Serum prolactin levels and mortality in adults without prolactinoma: A meta-analysis.

PURPOSE: Prolactin is a highly versatile, multifunctional hormone synthesized and secreted by lactotroph cells of the anterior pituitary. Its metabolic role has been extensively studied even in normoprolactinemic populations. Recently, a wealth of observational data outlines the potential prognostic value of prolactin in various clinical settings. This systematic review aims to systematically evaluate and quantitatively synthesize the association between serum prolactin levels and risk of mortality in adults without prolactinoma. METHODS: A systematic literature search was conducted up to June 10, 2023 to identify studies reporting the association of serum prolactin levels with clinical outcomes of adults without prolactinoma. A random-effects meta-analysis was conducted to quantify the adjusted hazard ratios [(a)HRs] for all-cause and cardiovascular death during follow-up. RESULTS: Twenty-eight studies were deemed eligible reporting the outcomes of adults without prolactinoma, in whom serum prolactin levels were measured for risk-stratification. Fourteen studies reported appropriate data for meta-analysis encompassing a total of 23,596 individuals. Each unit of prolactin increase was independently associated with increased risk of all-cause (pooled aHR=1.17 [1.08-1.27]; I2=48%) and cardiovascular mortality (pooled aHR=1.54 [1.14-2.09]; I2=89%). Individuals belonging to the highest prolactin category had significantly higher risk for all-cause (pooled aHR=1.81 [1.43-2.30]; I2=65%) and cardiovascular (pooled aHR=1.59 [1.04-2.42]; I2=82%) mortality compared to their lowest prolactin category counterparts. The association between prolactin levels and in-hospital death did not reach statistical significance. CONCLUSIONS: Prolactin levels seem to be an independent predictor for mortality. Further validation is warranted before its role as a risk stratification tool can be delineated in clinical practice.

Risk of arterial thromboembolism, bleeding and mortality in atrial fibrillation patients with comorbid cancer: A systematic review and meta-analysis.

AIMS: Atrial fibrillation (AF) and cancer often co-exist. Each has been associated with an increased risk of morbidity and mortality. The aim of this meta-analysis was to synthesize available data regarding the incidence of arterial thromboembolism (TE), bleeding, and all-cause mortality in patients with AF with or without cancer. METHODS: Literature search was conducted in PubMed, Ovid MEDLINE, WebOfScience, Scopus, CENTRAL, OpenGrey, and EThOS databases to identify studies that included patients with AF and accounted for cancer status with the incidence of TE (ischemic stroke, transient ischemic attack, or arterial thrombosis), major or clinically relevant non-major bleeding, and all-cause mortality. A random-effects meta-analysis was used. RESULTS: Overall, 17 studies were included (3,149,547 patients). The risk of TE was similar in patients with AF with comorbid cancer compared with that in AF alone (pooled odds ratio [pOR] 0.97, 95% Confidence Interval [CI] 0.85-1.11, I2 = 87%). Major or clinically relevant non-major bleeding (pOR 1.65, 95% CI 1.35-2.02, I2 = 98%) and all-cause death (pOR 2.17, 95% CI 1.83-2.56, I2 = 98%) were significantly higher in patients with AF with cancer than in patients with AF only. The history of TE and hypertension and mean age were significant moderators of TE risk. CONCLUSION: In patients with AF, the presence of cancer is associated with a similar risk of TE as well as an increased risk of bleeding and all-cause death compared with the absence of cancer.

Association of clinical, laboratory and imaging biomarkers with the occurrence of acute myocardial infarction in patients without standard modifiable risk factors - rationale and design of the "Beyond-SMuRFs Study".

BACKGROUND: Acute myocardial infarction (AMI) remains the leading cause of mortality worldwide. The majority of patients who suffer an AMI have a history of at least one of the standard modifiable risk factors (SMuRFs): smoking, hypertension, dyslipidemia, and diabetes mellitus. However, emerging scientific evidence recognizes a clinically significant and increasing proportion of patients presenting with AMI without any SMuRF (SMuRF-less patients). To date, there are no adequate data to define specific risk factors or biomarkers associated with the development of AMIs in these patients. METHODS: The ''Beyond-SMuRFs Study'' is a prospective, non-interventional cohort trial designed to enroll patients with AMI and no previous coronary intervention history, who undergo coronary angiography in two academic hospitals in Thessaloniki, Greece. The rationale of the study is to investigate potential relations between SMuRF-less AMIs and the clinical, laboratory and imaging profile of patients, by comparing parameters between patients with and without SMuRFs. Complete demographic and comprehensive clinical data will be recorded, Venous blood samples will be collected before coronary angiography and the following parameters will be measured: total blood count, standard biochemistry parameters, coagulation tests, hormone levels, glycosylated hemoglobin, N- terminal pro-B-type natriuretic peptide and high-sensitivity troponin T levels- as well as serum levels of novel atherosclerosis indicators and pro-inflammatory biomarkers. Furthermore, all participants will undergo a complete and comprehensive transthoracic echocardiographic assessment according to a pre-specified protocol within 24 h from admission. Among others, 2D-speckle-tracking echocardiographic analysis of cardiac chambers and non-invasive calculation of myocardial work indices for the left ventricle will be performed. Moreover, all patients will be assessed for angiographic parameters and the complexity of coronary artery disease using the SYNTAX score. Multivariable linear and logistic regression models will be used to phenotypically characterize SMuRF-less patients and investigate independent clinical, laboratory, echocardiographic and angiographic biomarkers-predictors of SMuRF-less status in AMI.The first patient was enrolled in March 2022 and completion of enrollment is expected until December 2023. DISCUSSION: The ''Beyond-SmuRFs'' study is an ongoing prospective trial aiming to investigate potential clinical, laboratory and imaging biomarkers associated with the occurrence of AMIs in SMuRF-less patients. The configuration of these patients' profiles could lead to the development of personalized risk-stratification models predicting the occurrence of cardiovascular events in SΜuRF-less individuals. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05535582 / September 10, 2022.

The Effect of Corticosteroids on Temporal Artery Biopsy Positivity in Giant Cell Arteritis: Timing is Everything.

OBJECTIVE: Temporal artery biopsy (TAB) remains the standard criterion for the diagnosis of giant cell arteritis (GCA). Temporal artery biopsy is suggested to be performed within 2 weeks from the initiation of corticosteroids. However, the effects of TAB timing on the sensitivity of its findings still warrant further investigation. METHODS: We reviewed the medical records of patients with GCA from a tertiary medical center in Germany over an 8-year period. RESULTS: We analyzed data from 109 patients with a median age of 76 years and a median time from glucocorticoid treatment to TAB of 4 days. Approximately 60% of biopsies were positive. Our analysis yielded a nonsignificant trend toward shorter duration of corticosteroid treatment in the TAB(+) group ( p = 0.06). A more than 7 days' duration of steroid treatment was independently linked with lower rates of positive TAB (adjusted odds ratio, 0.33; 95% confidence interval, 0.11-1.00). CONCLUSION: We conclude that the duration of corticosteroid treatment seems to affect the positivity of TAB in patients with suspected GCA. Further larger studies are required to confirm the generalizability of our findings.

Volumetric Tissue Imaging of Surgical Tissue Specimens Using Micro-Computed Tomography: An Emerging Digital Pathology Modality for Nondestructive, Slide-Free Microscopy-Clinical Applications of Digital Pathology in 3 Dimensions.

OBJECTIVES: Micro-computed tomography (micro-CT) is a novel, nondestructive, slide-free digital imaging modality that enables the acquisition of high-resolution, volumetric images of intact surgical tissue specimens. The aim of this systematic mapping review is to provide a comprehensive overview of the available literature on clinical applications of micro-CT tissue imaging and to assess its relevance and readiness for pathology practice. METHODS: A computerized literature search was performed in the PubMed, Scopus, Web of Science, and CENTRAL databases. To gain insight into regulatory and financial considerations for performing and examining micro-CT imaging procedures in a clinical setting, additional searches were performed in medical device databases. RESULTS: Our search identified 141 scientific articles published between 2000 and 2021 that described clinical applications of micro-CT tissue imaging. The number of relevant publications is progressively increasing, with the specialties of pulmonology, cardiology, otolaryngology, and oncology being most commonly concerned. The included studies were mostly performed in pathology departments. Current micro-CT devices have already been cleared for clinical use, and a Current Procedural Terminology (CPT) code exists for reimbursement of micro-CT imaging procedures. CONCLUSIONS: Micro-CT tissue imaging enables accurate volumetric measurements and evaluations of entire surgical specimens at microscopic resolution across a wide range of clinical applications.

Nanotherapy based on magneto-mechanochemical modulation of tumor redox state.

Magnetic nanoparticles (MNs) are typically used as contrast agents for magnetic resonance imaging or as drug carriers with a remotely controlled delivery to the tumor. However, they can also potentiate the action of anticancer drugs under the influence of applied constant magnetic (CMFs) and electromagnetic fields (EMFs). This review demonstrates the role of magneto-mechanochemical effects produced by MNs alone and loaded with anticancer agents (MNCs) in response to CMFs and EMFs for modulation of tumor redox state. The combined treatment is suggested to act by two mechanisms: spin-dependent electron transport propagates free radical chain reactions, while magnetomechanical interactions cause conformational changes in drug molecules loaded onto MNs and generate reactive oxygen species (ROS). By adjusting the parameters of CMFs and EMFs during the magneto-mechanochemical synthesis and subsequent treatment, it is possible to modulate ROS production and switch redox signaling involved in ERK1/2 and NF-κB pathways from initiation of tumor growth to inhibition. Observations of tumor volume in different animal models and treatment combinations reported a 6%-70% reduction as compared with conventional drugs. Despite these results, there is a general lack of research in magnetic nanotheranostics that link redox changes across multiple levels of organization in the tumor-bearing host. Further multidisciplinary studies with more focus on the relationship between the electron transport processes in biomolecules and their effects on the tumor-host interaction should accelerate the clinical translation of magnetic nanotheranostics. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease Therapeutic Approaches and Drug Discovery > Emerging Technologies Nanotechnology Approaches to Biology > Nanoscale Systems in Biology.

Sex-Related Differences in Clinical Outcomes in Patients with Atrial Fibrillation and Coronary Artery Disease: A Sub-Study of the MISOAC-AF Randomized Controlled Trial.

BACKGROUND: There is limited "real-world" data on the prognostic role of gender in comorbid atrial fibrillation (AF) and coronary artery disease (CAD). METHODS: In this post-hoc analysis of the MISOAC-AF randomized trial (NCT: 02941978), consecutive patients with AF and CAD who were discharged from the cardiology ward between 2015 and 2018 were included. Multivariable Cox-regression analysis was performed for all-cause mortality and cardiovascular (CV) mortality. Competing-risk analysis was performed for the outcomes of stroke or systemic embolism, major bleeding, AF- or heart failure (HF)-related hospitalization, adjusted for the competing risk of all-cause death. RESULTS: Of 1098 patients with AF, 461 patients with comorbid CAD were analyzed. Women were older and more likely to have a history of diabetes mellitus and valvular heart disease, while men were more likely to have a history of smoking or myocardial infarction. Over a median follow-up of 31 months, 143 (43.4%) men and 71 (53.7%) women died. Women were at a higher risk for all-cause mortality (adjusted hazard ration [aHR] 1.65; 95% confidence interval [CI] 1.14-2.38) and stroke or systemic embolism (aHR 3.52; 95% CI 1.46-8.49) compared to men. The risks of CV mortality, major bleeding, AF-related hospitalization, and HF-related hospitalization were similar between genders. CONCLUSIONS: In recently hospitalized patients with AF and comorbid CAD, the female gender was independently associated with increased all-cause mortality and thromboembolic events.

Angiogenesis in gastrointestinal stromal tumors: From bench to bedside.

Gastrointestinal stromal tumors (GISTs) are rare neoplasms with an estimated incidence from 0.78 to 1-1.5 patients per 100000. They most commonly occur in the elderly during the eighth decade of life affecting predominantly the stomach, but also the small intestine, the omentum, mesentery and rectosigmoid. The available treatments for GIST are associated with a significant rate of recurrent disease and adverse events. Thorough understanding of GIST's pathophysiology and translation of this knowledge into novel regimens or drug repurposing is essential to counter this challenge. The present review summarizes the existing evidence about the role of angiogenesis in GIST's development and progression and discusses its clinical underpinnings.

Prognostic value of combined preoperative phase angle and handgrip strength in cardiac surgery.

OBJECTIVES: Phase angle (PA) constitutes a bioelectrical impedance measurement, indicating cell membrane health and integrity, hydration, and nutritional status. Handgrip strength (HS) has been also associated with body composition, nutritional status, inflammation, and functional ability in several chronic diseases. Although their prognostic significance as independent biomarkers has been already investigated regarding the outcomes of a cardiac surgery, our study is the first one to assess the combined predictive value of preoperative PA and HS. DESIGN AND METHODS: HS and PA measurements were performed preoperativelyin 195 patients undergoing cardiac surgery. The association ofthe combination of HS and PAwith all-cause mortality rates was the primary study outcome, while its association with the intensive care unit (ICU) length of stay (LOS) was the secondary one. RESULTS: PA was positively correlated with HS (r = 0.446, p < 0.005) and negatively with EuroSCORE II (r = - 0.306 p < 0.005). The combination of PA < 5.15 and HS < 25.5 was associated with higher one-year all-cause mortality (OR = 9.28; 95% CI 2.50-34.45; p = 0.001) compared to patients with PA > 5.15 and HS > 25.5, respectively. Patients with combined lower values of PA and HS (PA < 5.15 and HS < 30.7) were at higher risk of prolonged ICU LOS (OR = 4.02; 95% CI 1.53-10.56; p = 0.005) compared to those with higher PA-HS (PA > 5.15-HS > 30.7). The combination of PA-HS was also significantly linked with EuroSCORE II. CONCLUSION: The combination of low preoperative PA and HS values was significantly associated with higher risk of all-cause mortality at 12 months and prolonged ICU LOS; thereby it might serve as a clinically useful prognostic biomarker after cardiac surgery procedures.

Angiographic severity in acute coronary syndrome patients with and without standard modifiable risk factors.

Background: Routine coronary artery disease (CAD) secondary prevention strategies target standard modifiable cardiovascular risk factors (SMuRFs), which include: diabetes mellitus, dyslipidemia, hypertension, and smoking. However, a significant proportion of patients with acute coronary syndrome (ACS) present without any SMuRFs. The angiographic severity of disease in this population has not yet been investigated. Methods: After propensity score matching of patients without SMuRFs and patients with ≥1 SMuRFs (ratio 1:3), we used zero-inflated negative binomial regression modeling to investigate the relationship of SMuRF-less status with the angiographic severity of CAD, as measured by the SYNTAX score. Survival analysis was performed to investigate differences in all-cause mortality at 30 days and at the end of follow-up period. Results: We analyzed 534 patients presenting with ACS who underwent coronary angiography. Of them, 56 (10.5%) presented without any SMuRF. After propensity score matching, the median SYNTAX score was 13.8 (IQR 0-22.1) in 56 SMuRF-less patients and 14 (IQR 5-25) in 166 patients with ≥1 SMuRFs. SMuRF-less status was associated with increased odds of zero SYNTAX score [zero-part model: odds ratio = 2.11, 95% confidence interval (CI): 1.03-4.33], but not with decreased SYNTAX score among patients with non-zero SYNTAX score (count-part model: incidence rate ratio = 0.99, 95% CI: 0.79-1.24); the overall distribution of the SYNTAX score was similar between the two groups (p = 0.26). The 30-day risk for all-cause mortality was higher for SMuRF-less patients compared to patients with ≥1 SMuRFs [hazard ratio (HR) = 3.58, 95% CI: 1.30-9.88]; however, the all-cause mortality risk was not different between the two groups over a median 1.7-year follow-up (HR = 1.72, 95% CI: 0.83-3.57). Conclusion: Among patients with ACS, the absence of SMuRFs is associated with increased odds for non-obstructive CAD and with increased short-term mortality rates.

Polypharmacy and Major Adverse Events in Atrial Fibrillation.

ABSTRACT: Patients with atrial fibrillation (AF) often receive multiple medications daily. The purpose of this study was to examine the prognostic implications of polypharmacy in patients with AF. This is a retrospective post hoc analysis of 1113 AF patients, enrolled in a randomized trial during an acute hospitalization (MISOAC-AF, NCT02941978). The presence of polypharmacy (use of >4 drugs daily) was assessed at hospital discharge. Regression analyses were performed to identify clinical predictors of polypharmacy and compare the outcomes of patients with or without confirmed polypharmacy. The coprimary outcomes were all-cause and cardiovascular (CV) mortality. Among patients with polypharmacy, the difference in the risk of mortality was also assessed per each added drug as a numeric variable. Polypharmacy was found in 36.9% of participants. Dyslipidemia, coronary artery disease, lower left ventricular ejection fraction, and higher glomerular filtration rates were independent predictors of polypharmacy. Polypharmacy was an independent predictor for all-cause death (adjusted hazard ratio [aHR]: 1.29, 95% confidence interval [CI]: 1.01-1.64) and CV death (aHR: 1.39, 95% CI: 1.05-1.84). Among patients with polypharmacy, each additional concomitant medication was independently associated with a 4% increased risk of all-cause mortality (aHR = 1.04, 95% CI: 1.00-1.08) and a 5% increased risk of CV mortality (aHR = 1.05, 95% CI: 1.00-1.10). Polypharmacy was common among patients with AF hospitalized in a tertiary hospital and was incrementally associated with higher rates of mortality.

PERSISTENT FEVER IN A PATIENT WITH CONGENITAL HEART DISEASE AND A HIGH-VELOCITY SHUNT: A CASE REPORT.

In patients with congenital heart disease (CHD), presence of intracardiac shunt can be a substrate for infective endocarditis (IE). Our aim was to highlight that this diagnosis should always be suspected when CHD patients present with persistent fever. In this case report, we describe the case of a 33-year-old female patient with a history of perimembranous ventricular septal defect (VSD) who presented to the hospital with persistent fever. Six months ago, the patient had undergone a tooth extraction under antibiotic prophylaxis. The transthoracic echocardiogram revealed a mobile mass, consistent with vegetation in the tricuspid valve. The blood cultures grew Streptococcus mitis. Antimicrobial treatment was initiated for IE. Symptoms and inflammation markers improved, but the patient relapsed in the 4th week of treatment. Transesophageal echocardiogram revealed a new mobile vegetation attached to the right ventricular outflow tract and the patient was referred for surgery. Her postoperative course was uneventful.

Comparative efficacy and safety of oral P2Y12 inhibitors after non-ST-elevation acute coronary syndromes: a network meta-analysis.

BACKGROUND: Currently, potent P2Y12 inhibition with the use of prasugrel or ticagrelor is the mainstay of treatment after an acute coronary syndrome (ACS). The 2020 European Society of Cardiology (ESC) Guidelines recommend the use of prasugrel over ticagrelor in patients with non-ST-elevation ACS (NSTE-ACS) intended to receive invasive management (class IIa recommendation), however there are contradictory views regarding this recommendation. AIM: To compare oral P2Y12 inhibitors in NSTE-ACS in terms of efficacy and safety with a focus on patients intended to proceed to invasive management. METHODS: We systematically searched PubMed, Cochrane Central Register of Controlled Trials and Web of Science to identify studies that compared different oral P2Y12 inhibitors (clopidogrel, prasugrel and ticagrelor) in patients with NSTE-ACS. Efficacy outcomes included the major adverse cardiovascular events outcome and safety outcomes included minor and major bleedings. We performed a frequentist network meta-analysis. RESULTS: Nine studies (n=35 441 patients) were included in the systematic review. There was no difference between prasugrel and ticagrelor in the composite cardiovascular end point (prasugrel vs ticagrelor HR=0.80, 95% CI=0.61 to 1.06) in all patients with NSTE-ACS. In patients intended to receive invasive management, prasugrel resulted in a reduction of the composite cardiovascular end point both versus clopidogrel (HR=0.76, 95% CI=0.61 to 0.95) and ticagrelor (HR=0.74, 95% CI=0.56 to 0.98). Inconsistency was moderate and non-significant (I2=27%, total Q p=0.2). Prasugrel ranked as the most efficient treatment in the composite cardiovascular efficacy outcome, all-cause death, myocardial infarction and definite stent thrombosis, while clopidogrel ranked as safest in the bleeding outcomes. CONCLUSION: In patients with NSTE-ACS intended to receive invasive management, an antiplatelet strategy based on prasugrel is more efficient than a similar strategy based on ticagrelor on a moderate level of evidence. This analysis supports the current recommendations by the ESC guidelines.

Infrared Radiation in the Management of Musculoskeletal Conditions and Chronic Pain: A Systematic Review.

Infrared radiation (IR) is a promising complementary treatment for musculoskeletal conditions and chronic pain. By means of a systematic review, we evaluated the contribution of IR to the management of these ailments. PubMed-MEDLINE, Scopus, and Cochrane Library-Cochrane Central Register of Controlled Trials were systematically searched until 20 December 2021. The literature search yielded 233 relevant records. Following the screening of titles and abstracts, 42 full-texts were evaluated. As per inclusion/exclusion criteria, 13 publications were entered into the qualitative assessment. These studies described the effects of IR in humans: three studies focused on osteoarthritis, four studies on fibromyalgia, and six encompassed a wider range of diseases (ankylosing spondylitis, recovery from sports injuries, myofascial pain syndrome). Based on the findings of our systematic review, we noted a decrease in pain levels, as evaluated by the visual analog scale (VAS), in patients suffering from musculoskeletal disorders treated with IR. In addition, IR use led to a decrease in Fibromyalgia Impact Questionnaire (FiQ) scores in subjects diagnosed with fibromyalgia. Nevertheless, IR has failed to facilitate muscle recovery following athletic injuries.