Musculocontractural type of Ehlers-Danlos syndrome with novel CHST14 pathogenic variant in two siblings.

Musculocontractural Ehlers-Danlos syndrome (MC-EDS) is a rare entity worldwide with underlying pathogenic variant in the carbohydrate sulfotransferase 14 (CHST14) gene. Previous reports of the same entity from India were of two unrelated cases. Ours is the first report of two siblings in an Indian family with craniofacial dysmorphism and distal arthrogryposis with a clinical diagnosis of EDS, where an underlying pathogenic variant in CHST14 was detected by exome sequencing.

Hepatitis C virus core antigen: A diagnostic and treatment monitoring marker of hepatitis C virus in Indian population.

BACKGROUND: The diagnosis and treatment monitoring of hepatitis C is quite challenging. The screening test, i.e. antibody assay, is unable to detect acute cases, while the gold standard hepatitis C virus (HCV) reverse transcriptase polymerase chain reaction (RTPCR) assay is not feasible in resource-limited countries such as India due to high cost and infrastructure requirement. European Association for the Study of the Liver and World Health Organization have approved a new marker, i.e. HCV core antigen (HCVcAg) assay, as an alternative to molecular assay. In this study, we have evaluated HCVcAg assay for diagnosis and treatment monitoring follow-up in Indian population infected with hepatitis C. METHODS: Blood specimen of 90 clinically suspected cases of acute hepatitis C were tested simultaneously for anti-HCV antibody assay via ELISA (enzyme-linked immunoassay), HCVcAg assay by chemiluminescence immune assay (CLIA) and HCV RTPCR VL (viral load) assay. Thirty-four HCV RTPCR positive patients were further enrolled in treatment monitoring group whose blood samples were tested at the beginning of treatment, two weeks, four weeks and 12 weeks via HCV core Ag assay and HCV RTPCR Viral Load assay. RESULTS: Considering HCV RTPCR as gold standard, diagnostic performance of HCV core Ag assay and anti-HCV antibody assay was evaluated. The sensitivity and specificity of HCV core Ag assay were higher than that of anti-HCV Antibody assay, i.e. 88.3% and 100% vs. 23.3% and 83.3%, respectively. The overall diagnostic accuracy of HCV core Ag assay was 92.20%. Among treatment follow-up group, HCV core Ag levels correlated well with HCV viral load levels, at the beginning of treatment (baseline) till 12 weeks showing highly significant Spearman rank correlation coefficient of > 0.9 with HCV viral load levels. CONCLUSIONS: HCV core Ag assay is a cost-effective, practically feasible substitute of HCV RTPCR viral load assay for diagnosis as well as long duration treatment monitoring of hepatitis C infection in resource-limited settings.

Loeys-Dietz syndrome and Goldenhar syndrome unveiled together.

Haemifacial microsomia is an asymmetrical congenital tissue malformation developed from the first and second branchial arches with or without multi-system involvement. Alternatively recognised as Goldenhar syndrome or oculoauriculovertebral spectrum (OAVS), it is an aetiologically heterogeneous group of disorders showing dominant trends in inheritable form.We present a case of a boy in early childhood with concomitant craniofacial features of craniofacial microsomia with Loeys-Dietz syndrome. He had a unilateral hypoplastic face, asymmetrical ear malformations and multiple preauricular tags with epibulbar dermoid (features suggestive of Goldenhar syndrome). On detailed clinical evaluation, he met Beighton's criteria and was diagnosed with arterial tortuosity. Further molecular testing confirmed the diagnosis of Loeys-Dietz syndrome type II.Loeys-Dietz syndrome is characterised by aortic root enlargement or type A dissection with or without other vascular malformations and facial midline defects. Molecular testing is required to establish the diagnosis because of overlapping features with other connective tissue disorders.

Incidence of Middle Mesial Canals in Mandibular Molars during Root Canal Treatment and Nonsurgical Retreatment.

INTRODUCTION: Large-scale clinical studies on the incidence of middle mesial canals (MMCs) in nonsurgical root canal treatment (RCT) and retreatment of mandibular molars are lacking. The primary aim of this observational study was to determine the incidence of MMCs in mandibular first and second molars that received RCT or nonsurgical retreatment (NSRetx). The secondary aim was to determine factors associated with incidence of MMCs. METHODS: Included were 3018 mandibular molars that received RCT (n = 1624) or NSRetx (n = 1394) by 3 endodontists in a private practice. Demographic and procedural data were collected. Bivariate and multivariable (Poisson regression model) analyses were performed. RESULTS: Incidence of MMCs was 8.8% (n = 267). Although the bivariate analysis showed that NSRetx was significantly associated with incidence of MMCs, this association did not reach the threshold for statistical significance after controlling for all covariates (P = .07). Multivariable analysis on the entire cohort showed that incidence of MMCs was significantly associated with younger age (risk ratio [RR] = 1.62; 95% confidence interval [CI], 1.28-2.06), male gender (RR = 1.48; 95% CI, 1.18-1.85), preoperative cone-beam computed tomography (CBCT) (RR = 1.48; 95% CI, 1.17-1.89), and first molar (RR = 2.30; 95% CI:1.74-3.05). Subgroup multivariable analyses revealed that incidence of MMCs was associated with male gender only in the RCT group (RR = 2.26; 95% CI, 1.55-3.30) but not in the NSRetx group (RR = 1.11; 95% CI, 0.82, 1.50); and with preoperative CBCT only in the NSRetx group (RR = 1.78; 95% CI, 1.28, 2.50) but not in the RCT group (RR = 1.10; 95% CI, 0.71, 1.69). Associations with younger age and first molar remained unchanged. CONCLUSIONS: Overall incidence of MMCs was 8.8%. Incidence of MMCs was significantly higher in younger patients and in mandibular first molars but was not associated with the type of treatment.

Primary antibiotic resistance of Helicobacter pylori in India over the past two decades: A systematic review.

BACKGROUND: Helicobacter pylori antibiotic resistance has undergone vast changes in the last two decades. No systematic review has been done on the prevalence of antibiotic resistant H. pylori in India in the last two decades. We evaluated the pattern of resistance rates across various regions of India. MATERIALS AND METHODS: A systematic review of the geographical variations in antibiotic resistance pattern of H. pylori was conducted using PubMed, Google Scholar, Web of Science, Science Direct, etc. for articles published between January 1, 2000 and May 30, 2023. Random effects-model-based Cochran's Q test, I2 statistics, and chi-squared tests were used to measure heterogeneity. RESULTS: The overall resistance was highest against metronidazole (77.65%) followed by amoxicillin (37.78%), levofloxacin (32.8%), clarithromycin (35.64%), furazolidone (12.03%), and tetracycline (11.63%). 14.7% of the H. pylori isolates were multi-drug resistant. Under meta-analysis of each antibiotic, high heterogeneity levels were observed having I2 ranges from 86.53% to 97.70% at p < 0.0001. In sub-group analysis, Metronidazole has a stable rate of resistance as compared to other antibiotics. Other antibiotics have had a downtrend in the last 5 years except for levofloxacin, which has had an uptrend in the resistance rate for the past 5 years. Hence, one should avoid using metronidazole for any kind of first-line treatment. CONCLUSIONS: Metronidazole resistance is high in most regions of India except Assam and Mumbai while clarithromycin is found to be ineffective in South India, Gujarat, and Kashmir. As compared to other antibiotics, resistance to amoxicillin is generally low except in certain regions (Hyderabad, Chennai, and the Gangetic belt of North India). Tetracycline and Furazolidone have the least resistance rates and should be part of anti- H. pylori regimens. The resurgence of high single and multidrug resistance to the commonly used drugs suggests the need for newer antibiotics and regular resistance surveillance studies.

Thurston syndrome with thalassaemia: a rare case devising a novel molecular and phenotypic variation.

A male infant presented with progressive paleness of the body since 3 months of age. On examination, the child had pallor, microcephaly with dysmorphic facies (depressed nasal bridge, low set ears, retrognathia, high arched palate and tongue hamartoma). Postaxial polydactyly in bilateral hands and feet, broad great toes, with syndactyly of left fourth and fifth toes were present. The haemogram showed severe anaemia with a microcytic hypochromic picture. High-performance liquid chromatography (HPLC) was normal. However, the parents' HPLC was suggestive of beta thalassaemia trait. Whole-exome sequencing revealed Thurston syndrome with beta-thalassaemia in homozygous pattern with a novel mutation. It is a rare genetic syndrome exclusively found in the South Asian population. Due to the rarity, identification of this syndrome is often difficult and requires awareness among clinicians. However, it is important to diagnose the disorder accurately in order to provide appropriate genetic counselling and prognostication to the parents.

Short Stature for Age in Children of 5 to 16 Years: The First Research from the Northern Himalayan Region of India.

Introduction: Anthropometric parameters play vital role in monitoring growth in pediatrics. Many etiological factors lead to short stature. So, before assessing the etiological factors short stature needs to be addressed. This study aimed to screen short stature for age in school-going children aged 5 to 16 years in Uttarakhand. Material and Methods: In this cross-sectional observational study, the height (through stadiometer) and weight (through weight machine) of 4189 students of government and private school in Rishikesh (Uttarakhand) aged 5-16 years were measured after the verbal assent of the students and individual's height is in the 3rd percentile for the mean height of a given age, sex, and population group and was considered short stature. The data collection was performed from October 2019 to July 2021. The data were categorized according to different age groups to 5-8 years, 9-12 years, and 13-16 years. The data were recorded in Microsoft (MS) Excel spreadsheet program. Statistical Package for the Social Sciences (SPSS) v23 (IBM Corp.) was used for data analysis. Descriptive statistics were elaborated in the form of means or standard deviations and medians or Interquartile range IQRs for continuous variables and frequencies and percentages for categorical variables. The Chi-square test was used for group comparisons for categorical data. Results: 7.1% of children were short stature (height 143.16 ± 15.09 cm) in the Himalayan belt, and males were more prone to short stature at age of 9-12 years. Conclusion: In the growing phase of children, the etiology of short stature has to be rectified, so the children can achieve such proper growth. Parents and physicians have to assess and monitor the growth of children timely. This study can be a stepping stone for further epidemiological studies.

Flare-ups After Nonsurgical Retreatments: Incidence, Associated Factors, and Prediction.

INTRODUCTION: The aims of this study were to determine the incidence, associated factors, and predictability of flare-ups after nonsurgical retreatments (NSRetx). METHODS: All patients (n = 3,666) who received NSRetx by 3 endodontists in 2 endodontic offices during a period of 6 years (2016-2022) were included. Demographic, diagnostic, and procedural data were collected. A flare-up was defined as moderate-severe pain with/without swelling that took place within 14 days of initiation of NSRetx and resulted in an unscheduled appointment. Bivariate analyses on the entire cohort and multivariable analyses on cases with complete dataset (n = 2,846) were performed to identify significant associations. A Random Forest algorithm was used to make a prediction model. RESULTS: Incidence of flare-ups was 3.95% (n = 145). Increased risk of flare-ups was associated with diabetes (adjusted odds ratio [AOR] = 2.01; 95% confidence interval [CI], 1.01-3.97), mandibular teeth (AOR = 1.67; 95% CI, 1.11-2.52), moderate-severe preoperative pain on percussion (AOR = 2.13; 95% CI, 1.31-3.50), and pain on palpation (AOR = 1.63; 95% CI, 1.01-2.64). Lower risk of flare-up was associated with high blood pressure (AOR = 0.44; 95% CI, 0.21-0.82) (P < .05). The prediction model was not able to predict flare-ups with sufficient confidence (precision = 0.13). CONCLUSIONS: Incidence of flare-ups following NSRetx was low (∼4%) and had a weak but significant association with the history of diabetes. Moderate-severe pain on percussion, pain on palpation (any intensity), and mandibular teeth had a significant association with flare-ups. The history of high blood pressure was associated with lower risk of flare-ups. Flare-ups were difficult to predict in this clinical setting.

A Case of Fibrinous Pericardial Effusion: Masquerading Presentation of Systemic Lupus Erythematosus.

Systemic lupus erythematosus (SLE) is a multisystem autoimmune disorder with varied presentations varying from nonspecific features like fever, malaise, and arthralgia to serious manifestations like serositis (pleural, pericardial effusions), neurological manifestations, and renal involvement (lupus nephritis). SLE is a great mimicker, especially for infections like tuberculosis (TB) which is rampant in low- and middle-income countries (LMIC). We report a case of massive pericardial effusion, which was initially diagnosed as TB on clinico-radiological basis, but the diagnosis was later revised owing to new findings.

Association between neutrophil lymphocyte ratio and status of symptom control in children and adolescents with bronchial asthma.

Neutrophil lymphocyte ratio (NLR), an easy and readily available biomarker of systemic inflammation, has been less studied so far as a putative marker of asthma control. Our study aimed to assess its feasibility. A total of 90 asthmatic children, aged 5-18 years, diagnosed according to Global Initiative for Asthma (GINA) guidelines, were. Control status of asthma was assessed using the asthma control test (ACT) or childhood ACT and categorized as controlled group-1 (ACT > 19) and uncontrolled group-2 (ACT ≤ 19). The difference between mean values in both groups was analysed, finding a significant difference between children with and without a family history (p = 0.004) and those with and without a need for admission (p = 0.045). Also, a significant association was established between NLR and the type of severity of asthma (p = 0.049), but none between NLR and age, gender, BMI, coexisting allergic rhinitis, or asthma exacerbation. Thus we found no significant association between NLR and symptom control status. However, NLR has the potential to be a putative marker of inflammation, although its relative status to CRP needs further studies.

A case of successful treatment of concurrent verrucous epidermal naevi and psoriasis with apremilast.

In a rare case of concurrent verrucous epidermal naevi (VEN) with psoriasis, previous treatments with oral methotrexate and acitretin showed minimal improvement. However, treatment with oral apremilast resulted in complete resolution of psoriasis and significant improvement in VEN lesions after 1 month. This is the first documented case of successful VEN treatment with apremilast, highlighting its potential efficacy in treating verrucous epidermal naevus. Further studies are needed to validate its effectiveness.

Prevalence and Associated Clinical Features of Type 1 Diabetes Mellitus Among Children Presented to a Tertiary Health Care Center of Himalayan Foothills.

Introduction Diabetes Mellitus (DM) is a complex metabolic disorder characterized by chronic hyperglycemia. Knowing its prevalence, associated clinical features, and complications is essential for diagnosing children having diabetes-like clinical features. Since there is a limited study from India and no similar study from this geographical part, the present study was carried out. Material and method It is a cross-sectional study, which includes children aged 1-18 years presented to the pediatric outpatient department (OPD), inpatient department (IPD), and emergency with clinical features of Type 1 Diabetes Mellitus (T1DM). The enrolled cases were assessed for confirmation of T1DM, and clinical features and associated complications were recorded in the case record form. Result A total of 218 children with clinical features of T1DM were enrolled, out of which 32 (14.7%) had T1DM. Among the 32 T1DM patients, 31 (96.9%) of the participants presented with polyuria, 29 (90.6%) had polydipsia, and 13 (40.6%) had polyphagia. Out of 32 children, 3 (9.38%) had diabetic neuropathy, and 1 (3.1%) had diabetic retinopathy. Conclusion We found that many children with diabetes have clinical features of T1DM and uncontrolled blood sugar. This emphasizes the need for early detection and treatment to prevent long-term complications.

Clinico-Microbiological Profile and Clinical Predictor of Urinary Tract Infection in Children: A Single-Center Study From Himalayan Foothills.

BACKGROUND:  Urinary tract infection (UTI) in children is one of the commonest bacterial infections seen in the pediatric population. Clinical presentation ranges from fever with or without focus and isolation of microbiological agents streamline the treatment. Moreover, local/regional microbial profiles are helpful in antibiotic selection, we conducted a study to assess the prevalence of urine culture positivity in a suspected case of UTI. In addition, antibiotic susceptibility patterns and ultrasonography (USG) finding in culture-positive patients were also studied. METHODS AND MATERIALS: It is a prospective observational study comprising symptomatic children aged one month to 18 years presenting to the outpatient department (OPD), inpatient department (IPD), and the emergency department of Pediatrics with UTI during the period of September 2019 to September 2020. The recorded variables were demographic, clinical presentation, anthropometry, physical examination, blood biochemistry, and outcome. Urine samples were collected and processed as per standard protocols. USG was done for all culture-positive children. Data were presented as frequency, mean (SD) and parametric and non-parametric data were analyzed by Wilcoxon-Mann-Whitney U Test, Chi-Squared Test, or Fisher's Exact Test.  Results: Of the total 354 children, 202 (57.1%) were male and the prevalence of UTI was 64 (18.1%). E. coli (70.3%) was the commonest isolated organism followed by Klebsiella spp (15.6%) and Pseudomonas spp (7%) respectively. The mean (SD) age (months) of presentation of symptoms was significantly lower in culture-positive children as compared to [ 83.49 (58.96) vs 110.10 (58.60); p=0.001] culture-negative children. Fever (96.6%) followed by dysuria (20.1%) were the most common symptoms presented for UTI however dysuria (p=0.003), pus cells (p<0.0001), and RBCs (p=0.002) were significantly present in culture positive children. This study shows increased resistance to third generation of cephalosporins. This study revealed significant differences among various groups (organism growth in positive culture) and the Antibiotic susceptibility test (AST) with a p-value of <0.001.  Conclusion: The prevalence of culture-positive UTI was similar to the reported literature and the presence of fever, dysuria, pus cells, and RBC in urine were commonly observed in the lower age group. Amikacin can be used in suspected UTIs with cephalosporin as empirical antibiotics in the Himalayan Foothills region.

Behavioral problems in infants and young children with spinal muscular atrophy and their siblings: A cross-sectional study.

INTRODUCTION: Older children and adults with spinal muscular atrophy (SMA) have been shown to have more anxiety, depression, and other behavioral problems in a few studies. But no similar studies have been performed in infants and young children with SMA. METHOD: Behavioral co-morbidities of young children with SMA were compared with healthy and children with chronic non-neurological illness control group. Infant Behavior Questionnaire-Revised (IBQ-R) and parent-report version of chid behavior checklist (CBCL) were used for infants and preschool-age children respectively. RESULTS: A total of 35 SMA children (age at symptom onset-5.9 ± 2.8 months, at enrolment-21.4 ± 7.1 months, 65% boys, 11, 19 and 5 were SMA 1, 2 and 3 respectively) and 24 siblings (38.6 ± 11.2 months, 71% boys) were enrolled. We also enrolled 15 children with nephrotic syndrome as age and gender matched control to SMA children in age-group 2-5 years (27.7 ± 9.1 months, 67% boys). In infants with SMA, the scale scores of IBQ-R were significantly higher for distress to limitation, fear, sadness, and falling reactivity/rate of recovery from distress (p = 0.005; 0.03; 0.001, and 0.04) and lower for soothability as compared to healthy control group (p = 0.04). Similarly, for the three dimensions of temperament computed from these 13 domains, the mean scale score for surgency/extraversion was lower and negative affectivity was higher (p = 0.04 and 0.03), in infants with SMA as compared to healthy controls. For preschool age group, the internalizing problem scores (p = 0.009 and 0.03) and stress problem scores (p = 0.002 and 0.04) were higher in the SMA group, as compared to both the healthy control group and diseased control group. While assessing the syndrome scale scores, the score was higher for emotionally reactive (p = 0.0002 and 0.01) and anxious domains (p < 0.0001 and p = 0.0002) compared to both healthy and diseased control groups. CONCLUSION: Infants and young children with SMA suffer from increased internalizing problems like anxiety, depression and probably their healthy siblings are also at increased levels of stress, depicted by increased somatic complaints.