Novel Biomarkers and Their Role in the Diagnosis and Prognosis of Acute Coronary Syndrome.

The burden of cardiovascular diseases and the critical role of acute coronary syndrome (ACS) in their progression underscore the need for effective diagnostic and prognostic tools. Biomarkers have emerged as crucial instruments for ACS diagnosis, risk stratification, and prognosis assessment. Among these, high-sensitivity troponin (hs-cTn) has revolutionized ACS diagnosis due to its superior sensitivity and negative predictive value. However, challenges regarding specificity, standardization, and interpretation persist. Beyond troponins, various biomarkers reflecting myocardial injury, neurohormonal activation, inflammation, thrombosis, and other pathways are being explored to refine ACS management. This review article comprehensively explores the landscape of clinically used biomarkers intricately involved in the pathophysiology, diagnosis, and prognosis of ACS (i.e., troponins, creatine kinase MB (CK-MB), B-type natriuretic peptides (BNP), copeptin, C-reactive protein (CRP), interleukin-6 (IL-6), d-dimers, fibrinogen), especially focusing on the prognostic role of natriuretic peptides and of inflammatory indices. Research data on novel biomarkers (i.e., endocan, galectin, soluble suppression of tumorigenicity (sST2), microRNAs (miRNAs), soluble oxidized low-density lipoprotein receptor-1 (sLOX-1), F2 isoprostanes, and growth differentiation factor 15 (GDF-15)) are further analyzed, aiming to shed light on the multiplicity of pathophysiologic mechanisms implicated in the evolution of ACS. By elucidating the complex interplay of these biomarkers in ACS pathophysiology, diagnosis, and outcomes, this review aims to enhance our understanding of the evolving trajectory and advancements in ACS management. However, further research is necessary to establish the clinical utility and integration of these biomarkers into routine practice to improve patient outcomes.

Endoscopic bariatric therapies for obesity: a review.

▪ Obesity is reaching pandemic proportions globally, with overweight or obesity affecting at least two-thirds of Australian adults. ▪ Bariatric surgery is an effective weight loss strategy but is constrained by high resource requirements and low patient acceptance. ▪ Multiple endoscopic bariatric therapies have matured, with well established and favourable safety and efficacy profiles in multiple randomised controlled trials (RCTs), and are best used within a multidisciplinary setting as an adjuvant to lifestyle intervention. ▪ Three types of intragastric balloon are currently in use in Australia offering average total weight loss ranging from 10% to 18%, with others available internationally. ▪ Endoscopic sleeve gastroplasty produces average total weight loss of 15-20% with low rates of severe complications, with RCT data anticipated in December 2021. ▪Bariatric and metabolic endoscopy is rapidly evolving, with many novel, promising therapies currently under investigation.

Concurrent Placements of a Duodenal-Jejunal Bypass Liner and an Intragastric Balloon Among Severely Obese Patients: A Case Series.

The duodenal-jejunal bypass liner and the intragastric balloon are endoscopically deployed devices used in the treatment of obesity and diabetes. These devices use differing mechanisms of action, and concurrent use may lead to improved efficacy. Three obese patients who suffered from weight loss plateau with the liner had the intragastric balloon inserted concurrently. All 3 patients reported subsequent significant weight loss. None of the patients reported any symptom that indicate the interference between the devices. This is the first case series in humans of successfully combining 2 independent endoscopic bariatric therapies to overcome weight loss plateau in the primary treatment of obesity.

Non-natriuretic peptide biomarkers in heart failure with preserved and reduced ejection fraction.

Heart failure (HF) with reduced and preserved ejection fraction constitutes two entities with distinct pathogenetic backgrounds sharing common features. Beyond natriuretic peptides, several novel biomarkers have been proven useful in the diagnosis, prognosis and treatment of HF. Biomarkers of myocardial fibrosis have a low diagnostic yield in subjects with acute HF but may add prognostic information, especially in patients with HF and preserved ejection fraction. Biomarkers of renal impairment identify subjects with worse prognosis independently of left ventricle ejection fraction while inflammatory markers have not been proven useful in patients with systolic or diastolic impairment. In this review article, we summarize the main differences and application of non-natriuretic peptide biomarkers in HF patients with preserved and reduced ejection fraction.

Endoscopic Sleeve Gastroplasty (ESG) Is a Reproducible and Effective Endoscopic Bariatric Therapy Suitable for Widespread Clinical Adoption: a Large, International Multicenter Study.

OBJECTIVE: Endoscopic sleeve gastroplasty (ESG), an incisionless endoscopic bariatric procedure, has shown impressive results in case series. This study examines the reproducibility, efficacy, and safety in three centers across two countries, and identifies key determinants for procedural success. DESIGN: Patients who underwent ESG between February 2016 and May 2017 at one of three centers (Australia and USA) were retrospectively analyzed. All procedures were performed on an outpatient basis using the Apollo OverStitch device (Apollo Endosurgery, Austin, TX). Primary outcomes included absolute weight loss (ΔWeight, kg), change in body mass index (∆BMI, in kg/m2), total body weight loss (TBWL, %), excess weight loss (EWL, in %), and immediate and delayed adverse events. RESULTS: In total, 112 consecutive patients (male 31%, age 45.1 ± 11.7 years, baseline BMI 37.9 ± 6.7 kg/m2) underwent ESG. At 1, 3, and 6 months, Δweight was 9.0 ± 4.6 kg (TBWL 8.4 ± 4.1%), 12.9 ± 6.4 kg (TBWL 11.9 ± 4.5%), and 16.4 ± 10.7 kg (TBWL 14.9 ± 6.1%), respectively. The proportion of patients who attained greater than 10% TBWL and 25% EWL was 62.2 and 78.0% at 3 months post-ESG and 81.0 and 86.5% at 6 months post-ESG. Weight loss was similar between the three centers. Multivariable analysis showed that male sex, greater baseline body weight, and lack of prior endoscopic bariatric therapy were predictors of greater Δweight at 6 months. Three (2.7%) severe adverse events were observed. CONCLUSIONS: ESG is an effective, reproducible, and safe weight loss therapy that is suitable for widespread clinical adoption.

Weight loss and improved quality of life with a nonsurgical endoscopic treatment for obesity: clinical results from a 3- and 6-month study.

BACKGROUND: The TransPyloric Shuttle™ (TPS) is a nonsurgical device that is endoscopically delivered to and removed from the stomach to treat obesity. The device consists of a large spherical bulb connected to a smaller cylindrical bulb by a flexible tether. The larger bulb prevents migration from the stomach, while the smaller bulb passes freely into the duodenum to position the TPS across the pylorus. Transpyloric positioning may delay gastric emptying, reducing caloric intake and enabling weight loss. The purpose of this feasibility study was to evaluate the safety and efficacy of the clinical procedure and device. METHODS: Twenty patients with a mean body mass index (BMI) of 36.0 kg/m(2) were assigned to 2 groups of 10 patients scheduled to have the device for 3 or 6 months. Primary outcomes included % excess weight loss (%EWL), % excess BMI loss (%EBMIL), % weight loss (%WL), and adverse events. RESULTS: Devices were deployed and retrieved in all patients with no complications. Three-month patients had mean %EWL of 25.1%, mean %EBMIL of 33.1%, and mean %WL of 8.9%. Six-month patients had mean %EWL of 41.0%, mean %EBMIL of 50.0%, and mean %WL of 14.5%. Early device removal occurred in 2 patients due to symptomatic gastric ulcerations, which resolved after device removal. CONCLUSIONS: The TPS is a promising technology that provides a, nonsurgical, ambulatory method for weight loss.

Management of minor medical problems and trauma: the role of general practice.

INTRODUCTION: It has been established that patients prefer receiving health information from primary care physicians. In Greece, recent reforms supporting urban primary healthcare have not been enacted, and long waiting times in Athens' emergency departments are common. AIM: To evaluate cases treated in the emergency department of a Greek general hospital and explore the potential role of primary care in managing these cases. METHODS: A total of 53,926 patients visited the emergency department studied during on-call days from February 2005 to February 2006. The cases were classified into 6 groups according to their main complaint: (1) internal medicine; (2) surgical; (3) orthopedic; (4) otorhinolaryngology (ENT); (5) eye disorders (ophthalmology); and (6) gynecology-obstetric. RESULTS: Of the 53,926 patients studied, 9167 (17%) came from a rural area. The internal medicine department was most commonly attended (15,373; 28.5%), followed by orthopedics (16.9%). In the surgical, ENT, ophthalmology and gynecology groups, almost one in three patients could have been managed by a GP, as could 40% of orthopedic cases. Orthopedic and ENT patients had the highest rate of X-rays performed. CONCLUSION: Many emergency patients visiting hospitals can be managed at the primary care level. The development of a 'practice-based curriculum' for GPs would be an excellent method to obtain higher professional standards.

The potential role of primary care in the management of common ear, nose or throat disorders presenting to the emergency department in Greece.

BACKGROUND: The aim of this study was to assess the prevalence of common ear, nose or throat (ENT) conditions presenting to emergency departments that could be managed by a primary healthcare system Method: Between January 2001 and January 2006 a total of 33 792 patients attended the ENT emergency department of one hospital. All cases were included in this retrospective study. The registry of ENT emergency department was analysed; age, sex and clinical diagnosis were tabulated. All patients were evaluated by a specialist. Classification of the cases was based on the main symptom seeking care. RESULTS: A total of 33 792 patients visited the otorhinolaryngology emergency department. Of these, 17 775 patients (52.6%) were men and 16 017 (47.4%) were women. Over 40% of the cases were classified in eight major groups of diagnosis. Acute tonsillitis (12.5%) and acute pharyngitis (11.4%) followed by acute otitis externa (5.9%) were the most common causes of all ENT emergency department visits. The admission rate was 1.2 % and only 0.6% (84) of patients were referred to other specialties. CONCLUSION: Most common ENT disorders presenting to the emergency department in Greece could be managed at the level of primary health care. Incorporating ENT expertise into educational and training programmes of general practitioners may be successful in managing ENT problems in primary care in future.

Avian flu: how informed are children in Greece?

OBJECTIVES: The current cluster of avian influenza outbreaks in birds has occurred in areas where humans live in proximity to poultry. Dissemination of accurate information may be the cornerstone for proper community preparation. In the herein presented study, we attempted to asses the information level among Greek children regarding avian flu. METHODS: A descriptive study was carried out in 2006 in ten Greek prefectures to determine the information level among students about transmission ways, symptoms and prevention measures of avian flu. RESULTS: A total of 1400 Greek students participated in the study. Approximately 75% of the students reported to know what bird flu is and 53% reported to know that there has been at least one case of avian flu in Greece. More than half (55.6%) reported that an effective vaccine against avian flu does exist; of the students asked, 47% reported that avian flu can be transmitted from human to human whereas 21.4% believed that humans can suffer from avian flu. Media contribution in providing information was very high among students. CONCLUSION: The level of information about avian flu among Greek students was found inadequate especially in some questions regarding serious aspects of avian flu. This study highlights the need for adaptation of health programs in Greek schools, which should include the provision of accurate information.

Primary care in the management of common orthopaedic problems.

BACKGROUND: Improving national healthcare services through the enhancement of primary care, is a major challenge in many countries. AIM: To assess the prevalence of those orthopaedic cases that could be managed by a primary healthcare system. METHOD: Between January 2001 and January 2006 a total of 39 172 patients attended the orthopaedic emergency department (ED) of Laikon University Hospital. All cases were included in this retrospective study. The registry of the orthopaedic ED was analysed by age, sex and clinical diagnosis. All patients were evaluated by a specialist. Classification of the cases was based on the main symptom of those seeking care. RESULTS: A total of 39 172 patients visited the orthopaedic ED; 17 040 (43.5%) of these patients were stratified in six major groups of diagnosis. Back pain (17.1%) was the most common reason for seeking care in the orthopaedic ED, followed by ankle injuries (10.3%). The admission rate was 1.2%, and X-ray examination was necessary for 93.4% (15 220) of patients. CONCLUSION: This study confirms the widely held view that most cases attending the orthopaedic ED could have been managed by appropriately equipped primary care settings. In this context, the role of general practitioners should be re-appraised and strengthened.

Assessing the level of awareness of avian influenza among Greek students.

INTRODUCTION: Current concern regarding avian influenza, the so-called 'bird flu', concerns H5N1, a highly pathogenic avian influenza form that has spread across Asia, into Western Europe and Africa. The wide spread of bird flu makes it a serious threat to humans. A key factor in reducing the risk of an influenza pandemic is adequate preparedness, including providing prospective, accurate information to the public. In our study, we attempted to assess the level of information among Greek students aged 8 to 15 years, regarding avian influenza. METHODS: A descriptive study was carried out in 6 Greek prefectures to determine the information level regarding avian influenza among students, concerning methods of transmission, symptoms and prevention measures. RESULTS: In total, 2805 Greek students participated in the study (47% male and 53% female). Approximately 90% of the students reported knowing what 'bird flu' is, and 25% wrongly answered that there had been at least one human infection from avian influenza in Greece. Nearly half the students (46.2%) reported that an effective vaccine exists against avian influenza, and almost all the study participants (95.7%) believed that they should not touch an ill or dead bird. Forty-two per cent of the students reported that avian influenza can be transmitted from human to human, and only 11.9% believed that humans can present symptoms after being infected. The media was their main source of information. CONCLUSION: The level of information about avian influenza among Greek students was found to be satisfactory, if not ideal. These findings, along with the potential for a future avian influenza pandemic, highlight the need for intensified health education programs in Greek schools, in order to deal with this serious public health problem.

Endovascular repair of a type III thoracoabdominal aortic aneurysm in a patient with occlusion of visceral arteries.

The successful endovascular repair of a type III thoracoabdominal aortic aneurysm (TAAA) with the use of a tube endograft is reported. A 56-year-old male with a 6.4-cm type III TAAA, a 4.2-cm infrarenal abdominal aortic aneurysm, and chronic renal insufficiency presented with flank pain, nausea, acute anuria, and serum creatinine of 6.1 mg/dl. Acute occlusion of the left solitary renal artery was diagnosed and emergent recanalization with percutaneous transluminal angioplasty and stenting was performed successfully, with reversal of the serum creatinine level at 1.6 mg/dl. Further imaging studies for TAAA management revealed ostial occlusion of both the celiac artery (CA) and the superior mesenteric artery (SMA) but a hypertrophic inferior mesenteric artery (IMA) providing retrograde flow to the aforementioned vessels. This rare anatomic serendipity allowed us to repair the TAAA simply by using a two-component tube endograft without fenestrations (Zenith; William Cook, Bjaeverskov, Denmark) that covered the entire length of the aneurysm, including the CA and SMA origins, since a natural arterial bypass from the IMA to the CA and SMA already existed, affording protection from gastrointestinal ischemic complications. The patient had a fast and uneventful recovery and is currently doing well 6 months after the procedure. To our knowledge, this is the first report in the English literature of successful endovascular repair of a TAAA involving visceral arteries with the simple use of a tube endograft.

Pre-ejection tissue-Doppler velocity changes during low dose dobutamine stress predict segmental myocardial viability.

INTRODUCTION: We tested the hypothesis that low dose dobutamine stress echocardiography (LDDSE) combined with tissue Doppler imaging (TDI) can be used for the quantitative assessment of the content of viable myocardium. METHODS: Forty-one patients with coronary artery disease and left ventricular dysfunction (ejection fraction < or =40%), already scheduled for revascularisation, underwent echocardiographic assessment of viability at rest and during low-dose dobutamine infusion (2.5 microg/kg/min up to 10 micro/kg/min) at two time points, 2 days before and 3 months after revascularisation. Pulsed-wave TDI was performed at rest and during LDDSE; ejection (Ej), pre-ejection (pre-Ej) and diastolic velocities (Ea, Aa) were recorded at rest and at 10 microg/kg/min dobutamine infusion. Recovery of regional function was defined as improvement of one or more grades 3 months post-revascularisation. RESULTS: A total of 112 vessels were revascularised. Out of 492 segments, 274 segments were characterised as viable and the remaining 218 as non-viable, according to postoperative functional myocardial recovery. Conventional qualitative LDDSE showed a sensitivity of 78% and specificity of 85% in predicting myocardial recovery. Ej, pre-Ej and Ea velocities increased significantly during LDDSE, while Aa velocity did not change significantly. Using ROC curves, the optimal cut-off value for viability assessment was an increase of 0.5 cm/s in Ej during LDDSE (80% sensitivity and 88% specificity, area under the curve 0.801), 0.6 cm/s in pre-Ej (91% sensitivity and 90% specificity, area under the curve 0.890), and 0.44 cm/s in Ea velocity (80% sensitivity and 81% specificity, area under the curve 0.780). CONCLUSIONS: Despite its technical limitations, the measurement of ejection and pre-ejection velocities during dobutamine stimulation appears to be an effective way of predicting myocardial segmental recovery following reperfusion.

Circadian variation in expression of G1 phase cyclins D1 and E and cyclin-dependent kinase inhibitors p16 and p21 in human bowel mucosa.

AIM: To evaluate whether the cellular proliferation rate in the large bowel epithelial cells is characterized by circadian rhythm. METHODS: Between January 2003 and December 2004, twenty patients who were diagnosed as suffering from primary, resectable, non-metastatic adenocarcinoma of the lower rectum, infiltrating the sphincter mechanism, underwent abdominoperineal resection, total mesorectal excision and permanent left iliac colostomy. In formalin-fixed and paraffin-embedded biopsy specimens obtained from the colostomy mucosa every six hours (00:00, 06:00, 12:00, 18:00 and 24:00), we studied the expression of G(1) phase cyclins (D(1) and E) as well as the expression of the G(1) phase cyclin-dependent kinase (CDK) inhibitors p16 and p21 as indicators of cell cycle progression in colonic epithelial cells using immunohistochemical methods. RESULTS: The expression of both cyclins showed a similar circadian fashion obtaining their lowest and highest values at 00:00 and 18:00, respectively (P<0.001). A circadian rhythm in the expression of CDK inhibitor proteins p16 and p21 was also observed, with the lowest levels obtained at 12:00 and 18:00 (P<0.001), respectively. When the complexes cyclins D(1) -p21 and E-p21 were examined, the expression of the cyclins was adversely correlated to the p21 expression throughout the day. When the complexes the cyclins D(1) -p16 and E-p16 were examined, high levels of p16 expression were correlated to low levels of cyclin expression at 00:00, 06:00 and 24:00. Meanwhile, the highest expression levels of both cyclins were correlated to high levels of p16 expression at 18:00. CONCLUSION: Colonic epithelial cells seem to enter the G(1) phase of the cell cycle during afternoon (between 12:00 and 18:00) with the highest rates obtained at 18:00. From a clinical point of view, the present results suggest that G(1) -phase specific anticancer therapies in afternoon might maximize their anti-tumor effect while minimizing toxicity.

Predicting sustained virological responses in chronic hepatitis C patients treated with peginterferon alfa-2a (40 KD)/ribavirin.

BACKGROUND/AIMS: Prediction of sustained virological response (SVR) during treatment would allow clinicians to identify patients most likely to benefit from therapy. METHODS: Retrospective analysis of data from 1121 adults with chronic hepatitis C treated for 48 weeks with peginterferon alfa-2a (40 KD) 180 microg/week plus placebo or ribavirin (1000/1200 mg/day), or interferon alfa-2b 3 MIU three times/week plus ribavirin in a randomized, multinational, study. RESULTS: 67% of patients treated with peginterferon alfa-2a (40 KD)/ribavirin with early virological responses (HCV RNA negative or > or = 2 log10 decrease) at week 12 had SVRs at week 72 (HCV RNA < 50 IU/mL). The negative predictive value (NPV) was 97%. The probability of an SVR increased with the rapidity of HCV RNA suppression. The highest SVR rates were achieved in patients with rapid virological responses at week 4, but the corresponding NPV (74%) is too low for a decision criterion. In patients with early virological responses by week 12, the SVR rate was approximately 20% lower in those who received <80% compared with patients who received > or = 80% of the planned ribavirin dose. CONCLUSIONS: Early, sustained suppression of HCV replication portends an SVR. Cessation of treatment may be contemplated in patients without a > or = 2 log10 reduction in HCV RNA after 12 weeks.

Prevalence of production of virus-specific interferon-gamma among seronegative hepatitis C-resistant subjects reporting injection drug use.

This report describes subjects who were highly likely to have been repeatedly exposed to hepatitis C virus (HCV) through injection drug use and who remained negative for anti-HCV antibody. Production of virus-specific interferon- gamma by peripheral blood mononuclear cells was seen in the majority of subjects (72%) and was associated with higher-risk behavior. For 92% of the subjects, results of recombinant immunoblot assays demonstrated faint bands against nonstructural proteins. The immune responses described are likely to have been primed and maintained by episodes of subclinical infection without classic seroconversion and may indicate a hepatitis C-resistant phenotype. Vaccine strategies to mimic this response may provide protection against persistent HCV infection.

Clearance of hepatitis C viremia associated with cellular immunity in the absence of seroconversion in the hepatitis C incidence and transmission in prisons study cohort.

Understanding the earliest virological and immunological events in acute hepatitis C virus (HCV) infection may provide insight into the determinants of protective immunity. Four cases of HCV viremia with subsequent viral clearance, but without biochemical hepatitis or anti-HCV seroconversion, are reported from a prospective cohort study of prison inmates. Two of the subjects who developed sustained viremia were assessed for production of interferon (IFN)- gamma, by use of the enzyme-linked immunospot (ELISPOT) method and by assessment of HCV cytotoxic T lymphocyte (CTL) activity, CD4 lymphocyte proliferative responses, HCV load, and genotype. After 2-6 months of viremia, all 4 subjects cleared serum HCV RNA. Specific cellular responses were detected in both of the subjects who were assessed, and production of IFN- gamma was demonstrated in one subject. All subjects had weak, but consistent, serological reactivity against HCV nonstructural proteins on immunoblot testing, despite repeatedly nonreactive HCV ELISA tests. These cases highlight the potential for cellular immune responses against HCV to facilitate viral clearance, responses that may model those required for effective HCV vaccination.

The impact of peginterferon alfa-2a plus ribavirin combination therapy on health-related quality of life in chronic hepatitis C.

BACKGROUND/AIMS: Peginterferon alfa-2a plus ribavirin improves sustained virological responses compared with interferon alfa-2b and ribavirin, or peginterferon alfa-2a alone in chronic hepatitis C. We examined the impact of these treatments on health related quality of life (HRQOL). METHODS: Patients (n=1121) were randomized to peginterferon alfa-2a weekly plus ribavirin or placebo, or interferon alfa-2b thrice weekly plus ribavirin. HRQOL was assessed with the SF-36 Health Survey and Fatigue Severity Scale (FSS). RESULTS: Patients receiving peginterferon alfa-2a plus ribavirin reported better HRQOL than those receiving interferon alfa-2b plus ribavirin. These differences were statistically significant for three SF-36 domains and both FSS scores (p<=0.05). Patients receiving peginterferon alfa-2a plus placebo had the least impairment; adding ribavirin significantly decreased five domains of the SF-36 and both FSS scores. Sustained virological response was associated with improvement at follow-up on all SF-36 and FSS scores. CONCLUSIONS: The effects of combination therapy on HRQOL and fatigue are less with peginterferon alfa-2a plus ribavirin than interferon alfa-2b plus ribavirin. Each medication in combination therapy with interferon and ribavirin, affects patients' quality of life differently. Understanding the relationship of specific therapeutic options to HRQOL may help physicians minimize the impact of therapy on HRQOL.

Expression of the chemokine IP-10 (CXCL10) by hepatocytes in chronic hepatitis C virus infection correlates with histological severity and lobular inflammation.

The factors influencing lymphocyte trafficking to the liver lobule during chronic hepaititis C virus (HCV) infection are currently not well defined. Interferon-gamma-inducible protein 10 (IP-10), a chemokine that recruits activated T lymphocytes, has recently been shown by in situ hybridization to be expressed in the liver during chronic HCV infection. This study sought to define the cellular source of IP-10 in the liver by immunohistochemistry, to examine the expression of its receptor, CXCR3, on T lymphocytes isolated from blood and liver tissue, and to correlate IP-10 expression with the histological markers of inflammation and fibrosis. IP-10 was expressed by hepatocytes but not by other cell types within the liver, and the most intense immunoreactivity was evident in the areas of lobular inflammation. The IP-10 receptor was expressed on a significantly higher proportion of T lymphocytes in the liver compared with blood. CD8 T lymphocytes, which predominate in the liver lobule, were almost uniformly CXCR3-positive. The expression of IP-10 mRNA correlated with lobular necroinflammatory activity but not with inflammation or fibrosis in the portal tracts. These findings suggest that IP-10 may be induced by HCV within hepatocytes and may be important in the pathogenesis of chronic HCV infection, as recruitment of inflammatory cells into the lobule is an important predictor of disease progression.