Increased Survival Rate Research Articles

Medicaid Expansion and Overall Survival of Lower Gastrointestinal Cancer Patients After Cytoreductive Surgery and Heated Intraperitoneal Chemotherapy.

In the United States, often only tertiary centers offer cytoreductive surgery and heated intraperitoneal chemotherapy (CRS+HIPEC) for peritoneal metastases in advanced lower gastrointestinal malignancies. Growing evidence shows that Medicaid expansion under the Affordable Care Act (ACA) of 2010 enhanced healthcare access and outcomes. We sought to determine whether Medicaid expansion was associated with decreased all-cause mortality of lower gastrointestinal cancer patients following CRS+HIPEC. We analyzed data from the National Cancer Database (2010-2019) on lower gastrointestinal cancer patients who underwent CRS+HIPEC. Medicaid expansion, introduced under the ACA in 2010, extends health insurance to low-income adults. We categorized states by expansion timing: early (2010-2013), immediate (January 2014), late (after January 2014), or no expansion to assess the impact of Medicaid expansion on mortality using a multivariable Cox regression model. Of the 1001 study patients, 671 (67%) were diagnosed in Medicaid expansion states. Grade and Medicaid expansion status were the only factors independently associated with overall survival on multivariable analysis. On average, patients in Medicaid expansion states experienced a 4% increase in annual survival compared with those in non-expansion states who had a 1% decrease in annual survival over the study period. Patients from states that had an early expansion of Medicaid and patients with lower-grade tumors had significantly better overall survival. Our study findings suggest that improved access to healthcare through Medicaid expansion was associated with increased survival rates of lower gastrointestinal cancer patients who undergo CRS+HIPEC for the treatment of peritoneal metastases.

Early Palliative Care in Advanced Non-Small Cell Lung Cancer Patients: A Meta-Analysis.

This study aims to assess the efficacy of Early Palliative Care (EPC) in non-small cell lung cancer (NSCLC) through a meta-analysis approach. A computerized search was conducted in databases such as PubMed, Cochrane Library, Scopus, Embase, and Web of Science for prospective randomized controlled trials (RCTs) investigating the application of EPC in advanced NSCLC. Outcome measures including Overall Survival (OS), quality of life, and psychological status were extracted and subjected to pooled analysis. After the computerized search, a total of 7 studies comprising 1185 participants were included, with 597 patients receiving EPC intervention and 588 patients receiving Standard Care (SC) intervention. Three studies reported OS after the intervention, demonstrating a significant improvement in OS for patients receiving EPC (pooled HR = 1.60, 95% CI: 1.22, 1.98). Five studies analyzed the Functional Assessment of Cancer Therapy (FACT) scores after the intervention, revealing a significant improvement in FACT scores for patients receiving EPC (pooled SMD = 1.18, 95% CI: 1.04, 1.31). No significant differences were found in anxiety and depression scores between the 2 interventions in the 5 studies. In advanced NSCLC, EPC provides benefits in terms of increased survival rates and improved quality of life. EPC should be considered as part of multidisciplinary treatment for patients with advanced NSCLC.

LeAf Trauma- an intersectoral prospective multicenter study assessing quality of life and return to work after majortrauma-study protocol.

With increasing survival rates, the functional outcome and quality of life of trauma patients are gaining more importance. Survivors suffer from chronic pain, psychosomatic disorders, and unemployment as well as increased post-traumatic morbidity, which can lead to an impaired quality of life. So far, the TraumaRegister DGU® records patient data during in-hospital treatment. In this study severely injured patients after major trauma are assessed when discharged from hospital, as well as 6, 12 and 18 months after trauma. The aim is to document cross-sector patient pathways and to identify and quantify the factors influencing the health-related quality of life (hrQoL) and the return to work (RTW), using patient-reported experience measures (PREM) and patient reported outcome measures (PROM). Patients are recruited in certified trauma centers of the German Society for Trauma Surgery (DGU). This study protocol describes the methodology of the prospective multicentre study of LeAf Trauma. Translation of the results will be implemented by using the network structures of the German Society for Trauma Surgery (DGU) for the treatment of patients with major trauma.

Detection and molecular characterization of carbapenem-resistant gram-negative bacterial isolates.

Antimicrobial-resistant bacteria (ARB) are responsible for increased mortality and morbidity. Therefore, this study focuses on evaluating traditional and molecular diagnostic tools of carbapenem-resistant gram-negative bacteria (CRGNB). In order to achieve this, 94 samples, from different patients' specimens, and surrounding environment, were collected from intensive care units (ICUs) at Ain Shams University Specialized Hospital and the National Cancer Institute, Cairo, Egypt. The swabs were cultured on appropriate media, including Chromogenic medium (HiCrome KPC Agar Base "HIMEDI AM1831"), and MacConkey-10µg imipenem disc resulting in 136 isolates with different culture characteristics. Next, the selected isolates were subjected to VITEK 2 machine and 16SrRNA (16S ribosomal RNA) sequencing. The sensitivity of HiCROME KPC agar for CRGNB detection was 99.3% and 94.7%, in reference to the MacConkey-disc and VITEK-2 methods, respectively. The HiCrome KPC agar assumptions for bacterial identification were not as consistent as those of VITEK 2 (with only 47.4% agreement) and 16SrRNA gene sequencing analysis. The approaches discussed in this study facilitate providing rapid diagnosis and treatment of CRGNB, which helps increase survival rates. HiCrome KPC agar is considered a relatively accurate and easy method that can be used in any laboratory. In addition, the selected strains were deposited in the gene bank with the accession numbers OR553657, OR553658, and OR553659. It is noteworthy that Genus Acinetobacter is the major CRGNB isolated from the patients and environmental surfaces in the hospitals. This highlights the importance of proper environmental and terminal cleaning procedures in healthcare facilities and applying control measures to ensure infection prevention.

Abstract 4134692: In-Hospital Mortality Rate and Predictors of 30-Day Readmission in Cancer Patients with MI Undergoing PCI -A Cross Sectional Study From Nationwide Readmission Database

Background and objectives: Data regarding readmission rates and predictors of readmission in cancer patients undergoing PCI are sparce. With the increasing survival rates and prevalence of cardiovascular complications in cancer patients, understanding the patterns and predictors of readmission in this population is paramount for optimizing their outcomes. Cancer patients pose unique clinical challenges due to their combined prothrombotic state and propensity for bleeding. We attempted to identify factors associated with readmission in cancer patients. Methods: We utilized the Nationwide Readmission Database from 2016 to 2020 and included patients more than 18 years of age with primary diagnosis of myocardial infarction(MI) who underwent percutaneous coronary intervention(PCI) and have a preexisting diagnosis of cancer. We used International Classification of Disease, Tenth Revision, Clinical Modification (ICD10 CM) codes to define MI, PCI, and cancer. The primary outcome was the 30-day readmission rate, and secondary outcomes were mortality rates, predictors of readmission, and common causes of readmission. The independent predictors of readmission were analyzed using cox regression analysis. Results: Of the 52,307 cancer patients who underwent PCI, 7,767 were readmitted within a 30-day period. The readmission rate for these patients was 15.70%. The mortality rate was 6.05% for index admission and 6.80% for readmitted cases. Among the readmitted patients in the strongest independent predictor for readmission were leaving against medical advice(AMA), anemia, congestive heart failure, and discharge to a skilled nursing facility or home health. Common causes of readmission within this time included hypertensive heart disease with concomitant CKD stage I-IV and heart failure (6.21%), sepsis (6.12%), NSTEMI (5.60%), hypertensive heart disease with concomitant heart failure (4.62%) and acute kidney injury (1.98%). Conclusions: Thirty-day readmission rate was 15.70%. Independent predictors of readmission were anemia, diabetes mellitus, congestive heart failure, malnutrition, peripheral artery disease, leaving against medical advice, and discharge to facility. Most common cause of readmission was hypertensive heart and kidney disease with heart failure, which comprised 6.21%.

Bystander Response and Out-of-Hospital Cardiac Arrest Outcomes (Bro. Study) in 3 Gulf Countries: Protocol for a Prospective, Observational, International Collaboration Study.

: Globally, there is significant variation in the out-of-hospital cardiac arrest (OHCA) survival rate. Early links in the chain of survival, including bystander cardiopulmonary resuscitation (CPR) and the use of an automated external defibrillator at the scene, are known to be of crucial importance, with strong evidence of increased survival rate with good neurological outcomes. The data from the Middle East are limited and report variable rates of bystander CPR and survival. It is crucial to get prospective, reliable data on bystander response in these regions to help plan interventions to improve bystander response and outcomes. This international collaborative study aims to describe the characteristics, including bystander interventions and outcomes, of OHCAs brought to hospitals enrolled in the study from Abu Dhabi, United Arab Emirates; Doha, Qatar; and Muscat, Oman. It also aims to describe the strength of the association between bystander response and OHCA outcomes, including the return of spontaneous circulation, survival to hospital admission, survival to discharge, and good neurological outcome at discharge in the local context of low bystander CPR rates. This multicenter, prospective, noninterventional observational study (Bro. Study) will be conducted at the emergency departments of 4 participating tertiary care hospitals in 3 countries. The data will be collected prospectively according to the Utstein style (a set of internationally accepted guidelines for uniform reporting of cardiac arrests) on demographic variables (age, sex, nationality, country, participating center, and comorbidities), peri-cardiac arrest variables (location, witnessed or not, bystander CPR, use of automated external defibrillator, time of emergency medical services arrival, initial rhythm, number of shocks, and time of prehospital CPR), and outcome variables (return of spontaneous circulation, survival to discharge, and neurological outcome at discharge and 3 months). Univariate and multivariate analysis with logistic regression models will be used to measure the strength of the association of bystander interventions with outcomes using SPSS (version 22). Data collection began in November 2023 and will continue for 2 years, with publication expected by early 2026. Bystander response to an OHCA is critical to a favorable outcome. The reliable, baseline bystander CPR data will be a cornerstone in the team's next planned projects, which are to qualitatively identify the barriers to bystander CPR, conduct a scoping review of community interventions in the Gulf and other Asian countries, and design and implement strategies to help improve the bystander CPR rate in the community. DERR1-10.2196/58780.

Investigation of the efficacy of siRNA-mediated KRAS gene silencing in pancreatic cancer therapy

Aim Pancreatic carcinoma is an aggressive cancer that progresses without many symptoms. The difficulty of early diagnosis and an inadequate response to traditional treatments also cause the survival rate of pancreatic cancer to be low. Current research is focusing on methods of diagnosis and treatment, such as gene therapy, to increase survival rates. Small interfering ribonucleic acid (siRNA) has emerged as a promising advanced therapeutic strategy for cancer treatment. This study sought to silence the KRAS gene in the human pancreatic carcinoma cell line using a complex of small interfering ribonucleic acid (siRNA) and gold nanoparticles (AuNP). Methods In this study, 25 nM siRNA and gold nanoparticles at 0.5 mg/ml, 0.25 mg/ml, and 0.125 mg/ml concentrations were used to silence the KRAS gene in the CAPAN-1 cell line. Real-time PCR analysis, agarose gel electrophoresis, and double staining were carried out, and xCelligence real-time cell analysis (RTCA) was used to measure proliferation. Results The PCR analysis revealed crossing point (CP) values of actin beta (ACTB) ranging from 33.04 to 35.98, which was in the expected range for all samples. The interaction between the gold nanoparticle/siRNA complex in the double staining analysis revealed that the most effective concentration of gold nanoparticle was 0.125 mg/ml. The WST-1 technique showed that siRNA/AuPEI cells in application groups had a viability rate of over 90%, indicating no toxicity or side effects. The xCELLigence RTCA® showed that at hour 72, there was a significant difference in proliferation in the 0.5 mg/mL PEI/AuNP-siRNA, 0.25 mg/mL PEI/AuNP-siRNA, and 0.125 mg/mL PEI/AuNP-siRNA application groups compared to the control and siRNA groups (p < 0.05). By hour 96, all three groups were statistically different from the control and siRNA groups in terms of proliferation (p < 0.05). Conclusions The results of this analysis suggest that the AuPEI/siRNA complex can be effectively used to silence the target gene, but more studies are needed to verify these results.

Evaluate the Differential Effectiveness of the Case Management and Primary Nursing Models in the Implementation of Discharge Planning.

This study aims to compare the effectiveness of the case management model and the primary nursing care model by focusing on hospital stay length, readmission, follow-up resource utilisation and survival. To improve patient continuity of care, a discharge planning team has been established at the hospital to implement the service concept of long-term medical care. The team works with a multidisciplinary medical team to provide case management, which ensures high-quality patient care. Retrospective case-control study. This study collected data from the medical record information system database and the Ministry of Health and Welfare's care service management information system to explore medical and follow-up care utilisation of patients discharged between 2017 and 2018. This study followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines, with the checklist used to ensure transparent and complete reporting of the methodology and results. To ensure comparability between the case management model group and the primary nursing model group, propensity score matching was used. After matching, 660 individuals from the case management model group and 2876 individuals from the primary nursing model group were selected for further analysis. In this study, patients were primarily involved in the research as participants, providing data through their medical records for analysis. However, no direct involvement from the public or patients was used in the planning or design stages of the research. The study found that factors such as activities of daily living (ADL) score ≤ 60 points, catheterisation, poor chronic disease control and inadequate primary caregiver capacity can lead to longer hospitalisations. Males and patients with catheters have a higher risk of readmission within 30 days, and men, those aged ≥ 75 years, those with ADL score ≤ 60, catheterisation, pressure sores or unclean wounds, financial problems, insufficient primary caregiver capacity and those readmitted within 14 days after discharge had significantly increased mortality after discharge. Although the case management model group had higher hospitalisation days, they had lower readmission rates and higher survival rates than the primary nursing model group. Early consultation with the case manager for discharge planning can help patients to continue to receive care and utilise relevant resources after returning home. Identifying and addressing patient-specific factors can significantly improve patient outcomes by reducing hospitalizations and readmissions, and lowering mortality rates. The case management model is more effective than the primary nursing care model in reducing readmission rates and increasing survival rates. Early consultation with case managers for discharge planning is crucial to ensuring patient care continuity and resource utilization.

Exploring Sex-Based Neuropsychological Outcomes in Pediatric Brain Cancer Survivors: A Pilot Study

Background: The increasing survival rates among pediatric cancer patients underscore the critical need to understand the long-term psychosocial impacts of cancer treatments, such as cisplatin and carboplatin. While these treatments are lifesaving, they may pose risks to neurodevelopmental processes. Despite the substantial body of research highlighting cognitive impairments associated with cancer treatments, there remains a gap in understanding how these effects differ by sex. As sex differences could inform tailored interventions and support mechanisms for affected individuals, this pilot study aimed to examine the sex differences in neuropsychological outcomes in patients treated for brain cancer with cisplatin and/or carboplatin. Methods: Our study employed rigorous/structured neuropsychological assessments to evaluate executive functions in pediatric cancer survivors treated with cisplatin and/or carboplatin. We utilized the BRIEF and TOL tests to assess the key domains of executive function, including inhibitory control, cognitive flexibility, and problem-solving abilities. Additionally, psychosocial factors were evaluated using the Resiliency Scale to measure resilience and the PAT test to assess family psychosocial risk. Results: In our cohort of 17 patients, significant sex differences emerged, where males outperformed females in areas such as inhibitory control, impulse regulation, and strategic planning. Conclusions: These findings highlight the complexity of cognitive outcomes in pediatric cancer survivors. Understanding sex-specific differences is essential for developing tailored interventions that optimize cognitive and psychosocial outcomes. Future research should focus on larger cohorts and longitudinal studies to validate these findings and guide targeted interventions to improve survivorship outcomes.

Impact of physical activity on physical function and quality of life after liver transplantation

Introduction and aim of the study: Liver-related diseases are very common in our society, and as a result, the number of people requiring liver transplantation is likewise increasing. In our research, we intended to analyze the topic of increasing survival rates and improving comfort along with the quality of life while waiting for a transplant, as well as in the postoperative period. We determined that we would investigate the impact of physical activity on risk factors that increase hospitalizations after surgery and decrease quality of life. We summarized the effect and type of exercise on sarcopenia, frailty, and their direct relation to the pre- and post-operative period of liver transplantation. In addition, we analyzed possible obstacles and difficulties arising from the implementation of physical activity in liver transplant recipients. Materials and methods: The authors conducted an extensive review of articles available in PubMed, Google Scholar, UpToDate, Science Direct, and Cochrane databases. The keywords liver transplantation, physical activity, quality of life, sarcopenia, and frailty were the basis of the review. Studies published between 2001 and 2024 were included in the review. Results: The vast majority of the studies emphasized the positive effects of exercise, particularly aerobic and resistance training, on improving the clinical conditions and well-being of liver transplant patients. The papers with inconsistent results nevertheless underscored the need to delve further into this topic. Thus, the overall evidence supports the inclusion of physical exercise in post-transplant care as a key strategy for improving health and quality of life. Conclusion: Regular physical activity is beneficial for clinical outcomes and patients’ quality of life after liver transplantation.

Perioperative Considerations in Patients with Rett Syndrome as Compared to Those with Cerebral Palsy.

Retrospective cohort study. This study aimed to compare perioperative outcomes of Rett syndrome and Cerebral palsy patients undergoing posterior spinal fusion for neuromuscular scoliosis. Surgical correction in the treatment of scoliosis for patients with Rett syndrome (RS) has been shown to increase survival rate. Cerebral palsy (CP) patients, like RS patients, are often nonverbal, nonambulatory, with frequent surgical complications. Retrospective review of 36 RS and 80 CP patients undergoing PSF from 2005-2023. Data and x-ray measurements were collected pre- and post-operatively. Sub-analysis was performed comparing non-ambulatory patients (GMFCS IV-V). Wilcoxon-Rank Sum, Fisher's Exact, and Chi-square tests were utilized. The primary outcome measure, complication rates, was similar between the groups (P=0.09). Preoperative Cobb angle, levels fused, fixation points, and LOS were similar (P>0.05). EBL was significantly higher in CP patients as was rate of transfusion (P=0.001) and surgical time (P=0.001). Postoperative Cobb angle (P=0.002) was significantly higher for CP patients. There was no significant difference between CP and RS patients in both preoperative (P=0.383) and postoperative (P=0.051) coronal decompensation. Nonambulatory status was associated with increased odds of having a postoperative complication (OR=6.17, 95% C.I. 1.36 - 28.04). Sub-analysis of non-ambulatory RS and CP patients revealed significantly higher postoperative Cobb (P=0.008), EBL (P=0.019) and surgical time (P=0.017) in CP patients compared to RS patients. There were no significant differences in preoperative Cobb, levels fused, fixation points, hospital stay, or complication rate (P>0.05). RS patients are shown to have better outcomes to CP patients in terms of surgical, perioperative, and radiographic variables. Ambulatory status was identified as an independent risk factor for complications.

Fertility Preservation in Postpubertal Males Undergoing Cancer Treatment in a Middle-Income Country: Is it Possible Despite the Barriers?

Increased survival rates in childhood cancer have led to an emphasis on the importance of treatment-related infertility. Fertility preservation methods should be explained to every patient and their families (PaFs) before treatment. Establishing good communication with PaFs is crucial in this regard despite many barriers such as cultural and financial barriers. Routine feasibility of sperm preservation (SP) in adolescent males newly diagnosed with cancer was evaluated after the implementation of reimbursement for the procedure and storage by the national healthcare system. Males <18 years of age planned to undergo cancer treatment between 2021 and 2023 were included. Patient and their families were informed by the treating physician about the disease, treatment modality, side effects, the importance of SP, and the method. Information about the purpose and technique of SP was provided to the patient alone in a comfortable environment. Questions from PaFs were answered, and consent was obtained. The procedure and storage cost was covered by the social security institution. Seventeen patients (median age 15) (15 with bone/soft tissue sarcoma, 1 brain tumor, and 1 Hodgkin lymphoma) were included. There were no refusals for SP. Eleven patients were able to provide sperm samples. Of the 6 patients who could not provide sperm, 3 stated embarrassment, 2 anxiety, and 1 cancer-related pain. Increasing awareness among physicians about the importance of treatment-related infertility, allocating sufficient time to inform PaFs about fertility preservation, and providing information taking into account societal or socio-cultural factors will contribute to preventing treatment-related infertility. Establishing close communication with the Reproductive Health Center (RHC), along with the rapid and cost-free nature of the procedure, enhances success.

Time to Rethink Bronchiolitis Obliterans Syndrome Following Lung or Hematopoietic Cell Transplantation in Pediatric Patients.

Background: Similar in histological characteristics and clinical manifestations, bronchiolitis obliterans syndrome (BOS) can develop following lung transplantation (LTx) or hematopoietic cell transplantation (HCT). In contrast to lung transplantation, where BOS is restricted to the lung allograft, HCT-related systemic graft-versus-host disease (GVHD) is the root cause of BOS. Because lung function declines following HCT, diagnosis becomes more difficult. Given the lack of proven effective medicines, treatment is based on empirical evidence. Methods: Cross-disciplinary learning is crucial, and novel therapies are under investigation to improve survival and avoid LTx. Recent advances have focused on updating the understanding of the etiology, clinical features, and pathobiology of BOS. It emphasizes the significance of learning from experts in other transplant modalities, promoting cross-disciplinary knowledge. Results: Our treatment algorithms are derived from extensive research and expert clinical input. It is important to ensure that immunosuppression is optimized and that any other conditions or contributing factors are addressed, if possible. Clear treatment algorithms are provided for each condition, drawing from the published literature and consensus clinical opinion. There are several novel therapies currently being investigated, such as aerosolized liposomal cyclosporine, Janus kinase inhibitors, antifibrotic therapies, and B-cell-directed therapies. Conclusions: We urgently need innovative treatments that can greatly increase survival rates and eliminate the need for LTx or re-transplantation.

Evaluating the Impact of Adjunctive Partial Cryoablation on Dual Checkpoint Inhibitor Immunotherapy Response in a Murine Model.

Purpose To evaluate the impact of adjunctive partial cryoablation on checkpoint inhibitor (CPI) immunotherapy response. Materials and Methods One hundred fifty-six mice (equal number of male and female animals) with dual-implanted tumor models were treated with dual CPI or a vehicle and randomized to treatment of a single tumor with partial cryoablation. Tumors were followed for 60 days following cryoablation for response assessment. In additional groups, the tumor microenvironment was characterized via flow cytometry, cytokine analysis, and immunohistochemistry. Statistical comparison was made between the different treatment groups regarding T-cell infiltration and activation characteristics within the noncryoablated tumor and cytokine levels within the partially ablated tumor. Additionally, qualitative assessment of T-cell activation within the cryoablated and noncryoablated tumors at immunofluorescence was carried out. Results At 60 days following treatment, CPI and adjunctive cryoablation-treated MC-38 mice had a significantly increased survival rate (79%) compared with mice treated with CPI alone (61%; P < .001). CT-26 mice also had an increased survival rate (57% vs 35%, respectively; P = .04). Following cryoablation, increases in inflammatory cytokines and chemokines within the treated tumors were observed. Flow cytometry of noncryoablated tumor showed increased CD8 T-cell activation. Immunofluorescence and histologic evaluation following cryoablation further demonstrated a robust CD8 T-cell and myeloid infiltrate. Conclusion Adjunctive cryoablation significantly increased the response to dual CPI in multiple cancer models at both partially ablated and distant (nonablated) tumor sites. Immune analysis suggests cryoablation promotes a vigorous immune response within the partially cryoablated tumor that increases activation of the adaptive immune system within distant tumor sites. Keywords: Cancer, Cryoablation, Checkpoint Inhibitor Immunotherapy, Tumor Response Supplemental material is available for this article. © RSNA, 2024.

Eukaryotic expression of chitinase from dark sleeper (Odontobutis potamophila) and its effects on growth and immunity

Chitinase, an enzyme that hydrolyzes β-1,4-glycosidic bonds to degrade chitin, is essential for the digestion of chitin in fish. In this study, the chitinase OpCht from Odontobutis potamophila was expressed in Pichia pastoris, and its enzymatic properties and functional effects were evaluated. The findings revealed that OpCht exhibited optimal activity at pH 6.0 and 50 °C, with stability in the pH range of 4–8 and temperatures from 4 to 40 °C. K+, Na+, Ca2+, Mg2+, Mn2+, Hg2+, and Al3+ showed varying degrees of activation on the enzyme. At the end of the 8-week trial, the addition of OpCht significantly increased the height of intestinal villi and the thickness of the muscular layer, leading to significantly weight in the treated groups. The alleviation of intestinal inflammation also resulted in an increased survival rate (SR) of O. potamophila. High concentration treatment groups (2, 4 μg/g) showed significantly elevated digestive enzyme activities, as well as increased antioxidant enzyme activities and immune parameters. These results demonstrate that the P. pastoris expression system has successfully produced the chitinase OpCht from O. potamophila, and the addition of a certain concentration of OpCht can promote fish growth and enhance immune functions, offering a promising enzyme preparation for the aquaculture industry.

In situ endoscopic photodynamic therapy combined with immature DC vaccination induces a robust T cell response against peritoneal carcinomatosis.

Immunogenic cell death (ICD) and ferroptosis have recently emerged as key factors in the anticancer immune response. Among the treatments able to induce ICD and the associated release of danger signals is photodynamic therapy (PDT). Ferroptosis for its part results from lipid peroxidation and is induced by CD8+ T cells to kill nearby cancer cells on IFN-γ production. We aimed to combine the two concepts, that is, to evaluate whether the strong pro-oxidant effects of PDT may promote ferroptosis and antigen release and to develop a procedure for in situ PDT to prepare the soil for highly endocytotic immature dendritic cell (iDC) adoptive transfer. This approach was implemented for managing peritoneal carcinomatosis, a lesion often associated with poor outcomes. We used three-dimensional (3D) heterotypic spheroids made of cancer cells, exposed them to a white light-activated OR141 photosensitizer (PS), and subsequently complexified them by adding iDC and naive lymphocytes. We next used a model of mouse peritoneal carcinomatosis and administered PDT using laparoscopy to locally induce photoactivation using the endoscope light. The immune response following adoptive transfer of iDC was tracked both in vivo and ex vivo using isolated immune cells from in situ vaccinated mice. Cancer cells undergoing PDT-induced cell death significantly increased ICD markers and the infiltration of iDCs in spheroids, relying on ferroptosis. These actions induced the sequential activation of CD8+ and CD4+ T cells as revealed by a significant spheroid 3D structure deterioration and, remarkably, were not recapitulated by conventional ferroptosis inducer RSL3. Using LED light from an endoscope for in situ photoactivation of PS enabled us to apply the vaccination modality in mice with peritoneal tumors. Consecutive intraperitoneal injection of iDCs resulted in delayed tumor growth, increased survival rates, and prevented tumor relapse on rechallenge. CD8+ T cell response was supported by depletion experiments, nodal detection of early activated T cells, and ex vivo T cell-induced cytotoxicity toward spheroids. The combination of in situ PDT locally delivered by an endoscope light and iDC administration induces a durable memory immune response against peritoneal carcinomatosis thereby opening new perspectives for the treatment of a life-threatening condition.

Cells and signals of the leukemic microenvironment that support progression of T-cell acute lymphoblastic leukemia (T-ALL).

Current intensified chemotherapy regimens have significantly increased survival rates for pediatric patients with T-cell acute lymphoblastic leukemia (T-ALL), but these treatments can result in serious adverse effects; furthermore, patients who are resistant to chemotherapy or who relapse have inferior outcomes, together highlighting the need for improved therapeutic strategies. Despite recent advances in stratifying T-ALL into molecular subtypes with distinct driver mutations, efforts to target the tumor-intrinsic genomic alterations critical for T-ALL progression have yet to translate into more effective and less toxic therapies. Ample evidence now indicates that extrinsic factors in the leukemic microenvironment are critical for T-ALL growth, infiltration, and therapeutic resistance. Considering the diversity of organs infiltrated by T-ALL cells and the unique cellular components of the microenvironment encountered at each site, it is likely that there are both shared features of tumor-supportive niches across multiple organs and site-specific features that are key to leukemia cell survival. Therefore, elucidating the distinct microenvironmental cues supporting T-ALL in different anatomic locations could reveal novel therapeutic targets to improve therapies. This review summarizes the current understanding of the intricate interplay between leukemia cells and the diverse cells they encounter within their tumor microenvironments (TMEs), as well as opportunities to therapeutically target the leukemic microenvironment.

Evolving Role of Lymphedema Surgery on Breast Reconstruction: A Systematic Review and Multi-Institutional Algorithmic Approach.

Background/Objectives: Recent advancements in breast cancer treatment have led to increased survival rates, prompting a shift towards addressing breast cancer-related lymphedema (BCRL). Despite the evolving role of lymphatic surgery in breast reconstruction, there is limited literature evaluating the current role of lymphatic surgery in breast reconstruction. This review aims to evaluate the state of lymphatic surgery in breast reconstruction, analyzing surgical techniques and proposing a multi-institutional algorithmic approach. Methods: Through a search and screening of literature, data regarding the study type, type of operation (bypass, pLVB/ILR/LYMPHA, VLNT, or a combination of treatments), and clinical outcomes were collected. Results: The systematic review included 184 studies. Overall, the number of publications on lymphatic surgery increased from 4.4 per year (2010-2016) to 21.1 per year since 2017. The most published procedure was vascularized lymph node transfer (34.6%), followed by preventive lymphatic surgery (31.4%), therapeutic lymphovenous bypass (23.3%), and combined breast and lymphatic reconstruction (10.7%). While VLNT was the most published procedure, preventive surgery has been the most published topic since 2020, with 11.7 articles per year since. Similarly, there has been an increase in studies on combined lymphatic surgery and breast reconstruction in the last five years, with 16 articles published. Conclusions: The role of lymphatic surgery in breast cancer patients is evolving, with an increasing emphasis on preventive procedures and combined reconstructive approaches. However, our study shows that the current literature is predominantly based on lower-level evidence, highlighting the need for more randomized controlled trials to establish stronger clinical recommendations.

Prim-O-glucosylcimifugin alleviates influenza virus-induced pneumonia in mice by inhibiting the TGF-β1/PI3KCD/MSK2/RELA signalling pathway.

Prim-O-glucosylcimifugin (POG) is a chromone derived primarily from Saposhnikovia divaricata (Turcz) Schischk and Cimicifuga simplex. Previous research has shown that POG possesses antibacterial, anticancer, anti-inflammatory, antioxidant, anticonvulsant, antipyretic, and analgesic properties. However, the specific impact of POG on influenza-virus-induced pneumonia is not well understood. In this study, we investigated the protective effects and underlying mechanisms of POG in pneumonia caused by influenza A virus (IAV). In vitro, POG was found to have a protective effect against infections caused by the respiratory viruses respiratory syncytial virus (RSV), human coronavirus OC43, and influenza A virus. POG inhibited A/FM/1/1947(H1N1) infection with an EC50 ranging from 3.01 to 10.43 in vitro. Intraperitoneal infection of mice with POG at a dose of 5 or 10 mg/kg resulted in a reduction in IAV-induced pneumonia, as evidenced by decreased pulmonary edema, improved lung histopathology, and reduced inflammatory cell accumulation. At the higher dose (10 mg/kg), POG treatment significantly increased survival rates, decreased viral titres in the lungs, improved lung histology, and reduced lung inflammation in IAV-infected mice. POG also effectively alleviated pulmonary fibrosis by reducing the levels of fibrotic markers (hydroxyproline [Hyp] and transforming growth factor β1 [TGF-β1]) and suppressing the expression of alpha smooth muscle actin (α-SMA), p focal adhesion kinase (p-FAK), and TGF-β1 in lung tissues. In addition, POG inhibited the expression of the RELA proto-oncogene (RELA), phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta (PIK3CD), and mitogen- and stress-activated protein kinase 2 (MSK2) in lung tissues. These results indicate that POG may have a protective effect against IAV-induced pneumonia by downregulating the TGF-β1/PI3KCD/MSK2/RELA signalling pathway in the lungs.

Myocardial infarction risk across cancer subtypes - nationwide registry study

Abstract Background Progress in cancer treatments have significantly improved patient outcomes, leading to increased survival rates. However, patients with cancer continue to have higher rates of cardiovascular events an area that has traditionally not received much attention. Purpose The aim of this study was to examine the risk of myocardial infarction in patients with different types of cancer compared with age- and sex-matched population controls with benign skin cancer. Methods Patients with cancer between 2000-2016 were identified within the Danish National Patient Registry. Cox regression was used accounting for the competing risk of death reporting hazard ratios (HR) for both myocardial infarction and mortality. Models were adjusted for age, sex, hypercholesterolemia, atrial fibrillation, hypertension and anticoagulant therapies of all included subjects. Patients with a previous myocardial infarction were excluded from the analysis. Results A total of 503.616 patients were included in the final analysis of whom 355.920 had cancer with different cancer types and 147.696 were controls with benign skin cancer. The one-year outcome of myocardial infarction (Figure 1) was overall significant higher for all subtypes of cancer especially lymphoma HR 1.66 (interquartile range [IQR]: 1.45-1.89), bladder cancer HR 1.64 (IQR: 1.39-1.94), and gastrointestinal cancer HR 1.53 (IQR: 1.40-1.69). Hepatobiliary and pancreatic cancer, breast cancer and malignant melanoma had reduced but not significantly different HRs of 0.96 (IQR: 0.80-1.15), 0.92 (IQR: 0.79-1.07), and 0.76 (IQR: 0.60-0.96), respectively. The one-year competing risk of death (Figure 2) was overall higher for all subtybes of cancer especially hepatobiliary and pancreatic cancer and lung cancer with HRs of 52.11 (IQR: 50.18-54.11) and 41.62 (IQR: 40.17-43.12). Conclusion The one-year risk of myocardial infarction varied across cancer subtypes. Notably, lymphoma, bladder, and gastrointestinal cancers were associated with higher risks, whereas hepatobiliary and pancreatic, breast, and malignant melanoma cancer showed no statistically significant associations. The clinical significance of these differences must be viewed within the context of the significant competing risk of death in this cancer population.Risk Of Myocardial InfarctionCompeting Risk Of Death