Death In Patients Research Articles

SGLT2 inhibitors for patients with type 2 diabetes mellitus after myocardial infarction: a nationwide observation registry study from SWEDEHEART

Sodium-glucose co-transporter 2 (SGLT2) inhibitors have been shown to reduce rates of heart failure hospitalisations and cardiovascular death in patients with type 2 diabetes and prior cardiovascular disease. We hypothesised that SGLT2 inhibitors could provide cardiovascular benefits in the post-myocardial infarction setting. We aimed to investigate cardiovascular outcomes of SGLT2 inhibitor therapy in patients with type 2 diabetes mellitus after myocardial infarction in a Swedish nationwide registry. We included all patients with type 2 diabetes surviving a type 1 acute myocardial infarction from January 1, 2018 to December 31, 2021. Patients were included if they were discharged with an estimated glomerular filtration rate (eGFR)>30mL/min/1.73 m2 in the nationwide Swedish Web-system for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapies (SWEDEHEART) registry. We identified all patients discharged with or without an SGLT2 inhibitor prescription 120 days before or within three days after discharge from the cardiac care unit. The primary outcome measure was a composite of death and first hospitalisation for heart failure after one year analysed using an adjusted Cox regression. A total of 11,271 patients were included. Of these, 2498 (22.2%) received SGLT2 inhibitor treatment. Patients who were prescribed SGLT2 inhibitors were younger, more often presented with a STEMI and had worse left ventricular ejection fraction at index hospitalisation. SGLT2 inhibitor use was associated with lower rates of the composite outcome (hazard ratio (HR) of 0.70 (95% confidence interval (CI) 0.59-0.82). Treatment with SGLT2 inhibitors after myocardial infarction in patients with type 2 diabetes was associated with a lower rate of cardiovascular events. This work was supported by Hjärt-Lungfonden, Vetenskapsrådet, Knut and Alice Wallenberg Foundation, ALF, the Bundy Academy, and Skåne University Hospital funds.

Mortality rate analysis of patients on invasive mechanical ventilation in the intensive care unit on day 28.

Outcomes in patients receiving invasive mechanical ventilation (IMV) are currently unclear. The present study aimed to explore the prognostic factors of the mortality rate on day 28 in patients treated in the intensive care unit (ICU) and undergoing IMV. The IMV Mortality Prediction Score (IMPRES) of 129 patients in the ICU receiving IMV after emergency (or selective) endotracheal intubation from March 2018 to August 2020 was calculated. The patients were divided into survival (n=73) and death groups (n=56) on day 28. The predictive factors of independent and combined mortality rates were determined using a receiver operating characteristic (ROC) curve and the area under the ROC curve (AUC). The AUC of the IMPRES for predicting patient death on day 28 was 0.785 (95% confidence interval (CI): 0.704-0.864, P<0.01). When the IMPRES cut-off was 4.50, the Youden index was at its maximum (0.487) with a sensitivity of 85.7% and a specificity of 63.0%. The AUC of the ventilator use time (days) at 12.5 days cut-off was 0.653 (95% CI: 0.56-0.746, P<0.01), the Youden index was 0.235 with a sensitivity of 52.1% and a specificity of 71.4%. The AUC of the IMPRES combined with the duration of ventilator use was 0.856 (95% CI: 0.789-0.922, P<0.001), the Youden index was 0.635 with a sensitivity of 84.9% and a specificity of 78.6%. The IMPRES was observed to be the main factor influencing the mortality rate of patients receiving IMV at the ICU on day 28, and the IMPRES combined with the duration of ventilator use had a significant predictive value for the 28-day mortality rates of these patients.

Effect of fruits granola (Frugra®) consumption on blood pressure reduction and intestinal microbiome in patients undergoing hemodialysis

AbstractCardiovascular diseases (CVDs) are a major cause of death in patients undergoing hemodialysis (HD). Blood pressure (BP) and uremic toxins are well-known risk factors for CVDs, which are influenced by diet. Dietary fiber supplementation in patients undergoing HD may reduce the risk of CVDs by improving lipid profiles and inflammatory status and lowering the levels of the uremic toxin indoxyl sulfate (IS). In this study, we investigated the relationship between the intestinal microbiota and risk factors for CVDs, such as BP and serum IS, in patients undergoing HD who consumed fruits granola (FGR). The study participants were selected from patients undergoing HD at the Izu Nagaoka Daiichi Clinic and consumed FGR for 2 months. Body composition and blood samples were tested at months 0, 1, 2 and fecal samples were collected at months 0 and 2 for intestinal microbiota analysis. FGR consumption decreased systolic and diastolic BP, estimated salt intake, and serum IS levels and improved the stool characteristics according to the Bristol Stool Form Scale (N = 24). Gut microbiota analysis showed an increase in the alpha diversity and abundance of Blautia and Neglecta. The abundance of lactic acid- and ethanol-producing bacteria also significantly increased, whereas the abundance of indole-producing bacteria significantly decreased. FGR consumption could be a useful tool for salt reduction, fiber supplementation, and improvement of the intestinal environment, thus contributing to improvement of BP and the reduction of other risk factors for CVDs in patients undergoing HD.

Epidemiology and SARIMA model of deaths in a tertiary comprehensive hospital in Hangzhou from 2015 to 2022

BackgroundBy analysing the deaths of inpatients in a tertiary hospital in Hangzhou, this study aimed to understand the epidemiological distribution characteristics and the composition of the causes of death. Additionally, this study aimed to predict the changing trend in the number of deaths, providing valuable insights for hospitals to formulate relevant strategies and measures aimed at reducing mortality rates.MethodsIn this study, data on inpatient mortality at a tertiary hospital in Hangzhou from 2015 to 2022 were obtained via the population information registration system of the Chinese Center for Disease Control and Prevention. The death data of inpatients were described and analysed through a retrospective study. Excel 2016 was utilized for data sorting, and SPSS 22.0 software was employed for data analysis. The statistical inference of single factor differences was conducted via χ2 tests. The SARIMA model was established via the forecast, aTSA, and tseries software packages (version 4.3.0) to forecast future changes in the number of deaths.ResultsA total of 1938 inpatients died at the tertiary hospital in Hangzhou, with the greatest number of deaths occurring in 2022 (262, 13.52%). The sex ratio was 2.22:1, and there were significant differences between sexes in terms of age, marital status, educational level, and place of residence (P < 0.05). The percentage of males in the groups aged of 20 to 29 and 30 to 39 years was significantly greater than that of females (χ2 = 46.905, P < 0.001). More females than males died in the widowed group, and divorced and married males experienced a greater number of deaths than divorced and married females did (χ2 = 61.130, P < 0.001). The proportions of male students with a junior college and senior high school education were significantly greater than that of female students (χ2 = 12.310, P < 0.05). The primary causes of mortality within the hospital setting included circulatory system diseases, injury, poisoning, tumours, and respiratory system diseases. These leading factors accounted for 86.12% of all recorded deaths. Finally, the SARIMA (2, 1, 1) (1, 1, 1)12 model was determined to be the optimal model, with an AIC of 380.23, a BIC of 392.79, and an AICc of 381.81. The MAPE was 14.99%, indicating a satisfactory overall fit of this model. The relative error between the predicted and actual number of deaths in 2022 was 8.02%. Therefore, the SARIMA (2, 1, 1) (1, 1, 1)12 model demonstrates good predictive performance.ConclusionsHospitals should enhance the management of sudden cardiac death, acute myocardial infarction, severe craniocerebral injury, lung cancer, and lung infection to reduce the mortality rate. The SARIMA model can be employed for predicting the number of deaths.

The roles of rabies virus structural proteins in immune evasion and implications for vaccine development

Rabies is a zoonotic infectious disease that targets the nervous system of human and animals and has about 100% fatality rate without treatment. Rabies virus is a bullet-like viral particle composed of five structural proteins, including nucleoprotein (N), phosphorylated protein (P), matrix protein (M), glycoprotein (G), and large subunit (L) of RNA-dependent RNA polymerase. These multifunctional viral proteins also play critical roles in the immune escape by inhibiting specific immune responses in the host, resulting in massive replication of the virus in the nervous system and abnormal behaviors of patients such as brain dysfunction and hydrophobia, which ultimately lead to the death of patients. Herein, the role of five structural proteins of rabies virus in the viral replication and immune escape and its implication for the development of vaccines were systemically reviewed, so as to shed light on the understanding of pathogenic mechanism of rabies virus.

The long-term time course of septic arthritis.

The aims of this study were to: 1) report on a cohort of skeletally mature patients with native hip and knee septic arthritis over a 14-year period; 2) to determine the rate of joint failure in patients who had experienced an episode of hip or knee septic arthritis; and 3) to assess the outcome following septic arthritis relative to the infecting organism, whether those patients infected by Staphylococcus aureus would be more likely to have adverse outcomes than those infected by other organisms. All microbiological samples from joint aspirations between March 2000 and December 2014 at our institution were reviewed in order to identify cases of culture-proven septic arthritis. Cases in children (aged < 16 years) and prosthetic joints were excluded. Data were abstracted on age at diagnosis, sex, joint affected (hip or knee), type of organisms isolated, cause of septic arthritis, comorbidities within the Charlson Comorbidity Index (CCI), details of treatment, and outcome. A total of 142 patients were confirmed to have had an episode of septic arthritis in a native hip (n = 17) or knee joint (n = 125). S. aureus accounted for 57.7% of all hip and knee joint infections. There were 13 inpatient deaths attributed to septic arthritis. The median age of the patients who died was 77.5 (46.9 to 92.2) and their median age-adjusted CCI was 8 (6 to 12). A failure of the joint occurred in 26 knees (21%) and nine hips (53%). Of the knee joints infected by S. aureus (n = 71), 23 knees (32%) went into failure of joint, whereas of those infected by other organisms (n = 54), only three knees (6%) failed. Based on our study findings, hip and knee septic arthritis long-term outcomes were substantially worse than their immediate outcome suggested. Failure of knee joint is 6.1 times more likely to occur in those infected with S. aureus.

A single-institution retrospective study of comprehensive genomic profiling tests based on C-CAT findings for advanced solid cancers

Abstract Background In recent years, as the availability of precision therapies expands, there is increasing reliance on genomic profiling assays to help identify the most appropriate treatment options for patients with advanced cancers. We retrospectively investigated the results of comprehensive genomic profiling tests from the time insurance coverage began until recently and examined the status of genetic analysis. Methods We retrospectively reviewed the analysis results of 300 patients with advanced solid tumors who consented to comprehensive genomic profiling tests from October 2019 to December 2022. Results Of the 300 patients who underwent comprehensive genomic profiling tests, analysis results for 274 patients were obtained, and were reviewed by the Clinical Genome Expert Panel. Six specimens (2%) were discontinued due to patient deaths and deteriorations in general condition. The three most frequently occurring actionable genomic alterations observed were TP53 (47.4%), KRAS (28.1%) and CDKN2A (20.4%). The most common druggable variant was CDKN2A, which was noted in 52 (19%) of 274 patients. The next most common were PIK3CA, BRAF, KRAS and PTEN. The cancer types that showed a greater median number of actionable alterations comprised thyroid cancer, pancreatic cancer and colorectal cancer. Conclusions In conclusion, comprehensive genomic profiling tests have the potential to be valuable in identifying genomic abnormalities. Even if there is no effective treatment at present, it may lead to a treatment in the future. Comprehensive genomic profiling tests should be considered for any cancer.

An Update on the Survival of the First 50 Face Transplants Worldwide.

Since 2005, a total of 50 face transplants have been reported from 18 centers in 11 countries. The overall survival of the grafts has not yet been established. To assess the survival of the face transplant grafts and evaluate factors potentially influencing it. Data on all the transplants included in this multicenter cohort study were collected at participating transplant centers for updated nonpublished data, supplemented with literature review for nonparticipating centers. Data from 2005 until September 2023, were included. Data were analyzed from November 11, 2005, through September 18, 2023. Patients included the first 50 patients in the world to have received a face transplant. Face transplant graft. The primary outcome was the overall survival of the face transplant graft, defined as either transplant loss or patient death. The secondary outcome was the number of acute rejection episodes per year. The 50 transplants were performed on 39 men (81%) and 9 women (19%) with a median age of 35 (range, 19-68) years at the time of the transplant. The median follow-up time was 8.9 (range, 0.2-16.7) years. During the follow-up, 6 transplants were lost with 2 patients retransplanted. There were 10 patients who died, 2 of whom had lost a transplant. The 5- and 10-year survival of the transplants was 85% (SD, 5%) and 74% (SD, 7%), respectively. The sequential number of the transplant in the world was a significant predictor of survival (hazard ratio, 95; 95% CI, 90-100; P < 05). The median number of acute rejection episodes per year was 1.2 (range, 0-5.3) for the transplants that were lost and 0.7 (range, 0-4.6) for the transplants that survived. No correlation with patient and transplant variables was detected for either the transplant survival or the number of rejection episodes. In this study, the overall survival of the face transplants is encouraging. These data suggest that the acceptable long-term survival of face transplants makes them a reconstructive option for extensive facial defects.

IMPACT OF CHRONIC KIDNEY DISEASE ON THE COURSE AND OUTCOME OF COVID-19

COVID-19 is primarily a respiratory disease, but it brings a significant risk of acute kidney injury or exacerbation of pre-existing kidney disease, especially in patients with comorbidities such as hypertension, coronary artery disease, chronic liver disease, chronic kidney disease, and malignancies. We reviewed studies that assessed the association between chronic kidney disease and the risk of SARS-CoV-2 coronavirus infection and infection outcomes, including hospitalization, severe COVID-19, need for intensive care, COVID-19 progression, and patient death. The results of the studies are varied and often contradictory, as the baseline data differ in many parameters, such as the period of the pandemic, the quality and size of the sample, and the degree of comorbidity. Nevertheless, all authors conclude that, in general, chronic kidney disease is an unfavorable factor with regard to SARS-CoV-2 infection. In patients with COVID-19, the presence of concomitant chronic kidney disease predisposes to severe COVID-19, viral pneumonia, development of acute respiratory distress syndrome, acute kidney injury and other complications, which in turn are a negative prognostic factor for mortality. Patients with chronic kidney disease who survived COVID-19 are more likely to develop post-COVID syndromes with a variety of persistent or recurrent symptoms than convalescents without renal comorbidity. This category of patients requires long-term monitoring, optimization of therapy and priority for vaccination.

Smoking and sudden cardiac death in patients with previous coronary artery disease.

Smoking is a known risk for sudden cardiac death (SCD) in the general population. However, its significance in patients with acute coronary syndrome (ACS), a condition that also elevates the risk of SCD, is disputable. A total of 9704 consecutive ACS patients with available smoking data were included in the analysis. Comprehensive patient data were obtained from the Mass Data in Detection and Prevention of Serious Adverse Events in Cardiovascular Disease research database. A composite endpoint of SCD, SCD aborted by successful resuscitation and accurate implantable cardioverter defibrillator therapy to otherwise potentially fatal ventricular fibrillation/ventricular tachycardia was used. Univariate, age- and sex-adjusted, and a multivariate fine-gray competing risk regression with adjustment to traditional risk factors was conducted. Median follow-up time was 6.8 years (IQR, 4.1-10.2), and 454 (4.7%) SCD cases were identified. At the baseline, 23.7% (N = 2444) were active smokers, and 20.8% (N = 2146) were ex-smokers. In the multivariate model, active smokers had an elevated risk of 1.79 (95% CI, 1.41-2.27; P < 0.001) for future SCD. Ex-smokers had no elevated risk for SCD in fine-gray subdistribution hazard. Also, active smokers were notably younger (mean age 58.7 years) than non- or ex-smokers (71.1 years and 68.9 years, respectively, P < 0.001 for both comparisons). Active smokers had a 79% higher risk of SCD when compared with nonsmokers. Smoking cessation should be heavily encouraged after ACS. Also, a person's smoking status should be considered in further studies developing SCD and implantable cardioverter defibrillator-benefit risk scores.

Biocatalytic Clusterzyme Patches Restore Lung Function via Immunomodulation and Mitochondria Protection.

Currently, pulmonary complications such as lung infections during the perioperative period are still the main cause of prolonged hospitalization and death in patients with lung injury due to the lack of effective drugs. Clusterzyme, a kind of artificial enzyme with a high enzyme-like activity and safety profile, exhibits good effects on reducing oxidative stress and immunomodulation. Here, we present the functionalized patches that is administered on the lung airways and rescues the injured organ via clusterzymes. The long-term antioxidant capacity of the patches significantly ameliorated lipopolysaccharide-induced lung function impairment with a significant reduction in lung goblet cell metaplasia and oxidative stress. The inflammatory factors such as cytokines interleukin-1β, interleukin-6, and tumor necrosis factor-α levels decreased by 50%, while the mtDNA copy number increased by 50% and ATP production increased by 100%. Mice lung function was significantly improved, suggesting that the patches can rescue lung injury by modulating oxidative stress and immune responses as well as protecting the mitochondria, providing an avenue for effective intervention of lung injury.

Treatment of recurrent ureteral stricture after kidney transplantation with nitinol stent

Introduction. Urological complications make up a significant percentage in the structure of kidney graft loss and patient death in the early and long-term period after transplantation. The most common urological complication in the long-term period is ureter or anastomotic stricture, which, according to various authors, occurs in 0.9–34%. However, now there is no consensus in the treatment for recurrent strictures.Case report. We have presented a clinical case of successful treatment for the stricture of the ureterovesical anastomosis after kidney transplant from a brain-dead donor. During the first year after kidney transplantation, after two reconstructive surgeries and repeated placement of plastic stents, the patient was diagnosed with recurrent stricture of the ureterovesical anastomosis, and therefore a coated nitinol ureteral stent was implanted.Conclusion. This clinical case report demonstrates the feasibility of effectively using a nitinol stent in the treatment of recurrent strictures of the ureterovesical anastomosis after kidney transplantation. In some cases, this technique can be considered as an alternative to repeated surgical interventions. Further studies are needed to determine a more precise treatment algorithm.

Progress in Research of Nanotherapeutics for Overcoming Multidrug Resistance in Cancer

Chemotherapy has been widely applied in oncotherapy. However, the development of multidrug resistance (MDR) has diminished the effectiveness of anticancer drugs against tumor cells. Such resistance often results in tumor recurrence, metastasis, and patient death. Fortunately, nanoparticle-based drug delivery systems provide a promising strategy by codelivery of multiple drugs and MDR reversal agents and the skillful, flexible, smart modification of drug targets. Such systems have demonstrated the ability to bypass the ABC transporter biological efflux mechanisms due to drug resistance. Hence, how to deliver drugs and exert potential antitumor effects have been successfully explored, applied, and developed. Furthermore, to overcome multidrug resistance, nanoparticle-based systems have been developed due to their good therapeutic effect, low side effects, and high tumor metastasis inhibition. In view of this, we systematically discuss the molecular mechanisms and therapeutic strategies of MDR from nanotherapeutics. Finally, we summarize intriguing ideas and future trends for further research in overcoming MDR.

Mortality associated with osteoporosis and pathological fractures in the United States (1999–2020): a multiple-cause-of-death study

BackgroundOsteoporosis with pathological fractures is a significant public health issue, contributing to morbidity, disability, diminished quality of life, and increased mortality. Understanding mortality trends related to this condition is crucial for developing effective interventions to reduce mortality and improve healthcare outcomes. This study aimed to analyze trends and causes of death associated with osteoporosis and pathological fractures in the United States using a multi-cause approach.MethodsAnnual death and age-standardized mortality rate (ASMR) data from 1999 to 2020 were obtained from the Centers for Disease Control and Prevention (CDC) mortality database. Death certificates listing ICD-10 M82 (osteoporosis with pathological fracture) as an underlying or related cause of death were analyzed. Epidemiological data were analyzed, and the ASMR data were calculated for each year, and trends were assessed using the Cochran-Armitage trend test.ResultsFrom 1999 to 2020, there were 40,441 deaths related to osteoporosis with pathological fractures in the United States, with a female-to-male ratio of 5.6:1. Among these, 12,820 deaths (31.7%) listed osteoporosis with pathological fractures as the underlying cause of death (UCD), yielding a female-to-male ASMR ratio of approximately 5.0-7.7:1. When classified as a non-UCD, the ASMR ratio was approximately 4.8–6.2:1. At the same time, we found that the total number of deaths classified as UCD and multiple causes of death (MCD), but the trend ratio of the two groups in different years did not change statistically significant (P > 0.05), and the ASMR of both groups showed a downward trend. The UCD-to-MCD ratio increased between 1999 and 2007, then decreased from 2007 to 2020. As MCD, the number of female deaths was more than that of male, and both showed a decreasing trend, but there was no statistical significance in the change of trend ratio in different years (P > 0.05). Deaths were predominantly concentrated in individuals over 75 years of age, with those over 84 years being the most affected. The number of deaths in different age groups showed a decreasing trend, and the change of trend ratio in different years was statistically significant (P < 0.05). White individuals had the highest number of deaths. The leading causes of death were heart diseases, chronic lower respiratory diseases, and alzheimer’s disease. In addition, the number of deaths of patients with prostate cancer and breast cancer showed a significant downward trend, and the change of trend ratio between the two groups in different years was statistically significant (P < 0.05).ConclusionsAlthough mortality from osteoporosis with pathological fractures is decreasing, anti-osteoporosis therapy remains essential for elderly patients. Healthcare providers should remain vigilant for potential complications, including malignant neoplasms, and ensure timely diagnosis and treatment to further reduce mortality in this population.

Abstract C005: Exploratory biomarker evaluation of the randomized Phase 2 cohort of CM24 in combination with nivolumab and chemotherapy in advanced/metastatic pancreatic cancer

Abstract Background: CM24 (mAb) blocks CEACAM1 interactions, has key roles in cancer progression, immune escape and metastasis. CEACAM1 is part of the neutrophil extracellular trap (NET) complex, involved in tumor immune evasion, metastasis and cancer-associated thrombosis, affecting patient survival. We demonstrated that CM24 binds to NET and suppresses NET-induced migration of cancer cells (AACR Cancer Metastasis Nov.2022) and that CM24+nivolumab (nivo) treatment of pancreatic ductal adenocarcinoma (PDAC) patients markedly reduced serum levels of the NET marker, Myeloperoxidase (MPO; AACR on pancreatic cancer Sept.2023). In a Phase 2 study (NCT04731467) 31 patients with advanced/metastatic PDAC progressed after 1st line therapy, were randomized for CM24 (20mg/kg q2wk), nivo (240mg/kg q2wk) and liposomal irinotecan, 5 fluorouracil and leucovorin (Nal-IRI/5FU/LV, q2wk) treatment (experimental arm) vs Nal-IRI/5FU/LV only (control arm). Interim analysis of the data showed Median OS for the experimental arm was 7.72m (95% CI: 4.00-8.11) vs. 5.62m (95% 3.22 -7.89) for the control arm (HR: 0.74; 95% CI: 0.31-1.77). Median PFS for the experimental group was 3.8m (95% 1.8-5.0) vs. 1.9m (95% 0.9, 3.6) for the control arm (HR 0.72; 95% CI: 0.33-1.60) (ASCO2024-LBA4143). Here we present a subgroup analysis evaluating serum MPO as a potential biomarker for CM24-based therapy. Methods: Patients were randomized as described above. Pre-dose serum samples were collected from 30 out of 31 pts and serum MPO levels were evaluated using ELISA (Cayman), where the measured mean serum MPO in healthy subjects (n=30) was 53 +/-7[SE]. NET-induced blood coagulation was tested using platelet aggregation assay. Results: Mean pre-dose MPO level in patients (n=30) was 359 +/- 46 [SE] and was selected as a threshold for biomarker analysis. OS for patients with MPO levels below the threshold (n=9/16) was 8.1 mo in the experimental arm (HR 0.34; (95% CI: 0.099-1.149)) vs 4.5mo in the control (n=9/15). PFS for patients with MPO levels below the threshold was 4.2mo in the experimental arm vs. 1.7 mo in the control (HR 0.24 (95% CI: 0.20-1.59)). NET-associated blood coagulation and the inhibitory effect of CM24 were tested in vitro. NETs induced platelet aggregation in a dose-dependent manner, and CM24 significantly reduced it (50-70% reduction, p value &amp;lt; 0.0001) at NET levels related to the selected biomarker range (MPO&amp;lt;357) but was less effective at higher NET levels (MPO&amp;gt;500), which relate to MPO above the threshold. These results are in line with the proposed CM24 MoA, affecting NET-related cancer complications. Conclusions: Exploratory biomarker analysis suggests serum MPO as a potential predictive biomarker for CM24-based therapy showing prolonged median OS, PFS and 66% reduction in risk of death vs control in PDAC patients with MPO levels below threshold compared to interim analysis that estimated OS and PFS risk reduction of 26% and 28%, respectively. These findings will be further evaluated in upcoming clinical studies. Citation Format: Teresa Macarulla, Michael Cecchini, Rocio Garcia-Carbonero, Talia Golan, Ruth Perets, Erkut Borazanci, Manuel Pedegral, Mariano Ponz-Sarvisé, Mohammed Najeeb Al Hallak, Shubham Pant, Valentina Boni, Omar Saavedra, María José de Miguel-Luken, Alexis D. Leal, Andrés J. Muñoz Martín, Tamara Sauri-Nadal, Michael Schickler, Hava Ben David, Hadas Reuveni. Exploratory biomarker evaluation of the randomized Phase 2 cohort of CM24 in combination with nivolumab and chemotherapy in advanced/metastatic pancreatic cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pancreatic Cancer Research; 2024 Sep 15-18; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(17 Suppl_2):Abstract nr C005.

Incidence and risk of arterial and venous thrombotic events in Systemic Lupus Erythematosus patients: a population-based study.

Current data on arterial and venous thrombotic events (ATE & VTE) and cardiovascular (CV) risk management in European systemic lupus erythematosus (SLE) population are limited. This study aimed to investigate the incidence and risk of thrombotic events and all-cause death in an Italian SLE cohort over the past decade, along with its pharmacotherapy. Incident SLE cases between 2010 and 2019 were identified using administrative health databases of the Lombardy Region. The association between SLE and outcomes, compared with age- and sex-matched controls, was reported as incidence rate per 1000 person-years and as adjusted hazard ratios with 95% confidence intervals. Overall, 2133 SLE patients and 21 283 no-SLE individuals were included. A higher incidence rate of ATE (4.22 vs 2.26 1000 PY), VTE (1.85 vs 0.67 1000 PY,) and all-cause death (15.18 vs 6.22 1000 PY) was reported in SLE patients than in those without (p< 0.0001) as well as an increased risk of ATE (HR, 1.65; 95% CI, 1.20-2.26), VTE (HR, 2.25; 95% CI, 1.35-3.74), and all-cause death (HR, 1.81; 95% CI, 1.52-2.15). After SLE diagnoses, hydroxychloroquine and glucocorticoids were prescribed for at least 60% of patients. Additionally, a higher exposure to cardiovascular medications was also seen in SLE patients. Our findings confirmed higher risks of ATE, VTE and all-cause death in SLE patients. While increased CV medications use after SLE diagnoses suggests heightened awareness to CV risk profile, more attention is required to balance SLE disease activity with minimizing exposure to drugs associated with exacerbating CV risk.

Preoperative geriatric assessment to predict functional outcome after major urologic operations: Results from a multicenter study

IntroductionMajor urological tumor surgery entails a severe risk of unexpected adverse events, persistent functional deterioration, and death in older patients. The Erlangen Index (EI) geriatric assessment tool has previously been shown to predict incomplete functional recovery following major urological tumor surgery in an elderly patient collective. We prospectively evaluated assessment tools including EI in a multicenter setting. Materials and methodsA total of 340 patients over the age of 65 were assessed prospectively before and after cystectomy, prostatectomy, or renal tumor surgery at three academic centers in Germany and Austria. Endpoints were long-term functional deterioration (Activities of daily living (ADL) measured by Barthel-Index) at day 30 and day 180, and mortality at day 180. ResultsIn this study 58 (17.0 %) patients underwent cystectomy, 140 (41.2 %) prostatectomy and 142 (41.8 %) a kidney tumor operation. Mean age was 74.8 years. ADL impairment as a measure of incomplete recovery at day 30 and 180 after surgery were recorded in 47.6 % and 37.4 % of cases, respectively. The EI showed good sensitivity for mortality at day 180 (reference cohort: 85 %, validation center 1: 100 %, validation center 2: 50 %) and for ADL impairment at day 180 (reference cohort 75.4 %, validation center 1 72.3 %, validation center 2 83.3 %). ConclusionElderly patients with a poor performance status have a high risk of persistent functional deterioration. Data from this multicenter external validation trial confirms the EI as an accurate and reliable tool to identify patients with high risk of mortality or persistent postoperative functional impairment.

A Study on the Binding Mechanism and the Impact of Key Residue Mutations between SND1 and MTDH Peptide through Molecular Dynamics Simulations.

Metastasis of breast cancer is the main cause of death for patients with breast cancer. The interaction between metadherin (MTDH) and staphylococcal nuclease domain 1 (SND1) plays a pivotal role in promoting breast cancer development. However, the binding details between MTDH and SND1 remain unclear. In this study, we employed all-atom molecular dynamics simulations (MDs) and conducted binding energy calculations to investigate the binding details and the impact of key residue mutations on binding. The mutations in key residues have not significantly affected the overall stability of the structure and the fluctuation of residues near the binding site; they have exerted a substantial impact on the binding of SND1 and MTDH peptide. The electrostatic interactions and van der Waals interactions play an important role in the binding of SND1 and the MTDH peptide. The mutations in the key residues have a significant impact on electrostatic and van der Waals interactions, resulting in weakened binding. The energy contributions of key residues mainly come from the electrostatic energy and van der Waals interactions of the side chain. In addition, the key residues form an intricate and stable network of hydrogen bonds and salt-bridge interactions with the MTDH peptide. The mutations in key residues have directly disrupt the interactions formed between SND1 and MTDH peptide, consequently leading to changes in the binding mode of the MTDH peptide. These analyses unveil the detailed atomic-level interaction mechanism between SND1 and the MTDH peptide, providing a molecular foundation for the development of antibreast cancer drugs.

Temporal trends in mortality and causes of death in patients with incident atrial fibrillation: a nationwide register study from 2010 to 2018

ObjectivesAtrial fibrillation (AF) is associated with increased mortality. Previous studies have reported conflicting results in temporal trends of mortality after AF diagnosis. We aim to address this disparity by investigating...

Machine learning for identifying risk of death in patients with severe fever with thrombocytopenia syndrome

Machine learning for identifying risk of death in patients with severe fever with thrombocytopenia syndrome