A novel prognostic signature related to programmed cell death in osteosarcoma.

Background: Osteosarcoma primarily affects children and adolescents, with current clinical treatments often resulting in poor prognosis. There has been growing evidence linking programmed cell death (PCD) to the occurrence and progression of tumors. This study aims to enhance the accuracy of OS prognosis assessment by identifying PCD-related prognostic risk genes, constructing a PCD-based OS prognostic risk model, and characterizing the function of genes within this model. Method: We retrieved osteosarcoma patient samples from TARGET and GEO databases, and manually curated literature to summarize 15 forms of programmed cell death. We collated 1621 PCD genes from literature sources as well as databases such as KEGG and GSEA. To construct our model, we integrated ten machine learning methods including Enet, Ridge, RSF, CoxBoost, plsRcox, survivalSVM, Lasso, SuperPC, StepCox, and GBM. The optimal model was chosen based on the average C-index, and named Osteosarcoma Programmed Cell Death Score (OS-PCDS). To validate the predictive performance of our model across different datasets, we employed three independent GEO validation sets. Moreover, we assessed mRNA and protein expression levels of the genes included in our model, and investigated their impact on proliferation, migration, and apoptosis of osteosarcoma cells by gene knockdown experiments. Result: In our extensive analysis, we identified 30 prognostic risk genes associated with programmed cell death (PCD) in osteosarcoma (OS). To assess the predictive power of these genes, we computed the C-index for various combinations. The model that employed the random survival forest (RSF) algorithm demonstrated superior predictive performance, significantly outperforming traditional approaches. This optimal model included five key genes: MTM1, MLH1, CLTCL1, EDIL3, and SQLE. To validate the relevance of these genes, we analyzed their mRNA and protein expression levels, revealing significant disparities between osteosarcoma cells and normal tissue cells. Specifically, the expression levels of these genes were markedly altered in OS cells, suggesting their critical role in tumor progression. Further functional validation was performed through gene knockdown experiments in U2OS cells. Knockdown of three of these genes-CLTCL1, EDIL3, and SQLE-resulted in substantial changes in proliferation rate, migration capacity, and apoptosis rate of osteosarcoma cells. These findings underscore the pivotal roles of these genes in the pathophysiology of osteosarcoma and highlight their potential as therapeutic targets. Conclusion: The five genes constituting the OS-PCDS model-CLTCL1, MTM1, MLH1, EDIL3, and SQLE-were found to significantly impact the proliferation, migration, and apoptosis of osteosarcoma cells, highlighting their potential as key prognostic markers and therapeutic targets. OS-PCDS enables accurate evaluation of the prognosis in patients with osteosarcoma.

Small nucleolar RNA expression profiles: A potential prognostic biomarker for non-viral Hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a challenging cancer with high mortality rates, limited predictability, and a lack of effective prognostic indicators. The relationship between small nucleolar RNAs (snoRNAs) and HCC is poorly understood. Based on the literature data, snoRNA studies were primarily focused on viral-related causes of HCC, such as Hepatitis B or C viruses (HBV or HCV). According to these studies, we selected four snoRNAs (snoRA12, snoRA47, snoRA80E, and snoRD126) for exploration in the context of non-viral-related causes, including non-alcoholic steatohepatitis (NASH), non-alcoholic fatty liver diseases (NAFLD), and alcohol steatohepatitis. The primary goal of this study was to gain a deeper understanding of how snoRNA expression affects patient outcomes and whether it can serve as a prognostic tool for non-viral HCC. We conducted a study on tissue samples from 35 HCC patients who had undergone resection at Pilsen University Hospital. SnoRA12, snoRA47, snoRA80E, and snoRD126 were studied by quantitative real-time PCR (qRT-PCR) in tumor and non-tumor adjacent tissue (NTAT) samples. Kaplan-Meier analysis was performed to assess the association of snoRNAs expression levels with patient outcomes: time to recurrence (TTR), disease-free survival (DFS) and overall survival (OS). In tumor tissues, snoRA12, snoRA47 and snoRA80E were upregulated, while snoRD-126 was downregulated compared to NTAT. Low expression of snoRA47 and snoRD126 in patients was associated with longer TTR and DFS. The individual expression of snoRA12 and snoRA80E did not show associations with TTR and DFS. However, a combination of medium expression of snoRD126 and snoRA80E was associated with longer TTR and DFS, while high and low expressions of the combined snoRA126 and snoRA80E showed no significant association with TTR, DFS, and OS. Conversely, a combination of high expression of snoRA12 and snoRD126 was associated with shorter TTR. In conclusion, the results indicate that snoRA47 and snoRD126 exhibit good prognostic power specifically for non-viral related HCC. Both snoRA47 and snoRD126 showed favorable prognostication in single and combined analysis when assessing patient outcomes. Also, in combination analysis, snoRA80E and snoRA12 showed favorable prognosis, but not alone.

Diffusion weighted MRI and apparent diffusion coefficient as a prognostic biomarker in evaluating chemotherapy-antiangiogenic treated stage IV non-small cell lung cancer: A prospective, single-arm, open-label, clinical trial (BevMar).

PURPOSE: When treating Lung Cancer, it is necessary to identify early treatment failure to enable timely therapeutic adjustments. The Aim of this study was to investigate whether changes in tumor diffusion during treatment with chemotherapy and bevacizumab could serve as a predictor of treatment failure. MATERIAL AND METHODS: A prospective single-arm, open-label, clinical trial was conducted between September 2014 and December 2020, enrolling patients with stage IV non-small cell lung cancer (NSCLC). The patients were treated with chemotherapy-antiangiogenic combination. Diffusion weighted magnetic resonance imaging (DW-MRI) was performed at baseline, two, four, and sixteen weeks after initiating treatment. The differences in apparent diffusion coefficient (ADC) values between pre- and post-treatment MRIs were recorded as Delta values (ΔADC). We assessed whether ΔADC could serve as a prognostic biomarker for overall survival (OS), with a five year follow up. RESULTS: 18 patients were included in the final analysis. Patients with a ΔADC value ≥ -3 demonstrated a significantly longer OS with an HR of 0.12 (95 % CI; 0.03- 0.61; p = 0.003) The median OS in patients with a ΔADC value ≥ -3 was 18 months, (95 % C.I; 7-46) compared to 7 months (95 % C.I; 5-9) in those with a ΔADC value < -3. CONCLUSION: Our findings suggest that early changes in tumor ADC values, may be indicative of a longer OS. Therefore, DW-MRI could serve as an early biomarker for assessing treatment response in patients receiving chemotherapy combined with antiangiogenic therapy.

Interaction between inflammatory bowel disease, physical activity, and myokines: Assessment of serum irisin levels.

Inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis, showed a wide spectrum of intestinal and extra-intestinal manifestations, which rendered the patients physically inactive and impaired their quality of life. It has been found that physical activity is a non-pharmacological intervention that improves the quality of life for those patients. Irisin is one member of the myokines secreted by muscle contraction during exercise and could be used as an anti-inflammatory biomarker in assessing the physical activity of IBD patients. In addition, experimental studies showed that exogenous irisin significantly decreased the inflammatory markers and the histological changes of the intestinal mucosa observed in experimental colitis. Furthermore, irisin produces changes in the diversity of the microbiota. Therefore, endogenous or exogenous irisin, via its anti-inflammatory effects, will improve the health of IBD patients and will limit the barriers to physical activity in patients with IBD.

Tumor Budding as a Prognostic Marker in Primary Colon Cancer - A Single Center Experience.

Introduction: Tumor budding (TB) is considered to be a morphological and prognostic factor relevant to colon cancer (CC). The aim of our study is to assess the TB and to evaluate its relationship to clinicopathological findings within stage II and III CC patients as a single center experience. Materials and methods: A total of 120 CC patients operated between 2018 and 2021 at the University Clinic of Digestive Surgery in Skopje, the Republic of North Macedonia were included in this retrospective, single center study. TB was evaluated by the magnification of 200x along the invasive front of the primary tumor on H&E and CKAE1/AE3 immunohistochemically stained sections. Two grades were used: low grade (TB1, 0-4 TBs) and high-grade, which includes intermediate (TB2, 5-9 TBs) and high grade (TB3 ≥10TBs) of TBs. Results: A statistically significant correlation has been identified between high-grade TB and age (p=0.05) of the patients. There was also a significantly higher occurrence of high-grade TB in patients within stage III CC. Statistically significant correlations were also found in lymph node status (p<0.01), vascular invasion (p<0.05), lymphatic invasion (p<0.01), postoperative relapse (p<0.01), and death (p<0.01). Tumor relapse and death were significantly more frequent in patients with high-grade TB than those with low-grade TB. Patients with registered high-grade TB demonstrated significantly lower relapse-free survival (RFS) and overall survival (OS) rates than patients with low-grade TB over the observation period (RFS: 53.8% vs. 98.5%, p<0.001; OS: 65.4% vs. 97.1%, p<0.001, respectively). Patients with lung and liver postoperative relapses had higher percentage of cases with high-grade TB (94.1%). Conclusion: Our results are highly suggestive that TB should be included as a histological biomarker in the pathology report of patients with stage II and stage III CC, because of its prognostic value.

SLC11A1 predicts the overall survival of patients with colorectal cancer.

Colorectal cancer (CRC) remains a significant contributor to cancer-related mortality, emphasizing the critical need for identifying biomarkers that can improve clinical management and patient outcomes. In this retrospective study, we analyzed tumor samples from 25 patients with metastatic CRC, categorized based on long-term (> 50 months) or short-term (< 10 months) survival. Employing the PanCancer Immune Profile Panel, encompassing 770 genes, in the discovery dataset, we identified 54 differentially expressed genes (DEGs) within the tumor microenvironment of metastatic CRC. Validation of potential biomarkers was performed using two publicly available RNA-based sequencing datasets (TCGA 1 (n=371) and TCGA 2 (n=566)). Univariate COX regression unveiled that three significant biomarkers were associated with overall survival in CRC within the discovery dataset, which were SLC11A1 (hazard ratio (HR): 4.09, P=0.012), TNFSF11 (HR: 3.67, P=0.02), and MEF2C (HR: 0.34, P=0.037). Kaplan-Meier survival curve analyses confirmed the correlation between SLC11A1 expression and overall survival in CRC across the discovery set (P=0.0071) and the two independent datasets (TCGA 1 (P=0.0016) and TCGA 2 (P=0.025)). Receiver operating characteristic curve analysis demonstrated an area under the curve ranging from 0.64 to 0.76, with sensitivity of 59% to 87% and specificity of 60% to 73% for predicting CRC overall survival. Immunohistochemistry staining further validated the strong expression of SLC11A1 protein in CRC tumor cells, with high expression correlating with short-term survival. These findings suggest that SLC11A1 serves as a predictive biomarker for overall survival in CRC patients.

MUC16 as a serum-based prognostic indicator of prometastatic gastric cancer.

Metastatic gastric cancer (GC) presents significant clinical challenges due to its poor prognosis and limited treatment options. To address this, we conducted a targeted protein biomarker discovery study to identify markers predictive of metastasis in advanced GC (AGC). Serum samples from 176 AGC patients (T stage 3 or higher) were analyzed using the Olink Proteomics Target panels. Patients were retrospectively categorized into nonmetastatic, metastatic, and recurrence groups, and differential protein expression was assessed. Machine learning and gene set enrichment analysis (GSEA) methods were applied to discover biomarkers and predict prognosis. Four proteins (MUC16, CAIX, 5'-NT, and CD8A) were significantly elevated in metastatic GC patients compared to the control group. Additionally, GSEA indicated that the response to interleukin-4 and hypoxia-related pathways were enriched in metastatic patients. Random forest classification and decision-tree modeling showed that MUC16 could be a predictive marker for metastasis in GC patients. Additionally, ELISA validation confirmed elevated MUC16 levels in metastatic patients. Notably, high MUC16 levels were independently associated with metastatic progression in T3 or higher GC. These findings suggest the potential of MUC16 as a clinically relevant biomarker for identifying GC patients at high risk of metastasis.

Geriatric Nutritional Risk Index as Prognostic Marker for Elderly Patients With Small Cell Lung Cancer.

Background/Aim: The Geriatric Nutritional Risk Index (GNRI) indicates nutritional status based on serum albumin concentration and ideal body weight. Pretreatment GNRI has been suggested as a prognostic factor for various malignancies. However, little is known about the clinical value of GNRI for small-cell lung cancer (SCLC), especially in elderly patients. Patients and Methods: We retrospectively analyzed 53 elderly (≥71) patients with extensive-disease (ED) SCLC treated with first-line platinum-doublet chemotherapy in relation to the pretreatment GNRI level in a real-world setting. Results: Thirty-six patients with a low GNRI (<92) had statistically poorer progression-free survival (PFS) and overall survival (OS) than 17 patients with a high GNRI (≥92) (median PFS=80 days vs. 133 days, respectively; p=0.002; median OS=123 days vs. 274 days, respectively; p=0.004). In a multivariate analysis, a low GNRI was also an independent poor prognostic factor for PFS [hazard ratio (HR)=0.396; 95% confidence interval (CI)=0.199-0.789; p=0.008] and OS (HR=0.295; 95%CI=0.143-0.608; p<0.001). Conclusion: The GNRI might be a predictive and prognostic marker in elderly patients with ED-SCLC treated with platinum-doublet chemotherapy.

Heparin-Binding Protein Stratifies Mortality Risk Among Ugandan Children Hospitalized With Respiratory Distress.

Background: Current prognostic tools do not reliably and objectively identify children with pneumonia at risk of a severe or life-threatening episode. Heparin-binding protein (HBP) is a host immune protein that is released in response to infection. We hypothesized that measuring HBP concentrations at hospital admission could help risk-stratify children with pneumonia and identify those at higher risk of an adverse prognosis. Methods: We evaluated the prognostic accuracy of HBP for predicting in-hospital mortality among children with respiratory distress, and whether HBP could improve the accuracy of validated composite clinical severity scores. Results: Of 778 Ugandan children under 5 years of age and presenting with clinically defined pneumonia, 60 (7.7%) died during hospital admission. HBP concentrations at presentation were significantly higher in children with fatal outcomes (median, 76 ng/mL [interquartile range {IQR}, 41-150]) compared to children who survived (median, 31 ng/mL [IQR, 18-57]) (P < .001). Children with HBP >41 ng/mL on admission had an elevated risk of death (hazard ratio, 5.3 [95% confidence interval {CI}, 2.9-9.5]; P < .0001). In receiver operating characteristic (ROC) curve analysis, HBP concentrations distinguished between fatal and nonfatal outcomes (area under the ROC curve, 0.75 [95% CI, .66-.84]) and significantly improved the prediction provided by the Respiratory Index of Severity in Children, a composite clinical severity score (P = .0026). Conclusions: Measuring HBP at presentation could help identify children at risk of severe and fatal pneumonia. Adding HBP to clinical scores could improve the recognition and triage of children with pneumonia at risk of death.

The Significance of Systemic Inflammatory Markers in 'New-Onset Atrial Fibrillation' Following Cardiac Surgeries.

Postoperative atrial fibrillation (AF) is a known complication of postoperative morbidity and mortality in cardiac surgery. The purpose of this retrospective study was to look into the association between the incidence of new-onset AF in patients undergoing cardiac surgery and preoperative systemic inflammatory markers. Patients were divided into two groups (Group A: new-onset AF, Group B: no AF) depending on the occurrence of AF in the postoperative period, and a retrospective analysis was performed to look for the association between the incidence of new-onset AF and levels of systemic inflammatory markers. Five hundred patients were enrolled in the study, and the duration was three years. One-hundred and fifty out of 500 patients who underwent cardiac surgeries between 2020 and 2023 had higher levels of preoperative inflammatory markers. The systemic immune inflammation index (SII), neutrophil scores, platelet counts, and C-reactive protein (CRP) levels were examined. Compared to patients without AF (Group B), those who developed AF (Group A) had significantly higher mean levels of CRP (6.2 ± 1.8 mg/L), platelet count (320 ± 50 x109/L), neutrophil scores (4.6 ± 0.9), and SII (650 ± 120) (p<0.05 for all). Higher thresholds of these inflammatory markers were related to a notable increase in the prevalence of AF, with odds ratios showing significantly higher risks associated with raised marker levels. In summary, there was a significant correlation found between an increased risk of new-onset AF after surgery and elevated preoperative inflammatory markers, such as CRP levels, platelet counts, neutrophil scores, and SII. These findings could be used as prognostic markers to identify patients who are more likely to experience postoperative AF. Further prospective studies will be required to analyze their predictive value. Limitations of our study include the relatively small sample size, potential bias from single-institutional data, and the retrospective nature of the study design.

The Role of Neutrophil-to-Lymphocyte Ratio in Predicting Outcomes of Acute Organophosphorus Poisoning: A Comprehensive Review.

Organophosphorus poisoning (OPP) poses a significant threat to human health, necessitating accurate prognostic markers for timely intervention and improved outcomes. This review evaluates the potential of the neutrophil-to-lymphocyte ratio (NLR) as a prognostic indicator in acute organophosphorus poisoning (AOPP). A comprehensive analysis of existing literature reveals that elevated NLR values correlate with increased severity of poisoning and adverse clinical outcomes, including mortality and morbidity. NLR assessment offers valuable prognostic information beyond traditional markers, aiding risk stratification and guiding clinical decision-making. Integration of NLR into clinical practice holds promise for optimizing patient care through the early identification of high-risk individuals and tailored therapeutic interventions. Further research is needed to validate the utility of NLR in larger patient cohorts and standardize its incorporation into clinical guidelines. Leveraging NLR as a prognostic tool can enhance risk stratification, optimize treatment strategies, and ultimately improve outcomes in AOPP.

Differential expression and clinical significance of long non-coding RNAs in the development and progression of lung adenocarcinoma.

With the development of gene testing technology, we have found many different genes, and lncRNA is one of them. LncRNAs refer to a non-protein coding RNA molecule with a length of more than 200bp, which is one of the focuses of research on human malignant diseases such as LUAD. LncRNAs act as an oncogene or inhibitor to regulate the occurrence and progression of tumors. The differential expression of LncRNAs promotes or inhibits the progression of lung adenocarcinoma by affecting cell proliferation, metastasis, invasion, and apoptosis, thus affecting the prognosis and survival rate of patients. Therefore, LncRNAs can be used as a potential target for diagnosis and treatment of cancer. The early diagnosis of the disease was made through the detection of tumor markers. Because lung adenocarcinoma is not easy to diagnose in the early stage and tumor markers are easy to ignore, LncRNAs play an important role in the diagnosis and treatment of lung adenocarcinoma. The main purpose of this article is to summarize the known effects of LncRNAs on lung adenocarcinoma, the effect of differential expression of LncRNAs on the progression of lung adenocarcinoma, and related signal transduction pathways. And to provide a new idea for the future research of lung adenocarcinoma-related LncRNAs.

Identification of prognostic biomarkers for cholangiocarcinoma by combined analysis of molecular characteristics of clinical MVI subtypes and molecular subtypes.

Cholangiocarcinoma (CCA) is widely noted for its high degree of malignancy, rapid progression, and limited therapeutic options. This study was carried out on transcriptome data of 417 CCA samples from different anatomical locations. The effects of lipid metabolism related genes and immune related genes as CCA classifiers were compared. Key genes were derived from MVI subtypes and better molecular subtypes. Pathways such as epithelial mesenchymal transition (EMT) and cell cycle were significantly activated in MVI-positive group. CCA patients were classified into three (four) subtypes based on lipid metabolism (immune) related genes, with better prognosis observed in lipid metabolism-C1, immune-C2, and immune-C4. IPTW analysis found that the prognosis of lipid metabolism-C1 was significantly better than that of lipid metabolism-C2 + C3 before and after correction. KRT16 was finally selected as the key gene. And knockdown of KRT16 inhibited proliferation, migration and invasion of CCA cells.

Comprehensive pan-cancer analysis of the C2ORF40 expression: Infiltration associations and prognostic implications.

In recent years, C2ORF40 has been identified as a tumor suppressor gene with multiple functions, including roles in cell proliferation, migration, and senescence. To explore the role of the C2ORF40 gene in different tumors, we used multiple databases for analysis. Compared to adjacent normal tissues, C2ORF40 is downregulated in a variety of malignant tumors, including tumors such as breast cancer, colorectal cancer, bladder cancer, hepatocellular carcinoma and prostate cancer. Notably, low expression of the gene is significantly associated with poor overall survival and relapse-free survival rates. In specific cancers including colon cancer and prostate cancer, the expression of C2ORF40 is correlated with the infiltration of CAFs. C2ORF40 is also involved in biological processes such as cell apoptosis and regulation of protein stability. In conclusion, C2ORF40 can hold promise as a prognostic marker for pan-cancer analysis.

Overexpression of H2AFX gene in neuroblastoma is associated with worse prognosis.

BACKGROUND: Neuroblastoma (NB) is the most common solid tumour in childhood, and rises in the sympathetic nervous system. Here, we addressed the in silico analysis of the association between the expression of H2AFX gene involved in DNA damage response, and the survival of a cohort of 786 NB patients. METHODS: In silico gene expression was retrieved from the publicly available dataset summarised by Cangelosi et al., including 13,696 gene expression profiles of 786 NB tumours at onset of disease. The prognostic value of H2AFX (H2A histone family member X) gene expression for event-free survival (EFS) and overall survival (OS) was evaluated by Kaplan-Meier and Cox regression analysis. The main results were validated on another openly accessible in silico database (NRC-283) containing 13,489 gene expressions in 283 NB patients. The expression of H2AFX protein was then tested by immunofluorescence on 48 primary NB samples of different tumour stages. H2AFX activity as an oncogene has been further validated in vitro by silencing the molecule in two NB cell lines, characterised by MYCN amplified or not, and performing cell growth and migration assays. RESULTS: A strong inverse association between H2AFX expression and patients' survival was observed and confirmed by immunofluorescence results on primary NB tissue sections. Cox regression analysis also disclosed H2AFX as an independent predictor of EFS and OS. The gene-silencing experiments strongly suggested an oncogenic role for H2AFX on NB cells, regardless of MYCN amplification. CONCLUSIONS: H2AFX is a prognostic marker for unfavourable NB and could be considered a target for therapeutic interventions.

The novel prognostic marker SPOCK2 regulates tumour progression in melanoma.

Secreted protein acidic and cysteine rich/osteonectin, cwcv and kazal-like domain proteoglycan 2 (SPOCK2) is a protein that regulates cell differentiation and growth. Recent studies have reported that SPOCK2 plays important roles in the progression of various human cancers; however, the role of SPOCK2 in melanoma remains unknown. Therefore, this study investigated the roles of SPOCK2 and the related mechanisms in melanoma progression. To evaluate the clinical significance of SPOCK2 expression in patients with melanoma, we analysed the association between SPOCK2 expression and its prognostic value for patients with melanoma using systematic multiomic analysis. Subsequently, to investigate the roles of Spock2 in melanoma progression in vitro and in vivo, we knocked down Spock2 in the B16F10 melanoma cell line. High SPOCK2 levels were positively associated with good prognosis and long survival rate of patients with melanoma. Spock2 knockdown promoted melanoma cell proliferation by inducing the cell cycle and inhibiting apoptosis. Moreover, Spock2 downregulation significantly increased cell migration and invasion by upregulating MMP2 and MT1-MMP. The increased cell proliferation and migration were inhibited by MAPK inhibitor, and ERK phosphorylation was considerably enhanced in Spock2 knockdown cells. Therefore, Spock2 could function as a tumour suppressor gene to regulate melanoma progression by regulating the MAPK/ERK signalling pathway. Additionally, Spock2 knockdown cell injection induced considerable tumour growth and lung metastasis in C57BL6 mice compared to that in the control group. Our findings suggest that SPOCK2 plays crucial roles in malignant progression of melanoma and functions as a novel therapeutic target of melanoma.

Elevated neutrophil-to-hemoglobin ratio as an indicator of poor survival in hepatitis B virus-related decompensated cirrhosis.

Aim: Our goal was to explore the prognostic value of the neutrophil-to-hemoglobin ratio (NHR) in HBV-related decompensated cirrhosis (HBV-DC) patients. Methods: 172 HBV-DC patients were enrolled. Multivariate analyses were used to identify risk factors influencing 30-day mortality. Results: The 30-day mortality was 12.8% (22/172). nonsurvivors exhibited a higher NHR than survivors. On multivariate analysis, NHR and model for end-stage liver disease (MELD) score were the only independent predictors of mortality. Notably, the predictive capabilities of NHR were found to be comparable to those of the MELD score. Conclusion: High NHR was associated with poor prognosis in HBV-DC patients, and NHR can serve as an effective and readily available indicator for the prediction of mortality in these patients.

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Nucleated red blood cells as a prognostic marker for mortality in patients with SARS-CoV-2-induced ARDS: an observational study.

BACKGROUND: The presence of nucleated red blood cells (NRBCs) in the peripheral blood of critically ill patients is associated with poor outcome. Evidence regarding the predictive value of NRBCs in patients with SARS-CoV-2-induced acute respiratory distress syndrome (ARDS) remains elusive. The aim of this study was to evaluate the predictive validity of NRBCs in these patients. METHODS: Daily NRBC values of adult patients with SARS-CoV-2-induced ARDS were assessed and their predictive validity for mortality was statistically evaluated. A cut-off level based on the patient's maximum NRBC value during ICU stay was calculated and further specified according to Youden's method. Based on this cut-off value, further analyses such as logistic regression models and survival were performed. RESULTS: 413 critically ill patients with SARS-CoV-2-induced ARDS were analyzed. Patients who did not survive had significantly higher NRBC values during their ICU stay compared to patients who survived (1090/µl [310; 3883] vs. 140/µl [20; 500]; p < 0.0001). Patients with severe ARDS (n = 374) had significantly higher NRBC values during ICU stay compared to patients with moderate ARDS (n = 38) (490/µl [120; 1890] vs. 30/µl [10; 476]; p < 0.0001). A cut-off level of NRBC ≥ 500/µl was found to best stratify risk and was associated with a longer duration of ICU stay (12 [8; 18] vs. 18 [13; 27] days; p < 0.0001) and longer duration of mechanical ventilation (10 [6; 16] vs. 17 [12; 26] days; p < 0.0001). Logistic regression analysis with multivariate adjustment showed NRBCs ≥ 500/µl to be an independent risk factor of mortality (odds ratio (OR) 4.72; 95% confidence interval (CI) 2.95-7.62, p < 0.0001). Patients with NRBC values below the threshold of 500/µl had a significant survival advantage over those above the threshold (median survival 32 [95% CI 8.7-43.3] vs. 21 days [95% CI 18.2-23.8], log-rank test, p < 0.05). Patients who once reached the NRBC threshold of ≥ 500/µl during their ICU stay had a significantly increased long-term mortality (median survival 489 days, log-rank test, p = 0.0029, hazard ratio (HR) 3.2, 95% CI 1.2-8.5). CONCLUSIONS: NRBCs predict mortality in critically ill patients with SARS-CoV-2-induced ARDS with high prognostic power. Further studies are required to confirm the clinical impact of NRBCs to eventually enhance decision making.

Clinical characteristics and prognostic marker for hospitalization in children with influenza infection in an emergency setting.

BACKGROUND: Influenza is a main cause of illnesses during seasonal outbreaks. Identifying children with influenza who may need hospitalization may lead to better influenza outcomes. OBJECTIVE: To identify factors associated with the severity of influenza infection, specifically among children who were admitted to the hospital after being diagnosed with influenza at the emergency department. METHODS: A retrospective cohort study was conducted among pediatric patients (age < 18 years) with a positive influenza rapid test who visited the emergency department at Srinagarind hospital between January2015-December2019. The dependent variable was hospital admission, while the independent variables included clinical parameters, laboratory results, and emergency severity index(ESI). The association between these variables and hospital admission was analyzed. RESULTS: There were 542 cases of influenza included in the study. The mean age was 7.50 ± 4.52 years. Males accounted for 52.4% of the cases. A total of 190(35.05%) patients, needed hospitalization. Patients with pneumonia, those who required hospitalization or were admitted to the critical care unit, consistently exhibited an elevated absolute monocyte count and a reduced lymphocyte-to-monocyte ratio (LMR). Various factors contribute to an increased risk for hospitalization, including ESI level 1-2, co-morbidity in patients, age < 1 year old, and an LMR below 2. CONCLUSIONS: ESI level 1-2 and co-morbidity in patients represent significant risk factors that contribute to higher hospitalization admissions. A LMR below 2 can be used as a prognostic marker for hospitalization in children with influenza infection.

Tumor thickness and depth of invasion in squamous cell carcinoma of tongue as indicators of the loco-regional spread of the disease: A preliminary study.

Background: Magnetic resonance imaging (MRI) is a routinely used imaging modality for pre-treatment radiologic evaluation of tongue carcinoma, providing accurate information regarding the extent of the disease. Aims and objectives: To investigate the role of MRI-derived depth of invasion and tumor thickness evaluation in squamous cell carcinoma of the tongue, and to assess if any correlation exists between depth of invasion, tumor thickness, nodal metastasis, muscles, and space involved. Materials and methods: Thirty-three patients with oral squamous cell carcinoma of the tongue who had undergone pre-treatment MRI and excisional biopsy were included. The tumor thickness (TT) and depth of invasion (DOI) were evaluated on MRI and histopathologic images. Result: The relation between different methodologies for assessing showed a very high correlation for the tumor tissue thickness (r = 0.99, p < 0.05) and depth of invasion (r = 0.82, p < 0.05). The tumor thickness and the depth of invasion increased with the loss of differentiation in the carcinoma histopathologically. As the depth of invasion increases, the extent of the spread of the carcinoma to tongue musculature, lingual septum, and spaces also increases. Conclusion: The present study has depicted a high correlation between the tumor thickness and the depth of invasion between MRI and histopathological findings and is the first of its kind to correlate DOI to the invasiveness of the disease.