Nitric oxide in modulating oxidative stress mediated skeletal muscle insulin resistance.

Insulin resistance (IR) being the major cause behind different metabolic disorders, has attracted a lot of attention. Epidemiological data shows marked rise in the cases over a period of time. Nitric oxide (NO), produced from nitric oxide synthases (NOS), is involved in a variety of biological functions, alteration in which causes various disorders like hypertension, atherosclerosis, and angiogenesis-associated disorders. IR has been found to be a contributing factor, which is associated with abnormal NO signalling. Skeletal muscle is essential for metabolism, both for its role in glucose uptake and its importance in metabolic disease. In this article, we give an overview of the significance of NO in oxidative stress (OS) mediated IR, describing its role in different conditions that are associated with skeletal muscle IR. NO is found to be involved in the activation of insulin receptor downstream pathway, which suggests absence of NO could lead to reduced glucose uptake, and may ultimately result in IR.

Mechanistic Review on the Role of Gut Microbiota in the Pathology of Cardiovascular Diseases.

Cardiovascular diseases (CVDs), which stand as the primary contributors to illness and death on a global scale, include vital risk factors like hyperlipidemia, hypertension, diabetes, and smoking, to name a few. However, conventional cardiovascular risk factors offer only partial insight into the complexity of CVDs. Lately, a growing body of research has illuminated that the gut microbiome and its by-products are also of paramount importance in the initiation and progression of CVDs. The gastrointestinal tract houses trillions of microorganisms, commonly known as gut microbiota, that metabolize nutrients, yielding substances like trimethylamine-N-oxide (TMAO), bile acids (BAs), short-chain fatty acids (SCFAs), indoxyl sulfate (IS), and so on. Strategies aimed at addressing these microbes and their correlated biological pathways have shown promise in the management and diagnosis of CVDs. This review offers a comprehensive examination of how the gut microbiota contributes to the pathogenesis of CVDs, particularly atherosclerosis, hypertension, heart failure (HF), and atrial fibrillation (AF), explores potential underlying mechanisms, and highlights emerging therapeutic prospects in this dynamic domain.

Clinicopathological and oncological outcomes in upper extremity Ewing's sarcoma: A single institutional experience.

Background: Ewing's sarcoma is highly aggressive bone tumor having predilection for younger age groups with t (11,22) translocation, recombines the FLI-1 and EWS genes on chromosome 22. This disease requires multi-disciplinary treatment withneo-adjuvant chemotherapy followed by surgery or radiotherapy and adjuvant chemotherapy. This study was aimed to assess the demographic distribution, clinical behaviour and oncological outcome of Ewings Sarcoma involving upper extremity. Methods: From 2015 to 2022, 45 patients of upper extremity Ewing's sarcoma underwent treatment at a territory cancer centre. A total of 26 patients treated with surgical management were included in the study comprising 15 males (57.7 %) and 11 females (42.3 %). Mean age of presentation was 26 years (3-43 years). The most common site for Ewings sarcoma of upper extremity was Humerus(42 %) followed by Scapula(27 %), Radius(15 %), Ulna(8 %), Metacarpals(4 %) and Clavicle(4 %). Out of 26 cases, 19 (73%) underwent limb salvage surgery and 7 (27%) underwent ampuation surgery. Results: In limb salvage group reconstruction with Extra-corporeal radiotherapy (ECRT), Ulna centralization, Megaprosthesis and 3D printed scapula was performed following wide resection of tumor. In Amputation group ray resection in one case and forequarter amputation was performed in six cases. Mean serum LDH value was 335 IU/L (2.3X Normal value) and serum albumin was 4.04 gm/dl. Mean tumour necrosis after neo-adjuvant chemotherapy was 68 %. Out of 26 cases, 19(73 %) cases underwent limb salvage and 7 patients underwent amputation surgery. Out of 26, 13 (50 %) patients developed metastasis on follow up. The Event free survival (EFS) in current study was 70 % at 12 months and 40 % at 24 months. Mean Event free survival (EFS) in current study was 33.5 months (22.3-44.6) and Median Event free survival (EFS) in current study was 25 months (19.7-30.2). Conclusion: This study characterises demographic and oncologic outcomes of upper extremity ewings sarcoma in Indian subpopulation. Pain and swelling were prominent clinical findings at presentation in patients with upper extremity Ewing's sarcoma. The survival rate following limb salvage surgery in Ewings sarcoma of upper extremity was comparable to that of patients with amputation surgery. Ewings sarcoma of upper extremity was associated with higher LDH level which was raised more than twice the normal range and can led to worse oncologic outcomes. A comparative study on upper extremity and lower extremity ewings sarcoma will be of help to improve literature on this rare disease.

Role of bone scintigraphy (bone scan) in skeletal osteosarcoma: A retrospective audit and review from tertiary oncology centre.

Introduction: Bone scan is a investigation which uses radionuclide phosphonate compound for whole skeletal survey. In this current study we have done the analysis of the role of bone scan in skeletal osteosarcoma at tertiary oncology care centre. Material & methods: This is a retrospective study conducted in a tertiary oncology centre from January 2022 to February 2023. A total of 92 patients with skeletal OGS were included in our study undergone 99 mTCcMDP whole body bone scan. 99 mTc MDP was prepared freshly every morning and dose for each patient were calculated as per EANM guidelines. Images were acquired 2-3 h of post injection. All images were acquired at GE infinia dual head machine with peak setting at 140Kev and LEAP collimator. Suspicious lesions on planer bone scan were correlated with SPECT fused with CT. All the bone scans were reviewed retrospectively by two independent nuclear medicine physicians. Results: In this study group, 86 patients with biopsy proven skeletal OGS underwent 99 mTCcMDP bone scan of which 63 were males and 23 were females (2.7:1) with age of study group ranging from 7years to 48years. Patients referred for bone scan were retrospectively categorized in two groups, first group patients (52) were referred for initial staging of disease and second group of patients (34) were referred for follow-up or re-staging of the disease. Total 09 patients showed distant skeletal metastases on bone scan, out of which 05 were in initial staging group and 04 in follow up group. Conclusion: Osteosarcoma has propensity to metastasize to many sites in the body however most common site being lung followed by skeletal, nodal and rarely soft tissue metastasis. Bone scan enjoys a optimal sensitivity in case of osteosarcoma to detect skeletal metastasis but have low specificity. However being a cost effective and faster investigation makes it a wise investigation of choice in case of osteosarcoma for skeletal metastasis evaluation.

Neoadjuvant Chemoradiation Followed by Surgery for Locally Advanced Squamous Cell Carcinoma Esophagus: Demographics and Evaluation of Prognostic Factors at a Tertiary Care Center in India.

Neoadjuvant chemoradiation followed by surgery has been the standard of care for locally advanced carcinoma esophagus. We present our experience and inference of various factors associated with the same treatment and the prognostic influence of the same. A retrospective analysis of a cohort of 132 squamous cell carcinoma esophagus patients post neoadjuvant chemoradiation operated with curative intent was carried out. The 2-year overall survival rate was 64.5%. A pathological complete response was achieved in 32.5% of patients and was the only factor that significantly determined overall survival (p = 0.048). Neoadjuvant chemoradiation before surgery for locally advanced squamous cell cancer of the esophagus remains the standard of care with a pathological complete response being a significant factor in predicting overall survival. More prospective randomized studies are necessary to analyze factors affecting and predicting a pathological complete response which would help organ preservation in patients with a complete response.

Secretory Carcinoma of Salivary Glands: A Case Series and Review of Literature.

Mammary analogue of secretory carcinoma is a recently described entity in WHO 2017 classification of head and neck tumours. It resembles secretory carcinoma of breast. It usually affects the salivary glands and has an indolent behaviour. We reviewed five cases of Mammary analogue of secretory carcinoma in our institute and compared our results with existing literature. All the patients underwent surgical resections and appropriate adjuvant treatment. Immunohistochemistry is an alternative cost effective tool as compared to genetic testing to differentiate secretory carcinoma from its mimickers. Surgery with adequate margins followed by adjuvant therapy is the treatment of choice.

Mucosal Malignant Melanoma of Head and Neck: A Case Series from a Single Institute and Review of Literature Abstract.

Malignant melanoma is an aggressive malignancy of melanocytes which is usually found on sun exposed areas of the body. A rare variant of this disease with no etiological association is the mucosal malignant melanoma found on all mucosal surfaces of the body including the oral cavity, respiratory mucosa and anorectal region. In the head and neck region, this disease is almost always diagnosed at an advanced stage and requires a very high index of suspicion for diagnosis. It is more commonly found in females than males.Indians are more prone to this disease as compared to Caucasians.Due to the obscure location within the oral and nasal cavity, it is clinically found at an advanced stage and requires surgical resection with adequate margins for complete eradication. This may be achieved either endoscopically in the nasal cavity or with wide local resection in the oral cavity. this in certain cases may not be feasible due to vicinity of vital structures. In such cases, adjuvant radiotherapy helps in the local control of disease. Histopathological evaluation of the specimen helps to determine aggressive biology of tumor with factors such as presence of ulceration, nodular morphology and perineural invasion being high risk features for development of local and regional recurrence. Supplementary Information: The online version contains supplementary material available at 10.1007/s12070-023-04001-y.