Bad Prognostic Marker Research Articles

Serum Stabilin1 as a Prognostic Marker in Adults Acute Leukemia Patients

Abstract Background STAB-1 (common lymphatic endothelial and vascular endothelial receptor) was found to be expressed on tumor lymphatic vessels in different malignancies and it is a bad prognostic marker. This study will assess the role of serum stabilin1 (STAB1) as a prognostic marker in adult patients with newly diagnosed acute leukemia and correlate it with the other well established prognostic markers. Acute lymphoblastic leukemia (ALL) is a hematologic malignancy arising from precursors of the lymphoid lineage. Conventional cytotoxic chemotherapies have resulted in high cure rates of up to 90% in pediatric ALL, but the outcomes for adult patients remain suboptimal with 5-year survival rates of only 30%-40%. Aim of the Work To measure STAB1 expression in patients with AML and patients with ALL and assess its role as a prognostic factor with correlating it with other prognostic factors. Patients and Methods A case control study in Ain Shams University Hospitals, Clinical Haematology and Oncolgy division of Internal Medicine Department for one year on total 75 subjects divided into: 25 patients with newly diagnosed acute myeloid leukemia (AML), 25 patients with newly diagnosed acute lymphoblastic leukemia (ALL) and 25 age and sex matched healthy control subjects. The study population was recruited from Ain Shams University Hospitals, Clinical Haematology and Oncolgy division of Internal Medicine Department. Results There was no significant difference between cases of acute leukemia pts and control group as there was no statistically significant difference between control and patients group regarding sex, age, spleen size, liver size, LDH, CRP, uric acid and ESR of the studied subjects. Our study shows that as regard CBC; there was significant difference between the studied groups as regard leucocytic count, BUT Platelets, and hemoglobin was insignificant, which was also described in the study. Our study showed that there was high statistically significant difference between the acute leukemia patients and the healthy control group as regard sabilin1. Our study shows that the mean serum level of stabilin1 in the patients who didn’t respond to chemotherapy was higher than that of the patients that responded to chemotherapy. Conclusion There was high statistically significant difference between the studied groups as stabilin1. There was significant correlation between stabilin2 and chemotherapy response. Stabilin1 expression levels also identified a new subgroup at a higher risk for relapse and with a poor prognosis in acute leukemia patients. Stabilin 1 can be used as a prognostic factor in patients with acute leukemia.

Prognostic significance of serum miR-18a-5p in severe COVID-19 Egyptian patients

BackgroundThe identification of miRNAs as well as characterization of miRNA-mRNA interactions in SARS-CoV-2 infection is important to understand their role in disease pathogenesis. Therefore the aim of the present study was to measure the expression levels of hsa-mir-18a-5p in the sera of severe COVID-19 Egyptian patients admitted to ICU to investigate its roles in the pathogenesis and severity of COVID-19 disease. MethodsA total of 180 unvaccinated severe COVID-19 patients were enrolled in our study. Besides the routine laboratory work, the expression level of hsa-mir-18a-5p was done using reverse transcription quantitative real-time PCR (RTqPCR) technique. Also, target genes of hsa-mir-18a-5p were explored by using online bioinformatics databases. ResultsThe expression level of hsa-mir-18a-5p decreased in nonsurvival severe COVID-19 patients (0.38 ± 0.26) when compared to the survival ones (0.84 ± 0.23). While as a prognostic tool for the prediction of bad prognosis and mortality among severe COVID-19 patients, our results showed that the serum hsa-mir-18a-5p expression level is a good sensitive and specific marker. By using bioinformatics tools, our results revealed that the decreased hsa-mir-18a-5p expression level may have a crucial role in COVID-19 pathogenesis and severity through decreased immunological responses (interpreted as lymphopenia) or increased inflammation (interpreted as increased serum levels of IL-6, CRP, LDH). ConclusionTaken together, the decreased expression level of hsa-mir-18a-5p could be a bad prognostic marker and therapeutic overexpression of hsa-mir-18a-5p could be a novel approach in the treatment of COVID-19 disease.

Abstract 6719: Osteopontin-c is worse prognostic marker and mediate key steps associated with central nervous system infiltration in B-cell acute lymphoblastic leukemia cells

Abstract B-cell acute lymphoblastic leukemia (B-ALL) is the most common pediatric malignance, but 35% of patients still relapse after chemotherapy treatment, mainly in the central nervous system (CNS). In order to search for new biomarkers that could predict CNS infiltration and relapse, many studies are trying to find gene products aberrantly expressed in these patients, including osteopontin (OPN). The OPN primary transcript undergoes alternative splicing, generating at least five OPN splicing isoforms (OPN-SI), named OPNa, OPNb, OPNc, OPN4 and OPN5, that have tumor specific roles and have been reported as biomarkers in solid tumors. However, knowledge regarding OPN-SI in B-ALL is scarce. This study aimed to investigate the expression patterns and roles of OPN-SI in CNS infiltration in B-ALL. OPN-SI transcript levels were analyzed by quantitative real time PCR (qRT-PCR) assays using RNA extracted from 54 B-ALL pediatric patient blood samples or from RS4,11 cell line. OPNc transcript knock-down in RS4;11 cells (a B-ALL cell line containing the MLL gene fusion) was performed using anti-OPNc or control scrambled antisense DNA oligomers (anti-OPNc-ASOs and Scbl-ASO, respectively). These oligomers were transfected in RS4;11 cells and the in vitro effects of OPNc knock-down were evaluated by several functional assays, such as cell viability by MTT analysis, cell adhesion, and transmigration and invasion assays using a boyden chamber device. Among tested OPN-SI, OPNc is the most highly expressed OPN-SI in B-ALL patient samples containing the MLL fusion gene, when compared to those samples harboring the ETV6-RUNX1 fusion gene (p<0,005). High OPNc expression levels were significantly associated with poor prognostic features, such as high-risk classification (p<0,005), CNS infiltration and high white blood cell counting (p<0,05). The RS4;11 cells in which OPNc was knocked-down decreased their OPNc expression levels in 85% in relation to control Scbl-ASO transfected cells (p<0,005). These cells decreased their viability in 41% (p<0,05), besides displaying a 55% decrease in RS4;11 cell adhesion to matrigel. In addition, these cells decreased their capacity to transmigrate (54%) and invade the matrigel (51%) in comparison to control cells. In summary, these results suggest that OPNc transcript levels are associated with B-ALL worse prognostic features and that it may mediate some key steps involved on CNS infiltration mechanistic. Hence, our data provide important basis for the potential use of OPNc as a biomarker for B-ALL CNS relapse and for the involvement of this isoform on some steps that can mediate CNS invasion, opening new opportunities to improve B-ALL pediatric patients’ survival rates and quality of life. Citation Format: Ana Clara Ana Clara Santos da Fonseca Bastos, Luciana Bueno Ferreira, Mariana Emerenciano, Etel Rodrigues Pereira Gimba. Osteopontin-c is worse prognostic marker and mediate key steps associated with central nervous system infiltration in B-cell acute lymphoblastic leukemia cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6719.

Discoidin Domain Receptor 2 Expression as Worse Prognostic Marker in Invasive Breast Cancer.

Discoidin domain receptor 2 (DDR2) is arising as a promising therapeutic target in breast carcinoma (BC). The ability of DDR2 to bind to collagen promotes protumoral responses in cancer cells that influence the tumor microenvironment (TME). Nonetheless, the interrelation between DDR2 expression and TME modulation during BC progression remains poorly known. For this reason, we aim to evaluate the correlation between intratumoral expression of DDR2 and the infiltration of the main TME cell populations, cancer-associated fibroblasts (CAFs), and tumor-associated macrophages (TAMs). First, collagen and DDR2 expression levels were analyzed in human invasive BC samples. Then, DDR2 status correlation with tumor aggressiveness and patient survival were retrieved from different databases. Subsequently, the main pathways, cell types, and tissues correlated with DDR2 expression in BC were obtained through bioinformatics approach. Finally, we studied the association of DDR2 expression with the recruitment of CAFs and TAMs. Our findings showed that, together with the expected overexpression of TME markers, DDR2 was upregulated in tumor samples. Besides, we uncovered that altered TME markers were linked to DDR2 expression in invasive BC patients. Consequently, DDR2 modulates the stromal reaction through CAFs and TAMs infiltration and could be used as a potential worse prognostic factor in the treatment response of invasive BC.

Expression of PD-L1 in Urothelial Carcinoma and its Association with Clinicopathological Parameters

Introduction: Urothelial cancer poses a substantial medical and public health challenge in most parts of the world. Programmed Death Ligand 1 (PD-L1) is a cell surface glycoprotein that plays an important role in the suppression of cellular immune responses to tumour and is now emerging as a new target for immunotherapy. Aim: To examine PD-L1 expression in urothelial carcinoma and its relationship with various clinicopathological parameters. Materials and Methods: A retrospective analysis study was conducted on 50 cases of Urothelial Carcinomas diagnosed in Sri Guru Ram Das Institute of Medical Sciences and Research, Amritsar, Punjab, India from January 2016 to January 2019. Detailed clinical data of the patients’ was collected and the analysis was undertaken between February 2019 and April 2019. Tissues were formalin fixed, paraffin embedded and were studied for histopathological grading after staining with haematoxylin and eosin. All cases were subjected to immunohistochemistry for PD-L1 expression. Chi-square test was used to assess the relationship between PD-L1 positivity and various clinicopathological parameters. A p-value <0.05 was considered as statistically significant. Results: A total of of 50 cases were included and 54% (27 cases out of total 50) were low grade cases. The maximum incidence was seen in 5th-7th decade of life with male preponderance. 27 cases out of the total 50 were low grade cases while the rest 46% (23 cases) were high grade. The PD-L1 positivity was observed in 19 cases (38%). The PD-L1 expression was significantly associated with high grade of tumour, increase in size of tumour and lamina propria invasion. Age, gender and muscle invasion however had no association with PD-L1 expression. Conclusion: The present study concluded that expression of PDL1 was significantly correlated with poorer clinicopathological variables including increasing size, higher grade and lamina propria invasion. PD-L1 positivity is therefore a bad prognostic marker

Influence of Pretransplant Anemia on Red Blood Cell Transfusions in Myeloma Patients Undergoing Autologous Hematopoietic Stem Cell Transplantation

Background and Objectives: Anemia during peripheral blood stem cells (PBSCs) transplant is considered a bad prognostic marker. The study aimed to determine whether pretransplant anemia influence peritransplant transfusion requirements in myeloma patients. Methods: Myeloma patients planned for PBSC transplant were stratified based on hemoglobin levels at time of mobilization, PBSC collection, and PBSC infusion. Univariate and multivariate analysis was performed to study the predictors for good mobilization, adequate CD34 yield by apheresis, and red blood cell (RBC) transfusion in the peritransplant period. Results: Of 67 patients, the prevalence of anemia at mobilization, PBSC collection, and PBSC infusion was 37%, 58%, and 70%, respectively. Eighty-five percent had good mobilization with peripheral blood CD34 count of 50 cells/μl (8–123) and 81% had adequate CD34 yield with first apheresis. Thirty-two percent patients received peritransplant RBC transfusion with the median of one unit (range: 0–5). Anemia on the day of infusion did influence the RBC transfusions in the peritransplant period (P = 0.03). Conclusion: One third of myeloma patients require RBC transfusion support in the peritransplant period. We identified pretransplant anemia neither influenced mobilization nor PBSC collection but increased the risk for RBC transfusion in the peritransplant period.

Diabetes Mellitus as a Bad Prognostic Marker in COVID-19 Patients and Its Relationship with Inflammatory Markers (CRP, D-dimer, LDH, and Ferritin)

Diabetes Mellitus as a Bad Prognostic Marker in COVID-19 Patients and Its Relationship with Inflammatory Markers (CRP, D-dimer, LDH, and Ferritin)

Second neoplasm in cutaneous T-cell lymphoma patients: a marker of worse prognosis?

Background Epidemiologic studies have shown that cutaneous T-cell lymphoma (CTCL) patients have an increased risk of the development of a second neoplasm (SN). The aim of our study was to evaluate the risk of SN and to correlate any possible change in CTCL course after the diagnosis of a subsequent neoplasm. Methods A ten-year retrospective study was carried out in two centres (Bologna and Florence) all the patients who developed a SN six months at least after a CTCL were included. Two groups were selected: Group 1 featuring patients who developed a SN and Group 2 characterised by patients affected by MF age and sex-matched with Group 1 (control group). Data concerning any stage change after SN, time between MF and SN onset, modified Severity Weighted Assessment Tool (mSWAT) score before and after SN, concerning Group 1 and after a median time of 36 months in Group 2 were analysed. Results Thirteen patients were detected. Before SN onset, early MF patients were mainly present, while SN cases in advanced-stage (ten patients) were observed. SN type predominant was lung cancer, along with prostate and pancreatic cancer, while isolated cases presenting with vulvar, colon, mammalian, prostate cancer along with Hodgkin's Lymphoma. Mean mSWAT at MF diagnosis and after SN showed a significant difference (p value=0.0037). After SN diagnosis, nine patients experienced an MF stage progression and ten patient died at follow up. Conclusions In all the instances, statistical analysis showed that mean mSWAT score before/after SN diagnosis had a significantly difference (p value=0.0037) suggesting that patients with a SN may have a worse clinical outcome. By secreting immunosuppressive cytokines or recruiting immunosuppressive cells, a sort of mutual help between the two neoplasms may be prompted. Our data suggest that SN development in MF patients may be regarded as a worse prognostic marker.

Cortactin Expression is a Novel Biomarker for Risk Stratification of T-Cell Acute Lymphoblastic Leukemia.

The role of cortactin in T-cell acute lymphoblastic leukemia (T-ALL) tissue infiltration has been previously reported. However, its impact on patients' responsiveness to therapy and patient's outcome was not previously addressed. This study was conducted on 60 T-ALL pediatric patients at diagnosis and 10 nonleukemic controls. Cortactin and HS1 expressions were identified by real-time polymerase chain reaction. Cortactin and HS1 expression were significantly higher in T-All patients as compared with controls as well as postinduction levels (P≤0.001 for both). The high cortactin expression was significantly associated with high peripheral white cell counts (P≤0.001), blood blast cells (P≤0.001) and central nervous system (CNS) infiltration (P≤0.001), and early precursor T-ALL subtype (P≤0.001) as compared with the remaining groups. The induction of remission response was significantly higher in T-ALL patients with lower cortactin expression levels as compared with T-ALL patients with higher one (P≤0.001). The high cortactin and HS1 expressions were significantly predictors of CNS infiltrations (hazard ratios [HR]: 1.051, confidence interval [CI]: 1.02-1.13, P=0.04 and HR: 1.87, CI: 1.23-2.091, P=0.002, respectively) and bone marrow relapse (HR: 1.43, CI: 1.18-1.92, P=0.004 and HR: 1.07, CI: 1.01-1.24, P=0.002, respectively). Furthermore, high cortactin expression levels were associated with shorter B-ALL patients' overall survival as compared with those with lower cortactin levels (P=0.002). In conclusion, high expression of cortactin and/or HS1 at diagnosis is a bad prognostic marker of T-ALL patients' outcome. Moreover, cortactin and/or HS1 expression could be used as a biomarker for refining risk stratification of T-ALL.

Clinical Value of NOTCH1 Mutations Detection among Chronic Lymphocytic Leukemia Patients.

Background:The data about the clinical impact of NOTCH1 mutations among Egyptians B – cell chronic lymphocytic patients is not previously identified. We herein, evaluate the prevalence and the prognostic significance of neurogenic locus notch homolog protein-1 (NOTCH1) mutations in B- cell lymphocytic leukemia (B-CLL). Methods:A cohort of 105 Egyptian B-CLL patients aging from 43 to 86 years. PCR products including NOTCH1 exon 26, 27, and distal part of exon 34 expanding the sequences encoding transcription activation domain (TAD) and a peptide sequence rich in proline (P), glutamic acid (E), serine (S), threonine (T) (PEST domains) were sequenced by direct DNA Sanger sequencing. Results:NOTCH1 mutations were detected in 48/105 of patients (45.7%). Mutations in B-CLL patients are insertions (n=21), point mutations (n=18) and deletions (n=12). NOTCH1 mutations showed significant impact on prognosis of B-CLL patients as they were associated with increased bone marrow lymphocytes, more relapse and high incidence of mortality, shortened overall survival and progression free survival, and lymphocytes doubling time, when compared with NOTCH1 wild type B-CLL patients (P= 0.001; 0,005; 0.042; 0.049; 0.008; 0.049 respectively). Conclusion:NOTCH1 mutations were considered as bad prognostic marker in B-CLL and suggested to be included in risk stratification of B-CLL patients at diagnosis.

Oxidative stress in CLL patients leads to activation of Th9 cells: an experimental and comprehensive survey

Older adults are mostly affected by chronic lymphocytic leukemia (CLL). The present study aimed to evaluate oxidative stress in CLL and to assess its impact on IL-9, Th9 cells levels and prognosis of cases. Seventy Egyptian CLL patients and 15 healthy controls were included. Th9 cell and immunophenotyping of abnormal B cells were assessed by flow cytometry, IL-9 level using ELISA, IL-9 mRNA by qRT-PCR, cytogenetics using FISH, and oxidative stress parameters were determined spectrophotometrically and with native gel electrophoresis. Oxidative stress was elevated in CLL that correlated with abnormal immunophenotyping, cytogenetic changes, bad prognosis, Th9 cells, and overexpression of IL-9. Levels of IL-9 and Th9 cells were strongly correlated with oxidative stress and bad prognostic markers in CLL, indicating that these cells may contribute to CLL by novel mechanisms that could include oxidant injury.

Second neoplasm in cutaneous T-cell lymphoma patients: a marker of worse prognosis?

Epidemiologic studies have shown that cutaneous T-cell lymphoma (CTCL) patients have an increased risk of the development of a second neoplasm (SN). The aim of our study was to evaluate the risk of SN and to correlate any possible change in CTCL course after the diagnosis of a subsequent neoplasm. A ten-year retrospective study was carried out in two centers (Bologna and Florence) all the patients who developed a SN six months at least after a CTCL were included. Two groups were selected: group 1 featuring patients who developed a SN and group 2 characterized by patients affected by MF age and sex-matched with group 1 (control group). Data concerning any stage change after SN, time between MF and SN onset, modified Severity Weighted Assessment Tool (mSWAT) score before and after SN, concerning Group 1 and after a median time of 36 months in Group 2 were analyzed. Thirteen patients were detected. Before SN onset, early MF patients were mainly present, while SN cases in advanced stage (ten patients) were observed. SN type predominant was lung cancer, along with prostate and pancreatic cancer, while isolated cases presenting with vulvar, colon, mammalian, prostate cancer along with Hodgkin's Lymphoma. Mean mSWAT at MF diagnosis and after SN showed a significant difference (P value = 0.0037). After SN diagnosis, nine patients experienced an MF stage progression and ten patients died at follow-up. In all the instances, statistical analysis showed that mean mSWAT score before/after SN diagnosis had a significantly difference (P=0.0037) suggesting that patients with a SN may have a worse clinical outcome. By secreting immunosuppressive cytokines or recruiting immunosuppressive cells, a sort of mutual help between the two neoplasms may be prompted. Our data suggested that SN development in MF patients may be regarded as a worse prognostic marker.

Leukocyte-associated immunoglobulin-like receptor-1, T-cell leukemia/lymphoma protein-1, and nuclear factor κB expression in childhood acute lymphoblastic leukemia

Background Immune regulation is crucial for the pathogenesis of childhood acute lymphoblastic leukemia (ALL). Leukocyte-associated immunoglobulin-like receptor-1 (LAIR-1) is an immune regulator, expressed by T and B immune cells. T-cell leukemia/lymphoma protein-1 (TCL1) is a coactivator of α-serine/threonine-protein kinase, and when dysregulated, it causes lymphomagenesis and cancer progression. Nuclear factor-κB (NF-κB) is a transcription factor that regulates genes involved in immune responses. This study aimed to study the expression of LAIR-1, TCL1, and NF-κB on blasts in childhood ALL with evaluation of their prognostic value.Patients and methods This descriptive cross-sectional study was conducted on 60 newly diagnosed childhood ALL cases. They were divided into group 1 (n=47) of B-cell ALL and group 2 (n=13) of T-cell ALL. The expression pattern of LAIR-1, TCL1, and NF-κB on blasts was assessed using flow cytometry.Results Correlation studies in total patients with ALL (n=60) revealed significant positive correlation between percentage of blasts expressing LAIR-1% and total leukocytic count (r=0.262, P=0.043) and percentage of blasts infiltrating the peripheral blood (r=0.292, P=0.025). A significant positive correlation of LAIR-1 mean fluorescence intensity with percentage of blasts expressing CD13 (r=0.293, P=0.026) and CD33 (r=0.373, P=0.004) was found. In group 2, a significant positive correlation was seen between percentage of blasts expressing TCL1 and LAIR-1 mean fluorescence intensity (r=0.566, P=0.044). According to Cox regression analysis, the percentage of blasts expressing NF-κB was seen to significantly increase the risk of death, in childhood ALL (hazard ratio=1.085, 95% confidence interval=1.02–1.16, P=0.01).Conclusion LAIR-1 expression carries the potentiality of being a bad prognostic marker in childhood ALL. A relation is suggested between the expression of both LAIR-1 and TCL1 on blasts. NF-κB expression might negatively influence the survival rate in childhood ALL.

IL‑17F and IL- 23 gene polymorphism in patients with acute myeloid leukemia, an Egyptian study

Background: Acute myeloid leukemia (AML) is a highly fatal disease occurring due to the proliferation and accumulation of myeloid progenitor cells. Th17 cells had been claimed by many studies to play a role in the development of AML. Aim Of work: This work aimed to detect the possible role of IL 17 F and IL 23 gene polymorphisms in the pathogenesis of AML, relation to prognosis, and response to treatment. Subjects, materials, and methods: This study was done on 68 patients with newly diagnosed AML (as a patient group), together with 56 matched healthy volunteers (control group). IL 17 F and IL 23 gene polymorphisms were genotyped by real-time polymerase chain reaction (Real-time PCR). Results: No significant differences were detected between patients and controls in respect to IL 17 genotype distribution, there were statistically significant differences between patients and controls regarding IL 23 genotype distribution. No statistically significant relation was found between interleukin 17 and interleukin 23 and any of the bad prognostic markers. Conclusion: We concluded that IL23 gene polymorphism could be considered an independent risk factor in the pathogenesis of AML, while we could not prove that IL 17 gene polymorphism has a role in the development of AML.

Eccrineporocarcinoma of thigh : A rare adnexal tumour

We report a rare case of eccrine porocarcinoma (EPC) in a 65 year old male patient. EPC arises from the intraepidermal portion of the eccrine sweat glands (acrosyringium). Previously the tumour was known as eccrine adenocarcinoma or malignant eccrine poroma with incidence predominantly in extreme of old age. The tumour arises most commonly on hands and feet. Rare sites like scalp, face, penis and abdomen are also reported in the literature. The distinction of porocarcinoma and basal cell carcinoma can be a diagnostic dilemma on a superficial biopsy. The histological features of high mitotic rate, tumour depth and lymphovascular invasion are bad prognostic markers. Immunohistochemistry for CK15, CK7, epithelial membrane antigen (EMA) and estrogen confirmed the diagnosis of EPC. This tumour is preferably treated with Moh’s surgery though few cases of metastasis are reported. DOI:10.21276/APALM.1713

Copy number variations in atypical fibroxanthomas and pleomorphic dermal sarcomas.

Atypical fibroxanthomas (AFX) and pleomorphic dermal sarcomas (PDS) are frequent cutaneous sarcomas typically arising on sun-exposed skin in elderly patients. In contrast to AFX, which generally do not recur after complete excision, PDS locally recur in up to 50% and metastasize in up to 20%.We recently detected characteristic UV-induced TP53 mutations as potential driver mutation in almost all PDS investigated as well as activating PIK3CA and RAS gene mutations in around one third of our tumors representing targets for personalized treatments in patients with unresectable or metastasized PDS.In the present study, we identified amplifications and deletions in a small part of the PDS (6 of 27 cases) but not in AFX suggesting that copy number variations (CNV) might not be an initial event in tumor development but rather important during tumor progression. In addition to BRAF, KNSTRN, IDH1 and PDGFRA amplification, CNV analyses revealed deletions in the CDKN2A, KIT and PDGFRA genes. In cases where an appropriate FISH assay was established, the CNV results could be verified by FISH analysis.Amplification of BRAF, KIT or PDGFRA and/or losses of CDKN2A might represent bad prognostic markers, although larger studies are needed to clarify their association with prognosis or progression in PDS.

Hyperglycemia on admission and hospitalization outcomes in patients with atrial fibrillation.

We evaluated the association of admission blood glucose (ABG) and mortality in patients with and without diabetes mellitus (DM) hospitalized for atrial fibrillation (AF). Hyperglycemia on admission is a bad prognostic marker in patients with AF. Observational data were collected from electronic records of patients age ≥ 18 years hospitalized for AF in 2011-2013. Twelve-month data were available in all cases. ABG levels were classified as follows: 70 to 110 mg/dL, normal; 111 to 140 mg/dL, mildly elevated; 141 to 199 mg/dL, moderately elevated; ≥200 mg/dL, markedly elevated. Cox proportional hazards model was used to assess overall survival by ABG categories, adjusted for study variables. Primary outcome measure was mortality at end of follow-up. The cohort included 1127 patients (45% male; median age, 75 ± 13 years), of whom 331 had DM. Mortality rates by ABG levels were 19% (77/407 patients), normal ABG; 26% (92/353 patients), mildly elevated ABG; 28% (69/244 patients), moderately elevated ABG; and 41% (50/123 patients), markedly elevated ABG. Data were analyzed for the entire cohort following adjustment for age, sex, CHADS2 score, ischemic heart disease, smoking, and alcohol consumption. Compared with normal ABG, the adjusted hazard ratio for mortality was higher in patients with moderately elevated ABG (2.1, 95% confidence interval: 1.19-7.94, P < 0.05) and markedly elevated ABG (1.6, 95% confidence interval: 1.02-5.31, P < 0.05). In patients with and without DM hospitalized for AF, moderately to markedly elevated ABG levels are associated with increased mortality.

Admission Glucose and In-hospital Mortality after Acute Myocardial Infarction in Patients with or without Diabetes: A Cross-sectional Study.

Background:Hyperglycemia on admission has been found to elevate risk for mortality and adverse clinical events after acute myocardial infarction (AMI), but there are evidences that the relationship of blood glucose and mortality may differ between diabetic and nondiabetic patients. Prior studies in China have provided mixed results and are limited by statistical power. Here, we used data from a large, nationally representative sample of patients hospitalized with AMI in China in 2001, 2006, and 2011 to assess if admission glucose is of prognostic value in China and if this relationship differs depending on the presence or absence of diabetes.Methods:Using a nationally representative sample of patients with AMI in China in 2001, 2006, and 2011, we categorized patients according to their glucose levels at admission (< 3.9, 3.9–7.7, 7.8–11.0, and ≥11.1 mmol/L) and compared in-hospital mortality across these admission glucose categories, stratified by diabetes status. Among diabetic and nondiabetic patients, separately, we employed logistic regression to assess the differences in outcomes across admission glucose levels while adjusting for the same covariates.Results:Compared to patients with euglycemia (5.8%), patients with moderate hyperglycemia (13.1%, odds ratio [OR] = 2.44, 95% confidence interval [CI, 2.08–2.86]), severe hyperglycemia (21.5%, OR = 4.42, 95% CI [3.78–5.18]), and hypoglycemia (13.8%, OR = 2.59, 95% CI [1.68–4.00]), all had higher crude in-hospital mortality after AMI regardless of the presence of recognized diabetes mellitus. After adjustment for patients’ characteristics and clinical status, however, the relationship between admission glucose and in-hospital mortality was different for diabetic and nondiabetic patients (P for interaction = 0.045). Among diabetic patients, hypoglycemia (OR = 3.02, 95% CI [1.20–7.63]), moderate hyperglycemia (OR = 1.75, 95% CI [1.04–2.92]), and severe hyperglycemia (OR = 2.97, 95% CI [1.87–4.71]) remained associated with elevated risk for mortality, but among nondiabetic patients, only patients with moderate hyperglycemia (OR = 2.34, 95% CI [1.93–2.84]) and severe hyperglycemia (OR = 3.92, 95% CI [3.04–5.04]) were at elevated mortality risk and not hypoglycemia (OR = 1.12, 95% CI [0.60–2.08]). This relationship was consistent across different study years (P for interaction = 0.900).Conclusions:The relationship between admission glucose and in-hospital mortality differs for diabetic and nondiabetic patients. Hypoglycemia was a bad prognostic marker among diabetic patients alone. The study results could be used to guide risk assessment among AMI patients using admission glucose.Trial Registration:www.clinicaltrials.gov, NCT01624883; https://clinicaltrials.gov/ct2/show/NCT01624883

Survivin in breast lesions: immunohistochemical analysis of 196 cases.

We examined the survivin expression pattern by immunohistochemistry in 43 fibroadenomas and 153 ductal carcinomas of the breast. The subcellular localization of survivin and the intensity of immunoreaction were assessed. We analyzed the differences of survivin expression between fibroadenomas and carcinomas. We also correlated the survivin expression pattern in carcinomas with other clinicomorphological parameters such as the age of patients, the grade and size of primary tumor as well as the lymph node metastasis. Overall, survivin was detected in 107/153 carcinomas (69.9%) and in 26/43 fibroadenomas (60.5%). Statistical analysis confirmed significant correlations between the assessed parameters in fibroadenomas and carcinomas. Grade of carcinomas was significantly related to survivin expression in both subcellular localization and the intensity of immunoreaction. Tumor grade 3 was associated with nuclear positivity and combined nuclear and cytoplasmic localization. Carcinomas larger than 20 mm showed nuclear and combined localization in 81% of cases and higher intensity of survivin immunoreaction was also notably related to larger carcinomas. Statistically significant differences were also observed between subcellular survivin localization and intensity of immunoreaction. Our result suggest that nuclear accumulation of survivin is associated with proliferative fenotype and survivin was shown to be a worse prognostic marker in breast ductal carcinoma.

Fascin expression is inversely correlated with breast cancer metastasis suppressor 1 and predicts a worse survival outcome in node-negative breast cancer patients.

Background: Fascin is an actin-bundling protein that promotes cancer cell migration and invasion. By contrast, breast cancer metastasis suppressor 1 (BRMS1) inhibits cancer metastasis by targeting multiple steps of the metastatic cascade. We evaluated whether expression patterns of fascin and BRMS1 correlate with clinicopathological features and patient outcome.Methods: Immunohistochemistry for fascin and BRMS1 was performed using a tissue microarray constructed from 183 human breast cancer tissues. Fascin expression determined by the proportion of stained tumor cells (0: 0-5%, 1: 6-25%, 2: 26-50%, 3: 51-75%, or 4: >75%) and staining intensity (0: negative, 1: weak, 2: moderate, or 3: strong) were multiplied and defined as negative (0-3) or positive (4-12). BRMS1 expression was scored separately based on nuclear and cytoplasmic staining intensity (0: negative, 1: weak, 2: moderate, 3: strong). We obtained the BRMS1 H score by summing the nuclear and cytoplasmic scores and defined it as negative (0-2) or positive (3-6).Results: Expression of BRMS1 showed a significant inverse correlation with that of fascin. Fascin+ tumors were significantly associated with no lymph node metastasis, higher histological and higher nuclear grade, ER/PR/HER2 negativity, and triple-negative subtype (all ps < 0.05). These clinicopathological differences showed the same trend in a comparison of fascin-/BRMS1+ and fascin+/BRMS1- tumors. Negative or weak BRMS1 cytoplasmic expression was significantly associated with shorter disease-free survival (DFS; p = 0.043). Fascin positivity was significantly associated with shorter DFS (p = 0.005) and overall survival (p = 0.020) when analyses were confined to node-negative patients.Conclusions: This study confirms an inverse correlation between expression of fascin and expression of BRMS1 using a quite large cohort of human breast cancer tissues. Fascin alone or combined with BRMS1 was a worse prognostic marker, particularly in node-negative breast cancer patients.