Comparison of thrombolytic agents in treatment of patients with acute ischemic stroke; findings from a single centre follow up study in real-life settings.

BACKGROUND AND OBJECTIVES: Health outcome data of thrombolysis in patients with acute ischemic stroke in real life-settings in India are scarce. We studied the clinical profile, risk factors and functional outcome of patients with acute ischemic stroke (AIS) who were thrombolysed. METHODS: In a single centre retrospective study from January 2017 to June 2020, we analysed the data of adult patients with AIS presented within 4.5 h of symptom onset. We included patients if they had NIHSS score ≥4, modified Rankin score of 2 or less before the stroke onset and without evidence of haemorrhage. Modified Rankin score of two or less at the end of three months was defined as the primary efficacy outcome. The development of symptomatic intracerebral haemorrhage was considered as the primary safety outcome. We tried to analyse the primary safety and efficacy outcomes between two thrombolytic agents. RESULTS: Ninety patients (Tenecteplase = 61; Alteplase, n = 29) underwent stroke thrombolysis during the study period. The mean age was 64.3 years in Tenecteplase group and 63.2 years in Alteplase group. Twenty patients were aged more than 75 years. Hypertension was the most common comorbidity in both the groups (72% and 72.4%). Median mRS score at 3-months was 1 in Tenecteplase group and 0.5 in Alteplase group (p < 0.001), however there was no statistically significant difference between both treatment groups in terms of NIHS score at 24 h (70.4% vs 51.7%, p = 0.08), functional recovery calculated with mRS at 3-month (83.6% vs 79.3%, p = 0.62) or in terms of symptomatic ICH (9.8% and 17.2% p = 0.36). CONCLUSION: Tenecteplase appears to have similar clinical outcomes as Alteplase for stroke thrombolysis. Given the relatively low-cost and ease of administration, Tenecteplase may be better than Alteplase for management of acute ischemic stroke.

Neurological Disorders Seen During Second Wave of SARS-CoV-2 Pandemic from Two Tertiary Care Centers in Central and Southern Kerala.

Background and Objective: SARS-CoV-2 infections present with predominant respiratory symptoms. Only a few anecdotal reports of neurological involvement have come out from India so far. Adverse neurological events following immunization (AEFI) were also reported. We present the neurological symptoms seen either in association with vaccination or COVID-19 infection during the second wave. Methods: This was a retrospective study that included consecutive COVID-19 patients' admissions during the second wave of COVID-19 pandemic in two tertiary health care centres in Kerala. Neurological symptoms two weeks prior or thirty days after a positive status of antigen or RTPCR was termed as COVID-19-Associated Neurological Disorders (CAND) and those with neurological symptoms within one month of COVID-19 vaccination was termed as Post-Vaccinal Neurological Disorders (PVND). Results: During the study period, 1270 COVID-19 admissions were reported. We identified neurological symptoms in 42 patients (3.3%), of which 35 were CAND and 7 were PVND. Stroke was the most common (50%), followed by seizures and peripheral nervous system disorders (14.2% each). Encephalitis/demyelination (11.9%) and COVID-19-associated infections (9.5%) were also seen. Conclusion: During the SARS-CoV-2 pandemic, CAND and PVND have been emerging. Association of some of these may be fortuitous; however it is worth mentioning as pathogenic mechanisms of COVID-19 affecting various organ systems still remain unclear. Moreover, this may be helpful in future studies designing management options.

Spotted fever rickettsiosis presenting with bilateral anterior uveitis and retinitis: A case report.

Spotted fever is a common rickettsial disease in India. It is caused by Rickettsia conorii, which demonstrates vascular tropism and causes endothelial injury. Ocular manifestations include multifocal retinitis and disc edema. Anterior uveitis as a presenting feature of spotted fever is uncommon. We present a 32-year-old man with spotted fever and bilateral anterior uveitis.

Multiscale connected chain topological modelling for microcalcification classification.

Computer-aided diagnosis (CAD) systems can be employed to help classify mammographic microcalcification clusters. In this paper, a novel method for the classification of the microcalcification clusters based on topology/connectivity has been introduced. The proposed method is distinct from existing techniques which concentrate on morphology and texture of microcalcifications and surrounding tissue. The proposed approach used multiscale morphological relationship of connectivity between microcalcifications where connected chains between nearest microcalcifications were generated at each scale. Subsequently, graph connectivity features at each scale were extracted to estimate the topological connectivity structure of microcalcification clusters for benign versus malignant classification. The proposed approach was evaluated using publicly available digitized datasets: MIAS and DDSM, in addition to the digital OPTIMAM dataset. The classification of features using KNN obtained a classification accuracy of 86.47±1.30%, 90.0±0.00%, 82.5±2.63%, 76.75±0.66% for the DDSM, MIAS-manual, MIAS-auto and OPTIMAM datasets respectively. The study showed that topological/connectivity modelling using a multiscale approach was appropriate for microcalcification cluster analysis and classification; topological connectivity and distribution can be linked to clinical understanding of microcalcification spatial distribution.

Comparative Study on Local Binary Patterns for Mammographic Density and Risk Scoring.

Breast density is considered to be one of the major risk factors in developing breast cancer. High breast density can also affect the accuracy of mammographic abnormality detection due to the breast tissue characteristics and patterns. We reviewed variants of local binary pattern descriptors to classify breast tissue which are widely used as texture descriptors for local feature extraction. In our study, we compared the classification results for the variants of local binary patterns such as classic LBP (Local Binary Pattern), ELBP (Elliptical Local Binary Pattern), Uniform ELBP, LDP (Local Directional Pattern) and M-ELBP (Mean-ELBP). A wider comparison with alternative texture analysis techniques was studied to investigate the potential of LBP variants in density classification. In addition, we investigated the effect on classification when using descriptors for the fibroglandular disk region and the whole breast region. We also studied the effect of the Region-of-Interest (ROI) size and location, the descriptor size, and the choice of classifier. The classification results were evaluated based on the MIAS database using a ten-run ten-fold cross validation approach. The experimental results showed that the Elliptical Local Binary Pattern descriptors and Local Directional Patterns extracted most relevant features for mammographic tissue classification indicating the relevance of directional filters. Similarly, the study showed that classification of features from ROIs of the fibroglandular disk region performed better than classification based on the whole breast region.

Integrating lipid screening with ideal cardiovascular health assessment in pediatric settings.

Pediatric lipid screening and management with the aim of reducing and preventing adult disease is an internationally accepted concept, and guidelines have been published in several countries. However, implementation by the practicing pediatric community in the United States has been less than expected and delays have been attributed to uncertainty among providers. Reduced screening rates have also been reported for conditions contributing to arterial wall pathology such as obesity, hypertension, and prediabetes despite accumulating evidence that detection and intervention can lead to risk reversal. Consistent with graded and evidence-based national guidelines for comprehensive cardiovascular risk assessment and management, we present how the American Heart Association ideal cardiovascular health (ICVH) model can be integrated with lipid screening, and how it can be compatible with comprehensive pediatric lipidology practice and enhanced familial hypercholesterolemia detection. Since being introduced and retrospectively validated in adults and children in cross-sectional studies, ICVH evaluates thresholds for seven ideal health metrics representing measurements of obesity, dyslipidemia, diabetes risk, and blood pressure, and includes exercise, diet, and smoking behaviors. When each metric is valued as a point, the maximum health score is 7, but national surveys have shown unacceptable low scores in adolescence. Inverse correlation of scores with arterial structural change supports use of ICVH as a collection of treatable targets forming a cardiovascular prevention construct including and supporting lipid screening in pediatric settings, but implementation in clinical practice requires more expertise and administrative support than lipid screening alone.

Feasibility of Ideal Cardiovascular Health Evaluation in a Pediatric Clinic Setting.

The feasibility of "point-of-care" screening for ideal cardiovascular health was explored in a pediatric specialty clinic setting. Children and adolescents aged 9-18 years (n=91) with treated and stabilized diseases were recruited at a pediatric endocrinology clinic. A table-top device was used to assay fingerstick samples for non-HDL cholesterol (non-HDL-C), which was used to divide participants into two groups based on the non-HDL-C threshold for comparison of the remaining metrics between groups. A significant number of children had low scores, and score frequency distribution was similar to larger retrospective studies, with few participants achieving none or all of the health metrics. Healthy diet was the metric least often achieved. Those with a non-HDL-C above the ideal threshold of 3.1 mmol/L (120 mg/dl) had a higher BMI percentile (p<0.01) and diastolic blood pressure percentile (p<0.05). We conclude that pediatric risk factor screening and scoring can be performed in a specialty clinic with meaningful cardiovascular health scores for patients and providers. Association of abnormal "point-of care" non-HDL-C levels with elevated BMI and blood pressure supports evidence for risk factor clustering and use of the ideal health construct in pediatric clinic settings.

Human immune deficiency virus (HIV) infection and the hypothalamic pituitary adrenal axis.

The hypothalamic pituitary adrenal (HPA) axis is the most common of the endocrine lines/axis' to be affected by HIV infection. There are multiple factors that contribute to this HPA axis dysregulation. Direct invasion of the various organs in the axis can be either by opportunistic infections or infiltrative diseases. The soluble factors or cytokines released during viral infection and the chronic inflammatory state that follows, also contribute to these alterations. The actions of these cytokines released by the immune response can both activate the HPA axis and cause a glucocorticoid resistant state. Further, many of the anti-retroviral and other medications used to treat HIV infection can contribute to HPA axis dysfunction. While the diagnosis and treatment of endocrine dysfunction is the same as in any other patient, management pathways may be quite different. While some may be adaptive responses, life threatening adrenal insufficiency can also be present. It is important the latter be picked up expeditiously and treated promptly to avoid mortality.

Current treatment options for type 2 diabetes mellitus in youth: today's realities and lessons from the TODAY study.

The incidence of type 2 diabetes in children and adolescents has increased over the last 2 decades, paralleled by an increase in obesity over the same time period. Although the value of lifestyle modification in obese youth is unquestioned, scant evidence for optimal treatment of type 2 diabetes in this age group exists. Despite recent therapeutic drug trials, metformin and insulin are the only medicines currently approved by the U.S. Food and Drug Administration for the treatment of type 2 diabetes in youth. Because of recently amended pharmaceutical regulations, however, it is likely that more antidiabetic medications soon will be added to the armamentarium of therapeutic options for youth with type 2 diabetes. Additionally, the recently published TODAY study comparing safety and efficacy of three treatment regimens in maintaining glycemic control in youth with type 2 diabetes has shed new light on the problem.

Role of 11ßHSD type 2 enzyme activity in essential hypertension and children with chronic kidney disease (CKD).

BACKGROUND: The mineralocorticoid receptor is protected from excess of glucocorticoids by conversion of active cortisol to inactive cortisone by enzyme 11ß-hydroxysteroid dehydrogenase type 2 present in the kidney. The metabolites of cortisol and cortisone are excreted in the urine as tetrahydrocortisol (5αTHF+5ßTHF) and tetrahydrocortisone (THE), respectively. HYPOTHESIS: Patients with chronic kidney disease (CKD) and essential hypertension have a functional defect in their ability to convert cortisol to cortisone, thus leading to the activation of mineralocorticoid receptor. OBJECTIVE: The objective of the investigation was to study the ratio of urinary steroids (5αTHF+5ßTHF) to THE in patients with CKD, postrenal transplant, and essential hypertension and to compare the ratio with controls. DESIGN/METHODS: We enrolled 44 patients (17 with CKD, eight postrenal transplant, 19 with essential hypertension) and 12 controls. We measured spot urinary 5α-THF, 5ß-THF, THE, free active cortisol and inactive cortisone by gas chromatography/mass spectrometry. We collected data on age, sex, cause of kidney disease, height, weight, body mass index, blood pressure, serum electrolytes, aldosterone, and plasma renin activity. Blood pressure percentiles and z-scores were calculated. The glomerular filtration rate was calculated using the modified Schwartz formula. RESULTS: The ratios of 5αTHF+5ßTHF to THE were significantly higher in patients with CKD [mean±sd score (SDS)=1.31±1.07] as compared with essential hypertension (mean±SDS=0.59±0.23; P=0.02) and controls (mean±SDS=0.52±0.25; P=0.01). In the postrenal transplant group, the ratio was not significantly different (mean±SDS=0.71±0.55). The urinary free cortisol to free cortisone ratios were significantly higher in the hypertension and CKD groups as compared with the controls. The 5αTHF+5ßTHF to THE ratio negatively correlated with the glomerular filtration rate and positively correlated with systolic and diastolic blood pressure z-scores. The correlation of the blood pressure z-scores with ratios was stronger in the CKD group than the essential hypertension and posttransplant groups. CONCLUSIONS: We have elucidated a functional deficiency of 11ß-hydroxysteroid dehydrogenase type 2 in children with CKD and a subset of essential hypertension. Urinary 5α-THF, 5ß-THF, and THE analysis by gas chromatography/mass spectrometry should be a part of routine work-up of CKD and hypertensive patients.

Blood Pressure over Height Ratios: Simple and Accurate Method of Detecting Elevated Blood Pressure in Children.

Background. Blood pressure (BP) percentiles in childhood are assessed according to age, gender, and height. Objective. To create a simple BP/height ratio for both systolic BP (SBP) and diastolic BP (DBP). To study the relationship between BP/height ratios and corresponding BP percentiles in children. Methods. We analyzed data on height and BP from 2006-2007 NHANES data. BP percentiles were calculated for 3775 children. Receiver-operating characteristic (ROC) curve analyses were performed to calculate sensitivity and specificity of BP/height ratios as diagnostic tests for elevated BP (>90%). Correlation analysis was performed between BP percentiles and BP/height ratios. Results. The average age was 12.54 ± 2.67 years. SBP/height and DBP/height ratios strongly correlated with SBP & DBP percentiles in both boys (P < 0.001, R(2) = 0.85, R(2) = 0.86) and girls (P < 0.001, R(2) = 0.85, R(2) = 0.90). The cutoffs of SBP/height and DBP/height ratios in boys were ≥0.75 and ≥0.46, respectively; in girls the ratios were ≥0.75 and ≥0.48, respectively with sensitivity and specificity in range of 83-100%. Conclusion. BP/height ratios are simple with high sensitivity and specificity to detect elevated BP in children. These ratios can be easily used in routine medical care of children.

Isolated mild clitoral hypertrophy may reveal 46,XY disorders of sex development in infancy due to 17ßHSD-3 defect confirmed by molecular analysis.

AIMS: 17-ß-Hydroxysteroid dehydrogenase type 3 (17ßHSD-3) is expressed exclusively in the testes where it converts Δ4 androstenedione (Δ4) to testosterone (T). Here, we report a patient with a rare mutation at a critical site in HSD17B3 gene leading to deficiency of 17ß HSD-3 enzyme. METHODS: We describe a 3-year old healthy female of consanguineous Lebanese descent, who presented to the endocrine service with isolated mild clitoromegaly. Adrenocorticotropic hormone (ACTH) and human chorionic gonadotrophin (hCG) stimulation tests were performed. Genes for sex-determining region Y (SRY), steroidogenic factor-1 (SF-1) and 17ßHSD-3 (HSD17B3) were sequenced. RESULTS: The post-hCG stimulation T levels and T/Δ4 ratio was low. Patient had a 46,XY karyotype. Sequence analysis of the HSD17B3 gene revealed a homozygous R80W missense mutation on exon 3. No mutation was found in SRY and SF1 genes. Mullerian structures were not detected on pelvic imaging. CONCLUSIONS: A low T/Δ4 ratio is indicative of 17ßHSD-3 deficiency and associated with isolated clitoromegaly. The R80 site is critical for NADPH binding, thus the mutation at this site leads to 17ßHSD-3 deficiency presenting as 46,XY disorder of sex development.

The clinical and molecular heterogeneity of 17ßHSD-3 enzyme deficiency.

17-ß-Hydroxysteroid dehydrogenase type 3 (17ßHSD-3) deficiency is a rare, but frequently misdiagnosed autosomal recessive cause of 46,XY disorder of sex development (DSD). 17ßHSD-3 enzyme is present almost exclusively in the testes and converts Δ4-androstenedione (Δ4) to testosterone (T). The diagnosis can be easily missed in early childhood as the clinical presentation may be subtle. Any young girl with an inguinal hernia, mild clitoromegaly, single urethral opening or urogenital sinus should raise suspicion. If not diagnosed early, patients present with severe virilization and primary amenorrhea in adolescence and may undergo a change from a female to male gender role. A low T/Δ4 ratio on baseline or hCG (human chorionic gonadotropin)-stimulated testing is suggestive of 17ßHSD-3 deficiency. The diagnosis can be confirmed with molecular genetic studies. This review summarizes the clinical presentations, reported mutations, diagnosis, treatment and clinical course of this disorder. The Arg80 site in exon 3 is the most common location of repeated mutations and can be considered a hot spot in certain Arab populations.

The prevalence of metabolic syndrome in inner city obese African-American youth.

BACKGROUND: In children and adolescents, obesity increases the risk of metabolic syndrome (MS). OBJECTIVE: We examined the prevalence of MS among obese and morbidly obese children and adolescents referred to an obesity clinic in a university-based hospital center. DESIGN/METHODS: A total of 194 obese (BMI > 95%) children and adolescents were evaluated. Fasting glucose, insulin, lipid panel, BMI, blood pressures were obtained. Main outcome measures were prevalence of components of MS by modified National Cholesterol Education Program (NCEP or Adult Treatment Panel 111 (ATP 111), with MS defined as > or = 3 components. RESULTS: There were 113 females (58%) and 81 males (42%); mean age of the cohort was 11.9 years (range: 3.4-18.8 years). One hundred seventy four (90%) of the cohort were African-American, 14 (7%) were Hispanic and 6 (3%) were others. Mean BMI z- score was 2.5 and ranged from 1.7 to 4.8. Thirty five percent of the total cohort had MS. Among the morbidly obese patients (BMI z-score > 2.5), the prevalence of the MS increased to 44%. Impaired fasting glucose (5.8 %), impaired glucose tolerance (6.5%) and silent diabetes mellitus (2.4%) were also identified. CONCLUSIONS: One third of obese patients referred to a hospital-based obesity center had the MS and nearly half of morbidly obese children and adolescents had MS.