Activation of Stimulator of Interferon Genes (STING): Promising Strategy to Overcome Immune Resistance in Prostate Cancer.

Prostate cancer (PCa) is the most frequent and second-lethal cancer among men. Despite considerable efforts to explore treatments like autologous cellular immunotherapy and immune checkpoint inhibitors, their success remains limited. The intricate tumor microenvironment (TME) and its interaction with the immune system pose significant challenges in PCa treatment. Consequently, researchers have directed their focus on augmenting the immune system's anti-tumor response by targeting the STimulator of the Interferon Genes (STING) pathway. The STING pathway is activated when foreign DNA is detected in the cytoplasm of innate immune cells, resulting in the activation of endoplasmic reticulum (ER) STING. This, in turn, triggers an augmentation of signaling, leading to the production of type I interferon (IFN) and other pro-inflammatory cytokines. Numerous studies have demonstrated that activation of the STING pathway induces immune system rejection and targeted elimination of PCa cells. Researchers have been exploring various methods to activate the STING pathway, including the use of bacterial vectors to deliver STING agonists and the combination of radiation therapy with STING agonists. Achieving effective radiation therapy with minimal side effects and optimal anti-tumor immune responses necessitates precise adjustments to radiation dosing and fractionation schedules. This comprehensive review discusses promising findings from studies focusing on activating the STING pathway to combat PCa. The STING pathway exhibits the potential to serve as an effective treatment modality for PCa, offering new hope for improving the lives of those affected by this devastating disease.

Isolated Tricuspid Valve Repair Versus Replacement: Predictors of Mortality on the National Level.

OBJECTIVE: Isolated tricuspid valve surgery (TVR) is rarely performed, and literature reports are confined to small sample sizes and old studies. Thus, the advantage of repair over replacement could not be determined. We aimed to evaluate repair and replacement outcomes along with predictors of mortality for TVR on a national level. METHODS: All adult patients (18+ years old) who underwent TVR from 2011 to 2020 were identified using the National Inpatient Sample dataset. The primary outcome was in-hospital mortality. Secondary outcomes included complications, length of stay (LOS), hospitalization cost, and discharge disposition. RESULTS: Over a 10-year period, 37,931 patients had TVR and predominantly underwent repair (n = 25,027, 66.0%). In comparison with patients who underwent tricuspid replacement, more patients with a history of liver disease and pulmonary hypertension presented for repair surgery, and fewer patients had endocarditis and rheumatic valve disease (P < 0.001). The repair group had less mortality, less stroke, shorter LOS, and reduced cost, while the replacement group had fewer myocardial infarctions (P < 0.05). However, the outcomes were not different for cardiac arrest, wound complications, or bleeding. After excluding congenital TV disease and adjusting for relevant factors, TV repair was associated with a reduced in-hospital mortality by 28% (adjusted odds ratio [aOR] = 0.72, P = 0.011). Older age increased mortality risk by 3-fold, prior stroke by 2-fold, and liver diseases by 5-fold (P < 0.001). Patients undergoing TVR in recent years had a better chance of survival (aOR = 0.92, P < 0.001). CONCLUSIONS: TV repair has better outcomes than replacement does. Patient comorbidities and late presentation play an independently significant role in determining outcomes.

The World-Wide Adaptations of Diabetic Management in the Face of COVID-19 and Socioeconomic Disparities: A Scoping Review.

Diabetes is an increasingly prevalent chronic disease throughout the world. It is imperative for patients to have access to reliable treatment and resources in order to avoid long-term complications. Economic and social factors contribute to the accessibility of these resources and have a direct impact on diabetes management. Socioeconomic status (SES) presents challenges to diabetic management due to financial and geographical access to care, medications, educational resources, healthy food options, and physical activity. The coronavirus (COVID-19) pandemic exacerbated these challenges, especially during the height of lockdowns. Therefore, it is important to gain insight into how the pandemic challenged diabetes management, taking into consideration socioeconomic disparities. The objective is to assess how the COVID-19 pandemic has impacted the care of chronic diabetic patients internationally and determine how these outcomes vary between patients of different socioeconomic classes. The following study was designed as a scoping review and utilized PubMed, EMBASE, CINAHL, and Web of Science. A Boolean search strategy combined search terms as follows: (((COVID-19) AND (diabetes)) AND ((socioeconomic factors) OR (social inequality OR standard of living))) AND (treatment OR management). Inclusion criteria included studies addressing diabetic patients, socioeconomic variables (income, occupation, level of education, and ethnicity), glycemic control, and degree of access to quality healthcare. Studies exploring the pathophysiology of COVID-19 or diabetes mellitus were excluded. In addition, studies were chosen between the years 2020 and 2022. The search resulted in 214 articles. The full-text assessment was then conducted on the remaining 67 articles. After screening for eligibility and relevance, 19 articles were retained for this review. The results of this study indicate that 8 out of the 18 studies revealed worse outcomes for those with diabetes mellitus and concomitant COVID-19 infection. Patients with diabetes were more likely to be hospitalized and represent a larger percentage of COVID-19 fatalities. In addition, patients with diabetes and co-morbid COVID-19 infection were more likely to have a higher hemoglobin A1c (HbA1c), belong to a lower SES, and have worse glycemic control due to pandemic-associated lockdown. In order to combat the effects of the pandemic, many countries created novel and innovative management strategies. Overall, there are positive and negative effects from the pandemic on diabetic management strategies. This scoping review identified successes in diabetic treatment under pandemic conditions and areas that need optimization. The successful adaptations of many nations convey the capacity for new policy implementation to care for diabetic patients regardless of SES.

Acquisition of IDH2 mutations in relapsed/refractory AML is associated with worse patient outcomes.

OBJECTIVES: The presence of targeted therapy, Enasidenib, for IDH2-mutated AML underscores the importance of understanding the clonal dynamics of IDH2 mutations, which has not been elucidated. In the largest study of IDH2 clonal dynamics, we detail the IDH2-evolutionary patterns and their clinical significance. METHODS: We analyzed ~6000 patients with NGS results to identify 120 AML patients with IDH2 mutations and longitudinal NGS testing. IDH2 mutation status was recorded at diagnosis, remission, relapse, and persistent disease. RESULTS: One hundred and five patients were IDH2-positive at the initial diagnosis, and 15 acquired the mutation later. Of those 15 patients, 7 patients gained the mutation during persistent disease, 6 during relapse, and 2 at remission. Twenty-one patients (18%) who were IDH2-positive in a prior test remained IDH2-positive in remission. Twenty-four patients with IDH2-positive AML were IDH2-positive at relapse. IDH2-positive at diagnosis had better survival than IDH2 mutation acquired later in disease (P = .024). Patients who were IDH2-negative in remission had significantly improved survival (P = .002). Also, loss-of-IDH2 mutation with persistent disease had better OS (P = .035). CONCLUSIONS: There are 70% that clear IDH2 in disease remission. 12% gain IDH2 mutation later, usually in the setting of refractory/relapsed AML. These patients fared worse. Longitudinal IDH2 testing may be helpful in prognostic stratification.