and quenched antioxidant pool are foremost consequences of arsenic threat. On the contrary, Vitamin E (VE) and C (VC) are persuasive antioxidants and conventionally used in toxicity management. Present study was designed to explore the extent of efficacy of combined VE and VC (VEC) against Sodium arsenite (NaAsO2) mediated ovarian damage. Thirty-six female Wistar rats were randomly divided into three groups (Grs) and treated for consecutive 30 days; Gr I (control) was vehicle fed, Gr II (treated) was gavaged with NaAsO2 (3 mg/kg/day), Gr III (supplement) was provided with VE (400 mg/kg/day) & VC (200 mg/kg/day) along with NaAsO2. Marked histological alterations were evidenced by disorganization in oocyte, granulosa cells and zona pellucida layers in treated group. Considerable reduction of different growing follicles along with increased atretic follicles was noted in treated group. Altered activities ofΔ5 3ß-Hydroxysteroid dehydrogenase and 17ß-Hydroxysteroid dehydrogenase accompanied by reduced luteinizing hormone, follicle-stimulating hormone and estradiol levels were observed in treated animals. Irregular estrous cyclicity pattern was also observed due to NaAsO2 threat. Surplus ROS production affected ovarian antioxidant strata as evidenced by altered oxidative stress markers. Provoked oxidative strain further affects DNA status of ovary. However, supplementation with VEC caused notable restoration from such disparaging effects of NaAsO2 toxicities. Antioxidant and antiapoptotic attributes of those vitamins might be liable for such restoration.

Molecular basis of fluoride toxicities: Beyond benefits and implications in human disorders.

Detrimental impacts of fluoride have become a global concern for several decades. Despite its beneficial role which is restricted only in skeletal tissues, deleterious effects are also observed in soft tissues and systems. The generation of enhanced oxidative stress is the commencement of excess fluoride exposure which may lead to cell death. Fluoride causes cell death through autophagy via Beclin 1 and mTOR signaling pathways. Beside these, several organ specific anomalies through different signaling pathways have been documented. Mitochondrial dysfunction, DNA damage, autophagy and apoptosis are the damaging outcomes in case of hepatic disorders. Urinary concentration defects and cell cycle arrest have been reported in renal tissues. Abnormal immune response has been characterized in the cardiac system. Cognitive dysfunction, neurodegenerative condition and learning impairment have also been observed. Altered steroidogenesis, gametogenic abnormalities, epigenetic alterations and birth defect are the major reprotoxic conclusions. Abnormal immune responses, altered immunogenic proliferation, differentiation as well as altered ratio of immune cells are well-defined anomalies in the immune system. Though the mechanistic approach of fluoride toxicity in physiological systems is common, it follows different signaling cascades. This review emphasizes diverse signaling pathways which are the targets of overexposed fluoride.

A comparative study of IL-6, CRP and NT-proBNP levels in post-COVID multisystem inflammatory syndrome in children (MISC) and Kawasaki disease patients.

BACKGROUND: Post-COVID multisystem hyperinflammatory syndrome in children (MISC) has clinical and laboratory similarities with Kawasaki disease (KD). Inflammatory markers like C-reactive protein (CRP), interleukin 6 (IL6) as well as N-terminal probrain natriuretic peptide (NT-proBNP) are elevated in both. This study attempts a comparative analysis of the 3 markers in an attempt at early differentiation for planning appropriate management. METHODOLOGY: This analytical study conducted at the Institute of Child Health, Kolkata, India compared the levels of the above 3 markers at admission between 72 patients with KD, 30% of whom had coronary artery lesions (CALs) collected over a period of 18 months (Jan 2017-June 2018), with 71 MISC patients over a period of 6 months (July 2020-December 2020). The non-parametric Mann-Whitney U test was used to test for similarity in distributions of the samples of CRP, NT-proBNP and IL6 in KD and MISC patients using correction factor for similar ranks. The 3 parameters were compared using receiver operating characteristic (ROC) curve analysis. RESULTS: Mean IL6 value in KD was 83.22 pg/mL and in MISC 199.91 pg/mL, which was not found to be statistically significant (P = .322 > .05).However mean NT-proBNP (914.91 pg/mL) with CRP level (96.32 mg/L) in KD was significantly lower (P < .05 for both cases) than that in MISC (9141.16 pg/mL and 145.66 mg/L respectively). ROC analysis showed NT-proBNP has the best sensitivity and specificity in predicting MISC. CONCLUSION: NT-proBNP and CRP are significantly higher among MISC patients; ROC analysis shows levels >935.7 pg/mL and >99.55 mg/L respectively might act as a guide to differentiate between them.