Higher Mortality In Patients Research Articles

GlmS plays a key role in the virulence factor expression and biofilm formation ability of Staphylococcus aureus promoted by advanced glycation end products

ABSTRACT Staphylococcus aureus (S. aureus) is well known for its biofilm formation ability and is responsible for serious, chronic refractory infections worldwide. We previously demonstrated that advanced glycation end products (AGEs), a hallmark of chronic hyperglycaemia in diabetic tissues, enhanced biofilm formation by promoting eDNA release via sigB upregulation in S. aureus, contributing to the high morbidity and mortality of patients presenting a diabetic foot ulcer infection. However, the exact regulatory network has not been completely described. Here, we used pull-down assay and LC-MS/MS to identify the GlmS as a candidate regulator of sigB in S. aureus stimulated by AGEs. Dual-luciferase assays and electrophoretic mobility shift assays (EMSAs) revealed that GlmS directly upregulated the transcriptional activity of sigB. We constructed NCTC 8325 ∆glmS for further validation. qRT-PCR analysis revealed that AGEs promoted both glmS and sigB expression in the NCTC 8325 strain but had no effect on NCTC 8325 ∆glmS. NCTC 8325 ∆glmS showed a significant attenuation in biofilm formation and virulence factor expression, accompanied by a decrease in sigB expression, even under AGE stimulation. All of the changes, including pigment deficiency, decreased haemolysis ability, downregulation of hla and hld expression, and less and sparser biofilms, indicated that sigB and biofilm formation ability no longer responded to AGEs in NCTC 8325 ∆glmS. Our data extend the understanding of GlmS in the global regulatory network of S. aureus and demonstrate a new mechanism by which AGEs can upregulate GlmS, which directly regulates sigB and plays a significant role in mediating biofilm formation and virulence factor expression.

Ultrasound evaluation of portal venous gas and its mimics.

Portal venous gas on abdominal ultrasound classically represents an indirect indicator of bowel ischemia, a critical condition which poses a high patient mortality and therefore warrants emergent corrective action. While the classic appearance of portal venous gas on ultrasound is well-described in the literature, the characteristic descriptors are nonspecific and may actually represent other less emergent mimics. Therefore, while radiologists should remain vigilant for the detection of findings corresponding to portal venous gas, they should also be aware of similar-appearing entities in order to provide the most accurate diagnosis. This pictorial essay will open with imaging examples of true portal venous gas attributable to bowel ischemia and describe the classic features which should alert radiologists to this specific diagnosis. Subsequently, this pictorial essay will provide imaging examples of other various other clinical entities which on ultrasound may share similar imaging characteristics. An important objective of this pictorial essay is to highlight distinguishing imaging features along with specific clinical circumstances for each pathological entity which can direct radiologists into identifying the correct diagnosis.

Integration of network pharmacology and proteomics analysis to identify key target pathways of Ginsenoside Re for myocardial ischemia

BackgroundClinically, various diseases cause myocardial ischemia (MI), which further induces severe cardiac injury and leads to high mortality in patients. Ginsenoside Re, one of the major ginsenosides in ginseng, can regulate the level of oxidative stress in the injured myocardium. Thus, it may attenuate MI injury, but the related mechanism has not been comprehensively studied. PurposeThis study aimed to investigate the anti-MI effect and comprehensively mechanisms of Ginsenoside Re. Study Design/MethodsOxygen–glucose deprivation (OGD), oxidative-induced cardiomyocyte injury, and isoproterenol-induced MI mice were used to explore their protective effect of Ginsenoside Re. An integrated approach of network pharmacology, molecular docking, and tandem mass tag proteomics was applied to determine the corresponding common potential targets of Ginsenoside Re against MI, such as target proteins and related pathways. The major anti-MI target proteins and related pathways were validated by immunofluorescence (IF) assay and Western blotting (WB). ResultsGinsenoside Re (1.32–168.93 µM) had low toxicity to normal cardiomyocytes, and increased the survival of oxidative stress-injured (OGD-induced injury or H2O2-induced injury) cardiomyocytes in this concentration range. It regulated the reactive oxygen species (ROS) level in OGD-injured cardiomyocytes; stabilized the nuclear morphology, mitochondrial membrane potential (MMP), and mitochondrial function; and reduced apoptosis. Meanwhile, Ginsenoside Re (5–20 mg/kg) alleviated cardiac injury in MI mice and maintained cardiac function. Through network pharmacology and proteomics, the relevant mechanisms revealed several key pathways of Ginsenoside Re anti-MI, including inhibition of MAPK pathway protein phosphorylation, downregulation of phosphorylated PDPK1, AKT, and STAT3, and upregulation of TGF-β3, ferroptosis pathway (upregulation of GPX4 and downregulation of phosphorylation level of MDM2) and AMPK pathway (regulating the synthesis of cholesterol in the myocardium by downregulation of HMGCR). The key proteins of these target pathways were validated by IF and/or WB. ConclusionGinsenoside Re may target MAPK, AKT, ferroptosis pathways and AMPK pathway to prevent and/or treat MI injury and protect cardiomyocytes from oxidative damage.

Lithium levels in drinking water predicted the ratio of attempted to completed suicides in regions with high incidence of affective disorders: Insights from ecological study

IntroductionLithium has demonstrated significant antisuicidal effects: it significantly reduces the high excess overall mortality of patients with affective disorders. MethodsPublic drinking water samples were collected in 53 Lithuanian municipalities during a two-month period. Linear models used lithium level in public drinking water as predictor and ratio of suicide attempts to suicide mortality as outcomes across the municipalities. ResultsLithium in drinking water predicted the ratio of attempted to completed suicides (A/S) nonlinearly, described by a U-shaped curve. The curves for visualization of the association of incidence of affective disorders and suicide standard mortality rate with lithium level displayed significant suicide curve decrements and invers direction in affective disorders curve. Multivariate regression model for ratio A/S in high lithium exposure group (> 7 µg/L, N = 26) suggests that the lithium level can explain 54.3 % of variance of ratio A/S in municipalities with exposure of lithium above median and with high incidence of affective disorders. ConclusionsThe findings provide confirmatory evidence that in municipalities with high incidence of affective disorders higher lithium levels in the public drinking water are associated with higher ratio A/S due to an unchanging number of suicide attempts and due to decreasing suicide lethal outcomes. LimitationsNevertheless, the methods employed detected several factors with well-established associations with suicide. Finally, cohort, prospective or intervention studies are needed to verify the causal inverse relationship of these variables and to speculate the mechanism for this relationship.

Empagliflozin Mitigates TMAO-Induced NLRP3 Inflammation and Alters Transporter Expression in Renal Proximal Tubular Cells

The gut-microbe-derived metabolite, trimethylamine N-oxide (TMAO), not only exhibits elevated levels but also serves as a predictor of higher mortality in patients with chronic kidney disease (CKD). In additional to CKD, elevated TMAO levels were also observed in organic anion transporter 3 (OAT 3) knockout mice and in the presence of trimethoprim, an antibiotic known for inhibiting multiple transporters on renal proximal tubule (PT) cells. These findings suggest that plasma TMAO level is a marker for diminished transporter function in PT cells. Moreover, the pro-inflammatory effects of TMAO on PT cells is relatively underexplored. Besides reno-protective effect, a recent study has shown that the sodium-glucose cotransporter 2 (SGLT2) inhibitor empagliflozin attenuates hyperuricemia by enhancing efflux transporter function. Therefore, we propose that empagliflozin can ameliorate TMAO-induced inflammation in PT cells by regulating the expression of membrane transporters. Western blotting results revealed that empagliflozin mitigated TMAO-induced NLRP3 inflammatory cytokines IL-1β, and IL-18. Additionally, empagliflozin reduced the elevated serum levels of TMAO in a CKD mouse model resulting from 5/6 nephrectomy (5/6Nx). Immuno-fluorescent staining demonstrated that TMAO decreased the expression of the basolateral transporter organic anion transporter 1 (OAT1) but increased the expression of apical membrane transporters ATP-binding cassette super-family G member 2 (ABCG2) on the PT cells of 5/6Nx mice. Our in vitro study indicated that TMAO reduced the expression of basolateral membrane transporters OAT1 and OAT3. But empagliflozin significantly increased the expression of OAT3 and ABCG2 in TMAO-treated HK-2 cells. In summary, TMAO induced NLRP3 inflammation in PT cells, while empagliflozin ameliorated the inflammation. Empagliflozin also lowered TMAO levels and influenced transporter expressions in a CKD mouse model. In conclusion, we have shown that empagliflozin mitigate TMAO-induced NLRP3 inflammation. Beyond inhibiting SGLT2, empagliflozin possesses additional effect on the expression of membrane transporters in PT, particularly in CKD mice. This research was funded by Chang Gung Medical Foundation CMRPG8K0011 and CMRPG8M0311. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Clinical Outcomes and Resource Utilization in Patients With Peripheral Arterial Disease Hospitalized for Acute Coronary Syndrome

Previous studies have shown an association between acute limb ischemia and higher mortality in patients with Acute Myocardial Infarction. Although Peripheral Artery Disease is a well-known risk factor for development of macrovascular pathology, the effect of its severity is not well investigated in patients hospitalized for Acute Coronary Syndrome (ACS). Using a national cohort of patients with various degrees of Peripheral Arterial Disease, we investigated in-hospital outcomes in patients who were admitted for ACS. Using the 2016-2020 Nationwide Readmissions Database, we queried all patients who were hospitalized for ACS (Unstable Angina, Non ST-Elevation Myocardial Infarction, and ST-Elevation Myocardial Infarction). Patients were further divided into three groups, either No Peripheral Arterial Disease (Non-PAD), Peripheral Arterial Disease (PAD) or Critical Limb Ischemia (CLI). Multivariable models were designed to adjust for patient and hospital factors and examine the association between ACS and PAD severity. Of an approximately 3,834,181 hospitalizations for ACS, 6.4% had PAD, 0.2% had CLI and all other were Non-PAD. Following risk adjustment, in hospital mortality was higher by 24% in PAD (AOR 1.24, 95%CI 1.21-1.28) and 86% in CLI (AOR 1.86, 95%CI 1.62-2.09) compared to Non-PAD. Furthermore, PAD and CLI were linked to 1.23-fold (95%CI 1.20-1.26) and 1.67-fold (95%CI 1.45-1.86) greater odds of cardiogenic shock compared to Non-PAD. Additionally, PAD and CLI were linked with higher odds of mechanical circulatory support usage, cardiac arrest and acute kidney injury compared to Non-PAD. Lastly, duration of hospital stay, hospitalization costs and odds of non-home discharge and 30-day readmissions were greater in patients with PAD and CLI compared to Non-PAD. PAD severity was associated with worse clinical outcomes in patients with ACS, including in hospital mortality and resource utilization.

Review article: Evaluation and care of the critically ill patient with cirrhosis.

The increase in prevalence of liver disease globally will lead to a substantial incremental burden on intensive care requirements. While liver transplantation offers a potential life-saving intervention, not all patients are eligible due to limitations such as organ availability, resource constraints, ongoing sepsis or multiple organ failures. Consequently, the focus of critical care of patients with advanced and decompensated cirrhosis turns to liver-centric intensive care protocols, to mitigate the high mortality in such patients. Provide an updated and comprehensive understanding of cirrhosis management in critical care, and which includes emergency care, secondary organ failure management (mechanical ventilation, renal replacement therapy, haemodynamic support and intensive care nutrition), use of innovative liver support systems, infection control, liver transplantation and palliative and end-of life care. We conducted a structured bibliographic search on PubMed, sourcing articles published up to 31 March 2024, to cover topics addressed. We considered data from observational studies, recommendations of society guidelines, systematic reviews, and meta-analyses, randomised controlled trials, and incorporated our clinical expertise in liver critical care. Critical care management of the patient with cirrhosis has evolved over time while mortality remains high despite aggressive management with liver transplantation serving as a crucial but not universally available resource. Implementation of organ support therapies, intensive care protocols, nutrition, palliative care and end-of-life discussions and decisions are an integral part of critical care of the patient with cirrhosis. A multi-disciplinary approach towards critical care management is likely to yield better outcomes.

Herpes simplex (HSV1) encephalitis in an infant: a case report study

Introduction and importance: The herpes simplex virus (HSV) is the most common cause of acute sporadic encephalitis, a severe and often fatal disease in humans. It is associated with high mortality and morbidity rates in untreated patients. Case presentation: An 11-month-old child was admitted to the hospital presenting with acute fever and seizures characterized by staring episodes and spastic movements affecting the left side of the body. Diagnostic workup revealed abnormal T2 flair hyperintense foci in bi-temporoparietal lobes and right thalamus, and bilateral otomastoiditis were detected. A positive result for HSV-1 was obtained through HSV type 1/2 PCR testing, leading to a diagnosis of herpes encephalitis. Clinical discussion: While acyclovir has proven to be an effective therapeutic option, mortality and neurological sequelae continue to be reported in a notable fraction of patients. HSV encephalitis is mainly caused by two strains of the herpes simplex virus: HSV-1, more frequently observed in children and adults, and HSV-2, commonly seen in neonates and those with compromised immune systems. MRI scans often reveal that the brain lesions are localized to certain areas, although temporal involvement may not always be evident. The symptoms of herpetic encephalitis can greatly vary, making early diagnosis and treatment vital for improving patient outcomes. Conclusion: this case report highlights the clinical presentation, diagnostic challenges, and treatment strategies for HSV-1 encephalitis and underscores the importance of early recognition and prompt initiation of antiviral therapy in suspected cases of HSV-1 encephalitis.

Incidental finding of Taenia saginata during laparotomy for penetrating abdominal trauma by stab wound

Taenia saginata (T. saginata) is worldwide in distribution. T. saginata has been known as intestinal parasite of man from very ancient times. We report a case of incidental finding of T. saginata during laparotomy for penetrating abdominal trauma by stab wound. The incidental finding of T. saginata during surgery for penetrating abdominal trauma though rare but it accounts for high mortality and morbidity in patients who have penetrating abdominal trauma. It is therefore importance in increasing public knowledge about food hygiene and elimination of worm for better postoperative outcome in patient with abdominal trauma.

Mortality in fracture of the distal femoral bone (review)

Distal femur fractures in the elderly can lead to the exacerbation of chronic diseases and fatal outcomes similar to those observed in femoral neck fractures in the same category of individuals. Thus, this study aimed to determine the factors influencing the mortality of patients with distal femur fractures based on the analysis of foreign studies and results of treated patients. Review of foreign literature was conducted using the databases of medical publications PubMed, CyberLeninka, Google Scholar, Scopus, Medline, and Cochrane among articles in English, Chinese, Italian, and Russian, as well as through the Web of Knowledge. We analyzed publications for the last 10 years. Evaluation of treated patients included patients aged 60 years with distal femoral fractures between 2021 and 2023. Analysis of the literature data showed that distal femur fractures are accompanied by high mortality in patients in the first years after injury (from 18% to 35%), commonly in elderly patients without surgical treatment (90%–100%), and the presence of several concomitant diseases accompanied by contractures of the femur, knee joint, and false joint and displacement or fracture of the metal retainer. Early surgical treatment (first 48 h) is an effective treatment method that significantly reduces mortality after distal femur fracture (by 2.8 times).

Factors associated with post-hospitalization dialysis dependence in ECMO patients who required continuous renal replacement therapy

Objective This single center retrospective study aimed to describe the variables associated with outpatient dialysis dependence in extracorporeal membrane oxygenation (ECMO) patients who needed continuous renal replacement therapy (CRRT) for acute kidney injury (AKI) during their hospitalization. Methods Retrospective study of patients who required ECMO-CRRT. Results Between the years of 2016 and 2022, 202 patients required ECMO-CRRT. One hundred and six patients (52.5%) survived their hospitalization and were followed up for a median of 391 [133, 1005] days. Eighty-one patients (76.5%) recovered kidney function and were dialysis-free before hospital discharge. Twenty-five patients (23.5%) were hemodialysis-dependent after hospitalization. On multivariate regression analysis, hyperlipidemia (odds ratio, OR 6.08 [1.67–22]) and CRRT duration (OR 1.09 [1.03–1.15]) were associated with the need for dialysis post-hospitalization. In this group, 16 patients eventually became dialysis-free, after a median of 49 [34.7, 78.5] days. These patients had a higher median baseline glomerular filtration rate (GFR) compared to those who never recovered renal function (93 mL/min/1.73 m2 [82.4, 104.3] vs. 63.8 mL/min/1.73 m2 [37.9, 83], p = .009). Their follow-up GFR was lower compared to those who recovered renal function before hospital discharge; (87 mL/min/1.73 m2 [68.2, 98.9] vs. 99 mL/min/1.73 m2 [79, 118], p = .07). Conclusions AKI requiring CRRT was associated with high mortality in patients receiving ECMO. Nonetheless, most ECMO survivors became dialysis-free before hospital discharge. Variables associated with the need for outpatient dialysis included hyperlipidemia and prolonged need for CRRT during hospitalization.

Higher Mortality in Patients With Diffuse Large B-cell Lymphoma Pre-Existing Arterial Hypertension—Real World Data of the Polish Lymphoma Research Group

Arterial hypertension is mentioned as a risk factor in cardio-oncology. This study aimed to assess the long-term prognostic value of arterial hypertension (AH) in diffuse large B-cell lymphoma (DLBCL). We analysed data collected by the Polish Lymphoma Research Group for the evaluation of the outcomes associated with the use of first-line rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone therapy in patients with DLBCL with coexisting AH. Patients with other cardiovascular comorbidities or premature chemotherapy discontinuation due to cardiovascular toxicity were excluded. Pre-existing AH was diagnosed in 65 of 232 patients with DLBCL (28%) included in the study, and was associated with significantly shorter overall survival values (p<0.00001). The rates of DLBCL recurrence, administration of second-, third-, or fourth-line chemotherapy, and lymphoma-related deaths were similar in patients with and those without AH. Cardiovascular deaths were significantly more frequently observed in patients with pre-existing AH (38.5% vs 3.6%, p<0.0001). In the univariate analysis, AH (p=0.000001), older age (p<0.000001), and diabetes (p=0.0065) were identified as significant predictors of all-cause mortality; however, cardiovascular mortality was associated with AH (p<0.000001), older age (p=0.000008), and dyslipidaemia (p=0.03). Multivariate analysis revealed AH as an age-independent significant predictor of all-cause (p=0.00045) and cardiovascular mortality (p<0.000001). In the long-term follow-up of patients with DLBCL, the role of AH, as an important age-independent predictor of premature cardiovascular mortality, was so strong that it may have value for use in close surveillance in cardio-oncology clinics.

Transjugular Intrahepatic Portosystemic Shunt as a Bridge to Abdominal Surgery in Cirrhosis.

Abdominal surgery is associated with high postoperative mortality and morbidity in cirrhotic patients. Despite improvements in surgical techniques, clinical management, and intensive care, the outcome could be influenced by the degree of portal hypertension, the severity of hepatopathy, or the type of surgery. Preoperative transjugular intrahepatic portosystemic shunt (TIPS) placement, in addition to medical therapy, plays an important role in managing the complications of portal hypertension such as ascites, hepatic encephalopathy, variceal bleeding or portal vein thrombosis. To date, the improvement of post-surgery outcomes in cirrhotic patients after TIPS placement remains unclear. Only observational data existing in the literature and prospective studies are urgently needed to evaluate the efficacy and safety of TIPS in this setting. This review aims to outline the role of TIPS as a tool in postoperative complications reduction in cirrhotic patients, both in the setting of emergency and elective surgery.

Bendopnea prevalence and prognostic value in older patients with heart failure: FRAGILE-HF-SONIC-HF post hoc analysis.

This study aimed to investigate the prevalence, clinical characteristics, and prognostic value of bendopnea in older patients hospitalized for heart failure. This post hoc analysis was performed using two prospective, multicentre, observational studies: the FRAGILE-HF (main cohort) and SONIC-HF (validation cohort) cohorts. Patients were categorized based on the presence of bendopnea, which was evaluated before discharge. The primary endpoint was 2-year all-cause mortality after discharge. Among the 1243 patients (median age, 81 years; 57.2% male) in the FRAGILE-HF cohort and 225 (median age, 79 years; 58.2% men) in the SONIC-HF cohort, bendopnea was observed in 31 (2.5%) and 10 (4.4%) patients, respectively. Over a 2-year follow-up period, all-cause death occurred in 20.8 and 21.9% of the patients in the FRAGILE-HF and SONIC-HF cohorts, respectively. Kaplan-Meier survival curves demonstrated significantly higher mortality rates in patients with bendopnea than in those without bendopnea in the FRAGILE-HF (log-rank P = 0.006) and SONIC-HF cohorts (log-rank P = 0.014). Cox proportional hazard analysis identified bendopnea as an independent prognostic factor for all-cause mortality in both the FRAGILE-HF [hazard ratio (HR) 2.11, 95% confidence interval (CI) 1.18-3.78, P = 0.012] and SONIC-HF cohorts (HR 4.20, 95% CI 1.63-10.79, P = 0.003), even after adjusting for conventional risk factors. Bendopnea was observed in a relatively small proportion of older patients hospitalized for heart failure before discharge. However, its presence was significantly associated with an increased risk of all-cause mortality.

Deaths of patients diagnosed with psychotic disorder due to SARS Cov-2 in Avilés, Spain

IntroductionPsychotic patients are a vulnerable population from a social and health point of view. The SARS Cov-2 pandemic affected millions of people around the world, however, its effects on psychotic patients in Avilés Spain, have not been analized.ObjectivesThe objective of this study was to determine and compare the mortality of patients with psychosis due to SARS Cov-2 in Avilés, Spain with others regions and countries in the European Union. Determine the influence of social condition and antipsychotic treatment on the condition of these patients.MethodsThis is a descriptive, observational study, in which patients diagnosed with psychosis in the period 2020-2021 who contracted SARS Cov-2 infection in Avilés, Spain, were studied to determine those who died from this cause. The influence of social status and antipsychotic medication, as well as sociodemographic factors (age, sex, marital status) were analyzed and compared with other regions and countries of the European Union.ResultsDespite the high mortality rate in patients with psychosis, during the years of the pandemic SARS Cov-2 played an important role given the vulnerability of these patients.ConclusionsThe negative effects and deaths during the COVID-19 pandemic were at the time a major problem for public health worldwide. This study concluded that the morbidity and mortality of psychotic patients who contracted COVID-19 was lower than the rest of the population.Disclosure of InterestNone Declared

Long noncoding RNA TUG1 promotes cisplatin resistance in ovarian cancer via upregulation of DNA polymerase eta.

Chemoresistance is a major cause of high mortality and poor survival in patients with ovarian cancer (OVCA). Understanding the mechanisms of chemoresistance is urgently required to develop effective therapeutic approaches to OVCA. Here, we show that expression of the long noncoding RNA, taurine upregulated gene 1 (TUG1), is markedly upregulated in samples from OVCA patients who developed resistance to primary platinum-based therapy. Depletion of TUG1 increased sensitivity to cisplatin in the OVCA cell lines, SKOV3 and KURAMOCHI. Combination therapy of cisplatin with antisense oligonucleotides targeting TUG1 coupled with a drug delivery system effectively relieved the tumor burden in xenograft mouse models. Mechanistically, TUG1 acts as a competing endogenous RNA by downregulating miR-4687-3p and miR-6088, both of which target DNA polymerase eta (POLH), an enzyme required for translesion DNA synthesis. Overexpression of POLH reversed the effect of TUG1 depletion on cisplatin-induced cytotoxicity. Our data suggest that TUG1 upregulation allows OVCA to tolerate DNA damage via upregulation of POLH; this provides a strong rationale for targeting TUG1 to overcome cisplatin resistance in OVCA.

Effects of Glycemic Variability in Critically Ill Patients with Coronavirus Disease 2019: A Retrospective Observational Study.

Hyperglycemia is considered an adaptive metabolic manifestation of stress and is associated with poor outcomes. Herein, we analyzed the association between glycemic variability (GV) and hospital mortality in patients with coronavirus disease 2019 (COVID-19) admitted to the intensive care unit (ICU), and the association between GV and mechanical ventilation (MV), ICU stay, length of hospital stays, renal replacement therapy (RRT), hypoglycemia, nosocomial infections, insulin use, and corticosteroid class. In this retrospective observational study, we collected information on blood glucose levels during the first 10 days of hospitalization in a cohort of ICU patients with COVID-19 and its association with outcomes. In 239 patients, an association was observed between GV and hospital mortality between the first and last quartiles among patients without diabetes [odds ratio (OR), 3.78; confidence interval, 1.24-11.5]. A higher GV was associated with a greater need for RRT (p = 0.002), regular insulin (p < 0.001), and episodes of hypoglycemia (p < 0.001). Nosocomial infections were associated with intermediate GV quartiles (p = 0.02). The corticosteroid class had no association with GV (p = 0.21). Glycemic variability was associated with high mortality in patients with COVID-19 and observed in the subgroup of patients without diabetes. Glycemic control in critically ill patients remains controversial and hyperglycemia is associated with worse outcomes. Diabetes mellitus (DM) is one of the most prevalent comorbidities in patients with COVID-19. In addition, they require corticosteroids due to pulmonary involvement, representing a challenge and an opportunity to better understand how glycemic changes can influence the outcome of these patients. Boschi E, Friedman G, Moraes RB. Effects of Glycemic Variability in Critically Ill Patients with Coronavirus Disease 2019: A Retrospective Observational Study. Indian J Crit Care Med 2024;28(4):381-386.

Rib Fractures and Frailty in Geriatric Trauma Patients.

As rib fractures are a common injury in the geriatric trauma population and can result in increased morbidity and mortality, we sought to understand predicting outcomes in this population. We hypothesized that frail geriatric rib fracture patients would have worse outcomes than their non-frail counterparts. This single-center retrospective study includes patients from July 2019 to June 2022 who were ≥65years-old, had ≥ 2 rib fractures, and a documented Clinical Frailty Scale score. Univariate analysis was conducted comparing frail vs non-frail, and ≤3 rib fractures vs >3 rib fractures. Multivariate logistic regressions for risk of mortality and of frailty were performed. We found higher mortality in patients with >3 rib fractures on univariate analysis; however, this did not hold true on multivariate analysis. Frail patients were less likely discharged home and had a lower functional status at discharge. Further investigation is needed to effectively improve outcomes for geriatric trauma patients with rib fractures.

Abstract 2752: ICA1 promotes prostate cancer progression and metastasis via AR down-regulation

Abstract Cancer metastasis, one of the main characteristics in malignancy, contributes to high mortality in cancer patients. Prostate cancer (PCa) is the most common cancer among men and the second leading cause of cancer-related death in Europe and the United States. In China, its incidence has been dramatically increased over past years. However, the mechanism of PCa progression and metastasis remains unclear. The androgen receptor (AR) has been demonstrated to play an important role in PCa progression and metastasis. We have previously established mouse models of PCa bone metastasis and PCa lung metastasis. We have obtained cell clones with bone-specific or lung-specific metastatic capability. By transcriptomic analysis of highly metastatic cell clones and their parental cells, we found a gene group including islet cell autoantigen 1 (ICA1) that are highly expressed in both metastatic cell clones. We further compared these results with RNA array data in clinical samples. Data comparison and correlation analysis showed that ICA1 was negatively correlated with AR expression. Survival analysis of PCa and lung cancer patients showed higher expression of ICA1 but with shorter overall survival. Down-regulation of ICA1 expression in highly metastatic tumor cells significantly inhibited cell growth, colony formation, migration, and invasion. ICA1 overexpression in parental RM1 cells apparently increased cell growth, migration, and metastasis. Interestingly, down-regulation of ICA1 also significantly activated AMPK/mTOR signaling pathway. These findings are anticipated to shed light on the novel pathogenic mechanism underlying PCa and propose a compelling theoretical basis for the application of ICA1 in PCa. This work supported by the NSFC projects (81972420, 81972766, 82173336), as well as grants from the Science and Technology Project of Shenzhen (JCYJ20210324104214040, JCYJ20190809161811237).Keywords: prostate cancer, metastasis, ICA1, androgen receptor Citation Format: Fuhao Wang, Yu He, Xin Huang, Ming Chang, Xiao Zhang, Xiaoyi Li, Xinyu Ye, Yi Lu. ICA1 promotes prostate cancer progression and metastasis via AR down-regulation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2752.

Abstract 4101: Immune inhibition of murine colorectal cancer by a p53 peptide mucosal vaccine

Abstract Colorectal cancer (CRC) is among the most common cancers with high morbidity and mortality for patients despite multi-modality treatment options. Immune checkpoint inhibitors often have impact in the 15% of CRC patients with microsatellite instability-high status CRCs but have limited utility in the remaining 85% of CRC patients. Given the presence of p53 mutations in CRC, we pursued a vaccine approach against tumor cells expressing murine CRC Trp53 codon 270 missense alleles (codon 273 mutation in human cancer) using a combination of R270H p53 peptide, wild type p53 recombinant protein and used a mucosal adjuvant (MA) to drive epithelial immune responses. The vaccine (p53/MA) was studied in a CDX2-CreERT2 (tamoxifen-induced Cre-Lox) transgenic mouse CRC model where tumors arise in the cecum and proximal colon epithelium following combined ApcΔ580, KrasG12D, and Trp53R270H mutations (AKP model). The p53/MA vaccine treatment was administered intranasally to the mice at defined time points after tamoxifen tumor induction. p53/MA vaccinated animals had increased anti-p53 IgG (p&amp;lt;0.01), IgG2a (p&amp;lt;0.01), and IgG2b (p&amp;lt;0.001) in sera compared to control mice. The treatment enhanced antigen-specific Th1 and Th17 cellular immune responses, as shown by increasing of IFN-ɤ (p&amp;lt;0.05), IL-17a (p&amp;lt;0.01) and IL-2 (p&amp;lt;0.01) both in splenocytes and draining lymph nodes measured by Luminex assay. Vaccinated mice also showed significant more cells producing IFN-ɤ (p&amp;lt;0.001) and IL-17a (p&amp;lt;0.001) as analyzed by ELISpot. Importantly, the immunized animals had decreased tumor size/volume (p&amp;lt;0.001) and prolonged survival (p&amp;lt;0.05) compared to control animals that received only saline or MA respectively. Tumors from vaccinated mice also showed more mononuclear cell infiltrates than tumors from the control animals. In conclusion, novel p53/MA vaccinations can induce significant p53-specific immune responses and anti-tumor effects in the mouse AKP CRC model. Citation Format: Suhe Wang, Zhengyi Cao, Katarzyna W. Janczak, Ying Feng, Maranne Green, Eric R. Fearon, James R. Baker Jr. Immune inhibition of murine colorectal cancer by a p53 peptide mucosal vaccine [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4101.