Large Indian Cohort Research Articles

Spinocerebellar ataxia type 27B (SCA27B) in India: insights from a large cohort study suggest ancient origin.

The ethnic diversity of India provides a unique opportunity to study the history of the origin of mutations of genetic disorders. Spinocerebellar ataxia type 27B (SCA27B), a recently identified dominantly inherited cerebellar disorder is caused by GAA-repeat expansions in intron 1 of Fibroblast Growth Factor 14 (FGF14). Predominantly reported in the European population, we aimed to screen this mutation and study the founder haplotype of SCA27B in Indian ataxia patients. We have undertaken screening of GAA repeats in a large Indian cohort of ~ 1400 uncharacterised ataxia patients and kindreds and long-read sequencing-based GAA repeat length assessment. High throughput genotyping-based haplotype analysis was also performed. We utilized ~ 1000 Indian genomes to study the GAA at-risk expansion alleles. We report a high frequency of 1.83% (n = 23) of SCA27B in the uncharacterized Indian ataxia cohort. We observed several biallelic GAA expansion mutations (n = 5) with younger disease onset. We observed a risk haplotype (AATCCGTGG) flanking the FGF14-GAA locus over a 74kb region in linkage disequilibrium. We further studied the frequency of this risk haplotype across diverse geographical population groups. The highest prevalence of the risk haplotype was observed in the European population (29.9%) followed by Indians (21.5%). The observed risk haplotype has existed through ~ 1100 generations (~ 22,000 years), assuming a correlated genealogy. This study provides valuable insights into SCA27B and its Upper Paleolithic origin in the Indian subcontinent. The high occurrence of biallelic expansion is probably relevant to the endogamous nature of the Indian population.

Revisiting Friedreich's Ataxia: Phenotypic and Imaging Characteristics.

Friedreich's ataxia (FRDA) is a common cause of autosomal recessive cerebellar ataxia. The phenotype is dependent on the repeat size and duration of the disease. We aimed to study the clinical, electrophysiologic, and radiologic profiles in a large Indian cohort of genetically proven FRDA patients. A retrospective cross-sectional, descriptive analysis of genetically proven FRDA patients was performed. A detailed review of all the hospital case records was done to analyze the clinical, radiologic, and electrophysiologic details. A total of 100 FRDA patients were selected for the analysis. Eighty-six patients had an age at onset between 5 and 25 years. Eight patients (8%) were classified as late-onset FRDA and six patients (6%) as early-onset FRDA. The median age at presentation was 19 years. The median age at onset was 14 years, and the median duration of illness was 4 years. All patients had gait ataxia as the initial symptom. Gait ataxia, loss of proprioception, and areflexia were seen in all patients. Dysarthria, nystagmus, amyotrophy, spasticity, extensor plantars, pes cavus, and scoliosis occurred in one-third of patients. Cardiomyopathy (18%) and diabetes (5%) were less common. Sensory polyneuropathy (87.5%) was the most common nerve conduction abnormality. Cortical somatosensory evoked responses were absent in all 43 tested patients (100%). Brainstem auditory evoked response test was done in 24 patients and it showed absent reactions in six patients (25%). Visual evoked potential was tested in 24 patients and it showed absent P100 responses in five patients (21%). Cerebellar and cord atrophy was seen on magnetic resonance imaging in 50% of patients. Most FRDA patients (86%) had an age at onset of less than 25 years, with typical symptoms of gait ataxia, areflexia, and loss of proprioception found in all patients. Dysarthria, nystagmus, amyotrophy, spasticity, extensor plantars, pes cavus, scoliosis, cardiomyopathy, and diabetes were not seen in all patients. Cerebellar atrophy can occur in FRDA patients. Knowledge regarding the clinical, radiologic, and electrophysiologic profile of FRDA will aid in proper phenotypic characterization.

Expression of cell surface zinc transporter LIV1 in triple negative breast cancer is an indicator of poor prognosis and therapy failure.

Triple negative breast cancers (TNBC) are an aggressive molecular subtype of breast carcinoma (BC) identified by the lack of receptor expression for estrogen, progesterone, & human epidermal growth factor receptor-2. Lack of tangible drug targets warrants further research in TNBC. LIV1, is a zinc (Zn) transporter known to be overexpressed in few cancer types including BCs. Recently, in the United States of America, FDA approved the use of a new drug targeting LIV1, antibody drug conjugate SGN-LIV1A for treatment of TNBC patients. Though LIV1 also has a role in modulating immune cells by its differential transport of Zn, a correlation between the tumor cell expression of LIV1 and immune cell infiltrations were scantily reported. Further adequate baseline data on LIV1 expression in other populations have not been documented. Our objective was to screen a large Indian cohort of TNBC patient samples for LIV1, categorize the immune cell infiltration using CD4/CD8 expression and correlate the findings with therapy outcomes. Further, we also investigated for LIV1 expression in matched samples of primary & secondary tumors; pre & postchemotherapy in TNBC patients. Results showed an elevated expression of LIV1 in TNBC samples as compared to adjacent normal, the mean Q scores being 183.06 ± 6.39 and 120.78 ± 7.37 (p < 0.0001), respectively. Similarly, LIV1 levels were elevated in secondary tumors than primary & in patient samples postchemotherapy as compared to naïve. In the TNBC cohort, using automated method, cell morphology parameters were computed and analysis showed LIV1 levels were elevated in grade 3 TNBC samples presenting with altered cell morphology parameters namely cell size, cell perimeter, & nucleus size. Thus indicating LIV1 expressing TNBC samples portrayed an aggressive phenotype. Finally, TNBC patients with 3+ staining intensity showed poor survival (4.44 year) as compared to patients with 2+LIV1 expression (5.47 year), emphasizing that LIV1 expression is a poor prognostic factor in TNBC. In conclusion, the study reports elevated expression of LIV1 in a large Indian TNBC cohort; high expression is a poor prognostic factor and correlated with aggressive disease and indicating the need for LIV1 targeted therapies.

P769 Impact of discontinuation of anti-TNF therapy: A long term follow-up data of risks and predictors relapse in a large Indian cohort

Abstract Background Discontinuation of anti-TNF therapy in IBD is an important consideration in TB endemic low resource settings of the developing world. There are no established guidelines on withdrawal of biologics. A proper exit strategy on when and how biologics can be stopped is therefore warranted. We aimed to identify risk factors and rates of relapse post withdrawal in a large real-life cohort of patients from India. Methods Prospectively collected data of consecutive patients treated with anti-TNFs from the IBD registry of a large tertiary care centre was analyzed. Demographics,baseline disease characteristics,reasons for discontinuation, response to anti-TNF,and relapse rate after withdrawal were analysed. Time to event analysis was done to evaluate relapse rates over time. Cox proportional hazard analysis and non-parametric tests were performed to identify risk factors of relapse. Results Of 8300 patients, only 725(8.7%),(Median age-36y,IQR:26-47,61.2% male,61.2%CD, 32%UC, IBD-U 1.8%) received anti-TNFs. 445 (61.3%) discontinued with median follow up of 54 m(IQR:31-81). Reasons for discontinuation were primary non-response(64,14.3%);secondary loss of response (44,9.8%);financial constraints(27,6.1%);TB reactivation (18,4%), side effects(17,3.2%); infusion reactions(20,4.4%);non-compliance(4,0.9%), and COVID lockdown (6,1.3%). Overall, 232/445 (52%) were in clinical and endoscopic remission while stopping anti-TNFs with median follow up of 41 months(IQR:24.5-67). Relapse rates at 1,2,3,4, and 5 years after discontinuation were 16%,5.6%,5.2%,2.6% and 1.3% respectively. Overall,161/232(69%) patients remained in remission(Fig1A). Patients who stopped after clinical and endoscopic remission had higher likelihood of maintaining remission after discontinuation of biologics (Log-rank test,p=0.001). On multivariate analysis, fistulizing disease(p=0.03), prior history of bowel surgery (p=0.019), immunomodulator usage (p=0.001) and shorter duration of therapy (p=0.017) were associated with significantly higher rate of relapse(Table1). Cumulative time to relapse was significantly longer in those with or without endoscopic remission (median 17.3 vs 7 months;p=0.04)(Fig1B). On the other hand, shorter disease duration (p=0.001) and absence of extra-intestinal manifestations (p=0.009) were associated with lower risks of relapse. Conclusion 60% of patients discontinued anti-TNF therapy in this real world cohort. However, long-term cumulative relapse rates were low(30%), particularly in non-fistulizing disease, with no history of bowel surgery or extra intestinal manifestations and in endoscopic remission. A definite exit strategy appears feasible and would be a practical and affordable management approach.

Validation testing of OUTPATSAT-35RT questionnaire to assess satisfaction in patients on outpatient radiotherapy in a large Indian cohort

ABSTRACT Background: This study reports the psychometric properties of OUTPASAT-35RT questionnaire from a large Indian cancer cohort treated with ambulatory radiotherapy (RT) at a tertiary-care comprehensive cancer center. Materials and Methods: Adults with a pathologically proven diagnosis of cancer undergoing fractionated RT (≥10 fractions) with the ability to read and understand English, Hindi, or Marathi were accrued after written informed consent. Patients were administered a language-appropriate version of OUTPATSAT-35RT along with European Organization for Research and Treatment of Cancer (EORTC) generic quality-of-life questionnaire (QLQ-C30) at conclusion of RT (±3 days). Psychometric properties of OUTPATSAT-35RT were analyzed. Results: A total of 314 patients were accrued between 2018 and 2020. A negligible floor effect (&lt;2%) but a high ceiling effect (&gt;15%) was observed for OUTPATSAT-35RT. Multi-trait analysis revealed satisfactory validity and reliability of the questionnaire. Pearson’s correlation coefficient (PCC) of individual item score with own scale was &gt;0.4 suggesting good convergent validity. Discriminant validity was satisfactory as the PCC with its own scale/own domain was greater than with other scales of the same domain and other domains of OUTPATSAT-35RT, respectively. Correlation of scales of OUTPATSAT-35RT with scales of QLQ-C30 demonstrated acceptable divergent validity (all values of PCC &lt;0.3). Cronbach’s alpha was &gt;0.7 suggesting good internal consistency. Test–retest reliability was good with intra-class coefficient being &gt;0.7. Economic status was the only socio-demographic factor correlating significantly with OUTPATSAT-35RT scores; satisfaction of patients with the delivery of care increased with increasing family income. Conclusion: The psychometric properties of OUTPATSAT-35RT were found to be acceptable and satisfactory during validation testing in a large Indian cohort.

A Phase-IV Non-interventional Study to Assess Virological Effectiveness, Safety, and Tolerability of DTG-based Antiretroviral Therapy in HIV-1 Infected Indian Persons Living with HIV.

Dolutegravir (DTG) is a novel yet preferential first- and -second-line treatment for persons living with HIV (PLH). Owing to its recent introduction, DTG-based regimens have not undergone a comprehensive, systematic evaluation regarding their real-world utilization and safety profile among a sizeable Indian population. This study aimed to assess the 24 week immunovirological outcomes, anthropometric and metabolic changes, tolerability, and adverse events (AEs) of DTG-based antiretroviral (ART) regimens. A single-centre phase-IV non-interventional observational study involving 322 ART naïve and treatment-experienced PLH initiating DTG-based-regimens until October 2022 were followed up for outcomes at 24 weeks. At 24 weeks, all PLH (n = 113) in the naïve group, all PLH (n = 67) in the first-line substitution group, 93.9% PLH (n = 46) in the first-line failure group, and 95.7% PLH (n = 89) in the second-line substitution group were virologically suppressed to plasma HIV-RNA <1000 copies/mL. Virological suppression rates to plasma HIV-RNA <200 copies/mL and <50 copies/mL were consistent among PLH who received DTG as first- or second-line ART. The mean-unadjusted weight gain observed was 3.5 kg (SE: 0.330), and it was significantly higher in PLH with poorer health at baseline (either HIV-RNA ≥ 1000 copies/ml or CD4 cell count <350 cells/μL). Overall, 27.3% PLH (n = 88) gained ≥10% of their baseline body weight, corresponding to 3.7% incidence (n = 12) of treatment-emergent clinical obesity. DTG had an overall lipid-neutral effect, with an advantageous effect being observed in PLH switching from non-nucleoside analogue reverse-transcriptase inhibitors (NNRTI) or ritonavir-boosted protease inhibitors (b/PI), especially in dyslipidemic pre-treated PLH (median change in total cholesterol: 28.5 mg/dL and triglycerides: 51 mg/dL), possibly emanating from the withdrawal of the offending ART. The incidence of DTG-specific AEs, including CNS AEs, was low. Two PLH developed proximal myopathy and one developed transaminitis, warranting DTG discontinuation. Asymptomatic serum-CPK elevation and drug-induced transaminitis were seen in 25.2% (n = 27) and 3.2% (n = 10) PLH, respectively. No apparent negative effects on renal function were detected. Our results from a large Indian cohort indicate a favourable virological and metabolic response, with good tolerance of DTG-based ART at 24 weeks.

Validation of novel Japanese 5-5-500 criteria in large Indian LDLT cohort: a retrospective study

Validation of novel Japanese 5-5-500 criteria in large Indian LDLT cohort: a retrospective study

Baseline neurocognitive dysfunction is ubiquitous in intrinsic brain tumors– results from a large Indian cohort of patients and analysis of factors associated with domain-specific dysfunction

BackgroundNeurocognitive function (NCF) before surgery is an important marker of baseline performance in patients with brain tumors. Increasingly, neurocognitive deficits (NCD) have been demonstrated in a high proportion of patients. Selection bias (patient, tumor, and surgical procedure related) may influence the prevalence and type of domains involved in patients with gliomas. MethodsWe evaluated baseline NCF in a consecutive cohort of intra-axial tumors in Indian patients (n = 142). A comprehensive battery evaluating five domains – attention & executive function (EF), memory, language, visuospatial function and visuomotor abilities was used. Deficits were categorized as severe and mild-moderate. Factors associated with severe NCD were evaluated. ResultsSevere NCD was present in 90% of the patients, 70% of them having affection of at least 2 domains. Attention-EF, memory and visuomotor speed were most affected. 132 underwent surgery (69 awake, 63 under general anesthesia - GA). The awake cohort had younger patients with lower grade gliomas and more left sided tumors. Multi-domain dysfunction was seen almost equally in awake/GA groups as well as left/right sided tumors. On multivariate analysis, older age, lower educational status and larger tumor volume adversely affected NCF in many of the domains. Only language dysfunction was location specific (temporal lobe tumors) though not laterality (left/right) specific. ConclusionsNCD were seen in a large majority of cases before surgery, including those undergoing awake surgery. Language may be affected even in tumors in the non-dominant hemisphere. Attention-EF and memory are most affected and need to be factored in while assessing patient performance intraoperatively during awake surgery as well as tailoring rehabilitative measures subsequently.

Adverse impact of Covid-19 pandemic on the glycemic status of persons with diabetes: Experience from a large Indian cohort

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Poster: MM-356 Deep Coverage Targeted Next Generation Sequencing Approach to Determine Somatic Mutational Spectrum of Recurrently Mutated Genes in Newly Diagnosed Multiple Myeloma in a Large Indian Cohort

Poster: MM-356 Deep Coverage Targeted Next Generation Sequencing Approach to Determine Somatic Mutational Spectrum of Recurrently Mutated Genes in Newly Diagnosed Multiple Myeloma in a Large Indian Cohort

MM-356 Deep Coverage Targeted Next Generation Sequencing Approach to Determine Somatic Mutational Spectrum of Recurrently Mutated Genes in Newly Diagnosed Multiple Myeloma in a Large Indian Cohort

To determine the mutational spectrum of recurrently mutated genes in a large cohort of Indian patients presenting with multiple myeloma (MM) in our center by performing deep coverage-targeted NGS. Samples of 151 multiple myeloma patients (149 NDMM and 6 follow-up) were sequenced. Patients were diagnosed with MM per IMWG criteria 2014. The study was initiated following approval from the institute's ethical committee, and written informed consent was obtained from all patients. BMA was subjected to plasma cell isolation using CD138+ MACS. DNA underwent automated extraction using the Maxwell System. Mutations were tested on a commercially available 47-gene custom panel (Illumina) specifically designed for MM. Libraries were prepared using a TruSeq Custom Amplicon Low Input Kit (Illumina). DNA (25 ng) was hybridized with oligos specific for targeted regions of interest. Libraries were pooled. Paired-end sequencing was carried out on Illumina's MiSeq sequencer using micro flow cell with V3 chemistry and MS600 V3 series reagent cartridge. Sequenced reads were mapped to GRCh37/Hg19 reference and data obtained as FASTQ files and processed with MiSeq Reporter. As output, .vcf files were generated. Genomic variants were annotated by ANNOVAR. Sequencing coverage of 4771 X (Range 2063X-10980X) revealed different types of variants (exonic, intronic, splice region, 3' and 5' UTR, and upstream gene). Pathogenicity was checked by COSMIC. At least one pathogenic mutation was found in 77% (116/151) of patients (median 1 mutation per patient, range 0-7) and 51% (24/47) of genes. Forty-five percent (68/151) of patients had mutations in more than one gene. The most frequently mutated genes were KRAS, NRAS, BRAF, TP53, DIS3, FAT4, FAT3, and DNAH5. Genomic aberrations found were compared with the frequency of mutations as per the MMRF and TCGA datasets and related literature; good concordance was found (especially in MAPK pathway genes). BRAF and RAS mutations were mutually exclusive. Few mutations were validated by Sanger sequencing. The high frequency of mutations in MAPK pathway genes (KRAS, NRAS, BRAF) suggested the importance of this pathway in myelomagenesis and therapeutics. Follow-up sample sequencing may help deduce clonal evolution during disease course. Identification of clinically relevant target driver mutations may aid in prognosis and therapy personification.

Central Skull Base Osteomyelitis: Multimodality Imaging and Clinical Findings from a Large Indian Cohort.

Central or atypical skull base osteomyelitis (CSBO) often presents with severe unrelenting headache and progressive mono or polyneuritis cranialis. MRI and CT are used as initial imaging techniques but have a poor specificity and sensitivity. To analyze our cohort of CSBO. Over a 5-year period [2015-2020], we retrospectively analyzed the records of all patients with CSBO who had undergone a 3T MRI Brain, MR angiography, regional FDG PET-CT, and skeletal scintigraphy with 99mTc MDP/SPECT-CT. Surgical biopsy specimens were sent for bacterial and fungal cultures. In total, 17 patients with CSBO were identified. Typically, 88% of patients presented with severe unilateral headache. All patients had at least a cranial mono or polyneuritis. The majority of patients were diabetic [64%]. MRI was normal in 42% of patients, whereas PET-CT and with 99mTc MDP scan and SPECT-CT were abnormal in all patients. Our series of CSBO showed a 40% mortality rate with significant morbidity and relentless progression. Patients required repeated PET CT and bone scans to detect regression of disease activity. The average duration of IV therapy ranged from 3 weeks to 9 months and oral therapy for around 2-3 months. Cure was defined after taking into account the original diagnosis, symptom resolution, and concordant reduction of tissue uptake on PET CT and 99mTc bone scan. The combination of MRI, FDG PET CT, and 99mTc bone scan with concurrent SPECT CT was able to detect disease and disease progression in all patients.

P-056: Deep coverage targeted next generation sequencing approach to determine somatic mutational spectrum of recurrently mutated genes in newly diagnosed multiple myeloma in a large Indian cohort

P-056: Deep coverage targeted next generation sequencing approach to determine somatic mutational spectrum of recurrently mutated genes in newly diagnosed multiple myeloma in a large Indian cohort

All EGFR mutations are (not) created equal: focus on uncommon EGFR mutations.

Most common EGFR mutations in NSCLC include del19 and exon 21 L858R. Approximately 10% of patients have uncommon EGFR mutations (indels, missense mutations involving G719, L861 and S768 codons, and exon 20 insertions) that do not respond to TKIs. Of 490 EGFR mutated NSCLC samples, 60 cases harboring uncommon/compound EGFR mutations were reviewed retrospectively, and 44 were included for survival analysis. Sixty (12.2%) patients with a median age of 63 years (25-84years) had uncommon/compound EGFR mutations. Majority had no history of smoking (52; 86.7%). Most common major uncommon mutations (G719X in exon 18, L861Q in exon 21 and S768I in exon 20) were identified in 19 (31.7%) patients. 17 (28.3%) cases demonstrated exon 20 insertions. De novo T790M was observed in 7 (11.7%) cases and 9 cases exhibited compound/dual mutations. Among the 12 patients who received first-line EGFR TKI, 7 received afatinib. Median progression-free survival of patients following first-line afatinib was 8.13months, irrespective of mutation type exhibited. Overall response rate to first-line afatinib therapy was 57.1%. The current study highlighted that rare/dual EGFR mutations are heterogeneous with distinct clinical features in a large Indian cohort of EGFR mutated patients with NSCLC.

100P Outcomes of non-metastatic triple negative breast cancers: Real-world data from a large Indian cohort

100P Outcomes of non-metastatic triple negative breast cancers: Real-world data from a large Indian cohort

Outcomes of non-metastatic triple negative breast cancers: Real-world data from a large Indian cohort

BackgroundTriple negative Breast tumor (TNBC) is an aggressive tumor with sparse data worldwide. MethodsWe analyzed non-metastatic TNBC from 2013 to 2019 for demographics, practice patterns, and survival by the Kaplan Meir method. Prognostic factors for OS and DFS were evaluated using Cox Proportional Hazard model estimator for univariate and multivariable analysis after checking for collinearity among the variables. ResultsThere were 1297 patients with median age of 38 years; 41 (33.3%) among 123 tested were BRCA-positives. Among these 593 (45.7%) had stage III disease, 1279 (98.6%) were grade III, 165 (13.0%) had peri-nodal extension (PNE), 212 (16.0%) lympho-vascular invasion (LVI), and 21 (1.6%) were metaplastic; 1256 (96.8%) received chemotherapy including 820 (63.2%) neoadjuvant with 306 (40.0%) pCR. Grade ≥3 toxicities occurred in 155 (12.4%) including two deaths and 3 s-primaries. 1234 (95.2%) underwent surgery [722 (55.7%) breast conservations] and 1034 (79.7%) received radiotherapy.At a median follow-up of 54 months, median disease-free (DFS) was 92.2 months and overall survival (OS) was not reached. 5-year estimated DFS and OS was 65.9% and 80.3%. There were 259 (20.0%) failures; predominantly distant (204, 15.7%) - lung (51%), liver (31.8%).In multivariate analysis presence of LVI (HR-2.00, p-0.003), PNE (HR-2.09 p-0.003), older age (HR-1.03, p-0.002) and stage III disease (HR-4.89, p-0.027), were associated with poor OS. ConclusionRelatively large contemporary data of non-metastatic TNBC confirms aggressive biology and predominant advanced stage presentation which adversely affects outcomes. The data strongly indicate the unmet need for early detection to optimize care.

Mutational spectrum of dysferlinopathies in a large Indian cohort

Mutational spectrum of dysferlinopathies in a large Indian cohort

Correlation of TTF-1 immunoexpression and EGFR mutation spectrum in non-small cell lung carcinoma.

BackgroundThyroid transcription factor (TTF-1) is a diagnostic marker expressed in 75%–85% of primary lung adenocarcinomas (ACs). Activating mutations in the tyrosine kinase domain of the epidermal growth factor receptor (EGFR) gene is the most common targetable driver alteration in lung AC. Previous studies have shown a positive correlation between TTF-1 and EGFR mutation status. We aimed to determine the predictive value of TTF-1 immunoexpression for underlying EGFR mutation status in a large Indian cohort. MethodsThis retrospective designed study was conducted with medical record data from 2011 to 2020. All cases of primary lung AC and non–small cell lung carcinoma not otherwise specified (NSCLC, NOS) with known TTF-1 expression diagnosed by immunohistochemistry using 8G7G3/1 antibodies and EGFR mutation status diagnosed by quantitative polymerase chain reaction were retrieved, reviewed, and theresults were analyzed. ResultsAmong 909 patient samples diagnosed as lung AC and NSCLC, NOS, TTF-1 was positive in 76.8% cases (698/909) and EGFR mutations were detected in 29.6% (269/909). A strong positive correlation was present between TTF-1 positivity and EGFR mutation status (odds ratio, 3.61; p < .001), with TTF-1 positivity showing high sensitivity (90%) and negative predictive value (87%) for EGFR mutation. TTF-1 immunoexpression did not show significant correlation with uncommon/dual EGFR mutations (odds ratio, 1.69; p = .098). EGFR–tyrosine kinase inhibitor therapy was significantly superior to chemotherapy among EGFR mutant cases irrespective of TTF-1 status; however, no significant differences among survival outcomes were observed. ConclusionsOur study confirms a strong positive correlation between TTF-1 expression and common EGFR mutations (exon 19 deletion and exon 21 L858R) in advanced lung AC with significantly high negative predictive value of TTF-1 for EGFR mutations.

Myositis-specific and myositis-associated autoantibodies in a large Indian cohort of inflammatory myositis

BackgroundThe Idiopathic Inflammatory Myositis (IIM) are heterogenous with distinct clinical phenotypes associated with specific myositis specific antibodies (MSA) and myositis associated antibodies (MAA). ObjectivesTo evaluate the frequency, pattern and associations of MSA/MAA in a large Indian cohort of IIM. MethodsAdult and juvenile IIM (2017 ACR/EULAR criteria), were recruited in the MyoCite cohort between 2017and 2020 at a tertiary center in Northern India. Standardized clinical and laboratory variables were extracted from the database archive. Serum samples were evaluated for the presence of MSAs/MAAs by Line immunoassay and anti-nuclear antibodies (ANA) by Immunofluorescence assay (IFA). The prevalence and clinical associations of different MSA/MAAs were assessed. ResultsMSA and MAAs were tested in 250 IIM patients (214 adults, 36 children) of age [40 (30–49), 13 (7.5–16) years] and disease duration [ 7 (3–17), 6 (2–17) months] comprising predominantly of Dermatomyositis (DM) followed by Overlap myositis (OM). MSAs/MAAs were found in 148 (59.2%, 60.7% adults and 50% JIIM), of which two-thirds were MSA (95, 64% overall). Two cases (0.8%) had more than one MSA. In adult IIM, the most common MSA was anti-Jo-1 (10%), whereas it was anti-MDA5 and anti-NXP2 4 (11%) each in Juvenile IIM (JIIM). 76.0% (172/226) were ANA positive, with speckled pattern being the most common (37%,). Nearly two-thirds (54, 61%) of those with negative ANA had MSA/ MAA. Nearly half (18/54, 54.6%) had MSA associated with cytoplasmic patterns. ARS (anti-aminoacyl-tRNA synthetase) were associated with mechanic's hands (OR-7.06), ILD (OR-4.4), and arthritis (OR-2.23). Clinical associations of anti-Jo-1 and non-Jo-1 Anti synthetase syndrome (ASS) did not differ. Anti-MDA-5 associated with oral ulcers (OR-8.3), fever (OR-8.6) and weight loss (OR-7.35) in adults, and arthritis (OR-11.5), and periungual rash (OR-9.6) in children. Anti-TIF-1γ associated with photosensitivity (OR-10.44) and malignancy (OR-34) in adults, and cuticular overgrowth (OR-11.2) in children. ConclusionMyositis autoantibodies are seen in two-thirds IIMs and are associated with distinct clinical subsets. Jo-1 and non-Jo-1 ASS exhibit similar characteristics. The association of anti-TIF1 γ with malignancy was confirmed in adults. MSA/MAA were present in two-thirds of those with negative ANA and MSA were nearly always mutually exclusive.

CAH Newborn Screening in India: Challenges and Opportunities.

Congenital adrenal hyperplasia (CAH) is a common treatable disorder which is associated with life-threatening adrenal crisis, sexual ambiguity, and/or abnormal growth if undiagnosed. Newborn screening is a cost-effective tool to detect affected babies early after birth to optimize their treatment and follow-up. Newborn screening however is in its nascent stage in India where it is not yet introduced universally for all babies. The following review briefly highlights the challenges (e.g., lack of universal screening, healthcare resources) and opportunities (e.g., reduction in morbidity and early correct gender assignment in females) associated with newborn screening for CAH in a large Indian birth cohort.