Validation of a novel NGS based BCR::ABL1 kinase domain mutation detection assay in Indian cohort.

The efficacy and treatment outcome of a CML patient are heavily dependent on BCR::ABL1 kinase domain (KD) mutation status. Next-generation sequencing technology is a bright alternative to the previously used sanger sequencing method due to its global presence in diagnostic setups, massive parallel sequencing ability, and far better sensitivity. In the present study, we have demonstrated a new protocol for kinase domain mutation analysis using the next-generation sequencing (NGS) method using the ion torrent sequencing platform. This protocol uses RNA as the starting material, followed by nested PCR to amplify the fusion transcript, which is subsequently used as a template for NGS. Initial validation and comparison of this assay with the sanger sequencing (SS) method yielded 95.23% agreement. CML samples (n = 121) with a failure to TKI response were subjected to this newly developed NGS-based assay to detect KD mutations, from which samples were found to have mutations with a sensitivity ranging from 2.32 to 93.41%. A total of 34.71% of samples (n = 42) were found to be positive for one or more KD mutations, whereas 65.29% of samples (n = 81) were found to be negative. Nine samples out of 42 positive samples, i.e., 21.42%, were found to have compound mutations. This is one of the first studies from India, which includes more than 160 samples and is analyzed by the NGS approach for KD mutation analysis.

Refining Field Cancerization: An Institutional Cohort Analysis of Patient Characteristics in a Validation Cohort.

BACKGROUND: Field cancerization is poorly defined in dermatology. The author group previously proposed and applied a classification system in an original cohort to risk-stratify patients with field cancerization. OBJECTIVE: Apply the authors' classification system within a validation cohort. METHODS: Patients with keratinocyte carcinoma history completed a survey regarding demographic information, medical history, and chemoprevention use. Patients were assigned a field cancerization class, and differences between validation and original cohorts were assessed. RESULTS: A total of 363 patients were enrolled (mean age 67.4; 61.7% male). After comparing validation and original cohorts, there were differences in age between class II (p = .02) and class IVb (p = .047), and differences in chemoprevention use in class III (p = .04). Similar to the original cohort, the validation cohort was associated with increases in total number of skin cancers in the last year (p < .001), 5 years (p < .001), lifetime (p < .001), years since first skin cancer (p < .001), and chemoprevention use (p < .001). In the validation cohort, there were increases in age (p = .03) and immunocompromised status (p = .04) with increasing class, which were not observed in the original cohort. CONCLUSION: Differences among field cancerization classes were similar in a validation cohort, further highlighting the importance of class-specific treatment and management.

Evaluation of the Tolerability of Hedgehog Pathway Inhibitors in the Treatment of Advanced Basal Cell Carcinoma: A Narrative Review of Treatment Strategies.

Hedgehog pathway inhibitors (HHIs) have broadened the treatment options available for patients with advanced basal cell carcinoma (BCC) for whom traditional therapeutic approaches are not feasible or effective. Sonidegib and vismodegib are oral HHIs that were approved for treatment of patients with advanced BCC after demonstrating promising efficacy in the pivotal Phase II BOLT (NCT01327053) and ERIVANCE (NCT00833417) trials, respectively. However, the incidence and types of treatment-emergent adverse events (AEs) observed with these agents may limit continuous use of HHIs and ultimately impact clinical outcomes. In this review, we summarize the safety and tolerability profiles of sonidegib and vismodegib and discuss potential management strategies for HHI class-effect AEs, including muscle spasms, creatine phosphokinase increase, alopecia, and dysgeusia. These AEs primarily occur early in treatment and can lead to treatment discontinuation. Differences in the pharmacokinetic profiles of sonidegib and vismodegib may contribute to the variability noted in times to onset and resolution of these and other AEs. Evidence suggests that protocol modifications, such as treatment interruptions and dose reductions, are effective ways to manage AEs while maintaining disease control. Nonpharmacologic and pharmacologic interventions may also be considered as part of an AE management strategy. Overall, healthcare providers and patients with advanced BCC should be aware of the HHI class-effect AEs and plan effective management strategies to avoid treatment discontinuation and optimize therapeutic response.

Inequalities in cardiovascular disease among elderly Indians: A gender perspective analysis using LASI wave-I (2017-18).

BACKGROUND: While Cardiovascular disease (CVD) affects both men and women, emerging evidence suggests notable gender differentials in disease prevalence. This study aims to explore and analyse the gender differentials in CVD disease prevalence in India. METHODS: The present study utilizes data from first wave of the nationally representative survey "Longitudinal Ageing Study in India" (LASI, WAVE-I, 2017-18) with the eligible sample size of 31,464 individuals aged 60 years and above. Logistic regression analysis was used to understand risk of CVD by demographic characteristics. Factors contribution to gender differences in CVD prevalence was examined using a non-linear Fairlie decomposition. RESULTS: The prevalence of CVD was lower in men (31.06%) compared to women (38.85%). Women have a 33% higher likelihood of CVD compared to men (OR: 1.33; 95% CI: 1.25-1.42). Lack of education also confers a lower risk, more pronounced in women with no schooling (OR: 0.81; 95% CI: 0.7-0.94) compared to men (OR: 0.52; 95% CI: 0.47-0.58). Morbidity influences CVD presence more among women than men, with individuals suffering from three or more diseases having markedly increased odds (Men: OR: 3.89; 95% CI: 3.54-4.3, Women: OR: 6.97; 95% CI: 6.48-10.11). Smoking accounted increase in (20.52%) the gender gap while years of schooling dramatically lessened the gender gap (-46.30%). CONCLUSION: Result show gender differential in CVD prevalence and underlying risk factors, underscoring the need for gender-specific preventive strategies and interventions. Our findings highlight the importance of refined approach to cardiovascular health that considers the complex interplay of biological, social, and environmental determinants.

United Kingdom oral and maxillofacial surgeons support changes to current specialty recruitment process, which could include 'Walport' style local selection and national benchmarking.

Recruitment to oral and maxillofacial Surgical (OMFS) specialty training was centralised in 2010. The 'flexibility' for OMFS to respond to specialty specific recruitment issues is reducing and many Specialty Trainees' (ST) posts are left unfilled. The National Institute for Health and Care Research (NIHR) appointment process designed to address the problem of recruiting and appointing academic surgeons with local selection with national benchmarking has worked. Using a database of all UK OMFS consultants/trainees, an electronic questionnaire was shared by e-mail, WhatsApp, and other social media. Of 306 replies, 125 (41%) were Consultants/post-certificate of completion training (CCT) individuals, 66 (22%) ST, 61 (20%) second degree students, 27 (9%) pre-second degree, 26 (9%) dual degree pre-ST trainees, and one did not indicate their status. A total of 249 (76%) studied dentistry first and 230 (75%) were male. Of those replying, 147 (48%) had no direct experience of national selection. 120 (39%) had experience as a candidate, 20 (7%) as a selector only, 17 (6%) as a candidate and selector, and two did not record their experience. Of 250 expressing an opinion, 156 (62%) supported local selection with 140 (56%) supporting local selection and national benchmarking, which is a process used for research training posts by the NIHR. Geographical continuity was most important for 78% of pre-second-degree trainees, 45% of STs, and 54% of second-degree students. A total of 57 respondents completed free text comments. There is support for changes in OMFS ST selection including creating OMFS posts which include Foundation and second-degree training in NIHR style locally recruited nationally benchmarked posts.

Prevalence of human papillomavirus in head and neck cancer patients in India: a systematic review and meta-analysis.

BACKGROUND: Human papillomavirus (HPV) is increasingly recognized as a significant risk factor in the development of head and neck cancers (HNCs), with varying prevalence and impact. This study aims to systematically review and analyze the prevalence of HPV in HNCs in India, providing insights into regional variations. METHODS: A comprehensive literature search was carried out using PubMed, Embase, and Web of Science up to November 10, 2023. Inclusion criteria focused on original research reporting HPV-positive cases among HNC patients in India. We used Nested-Knowledge software, for screening, and data extraction. The modified Newcastle-Ottawa Scale was used for quality assessment of included studies. We pooled the prevalence of HPV among HNC patients and performed a random-effects model meta-analysis using R software (version 4.3). RESULTS: The search yielded 33 studies, encompassing 4654 HNC patients. The pooled prevalence of HPV infection was found to be 33% (95% CI: 25.8-42.6), with notable heterogeneity (I² = 95%). Analysis of subgroups according to geographical location indicated varying prevalence rates. Specifically, the prevalence was 47% (95% CI: 32.2-62.4) in the eastern regions and 19.8% (95% CI: 10.8-33.4) in the western regions. No evidence of publication bias was detected. CONCLUSION: The observed considerable regional disparities on the prevalence of HPV in HNC patients in India emphasizes the need for integrated HPV vaccination and screening programs in public health strategies. The findings underline the necessity for further research to explore regional variations and treatment responses in HPV-associated HNCs, considering the impact of factors such as tobacco use and the potential benefits of HPV vaccination.

Efficacy of stem cell therapy in patients with chronic liver disease: an umbrella review of systematic reviews.

BACKGROUND: Stem cell therapy offers promising benefits like modulating immune responses, reducing inflammation, and aiding liver regeneration. This umbrella review seeks to compile evidence from systematic reviews to assess the efficacy of stem cell therapy for improving liver function and survival rates in chronic liver disease patients. METHODS: We searched electronic databases up to February 15, 2024. The selection process focused on systematic reviews comparing stem cell therapy with standard care or a placebo. The primary outcomes evaluated were changes in liver enzymes, the MELD score, and survival rates. Nested Knowledge software was utilized for screening and data extraction. All statistical analyses were performed using R software, version 4.3. RESULTS: Our umbrella review included 28 systematic reviews. The meta-analysis showcased a notable improvement in survival rates with a pooled RR of 1.487 (95% CI: 1.281 to 1.727). In non-randomized studies, albumin levels exhibited an SMD of 0.786 (95% CI: 0.368 to 1.204), indicating positive therapeutic effects. For ALT, the meta-analysis revealed a decrease in levels with an SMD of -0.499 (95% CI: -0.834 to -0.164), and for AST, an overall SMD of -0.362 (95% CI: -0.659 to -0.066) was observed, suggesting hepatoprotective effects. No significant changes were observed in total bilirubin levels and MELD scores in RCTs. CONCLUSION: Stem cell therapy exhibits potential as a novel treatment for chronic liver diseases, as it has demonstrated improvements in survival rates and certain liver function markers. More high-quality RCTs are needed in the future to fully ascertain the efficacy of stem cell therapy in this patient population.

UK OMFS consultants and trainees strongly support the recommendations of the 2008 Postgraduate Medical Education and Training Board (PMETB) Review of Training in OMFS. The time for delivering them is now.

When the Postgraduate Medical Education and Training Board's (PMETB) Review of Oral and Maxillofacial Surgery (OMFS) Training was published in 2008 it contained five recommendations about OMFS training. As yet, none of these recommendations has been delivered. An online survey was designed to assess awareness of the PMETB review and the current views of OMFS trainees and consultants about its recommendations. Replies were invited using email and social media (WhatsApp, Twitter, and Facebook). As a result of using social media no denominator for the response rate was possible. A total of 304 responses were received, eight of which were anonymous. There was strong support for all the OMFS-specific recommendations: 1: the OMFS specialty should remain a dual medical and dental degree specialty (255, 84%); 2: OMFS training should be shortened (283, 93%); 3: OMFS training should start at the beginning of the second degree (203, 67%); 4: there should be a single medical regulator (General Medical Council) for OMFS (258, 85%); and 6: the need for a second Foundation Year should be removed (260, 86%). Other suggestions about improving OMFS training were also made by participants in the survey. There remains strong support within the specialty for the recommendations of the review. This support is present across consultants, specialty trainees, and those aiming for OMFS specialty training. Some of the original legislative obstructions to delivery of the recommendations have been removed by Brexit creating a unique opportunity for them to be delivered.

Association Between MR Elastography Liver Stiffness and Histologic Liver Fibrosis in Children and Young Adults With Autoimmune Liver Disease.

BACKGROUND. Liver fibrosis is an important clinical endpoint of the progression of autoimmune liver disease (AILD); its monitoring would benefit from noninvasive imaging tools. OBJECTIVE. The purpose of this study was to assess the relationship between MR elastography (MRE) liver stiffness measurements and histologic liver fibrosis, as well as to evaluate the performance of MRE and biochemical-based clinical markers for stratifying histologic liver fibrosis severity, in children and young adults with AILD. METHODS. This retrospective study used an existing institutional registry of children and young adults diagnosed with AILD (primary sclerosing cholangitis [PSC], autoimmune sclerosing cholangitis [ASC], or autoimmune hepatitis [AIH]). The registry was searched to identify patients who underwent both a research abdominal 1.5-T MRI examination that included liver MRE (performed for registry enrollment) and a clinically indicated liver biopsy within 6 months of that examination. MRE used a 2D gradient-recalled echo sequence. One analyst measured mean liver shear stiffness (in kilopascals) for each examination. Laboratory markers of liver fibrosis (aspartate aminotransferase-to-platelet ratio index [APRI] and fibrosis-4 [FIB-4] score) were recorded. For investigational purposes, one pathologist, blinded to clinical and MRI data, determined histologic Metavir liver fibrosis stage. The Spearman rank order correlation coefficient was calculated between MRE liver stiffness and Metavir liver fibrosis stage. ROC analysis was used to evaluate diagnostic performance for identifying advanced fibrosis (i.e., differentiating Metavir F0-F1 from F2-F4 fibrosis), and sensitivity and specificity were calculated using the Youden index. RESULTS. The study included 46 patients (median age, 16.6 years [IQR, 13.7-17.8 years]; 20 female patients, 26 male patients); 12 had PSC, 10 had ASC, and 24 had AIH. Median MRE liver stiffness was 2.9 kPa (IQR, 2.2-4.0 kPa). MRE liver stiffness and Meta-vir fibrosis stage showed strong positive correlation (ρ = 0.68). For identifying advanced liver fibrosis, MRE liver stiffness had an AUC of 0.81, with sensitivity of 65.4% and specificity of 90.0%; APRI had an AUC of 0.72, with sensitivity of 64.0% and specificity of 80.0%; and FIB-4 score had an AUC of 0.71, with sensitivity of 60.0% and specificity of 85.0%. CONCLUSION. MRE liver stiffness measurements were associated with histologic liver fibrosis severity. CLINICAL IMPACT. The findings support a role for MRE in noninvasive monitoring of liver stiffness, a surrogate for fibrosis, in children and young adults with AILD. TRIAL REGISTRATION. ClinicalTrials.gov NCT03175471.