Guntur Medical College

Breast cancer (BC) continues to be a significant challenge in oncology, primarily due to the emergence of drug resistance, which severely limits treatment efficacy and adversely affects patient outcomes. This review aims to elucidate the mechanisms underlying drug resistance in BC, focusing on the roles of the estrogen receptor (ER) and human epidermal growth factor receptor 2 (HER2) signaling pathways. It identifies advanced therapeutic strategies that effectively target and overcome resistance by analyzing these pathways. This review integrates a comprehensive selection of clinical data and cell lines with known resistance profiles, encompassing both clinical and laboratory settings. It employs cutting-edge techniques such as highthroughput sequencing, proteomics, and advanced imaging. Key measurements include receptor expression levels, pathway activation states, and drug response data, analyzed using bioinformatics tools for genetic and proteomic insights and statistical models to determine the clinical significance of the findings. The review identifies specific mutations and alterations in the ER and HER2 pathways that contribute to drug resistance. Notably, it highlights novel biomarkers and resistance mechanisms, including the upregulation of alternative signaling cascades and mutations in downstream effectors. It also emphasizes promising targeted therapeutic strategies, such as combination therapies and next-generation inhibitors, which have demonstrated encouraging results in preclinical models. In conclusion, this review provides critical insights into the intricate mechanisms of drug resistance in BC, underscoring the pivotal roles of the ER and HER2 signaling pathways. It identifies unique resistance mechanisms and potential therapeutic targets, paving the way for the development of advanced strategies to improve treatment outcomes.

This study presents a comprehensive comparison of various severe plastic deformation (SPD) techniques: high-pressure torsion, friction stir processing (FSP), accumulative roll bonding, and equal channel angular pressing, in refining the grain structure and enhancing the properties of AA2024 aluminum alloy. Microstructural results confirmed that all SPD methods led to notable grain refinement, with FSP achieving the smallest and most evenly distributed grains. Phase analysis revealed that each technique promoted effective dissolution and reprecipitation of precipitates, along with strain-induced phase transformations. Although a slight reduction in tensile strength was observed due to grain softening, the FSP sample showed a marked improvement in elongation. Corrosion behavior indicated enhanced corrosion resistance for all SPD-treated samples. FSP showed the most positive corrosion potential (Ecorr) and the lowest corrosion current density (Icorr). Wear tests demonstrated that FSP resulted in the least material loss and the lowest coefficient of friction, confirming improved wear performance in all processed variants. Among the SPD techniques, FSP emerged as the most effective in enhancing the mechanical, corrosion, and tribological properties of the AA2024 alloy, making it a promising method for demanding structural applications.

BACKGROUND:Minimally invasive liver resection is increasingly used for hepatic malignancies, with laparoscopic liver resection (LLR) achieving outcomes similar to open surgery. Limitations of laparoscopy in complex resections have led to the growing adoption of robotic liver resection (RLR). This meta-analysis compares peri-operative outcomes between laparoscopic and robotic approaches in hepatic resections. PATIENTS AND METHODS:This Preferred Reporting Items for Systematic Reviews and Meta-Analyses-compliant meta-analysis was conducted with a comprehensive search in February 2025 across PubMed, Cochrane, Scopus, CINAHL and Google Scholar for studies comparing RLR and LLR in adults undergoing hepatic resection. Primary outcomes included R0 resection rate, major complications (Clavien-Dindo ≥III), and conversion to open surgery. Secondary outcomes included operative time, blood loss and length of stay. RESULTS:Twenty-nine studies comprising 7678 patients (LLR: 5025 and RLR: 2653) were included. R0 resection and post-operative complications were comparable between approaches LLR was associated with a higher risk of conversion to open surgery (risk ratio: 1.83; 95% confidence interval [CI], 1.28-2.61) and shorter operative time (mean difference: -20.95 min; 95% CI, -40.53 to -1.38). RLR demonstrated lower intra-operative blood loss (mean difference: 68.22 mL; 95% CI, 38.05-98.38), while the length of hospital stay was similar between groups. CONCLUSION:Robotic and LLRs yield comparable oncologic and peri-operative outcomes, with robotics showing lower conversion rates and less blood loss but longer operative times.

Latent autoimmune diabetes in adults (LADA) is a slowly progressive form of autoimmune diabetes that is frequently misclassified as type 2 diabetes mellitus (T2DM) because of its gradual onset and initial responsiveness to oral hypoglycemic agents. This misclassification may delay appropriate insulin therapy and expose patients to medications that increase the risk of metabolic complications. Sodium glucose cotransporter-2 (SGLT2) inhibitors have been increasingly associated with euglycemic diabetic ketoacidosis (DKA), particularly in individuals with underlying insulin deficiency. Several reports describe euglycemic DKA as the presenting manifestation of previously unrecognized LADA. We report a case of a 55-year-old man with a nine-year history of presumed T2DM treated with metformin and canagliflozin who presented with vomiting, dehydration, and metabolic acidosis. Laboratory evaluation revealed high anion gap metabolic acidosis and marked ketosis despite only modest hyperglycemia, consistent with euglycemic DKA. The patient was successfully treated with intravenous fluids, insulin infusion, and electrolyte replacement. Further evaluation demonstrated markedly elevated anti-glutamic acid decarboxylase (GAD65) antibodies and reduced C-peptide levels, confirming autoimmune β-cell failure consistent with LADA. The SGLT2 inhibitor was discontinued, and the patient was transitioned to a basal-bolus insulin regimen with structured diabetes education. This case highlights how slowly progressive autoimmune diabetes may remain unrecognized for years and may be unmasked by metabolic stressors or SGLT2 inhibitor therapy. Clinicians should consider autoimmune diabetes in adults with atypical diabetes phenotypes or unexpected ketoacidosis and use antibody testing and C-peptide measurement to guide diagnosis and management.

Abstract Purpose Extraintestinal manifestations of inflammatory bowel disease (IBD) include anxiety and depression, with estimates varying across IBD types. We conducted a review and meta-analysis to estimate prevalence and incidence of anxiety and depression in IBD, compare psychiatric burden in Crohn’s disease (CD) and ulcerative colitis (UC), and identify heterogeneity. Methods MEDLINE (PubMed) and Embase were searched for anxiety/depression in IBD until May 2026. Random-effects meta-analyses calculated pooled prevalence/risk; heterogeneity was evaluated through Cochran’s Q, I², τ², and meta-regression. PROSPERO ID CRD420261297050. Results Twenty-two studies were included in the analysis. Thirteen studies ( n = 5,616) reported an anxiety prevalence of 24% (95% CI, 19–30%), and 15 studies ( n = 5,956) reported a depression prevalence of 24% (95% CI, 20–28%). Six cohort studies showed that IBD was associated with increased anxiety (HR 1.36, 95% CI, 1.17–1.59) and depression risk (HR 1.44, 95% CI, 1.35–1.54) versus non-IBD controls. No differences were observed between CD and UC for anxiety (OR 1.05, 95% CI, 0.64–1.73) or depression (OR 1.13, 95% CI, 0.86–1.48). Region explained heterogeneity, and instruments did not influence the estimates. The findings were robust, and no publication bias was identified. Conclusions One in four with inflammatory bowel disease (IBD) experiences anxiety or depression, and Crohn’s disease (CD) and ulcerative colitis (UC) burden suggest inflammation underlies this risk. Findings support assessment, clarify gut-brain links, and identify beneficiaries.