Predictive Marker In Patients Research Articles

Prognostic and predictive significance of soluble programmed death ligand 1 in bronchoalveolar lavage fluid in stage IV non-small cell lung cancer.

Patients with non-small cell lung cancer (NSCLC) have been shown to exhibit elevated levels of soluble programmed death-ligand 1 (sPD-L1) in the blood, associated with poor survival in NSCLC. The bronchoalveolar lavage fluid (BALF) composition reflects the tumor microenvironment of lung cancer. In this study, we investigated sPD-L1 levels in BALF and its role as a prognostic and predictive marker in patients with stage IV NSCLC. We prospectively obtained BALF from lung cancer patients who underwent bronchoscopy between January 2020 and September 2022 at Chungnam National University Hospital (CNUH). Finally, 94 NSCLC stage IV patients were included in this study. Soluble PD-L1 levels in BALF were measured using a human PD-L1 Quantikine ELISA kit. The correlation between PD-L1 expression in tumor cells and sPD-L1 in BALF was weakly positive (rho =0.314, P=0.002). The median overall survival (OS) of the low sPD-L1 in BALF group was 16.47 months [95% confidence interval (CI): 11.15-21.79 months], which is significantly longer than 8.87 months (95% CI: 0.0-19.88 months, P=0.001) in the high sPD-L1 in BALF group. In 64 patients treated with or without immune checkpoint inhibitors (ICIs), sPD-L1 in BALF was significantly associated with progression-free survival (PFS) and OS. In the subgroup analysis of 31 patients treated with ICI, the objective response rate (ORR) in the low sPD-L1 BALF group was significantly higher than in high sPD-L1 in BALF group (ORR: 60.9% vs. 12.5%, P=0.02). Soluble PD-L1 in BALF is a potential prognostic indicator for patients with stage IV NSCLC and a predictive marker for ICI treatment response.

Role of PLP-Level as a predictive marker for oral health status in adult hypophosphatasia

AimThe aim of this study was to investigate the role of pyridoxal-5-phosphate (PLP) level on the oral health status as a predictive marker in patients with hypophosphatasia (HPP).Materials and methodsThroughout a systematic retrospective assessment both bone metabolism and oral health status were analyzed. The oral health status was assessed by the decayed/missing/filled teeth index (DMFT), clinical attachment level (CAL), probing pocket depth (PPD), and the periodontal screening index (PSI).ResultsA total of 48 HPP patients (81.3% female) with a mean age of 42.21 years was included in this retrospective study. The study population was divided into two groups using the mean PLP level (87 µg/l) as a cut-off. Patients with a PLP level ≥ 87 µg/l (n = 14) showed a significantly poorer oral health status regarding DMFT index, CAL, PPD and PSI compared to patients with a PLP level < 87 µg/l (n = 34). No significant group differences for tooth loss were found.ConclusionThe results of the present study indicate that the PLP level is a suitable diagnostic predictor for the oral health status in HPP patients. HPP patients with PLP levels ≥ 70 µg/l should be included into a regular dental preventive program.Clinical RelevanceThe oral health status in HPP and its correlation with laboratory parameters (i.e. PLP) has been understudied. For clinical practice, the findings of the present study clearly demonstrated that high PLP levels correlate with a worse oral health status in HPP patients. Therefore, these patients should receive an intensive dental treatment and/or inclusion in a strict maintenance program in a specialized dental practice/university hospital with a PLP level ≥ 70 µg/l.

Alpha-fetoprotein and APRI as predictive markers for patients with Type C hepatitis B-related acute-on-chronic liver failure: a retrospective study

BackgroundType C hepatitis B-related acute-on-chronic liver failure (HBV-ACLF), which is based on decompensated cirrhosis, has different laboratory tests, precipitating events, organ failure and clinical outcomes. The predictors of prognosis for type C HBV-ACLF patients are different from those for other subgroups. This study aimed to construct a novel, short-term prognostic score that applied serological indicators of hepatic regeneration and noninvasive assessment of liver fibrosis to predict outcomes in patients with type C HBV-ACLF.MethodPatients with type C HBV-ACLF were observed for 90 days. Demographic information, clinical examination, and laboratory test results of the enrolled patients were collected. Univariate and multivariate logistic regression were performed to identify independent prognostic factors and develop a novel prognostic scoring system. A receiver operating characteristic (ROC) curve was used to analyse the performance of the model.ResultsA total of 224 patients with type C HBV-ACLF were finally included. The overall survival rate within 90 days was 47.77%. Age, total bilirubin (TBil), international normalized ratio (INR), alpha-fetoprotein (AFP), white blood cell (WBC), serum sodium (Na), and aspartate aminotransferase/platelet ratio index (APRI) were found to be independent prognostic factors. According to the results of the logistic regression analysis, a new prognostic model (named the A3Twin score) was established. The area under the curve (AUC) of the receiver operating characteristic curve (ROC) was 0.851 [95% CI (0.801-0.901)], the sensitivity was 78.8%, and the specificity was 71.8%, which were significantly higher than those of the MELD, IMELD, MELD-Na, TACIA and COSSH‐ACLF II scores (all P < 0.001). Patients with lower A3Twin scores (<-9.07) survived longer.ConclusionsA new prognostic scoring system for patients with type C HBV-ACLF based on seven routine indices was established in our study and can accurately predict short-term mortality and might be used to guide clinical management.

Abstract PO5-13-11: Quantitative Assessment of HER2 Expression in Intraductal Neoplasms of the Breast

Abstract HER2 (ERBB2) is an established prognostic and predictive marker for patients with invasive breast cancer and used in HER2-targeted therapy. The clinical and biological significance of expression of HER2 protein in patients with intraductal neoplasms of the breast is not well characterized. In this study, we used our HS-HER2 (High Sensitivity-HER2) which is a CAP/CLIA certified laboratory derived test (LDT) using quantitative immunofluorescence (QIF). We evaluated HER2 expression in DCIS (ductal carcinoma in situ), LCIS (lobular carcinoma in situ) and benign lesions to correlate with their clinicopathologic characteristics. Thirty- eight cases of DCIS, and fourteen cases of LCIS and thirty benign cases were selected from the Yale Pathology department archives and 252 ROIs (regions of interest) were annotated by a board-certified pathologist. DCIS is classified according to the three-tier nuclear grading system: low, intermediate, and high-nuclear grade. LCIS is classified as PLCIS (pleomorphic variant) and CLCIS (classic LCIS) according to the WHO classification of breast tumors. Serial sections of FFPE tumor specimens were used to accurately quantify the HER2 expression by the HS-HER2 assay and the acquisition by QuPath v.04 with Qymia extension. According to the LOD (limit of detection,3 amol/mm2), LOQ (limit of quantification, 9 amol/mm2) and LOL (limit of linearity, 23 amol/mm2) of the optimized HS-HER2 assay as performed in our CLIA lab shows a broad range of HER2 expression in both DCIS and LCIS lesions, ranging from 0.7 amol/mm2 to 111.4 amol/mm2 in DCIS and 3.6 amol/mm2 to 49.9 amol/mm2 in LCIS. High grade DCIS lesions express higher average HER2 levels (111.4 + 0.7 amol/mm2) than combined low and intermediate grade DCIS (77.9 +1.9 amol/mm2) with no significant difference between low/intermediate and high-grade DCIS. CLCIS lesions express higher average HER2 level (49.9 + 3.6 amol/mm2) than PLCIS (35.1 + 5.4amol/mm2) but again this is not statistically significant. HER protein expression is relatively low in benign lesions ranging from 0.8 to 8.4 amol/mm2. Using the HS-HER2 assay, our results show quantitative level HER2 levels in DCIS and LCIS breast lesions. These findings may be important as HER2 targeted therapies that work in gene-unamplified cancer (HER2 conjugated ADCs) gain broader usage in the clinic. Citation Format: Nay Nwe Nyein Chan, Haiying Zhan, Revekka Khaimova, Thazin Aung, Charles Robbins, Patricia Gaule, David Rimm. Quantitative Assessment of HER2 Expression in Intraductal Neoplasms of the Breast [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-13-11.

Abstract 7493: Real-time monitoring of CTC number, biomarker expression, and kinetics as prognostic and predictive markers in patients with GI malignancies

Abstract Background: Most of the utility in the clinic regarding liquid biopsies has been around circulating tumor DNA (ctDNA). ctDNA analysis provides valuable insight into mutational burden and therapeutic targets, but the speed and cost of analysis are prohibitive especially when it comes to serial testing. Using a cohort of patients with advanced or metastatic gastrointestinal (GI) cancers, we herein show the feasibility of using circulating tumor cell (CTC) enumeration, biomarker analysis, and kinetics as complementary to or as an alternative to ctDNA testing. Methods: Using the RareCyte platform, nucleated cells from blood were collected, spread on slides, stained, and imaged with CyteFinder® for CTC identification (CK/EpCAM+, CD45-) and quantification of biomarkers (PD-L1/HER2 or Ki67/EGFR). CTC enumeration (CLIA-accredited CTC test) and biomarker status for each patient were tracked over time and compared with ctDNA mutational analysis and tumor burden. Results: CTCs were detected in 60/70 samples (86%) and in 36/38 unique patients (95%). On average, more CTCs were detected in baseline samples from colorectal cancer patients compared to other subtypes (Table 1). Moreover, multiple patients showed pronounced changes in CTC number that correlated with treatment response, as well as strong correlation between CTC and tissue biomarker expression e.g. HER2. Rapid decline and/or CTC clearance was seen as early as a few days into starting effective systemic therapy. The average turnaround time for CTC testing was 5-7 days. Table 1. CTC values in initial baseline blood draw sample Gastrointestinal cancer subtype # of patients Average # of CTCs per 7.5mL blood Median # of CTCs per 7.5mL blood Minimum # of CTCs per 7.5mL blood Maximum # of CTCs per 7.5mL blood Colorectal carcinoma 27 84 3 0 1378 Cholangiocarcinoma 3 8 3 1 23 Pancreatic cancer 3 2 2 0 3 Hepatocellular carcinoma 2 4 5 0 10 Gallbladder cancer 1 6 6 3 8 Appendix cancer 1 2 2 1 3 Anal cancer 1 0 0 0 0 Conclusions: Our study emphasizes that real-time monitoring of CTCs is complementary to traditional tumor burden monitoring via imaging and ctDNA analysis. CTCs offer multiple unique advantages vs ctDNA including early response assessment within days of initiating therapy, a substantial decrease in cost of serial testing, and the ability to assess clinically relevant cell surface protein biomarkers e.g. HER2 and PD-L1. Citation Format: Erin G. Bayer, Brock M. Bartels, Rachel N. Ponting, Areeb Lutfi, Maaz K. Afghan, Arturo B. Ramirez, Pashtoon M. Kasi. Real-time monitoring of CTC number, biomarker expression, and kinetics as prognostic and predictive markers in patients with GI malignancies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7493.

Clinical outcomes of patients with remitting ulcerative colitis after discontinuation of indigo naturalis

Indigo naturalis is an effective treatment for ulcerative colitis. However, long-term use of indigo naturalis causes adverse events, such as pulmonary hypertension. The natural history of patients with ulcerative colitis who discontinued indigo naturalis after induction therapy is unknown. Moreover, the clinical features of patients who relapsed within 52 weeks after the discontinuation of indigo naturalis are unclear. This study aimed to assess the clinical outcomes of patients with ulcerative colitis after discontinuation of indigo naturalis and to identify potential markers responsible for relapse. This single-center retrospective study investigated the follow-up of 72 patients who achieved a clinical response 8 weeks after indigo naturalis treatment. We observed relapse in patients with ulcerative colitis after the discontinuation of indigo naturalis. We analyzed the factors predicting long-term outcomes after discontinuation of indigo naturalis. Relapse was observed in 24%, 57%, and 71% of patients at 8, 26, and 52 weeks, respectively. There were no predictive markers in patients who relapsed within 52 weeks after the discontinuation of indigo naturalis. The ulcerative colitis relapse rate after indigo naturalis discontinuation was high. Follow-up treatment is required after the discontinuation of indigo naturalis in patients with ulcerative colitis.

A Study of Blood Viscosity and Inflammatory Biomarkers’ Levels in Bilateral Primary Varicose Veins/Reticular Veins as Predictive Markers

Objectives Cross-sectional data was collected for a period of 1 year to assess the biomarkers of inflammation, and blood viscosity as predictive markers in patients with primary bilateral varicose veins or reticular veins that might progress to varicose veins. Material and Methods A sample of 40 participants, 20 controls and 20 patients aged 18–65 years falling under the reticular veins and symptomatic varicose veins (C1, 2s), primary etiology (Ep), superficial veins (As), reflux pathology (Pr) categories of Clinical, etiologic, anatomic, Pathophysiologic (CEAP) classification with the exception of telangiectatic veins, were included in the study. Blood viscosity was measured using a Capillary Viscometer. Evaluated inflammatory markers were tissue Plasminogen Activator (tPA), Plasminogen Activator Inhibitor-1 (PAI-1), and fibrinogen. Analysis was done using Statistical Package for the Social Sciences (SPSS) software and Chi-square, Fisher’s, Bonferroni, and Analysis of Variance (ANOVA) tests were applied. Results There was a statistically insignificant relationship between occupation and different study groups. Standing hours and serum fibrinogen levels had a significant difference in different study groups. Serum tPA, Serum PAI-1, and blood viscosity had an insignificant difference between different study groups. It was revealed that the pairwise group comparisons of study group C2 vs. control group C0, study group C1 vs. control group C0 and study group C2 vs. study group C1, and study group C2 vs. control group C0 each were significantly different pairwise. Conclusion Blood viscosity, tPA and PAI-1 cannot be used as predictive markers in patients with bilateral (B/L) primary varicose veins/reticular veins. Serum fibrinogen levels can be used as predictive markers for the development of B/L primary varicose veins and in our particular study with a predictive range of 189.4–327.9 mg/dL but not for B/L reticular veins. Prolonged standing, irrespective of the occupation of the patient, is associated with the development of B/L reticular veins and B/L varicose veins.

Blood glucose and lactate levels as early predictive markers in patients presenting with cardiogenic shock: A retrospective cohort study.

Lactate and glucose are widely used biochemical parameters in current predictive risk scores for cardiogenic shock. Data regarding the relationship between lactate and glucose levels in cardiogenic shock are limited. Thus, we aimed to analyze glucose and lactate as early markers for in-hospital mortality in cardiogenic shock. In this retrospective cohort study, 312 patients presenting with cardiogenic shock to a tertiary-care hospital between 2016 and 2018 were included. Apparent cardiogenic shock was defined as hypoperfusion with hemodynamic compromise and biochemical marker increase due to diminished tissue perfusion, corresponding to SCAI shock stages. In-hospital mortality was assessed as the primary endpoint. The median age of the study population was 71 (60-79) years and the etiology of cardiogenic shock was acute myocardial infarction in 45.8%. Overall in-hospital mortality was 67.6%. In the receiver operating curve analysis, the area under the receiver-operating curve (AUC) for prediction of in-hospital mortality was higher for lactate (AUC: 0.757) than for glucose (AUC: 0.652). Both values were significantly associated with outcome (groups created with best cutoff values obtained from the Youden index). Correlation analysis showed a significant non-linear association of both values. In a multivariable stepwise Cox regression analysis, lactate remained an independent predictor for in-hospital mortality, whilst glucose, despite being implicated in energy metabolism, was not independently predictive for mortality. Together, these data suggest that lactate at admission is superior for mortality prediction in patients with apparent cardiogenic shock. Glucose was not independently predictive for mortality.

SPP1+ TAM subpopulations in tumor microenvironment promote intravasation and metastasis of head and neck squamous cell carcinoma.

Macrophages are heterogeneous cells that play multifaceted roles in cancer progression and metastasis. However, the phenotypic diversity of tumor-associated macrophages (TAMs) in head and neck squamous carcinomas (HNSCC) remains poorly characterized. Here, we comprehensively analyzed the HNSCC single-cell transcriptomic dataset (GSE172577) and identified 5 subsets of myeloid-driven cells as TAMs using Seurat. Deciphering the lineage trajectory of TAMs, we revealed that FCN1+ TAMs could give rise to pro-angiogenesis SPP1+CCL18+ and SPP1+FOLR2+ populations through SPP1-CCL18+ and CXCL9+CXCL10+ TAMs. SPP1+CCL18+ and SPP1+FOLR2+ TAMs harbored pro-angiogenic and metastatic transcriptional programs and were correlated with poor survival of HNSCC patients. Our immunostaining examination revealed that infiltration of SPP1+ TAMs is associated with lymph node metastasis and poor prognosis in patients with HNSCC. Cell-cell communication analysis implied that SPP1+ TAM populations may employ SPP1 signaling to activate metastasis-related ECs. In vitro and in vivo studies, we demonstrated that SPP1hi TAMs enhanced tumor intravasation and metastasis in HNSCC in a manner dependent on the secretion of SPP1, CCL18, and CXCL8. Taken together, our study characterized the cellular heterogeneity of TAM populations and identified two SPP1+ TAM populations that play key roles in HNSCC intravasation and metastasis and serve as predictive markers for patients with HNSCC.

Clinical value of neutrophil-to-lymphocyte ratio and prognostic nutritional index on prediction of occurrence and development of diabetic foot-induced sepsis.

Diabetic foot-induced sepsis is a serious complication associated with increased disability and mortality in hospitalized patients. Early prediction of admission and detection effectively improve treatment options and prevent further deterioration. This study aims to evaluate the clinical value of the neutrophil-to-lymphocyte ratio (NLR) and prognostic nutritional index (PNI) to predict the risk of sepsis in patients with diabetic foot ulcers (DFU). Retrospective analysis was performed on 216 patients who were admitted to the Fujian Medical University Union Hospital between January 2015 and December 2022. Patients with DFU were divided into the non-sepsis (n = 166) and the DFU-induced sepsis (n = 50) groups. The independent factors of DFU-induced sepsis were determined by univariate and multivariate logistic regression analyses. A receiver operating characteristic (ROC) curve was performed to compare the area under the curves (AUC) of PNI and NLR. Multivariate logistic regression analysis revealed that the PNI, NLR, international normalized ratio (INR), thrombin time (PT), and C-reactive protein (CRP) were independent prognostic factors for DFU-induced sepsis. After adjusting for potential confounders, the adjusted odds ratios of NLR for DFU-induced sepsis were 1.121 (1.072-1.172), 1.132 (1.077-1.189), and 1.080 (1.022-1.142), while those of PNI were 0.912 (0.873-0.953), 0.902 (0.856-0.950), and 1.004 (1.001-1.006). Moreover, the AUC of NLR was significantly greater than that of CRP (0.790, 95% CI: 0.689-0.891, p < 0.001 vs. 0.780, 95% CI: 0.686-0.873, p < 0.001). NLR and PNI have been regarded as readily and independently predictive markers in patients with DFU-induced sepsis. NLR is critical for the early detection and effective treatment of DFU-induced sepsis and is superior to CRP.

The possible role of quinolinic acid as a predictive marker in patients with SARS-CoV-2

Background and aimsQuinolinic acid (QA) is a metabolite of the kynurenine pathway, which is activated by inflammatory stimuli during viral infection. We investigated the role of QA in patients infected with SARS-CoV-2, particularly its prognostic value for survival. MethodsOverall, 104 unvaccinated inpatients were included, divided into a survival (N = 80) and a deceased group (N = 24). Plasma levels of tryptophan, kynurenine, QA, C-reactive protein (CRP) and procalcitonin (PCT) were measured on admission and after seven days. The QA/TRP ratio and the relative differences between the measurements for QA (QA-Diff) and QA/TRP (Diff-QA/TRP) were calculated. ResultsAmong the kynurenine pathway markers, QA-Diff showed the highest discriminatory power for the survival prognosis (Youden index 0.467, cut-off −1.3 %, AUC 0.733, p < 0.001, sensitivity 0.79, specificity 0.675). Among the inflammatory markers, CRP showed the highest discriminatory power (Youden index 0.533, cut-off 25.0 mg/L, AUC 0.794, p < 0.001, sensitivity 0.958, specificity 0.575). A significant correlation between QA and PCT was found on admission and after one week (Spearman‘s rho 0.455 and 0.539, all p-values < 0.001). ConclusionsQA may serve as prognostic marker for survival in patients with SARS-CoV-2. The repeated measurements during the first week of the disease may enhance the prognostic power.

Liver fibrosis estimated using extracellular volume fraction obtained from dual-energy CT as a risk factor for hepatocellular carcinoma after sustained virologic response: A preliminary case–control study

PurposeTo assess hepatocellular carcinoma (HCC) risk after sustained virologic response (SVR) through clinical data analyses, including evaluation of liver fibrosis using the extracellular volume fraction (ECV) obtained from dual-energy computed tomography (DECT). MethodsNinety-two patients (52 men and 40 women; mean age, 69.9 years) with hepatitis C virus infection after SVR underwent DECT of the liver (3-minute equilibrium-phase images) between January 2020 and March 2022. The ECV was calculated by measuring iodine density; fibrous markers, including ECV, fibrosis-4 index, aspartate aminotransferase to platelet ratio index, and platelet count, were statistically analyzed (p < 0.05). The risk factors associated with HCC were analyzed using univariate and multivariate logistic regression analyses. ResultsThe ECV (26.1 ± 4.6 %) in patients with HCC (n,21) was significantly larger than the ECV (20.7 ± 3.3 %) in patients without HCC (n = 71) (p < 0.001). The cutoff value for the ECV was 24.3 %. The area under the operating characteristic curve of the ECV was 0.857, which was higher than that of the serum fibrosis markers. Older age, SVR achieved with interferon, alpha-fetoprotein level (>5 ng/mL), advanced fibrosis before treatment (>F3), and ECV were associated with HCC according to the univariate analysis. Multivariate analyses showed that ECV was the only factor independently associated with HCC (odds ratio 0.619, 95 % confidence interval 0.482–0.795, p < 0.001). ConclusionLiver fibrosis estimated using ECV can be a predictive marker in patients with HCC after SVR.

β2-adrenergic receptor expression in patients receiving bevacizumab therapy for metastatic melanoma.

Vascular endothelial growth factor (VEGF) was initially known as vascular permeability factor and identified as a driver of tumour angiogenesis. Recently, its role in supporting an immunosuppressive tumour microenvironment was demonstrated, and anti-VEGF treatment combined with immune checkpoint blockade is currently investigated. Further, beta-adrenergic signalling as a modifier of cancer hallmarks like immune response, angiogenesis and metastasis gained increased attention during past years. Focusing on the aspect of immunosuppression in upregulated beta-adrenergic signalling, we investigated predictive markers in patients with metastatic melanoma who received bevacizumab monotherapy, a specific VEGF-A binding antibody. We explored the expression of beta-2 adrenergic receptor (β2-AR), interleukin 6-receptor (IL6-R), cyclooxygenase 2 (COX2) and VEGF-A by immunohistochemistry in melanoma to assess the correlation between these proteins in melanoma cells and response to treatment. Strong β2-AR expression in metastases was associated with clinical benefit of bevacizumab. Furthermore, expression of the latter was positively linked to expression of VEGF-A and COX2. β2-AR expression in melanoma metastasis appears to distinguish a subgroup of patients that might benefit from anti-VEGF treatment. Our results strengthen further exploration of anti-VEGF therapy in combination with immune checkpoint blockade in clinical studies and the investigation of β2-AR as predictive marker.

Prognosis Predictive Markers in Patients with Chronic Obstructive Pulmonary Disease and COVID-19.

Some studies have reported that chronic respiratory illnesses in patients with COVID-19 result in an increase in hospitalization and death rates, while other studies reported to the contrary. The present research aims to determine if a predictive model (developed by combing different clinical, imaging, or blood markers) could be established for patients with both chronic obstructive pulmonary disease (COPD) and COVID-19, in order to be able to foresee the outcomes of these patients. A prospective observational cohort of 165 patients with both diseases was analyzed in terms of clinical characteristics, blood tests, and chest computed tomography results. The beta-coefficients from the logistic regression were used to create a score based on the significant identified markers for poor outcomes (transfers to an intensive care unit (ICU) for mechanical ventilation, or death). The severity of COVID-19, renal failure, diabetes, smoking status (current or previous), the requirement for oxygen therapy upon admission, high lactate dehydrogenase (LDH) and C-reactive protein level (CRP readings), and low eosinophil and lymphocyte counts were all identified as being indicators of a poor prognosis. Higher mortality was linked to the occurrence of renal failure, the number of affected lobes, the need for oxygen therapy upon hospital admission, high LDH, and low lymphocyte levels. Patients had an 86.4% chance of dying if their mortality scores were -2.80 or lower, based on the predictive model. The factors that were linked to a poor prognosis in patients who had both COPD and COVID-19 were the same as those that were linked to a poor prognosis in patients who had only COVID-19.

Prognostic and Predictive Markers for Patients With Anal Cancer.

Squamous cell carcinoma of the anus and anal canal is a rare malignancy with an increasing incidence in the United States. In the past 2 decades, the proportion of Americans diagnosed with incurable, metastatic anal cancer at the time of initial presentation has increased. Most cases are linked to prior infection with HPV. Although concurrent chemoradiotherapy has been the accepted standard treatment for patients with localized anal cancer over the past half century, therapeutic advances have increased options for patients with unresectable or incurable anal cancer over the past 5 years. Specifically, combination chemotherapy and immunotherapy with anti-PD-(L)1 antibodies has demonstrated efficacy in this setting. Greater understanding of molecular drivers of this viral-associated malignancy has provided critical insight into evolving biomarkers for the clinical management of anal cancer. The pervasiveness of HPV across cases of anal cancer has been leveraged for the development of HPV-specific circulating tumor DNA assays as a sensitive biomarker for prognosticating recurrence in patients with localized anal cancer who complete chemoradiation. For patients with metastatic disease, somatic mutations, well-characterized for anal cancer, have not shown utility in identifying patients who benefit from systemic treatments. Although the overall response rate to immune checkpoint blockade therapies is low for metastatic anal cancer, high immune activation within the tumor and PD-L1 expression may identify patients more likely to experience response. These biomarkers should be incorporated into the design of future clinical trials to personalize further treatment approaches in the evolving management of anal cancer.

Monocyte to high-density lipoprotein cholesterol ratio as highly predictive marker in patients with acute coronary syndrome.

Aim: This study examined the relationship between Thrombolysis inMyocardial Infarction (TIMI) score and monocyte to high-density lipoprotein cholesterol (HDL-C) ratio (MHR) with Global Registry of Acute Coronary Events (GRACE) in patients with acute coronary syndrome(ACS). Materials & methods: A total of1000patients with ACS admitted to the Cardiology Department of the Dustira Army Hospital were included in this study. Medical records were retrospectively reviewed from January 2019 to June 2020 with consecutive sampling. Results: In the group with a higher TIMI score, the MHR result was considerably higher. In the same way, MHR was more significant in the group with a high-risk than in low-risk GRACE. Conclusion: MHR is a convenient, reproducible and correlates with GRACE and TIMI score as predictive biomarkers in patients with ACS.

Clinicopathological Parameters and Immunohistochemical Expression of EGFR in Colorectal Carcinoma: A Cross-sectional Study

Introduction: Colorectal Carcinoma (CRC) is the third most common type of cancer worldwide and is one of the leading causes of cancer-related death. Adenocarcinoma is the most common type. Histopathological examination is necessary to determine the type and extent of the tumour, which is essential for patient management and prognosis. Molecular markers play a major role in CRC, among which Epidermal Growth Factor Receptor (EGFR) has prognostic significance. Aim: The aim of this study was to evaluate the immunohistochemical expression of EGFR in cases of colonic carcinoma and analyse its relationship with various histological and clinical parameters. Materials and Methods: An observational (cross-sectional) study was conducted in the Department of Pathology, Sree Mookambika Institute of Medical Sciences, Kulasekharam, Kanyakumari district, Tamil Nadu, India. Data from colonic carcinoma patients confirmed by Haematoxylin and Eosin (H&amp;E) staining were collected over a three-year period from January 2019 to December 2021. A total of 58 cases were included. The characteristics studied included age, sex, Carcinoembryonic Antigen (CEA) levels, tumour site, size, degree of histological differentiation (well, moderate, poor), TNM staging, and lymph node status. The EGFR score was obtained by multiplying the grade (% positive cells) by the intensity, and a composite score ranging from 0 to 9 was obtained. This score was used to define low EGFR expression (&lt;6) or high EGFR expression (&gt;6). Analysis was performed using the Chi-square test in Statistical Package for the Social Sciences (SPSS) version 20.0. Results: Among the 58 patients included in the study, the most common age group affected by CRC was 61 to 70 years (28 cases; 48.3%), with a mean age of 63.32±14.36 years. The most common histological variant was low-grade adenocarcinoma (47 cases; 81.03%). EGFR reactivity was positive in 50 patients (86.20%). EGFR overexpression was significantly associated with histopathological type (low-grade adenocarcinoma) and tumour stage, with p-values of 0.03 and 0.001, respectively. Conclusion: Immunohistochemical overexpression of EGFR in CRC is associated with histopathological type and tumour staging in this study. This overexpression is associated with poor prognosis and can be used as a predictive marker for patients who yield positive results with chemotherapy.

The emerging role of miR-20b in human cancer and other disorders: Pathophysiology and therapeutic implications.

miR-20b is a microRNA with diverse and somehow contradictory roles in the pathogenesis of human disorders, especially cancers. It has been known to be a tumor suppressor in colon cancer, renal cell carcinoma, prostate cancer, osteosarcoma and papillary thyroid cancer. In lung cancer and breast cancers, both tumor suppressor and oncogenic effects have been identified for this miRNA. Finally, in T cell leukemia, hepatocellular carcinoma, esophageal squamous cell carcinoma and cervical and gastric cancers, miR-20b is regarded as an oncogenic miRNA. In several types of cancer, dysregulation of miR-20b has been recognized as a predictive marker for patients' survival. Dysregulation of miR-20b has also been recognized in Alzheimer's disease, diabetic retinopathy, myocardial ischemia/infarction, chronic hepatitis B and multiple sclerosis. In the current review, we have summarized the miR-20b targets and related cellular processes. We have also provided a review of participation of this miRNA in different human disorders.

The clinical significance of HER2 expression in DCIS.

HER2 is an established prognostic and predictive marker for patients with invasive breast cancer. The clinical and biological significance of HER2 overexpression in patients with ductal carcinoma in situ (DCIS) remains poorly defined. DCIS is a heterogeneous disease and some patients with DCIS will not progress to invasive breast cancer. However, clinically significant recurrence rates have been reported after breast-conserving surgery for DCIS and approximately half of these cases will be life-threatening invasive recurrences. Since the incidence of DCIS is rising due to the widespread use of screening mammography, there is robust interest in selecting high-risk DCIS patients that may benefit from adjuvant therapies. Molecular prognostic and predictive models in early invasive breast cancer help clinicians identify patients that will benefit from chemotherapy. Molecular subtyping and profiling could also be useful in treating DCIS patients. According to current practice guidelines, HER2 testing is not recommended in DCIS patients. Nevertheless, evidence suggests that HER2-positive DCIS cases may be associated with adverse clinicopathological parameters and increased recurrence rates. This review summarizes the existing body of evidence linking HER2 expression and ipsilateral breast cancer recurrence in DCIS. HER2, as well as its correlation with other clinicopathological markers might be a useful prognostic and predictive marker, helping clinical decision-making in DCIS patients.

Pre-transplant platelet-to- lymphocyte ratio predicts outcome after allogeneic hematopoietic stem cell transplantation

For many patients with hematological malignancies such as acute leukemia or myelodysplastic syndrome allogeneic hematopoietic stem cell transplantation (allogeneic HSCT) is the only curative treatment option. Despite the curative potential of this treatment many patients experience relapse of their underlying disease or die due to multiple complications e.g. infections. Risk scores could help to assess the individual prognosis and guide patients and treating physicians to choose between different treatment options. Parameters reflecting the inflammatory status, such as neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), and platelet-to-lymphocyte ratio (PLR), have been demonstrated to be associated with prognosis and treatment complications in patients with various cancers. In this study, we evaluate pre-HSCT NLR, MLR and PLR as predictive markers in patients undergoing allogeneic HSCT. We demonstrate that a high (> 133) PLR level is associated with better clinical outcome. Patients with high pre-HSCT PLR show a significant better overall survival (p = 0.001), less relapses (p = 0.016), lower non-relapse-mortality (p = 0.022), less transfusions of red blood cells, platelets and fresh frozen plasma (p = 0.000), fewer episodes of fever (p = 0.002), considerably less different antibiotics (p = 0.005), fewer intensive care unit treatment (p = 0.017) and a lower in-hospital mortality (p = 0.024). Pre-HSCT PLR is easy to calculate by daily routine and could help to predict patient outcome after allogeneic HSCT.