Epidemiology of Hepatocellular Carcinoma in India - An Updated Review for 2024.

Hepatocellular carcinoma (HCC) is the most common form of primary liver cancer and is a significant cause of morbidity and mortality, especially in patients with chronic liver disease. As a reflection of geographical variations in India, there is significant variation in the prevalence and etiological factors of HCC. In contrast to previous studies reporting viral hepatitis as the most common etiology, recent data indicates a changing etiological pattern of cirrhosis and HCC, with alcohol and metabolic dysfunction-associated steatotic liver disease (MASLD) emerging as the foremost cause. Thus, there was a need for an updated review of the current literature and databases for the changing epidemiology and etiological spectrum of HCC in India. The review included data primarily from the National Cancer Registry Program and the Global Burden of Diseases, Injuries, and Risk Factors Study, with the inclusion of other studies from India. The highlights of the present review are summarized in the following lines. Although the current incidence (2.15 per 100,000), prevalence (2.27 per 100,000), and mortality (2.21 per 100,000) rate of HCC in India remain lower compared to the global data, the annual rates of change in these parameters are higher in India. Among Indians, the present incidence, prevalence, and mortality related to HCC are higher in males, while the annual rate of change is higher in females. The Northeastern states have higher incidence, prevalence, and mortality related to HCC, but the Western states of Gujarat, Maharashtra, Goa, and Kerala are emerging as newer hotspots with higher annual rates of change in incidence, prevalence, and mortality. The incidence of HCC related to hepatitis B is on a downtrend, while those related to alcohol and MASLD are rising. Public health initiatives, awareness campaigns, and focused treatments are all necessary to combat these changes, particularly in areas with high incidence rates.

Comparison of inflammatory markers in low-pressure pneumoperitoneum with deep neuromuscular block versus standard pressure pneumoperitoneum among patients undergoing laparoscopic cholecystectomy for gallstone disease: a randomized control trial.

BACKGROUND: Low-pressure pneumoperitoneum (LPP) is an attempt to improve laparoscopic surgery. Lower pressure causes lesser inflammation and better hemodynamics. There is a lack of literature comparing inflammatory markers in LPP with deep NMB to standard pressure pneumoperitoneum (SPP) with moderate NMB in laparoscopic cholecystectomy. METHODOLOGY: This was a single institutional prospective randomized control trial. Participants included all patients undergoing laparoscopic cholecystectomy for symptomatic gall stone disease. Participants were divided into 2 groups group A and B. Group A-Low-pressure group in which pneumoperitoneum pressure was kept low (8-10 mmHg) with deep Neuromuscular blockade (NMB) and Group B-Normal pressure group (12-14 mmHg) with moderate NMB. A convenience sample size of 80 with 40 in each group was selected. Lab investigations like CBC, LFT, RFT and serum IL-1, IL-6, IL-17, TNF alpha levels were measured at base line and 24 h after surgery and compared using appropriate statistical tests. Other parameters like length of hospital stay, post-operative pain score, conversion rate (low-pressure to standard pressure), and complications were also compared. RESULTS: Eighty participants were analysed with 40 in each group. Baseline characteristics and investigations were statistically similar. Difference (post-operative-pre-operative) of inflammatory markers were compared between both groups. Numerically there was a slightly higher rise in most of the inflammatory markers (TLC, ESR, CRP, IL-6, TNFα) in Group B compared to Group A but not statistically significant. Albumin showed significant fall (p < 0.001) in Group B compared to Group A. Post-operative pain was also significantly less (p < 0.001) in Group A compared to Group B at 6 h and 24 h. There were no differences in length of hospital stay and incidence of complications. There was no conversion from low-pressure to standard pressure. CONCLUSION: Laparoscopic cholecystectomy performed under low-pressure pneumoperitoneum with deep NMB may have lesser inflammation and lesser post-operative pain compared to standard pressure pneumoperitoneum with moderate NMB. Future studies with larger sample size need to be designed to support these findings.

VISH-Pred: an ensemble of fine-tuned ESM models for protein toxicity prediction.

Peptide- and protein-based therapeutics are becoming a promising treatment regimen for myriad diseases. Toxicity of proteins is the primary hurdle for protein-based therapies. Thus, there is an urgent need for accurate in silico methods for determining toxic proteins to filter the pool of potential candidates. At the same time, it is imperative to precisely identify non-toxic proteins to expand the possibilities for protein-based biologics. To address this challenge, we proposed an ensemble framework, called VISH-Pred, comprising models built by fine-tuning ESM2 transformer models on a large, experimentally validated, curated dataset of protein and peptide toxicities. The primary steps in the VISH-Pred framework are to efficiently estimate protein toxicities taking just the protein sequence as input, employing an under sampling technique to handle the humongous class-imbalance in the data and learning representations from fine-tuned ESM2 protein language models which are then fed to machine learning techniques such as Lightgbm and XGBoost. The VISH-Pred framework is able to correctly identify both peptides/proteins with potential toxicity and non-toxic proteins, achieving a Matthews correlation coefficient of 0.737, 0.716 and 0.322 and F1-score of 0.759, 0.696 and 0.713 on three non-redundant blind tests, respectively, outperforming other methods by over $10\%$ on these quality metrics. Moreover, VISH-Pred achieved the best accuracy and area under receiver operating curve scores on these independent test sets, highlighting the robustness and generalization capability of the framework. By making VISH-Pred available as an easy-to-use web server, we expect it to serve as a valuable asset for future endeavors aimed at discerning the toxicity of peptides and enabling efficient protein-based therapeutics.

Effect of Combined HAART Plus ATT in Patients of Extrapulmonary Tuberculosis in HIV Patients and Effect on Quality of Life.

HIV is a disease which reduces human resistant to fight. When our immunity becomes so weak that we are not able to fight even the common commensals of our body, this leads to what is called as an opportunistic infection. Tuberculosis is one of those most common type of opportunistic infection and in this pulmonary tuberculosis is more common. Extrapulmonary tuberculosis with HIV is the area of lesser research. In this study we tried to prove the Prevalence of extrapulmonary tuberculosis in AIDS patients and also the effect of combined HAART and ATT on prevalence of extrapulmonary tuberculosis and also its effect on Quality of life of the patient. This is a retrospective study conducted in a tertiary centre in the Department of Otorhinolaryngology & head and neck surgery from January 2020 to December 2020. A total of 80 patients were studied for 1 year. Confirmed cases of AIDS with extra pulmonary tuberculosis in head and neck region were studied, keeping all ethical issues in mind and after complete treatment of ATT along with HAART. After treatment, a significant number of patients got resolved with EPTB and gave positive response on their quality of life. Not only pulmonary tuberculosis, extrapulmonary tuberculosis with HIV is on the rise nowadays. Combined treatment of both can help in decreasing prevalence of extrapulmonary tuberculosis and improves quality of life.

Formulation and Characterization of Soybean Oil-in-Water Emulsions Stabilized Using Gelatinized Starch Dispersions from Plant Sources.

Consumers are concerned about employing green processing technologies and natural ingredients in different manufacturing sectors to achieve a "clean label" standard for products and minimize the hazardous impact of chemical ingredients on human health and the environment. In this study, we investigated the effects of gelatinized starch dispersions (GSDs) prepared from six plant sources (indica and japonica rice, wheat, corn, potatoes, and sweet potatoes) on the formulation and stability of oil-in-water (O/W) emulsions. The effect of gelatinization temperature and time conditions of 85-90 °C for 20 min on the interfacial tension of the two phases was observed. Emulsification was performed using a primary homogenization condition of 10,000 rpm for 5 min, followed by high-pressure homogenization at 100 MPa for five cycles. The effects of higher oil weight fractions (15-25% w/w) and storage stability at different temperatures for four weeks were also evaluated. The interfacial tension of all starch GSDs with soybean oil decreased compared with the interfacial tension between soybean oil and water as a control. The largest interfacial tension reduction was observed for the GSD from indica rice. Microstructural analysis indicated that the GSDs stabilized the O/W emulsion by coating oil droplets. Emulsions formulated using a GSD from indica rice were stable during four weeks of storage with a volume mean diameter (d4,3) of ~1 µm, minimal viscosity change, and a negative ζ-potential.

IL-22 promotes mucin-type O-glycosylation and MATH1+ cell-mediated amelioration of intestinal inflammation.

The interleukin (IL)-22 cytokine can be protective or inflammatory in the intestine. It is unclear if IL-22 receptor (IL-22Ra1)-mediated protection involves a specific type of intestinal epithelial cell (IEC). By using a range of IEC type-specific Il22Ra1 conditional knockout mice and a dextran sulfate sodium (DSS) colitis model, we demonstrate that IL-22Ra1 signaling in MATH1+ cells (goblet and progenitor cells) is essential for maintaining the mucosal barrier and intestinal tissue regeneration. The IL-22Ra1 signaling in IECs promotes mucin core-2 O-glycan extension and induces beta-1,3-galactosyltransferase 5 (B3GALT5) expression in the colon. Adenovirus-mediated expression of B3galt5 is sufficient to rescue Il22Ra1IEC mice from DSS colitis. Additionally, we observe a reduction in the expression of B3GALT5 and the Tn antigen, which indicates defective mucin O-glycan, in the colon tissue of patients with ulcerative colitis. Lastly, IL-22Ra1 signaling in MATH1+ progenitor cells promotes organoid regeneration after DSS injury. Our findings suggest that IL-22-dependent protective responses involve O-glycan modification, proliferation, and differentiation in MATH1+ progenitor cells.

Prevalence and outcome of sarcopenia in non-alcoholic fatty liver disease.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) includes a spectrum of conditions, progressing from mild steatosis to advanced fibrosis. Sarcopenia, characterized by decreased muscle strength and mass, shares common pathophysiological traits with NAFLD. An association exists between sarcopenia and increased NAFLD prevalence. However, data on the prevalence of sarcopenia in NAFLD and its impact on the outcomes of NAFLD remain inconsistent. AIM: To analyze the prevalence and outcomes of sarcopenia in patients with NAFLD. METHODS: We conducted a comprehensive search for relevant studies in MEDLINE, Embase, and Scopus from their inception to June 2023. We included studies that focused on patients with NAFLD, reported the prevalence of sarcopenia as the primary outcome, and examined secondary outcomes, such as liver fibrosis and other adverse events. We also used the Newcastle-Ottawa scale for quality assessment. RESULTS: Of the 29 studies included, the prevalence of sarcopenia in NAFLD varied widely (1.6% to 63.0%), with 20 studies reporting a prevalence of more than 10.0%. Substantial heterogeneity was noted in the measurement modalities for sarcopenia. Sarcopenia was associated with a higher risk of advanced fibrosis (odd ratio: 1.97, 95% confidence interval: 1.44-2.70). Increased odds were consistently observed in fibrosis assessment through biopsy, NAFLD fibrosis score/body mass index, aspartate aminotransferase to alanine aminotransferase ratio, diabetes (BARD) score, and transient elastography, whereas the fibrosis-4 score showed no such association. Sarcopenia in NAFLD was associated with a higher risk of steatohepatitis, insulin resistance, cardiovascular risks, and mortality. CONCLUSION: This systematic review highlights the critical need for standardized diagnostic criteria and measurement methods for sarcopenia in NAFLD patients. The variability in study designs and assessment methods for sarcopenia and liver fibrosis may account for the inconsistent findings. This review demonstrates the multidimensional impact of sarcopenia on NAFLD, indicating its importance beyond liver-related events to include cardiovascular risks, mortality, and metabolic complications.

Regulation of Notch signaling by non-muscle myosin II Zipper in Drosophila.

The Notch pathway is an evolutionarily conserved signaling system that is intricately regulated at multiple levels and it influences different aspects of development. In an effort to identify novel components involved in Notch signaling and its regulation, we carried out protein interaction screens which identified non-muscle myosin II Zipper (Zip) as an interacting partner of Notch. Physical interaction between Notch and Zip was further validated by co-immunoprecipitation studies. Immunocytochemical analyses revealed that Notch and Zip co-localize within same cytoplasmic compartment. Different alleles of zip also showed strong genetic interactions with Notch pathway components. Downregulation of Zip resulted in wing phenotypes that were reminiscent of Notch loss-of-function phenotypes and a perturbed expression of Notch downstream targets, Cut and Deadpan. Further, synergistic interaction between Notch and Zip resulted in highly ectopic expression of these Notch targets. Activated Notch-induced tumorous phenotype of larval tissues was enhanced by over-expression of Zip. Notch-Zip synergy resulted in the activation of JNK pathway that consequently lead to MMP activation and proliferation. Taken together, our results suggest that Zip may play an important role in regulation of Notch signaling.

Changing Etiological Spectrum of Hepatocellular Carcinoma in India-A Systematic Review and Meta-analysis.

Background: Recent studies from both India and outside India have shown a change in the etiological profile of hepatocellular carcinoma (HCC). We aimed to analyze the etiological spectrum and changing trends of HCC etiology in India using a systematic review of current literature and meta-analysis. Methods: Electronic databases of PubMed/Medline, Scopus, and Embase were searched from inception to July 2023 for studies reporting the data on the etiology of HCC from India. The pooled proportions with 95% confidence interval were calculated using summative statistics. Results: A total of 60 studies (n = 12,327) were included in the final analysis. The pooled proportions of HCC cases with at least one positive and negative viral marker were 56.0 (49.5-62.6) and 43.1% (36.5-49.8), respectively. The pooled proportion of HCC cases with positive hepatitis B virus (HBV) markers was 41.0 (35.8-46.1), while those with positive markers for hepatitis C virus were 20.3 (17.0-23.6). The pooled proportion of cases with HCC with significant alcohol intake was 19.0% (15.6-22.4), and those related to nonalcoholic fatty liver disease (NAFLD) were 16.9% (12.1-21.7). Around 7.9% (5.8-10.0) of the cases had HCC with multiple etiologies. Subgroup analysis showed a significant variation with the location of the study based on zone. Meta-regression analysis based on publication year (1990-2023) showed a significant reduction in the proportion of cases with HBV and an increase in cases with NAFLD. In contrast, the proportion of cases with hepatitis C virus and alcohol did not change significantly. Conclusion: Viral hepatitis is the most common etiology of HCC in India, predominantly HBV. The proportions of cases with HCC related to NAFLD are increasing, and those related to HBV are declining.

Furanocoumarins promote proteasomal degradation of viral HBx protein and down-regulate cccDNA transcription and replication of hepatitis B virus.

Nucleot(s)ide analogues, the current antiviral treatments against chronic hepatitis B (CHB) infection, are non-curative due to their inability to eliminate covalently closed circular DNA (cccDNA) from the infected hepatocytes. Preclinical studies have shown that coumarin derivatives can effectively reduce the HBV DNA replication. We evaluated the antiviral efficacy of thirty new coumarin derivatives in cell culture models for studying HBV. Furanocoumarins Fc-20 and Fc-31 suppressed the levels of pre-genomic RNA as well as cccDNA, and reduced the secretion of virions, HBsAg and HBeAg. The antiviral efficacies of Fc-20 and Fc31 improved further when used in combination with the hepatitis B antiviral drug Entecavir. There was a marked reduction in the intracellular HBx level in the presence of these furanocoumarins due to proteasomal degradation resulting in the down-regulation of HBx-dependent viral genes. Importantly, both Fc-20 and Fc-31 were non-cytotoxic to cells even at high concentrations. Further, our molecular docking studies confirmed a moderate to high affinity interaction between furanocoumarins and viral HBx via residues Ala3, Arg26 and Lys140. These data suggest that furanocoumarins could be developed as a new therapeutic for CHB infection.

Role of contrast-enhanced ultrasound for differentiation of benign vs. malignant portal vein thrombosis in hepatocellular carcinoma - A systematic review a meta-analysis.

Introduction/Purpose: Patients with cirrhosis and hepatocellular carcinoma (HCC) can develop both benign and malignant portal vein thrombosis (PVT). Characterising the nature of PVT is important for planning an optimal therapeutic strategy. In the absence of typical findings or contraindications to computed tomography (CT) or magnetic resonance imaging (MRI), contrast-enhanced ultrasound (CEUS) could help in this differentiation. The present meta-analysis aimed to evaluate the performance of CEUS for characterising PVT in patients with HCC. Methods: Electronic databases of PubMed, Embase and Scopus were searched from inception to 31 December 2022 for studies analysing the role of CEUS in the differentiation of benign and malignant PVT in HCC. Using the bivariate random effect model, pooled sensitivity and specificity were calculated, and the summary receiver operating characteristic (sROC) curve was plotted. Results: A total of 12 studies with data from 712 patients were included in the meta-analysis. The pooled sensitivity and specificity of CEUS for the diagnosis of tumour in vein were 97.0% (95% CI: 93.0-98.7) and 96.8% (95% CI: 92.1-98.7), respectively, without significant heterogeneity. A sROC curve was plotted, and the area under the receiver operating characteristic was 0.99 (95% CI: 0.98-1.00). Despite the presence of publication bias, sensitivity analysis did not show any change in sensitivity and specificity. Discussion: Our meta-analysis summarises the accuracy data from 12 studies, including >700 subjects. Contrast-enhanced ultrasound had excellent diagnostic accuracy with pooled sensitivity and specificity of 97.5% (95% CI: 93.5-99.1) and 98.2% (95% CI: 91.5-99.6), respectively, without any significant heterogeneity. Additionally, the pooled positive LR, negative LR and DOR were 54.6 (95% CI: 11.1-25.6), 0.02 (0.01-0.07) and 2186.8 (318.3-15022.2), respectively. A positive result increases the pretest probability of malignant PVT from 50% to 98%, whereas a negative result decreases it from 50% to 2%. Most of the studies included in our meta-analysis used identical techniques and 6-12-month follow-up scans to check for thrombus progression or regression. Our analysis showed no significant heterogeneity in the studies, and area under receiver operating characteristic curve (AUROC) with 95% CI was 1.00 (95% CI: 0.99-1.00). This critical meta-analysis thus propels CEUS to the forefront for differentiating benign from tumoural PVT and suggests routinely using CEUS in patients presenting with HCC and evidence of thrombus on greyscale ultrasound. Conclusion: Contrast-enhanced ultrasound is an effective diagnostic modality differentiation of benign and malignant PVT in patients with HCC and can be an alternative modality to CT or MRI. Further studies are required to study the role of CEUS as initial diagnostic modality for the characterisation of PVT in HCC.

Accelerated hypofractionated chemoradiation for locally advanced head and neck cancer during COVID 19 pandemic: A tertiary care experience.

PURPOSE: To assess the role of Accelerated Hypofractionated Chemoradiation for Locally Advanced Head & Neck squamous cell cancer (HNSCC) during COVID 19 pandemic. MATERIALS AND METHODS: Previously untreated 20 patients with locally advanced HNSCC (Oral cavity/oropharynx/larynx/hypopharynx) were treated with definitive hypofractionated radiotherapy of 60Gy in 25 fractions with concurrent cisplatin @35 mg/m2 once weekly for 5 weeks from March 2020 to November 2021. The patients were treated on 6MV LINAC with Volumetric modulated arc therapy (VMAT) by the Sequential boost technique and concurrent chemotherapy @35 mg/m2. All the patients received 48Gy in 20 fractions to low-risk volume (CTV LR) in Phase I followed by 12Gy in 5 fractions boost to High-risk volume (CTV HR) in Phase II. The organs at risk (OARs) were contoured and appropriate constraints were given considering the hypofractionated regimen. RESULTS: Out of 20 patients, most of the patients were Stage IV (15;75%) & stage III 20%, out of which (55%) 11 were of the oral cavity, (40%) 8 were of the oropharynx, and (5%) 1 of larynx. All patients were treated with 60Gy/25#/5 weeks with the majority of the patients (17;85%) completing their treatment in less than 45 days. The Median follow-up was of 214 days. The locoregional control at 6 Months was 55%. Maximum acute toxicity was grade 3 mucositis which was observed in 18 (90%) patients. Ryle's tube feeding was needed in 11 (55%) patient. Out of 20 patients, 5 patients did not receive concurrent chemotherapy, and 8 (40%) patients received all 5 cycles of chemotherapy. 7, 35% of the patients could not complete all 5 cycles of concurrent chemotherapy due to grade 3 mucositis. CONCLUSION: During a pandemic crisis with limited manpower & technical resources accelerated hypofractionated radiotherapy with concurrent chemotherapy can be considered a feasible therapeutic option for HNSCC which can significantly reduce the overall Treatment Time (OTT) with comparable local control and manageable toxicities.

Endoscopic retrieval of migrated Foley catheter: A clinical case series.

Use of Foley catheter in patients with ileostomy, for the decompression of large bowel distal to stoma or for the administration of large bowel enema through colostomy, either to treat constipation or for bowel preparation prior to colonoscopy, is a common practice. Accidental migration of catheter during bowel irrigation through stoma can take place if it is not secured externally to the skin. We present 2 such cases with intra-colonic migration of Foley catheter that occurred during bowel irrigation and were retrieved endoscopically. To our knowledge, this is the first case report of endoscopic removal of Foley catheter that migrated internally through the stoma.

A review on green approaches utilizing phytochemicals in the synthesis of vanadium nano particles and their applications.

In the modern era, inorganic nanoparticles have received profound attention as they possess boundless applications in various fields. Among these, vanadium-based nanoparticles (VNPs) are highly remarkable due to their inherent physiological and biological properties with many therapeutic and other applications, such as drug delivery systems for diseases like cancer, environmental remediation, energy storage, energy conversion, and photocatalysis. Moreover, physically, and chemically synthesized VNPs are very versatile, however, these synthesis routes cause concern to health and the environment due to the highly savage reaction conditions, using highly toxic and harsh chemicals, which compel the researchers to develop an eco-friendly, greener, and sustainable route for synthesis. In this outlook, to avoid the innumerable limitations, a bio approach is used over chemical and physical methods. This present review emphasis on the role of various biological components in the synthesis, especially Phyto-molecules that acts as capping and reducing agent, and solvent system for the nanoparticles synthesis. Furthermore, the influence of various factors on the biogenic synthesized nanoparticles has also been discussed. Finally, potential applications of as-synthesized VNPs, principally as an antimicrobial agent and their role as a nanomedicine, energy applications as a supercapacitor, and photocatalytic agents, have been discussed.

Clinical, immunological and molecular profiles of DOCK8 deficiency in six patients from a tertiary care centre in North India.

BACKGROUND: Dedicator of cytokinesis protein 8 (DOCK8) deficiency is an autosomal recessive form of combined immunodeficiency. This rare disorder is characterized by an increased predisposition to allergy, autoimmunity and malignancies. OBJECTIVES: To analyse clinical, immunological and molecular profiles of patients with DOCK8 deficiency. METHODS: Clinic records of all patients attending the primary immunodeficiency clinic from 2018 to 2021 were reviewed. Six patients from five families were found to have DOCK8 deficiency. RESULTS: Median age at diagnosis was 7.5 years (range 2-13), with a male/female ratio of 5 : 1. Among the six patients, recurrent eczematous skin lesions were the predominant cutaneous manifestation, present in five patients (83%). Warts and molluscum contagiosum were evident in two patients (33%) and one patient (16%), respectively. Two patients had recalcitrant prurigo nodularis lesions and two had epidermodysplasia verruciformis-like lesions. Food allergies and asthma were reported by one patient each. Of the six patients, recurrent sinopulmonary infections were detected in five (83%). Epstein-Barr virus-driven non-Hodgkin lymphoma with liver metastases was the only case of malignancy, in a 4-year-old boy. IgE was elevated in all patients. Lymphopenia and eosinophilia were observed in three patients (50%) and five patients (83.3%), respectively. Genetic analysis showed DOCK8 pathogenic variants in all patients: homozygous deletion mutations in two patients, compound heterozygous deletion mutations in one, and homozygous nonsense mutations in two. A novel pathogenic homozygous missense variant in the DOCK8 gene was identified in one patient. CONCLUSIONS: DOCK8 deficiency should be considered as a possibility in any patient with early onset eczema, cutaneous viral infections and increased predisposition to allergy, autoimmunity and malignancy.

Posterior keratometry changes after steep axis phacoemulsification: a prospective study.

Purpose: To measure changes in posterior corneal curvature after steep axis phacoemulsification and investigate the possibility of its effect on SIA. Methods: This was a prospective longitudinal study on 60 consecutive eyes of age-related cataract with regular astigmatism and absence of co-morbidities undergoing uneventful cataract surgeries with main incision at steep meridian. Preoperative and 4 weeks postoperative measurements of anterior and posterior corneal curvatures using Scheimpflug based corneal topographer were performed. Posterior corneal curvature was assessed at 3, 5- and 7-mm diameters. Results: The study found a statistically significant change in posterior corneal K1, K2 and mean astigmatism in all zones (3, 5 and 7 mm) at 4 weeks postoperative, when compared to preoperative readings. Conclusion: Posterior keratometry is likely to be an important determinant of Surgically Induced Astigmatism (SIA) and should be factored in for refractive cataract surgery.

Atezolizumab plus bevacizumab versus lenvatinib as first-line therapy for advanced hepatocellular carcinoma: A systematic review and meta-analysis.

Aim of the study: Studies comparing atezolizumab plus bevacizumab (ATE/BEV) vs. lenvatinib (LEN) for advanced hepatocellular carcinoma (aHCC) have shown conflicting results. With this background, we aimed to collate the available evidence comparing ATE/BEV and LEN in aHCC. Material and methods: A comprehensive search of three databases was conducted from inception to November 2022 for studies comparing ATE/BEV with LEN for managing aHCC. Results were presented with their 95% confidence intervals (95% CI) as the hazard ratio (HR) for time-to-event outcomes or odds ratios (OR) for dichotomous outcomes. Results: A total of 8 studies were included. On analysis of matched cohorts, there was no difference in the objective response rate (ORR) (adjusted odds ratio [aOR] = 1.15, 95% CI: 0.83-1.61) or disease control rate (DCR) (aOR = 0.83, 95% CI: 0.49-1.38) between groups. Three studies reported a significantly longer progression-free survival (PFS) with ATE/LEN, while one reported a longer PFS with LEN. The adjusted hazard ratio (aHR) for PFS available from three studies was comparable (HR = 1.06, 95% CI: 0.75-1.50). Data were insufficient to carry out a formal analysis for overall survival (OS), but none of the studies reported any difference in OS. On comparison of overall adverse events (AE) and ≥ grade 3 AE, there was no difference in the overall analysis, but higher risk of AE with LEN on sensitivity analysis. Conclusions: Based on the currently available literature, LEN was found to be non-inferior to ATE/BEV in terms of ORR, DCR, and PFS. However, LEN may be associated with a higher incidence of AEs. Further head-to-head trials are required to demonstrate the superiority of ATE/BEV over LEN.

Cost-effectiveness of population-based screening for oral cancer in India: an economic modelling study.

Background: Oral cancer screening reduces mortality associated with oral cancer. The current study evaluated the cost-effectiveness of commonly used screening techniques, namely conventional oral examination (COE), toluidine blue staining (TBS), oral cytology (OC), and light-based detection (LBD) in the Indian scenario. Methods: The study used a Markov modelling approach to estimate the cost and health outcomes of four different approaches (COE, TBS, OC, and LBD) for screening oral cancer over time from a societal perspective. The discount rate was assumed as 3%. The outcomes estimated were oral cancer incident cases, deaths averted, and quality-adjusted life years (QALYs). To address the high burden of risk factors (tobacco and/or alcohol) in India, two Markov models were developed: Model A adopted a mass-screening strategy, whereas Model B adopted a high-risk screening strategy versus no screening. Probabilistic sensitivity analysis (PSA) was undertaken to address any parameter uncertainty. Findings: Mass-screening using LBD at three years had the least incident cases (3271.68) and averted the maximum number of oral cancer deaths (459.76). High-risk screening using COE at ten years interval incurred the least lifetime cost of 2,292,816.21 US$ (182,794,468.26 INR). The high-risk strategies (US$/QALY), namely COE 5 years (-29.21), COE 10 years (-90.68), TBS 10 years (-60.54), and LBD 10 years (-13.51), were dominant over no-screening. Interpretation: The most cost-saving approach was the conventional oral examination at an interval of 10 years for oral screening in high-risk populations above 30 years of age. Funding: Department of Health Research, Ministry of Health & Family Welfare, Government of India.

Experimenting with ASL-based arterialized cerebral blood volume as a novel imaging biomarker in grading glial neoplasms.

BACKGROUND: Perfusion imaging is one of the methods used to grade glial neoplasms, and in this study we evaluated the role of ASL perfusion in grading brain glioma. PURPOSE: The aim is to evaluate the role of arterialized cerebral blood volume (aCBV) of multi-delay ASL perfusion for grading glial neoplasm. MATERIALS AND METHODS: This study is a prospective observational study of 56 patients with glial neoplasms of the brain who underwent surgery, and only cases with positive diagnosis of glioma are included to evaluate the novel diagnostic parameter. RESULTS: In the study, ASL-derived normalized aCBV (naCBV) and T2*DSC-derived normalized CBV (nCBV) are showing very high correlation (Pearson's correlation coefficient value of 0.94) in grading glial neoplasms. naCBV and nCBF are also showing very high correlation (Pearson's correlation coefficient value of 0.876). The study also provides cutoff values for differentiating LGG from HGG for normalized aCBV(naCBV) of ASL, normalized CBV (nCBV), and normalized nCBF derived from T2* DCS as 1.12, 1.254, and 1.31, respectively. ASL-derived aCBV also shows better diagnostic accuracy than ASL-derived CBF. CONCLUSION: This study is one of its kind to the best of our knowledge where multi-delay ASL perfusion-derived aCBV is used as a novel imaging biomarker for grading glial neoplasms, and it has shown high statistical correlation with T2* DSC-derived perfusion parameters.