A novel mutation in the KCNJ11 gene (p.Val36Glu), predisposes to congenital hyperinsulinemia.

The hypoglycemia induced by insulin hypersecretion in congenital hyperinsulinemia (CHI), a rare life-threatening condition can lead to irreversible brain damage in neonates. Inactivating mutations in the genes encoding KATP channel (ABCC8 and KCNJ11) as well as HNF4A, HNF1A, HADH, UCP2, and activating mutations in GLUD1, GCK, and SLC16A1 have been identified as causal. A 3-month-old male infant presenting tonic-clonic seizures and hyperinsulinemia was clinically assessed and subjected to genetic analysis. Besides the index patient, his parents were clinically investigated, and a detailed family history was also recorded. The laboratory investigations and the genetic test results of the parents were compared with the index patient. The biochemical and hormonal profile of the patient confirmed his suffering from CHI and did not respond to diazoxide treatment. The genetic testing revealed that the subject harbored a novel homozygous missense mutation in the KCNJ11 gene, (c.107T>A, p.Val36Glu.). The bioinformatic analysis revealed that valine is highly conserved and predicted that the variant allele (p.Val36Glu) is likely pathogenic and causal for CHI. Parents were heterozygous carriers and did not report any abnormal metabolic profile. Identification of such mutations is critical and likely to change the therapeutic interventions for such patients in the future.

Family history of menstrual irregularity or diabetes mellitus enhances the susceptibility to polycystic ovary syndrome among subjects harboring rs7903146 genetic variant of TCF7L2.

Purpose: TCF7L2 mediated Wnt signaling cascade regulates glucose homeostasis by orchestrating expression, processing, and hepatic clearance of insulin. Type 2 diabetes mellitus (T2DM) and polycystic ovary syndrome (PCOS) significantly overlap in pathophysiological features with insulin resistance as a central driver. While TCF7L2 is the most potent T2DM locus, studies on the association of TCF7L2 with PCOS are limited and inconclusive. Therefore, in addition to expression profiling, the association of TCF7L2 polymorphic variant rs7903146 with PCOS was evaluated. Methods: Using Rotterdam-2003 criteria for the diagnosis, 120 PCOS cases, and 120 age-matched controls were recruited. Subjects underwent clinical, biochemical, and hormonal assessment, followed by genotyping for rs7903146, carried out by PCR-RFLP and TCFL2 expression profiling by qRT-PCR. Genotype-phenotype correlation analysis was performed to evaluate any such associations. Odds ratios (ORs) with 95% confidence intervals (95% CIs) were computed by conditional logistic regression. Results: Higher odds of developing PCOS were observed in the women having a family history (FH) of either T2DM (OR = 3.86, 95% CI:1.90 - 7.83), hirsutism (OR = 4.74. 95%CI: 1.91 - 17.21) or menstrual irregularities (MI) (OR = 3.07, 95%CI: 1.61 - 8.54). The genotypes of rs7903146 did not confer any risk for developing PCOS (OR = 0.46;95%CI: 0.15 - 2.03). However, the elevated risk was seen in the subjects who harbored the variant allele and had FH of either T2DM (OR = 6.71; 95%CI: 1.89 - 23.78) or MI (OR = 9.71; 95% CI:1.89 - 23.78). Conclusion: TCF7L2 polymorphic variant rs7903146 is not independently linked to PCOS risk, but modulates the risk in the subjects having a family history of either T2DM or MI. Supplementary Information: The online version contains supplementary material available at 10.1007/s40200-022-01050-y.

Health-related quality of life in transplant eligible multiple myeloma patients with or without early ASCT in the real-world setting.

There is no comparative health-related quality of life (HR-QoL) data of transplant eligible (TE) multiple myeloma (MM) patients undergoing early autologous stem cell transplantation (ASCT) and those without in the era of novel drugs. This study prospectively evaluated the serial HR-QoL in TE-MM using the EORTC QLQ-C30 and MY20 questionnaires. Barring the transient worsening in QoL one-month after ASCT, there was a comparable improvement in most QoL domains in both early-ASCT and no-early ASCT cohorts. Post-early-ASCT patients had higher global health scores (71.9 vs. 60.8, p < .05) than no-early ASCT at 12-months. Patients belonging to lower socioeconomic status (SES) were more likely not to undergo ASCT than middle-high SES patients (38.6% vs. 74.5%, p < .05). While age, gender had no impact on QoL, performance status, staging, and induction therapy impacted QoL. This study shows that early ASCT maintains QoL and should be encouraged in all TE-MM patients.

Development, validation and evaluation of a novel self-instructional module in patients with chronic non-specific low back pain.

BACKGROUND: Low back pain (LBP) is ranked highest in terms of disability-adjusted life-years lived. Patient education and self-management have shown to play a crucial role in the overall pain management. However, the literature on the same with respect to Indian context is still lacking. The study was aimed to develop, validate and assess the acceptability and effectiveness of self-instructional educational module among Indian chronic LBP (CLBP) patients. METHODS: A prospective single-arm open-label study was conducted in a pain clinic of a tertiary care public hospital in North India with 'Backcare booklet-self-instructional module (SIM)' as an intervention in patients with CLBP. SIM was developed with the intent to provide up-to-date evidence-based information in an easy understanding way to patients with CLBP. 132 patients were administered SIM with a single session of verbal explanation. Pain intensity (numeric rating scale [NRS]), disability, fear-avoidance belief Questionnaire (FABQ), quality of life (EQ5D) and knowledge level were assessed at baseline and after 3 months of intervention. Student's paired t-test and Chi-square test were used. Data were analysed using SPSS version 15.0. RESULTS: 120 patients successfully completed the 3 months' follow-up. Significant reductions were observed in pain intensity (76[12] vs 55 [15, P < 0.01); disability (51[14] vs 43 [10], P < 0.01); FABQ (46[12] vs 41 [10], P < 0.01); EQ5D (0.35 [0.27] vs 0.18 [0.26], P < 0.01). CONCLUSION: Backcare booklet as an intervention, along with usual pharmacological care is a cost-effective educational medium to promote self-management of CLBP in the clinical outpatient settings.