Risk Factors For Unfavorable Prognosis Research Articles

Excessive accumulation of epicardial adipose tissue promotes microvascular obstruction formation after myocardial ischemia/reperfusion through modulating macrophages polarization

BackgroundOwing to its unique location and multifaceted metabolic functions, epicardial adipose tissue (EAT) is gradually emerging as a new metabolic target for coronary artery disease risk stratification. Microvascular obstruction (MVO) has been recognized as an independent risk factor for unfavorable prognosis in acute myocardial infarction patients. However, the concrete role of EAT in the pathogenesis of MVO formation in individuals with ST-segment elevation myocardial infarction (STEMI) remains unclear. The objective of the study is to evaluate the correlation between EAT accumulation and MVO formation measured by cardiac magnetic resonance (CMR) in STEMI patients and clarify the underlying mechanisms involved in this relationship.MethodsFirstly, we utilized CMR technique to explore the association of EAT distribution and quantity with MVO formation in patients with STEMI. Then we utilized a mouse model with EAT depletion to explore how EAT affected MVO formation under the circumstances of myocardial ischemia/reperfusion (I/R) injury. We further investigated the immunomodulatory effect of EAT on macrophages through co-culture experiments. Finally, we searched for new therapeutic strategies targeting EAT to prevent MVO formation.ResultsThe increase of left atrioventricular EAT mass index was independently associated with MVO formation. We also found that increased circulating levels of DPP4 and high DPP4 activity seemed to be associated with EAT increase. EAT accumulation acted as a pro-inflammatory mediator boosting the transition of macrophages towards inflammatory phenotype in myocardial I/R injury through secreting inflammatory EVs. Furthermore, our study declared the potential therapeutic effects of GLP-1 receptor agonist and GLP-1/GLP-2 receptor dual agonist for MVO prevention were at least partially ascribed to its impact on EAT modulation.ConclusionsOur work for the first time demonstrated that excessive accumulation of EAT promoted MVO formation by promoting the polarization state of cardiac macrophages towards an inflammatory phenotype. Furthermore, this study identified a very promising therapeutic strategy, GLP-1/GLP-2 receptor dual agonist, targeting EAT for MVO prevention following myocardial I/R injury.

Immune cell infiltration and prognostic index in cervical cancer: insights from metabolism-related differential genes.

Cervical cancer remains a significant gynecologic malignancy in both China and the United States, posing a substantial threat to women's lives and health due to its high morbidity and mortality rates. Altered energy metabolism and dysregulated mitochondrial function play crucial roles in the development, growth, metastasis, and recurrence of malignant tumors. In this study, we aimed to predict prognosis and assess efficacy of anti-tumor therapy in cervical cancer patients based on differential genes associated with mitochondrial metabolism. Transcriptomic data and clinical profiles of cervical cancer patients were retrieved from the TCGA and GEO databases. Differential gene-related cellular pathways were identified through GO, KEGG, and GSEA analyses. Prognostic indices were constructed using LASSO regression analysis. Immune cell infiltration was assessed using CIBERSORT and ssGSEA, and the correlation between immune checkpoint inhibitor genes and differential genes was examined. Tumor mutation load (TMB) and its association with prognostic indices were analyzed using nucleotide variant data from the TCGA database. Patient response to immunotherapy and sensitivity to antitumor drugs were determined using the TIDE algorithm and the oncoPredic algorithm, respectively. A prognostic index based on metabolism-related differential genes was developed to predict the clinical outcome of cervical cancer patients, enabling their classification into two distinct subtypes. The prognostic index emerged as an independent risk factor for unfavorable prognosis. The high-index group exhibited a significantly worse overall prognosis, along with elevated tumor mutation burden (TMB), increased immune cell infiltration, and lower TIDE scores, indicating a potential benefit from immunotherapy. Conversely, the low-index group demonstrated increased sensitivity to metabolism-related antitumor agents, specifically multikinase inhibitors. The aim of this study was to develop a prognostic index based on differential genes associated with mitochondrial metabolism, which could be used to predict cervical cancer patients' prognoses. When combined with TIDE and TMB analyses, this prognostic index offers insights into the immune cell infiltration landscape, as well as the potential efficacy of immunotherapy and targeted therapy. Our analysis suggests that the Iron-Sulfur Cluster Assembly Enzyme (ISCU) gene holds promise as a biomarker for cervical cancer immunotherapy.

Comparison of sex differences on outcomes after aneurysmal subarachnoid hemorrhage: a propensity score-matched analysis

ObjectiveSex differences in outcomes of patients with aneurysmal subarachnoid hemorrhage (aSAH) remain controversial. Therefore, the aim of this study was to investigate the sex differences in the prognosis of patients with aSAH.MethodsThis study retrospectively analyzed the clinical data of aSAH patients admitted to the Department of Neurosurgery of General Hospital of Northern Theater Command, from April 2020 to January 2022. The modified Rankin Scale (mRS) was used to evaluate outcomes at 3-month post-discharge. Baseline characteristics, in-hospital complications and outcomes were compared after 1:1 propensity score matching (PSM).ResultsA total of 665 patients were included and the majority (63.8%) were female. Female patients were significantly older than male patients (59.3 ± 10.9 years vs. 55.1 ± 10.9 years, P < 0.001). After PSM, 141 male and 141 female patients were compared. Comparing postoperative complications and mRS scores, the incidence of delayed cerebral ischemia (DCI) and hydrocephalus and mRS ≥ 2 at 3-month were significantly higher in female patients than in male patients. After adjustment, the analysis of risk factors for unfavorable prognosis at 3-month showed that age, sex, smoking, high Hunt Hess grade, high mFisher score, DCI, and hydrocephalus were independent risk factors.ConclusionFemale patients with aSAH have a worse prognosis than male patients, and this difference may be because females are more vulnerable to DCI and hydrocephalus.

Predictors of Unfavorable Prognosis in Patients with Heart Failure After Cardioverter-Defibrillator Implantation According to the Prospective Part of the Kuzbass Registry.

Identification of clinical and instrumental predictors for non-arrhythmic death in patients with heart failure (HF) and implantable cardioverter-defibrillator (ICD). Through a telephone survey and examination of medical records from hospital and polyclinic databases, data were obtained on the alive/dead status and causes of death for 260 patients with heart failure (HF) and ICD included in the Kuzbass Registry of Patients with ICD. The follow-up period was 1.5 years. Clinical and instrumental parameters entered into the registry before the ICD implantation were included in a univariate and multivariate step-by-step analysis using the logistic (for qualitative variables) and linear (for quantitative variables) regression with calculation of regression coefficients and construction of a prognostic regression model. The quality of the created model was assessed using a ROC analysis. During the observation period, 54 (20.8%) patients died. In 21 (38.8%) patients, death occurred in the hospital and was caused by acute decompensated heart failure in 15 (71.4%) patients, myocardial infarction in 3 (14.3%) patients, stroke in 1 (4.7%) patient, and pneumonia in 2 (9.5%) patients. 33 (61.2%) patients died outside the hospital; the cause of death was stated as the underlying disease associated with acute decompensated heart failure: in 9 (27.2%) patients, dilated cardiomyopathy; in 1 (3.0%) patient, rheumatic mitral disease; and in 23 (69.7%) patients, ischemic cardiomyopathy. According to the univariate regression model, the risk of death in the long-term period was increased by the QT interval prolongation (U 2.41, p = 0.0161); elevated pulmonary artery systolic pressure (U 4.30, p=0.0000) and increased left atrial size according to echocardiography (U 2.98, p=0.0029); stage IIB HF (OR 2.41; 95% CI: 1.26-4.6), NYHA III-IV (OR 3.03; 95% CI: 1.58-5.81); chronic obstructive pulmonary disease (OR 5.24; 95% CI: 2.04-13.45); and lack of optimal drug therapy (ODT) for HF before ICD implantation (OR 2.41; 95% CI: 1.29-4.49). The multivariate analysis identified the most significant factors included in the prognostic regression model: pulmonary artery systolic pressure above 45 mm Hg, social status, chronic obstructive pulmonary disease, and lack of ODT for HF. To ensure a maximum benefit from ICD, the factors that increase the likelihood of non-arrhythmic death should be considered before making a decision on ICD implantation. Particular attention should be paid to mandatory ODT for HF as the main modifiable risk factor for unfavorable prognosis.

Evaluating Clinical Presentations and Diagnostic Procedures in Pediatric Autoimmune Hepatitis

Background: The aim of the current research was to assess the clinical manifestations and diagnostic methods used in juvenile cases of Autoimmune Hepatitis (AIH). Methods: This study employed a retrospective cross-sectional design to investigate pediatric patients diagnosed with AIH at Children’s Medical Center Hospital, which is affiliated to Tehran University of Medical Sciences (TUMS), Tehran, Iran. The study included patients who received routine examinations, treatments, and follow-ups during the period from 2018 to 2021. Results: The present investigation encompassed the evaluation of 52 pediatric patients, mostly female, with a mean age of 7.76 years. The vast majority of patients have encountered the occurrence of acute AIH. Positive findings for the Anti-Smooth Muscle Antibodies (ASMA) test were seen in 50% of the patients. The mean score for fibrosis in the observed individuals was 2.56, whereas the mean value for the Hepatitis Activity Index (HAI) in a subset of 29 patients was found to be 7.34. One patient succumbed to the condition, one case underwent transplantation, and another individual was identified as a candidate for liver transplantation. Conclusion: Patients with AIH saw a decrease in long-term survival. There was no observed disparity in prognosis based on gender; nevertheless, it was noted that males had a shorter lifespan, perhaps attributable to an earlier beginning of the illness. The presence of cirrhosis at the time of diagnosis constituted a significant risk factor for unfavorable prognosis, as it was associated with an elevated overall risk of mortality owing to liver dysfunction.

Predictors for unfavorable prognosis after stroke with perforator artery disease.

Perforator artery disease (PAD) is an important subtype of ischemic stroke. The risk factors affecting the prognosis of patients with PAD are unclear. This study aimed to investigate the risk factors affecting the unfavorable prognosis of PAD. Patients with PAD were enrolled from Dushu Lake Hospital Affiliated to Soochow University and diagnosed as stroke with PAD during the period from September 2021 to July 2023 and followed up with a modified Rankin Scale (mRS) after 90 days, defining the mRS of 0-2 as a group with favorable prognosis, and 3-6 as a group with unfavorable functional outcome. Logistic regression was used to identify predictors for PAD. Multiple logistic regression analysis and receiver operating characteristics (ROC) were used to identify predictors of unfavorable prognosis. Of the 181 enrolled patients, 48 (26.5%) were identified with unfavorable prognosis. On multivariate analysis, increased age (OR = 1.076, 95% CI: 1.012 ~ 1.144, p = 0.019), higher National Institutes of Health Stroke Scale (NIHSS) score at admission (OR = 2.930, 95% CI: 1. 905 ~ 4.508, p < 0.001), and increased neutrophil-to-lymphocyte ratio (NLR) (OR = 3.028, 95% CI: 1.615 ~ 5.675, p = 0.001) were independent risk factors for unfavorable prognosis in patients with PAD, and the area under the receiver operating characteristic curve was 0.590, 0.905, and 0.798, and the multi-factor diagnostic model (Model 2) showed reliable diagnostic specificity and sensitivity (area under the curve = 0.956, p < 0.001, specificity 0.805, sensitivity 0.958, accuracy 0.845). Increased baseline NLR and NIHSS score and aging may be independent risk factors for unfavorable prognosis of patients with PAD. NLR can be used as a potential biological indicator to predict the prognosis of stroke with PAD.

Risk factors and dynamic nomogram for unfavorable prognosis of Marchiafava-Bignami disease.

Most patients with Marchiafava-Bignami disease (MBD) had unfavorable prognosis, with disability or death. We aimed to determine the risk factors of early unfavorable prognosis of MBD, and to develop a predictive nomogram for early unfavorable prognosis of MBD. MBD patients admitted to our hospital between 1 January 2013 and 31 December 2021 were included. Unfavorable prognosis was defined as mRS score ≥3, the independent risk factors for unfavorable prognosis of MBD with the odds ratio (OR) and 95% confidential interval (CI) acquired by multiple logistic regression were included in development of the predictive nomogram for early unfavorable prognosis of MBD, and the area under curve (AUC) of the receiver operating characteristic curve was calculated. The published case reports of MBD were used as the external validation group to verify the predictive ability of the nomogram. Independent risk factors for early unfavorable prognosis of MBD included Glasgow Coma Scale score (OR = 0.636, 95% CI = 0.506-0.800, p = 0.004) and pneumonia (OR = 2.317, 95% CI = 1.003-5.352, p = 0.049). The AUC of the nomogram was 0.852. Ninety-four case reports, a total of 100 cases of MBD were included as the external validation group, its AUC was 0.840. The online dynamic nomogram for early unfavorable prognosis of MBD was constructed. It is confirmed by external validation that the nomogram has a preferable predictive ability and clinical efficacy, and the dynamic online predictive nomogram is helpful for physicians to quickly assess the prognosis of MBD.

RISK FACTORS FOR UNFAVORABLE PROGNOSIS AND PROGRESSION OF CHRONIC HEART FAILURE IN COVID-19 PNEUMONIA

Introduction. Patients with chronic heart failure are vulnerable to coronavirus disease (COVID-19).&#x0D; Objectives. To investigate risk factors for unfavorable prognosis and progression of heart failure in hospitalized patients with chronic heart failure and COVID-19 pneumonia.&#x0D; Methods. A retrospective analysis of the medical records of 555 hospitalized patients diagnosed with COVID-19 was conducted. Subsequently, the data of 90 patients with chronic heart failure (CHF) and COVID-19 pneumonia from January – February 2021 were collected at Lviv Clinical Hospital of Emergency Medical Care. The following indices were evaluated: anthropometric and demographic data, complications, treatment results, results of clinical, laboratory, and instrumental examinations, and dynamic NT-proBNP.&#x0D; Results. CHF is recorded in 42.9% of hospitalized patients with COVID-19 and is accompanied by lower values of blood oxygen level (p=0.0474), hemoglobin (p=0.0090), prothrombin time (p=0.0196), prothrombin index (p=0.0196) and higher indicators of glucose (p=0.0032), creatinine (p=0.00001), interleukin-6 (p=0.0041). CHF decompensation is associated with lower values of body temperature (p=0.0047) and blood oxygen saturation (p=0.0076), while hemoglobin level (p=0.0026), higher creatinine values (p=0.0034), interleukin-6 (p=0.0300), aspartate aminotransferase (p=0.0035), troponin I (p=0.0061); are associated with the development of myocardial infarction (p=0.0014), acute arrhythmias (p=0.0011), hypertensive crisis (p=0.0096) and increased mortality (OR=5.72; 95). % CI: 1.84, 17.81; p=0.0026).&#x0D; Conclusions. CHF is common and often fatal in patients with COVID-19, especially in decompensated CHF. Low blood oxygen saturation, myocardial infarction, arrhythmia, hypertensive crisis, increased cardio cytolysis markers and pro-inflammatory cytokines preceding adverse cardiovascular risk factors contribute to CHF decompensation in patients with COVID-19.

Preoperative frailty assessment could be a predictive factor for the prognosis of elderly patients undergoing coronary artery bypass grafting: a retrospective case-control study

BackgroundFrailty has been considered to be associated with major mortality and increased length of stay after cardiac surgery. This study aimed to explore the predictive potential of frailty assessment in the prognosis of elderly patients undergoing bypass surgery.MethodsThis study assessed the preoperative frailty according to the Fried’s frailty phenotype, and included 150 frail and 150 non-frail elderly patients (≥ 65 y) who underwent bypass surgery. The present study evaluated the prognosis of elderly patients based on sequential organ failure assessment (SOFA) score, and collected clinical indicators to construct logistic regression models with the prognosis as the dependent variable, to explore the potential predictive ability of preoperative frailty. Moreover, this study focused on the complications and analyzed the relationship between preoperative frailty and postoperative complications.ResultsIn the present study, 244 patients were divided into the favorable prognosis group and 56 patients were divided into the unfavorable prognosis group. Logistic regression analysis showed that increased myoglobin and high cardiac function classification were independent risk factors for unfavorable prognosis in elderly patients undergoing bypass surgery. The discrimination of the clinical prediction model was determined by the receiver operating characteristic (ROC) curve, and the area under curve (AUC) was 0.928. After adding preoperative frailty assessment, the AUC was improved to 0.939. This study found a significant correlation between preoperative frailty and postoperative complications, mainly in the circulatory system.ConclusionPreoperative frailty assessment could be a predictive factor for the prognosis of elderly patients undergoing coronary artery bypass grafting. According to our study, frailty assessment and appropriate intervention before bypass surgery may be beneficial to the enhanced recovery after cardiac surgery.Trial registrationThe clinical study was approved by the Medical Ethics Committee of The First Affiliated Hospital of Nanjing Medical University (2021-SR-393). All patients signed an informed consent form.

Risk factors for unfavorable prognosis in patients with coronary artery disease and age-related disorders undergoing coronary artery bypass grafting

Highlights. Patients with coronary artery disease and age-related disorders (sarcopenia, osteopenic syndrome, osteosarcopenia) who underwent elective on-pump coronary artery bypass grafting are at higher risk of developing cardiovascular complications, non-infectious complications, and death.Musculoskeletal disorders (sarcopenia, osteopenic syndrome, osteosarcopenia) in combination with traditional predictors (age, diabetes mellitus, prior myocardial infarction and stroke, cancer) are risk factors for unfavorable prognosis of postoperative period of coronary artery bypass grafting. Aim. To assess risk factors for unfavorable prognosis in patients with coronary artery disease (CAD) undergoing elective on-pump coronary artery bypass grafting, taking into account age-related disorders (sarcopenia, osteopenic syndrome, osteosarcopenia).Methods. This single-center study included 387 CAD patients admitted for elective coronary artery bypass grafting. Taking into account the diagnosed age-related disorders, four groups of patients were formed. The first group consisted of 52 (13.4%) patients with sarcopenia, the second group was comprised of 28 (7.2%) patients with osteopenia (osteopenia/osteoporosis), the third group included 25 (6.5%) patients with osteosarcopenia, and the fourth group consisted of 282 (72.9%) participants with coronary artery disease and without musculoskeletal disorders (MSD). Risk factors for a composite endpoint (myocardial infarction, stroke, paroxysmal atrial fibrillation, cardiac rhythm disturbances) and death, and noninfectious complications (resternotomy for bleeding, pneumothorax aspiration and thoracentesis) were assessed.Results. The composite endpoint occurred more frequently in patients with osteopenia (group I – 9.6%, group II – 32.1%, group III – 12%, group IV – 12.8%; p = 0.029), and non-infectious complications occurred more frequently in patients with sarcopenia and osteosarcopenia (group I – 17.3%, group II – 7.1%, group III – 12%, group IV – 5.3%; p = 0.002). MSD were associated with the risk of composite endpoint (odds ratio (OR) 1.73, p = 0.035), and osteopenia increased it three-fold (OR 3.01, p = 0.046). Moreover, MSD were associated with higher risk of non-infectious complications (OR 1.71, p = 0.026), especially in patients with sarcopenia (OR 2.02, p = 0.034). The assessment of risk factors for unfavorable prognosis highlighted the presence of osteopenic syndrome (100 CU), prior stroke (88 CU) and myocardial infarction (85 CU). The risk of non-infectious complications was associated with prior ischemic events (ranking level for myocardial infarction – 100 CU, stroke – 75 CU), and MSD (89 CU) and its types (osteosarcopenia – 77 CU, osteopenia – 69 CU, sarcopenia – 52 CU).Conclusion. Age-related disorders in combination with MSD increase the risk of a composite endpoint and non-infectious complications by one to three times.

The oncogenic role of SNRPB in human tumors: A pan-cancer analysis.

Purpose: The purpose of this study was to explore the oncogenic role of small nuclear ribonucleoprotein polypeptides B and B1 (SNRPB) in human tumors. Materials and methods: Study cases were acquired from The Cancer Genome Atlas database, the Gene Expression Omnibus database, The Human Protein Atlas, and the Clinical Proteomic Tumor Analysis Consortium. We then used the R package and several online tools to analyze and visualize the role of SNRPB across tumors. Results: We found that the expression of SNRPB was significantly increased in 28 of 33 tumors, and higher expression was observed in late pathological and TNM stages. Significantly decreased levels of SNRPB promoter methylation were observed in 12 tumors. SNRPB was found to be a risk factor for decreased overall survival in 10 tumors (p < 0.05), a risk factor for decreased disease-specific survival in 8 tumors (p < 0.05), and a risk factor for decreased progression-free interval in 7 tumors (p < 0.05). The PPI network of SNRPB and the top 100 coexpressed genes revealed that CDK1, CDC6, AURKB, CCNB1, CCNA2, and CDC45 were the most closely interacting genes across tumors. The GO and KEGG enrichment analyses revealed that SNRPB and the above genes were mainly enriched with respect to functions in cell cycle-related genetic material replication, assembly, and distribution. SNRPB was significantly associated with immune cell infiltration and the expression of immunomodulation-related genes in several but not all tumors. Conclusion and limitations: The expression of SNRPB was significantly elevated in almost all tumors, and the decreased promoter methylation level may contribute to the elevated expression of SNRPB. SNRPB may facilitate the progression of pathological and TNM stages and is a risk factor for unfavorable prognosis across tumors. However, our research was based on data obtained from public databases, without further validation of our findings at the cellular and animal levels. Therefore, further studies are needed to clarify the oncogenic mechanism of SNRPB and its potential as a therapeutic target.

The Relationship Between Serum Netrin-1 Expression Levels and Prognosis in Revascularized Patients with Acute Ischemic Stroke.

This study aimed to explore the relationship between serum netrin-1 expression levels and acute prognosis in patients with acute ischemic stroke (AIS) within 24 hours after revascularization. A total of 121 revascularized patients admitted to the Jinshan Branch of the Shanghai Sixth People's Hospital, China, between July 2019 and July 2021 were selected as study subjects. The primary outcome was the modified Rankin Scale (mRS) score three months after revascularization: patients with an mRS score >2 were classified into the unfavorable prognosis group and others into the favorable prognosis group. Those with serum netrin-1 expression levels greater than the median of all patients were classified into the elevated protein group and others into the decreased protein group. Multivariate logistic regression analysis was used to analyze the independent risk factors for prognosis in patients with AIS after revascularization. The differences between the unfavorable prognosis group and the favorable prognosis group in gender, age, coronary heart disease, and netrin-1 levels were not statistically significant (p > 0.05). However, the National Institute of Health Stroke Scale (NIHSS) scores and number of patients with comorbid hypertension in the unfavorable prognosis group were significantly higher than in the favorable prognosis group (p < 0.05). Multivariate logistic regression analysis showed that NIHSS score before revascularization was an independent risk factor for unfavorable prognosis but that netrin-1 expression levels were not significantly associated with prognosis in patients after revascularization. Serum netrin-1 expression levels in the acute phase are not significantly associated with prognosis in patients with AIS after revascularization.

Postoperative morbidity adversely impacts oncological prognosis after curative resection for hilar cholangiocarcinoma.

BACKGROUNDPostoperative morbidity after curative resection for hilar cholangiocarcinoma (HCCA) is common; however, whether it has an impact on oncological prognosis is unknown.AIMTo evaluate the influence of postoperative morbidity on tumor recurrence and mortality after curative resection for HCCA.METHODSPatients with recently diagnosed HCCA who had undergone curative resection between January 2010 and December 2017 at The First Affiliated Hospital of Army Medical University in China were enrolled. The independent risk factors for morbidity in the 30 d after surgery were investigated, and links between postoperative morbidity and patient characteristics and outcomes were assessed. Postoperative morbidities were divided into five grades based on the Clavien-Dindo classification, and major morbidities were defined as Clavien-Dindo ≥ 3. Univariate and multivariate Cox regression analyses were used to evaluate the risk factors for recurrence-free survival (RFS) and overall survival (OS).RESULTSPostoperative morbidity occurred in 146 out of 239 patients (61.1%). Multivariate logistic regression revealed that cirrhosis, intraoperative blood loss > 500 mL, diabetes mellitus, and obesity were independent risk factors. Postoperative morbidity was associated with decreased OS and RFS (OS: 18.0 mo vs 31.0 mo, respectively, P = 0.003; RFS: 16.0 mo vs 26.0 mo, respectively, P = 0.002). Multivariate Cox regression analysis indicated that postoperative morbidity was independently associated with decreased OS [hazard ratios (HR): 1.557, 95% confidence interval (CI): 1.119-2.167, P = 0.009] and RFS (HR: 1.535, 95%CI: 1.117-2.108, P = 0.008). Moreover, major morbidity was independently associated with decreased OS (HR: 2.175; 95%CI: 1.470-3.216, P < 0.001) and RFS (HR: 2.054; 95%CI: 1.400-3.014, P < 0.001) after curative resection for HCCA.CONCLUSIONPostoperative morbidity (especially major morbidity) may be an independent risk factor for unfavorable prognosis in HCCA patients following curative resection.

Value of glycogen synthase 2 in intrahepatic cholangiocarcinoma prognosis assessment and its influence on the activity of cancer cells

ABSTRACT Intrahepatic cholangiocarcinoma (ICC) is the second most common primary liver tumor with increasing incidence worldwide. Metabolic reprogramming caused by metabolic related gene disorders is a prominent hallmark of tumors, among which Glycogen Synthase 2 (GYS2) is the key gene responsible for regulating cellular energy metabolism, and its expression disorders are closely related to various tumors and glycometabolic diseases. However, we still know nothing about its role in ICC. This study is intended to reveal the functional role of GYS2 in the ICC progress and explore the underlying mechanism. Based on the integrated pan-cancer analysis of GYS2 in the GEPIA database, the expression of GYS2 in paired ICC and adjacent non tumor tissues was detected by qPCR. It was found that the expression of GYS2 was significantly down-regulated in ICC. Further analysis showed that its low expression was not only associated with the degree of pathological differentiation, tumor size, microvascular invasion and lymph node metastasis, but also an independent risk factor for unfavorable prognosis. Functional studies have shown that GYS2 overexpression can significantly impair the proliferation, replication, cloning, migration and invasion of cholangiocarcinoma cells, while the silencing GYS2 dramatically promotes the development of the aforementioned phenotypes, the underlying mechanism may be that GYS2 activates the P53 pathway. In conclusions,low GYS2 expression in ICC predicted unfavorable patient outcomes; GYS2 overexpression could significantly impair the proliferation, migration and invasion of cholangiocarcinoma cells via activating the P53 pathway and GYS2 was expected to become a potential therapeutic target for such patients.

Risk factors for poor prognosis in children and adolescents with COVID-19: A systematic review and meta-analysis.

BackgroundThis study provides the first systematic review and meta-analysis to identify the predictors of unfavorable prognosis of COVID-19 in children and adolescents.MethodsWe searched literature databases until July 2021 for studies that investigated risk factors for unfavorable prognosis of children and adolescents with COVID-19. We used random-effects models to estimate the effect size with 95% confidence interval (CI).FindingsWe identified 56 studies comprising 79,104 individuals. Mortality was higher in patients with multisystem inflammatory syndrome (MIS-C) (odds ratio [OR]=58.00, 95% CI 6.39–526.79) and who were admitted to intensive care (OR=12.64, 95% CI 3.42–46.68). Acute respiratry distress syndrme (ARDS) (OR=29.54, 95% CI 12.69–68.78) and acute kidney injury (AKI) (OR=55.02, 95% CI 6.26–483.35) increased the odds to be admitted to intensive care; shortness of breath (OR=16.96, 95% CI 7.66–37.51) increased the need of respiratory support; and neurological diseases (OR=5.16, 95% CI 2.30–11.60), C-reactive protein (CRP) level ≥80 mg/L (OR=11.70, 95% CI 4.37–31.37) and D-dimer level ≥0.5ug/mL (OR=20.40, 95% CI 1.76–236.44) increased the odds of progression to severe or critical disease.InterpretationCongenital heart disease, chronic pulmonary disease, neurological diseases, obesity, MIS-C, shortness of breath, ARDS, AKI, gastrointestinal symptoms, elevated CRP and D-dimer are associated with unfavourable prognosis in children and adolescents with COVID-19.

Assessment of significance of erythrocyte indices as metabolic and microvascular complications markers in patients with type 1 and type 2 diabetes mellitus

Erythrocyte morphology is a reflection of both physiological and pathological reactions occurring in the body of patients with diabetes mellitus (hyperglycemia, adipose tissue dysfunction, dyslipidemia, lipid peroxidation, angiopathy, diabetic nephropathy, etc.). There are no available data in the literature that would characterize gradual and progressive changes in the morphology of the erythron system in patients with diabetes mellitus, the more so any analysis of the relationships with pathogenetic factors affecting them.Aim. The aim of the study was to evaluate the nature of erythrocyte index relationships with vascular and metabolic complications of type 1 and type 2 diabetes mellitus. The main objective of the study was to determine the changes in red blood cell indices at different stages of diabetic microangiopathies and in the presence of different indicators of metabolic control.Material and Methods. A total of 122 patients were enrolled in a single-stage, single-center, comparative, controlled study. Patients were assigned to three groups: group 1 comprised patients with type 1 diabetes mellitus (n = 41); group 2 comprised patients with type 2 diabetes mellitus (n = 67); and group 3 comprised control patients (n = 14). Statistical processing of the results was performed using the SPSS Statistics 20 software.Results. Patients with diabetes mellitus are characterized by qualitative changes in the erythron system manifesting as changes in red blood cell indices.The study identified the significant associations between the changes in erythron system (erythrocyte indices) and various phenotypic features of patients with type 1 and type 2 diabetes mellitus, namely: the duration of diabetes of over 10 years, type 2 diabetes mellitus in combination with obesity, and the presence of dyslipidemia, diabetic retinopathy, and poorly controlled diabetes mellitus if glycated hemoglobin exceeded 8% with a subsequent corresponding increase per each 1%.Conclusion. Additional studies are required to implement these markers, in particular, a red cell distribution width, as risk factors for unfavorable prognosis i.e. the risk of developing various diabetes mellitus complications.

Omental metastasis as a predictive risk factor for unfavorable prognosis in patients with stage III\u2013IV epithelial ovarian cancer

BackgroundEpithelial ovarian cancer has a clear predilection for the omentum as the site of metastasis; however, its contribution to clinical outcomes remains unresolved. This study aimed to evaluate the prognostic significance and efficacy of chemotherapy in the presence of omental metastasis.MethodsA retrospective cohort study was performed in 56 patients with stage III–IV ovarian cancer who underwent primary debulking surgery between 2004 and 2018 at Kumamoto University Hospital.ResultsThirty-six (64.3%) patients were categorized into the omental metastasis-positive group, whereas 20 (35.7%) patients were in the omental metastasis-negative group. The 5-year overall survival rates were 43.4% in the omental metastasis-positive group and 93.8% in the omental metastasis-negative group. Statistically significant differences were observed in overall survival (p = 0.002) and progression-free survival (p = 0.036) between the omental metastasis-positive and metastasis-negative groups. Notably, multivariate analysis demonstrated that the existence of omental metastasis is an independent risk factor for overall survival in patients with stage III–IV ovarian cancer (hazard ratio 8.90, 95% confidence interval 1.16–69.77; p = 0.038). Furthermore, the omental metastasis-positive group had significantly lower overall response rates to chemotherapy for recurrent disease, compared to the omental metastasis-negative group (31.6% vs. 85.7%, p = 0.026).ConclusionOur present data demonstrated that omental metastasis is closely associated with an unfavorable prognosis due to increased chemoresistance in patients with stage III–IV ovarian cancer. Elucidating the biological mechanism of omental metastasis will shed light on novel therapeutic approaches for the management of advanced ovarian cancer patients.

COVID-19, State of the Adult and Pediatric Heart: From Myocardial Injury to Cardiac Effect of Potential Therapeutic Intervention.

While the COVID-19 pandemic continues to spread rapidly, resulting in considerable morbidity and mortality worldwide, multiple efforts are being made by the international scientific community to understand the pathogenesis of the viral infection and its clinical outcome. Older age and comorbidities have consistently been reported as risk factors for unfavorable prognosis, with cardiovascular disease accounting for up to 10 % of comorbid conditions among the infected patients. An understanding of the mechanism underlying the effect of this infection on patients with cardiovascular disease is essential to manage and improve clinical strategies against the disease in that population. In this review, we summarize the impact of COVID-19 on patients with underlying cardiovascular conditions and the cardiac implications of known and emerging therapeutic strategies. Our future effort will aim to further elucidate how the type and severity of the cardiac disease, with particular regard to Congenital Heart Disease, influences the prognosis and the outcome of the viral infection.

Advances In Research Of Spreading Through Air Spaces And The Effects On The Prognosis Of Lung Cancer.

The concept of spread through air spaces (STAS) has been described as a new form of invasion in the lung in the 2015 WHO classification of Lung Tumors, namely invasion through alveolar spaces. STAS is a prognostic factor independent of growth pattern and tumor stage, and it is also an independent risk factor for unfavorable prognosis of stage I lung adenocarcinoma (ADC) and stage I lung squamous cell carcinoma (SCC). The pathological characteristics are different between ADC and SCC. STAS is not reported as routine, so setting a unified pathological reading standard, and hunting for STAS as a regular reading process is urgently advocated. We write this review to investigate the research progress of STAS and its effects on the prognosis of lung cancer.

Somatic mutations and promotor methylation of the ryanodine receptor 2 is a common event in the pathogenesis of head and neck cancer.

Genomic sequencing projects unraveled the mutational landscape of head and neck squamous cell carcinoma (HNSCC) and provided a comprehensive catalog of somatic mutations. However, the limited number of significant cancer-related genes obtained so far only partially explains the biological complexity of HNSCC and hampers the development of novel diagnostic biomarkers and therapeutic targets. We pursued a multiscale omics approach based on whole-exome sequencing, global DNA methylation and gene expression profiling data derived from tumor samples of the HIPO-HNC cohort (n = 87), and confirmed new findings with datasets from The Cancer Genome Atlas (TCGA). Promoter methylation was confirmed by MassARRAY analysis and protein expression was assessed by immunohistochemistry and immunofluorescence staining. We discovered a set of cancer-related genes with frequent somatic mutations and high frequency of promoter methylation. This included the ryanodine receptor 2 (RYR2), which showed variable promoter methylation and expression in both tumor samples and cell lines. Immunohistochemical staining of tissue sections unraveled a gradual loss of RYR2 expression from normal mucosa via dysplastic lesion to invasive cancer and indicated that reduced RYR2 expression in adjacent tissue and precancerous lesions might serve as risk factor for unfavorable prognosis and upcoming malignant conversion. In summary, our data indicate that impaired RYR2 function by either somatic mutation or epigenetic silencing is a common event in HNSCC pathogenesis. Detection of RYR2 expression and/or promoter methylation might enable risk assessment for malignant conversion of dysplastic lesions.