Integrative Bioinformatics-Gene Network Approach Reveals Linkage between Estrogenic Endocrine Disruptors and Vascular Remodeling in Peripheral Arterial Disease.

Vascular diseases, including peripheral arterial disease (PAD), pulmonary arterial hypertension, and atherosclerosis, significantly impact global health due to their intricate relationship with vascular remodeling. This process, characterized by structural alterations in resistance vessels, is a hallmark of heightened vascular resistance seen in these disorders. The influence of environmental estrogenic endocrine disruptors (EEDs) on the vasculature suggests a potential exacerbation of these alterations. Our study employs an integrative approach, combining data mining with bioinformatics, to unravel the interactions between EEDs and vascular remodeling genes in the context of PAD. We explore the molecular dynamics by which EED exposure may alter vascular function in PAD patients. The investigation highlights the profound effect of EEDs on pivotal genes such as ID3, LY6E, FOS, PTP4A1, NAMPT, GADD45A, PDGF-BB, and NFKB, all of which play significant roles in PAD pathophysiology. The insights gained from our study enhance the understanding of genomic alterations induced by EEDs in vascular remodeling processes. Such knowledge is invaluable for developing strategies to prevent and manage vascular diseases, potentially mitigating the impact of harmful environmental pollutants like EEDs on conditions such as PAD.

Gender Differences in Hospital Outcomes among COVID-19 Hospitalizations.

OBJECTIVES: Many epidemiological studies have shown that coronavirus disease 2019 (COVID-19) disproportionately affects males, compared with females, although other studies show that there were no such differences. The aim of the present study was to assess differences in the prevalence of hospitalizations and in-hospital outcomes between the sexes, using a larger administrative database. METHODS: We used the 2020 California State Inpatient Database for this retrospective analysis. International Classification of Diseases, Tenth Revision, Clinical Modification diagnosis code U07.1 was used to identify COVID-19 hospitalizations. These hospitalizations were subsequently stratified by male and female sex. Diagnosis and procedures were identified using the International Classification of Diseases, Tenth Revision, Clinical Modification codes. The primary outcome of the study was hospitalization rate, and secondary outcomes were in-hospital mortality, prolonged length of stay, vasopressor use, mechanical ventilation, and intensive care unit (ICU) admission. RESULTS: There were 95,180 COVID-19 hospitalizations among patients 18 years and older, 52,465 (55.1%) of which were among men and 42,715 (44.9%) were among women. In-hospital mortality (12.4% vs 10.1%), prolonged length of hospital stays (30.6% vs 25.8%), vasopressor use (2.6% vs 1.6%), mechanical ventilation (11.8% vs 8.0%), and ICU admission rates (11.4% versus 7.8%) were significantly higher among male compared with female hospitalizations. Conditional logistic regression analysis showed that the odds of mortality (odds ratio [OR] 1.38, 95% confidence interval [CI] 1.38-1.44), hospital lengths of stay (OR 1.35, 95% CI 1.31-1.39), vasopressor use (OR 1.59, 95% CI 1.51-1.66), mechanical ventilation (OR 1.62, 95% CI 1.47-1.78), and ICU admission rates (OR 1.58, 95% CI 1.51-1.66) were significantly higher among male hospitalizations. CONCLUSION: Our findings show that male sex is an independent and strong risk factor associated with COVID-19 severity.

Prevalence and effects of acute myocardial infarction on hospital outcomes among COVID-19 patients.

BACKGROUND: Acute myocardial infarction (AMI) is one of the most lethal complications of COVID-19 hospitalization. In this study, we looked for the occurrence of AMI and its effects on hospital outcomes among COVID-19 patients. METHODS: Data from the 2020 California State Inpatient Database was used retrospectively. All COVID-19 hospitalizations with age ≥ 18 years were included in the analyses. Adverse hospital outcomes included in-hospital mortality, prolonged length of stay (LOS), vasopressor use, mechanical ventilation, and ICU admission. Prolonged LOS was defined as any hospital LOS ≥ 75th percentile. Multivariate logistic regression analyses were used to understand the strength of associations after adjusting for cofactors. RESULTS: Our analysis had 94 114 COVID-19 hospitalizations, and 1548 (1.6%) had AMI. Mortality (43.2% vs. 10.8%, P  < 0.001), prolonged LOS (39.9% vs. 28.2%, P  < 0.001), vasopressor use (7.8% vs. 2.1%, P  < 0.001), mechanical ventilation (35.0% vs. 9.7%, P  < 0.001), and ICU admission (33.0% vs. 9.4%, P  < 0.001) were significantly higher among COVID-19 hospitalizations with AMI. The odds of adverse outcomes such as mortality (aOR 3.90, 95% CI: 3.48-4.36), prolonged LOS (aOR 1.23, 95% CI: 1.10-1.37), vasopressor use (aOR 3.71, 95% CI: 3.30-4.17), mechanical ventilation (aOR 2.71, 95% CI: 2.21-3.32), and ICU admission (aOR 3.51, 95% CI: 3.12-3.96) were significantly more among COVID-19 hospitalizations with AMI. CONCLUSION: Despite the very low prevalence of AMI among COVID-19 hospitalizations, the study showed a substantially greater risk of adverse hospital outcomes and mortality. COVID-19 patients with AMI should be aggressively treated to improve hospital outcomes.

Healthcare expenditure trends among adult stroke patients in the United States, 2011-2020.

BACKGROUND: In the US, between 2018 and 2019, approximately $57 billion were expended on stroke and related conditions. The aim of this study was to understand trends in direct healthcare expenditures among stroke patients using novel cost estimation methods and a nationally representative database. METHODS: This study was a retrospective analysis of 193,003 adults, ≥18 years of age, using the Medical Expenditure Panel Survey during 2009-2016. Manning and Mullahy's two-part model were used to calculate adjusted mean and incremental medical expenditures after adjusting for covariates. RESULTS: The mean (Standard Deviation) direct annual healthcare expenditure among stroke patients was $16,979.0 ($16,222.0- $17,736.0) and was nearly 3 times greater than non-stroke participants which were $5,039.7 ($4,951.0-$5,128.5) and were mainly spent on inpatient services, prescription medications, and office-based visits. Stroke patients had an additional healthcare expenditure of $4096.0 (3543.9, 4648.1) per person per year, compared to participants without stroke after adjusting for covariates (P<0.001). The total mean annual direct healthcare expenditure for stroke survivors increased from $16,142.0 (15,017.0-17,267.0) in 2007-2008 to $16,979.0 (16,222.0-17,736.0) in 2015-2016. CONCLUSION: Our study showed that stroke survivors had significantly greater healthcare expenses, compared to non-stroke individuals, mainly due to higher expenditures on inpatient services, prescription drugs, and office visits. These findings are concerning because the prevalence of stroke is projected to increase due to aging population and increased survival rates.

Adverse Outcomes in Hospitalizations for Amyloid-Related Heart Failure.

Transthyretin amyloid cardiomyopathy is being increasingly recognized as an important cause of heart failure (HF). In this study, we looked at adverse outcomes in hospitalizations with amyloid-related HF. This study was a retrospective analysis of the National Inpatient Sample data, collected from 2016 to 2019. Patients ≥41 years of age and admitted for HF were included in the study. In these hospitalizations, amyloid-related HF was identified through the International Classification of Diseases, Tenth Revision, Clinical Modification codes for amyloidosis. The primary outcome of the study was in-hospital mortality, whereas secondary outcomes were prolonged length of stay, mechanical ventilation, mechanical circulatory support, vasopressors use, and dispositions other than home. From 2016 to 2019, there were 4,705,274 HF hospitalizations, of which 16,955 (0.4%) had amyloid cardiomyopathy. In all HF hospitalizations, amyloid-related increased from 0.26% in 2016 to 0.46% in 2019 (relative increase, 76.9%, P for trend <0.001). Amyloid-related HF hospitalizations were more common in older, male, and Black patients. The odds of in-hospital mortality (odds ratio [OR], 1.29; 95% confidence interval [CI]: 1.11 to 1.38), prolonged hospital length (OR, 1.61; 95% CI: 1.49 to 1.73) and vasopressors use (OR, 1.59; 95% CI: 1.23 to 2.05) were significantly higher for amyloid-related hospitalizations. Amyloid-related HF hospitalizations are increasing substantially and are associated with adverse hospital outcomes. These hospitalizations were disproportionately higher for older, male, and Black patients. Amyloid-related HF is rare and underdiagnosed yet has several adverse outcomes. Hence, healthcare providers should be watchful of this condition for early identification and prompt management.

Effect of Frailty on Hospital Outcomes Among Pediatric Cancer Patients in the United States: Results From the National Inpatient Sample.

BACKGROUND: Studies on frailty among pediatric patients with cancer are scarce. In this study, we sought to understand the effects of frailty on hospital outcomes in pediatric patients with cancer. METHODS: This retrospective study used data collected and stored in the Nationwide Inpatient Sample (NIS) between 2005 and 2014. These were hospitalized patients and hence represented the sickest group of patients. Frailty was measured using the frailty definition diagnostic indicator by Johns Hopkins Adjusted Clinical Groups. RESULTS: Of 187,835 pediatric cancer hospitalizations included in this analysis, 11,497 (6.1%) were frail. The average hospitalization costs were $86,910 among frail and $40,358 for nonfrail patients. In propensity score matching analysis, the odds of in-hospital mortality (odds ratio, 2.08; 95% CI, 1.71-2.52) and length of stay (odds ratio, 3.76; 95% CI, 3.46-4.09) were significantly greater for frail patients. The findings of our study suggest that frailty is a crucial clinical factor to be considered when treating pediatric cancer patients in a hospital setting. CONCLUSIONS: These findings highlight the need for further research on frailty-based risk stratification and individualized interventions that could improve outcomes in frail pediatric cancer patients. The adaptation and validation of a frailty-defining diagnostic tool in the pediatric population is a high priority in the field.

Prevalence and trends of perioperative major adverse cardiovascular and cerebrovascular events during cancer surgeries.

Major adverse cardiovascular and cerebrovascular events (MACCE) is an important cause of morbidity and mortality during perioperative period. In this study, we looked for national trends in perioperative MACCE and its components as well as cancer types associated with high rates of perioperative MACCE during major cancer surgeries. This study was a retrospective analysis of the National Inpatient Sample, 2005-2014. Hospitalizations for surgeries of prostate, bladder, esophagus, pancreas, lung, liver, colorectal, and breast among patients 40 years and greater were included in the analysis. MACCE was defined as a composite measure that included in-hospital all-cause mortality, acute myocardial infarction (AMI), and ischemic stroke. A total of 2,854,810 hospitalizations for major surgeries were included in this study. Of these, 67,316 (2.4%) had perioperative MACCE. Trends of perioperative MACCE showed that it decreased significantly for AMI, death and any MACCE, while stroke did not significantly change during the study period. Logistic regression analysis for perioperative MACCE by cancer types showed that surgeries for esophagus, pancreas, lung, liver, and colorectal cancers had significantly greater odds for perioperative MACCE. The surgeries identified to have greater risks for MACCE in this study could be risk stratified for better informed decision-making and management.

Difference in 30-Day Readmission Rates After Laparoscopic Sleeve Gastrectomy Versus Laparoscopic Roux-En-Y Gastric Bypass: a Propensity Score Matched Study Using ACS NSQIP Data (2015-2019).

PURPOSE: There are very few studies that have compared the short-term outcomes of laparoscopic Roux-en-Y gastric bypass (LRYGB) and laparoscopic sleeve gastrectomy (LSG). Among short-term outcomes, hospital readmission after these procedures is an area for quality enhancement and cost reduction. In this study, we compared 30-day readmission rates after LSG and LRYGB through analyzing a nationalized dataset. In addition, we identified the reasons of readmission. MATERIALS AND METHODS: The current study was a retrospective analysis of data from National Surgical Quality Improvement Program (NSQIP) All adult patients, ≥ 18 years of age and who had LSG or LRYGB during 2014 to 2019 were included. Current Procedural Terminology (CPT) codes were used to identify the procedures. Multivariate logistic regressions were used to calculate propensity score adjusted odds ratios (ORs) for all cause 30-day re-admissions. RESULTS: There were 109,900 patients who underwent laparoscopic bariatric surgeries (67.5% LSG and 32.5% LRYGB). Readmissions were reported in 4168 (3.8%) of the patients and were more common among RYGB recipients compared to LSG (5.6% versus 2.9%, P < 0.001). The odds of 30-day readmissions were significantly higher among LRYGB group compared to LSG group (AOR, 2.20; 95% CI; 1.83, 2.64). In addition, variables such as age, chronic obstructive pulmonary disease, hypertension, bleeding disorders, blood urea nitrogen, SGOT, alkaline phosphatase, hematocrit, and operation time were significantly predicting readmission rates. CONCLUSIONS: Readmission rates were significantly higher among those receiving LRYGB, compared to LSG. Readmission was also affected by many patient factors. The factors could help patients and providers to make informed decisions for selecting appropriate procedures.

Burden of maternal and fetal outcomes among pregnant cancer survivors during delivery hospitalizations in the United States.

Existing studies on pregnancy-related outcomes among cancer survivors are limited by sample size or specificity of the cancer type. This study estimated the burden of adverse maternal and fetal outcomes among pregnant cancer survivors using a national database. This study was a retrospective analysis of National Inpatient Sample collected during 2010-2014. Multivariate regression models were used to calculate odds ratios for maternal and fetal outcomes. The study included a weighted sample of 64,506 pregnant cancer survivors and 18,687,217 pregnant women without cancer. Pregnant cancer survivors had significantly higher odds for death during delivery hospitalization, compared to pregnant women without cancer (58 versus 5 deaths per 100,000 pregnancies). They also had higher odds of severe maternal morbidity (aOR 2.00 [95% CI 1.66-2.41]), cesarean section (aOR 1.27 [95% CI 1.19-1.37]), labor induction (aOR 1.17 [95% CI 1.07-1.29]), pre-eclampsia (aOR 1.18 [95% CI 1.02-1.36]), preterm labor (aOR 1.55 [95% CI 1.36-1.76]), chorioamnionitis (aOR 1.45 [95% CI 1.15-1.82]), postpartum infection (aOR 1.68 [95% CI 1.21-2.33]), venous thromboembolism (aOR 3.62 [95% CI 2.69-4.88]), and decreased fetal movements (aOR 1.67 [95% CI 1.13-2.46]). This study showed that pregnancy among cancer survivors constitutes a high-risk condition requiring advanced care and collective efforts from multiple subspecialties.

Stroke Genomics: Current Knowledge, Clinical Applications and Future Possibilities.

The pathophysiology of stoke involves many complex pathways and risk factors. Though there are several ongoing studies on stroke, treatment options are limited, and the prevalence of stroke is continuing to increase. Understanding the genomic variants and biological pathways associated with stroke could offer novel therapeutic alternatives in terms of drug targets and receptor modulations for newer treatment methods. It is challenging to identify individual causative mutations in a single gene because many alleles are responsible for minor effects. Therefore, multiple factorial analyses using single nucleotide polymorphisms (SNPs) could be used to gain new insight by identifying potential genetic risk factors. There are many studies, such as Genome-Wide Association Studies (GWAS) and Phenome-Wide Association Studies (PheWAS) which have identified numerous independent loci associated with stroke, which could be instrumental in developing newer drug targets and novel therapies. Additionally, using analytical techniques, such as meta-analysis and Mendelian randomization could help in evaluating stroke risk factors and determining treatment priorities. Combining SNPs into polygenic risk scores and lifestyle risk factors could detect stroke risk at a very young age and help in administering preventive interventions.

Relationship between insurance status and interhospital transfers among cancer patients in the United States.

BACKGROUND: The relationship between insurance status and interhospital transfers has not been adequately researched among cancer patients. Hence this study aimed for understanding this relationship using a nationally representative database. METHODS: A retrospective analysis was conducted using National Inpatient Sample (NIS) data collected during 2010-2016 and included all cancer hospitalization between 18 and 64 years of age. Interhospital transfers were compared based on insurance status (Medicare, Medicaid, private, and uninsured). Weighted multivariable logistic regressions were used to calculate the odds of interhospital transfers based on insurance status, after adjusting for many covariates. RESULTS: There were 3,580,908 weighted cancer hospitalizations, of which 72,353 (2.02%) had interhospital transfers. Uninsured patients had significantly higher rates of interhospital transfers, compared to those with Medicare (P = 0.005) and private insurance (P < 0.001). Privately insured patients had significantly lower rates of interhospital transfers, compared to those with Medicare (P < 0.001) and Medicaid (P < 0.001). Logistic regression analyses showed that the odds of having interhospital transfers were significantly higher among uninsured (adjusted odds ratio [aOR], 1.57, 95% CI: 1.45-1.69), Medicare (aOR, 1.38, 95% CI: 1.32-1.45) and Medicaid (aOR, 1.23, 95% CI: 1.16-1.30) patients when compared to those with private insurance coverages. CONCLUSION: Among cancer patients, uninsured and Medicare and Medicaid beneficiaries were more likely to experience interhospital transfers. In addition to medical reasons, factors such as affordability and socioeconomic status are influencing interhospital transfer decisions, indicating existing healthcare disparities. Further studies should focus on identifying the causal associations between factors explored in this study as well as additional unexplored factors.

Association between vitamin D deficiency and hypothyroidism: results from the National Health and Nutrition Examination Survey (NHANES) 2007-2012.

PURPOSE: Many smaller studies have previously shown a significant association between thyroid autoantibody induced hypothyroidism and lower serum vitamin D levels. However, these finding have not been confirmed by large-scale studies. In this study, we evaluated the relationship between hypothyroidism and vitamin D levels using a large population-based data. METHODS: For this study, we used National Health and Nutrition Examination Survey (NHANES) during the years 2007-2012. We categorized participants into three clinically relevant categories based on vitamin D levels: optimal, intermediate and deficient. Participants were also split into hypothyroid and hyperthyroid. Weighted multivariable logistic regression analyses were used to calculate the odds of being hypothyroid based on vitamin D status. RESULTS: A total of 7943 participants were included in this study, of which 614 (7.7%) were having hypothyroidism. Nearly 25.6% of hypothyroid patients had vitamin D deficiency, compared to 20.6% among normal controls. Adjusted logistic regression analyses showed that the odds of developing hypothyroidism were significantly higher among patients with intermediate (adjusted odds ratio [aOR], 1.7, 95% CI: 1.5-1.8) and deficient levels of vitamin D (aOR, 1.6, 95% CI: 1.4-1.9). CONCLUSION: Low vitamin D levels are associated with autoimmune hypothyroidism. Healthcare initiatives such as mass vitamin D deficiency screening among at-risk population could significantly decrease the risk for hypothyroidism in the long-term.

Emerging Evidence on the Effects of Dietary Factors on the Gut Microbiome in Colorectal Cancer.

Dietary factors have important role in modulating the gut microbiome, which in-turn regulates the molecular events in colonic mucosa. The composition and resulting metabolism of the gut microbiome are decisive factors in colorectal cancer (CRC) tumorigenesis. Altered gut microbiome is associated with impaired immune response, and the release of carcinogenic or genotoxic substances which are the major microbiome-induced mechanisms implicated in CRC pathogenesis. Diets low in dietary fibers and phytomolecules as well as high in red meat are important dietary changes which predispose to CRC. Dietary fibers which reach the colon in an undigested form are further metabolized by the gut microbiome into enterocyte friendly metabolites such as short chain fatty acid (SCFA) which provide anti-inflammatory and anti-proliferative effects. Healthy microbiome supported by dietary fibers and phytomolecules could decrease cell proliferation by regulating the epigenetic events which activate proto-oncogenes and oncogenic pathways. Emerging evidence show that predominance of microbes such as Fusobacterium nucleatum can predispose the colonic mucosa to malignant transformation. Dietary and lifestyle modifications have been demonstrated to restrict the growth of potentially harmful opportunistic organisms. Synbiotics can protect the intestinal mucosa by improving immune response and decreasing the production of toxic metabolites, oxidative stress and cell proliferation. In this narrative review, we aim to update the emerging evidence on how diet could modulate the gut microbial composition and revive colonic epithelium. This review highlights the importance of healthy plant-based diet and related supplements in CRC prevention by improving the gut microbiome.

Deregulated Protein Kinases: Friend and Foe in Ischemic Stroke.

Ischemic stroke is the third leading cause of mortality worldwide, but its medical management is still limited to the use of thrombolytics as a lifesaving option. Multiple molecular deregulations of the protein kinase family occur during the period of ischemia/reperfusion. However, experimental studies have shown that alterations in the expression of essential protein kinases and their pharmacological modulation can modify the neuropathological milieu and hasten neurophysiological recovery. This review highlights the role of key protein kinase members and their implications in the evolution of stroke pathophysiology. Activation of ROCK-, MAPK-, and GSK-3ß-mediated pathways following neuronal ischemia/reperfusion injury in experimental conditions aggravate the neuropathology and delays recovery. Targeting ROCK, MAPK, and GSK-3ß will potentially enhance myelin regeneration, improve blood-brain barrier (BBB) function, and suppress inflammation, which ameliorates neuronal survival. Conversely, protein kinases such as PKA, Akt, PKCα, PKCε, Trk, and PERK salvage neurons post-ischemia by mechanisms including enhanced toxin metabolism, restoring BBB integrity, neurotrophic effects, and apoptosis suppression. Certain protein kinases such as ERK1/2, JNK, and AMPK have favourable and unfavourable effects in salvaging ischemia-injured neurons. Targeting multiple protein kinase-mediated pathways simultaneously may improve neuronal recovery post-ischemia.

Lipid Metabolite Biomarkers in Cardiovascular Disease: Discovery and Biomechanism Translation from Human Studies.

Lipids represent a valuable target for metabolomic studies since altered lipid metabolism is known to drive the pathological changes in cardiovascular disease (CVD). Metabolomic technologies give us the ability to measure thousands of metabolites providing us with a metabolic fingerprint of individual patients. Metabolomic studies in humans have supported previous findings into the pathomechanisms of CVD, namely atherosclerosis, apoptosis, inflammation, oxidative stress, and insulin resistance. The most widely studied classes of lipid metabolite biomarkers in CVD are phospholipids, sphingolipids/ceramides, glycolipids, cholesterol esters, fatty acids, and acylcarnitines. Technological advancements have enabled novel strategies to discover individual biomarkers or panels that may aid in the diagnosis and prognosis of CVD, with sphingolipids/ceramides as the most promising class of biomarkers thus far. In this review, application of metabolomic profiling for biomarker discovery to aid in the diagnosis and prognosis of CVD as well as metabolic abnormalities in CVD will be discussed with particular emphasis on lipid metabolites.

Biglycan: an emerging small leucine-rich proteoglycan (SLRP) marker and its clinicopathological significance.

Extracellular matrix (ECM) plays an important role in the structural organization of tissue and delivery of external cues to the cell. Biglycan, a class I small leucine-rich proteoglycans (SLRP), is a key component of the ECM that participates in scaffolding the collagen fibrils and mediates cell signaling. Dysregulation of biglycan expression can result in wide range of clinical conditions such as metabolic disorder, inflammatory disorder, musculoskeletal defects and malignancies. In this review, we aim to update our current understanding regarding the link between altered expression of biglycan and different clinicopathological states. Biglycan interacts with toll like receptors (TLR)-2 and TLR-4 on the immune cells which initiates inflammation and aggravates inflammatory disorders. ECM unbound soluble biglycan acts as a DAMP (danger associated molecular pattern) resulting in sterile inflammation. Dysregulation of biglycan expression is also observed in inflammatory metabolic conditions such as atherosclerosis and obesity. In cancer, high-biglycan expression facilitates tumor growth, invasion and metastasis which is associated with poor clinical outcome. As a pivotal structural component of the ECM, biglycan strengthens the musculoskeletal system and its absence is associated with musculoskeletal defects. Thus, SLRP biglycan is a potential marker which is significantly altered in different clinicopathological states.

Performance of a cardiac lipid panel compared to four prognostic scores in chronic heart failure.

The cardiac lipid panel (CLP) is a novel panel of metabolomic biomarkers that has previously shown to improve the diagnostic and prognostic value for CHF patients. Several prognostic scores have been developed for cardiovascular disease risk, but their use is limited to specific populations and precision is still inadequate. We compared a risk score using the CLP plus NT-proBNP to four commonly used risk scores: The Seattle Heart Failure Model (SHFM), Framingham risk score (FRS), Barcelona bio-HF (BCN Bio-HF) and Meta-Analysis Global Group in Chronic Heart Failure (MAGGIC) score. We included 280 elderly CHF patients from the Cardiac Insufficiency Bisoprolol Study in Elderly trial. Cox Regression and hierarchical cluster analysis was performed. Integrated area under the curves (IAUC) was used as criterium for comparison. The mean (SD) follow-up period was 81 (33) months, and 95 (34%) subjects met the primary endpoint. The IAUC for FRS was 0.53, SHFM 0.61, BCN Bio-HF 0.72, MAGGIC 0.68, and CLP 0.78. Subjects were partitioned into three risk clusters: low, moderate, high with the CLP score showing the best ability to group patients into their respective risk cluster. A risk score composed of a novel panel of metabolite biomarkers plus NT-proBNP outperformed other common prognostic scores in predicting 10-year cardiovascular death in elderly ambulatory CHF patients. This approach could improve the clinical risk assessment of CHF patients.

Lumican, pro-tumorigenic or anti-tumorigenic: A conundrum.

The extracellular matrix (ECM) consists of a myriad of structural and signaling molecules which potentially regulate cell function and homeostasis. Lumican, a class II SLRP (small leucine rich proteoglycan) is a ubiquitous ECM component which not only organizes the collagen based structural matrix, but also modulates cell proliferation signals as observed in cancer. In the perspective of cancer biology, lumican expression in the tumor microenvironment is associated with signaling, which can result in either pro-tumorigenic or anti-tumorigenic effects. Its pro-tumorigenic effects are mainly observed in gastric, bladder and liver cancers, which is associated with deterioration of clinical prognosis. Lumican mediated pro-tumorigenic effects involve activation of focal adhesion kinases (FAK), mitogen activated protein kinases (MAPK) and metalloproteinase-9 (MMP-9). On the contrary, in breast cancer, pancreatic cancer and melanoma, lumican demonstrates anti-tumorigenic effects, which are associated with favorable clinical outcomes. Anti-tumorigenic potential of lumican is clubbed with epithelial-mesenchymal transition reprogramming as well as downregulation of extracellular signal-regulated kinases (ERK), FAK and MMP-14 mediated pathways thereby preventing tumorigenesis. This review highlights that the expressional significance of lumican in cancer biogenesis is tumor specific and demands rigorous cancer-specific evaluation to understand its role as a potential anti-cancer target or a therapeutic molecule.