Pancreatic cancer survival prediction via inflammatory serum markers

Background For prognostic evaluation of pancreatic ductal adenocarcinoma (PDAC), the only well-established serum marker is carbohydrate antigen CA19-9. To improve the accuracy of survival prediction, we tested the efficacy of inflammatory serum markers. Methods A preoperative serum panel comprising 48 cytokines plus high-sensitivity CRP (hs-CRP) was analyzed in 173 stage I–III PDAC patients. Analysis of the effect of serum markers on survival utilized the Cox regression model, with the most promising cytokines chosen with the aid of the lasso method. We formed a reference model comprising age, gender, tumor stage, adjuvant chemotherapy status, and CA19-9 level. Our prognostic study model incorporated these data plus hs-CRP and the cytokines. We constructed time-dependent ROC curves and calculated an integrated time-averaged area under the curve (iAUC) for both models from 1 to 10 years after surgery. Results Hs-CRP and the cytokines CTACK, MIF, IL-1β, IL-3, GRO-α, M-CSF, and SCF, were our choices for the prognostic study model, in which the iAUC was 0.837 (95% CI 0.796–0.902), compared to the reference model’s 0.759 (95% CI 0.691–0.836, NS). These models divided the patients into two groups based on the maximum value of Youden’s index at 7.5 years. In our study model, 60th percentile survival times were 4.5 (95% CI 3.7–NA) years (predicted high-survival group, n = 34) and 1.3 (95% CI 1.0–1.7) years (predicted low-survival group, n = 128), log rank p < 0.001. By the reference model, the 60th percentile survival times were 2.8 (95% CI 2.1–4.4) years (predicted high-survival group, n = 44) and 1.3 (95% CI 1.0–1.7) years (predicted low-survival group, n = 118), log rank p < 0.001. Conclusion Hs-CRP and the seven cytokines added to the reference model including CA19-9 are potential prognostic factors for improved survival prediction for PDAC patients.

Chronic effects of blast injury on the microvasculature in a transgenic mouse model of Alzheimer’s disease related Aβ amyloidosis

Background Altered cerebrovascular function and accumulation of amyloid-β (Aβ) after traumatic brain injury (TBI) can contribute to chronic neuropathology and increase the risk for Alzheimer’s disease (AD). TBI due to a blast-induced shock wave (bTBI) adversely affects the neurovascular unit (NVU) during the acute period after injury. However, the chronic effects of bTBI and Aβ on cellular components of the NVU and capillary network are not well understood. Methods We exposed young adult (age range: 76–106 days) female transgenic (Tg) APP/PS1 mice, a model of AD-like Aβ amyloidosis, and wild type (Wt) mice to a single bTBI (~ 138 kPa or ~ 20 psi) or to a Sham procedure. At 3-months or 12-months survival after exposure, we quantified neocortical Aβ load in Tg mice, and percent contact area between aquaporin-4 (AQP4)-immunoreactive astrocytic end-feet and brain capillaries, numbers of PDGFRβ-immunoreactive pericytes, and capillary densities in both genotypes. Results The astroglia AQP4-capillary contact area in the Tg-bTBI group was significantly lower than in the Tg-Sham group at 3-months survival. No significant changes in the AQP4-capillary contact area were observed in the Tg-bTBI group at 12-months survival or in the Wt groups. Capillary density in the Tg-bTBI group at 12-months survival was significantly higher compared to the Tg-Sham control and to the Tg-bTBI 3-months survival group. The Wt-bTBI group had significantly lower capillary density and pericyte numbers at 12-months survival compared to 3-months survival. When pericytes were quantified relative to capillary density, no significant differences were detected among the experimental groups, for both genotypes. Conclusion In conditions of high brain concentrations of human Aβ, bTBI exposure results in reduced AQP4 expression at the astroglia-microvascular interface, and in chronic capillary proliferation like what has been reported in AD. Long term microvascular changes after bTBI may contribute to the risk for developing chronic neurodegenerative disease later in life.

Identification of RAGE and OSM as New Prognosis Biomarkers of Severe Pneumonia

Objective. To investigate efficiency of RAGE and OSM as new prognosis biomarkers of severe pneumonia. Methods. Eligible patients were classified into hypoxemia and nonhypoxemia groups. Meanwhile, the same cohort was divided into survival and nonsurvival groups after a post-hospital stay of 30 days. We analyzed risk factors for the hypoxia and death among these patients. Results. Compared with nonsurvival group, significant increase was noticed in PH, lymphocyte, albumin and platelet level in survival group, while significant decline was noticed in neutrophils, RBC, hemoglobin, hematocrit, creatinine, total bilirubin, CRP, PCT, OSM, RAGE and neutrophils/lymphocyte level. Oxygenation index level was related to APACHE II, LIS, SOFA, NUTRIC score, WBC, neutrophils, lymphocyte, RAGE, and albumin level ( p < 0.05 ). LIS, SOFA, NUTRIC score, lac, lymphocyte, platelet, BUN, total bilirubin, PCT, and OSM levels were associated with mortality rate ( p < 0.05 ). Conclusions. RAGE and OSM may serve as a new biomarker for poor prognosis in pneumonia patients.

In-Hospital Cardiac Arrest: Patient Characteristics and Factors Influencing Survival and Neurologic Outcomes

Objective: We aimed to determine the characteristics of in-hospital cardiac arrest (IHCA) patients, as well as the factors influencing survival to discharge and good neurologic outcome.Methods: We examined patients who experienced IHCA from January 1, 2011, to December 31, 2013, in Soonchunhyang University Seoul Hospital. They were divided into a survival group and non-survival group. The patient characteristics, including age, sex, comorbid disease, arrest time, arrest location, witnessed arrest, monitoring, arrest cause, arrest rhythm, and cardiopulmonary resuscitation (CPR) duration, were compared between the groups. Moreover, we assessed the factors associated with survival to discharge and good neurologic outcomes by using multivariate logistic regression analysis.Results: In total, 453 patients of IHCA were observed. The comorbidities in the survival group included neurologic disease (P < 0.001), arrhythmia (P = 0.001), and myocardial infarction (P = 0.032), pneumonia (P = 0.016). Other characteristics included cardiac arrest at daytime (P = 0.032), cardiogenic arrest cause (P = 0.019), and CPR duration < 15 minutes (P < 0.001). The factors associated with survival to discharge included comorbid neurologic disease (odds ratio [OR], 2.191; P = 0.031), arrhythmia (OR, 3.027; P = 0.009), pneumonia (OR, 3.243; P = 0.002), and CPR duration < 15 minutes (OR, 9.638; P < 0.001). The factors influencing good neurologic outcomes included age < 65 years (OR, 3.158; P = 0.007), comorbid disease as arrhythmia (OR, 4.921; P = 0.001), pneumonia (OR, 4.551; P = 0.001), hypotension (OR, 4.264; P = 0.021), and CPR duration < 15 minutes (OR, 6.652; P = 0.001).Conclusion: The factors influencing survival to discharge and good neurologic outcomes among IHCA patients included comorbidities, arrest cause, and CPR duration.

Efficacy of Tocilizumab in COVID-19: Single-Center Experience

Background. Cytokine release syndrome can be observed during the course of COVID-19. Tocilizumab is used for treating this highly fatal syndrome. We think that the starting time of tocilizumab is important. In this article, we aimed to discuss the efficacy of tocilizumab and to review the necessity of starting it in the early period and the laboratory values that guide us in determining the time of this early period. Methods. This retrospective study includes a total of 308 patients with a diagnosis of COVID-19 who were treated with tocilizumab, who were hospitalized in the University of Health Sciences, Gazi Yaşargil Training and Research Hospital between July 2020 and December 2020. The data of the patients were recorded on the day of hospitalization, the day of taking tocilizumab (day 0), and the 1st day, 3rd day, 7th day, and 14th day after taking tocilizumab. Data included age, gender, underlying diseases, where the patient was followed, duration of symptoms before admission to the hospital, duration of oxygen demand before tocilizumab, fever, saturation, and laboratory values. Patients were divided into the mortality group (group 1) and the survival group (group 2), and all data were compared. Results. The study consisted of 308 COVID-19 patients divided into two groups: the mortality group (group 1, n = 135 ) and the survival group (group 2, n = 173 ). The median age of the patients was 60 (min–max: 50-70) years, 75.3% ( n = 232 ) were male, and 56.8% had at least one comorbidity. While 88.9% of group 1 was in the intensive care unit, 26.6% of group 2 received tocilizumab while in the intensive care unit, and there was a statistically significant difference. Median SpO2 values and lymphocyte counts were significantly lower in group 1 than in group 2, both on the day of hospitalization and on the day of the first dose of tocilizumab treatment ( p < 0.001 for both). C-reactive protein, d-dimer, and alanine aminotransferase values were higher in the mortal group on the first day of hospitalization, and this was significant ( p = 0.021 , p = 0.001 , and p = 0.036 , respectively). In our study, d-dimer was 766.5 ng/mL in the survivor group and 988.5 ng/mL in the mortal group. In our patient group, the mean lymphocyte count was 700 × 10 3 / m m 3 in the group that survived the first day of TCZ and 500 × 10 3 / m m 3 in the mortal group. In addition, the CRP value was 135.5 mg/L in the survivor group and 169 mg/L in the mortal group. There was no difference between ferritin values. Conclusions. Tocilizumab is still among the COVID-19 treatment options and appears to be effective. But the start time is important. In order to increase its effectiveness, it may be important to know a cut-off value of the laboratory findings required for the diagnosis of cytokine release syndrome. Further studies are needed for this.

Lymphocyte and Platelet Counts, as well as Interleukin-6 Levels, Predict Mortality of Coronavirus Disease 2019 (COVID-19): A Systematic Review and Meta-Analysis

Objective. To systematically evaluate the value of lymphocytes, platelets, and interleukin-6 in predicting the mortality of patients with coronavirus disease 2019 (COVID-19) and to provide medical evidence for the long-term prognosis of patients with COVID-19. Methods. The latest studies published until July 1, 2021, were retrieved from databases including PubMed, Embase, and Cochrane Library to analyze the ability of lymphocyte and platelet counts as well as interleukin-6 levels to predict mortality in patients with COVID-19. Two reviewers independently screened the literature and extracted data, then evaluated the risk of bias of included studies using the Newcastle–Ottawa Scale (NOS), and used Stata 15.0 software for meta-analysis. Results. A total of nine studies were included, involving 4340 patients. There were 1330 patients in the death group and 3010 patients in the survival group. Meta-analysis showed that, compared with the survival group, lymphocyte counts in the death group were significantly lower (SMD = −0.64, 95% CI: −0.86–−0.43, p < 0.01 ), platelet counts were significantly lower (SMD = −0.47, 95% CI: −0.67–−0.27, p < 0.01 ), and interleukin-6 levels were significantly higher (SMD = 1.07, 95% CI: 0.62–1.53, p < 0.01 ). Conclusion. Lymphocyte and platelet counts, as well as interleukin-6 levels, can help predict the mortality of patients with COVID-19. Due to the limitation of the number and quality of the included studies, these conclusions need to be validated by additional high-quality studies.

Study on Risk Factors for Death from Cardiomyopathy and Effectiveness of Health Information Management

Objective. To explore risk factors for death from cardiomyopathy and the effectiveness of health information management (HIM). Methods. A total of 80 patients with cardiomyopathy admitted in ICU of our hospital (January 2016–January 2020) were selected as study subjects, and the clinical data of the patients were retrospectively analyzed. The patients were divided into the survival group (n = 72) and the death group (n = 14) according to the treatment outcome. Then, according to the management mode, the survival group was further equally divided into the conventional group and the HIM group to investigate the influence of risk factors on prognosis of patients with cardiomyopathy and the effectiveness of HIM. Results. No significant difference was found in baseline body mass, myocardial enzymes, troponin, infection factors, history of heart disease, and gender between the survival group and the death group ( P > 0.05). Compared with the survival group, the patients of the death group were older ( P < 0.05), LVEF of the death group was obviously lower ( P < 0.05), and the scores of APACHE II and SOFA of the death group were obviously higher ( P < 0.05). Further logistic regression analysis of the univariate factors influencing the risk of death from cardiomyopathy led to the conclusion that LVEF was an independent risk factor for death in patients with cardiomyopathy. LVEF below 24.69% examined by echocardiography had a high predictive value, with a sensitivity of 98.6% and a specificity of 78.6%. No obvious difference was found in general data between the conventional group and the HIM group ( P > 0.05). Compared with the conventional group, the disease remission rate, complication rate, awareness rate of health knowledge, ICU length of stay, and scores of self-management efficacy of the HIM group were obviously better ( P < 0.05). No significant difference was found in 5-year mean survival rate between the conventional group and the HIM group ( P > 0.05). Conclusion. Older age, lower LVEF, and higher scores of APACHE II and SOFA are all risk factors for death from cardiomyopathy. Lower LVEF is an independent risk factor, and LVEF below 24.69% is an important indicator of increased risk of death. Moreover, HIM can effectively improve short-term treatment efficacy but has little effect on the long-term survival rate.

COT-11 Relationship between preoperative liquid biopsy and prognosis of glioblastoma -Next Generation Sequencing of small noncoding RNA-

Background Non-invasive biomarkers are required in clinical practice of glioblastoma (GBM). We have previously reported the liquid biopsy for differentiating glioblastoma, central nervous system primary lymphoma and healthy control. In this study, we analyzed the relationship between the preoperative serum expression of circulating small non-coding RNAs and the prognosis of GBM patients. Methods Preoperative blood samples of GBM, IDH-wildtype patients (N=26) were centrifuged and collected all small RNAs in serum. The expression of small non-coding RNAs were analyzed using a next-generation sequencing system. The small non-coding RNAs that could predict short-term survivals in GBM patients were selected by the stepwise analysis. A diagnostic model was created using the combination of these RNAs and evaluated with ROC curve. Results GBM patients treated with adjuvant therapy of temozolomide and radiotherapy were divided into two groups: (1) a short-term survival group (N=11) with a survival time less than 15 months and (2) a long-term survival group (N=15) with a survival time more than 15 months. In the short-term survival group, the preoperative serum expression levels of small RNA-X and small RNA-Y were high, and the expression levels of small RNA-Z and small RNA-W were low. Using these four small non-coding RNAs, a prognostic model was created. The model was able to predict the short-term survival group of GBM patients with a sensitivity of 90.9% and specificity of 93.3% (AUC: 0.969). Conclusion The prognostic model developed with preoperative small non-coding RNA in GBM patients may be useful for estimating the survival of GBM patients treated with adjuvant therapy of temozolomide and radiotherapy.

The absolute and relative changes in high-sensitivity cardiac troponin I are associated with the in-hospital mortality of patients with fulminant myocarditis

Background We sought to describe the tendency and extent of high-sensitivity cardiac troponin I (hs-cTnI) changes in patients with fulminant myocarditis (FM) after admission and to explore the relationship between the in-hospital mortality of FM and the absolute and relative changes in hs-cTnI within 24 h and 48 h after admission. Methods In the retrospective study, the object are patients diagnosed with FM in our single centre. The value of cardiac troponin was recorded after patients admitted to hospital in succession. The absolute and relative changes in hs-cTnI within 24 h and 48 h were described as range distributions. Receiver operating characteristic (ROC) curve and Cox analyses were performed to determine the relationship between in-hospital mortality of FM and hs-cTnI changes. Results A total of 83 FM patients admitted to our centre from January 1, 2010 to December 31, 2019 were included; 69 patients survived and 14 patients died. In the survival group, 78% of patients experienced a decline in hs-cTnI within 24 h, while 36% of the mortality group exhibited a declining tendency in hs-cTnI (P = 0.003). Nearly 60% of survival group had a 0–2000 ng/l reduction in troponin from baseline within 24 h of admission. However, troponin levels of 50% of patients in the mortality group were 0–10,000 ng/ L higher than baseline 24 h after admission. Multivariable logistic analysis revealed that the declining tendency of hs-cTnI within 24 h, in addition to time from onset to admittance to hospital, intravenous immunoglobulin treatment and the abnormal level of creatinine, were associated with the in-hospital mortality of FM (for the declining tendency of hs-cTnI within 24 h, OR = 0.10, 95% CI 0.02–0.68, P = 0.018). The ROC curve revealed optimal cut-off values of − 618 ng/l for absolute change within 24 h (AUC = 0.800, P < 0.01), − 4389 ng/l for absolute change within 48 h (area under the curve = 0.711, P < 0.01), − 28.46% for relative change within 24 h (AUC = 0.810, P < 0.01), and − 52.23% for relative change within 48 h (AUC = 0.795, P < 0.01). Absolute changes and relative changes in hs-cTnI within 24 h and 48 h were strong predictors of in-hospital mortality by Cox regression analysis after adjustment for sex, time from onset to admission, and occurrence of ventricular tachycardia or ventricular fibrillation. Conclusion Most FM patients who survived experienced a decline in hs-cTnI within 24 h. The absolute and relative changes in hs-cTnI within 24 h and 48 h were strong predictors of in-hospital mortality.

Clinical Characteristics of Intraoperative Cardiac Arrest During Cancer Surgery

Purpose: Intraoperative cardiac arrest (IOCA) is rare, unpredictable, and may result in a poor outcome. The features of IOCA during cancer surgery and factors related to survival following an IOCA were examined.Methods: This was a retrospective study of patients who had cancer surgery under general anesthesia between March 2009 and March 2021 (n = 84,615) to determine the number of patients who had an IOCA. Patients’ clinical information, cause of IOCA, hypoxemia during anesthesia, and the duration of hypotension and CPR were analyzed.Results: A total of 22 cases of IOCA occurred during cancer surgery (overall incidence: 2.6 per 10,000 surgeries). Return of spontaneous circulation was achieved in 17 patients, but only 13 survived until discharge. There were statistically significant differences between the deceased and the survival cancer patient groups in; (1) duration of hypoxemia (survival group: 5 minutes, range: 2-18 minutes; deceased group: 60 minutes, range, 22.5-120 minutes; p = 0.019); (2) duration of hypotension (survival group: 35 minutes, range, 15-55 minutes; deceased group 160 minutes, range, 140-185 minutes; p = 0.007); and (3) total duration of CPR (survival group: 3 minutes, range: 1-15 minutes; deceased group: 40 minutes, range: 19-149 minutes; p = 0.005).Conclusion: The duration of hypoxemia and hypotension prior to the onset of IOCA, as well as the duration of CPR were associated with the prognosis of IOCA, highlighting the need to reduce multiorgan damage caused by hypoxemia and hypotension during surgery in high-risk patients.