Aggressive Course Research Articles

Molecular medicine-based IBD treatment strategies—we take it personally!

In light of potentially aggressive disease courses of either IBD type—CD or UC—marked by frequent flareups or non-subsiding inflammatory activity, effective immunosuppression is key to preventing progressive tissue destruction and permanent disability. However, over-treating patients with a high probability of an indolent disease course ought to be avoided. To solve this therapeutic dichotomy, there is a pressing need for a reliable classification of patients based on their biosignature to rate their individual prognosis and likelihood of response to a given therapy. This need for pinpoint therapeutic strategies is addressed by the concepts of PreM and the more stringently defined PerM. In this review we summarize the most pivotal study results published so far in the field of individualized IBD care with a special focus on molecular diagnostics and their applicability in the clinical setting.

Advances in the Management of Early-Stage Triple-Negative Breast Cancer.

Triple-negative breast cancer (TNBC) is a subtype of breast cancer with both inter- and intratumor heterogeneity, thought to result in a more aggressive course and worse outcomes. Neoadjuvant therapy (NAT) has become the preferred treatment modality of early-stage TNBC as it allows for the downstaging of tumors in the breast and axilla, monitoring early treatment response, and most importantly, provides important prognostic information that is essential to determining post-surgical therapies to improve outcomes. It focuses on combinations of systemic drugs to optimize pathologic complete response (pCR). Excellent response to NAT has allowed surgical de-escalation in ideal candidates. Further, treatment algorithms guide the systemic management of patients based on their pCR status following surgery. The expanding knowledge of molecular pathways, genomic sequencing, and the immunological profile of TNBC has led to the use of immune checkpoint inhibitors and targeted agents, including PARP inhibitors, further revolutionizing the therapeutic landscape of this clinical entity. However, subgroups most likely to benefit from these novel approaches in TNBC remain elusive and are being extensively studied. In this review, we describe current practices and promising therapeutic options on the horizon for TNBC, surgical advances, and future trends in molecular determinants of response to therapy in early-stage TNBC.

Breast cancer screening in germline mutation carriers. A literature review

Carriers of germline mutations have an increased risk of developing malignant neoplasms. Mutations in the BRCA1/2 gene are the most studied, leading to an increased risk of breast cancer, characterized by early manifestation and aggressive course. The development of screening measures aimed at identifying tumors characteristic of certain mutations will increase the patient’s chances for radical treatment, and therefore lower costs for the treatment of advanced forms of malignant neoplasms. It is important to know the correlation of mutations with the characteristics of their clinical manifestation, the study of this issue will lead to the formation of a medical and economic justification for additional diagnostic procedures.

Recalcitrant Pyoderma Gangrenosum: Clinical Burden and Unmet Needs.

Pyoderma gangrenosum (PG) is a rare, autoinflammatory disease leading to aseptic ulcers which carries a significant disease burden and is often difficult to treat, with many patients failing first-line treatment and requiring additional therapies. Such cases are typically referred to in the literature as "recalcitrant", "refractory", or "resistant", though little is known about the clinical characteristics of such cases. We performed a narrative literature review to characterize patient demographics and clinical course associated with difficult to treat pyoderma gangrenosum cases in order to identify trends to guide future clinical management and therapeutic innovation. We identified 148 cases with clinical manifestations and associated patient demographics stratified by ulcer and patient features. Consistent with previous work, a greater prevalence of PG was observed among female patients and those with a history of inflammatory bowel disease, however interestingly despite an aggressive course to their PG, few patients had comorbidities complicating their disease course. Additionally, despite the requirement of three or more treatments for most patients' disease to resolve, the majority healed within the typical window observed in previous clinical studies with low rates of recurrence. Biologics were the most common medication patients were on at time of remission. Collectively, our results suggest a potential benefit for a reduced threshold for biologic initiation in PG patients and a need for standardization of language in the field to facilitate treatment outcomes comparisons and interventions.

Experience of using talazoparib in the aggressive course of BRCA2-associated triple-negative breast cancer: a clinical observation

The median overall survival for patients with metastatic triple-negative breast cancer is about 12-14 months. Chemotherapy has been the only treatment option for this tumour subtype for a long time, irrespective of immunological and genetic characteristics. Straightforward therapy algorithms have not been defined, and the optimum sequencing of chemotherapy regimens is left to the discretion of the attending physician. Today, impressive findings from clinical studies on the use of immunotherapy and targeted therapy for cancer using PARP inhibitors reflect in current guidelines, raising the chances of patients to prolong life and maintain its high quality. Thus, the use of immunotherapy as first-line treatment of PD-L1-positive tumours allowed to significantly increase the overall survival of patients for the first time in many years. And the use of PARP inhibitors in carriers of BRCA1/2 germline mutations not only significantly prolongs progression-free survival, but also improves quality of life versus standard chemotherapy regimens. The benefit is also observed in patients with an aggressive course of the disease such as damage to the visceral organs and the central nervous system. The presence of BRCA1/2 germline mutations in the genes, damage to the CNS and visceral organs is associated with an extremely unfavourable prognosis and a significant decline in life expectancy. However, a high-quality diagnosis before initiation of treatment, creating proper treatment plans and the use of modern opportunities can improve the outcomes of treatment. The article discusses possible treatment options for metastatic TNBC, reflects current guidelines on the use of immuno- and targeted therapy. A clinical case report of the treatment of a patient with a significantly aggravated history and an aggressive course of TNBC is presented. The patient with visceral metastases, brain damage and early progression after primary treatment has been receiving therapy for two years, while maintaining a satisfactory quality of life.

Dermoscopic Pattern of Basal Cell Carcinoma in H- and Non-H-zones.

Basal cell carcinoma (BCC) localized in the H-zone, the region of fusion of embryonic masses, has been associated with a higher risk of deeper invasion and more frequent recurrence. The aim of the study was to compare dermoscopic features of BCC in H and non-H zone that may most appropriately characterize those two locations. Dermoscopy images of histopathologically confirmed BCCs from 120 patients were retro-spectively analyzed. Dermoscopy features of BCC in H- and non-H zone were described and a comparative study of the dermoscopic pattern of BCC between the two locations was performed. Of 120 BCC cases included in this study, 41 (34.2%) were located in the H-zone. The most frequent histological type was nodular (51.3% in H- zone and 61.6 % in non-H-zone) followed by superficial (5.1% and 19.8 % in H and non-H-zone respectively).In dermoscopy, there was a higher prevalence of ulceration (73.2% versus 43.6%, P < 0.001) in H-zone and a lower prevalence of brown globules (26.8% versus 53.2%; P = 0.01), when compared with the non-H-zone. Our results show that dermoscopic features of BCC on the face fulfill a typical pattern regardless of the region, except for the prevalence of the ulceration which is significantly more frequent in H-zone and the brown globules present significantly more often in the non-H-zone It can be hypothesized that H-zone might predispose to more aggressive course of BCC complicated by ulceration and consequently deeper tissue destruction.

Non-COVID-19 Cutaneous Mucormycosis from a Plastic Surgical Perspective.

Background Cutaneous mucormycosis is a rare and fulminant infection associated with high mortality. Plastic surgeons come across this infection in the settings of road traffic accidents, surgical site infections, and as a secondary infection with underlying bacterial soft tissue infections. Due to this infection's rarity and aggressive course, it is essential to initiate prompt multidisciplinary management at the first presentation. With this study, we aim to present a protocol for managing the condition. Methods This is a retrospective observational study of patients with cutaneous mucormycosis managed at a tertiary care hospital from January 1, 2016 to November 30, 2022 excluding patients with mucormycosis who tested positive for coronavirus disease 2019. Results Of 24 patients, 22 were males, and most were in the age group of 41 to 60 years. Sixteen patients survived and five out of eight deceased had comorbidities, six presented primarily without prior debridement, and six had trunk involvement. Conclusion A high index of clinical suspicion is necessary for early diagnosis and management of patients with invasive cutaneous mucormycosis. A multidisciplinary approach with appropriate medical and surgical management can improve outcomes in cases that otherwise carry a high mortality rate.

Liquid extramedullary disease in multiple myeloma strongly predicts a poor prognosis and is associated with bortezomib resistance gene upregulation

Background-aimPatients with multiple myeloma (MM) relapse with extramedullary disease (EMD) exhibits an aggressive disease course and poor prognostic features. Myelomatous effusion (ME) is a rare subtype of EMD. MethodsIn this retrospective study, we analyzed the baseline characteristics and therapies of 14 EMD patients relapse with ME and 21 EMD patients relapse without ME. ResultsPatients with ME relapse demonstrated higher concentrations of serum lactate dehydrogenase, a higher fraction in the International Staging System stage III, and poorer event-free survival (EFS) (9.3 vs. 36.57 months; P = 0.0013) and overall survival (OS) (12.06 vs. 42.64 months; P < 0.001). The multivariate analysis showed that the presence of ME (hazard ratio [HR] 12.57; P = 0.003) and lack of autologous hematopoietic stem cell transplantation therapy (HR 4.382; P = 0.014) were predictive factors for poor OS. Using single-cell RNA sequencing, we discovered several bortezomib resistance genes were highly expressed in extramedullary malignant plasma cells. ConclusionsThe presence of ME strongly predicts a poor prognosis in patients with MM relapse with EMD, and bortezomib resistance genes are highly expressed in extramedullary malignant plasma cells.

A rare case of neglected long-term pathologic fracture of the distal femur due to a giant cell tumor of bone

Giant cell tumor of bone is a histologically benign bone neoplasia that clinically has an aggressive course. In rare cases, it can give "benign" lung metastases or undergo malignant transformation. The World Health Organization defines this neoplasia as an "aggressive, potentially malignant lesion".&#x0D; Herein, we present a rare case of a neglected long-term pathologic fracture of the distal femur in a 20-year-old female patient. After a biopsy, a giant cell tumor of bone was diagnosed. The patient was treated with intralesional curettage, osteoplasty and plate fixation of the fracture. Eight months postoperatively, no local recurrence or metastasis of the tumor was observed.

Systemic Treatments and Molecular Biomarkers for Perivascular Epithelioid Cell Tumors: A Single-institution Retrospective Analysis.

This study examines systemic treatments for advanced PEComas, a rare group of sarcomas, and identifies molecular biomarkers of prognosis. Our results show that mTOR inhibitors have similar efficacy as chemotherapy, and that TFE3 overexpression, on IHC or FISH, correlates with a more aggressive disease course.

Significance of Tissue Inhibitors of Matrix Metalloproteinases Expression in Pathogenesis and Differential Diagnosis of Periodontal Pathology

Background. The balance of metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) is crucial for the manifestation and progression of periodontal diseases and is one of the promising areas of scientific research in terms of developing methods for selective inhibition of MMPs. Aims to determine the significance of TIMP1 and TIMP2 expression parameters in gingival biopsies to identify the type of periodontitis at the stage of disease manifestation. Methods. A prospective study with parallel inclusion of patients with different forms of periodontitis in the compared groups was performed. The object of this study were patients with various forms of periodontitis. Pathological examination with morphometric analysis of TIMPs expression and subsequent statistical data analysis was performed using AperioImageScope v12.4.0.5043, Statistica 10.0, MedCalc19.6. Results. The study included 67 patients with aggressive (AgP, Grade C, n = 19), chronic simplex (CSP, Grade В, n = 10) and chronic complex (CCP, in the presence of occlusal trauma, Grade В, n = 38) periodontitis and 15 conditionally healthy patients (control group). The expression of TIMP1 and TIMP2 was detected with variable intensity both in the epithelium and in the stroma of the gingiva, and was significantly higher in periodontitis groups compared with the control group (MeTIMP1/2 = 32%/70%). Parameters of TIMP1 and TIMP2 expression had no significant differences in the groups with AgP (MeTIMP1/2 = 84%/98%) and CCP (MeTIMP1/2 = 83%/94%), except for higher parameters of the positivity of epithelial expression of TIMP2 (U = 61 372; p 0.05) and lower levels of intensity of its expression in AgP (MeAgP/CCP=180/171; U = 56 491; p 0.001). Correlation analysis revealed an inverse relationship of TIMPs expression parameters with those MMPs, including those most significant for the development of AgP MMP1 ( = 0.40), MMP8 ( = 0.34), and MMP14 ( = 0.24). ROC analysis established acceptable informativeness of all studied parameters of total expression and positivity of epithelial expression of TIMP1, as well as positivity of total expression and intensity of epithelial expression of TIMP2 to distinguish between aggressive and chronic forms of periodontitis at the stage of disease manifestation. Conclusion. Our results show an increase in the expression of TIMP1 and TIMP2 in various forms of periodontitis and an inverse relationship with the MMPs inhibited by them. This complements both the fundamental knowledge of the development and progression of periodontal pathology and may have applied significance in terms of using the studied TIMP1 and TIMP2 expression criteria to establish the aggressive course of periodontitis already at the stage of disease manifestation, which will allow to individualize treatment, prevent or slow down tooth loss in order to preserve and/or improve the quality of life of this patient group.

Clinical efficacy and tolerability of venetoclax plus rituximab in patients with relapsed or refractory chronic lymphocytic leukemia—a real-world analysis of the Polish Adult Leukemia Study Group

The results of the MURANO trial showed encouraging progression-free survival (PFS) and overall survival (OS) in relapsed/refractory chronic lymphocytic leukemia (RR-CLL) patients treated with venetoclax-rituximab (VEN-R). A retrospective analysis was performed to evaluate the efficacy and safety of VEN-R within the Polish Adult Leukemia Study Group (PALG) centers. The study group included 117 patients with RR-CLL (with early relapse after immunochemotherapy or bearing TP53 aberrations) treated with VEN-R in 2019–2023 outside clinical trials. Patients were treated with a median of 2 (range 1–9) previous lines of therapy. Twenty-two participants were previously treated with BTKi (18.8% out of 117). The median follow-up was 20.3 months (range 0.27–39.1). The overall response rate (ORR) was 95.3% in the group of patients in whom a response to treatment was assessed and 86.3% for all patients. Twenty patients (17.1% out of 117) achieved a complete response (CR), 81 (69.2%) achieved a partial response (PR), and in 5 patients (4.3%), disease progression was noted (assessed as the best response during treatment). The median PFS in the whole cohort was 36.97 (95% CI 24.5, not reached) months, and the median OS was not reached (95% CI 27.03, not reached). Thirty-six patients died during the follow-up, 10 (8.5%; 27.8% of deaths) due to COVID-19 infection. All grade neutropenia (n = 87/117, 74.4%; grade 3 or higher n = 67/117, 57.3%) was the most common treatment adverse event. Forty-five patients (38.5%) remained on treatment, and twenty-two (18.8%) completed 24 months of therapy, while it was discontinued in fifty cases (42.7%). In this real-world setting of early access in very high-risk RR-CLL patients, the VEN-R regimen was associated with shorter median PFS compared with the results of the MURANO trial. This outcome, however, could be attributed to patients’ exposure to SARS-CoV-2 infection and the aggressive course of the disease as very high-risk patients, after multiple lines of prior therapies, were included in the Polish Ministry of Health reimbursement program.

Diagnosis and treatment of the giant malignant peripheral nerve sheath tumor in the anterior mediastinum: A case report

INTRODUCTION: Malignant peripheral nerve sheath tumor (MPNST) occurs in young and middle-aged people, more frequently in those with the genetic disease known as neurofibromatosis type 1 (NF1). Approximately, 50% of people with MPNST have NF1 and 13% of people with NF1 will get MPNST during their lifetime.&#x0D; CASE REPORT: A 30-year-old patient after surgery for MPNST of the right hip in 2013 was observed. In 2017, a relapse was detected, and combined treatment was performed, including surgical excision of the relapse and postoperative distance radiotherapy with a total focal dose of 66 Gy. In 2018, MPNST of the left femoral nerve was diagnosed, and the tumor was excised. In 2020, a chest X-ray diagnosed a single focus of localized opacity in the anterior mediastinum, adjacent to the right lung. Computed tomography (CT) was performed to further verify the neoplasm, which revealed a single hypodense focus in the anterior mediastinum, adjacent to the right lung. According to histological examination of a tumor biopsy obtained by transthoracic ultrasound-guided biopsy, MPNST was verified. Magnetic resonance imaging (MRI) with intravenous contrast enhancement, including real-time MRI, was performed to assess the invasion of the mass into soft tissues and vessels and to plan surgical treatment. The following surgeries were done: right thoracotomy, removal of a neoplasm of the anterior mediastinum with resection of the upper lobe of the right lung, and marginal resections of the lower lobe of the right lung. This case demonstrates a rare localization and non-standard instrumental diagnosis of mediastinal MPNST. Apart from CT scanning, the patient underwent MRI of the thoracic organs. MRI allows assessing the invasion of the neoplasm into the surrounding tissues. This cannot always be achieved by CT scans, including those with contrast enhancement. Invasion is an important component in the planning of further surgical treatment tactics.&#x0D; CONCLUSIONS: MPNST is a tumor with an aggressive course and a poor prognosis due to resistance to therapy. This clinical case demonstrates a rare localized MPNST with a recurrent course and metastases to the lungs. The current radiological methods, such as CT and MRI, may be used effectively both for diagnosing MPNST and determining the appropriate surgical access to the lesion and the extent of surgery.

Cytotoxicity screening of Thymus vulgaris L. in breast cancer: in vitro study.

Breast cancer is one of the leading causes of cancer-related deaths due to its aggressive course. There is an increasing need for alternative therapy strategies, including herbal medications, to treat the disease because of its high incidence. Medicinal plants, such as Thymus vulgaris L. (T. vulgaris), have recently attracted great interest due to the antitumor properties of their extracts. The purpose of this investigation was to ascertain whether T. vulgaris had any cytotoxic effects on two different breast cancer cell lines. MTT test was applied to evaluate the effect of T. vulgaris on cell viability. TUNEL method was used to determine its apoptotic effect. LC3 and Beclin-1 expression levels were determined by immunofluorescence staining method and its autophagic effect was evaluated. Our findings demonstrate that T. vulgaris greately lowers proliferation, both in terms of concentration and duration. Consistent with decreased proliferation, an increase in apoptotic and autophagic cell death were also observed. The migration capacity of MCF-7 and MDA-MB-231 breast cancer cells was greatly suppressed by T. vulgaris, while significantly reducing colony formation. This study is the first to look into how T. vulgaris methanol extract affects breast cancer cells. All of these findings demonstrate that T. vulgaris prevents breast cancer cells from developing a malignant phenotype. It is possible to say that the methanol extract of T. vulgaris is suitable for the treatment of breast cancer, including aggressive types. However, in vivo research should support these results.

Clinical characteristics of cervical cancer in patients infected with human immunodeficiency virus

Background. Infection caused by human immunodeficiency virus (HIV) is a slowly developing anthroponosis with a long course and a variety of clinical manifestations, which finally results in acquired immunodeficiency syndrome (AIDS). Over the past 4 decades, the HIV / AIDS pandemic has been considered as one of the world’s most serious public health problems. Globally, there were approximately 38 million people living with HIV in 2022; 53 % of them were women. The number of HIV-infected patients living in Russia reaches 1,168,000. The incidence and prevalence of HIV infectionvaries across different regions of Russia. High prevalence of cervical cancer usually correlates with HIV prevalence, which is associated with the long-term and aggressive persistence of human papillomavirus (HPV) in HIV patients. HIV co-infection is believed to be the main risk factor for HPV-related precancerous lesions to the cervical epithelium and their rapid progression to invasive cancer. Aim. To analyze risk factors for poor prognosis in HIV-infected patients with HPV. Materials and methods. This study included 15 HIV-infected patients with cervical cancer treated in Novosibirsk Regional Clinical Oncology Dispensary or Federal Research and Clinical Center for Specialized Medical Care and Medical Technologies, Federal Biomedical Agency of Russia between 2016 and 2021. Results. Median age of the patients was 38 years; all of them were HPV-positive. Their viral load was &gt;400 copies / mL and baseline CD4+ cell count ≥350 cells / mL. All patients were diagnosed with AIDS, given the presence of HPV infection. During the therapy for cervical cancer, patients also received combination antiretroviral treatment, including Lamivudine Advanced at a dose of 300 mg / day. Ten patients received comprehensive treatment, while 8 patients received chemoradiotherapy. Conclusion. Given the more aggressive course of cervical cancer in HIV-infected patients, their treatment plan should be developed by a multidisciplinary team, including an infectious disease specialist, clinical pharmacologist, radiotherapist, and gynecological oncologist. Such patients should receive maximal antitumor treatment, as well as intensive antiretroviral therapy. HIV-positive women with cervical cancer require special attention to ensure treatment completion and to optimize long-term outcomes.

Посткоитальный цистит как причина сексуальной дисфункции у женщин.

Introduction. Postcoital cystitis is a special form of recurrent cystitis. Against the background of this disease, especially with an aggressive course, the daily activity of patients may change, the quality of life may deteriorate, and sexual dysfunction may develop. Aim. Study the prevalence of sexual dysfunction in patients with recurrent postcoital cystitis, as well as to assess their quality of life. Material and methods. The study compared two groups of patients: the main (first group) and control (second group). The first group included 70 women with recurrent postcoital cystitis. The control group included 70 women without recurrent postcoital cystitis. To assess the prevalence of sexual dysfunction was used: Female Sexual Function Index (FSFI). Patients' quality of life indicators were determined using the SF12v2 questionnaire. Results. The total FSFI score between the groups was statistically significantly different. Sexual dysfunction was detected in patients with recurrent postcoital cystitis in 88.6% of cases, and in 15.7% among women in the control group. Quality of life indicators significantly differed between the groups. More pronounced changes were observed in the mental component of the quality of life. Conclusion. Our data indicate a high incidence of sexual dysfunction in patients with recurrent postcoital cystitis, as well as the impact of postcoital cystitis on the quality of life.

Small-Cell Carcinoma of the Prostate - Challenges of Diagnosis and Treatment: A Next of Kin and Physician Perspective Piece.

This article was co-authored by a patient's relative describing their experiences of receiving a diagnosis and subsequent clinical management of a rare form of prostate cancer, neuroendocrine prostate cancer (NEPC). The difficulty of receiving this diagnosis, particularly as this was terminal with no options for systemic treatment, and experiences throughout this process are detailed. The relative's questions regarding the care of her partner, NEPC and clinical management are answered. The treating physician's perspective regarding clinical management is enclosed. Prostate cancer remains one of the most common cancer diagnoses, with small-cell carcinoma (SCC) of the prostate representing 0.5-2% of these. Prostatic SCC frequently develops in patients previously treated for prostate adenocarcinoma, more rarely arising de novo. Diagnosis and management present clinical challenges owing to its rarity, frequently aggressive disease course, lack of specific diagnostic and monitoring biomarkers, and treatment limitations. Current pathophysiological understanding of prostatic SCC, genomics and contemporary and evolving treatment options in addition to current guidelines are discussed. Written principally from the patient's relatives and physician experience with discussion of current evidence, diagnostic and treatment options, we hope this piece is informative for both patients and healthcare professionals alike.

Cardiac autonomic neuropathy as risk factor of diabetic complications progression

Introduction. Diabetes mellitus (DM) is the most common and incapacitating endocrine disorder. Diabetic foot syndrome (DFS) is one of the most serious complications of DM, which is the main cause of nontraumatic lower-extremity amputations. Despite the efforts of the entire medical community, the survival rate of DFS patients with non-healing ulcers and after foot surgery does not exceed 50% over 5 years and is comparable to the survival rates of patients with colorectal cancer.Aim. It has been demonstrated that postsurgical diabetic foot wounds tend to chronization of inflammatory process. The diabetic autonomic neuropathy can be involved in diabetic foot damages. We hypothesized that progression of cardiovascular autonomic neuropathy (CAN) leads to aggressive microvascular complications of diabetes and delay the postsurgical wound healing in diabetic foot patients during 2 years of observation.Materials and methods. We examined 94 outpatients with postsurgical diabetic foot wounds and observation period of two years. The clinical neurological examination and standard cardiovascular autonomic reflex tests with identification of severe/advanced abnormalities were performed at baseline and after 2 years. The progression of CAN was diagnosed in cases of an increase in the amount of cardiovascular autonomic reflex tests by 1 score and more. The unsatisfactory result of wound treatment was detected in patients with wound healing delay and new cases of surgery debridement, foot amputations and Charcot foot during 2 years of observation.Results. The mean duration of diabetes was 10.7 year, HbA1c 8.3%, LDL-Chol 3.3 mmol/l, TG 1.8 mmol/l. The 51.1% patients had been amputated in the level of foot, 48.9% patients had surgery debridement. All patients had CAN, confirmed/severe forms in 57.4% cases. The progression of CAN was found in 22.3% patients, the most of them with functional stage at baseline. The aggressive course of CAN increased the risk of progression of diabetic sensomotor neuropathy (OR = 14.6; 95% CI 3.0–70.5; p = 0.0006), nephropathy (OR = 22.4; 95% CI 3.4–147.4; p = 0.0009) and unsatisfactory result of wound treatment (OR = 40; 95% CI 6.0–268.5; p = 0.0001).Conclusions. The patients with diabetic foot surgery wounds has high risk of confirmed/severe CAN and its progression during 2 years. The aggressive course of CAN associates with unsatisfactory result of wound treatment and progression of microvascular diabetic complications.

782-P: Efficacy of Tirzepatide in People with Young-Onset T2D in the SURPASS Program

Young-onset T2D, defined as diagnosed before age 40, presents with a more aggressive disease course, faster beta-cell deterioration and reduced response to diabetes treatment compared to later-onset T2D. Tirzepatide (TZP), a novel glucose-dependent insulinotropic polypeptide and glucagon-like peptide 1 receptor agonist, was recently approved for the treatment of type 2 diabetes (T2D). This post-hoc analysis assessed the effect of tirzepatide on glycemic control, body weight (BW) and cardiometabolic markers in participants with young-onset T2D from the SURPASS program. Changes from baseline in mean HbA1c, BW, waist circumference (WC), and cardiometabolic markers including lipids, and blood pressure (BP) were compared in participants with young-onset (N=873, 20.5%) vs later-onset T2D (N=3394, 79.5%) at Week 40 (SURPASS-1, -2, -5) or Week 52 (SURPASS-3). No differential treatment effect was observed for participants with young- vs later-onset T2D. Tirzepatide treatment led to similar improvements in HbA1c and BW in both subgroups at Week 40/52 for all TZP doses (Figure). Furthermore, TZP (all doses) improved WC, lipids (triglycerides and HDL) and systolic BP similarly between the two groups. In conclusion, tirzepatide treatment led to similar improvements in HbA1c, BW and cardiometabolic markers (WC, lipids, SBP) in participants regardless of having young-onset or later-onset T2D. Disclosure P.Zeitler: Consultant; Eli Lilly and Company, Boehringer Ingelheim Inc., Johnson &amp; Johnson. R.J.Galindo: Consultant; Novo Nordisk, Eli Lilly and Company, Sanofi, Pfizer Inc., Bayer Inc., WW (Weight Watchers), Research Support; Novo Nordisk, Eli Lilly and Company, Dexcom, Inc. M.J.Davies: Advisory Panel; Lilly, Boehringer-Ingelheim, Novo Nordisk, Sanofi, Lexicon Pharmaceuticals, Inc., Pfizer Inc., Medtronic, ShouTi Pharma Inc., Consultant; Lilly, Boehringer-Ingelheim, Novo Nordisk, Sanofi, Research Support; AstraZeneca, Novo Nordisk, Sanofi-Aventis U.S., Boehringer-Ingelheim, Janssen Pharmaceuticals, Inc., Speaker's Bureau; Lilly, Boehringer-Ingelheim, Novo Nordisk, AstraZeneca, Napp Pharmaceuticals Limited, Novartis, Sanofi. B.Bergman: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company. V.Thieu: None. C.Nicolay: Employee; Eli Lilly and Company. S.Allen: None. C.Lee: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company. Funding Eli Lilly and Company

Effects of Heterogeneity on Cancer: A Game Theory Perspective

In this study, we explore interactions between cancer cells by using the hawk–dove game. We analyze the heterogeneity of tumors by considering games with populations composed of 2 or 3 types of cell. We determine what strategies are evolutionarily stable in the 2-type and 3-type population games and what the corresponding expected payoffs are. Our results show that the payoff of the best-off cell in the 2-type population game is higher than that of the best-off cell in the 3-type population game. When these mathematical findings are transferred to the field of oncology they suggest that a tumor with low intratumor heterogeneity pursues a more aggressive course than one with high intratumor heterogeneity. Some histological and genomic data on clear cell renal cell carcinomas is consistent with these results. We underline the importance of identifying intratumor heterogeneity in routine practice and suggest that therapeutic strategies that preserve heterogeneity may be promising as they may slow down cancer growth.