An increase in the incidence of melanoma has been observed in recent decades, which poses a significant challenge due to its poor prognosis in the advanced and metastatic stages. Previously, chemotherapy and high doses of interleukin‑2 were available treatments for melanoma; however, they offered limited survival benefits and were associated with severe toxicities. The treatment of metastatic melanoma has been transformed by new developments in immunotherapy. Immune checkpoint inhibitors (ICIs), monoclonal antibodies that target cytotoxic T‑lymphocyte‑associated antigen‑4 (CTLA‑4), programmed cell death protein 1 (PD‑1) and its ligand, PDL‑1, have emerged as promising therapeutic options. Commonly used ICIs, such as ipilimumab, nivolumab and pembrolizumab, have been found to be associated with an improved median overall survival, recurrence‑free survival and response rates compared to traditional chemotherapies. Combination therapies involving different types of ICIs, such as anti‑PD1 with anti‑CTLA‑4, have further enhanced the overall survival and response rates by targeting various phases of T‑cell activation. Additionally, the development of novel biomarkers has facilitated the assessment of responses to ICI therapy, with tissue and serum‑based prognostic and predictive biomarkers now available. The increased response observed with ICIs also provides potential for immune‑related adverse effects on various organ systems. Further research is required to evaluate the efficacy and safety of various combinations of ICIs, while ongoing clinical trials explore the potential of newer ICIs. Concerns regarding the development of resistance to ICIs also warrant attention. The present review summarizes and discusses the advent of ICIs with a marked significant breakthrough in the treatment of metastatic melanoma, providing improved outcomes compared to traditional therapies.

Trichobezoars are concretions of retained, undigested material, mostly hair or hair-like fibers in the stomach. Rapunzel syndrome is the condition when trichobezoars extend into the small bowel, leading to various complications including bowel obstruction, and perforation due to pressure necrosis. We present an interesting case of trichobezoar in a 15-year-old female patient, who presented with abdominal pain for one month duration. The exam was notable for a firm palpable mass in the epigastric area associated with localized tenderness and guarding. Contrast-enhanced CT of the abdomen showed a distended stomach with the bezoar, dilated duodenal loops, and clumping of proximal jejunal loops. Upper gastrointestinal endoscopy showed a trichobezoar extending from the oesophagogastric junction to the pylorus. Endoscopic removal of the trichobezoar was not successful. An elective laparotomy was performed, during which the stomach, duodenum, and proximal jejunum were dilated. The trichobezoar, measuring 35 cm in length, extended from the body of the stomach to the proximal jejunum and caused jejunal perforation due to pressure necrosis. The trichobezoar was removed and primary closure of jejunal perforation with diversion gastrojejunostomy and jejunostomy was done. There were no postoperative complications. The patient followed up with psychiatry in the clinic after discharge, she was diagnosed with trichotillomania and started on fluoxetine, with improvement in her behavioral symptoms. In young female patients with nonspecific chronic abdomen pain and a palpable mass, trichobezoar should be considered in the differential diagnosis. Contrast-enhanced abdomen CT is the preferred imaging modality and removal of the trichobezoar with an appropriate endoscopic or surgical procedure is the treatment of choice. It is essential to diagnose and treat the underlying behavioral condition to prevent recurrent episodes.

Background and Objective: Tranexamic acid (TXA) has recently shown promising results in the treatment of melasma. The objective of this study was to generate statistical evidence on the efficacy of TXA with different routes. Materials and Methods: We searched studies in PubMed, Cochrane, ClinicalTrials.gov, and Scopus using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines. A change in melasma area and severity index (MASI)/modified MASI score from the baseline at the end of 8 and 12 weeks was seen. Inverse variance method was used for continuous data to measure standard mean difference (SMD) at a 95% confidence interval (CI). RevMan version 5.4 was used for analysis, and statistical heterogeneity across studies was reported using I² statistics. P < 0.05 was considered significant. Results: Totally, 28 randomized control trials were included. At 8 weeks, oral TXA showed a significant change in SMD of 1.61, 95% CI 0.44–2.79, P = 0.007; at 12 weeks, oral TXA showed SMD of 2.39, 95% CI 1.42–3.35, P < 0.00001 compared to adjuvant treatment. At 8 weeks, topical TXA did not show a significant change with SMD of -0.05, 95% CI -1.08–0.97, P = 0.92; at 12 weeks, topical TXA did not show a significant change with SMD of 0.66, 95% CI -0.10–1.42, P = 0.09 compared to adjuvant treatment. Similarly, for intradermal TXA at 8 weeks, results were not significant with SMD of 1.21, 95% CI -0.41–2.83, P = 0.14, and at 12 weeks, SMD was -0.55, 95% CI -2.27–1.18, P = 0.54 compared to adjuvant treatment. Conclusion: Tranexamic acid in an oral formulation can be used along with adjuvant treatment for the management of melasma. Data are still required for topical and intradermal routes. Owing to the fact that our included studies had a lot of heterogeneity, more research is needed along with addressing the adverse effects of tranexamic acid as well as its variation in different skin colors.

Background: Hypertrophic Cardiomyopathy (HCM) is a complex cardiac condition characterized by hypercontractility of cardiac muscle leading to a dynamic obstruction of left ventricular outlet tract (LVOT). Mavacamten, a first-in-class cardiac myosin inhibitor, is increasingly being studied in randomized controlled trials. In this meta-analysis, we aimed to analyse the efficacy and safety profile of Mavacamten compared to placebo in patients of HCM. Method: We carried out a comprehensive search in PubMed, Cochrane, and clinicaltrials.gov to analyze the efficacy and safety of mavacamten compared to placebo from 2010 to 2023. To calculate pooled odds ratio (OR) or risk ratio (RR) at 95% confidence interval (CI), the Mantel-Haenszel formula with random effect was used and Generic Inverse Variance method assessed pooled mean difference value at a 95% CI. RevMan was used for analysis. P<0.05 was considered significant. Results: We analyzed five phase 3 RCTs including 609 patients to compare mavacamten with a placebo. New York Heart Association (NYHA) grade improvement and KCCQ score showed the odds ratio as 4.94 and 7.93 with p<0.00001 at random effect, respectively. Cardiac imaging which included LAVI, LVOT at rest, LVOT post valsalva, LVOT post-exercise, and reduction in LVEF showed the pooled mean differences for change as -5.29, -49.72, -57.45, -36.11, and -3.00 respectively. Changes in LVEDV and LVMI were not statistically significant. The pooled mean difference for change in NT-proBNP and Cardiac troponin-I showed 0.20 and 0.57 with p<0.00001. The efficacy was evaluated in 1) A composite score, which was defined as either 1·5 mL/kg per min or greater increase in peak oxygen consumption (pVO2) and at least one NYHA class reduction, or a 3·0 mL/kg per min or greater pVO2 increase without NYHA class worsening and 2) changes in pVO2, which was not statistically significant. Similarly, any treatment-associated emergent adverse effects (TEAE), treatment-associated serious adverse effects (TSAE), and cardiac-related adverse effects were not statistically significant. Conclusion: Mavacamten influences diverse facets of HCM comprehensively. Notably, our study delved into the drug’s impact on the heart’s structural and functional aspects, providing insights that complement prior findings. Further large-scale trials are needed to evaluate the safety profile of Mavacamten.

With the advancements made in oncology, such as molecularly targeted therapies and immune checkpoint inhibitors, their use has significantly improved the outcomes of patients with cancer. In addition, these advancements have led to an increased incidence of cardiotoxicity, ranging from subclinical dysfunction to severe cardiomyopathy. Hence, it is imperative to enable the early detection and prevention of cardiotoxicity to mitigate irreversible cardiac damage. Exosomal microRNAs (miRNAs) have emerged as promising non‑invasive biomarkers due to their stability in biological fluids and their ability to reflect early myocardial stress and damage. Unlike traditional biomarkers such as troponins, which indicate damage after myocardial injury has occurred, miRNAs can detect subclinical changes earlier, enabling timely intervention. Exosomal miRNAs not only serve as diagnostic biomarkers, but also provide therapeutic potential by modulating molecular pathways associated with cardiotoxicity. Understanding the regulatory mechanisms of miRNA expression in chemotherapy‑induced cardiotoxicity can pave the way for personalized cardioprotective strategies, minimizing cardiovascular complications during cancer therapy. The present review discusses the role of various miRNAs as biomarkers for the early diagnosis of cardiotoxicity induced by chemotherapeutic agents.

Ghosal hematodiaphyseal dysplasia (GHDD) is a rare autosomal recessive disorder characterized by increased bone density involving diaphyses of long bones and defective hematopoiesis. It is due to biallelic variants in the TBXAS1 (OMIM*274180) gene, which encodes for thromboxane synthase. We present a rare case of a middle-aged woman who presented with chronic anemia and bone pain. About 31-year-old Southeast Asian female with a history of persistent iron deficiency anemia (6.1 gm/dL) presents with bilateral knee pain for 4 years. Autoimmune panel turned out to be negative. CT scan of the lower limbs showed multilamellated endosteal thickening specifically involving diaphyses with severe narrowing of medullary canal. PET CT scan revealed tubular remodeling, intramedullary ground glass matrix, and mild cortical thickening with increased FDG uptake in diaphyseal regions of femur and tibia. Bone marrow biopsy of left tibia revealed fibrocellular marrow with dyserythropoiesis. Considering the slow progression of illness over 4 years and radiological evidence suggestive of bone remodeling with severe narrowing of medullary canal as the cause of anemia, the patient underwent molecular analysis for GHDD. Results revealed homozygous p.Arg412Gln (exon 11) in TBXAS1 gene. Considering the effect of NSAIDs on cyclooxygenase and its downstream metabolites, oral Aspirin 150 mg/day was initiated. Hemoglobin improved to 11 gm/dL at 3-month follow-up visit. The complexity of reaching a diagnosis of GHDD underscores the importance of maintaining a high clinical suspicion and thorough analysis of radiological evidence. The treatment for GHDD involves aspirin, a readily available drug.