Chikungunya virus infection inhibits B16 melanoma-induced immunosuppression of T cells and macrophages mediated by interleukin 10.

Immunosuppression in cancer poses challenges for immunotherapy and highlights the vulnerability of immunocompromised patients to viral infections. This study explored how Chikungunya virus (CHIKV) infection potentially inhibits B16-F10 melanoma-induced immunosuppressive effects on T cells and RAW 264.7 macrophages. We found high expression of CHIKV entry genes in melanoma and other cancers, with B16-F10 cells demonstrating greater susceptibility to CHIKV infection than non-tumorigenic cells. Interestingly, the CHIKV-infected B16-F10 cell culture supernatant (B16-F10-CS) reversed the immunosuppressive effects of uninfected B16-F10-CS on T cells. This reversal was characterised by decreased STAT3 activation and increased MAPK activation in T cells, an effect amplified by interleukin 10 (IL-10) receptor blockade. In RAW 264.7 cells, B16-F10-CS enhanced CHIKV infectivity without triggering activation. However, blocking the IL-10 receptor (IL-10R) in RAW 264.7 reduced CHIKV infection. CHIKV infection and IL-10R blockade synergistically inhibited B16-F10-CS-mediated polarisation of RAW 264.7 cells towards immunosuppressive macrophage. Our findings suggest that CHIKV modulates cancer-induced immunosuppression through IL-10-dependent pathways, providing new insights into viral-cancer interactions. This research may contribute to developing novel antiviral immunotherapies and virotherapies beneficial for cancer patients and immunocompromised individuals.

Revolutionizing breast ultrasound diagnostics with EfficientNet-B7 and Explainable AI.

Breast cancer is a leading cause of mortality among women globally, necessitating precise classification of breast ultrasound images for early diagnosis and treatment. Traditional methods using CNN architectures such as VGG, ResNet, and DenseNet, though somewhat effective, often struggle with class imbalances and subtle texture variations, leading to reduced accuracy for minority classes such as malignant tumors. To address these issues, we propose a methodology that leverages EfficientNet-B7, a scalable CNN architecture, combined with advanced data augmentation techniques to enhance minority class representation and improve model robustness. Our approach involves fine-tuning EfficientNet-B7 on the BUSI dataset, implementing RandomHorizontalFlip, RandomRotation, and ColorJitter to balance the dataset and improve model robustness. The training process includes early stopping to prevent overfitting and optimize performance metrics. Additionally, we integrate Explainable AI (XAI) techniques, such as Grad-CAM, to enhance the interpretability and transparency of the model's predictions, providing visual and quantitative insights into the features and regions of ultrasound images influencing classification outcomes. Our model achieves a classification accuracy of 99.14%, significantly outperforming existing CNN-based approaches in breast ultrasound image classification. The incorporation of XAI techniques enhances our understanding of the model's decision-making process, thereby increasing its reliability and facilitating clinical adoption. This comprehensive framework offers a robust and interpretable tool for the early detection and diagnosis of breast cancer, advancing the capabilities of automated diagnostic systems and supporting clinical decision-making processes.

Aligned Fibroporous Matrix Generated from a Silver Ion and Graphene Oxide-Incorporated Ethylene Vinyl Alcohol Copolymer as a Potential Biomaterial for Peripheral Nerve Repair.

Developing an ideal nerve conduit for proper nerve regeneration still faces several challenges. The attempts to fabricate aligned substrates for neuronal growth have enhanced the hope of successful nerve regeneration. In this wok, we have attempted to generate an electrospun matrix with aligned fibers from a silver and graphene oxide-incorporated ethylene vinyl alcohol copolymer (EVAL). The presence of silver was analyzed using UV-visible spectra, XPS spectra, and ICP. Raman spectra and FTIR spectra confirmed the presence of GO. The complexation of Ag+ with - OH of EVAL enabled the generation of aligned fibers. The fiber diameter (>1 µm) provided sufficient space for forming focal adhesion by the neurites and filopodia of N2a and C6 cells, respectively. The fiber diameter enabled the neurites and filopodia of the cells to align on the fibers. The incorporation of GO has contributed to the cell-material interactions. The morphological and mechanical properties of fibers obtained in the study ensure that the EVAL-Ag-GO-0.01 matrix is a potential substrate for developing a nerve guidance conduit/nerve wrap (NGC/W).

Advanced female urethral adenocarcinoma: A case report.

ABSTRACT: Urethral cancer in females is a rare occurrence. Although initially believed to be derived from skene glands, there is no consensus on the cell of origin. Squamous cell carcinoma is the most common, whereas adenocarcinoma is the least common. We report the case of a 58-years-old lady with a history of voiding lower urinary tract symptoms, later requiring a suprapubic cystostomy for retention. Cystoscopy and biopsy showed prostate-specific antigen (PSA) negative adenocarcinoma and postiron emission computed tomography (PETCT) showing pelvic and inguinal nodal metastasis. The patient underwent neoadjuvant chemotherapy followed by anterior exenteration with pelvic lymphadenectomy and ileal conduit. Final histology showed ypT4 yN1 adenocarcinoma, not otherwise specified.

Cinnamon-mediated nano emulsion and its cryogenic activity on ROS-affected human sperm-A short study.

Oil-mediated nano emulsion, a more advanced technology than other commercial extenders, will protect spermatozoa for extended periods against ROS and cryo injuries. The study is designed to elucidate the most suitable extender to preserve infertile subjects' sperm cells against ROS damage. This is a significant step forward for the andrology society, as it introduces the use of a nano emulsion extender (natural oil extract) for the first time, particularly for those who are undergoing urology-related defects. The study involved forty-four (44) infertile subjects with smoking habits and forty-two (42) fertile subjects without smoking habits, as per CASA guidelines. Semen preservatives (glycerol and egg yolk citrate), along with our naturally derived nano emulsion components (CN, EN, and EL), were prepared and used to preserve the semen sample for 24 hours. Standard semen parameters (morphology, viability, and integrity), ROS, and sperm acrosome state by staining were measured before and after cryopreservation. The results indicated that the morphology and motility of sperm features were better maintained in the CN-oil-mediated nano emulsion than in other emulsions, and ROS-induced DNA damage was reduced.

Comparison of Trifecta and Pentafecta Outcomes across 3 Surgical Modalities of Partial Nephrectomy (PN) - Open, Lap, and Robotic.

Renal cell carcinoma (RCC) is the most common solid tumor in the kidney (90%), accounting for about 3% of all cancers in adults. Partial nephrectomy (PN) is the surgical procedure primarily used for the treatment of localized kidney tumors. Two commonly used terms to describe the complexity and success of a partial nephrectomy procedure are "trifecta" and "pentafecta." Trifecta is defined as Warm ischemia time (WIT) ≤ 25min or Cold ischemia time (CIT) ≤ 60min, Negative surgical margin (NSM), and no perioperative Clavien-Dindo complications (CDC) of Gr 3 or more [8], whereas pentafecta is defined as trifecta plus >90% preservation of e-Glomerular filtration rate (GFR) and no increase in chronic kidney disease (CKD) stage at 12-months post-operative period. We retrospectively analyzed all patients who underwent partial nephrectomy at a single high-volume tertiary centre, from 2012 to 2020. We included patients who underwent partial nephrectomy by any of the three routes including open (OPN), laparoscopic (LPN), or robotic-assisted (RPN), and in which the follow-up data was available. We compared the trifecta and pentafecta outcomes across the three surgical modalities. We had a total of 183 patients in our study. Twenty-nine percent (53 patients) underwent open surgery, 12.6% (23 patients) underwent laparoscopic surgery and 58.5% (107) underwent robotic assisted surgery. The number of patients who fell under the low risk category in the RENAL scoring system were 70(38.3%), intermediate risk 79 (43.2%) and high risk 34 (18.6%). In the high risk RENAL score group, trifecta was achieved in 5 (50%) patients in OPN, 1(50%) in LPN and 7(31.8%) in RPN with no statistically significant difference (p = 0.581) whereas pentafecta was achieved in 3 (30%) patients in OPN, 1 (50%) in LPN and 7 (31.8%) in RPN with no statistically significant difference (0.855). In the overall cohort, mean WIT, mean hospital stay and mean EBL were higher in OPN as compared to LPN and RPN which was statistically significant (p < 0.001), whereas there was no statistical difference in mean operative time between the three modalities (p = 0.580). Renal tumors can be safely treated by RPN or LPN with lesser morbidity as compared to OPN. Trifecta and Pentafecta outcomes had no significant difference among OPN, LPN, and RPN. RPN and LPN may be considered feasible and safe surgical approaches ensuring good functional outcomes.

Role of HSP90 in Type 2 Diabetes Mellitus and Its Association with Liver Diseases.

Non-alcoholic fatty acid liver disease (NAFLD), non-alcoholic steatohepatitis (NASH) and hepatocellular carcinoma (HCC) are the fatal liver diseases which encompass a spectrum of disease severity associated with increased risk of type 2 diabetes mellitus (T2DM), a metabolic disorder. Heat shock proteins serve as markers in early prognosis and diagnosis of early stages of liver diseases associated with metabolic disorder. This review aims to comprehensively investigate the significance of HSP90 isoforms in T2DM and liver diseases. Additionally, we explore the collective knowledge on plant-based drug compounds that regulate HSP90 isoform targets, highlighting their potential in treating T2DM-associated liver diseases. Furthermore, this review focuses on the computational systems' biology and next-generation sequencing technology approaches that are used to unravel the potential medicine for the treatment of pleiotropy of these 2 diseases and to further elucidate the mechanism.

Revisiting failures in mucogingival surgery.

Failures of soft tissue grafting are relatively common and can be stressful when encountered for both the clinicians and patients. Soft tissue grafting has predictable success most of the time when proper selection and implementation of surgical procedure is done. This case report describes management of soft-tissue surgery failure after multiple mucogingival grafting for enhancing the soft-tissue quality, quantity, and aesthetic outcomes. Augmentation by free gingival graft using periodontal microsurgical principle resulted complete coverage of the defect suggesting that careful treatment planning, immaculate execution by skillful technique definitely helped to achieve a successful result. Simultaneous use of photobiomodulation (PBM) helped in faster and better healing of the grafted area.

Study on Universal Health Coverage Scheme in India - The Stumper to Private Hospitals.

BACKGROUND: Many governments have introduced health insurance schemes for the poor sections of society to save them from catastrophic health expenditure. Private hospitals play a key role in India, as they are in significant number in secondary and tertiary care services. Private hospitals have to fund their infrastructure, staff salaries from the revenue of previous year. In this study, we compared money received by a private medical college hospital bed through government insurance scheme patient and private paying patient. METHODS: Observational study, comparing money reimbursed for top ten procedures treated in private medical college hospitals by Ayushman Bharat (AB) fund and the price offered by a paying patient in similar bed. RESULTS: On average 600 patients received medical care through the AB scheme per month at our tertiary care super-specialty hospital. Highest numbers were seen in specialties like cardiovascular, and cancer treatments and infectious diseases under general medicine specialty. The costs considered were surgeon's cost, medicines, devices, and hospitalization costs. The laparoscopic procedures were incurring a loss of 130%, knee replacements about 50%, coronary bypass grafting thankfully due to controlling of prices by central government is incurring a loss of 10%. The package amount offered accounts to 26-52% only of the costs incurred by the private hospitals. CONCLUSION: The private academic hospitals need 25% to 50% more than current prices offered, across various procedures.

Spermatogonial quantity in prepubertal boys undergoing fertility preservation is comparable between haematological and non-haematological cancers.

Fertility restoration potential of immature testicular tissue (ITT) depends on the number of spermatogonial cells in the retrieved tissue prior to cryopreservation in oncofertility programme. There are limited data on the association between type of malignancy and testicular germ cell population. Hence, this study is aimed to investigate the spermatogonial and Sertoli cell population in ITT retrieved from 14 pre-pubertal boys who opted for fertility preservation. Histopathological and immunochemical analysis of seminiferous tubules from haematological (N = 7) and non-haematological (N = 7) malignant patients revealed 3.43 ± 2.92 and 1.71 ± 1.81 spermatogonia per tubular cross section (S/T), respectively. The Sertoli cell number was comparable between haematological and non-haematological group (18.42 ± 3.78 and 22.03 ± 10.43). Spermatogonial quantity in ITT did not vary significantly between haematological and non-haematological cancers. This observation, though preliminary, would contribute to the limited literature on paediatric male oncofertility.

Evaluation of allylated gelatin as a bioink supporting spontaneous spheroid formation of HepG2 cells.

The spheroid culture system has gained significant attention as an effective in vitro model to mimic the in vivo microenvironment. Even though numerous studies were focused on developing spheroids, the structural organization of encapsulated cells within hydrogels remains a challenge. Allylated gelatin or GelAGE is used as a bioink due to its excellent physicochemical properties. In this study, GelAGE was evaluated for its capacity to induce spontaneous spheroid formation in encapsulated HepG2 cells. GelAGE was synthesized and characterized using 1HNMR spectroscopy and ninhydrin assay. Then the physicochemical and biological attributes of GelAGE hydrogel was examined. The results demonstrate that GelAGE has remarkable ability to induce the encapsulated cells to self-organize into spheroids.

Our Experience of OSAKA Regimen (Bladder Preservation) in Patients with Advanced Bladder Cancer.

Introduction and Objectives: OSAKA regimen is a novel bladder preservation therapy involving balloon-occluded selective arterial infusion of radio-sensitizing chemotherapeutic agent with concurrent hemodialysis (HD), followed by radiation therapy. Objectives are to study the feasibility of this novel regimen in patients with advanced cancer bladder (Ca Bladder). Methods: Two patients having advanced Ca Bladder with cisplatin ineligibility and poor performance status were managed with OSAKA regimen. Patients undergo super selective catheterisation of the anterior division of the internal iliac artery, followed by concurrent instillation of cisplatin (100 mg) via microcatheters and hemodialysis. Within 72 h, definitive radiation therapy is given. Image-guided radiation therapy (IGRT) with Helical Tomo using an Accuracy Radixact Tomography machine was used. 60 Gray/30 fractions is given to the bladder and nodes (50 Gray to bladder and nodes plus margin, with a boost of 10 Gray to bladder plus margin). Response is monitored by 3 monthly fluorodeoxyglucose positron emission tomography (FDG PET) imaging. Results: Our first patient tolerated the procedure well and showed a complete response at 3 months of FDG PET imaging, but unfortunately, 1 year of FDG PET showed bony metastases, and the patient was managed accordingly. Our second patient also tolerated the regimen well, showed a complete response at 3 and 12 months of FDG PET imaging, and is under follow-up. Conclusions: The OSAKA regimen, as a bladder preservation strategy, is feasible and safe in selective advanced Ca Bladder patients.

Deciphering oxygen distribution and hypoxia profiles in the tumor microenvironment: a data-driven mechanistic modeling approach.

Objective. The distribution of hypoxia within tissues plays a critical role in tumor diagnosis and prognosis. Recognizing the significance of tumor oxygenation and hypoxia gradients, we introduce mathematical frameworks grounded in mechanistic modeling approaches for their quantitative assessment within a tumor microenvironment. By utilizing known blood vasculature, we aim to predict hypoxia levels across different tumor types.Approach. Our approach offers a computational method to measure and predict hypoxia using known blood vasculature. By formulating a reaction-diffusion model for oxygen distribution, we derive the corresponding hypoxia profile.Main results. The framework successfully replicates observed inter- and intra-tumor heterogeneity in experimentally obtained hypoxia profiles across various tumor types (breast, ovarian, pancreatic). Additionally, we propose a data-driven method to deduce partial differential equation models with spatially dependent parameters, which allows us to comprehend the variability of hypoxia profiles within tissues. The versatility of our framework lies in capturing diverse and dynamic behaviors of tumor oxygenation, as well as categorizing states of vascularization based on the dynamics of oxygen molecules, as identified by the model parameters.Significance. The proposed data-informed mechanistic method quantitatively assesses hypoxia in the tumor microenvironment by integrating diverse histopathological data and making predictions across different types of data. The framework provides valuable insights from both modeling and biological perspectives, advancing our comprehension of spatio-temporal dynamics of tumor oxygenation.

Glutathione peroxidase (GPX1) - Selenocysteine metabolism preserves the follicular fluid's (FF) redox homeostasis via IGF-1- NMD cascade in follicular ovarian cysts (FOCs).

Follicular ovarian cysts (FOCs) are characterized by follicles in the ovaries that are >20 mm in diameter and persist for >10 days without the corpus luteum, leading to anovulation, dysregulation of folliculogenesis and subfertility in humans and livestock species. Despite their clinical significance, the precise impact of FOCs on oocyte reserve, maturation, and quality still needs to be explored. While FOCs are observed in both human and livestock populations, they are notably prevalent in livestock species. Consequently, livestock species serve as valuable models for investigating the molecular intricacies of FOCs. Thus, in this study, using goat FOCs, we performed integrated proteomic, metabolomic and functional analyses to demonstrate that oocyte maturation is hampered due to increased reactive oxygen species (ROS) in FOCs follicular fluid (FF) via downregulation of glutathione peroxidase (GPX1), a critical antioxidant seleno enzyme required to negate oxidative stress. Notably, GPX1 reduction was positively correlated with the FF's decline of free selenium and selenocysteine metabolic enzymes, O-phosphoryl-tRNA (Sec) selenium transferase (SEPSECS) and selenocysteine lyase (SCLY) levels. Adding GPX1, selenocysteine, or selenium to the culture media rescued the oocyte maturation abnormalities caused by FOCs FF by down-regulating the ROS. Additionally, we demonstrate that substituting GPX1 regulator, Insulin-like growth factor-I (IGF-1) in the in vitro maturation media improved the oocyte maturation in the cystic FF by down-regulating the ROS activity via suppressing Non-sense-mediated decay (NMD) of GPX1. In contrast, inhibition of IGF-1R and the target of rapamycin complex 1 (mTORC1) hampered the oocyte maturation via NMD up-regulation. These findings imply that the GPX1 regulation via selenocysteine metabolism and the IGF-1-mediated NMD may be critical for the redox homeostasis of FF. We propose that GPX1 enhancers hold promise as therapeutics for enhancing the competence of FOCs oocytes. However, further in vivo studies are necessary to validate these findings observed in vitro.

The Role of HSP90 and TRAP1 Targets on Treatment in Hepatocellular Carcinoma.

Hepatocellular Carcinoma (HCC) is the predominant form of liver cancer and arises due to dysregulation of the cell cycle control machinery. Heat Shock Protein 90 (HSP90) and mitochondrial HSP90, also referred to as TRAP1 are important critical chaperone target receptors for early diagnosis and targeting HCC. Both HSP90 and TRAP1 expression was found to be higher in HCC patients. Hence, the importance of HSP90 and TRAP1 inhibitors mechanism and mitochondrial targeted delivery of those inhibitors function is widely studied. This review also focuses on importance of protein-protein interactions of HSP90 and TRAP1 targets and association of its interacting proteins in various pathways of HCC. To further elucidate the mechanism, systems biology approaches and computational biology approach studies are well explored in the association of inhibition of herbal plant molecules with HSP90 and its mitochondrial type in HCC.

The longitudinal behavioral effects of acute exposure to galactic cosmic radiation in female C57BL/6J mice: implications for deep space missions, female crews, and potential antioxidant countermeasures.

Galactic cosmic radiation (GCR) is an unavoidable risk to astronauts that may affect mission success. Male rodents exposed to 33-beam-GCR (33-GCR) show short-term cognitive deficits but reports on female rodents and long-term assessment is lacking. Here we asked: What are the longitudinal behavioral effects of 33-GCR on female mice? Also, can an antioxidant/anti-inflammatory compound mitigate the impact of 33-GCR? Mature (6-month-old) C57BL/6J female mice received the antioxidant CDDO-EA (400 µg/g of food) or a control diet (vehicle, Veh) for 5 days and either Sham-irradiation (IRR) or whole-body 33-GCR (0.75Gy) on the 4th day. Three-months post-IRR, mice underwent two touchscreen-platform tests: 1) location discrimination reversal (which tests behavior pattern separation and cognitive flexibility, two abilities reliant on the dentate gyrus) and 2) stimulus-response learning/extinction. Mice then underwent arena-based behavior tests (e.g. open field, 3-chamber social interaction). At the experiment end (14.25-month post-IRR), neurogenesis was assessed (doublecortin-immunoreactive [DCX+] dentate gyrus neurons). Female mice exposed to Veh/Sham vs. Veh/33-GCR had similar pattern separation (% correct to 1st reversal). There were two effects of diet: CDDO-EA/Sham and CDDO-EA/33-GCR mice had better pattern separation vs. their respective control groups (Veh/Sham, Veh/33-GCR), and CDDO-EA/33-GCR mice had better cognitive flexibility (reversal number) vs. Veh/33-GCR mice. Notably, one radiation effect/CDDO-EA countereffect also emerged: Veh/33-GCR mice had worse stimulus-response learning (days to completion) vs. all other groups, including CDDO-EA/33-GCR mice. In general, all mice show normal anxiety-like behavior, exploration, and habituation to novel environments. There was also a change in neurogenesis: Veh/33-GCR mice had fewer DCX+ dentate gyrus immature neurons vs. Veh/Sham mice. Our study implies space radiation is a risk to a female crew's longitudinal mission-relevant cognitive processes and CDDO-EA is a potential dietary countermeasure for space-radiation CNS risks.

Silymarin enriched gelatin methacrylamide bioink imparts hepatoprotectivity to 3D bioprinted liver construct against carbon tetrachloride induced toxicity.

Three-dimensional liver bioprinting is an emerging technology in the field of regenerative medicine that aids in the creation of functional tissue constructs that can be used as transplantable organ substitutes. During transplantation, the bioprinted donor liver must be protected from the oxidative stress environment created by various factors during the transplantation procedure, as well as from drug-induced damage from medications taken as part of the post-surgery medication regimen following the procedure. In this study, Silymarin, a flavonoid with the hepatoprotective properties were introduced into the GelMA bioink formulation to protect the bioprinted liver against hepatotoxicity. The concentration of silymarin to be added in GelMA was optimised, bioink properties were evaluated, and HepG2 cells were used to bioprint liver tissue. Carbon tetrachloride (CCl4) was used to induce hepatotoxicity in bioprinted liver, and the effect of this chemical on the metabolic activities of HepG2 cells was studied. The results showed that Silymarin helps with albumin synthesis and shields liver tissue from the damaging effects of CCl4. According to gene expression analysis, CCl4 treatment increased TNF-α and the antioxidant enzyme SOD expression in HepG2 cells while the presence of silymarin protected the bioprinted construct from CCl4-induced damage. Thus, the outcomes demonstrate that the addition of silymarin in GelMA formulation protects liver function in toxic environments.

Fluorescence enhancing and quenching signal based on new approach for selective detection of multiple organochlorine pesticides using blue emissive-carbon dot.

Measuring the concentration of organochlorine pesticides (OCPs) in agriculture has engaged significant awareness for healthcare investigation since OCPs are harmful to many physiological processes. Excessive usage of these compounds can result in major contamination of the environment and food supply chains. As a result, more accurate and rapid ways to detect pesticide residues in food are required. In this work, we have portrayed the surface-engineered fluorescent blue emissive-carbon dot (B-CD) with a high quantum yield (49.3 %) via the hydrothermal method for fluorescent sensing of OCPs on real samples. The amine group functionalities of carbon dots have supported the direct coordination with -Cl and -OH groups of HEP, ENS, CDF and 2,4-DPAC for the sensitive detection of OCPs, by switching in the fluorescent intensity of B-CD. The functional group of OCPs exhibits a variety of binding interactions with B-CD to contribute a complex formation, which leads to static quenching via an insubstantial restricted electron transfer process. The synthesized carbon dots exhibit individuality in binding nature towards different OCPs. Fluorescence studies help to distinguish the target OCPs and their low detection limits (LODs) were 0.002, 0.099, 0.16 and 0.082 µM for Heptachlor (HEP - turn "on"), Endosulfan (ENS), Chlordimeform (CDF) and 2,4-dichlorophenoxyacetic acid (2,4-DPAC - turn "off") OCPs respectively. The real water samples and agriculture food samples were effectively investigated and the OCP toxicity was noted. Thus, the design of the fluorescence sensor is established as an easy and proficient sensing method for detecting OCPs.

Survival impact of post-operative immunotherapy in resected stage III cutaneous melanomas in the checkpoint era.

BACKGROUND: Checkpoint inhibitors have shown improvement in recurrence-free survival in the post-operative setting for node-positive melanoma and were first approved in late 2015. However, single-agent checkpoint therapies have yet to show benefit to overall survival (OS) for lower-risk stage III cancers. We evaluated the OS benefit of post-operative immunotherapy in the National Cancer Database (NCDB). PATIENTS AND METHODS: Patient cases were selected from the NCDB 2020 Participant Use File. Patients diagnosed with stage III cutaneous melanoma between 2016 and 2019 who underwent definitive resection for their melanoma were included. OS between those who received post-operative immunotherapy within 84 days of surgery and those who did not was analyzed by the Kaplan-Meier method. Demographic and clinical characteristics between the two groups were compared via Cox proportional hazard models. RESULTS: 14 978 patients with stage III melanoma were included. Of those, 34.9% (n = 5234) received post-operative immunotherapy and 65.1% (n = 9744) did not. Using the American Joint Committee on Cancer version 8 (AJCCv8) staging, 36-month survival was significantly higher in patients who received post-operative immunotherapy compared to no post-operative systemic therapy in those diagnosed with stage IIIB (88.0% versus 84.7%, P = 0.011), IIIC (75.6% versus 68.1%, P < 0.001), or IIID (59.2% versus 48.4%, P = 0.002). No significant improvement in 36-month survival was seen in patients who received post-operative immunotherapy in patients with stage IIIA disease (93.0% versus 92.2%, P = 0.218). CONCLUSIONS: Post-operative immunotherapy had an OS benefit in patients with AJCCv8 stage IIIB, IIIC, and IIID disease, but had no significant survival benefit for patients with stage IIIA melanomas.