Morphometric and functional changes in the kidney of rats induced by inorganic selenium.

Selenium (Se) is an essential trace element. Depending on concentration, Se can manifest both beneficial and harmful effects on the cell and can have both oxidative and antioxidant effects. Because the therapeutic index for Se is very narrow and it can depend on the form of Se used, we aimed to investigate the potential safety and side effects of inorganic Se on kidney function and structure in rats. After 8 days of treatment, no detectable signs of microscopic changes or oxidative stress in kidney tissue were observed. We detected a moderate increase in urea and creatinine levels in the blood as a sign of a slight decrease in kidney function. The most notable changes in our study were morphometric alterations in proximal tubules and glomeruli, both of which were considerably enlarged. The short-term application of inorganic Se to rats in a supratherapeutic dose induced mild functional and ultrastructural changes in the kidneys. The dose of inorganic Se used could be considered relatively safe for short-term application in situations where Se could be beneficial to the organism, such as the usage of known nephrotoxicants or high levels of oxidative stress in the body.

Redox Status and Telomere-Telomerase System Biomarkers in Patients with Acute Myocardial Infarction Using a Principal Component Analysis: Is There a Link?

In the present study, we examined redox status parameters in arterial and venous blood samples, its potential to predict the prognosis of acute myocardial infarction (AMI) patients assessed through its impact on the comprehensive grading SYNTAX score, and its clinical accuracy. Potential connections between common blood biomarkers, biomarkers of redox status, leukocyte telomere length, and telomerase enzyme activity in the acute myocardial infarction burden were assessed using principal component analysis (PCA). This study included 92 patients with acute myocardial infarction. Significantly higher levels of advanced oxidation protein products (AOPP), superoxide anion (O2•-), ischemia-modified albumin (IMA), and significantly lower levels of total oxidant status (TOS) and total protein sulfhydryl (SH-) groups were found in arterial blood than in the peripheral venous blood samples, while biomarkers of the telomere-telomerase system did not show statistical significance in the two compared sample types (p = 0.834 and p = 0.419). To better understand the effect of the examined biomarkers in the AMI patients on SYNTAX score, those biomarkers were grouped using PCA, which merged them into the four the most contributing factors. The "cholesterol-protein factor" and "oxidative-telomere factor" were independent predictors of higher SYNTAX score (OR = 0.338, p = 0.008 and OR = 0.427, p = 0.035, respectively), while the ability to discriminate STEMI from non-STEMI patients had only the "oxidative-telomere factor" (AUC = 0.860, p = 0.008). The results show that traditional cardiovascular risk factors, i.e., high total cholesterol together with high total serum proteins and haemoglobin, are associated with severe disease progression in much the same way as a combination of redox biomarkers (pro-oxidant-antioxidant balance, total antioxidant status, IMA) and telomere length.

HDL Subclasses and the Distribution of Paraoxonase-1 Activity in Patients with ST-Segment Elevation Acute Myocardial Infarction.

The aim of this multicentric study was to assess the impacts of oxidative stress, inflammation, and the presence of small, dense, low-density lipoproteins (sdLDL) on the antioxidative function of high-density lipoprotein (HDL) subclasses and the distribution of paraoxonase-1 (PON1) activity within HDL in patients with ST-segment elevation acute myocardial infarction (STEMI). In 69 STEMI patients and 67 healthy control subjects, the lipoproteins' subclasses were separated using polyacrylamide gradient (3-31%) gel electrophoresis. The relative proportion of sdLDL and each HDL subclass was evaluated by measuring the areas under the peaks of densitometric scans. The distribution of the relative proportion of PON1 activity within the HDL subclasses (pPON1 within HDL) was estimated using the zymogram method. The STEMI patients had significantly lower proportions of HDL2a and HDL3a subclasses (p = 0.001 and p < 0.001, respectively) and lower pPON1 within HDL3b (p = 0.006), as well as higher proportions of HDL3b and HDL3c subclasses (p = 0.013 and p < 0.001, respectively) and higher pPON1 within HDL2 than the controls. Independent positive associations between sdLDL and pPON1 within HDL3a and between malondialdehyde (MDA) and pPON1 within HDL2b were shown in the STEMI group. The increased oxidative stress and increased proportion of sdLDL in STEMI are closely related to the compromised antioxidative function of small HDL3 particles and the altered pPON1 within HDL.

The Importance of Immunohistochemical Heterogeneous Expression of MMR Protein in Patients with Colorectal Cancer in Stage II and III of the Disease.

Background and objectives: In patients with colorectal cancer (CRC), heterogeneous expression of Mismatch repair (MMR) proteins can manifest itself in several different forms and is not such a rare phenomenon. Therefore, it is very important to recognize the nuclear expression of MMR proteins of different MMR status in order to avoid false positive or false negative results. The aim of this study was to determine the frequency and distribution of heterogeneous expression of MMR proteins in patients with stages II and III of the disease as well as its association with clinical, demographic and pathological characteristics of CRC in relation to proficient and deficient expression of MMR proteins. Material and Methods: The study included 104 cases of colorectal cancer obtained from surgical colectomy material in stages II and III of the disease. Results: From a total of 104 patients with colorectal cancer, immunohistochemical analysis of the expression of all four MMR proteins showed that heterogeneous expression of MMR proteins (as well as deficient immunoreactivity of tumor cells) was present in 12 cases, while proficient expression of MMR proteins was detected in 80 tumors. Conclusions: Our study showed that the only independent predictors of the loss of MMR protein expression were younger patient age and right-sided anatomical location of the tumor. The study also established the existence of heterogeneous expression of MMR proteins in a non-negligible percentage of CRCs (11.5%), where heterogeneous nuclear expression of MMR proteins was described in several different forms.

Acute Coronary Syndrome Presenting during On- and Off-Hours: Is There a Difference in a Tertiary Cardiovascular Center?

Background and Objectives: ACS presents an acute manifestation of coronary artery disease and its treatment is based on timely interventional diagnostics and PCI. It has been known that the treatment and the outcomes are not the same for all the patients with ACS during the working day, depending on the availability of the procedures and staff. The aim of the study was to explore the differences in clinical characteristics and outcomes in patients admitted for ACS during on- and off-hours. Materials and Methods: The retrospective study included 1873 consecutive ACS patients admitted to a tertiary, university hospital that underwent coronary angiography and intervention. On-hours were defined from Monday to Friday from 07:30 h to 14:30 h, while the rest was considered off-hours. Results: There were more males in the off-hours group (on-hours 475 (56%) vs. off-hours 635 (62%); p = 0.011), while previous MI was more frequent in the on-hours group (on 250 (30%) vs. off 148 (14%); p < 0.001). NSTEMI was more frequent during on-hours (on 164 (19%) vs. off 55 (5%); p < 0.001), while STEMI was more frequent during off-hours (on 585 (69%) vs. off 952 (93%); p < 0.001). Patients admitted during on-hours had more multivessel disease (MVD) (on 485 (57%) vs. off 489 (48%); p = 0.006), as well as multivessel PCI (on 187 (22%) vs. off 171 (16%); p = 0.002), while radial access was preferred in off-hours patients (on 692 (82%) vs. off 883 (86%); p = 0.004). Left main PCI was performed with similar frequency in both groups (on 37 (4%) vs. off 35 (3%); p = 0.203). Death occurred with similar frequency in both groups (on 17 (2.0%) vs. off 26 (2.54%); p = 0.404), while major adverse cardio-cerebral events (MACCEs) were more frequent in the on-hours group (on 105 (12.4%) vs. off 70 (6.8%); p = 0.039) probably due to the more frequent repeated PCI (on 49 (5.8%) vs. off 27 (2.6%); p = 0.035). Conclusions: Patients admitted for ACS during working hours in a tertiary hospital present with more complex CAD, have more demanding interventions, and experience more MACCEs during follow-up mostly due to myocardial infarctions and repeated procedures.

The Functional Chameleon of Materials Chemistry-Combining Carbon Structures into All-Carbon Hybrid Nanomaterials with Intrinsic Porosity to Overcome the "Functionality-Conductivity-Dilemma" in Electrochemical Energy Storage and Electrocatalysis.

Nanoporous carbon materials can cover a remarkably wide range of physicochemical properties. They are widely applied in electrochemical energy storage and electrocatalysis. As a matter of fact, all these applications combine a chemical process at the electrode-electrolyte interface with the transport (and possibly the transfer) of electrons. This leads to multiple requirements which can hardly be fulfilled by one and the same material. This "functionality-conductivity-dilemma" can be minimized when multiple carbon-based compounds are combined into porous all-carbon hybrid nanomaterials. This article is giving a broad and general perspective on this approach from the viewpoint of materials chemists. The problem and existing solutions are first summarized. This is followed by an overview of the most important design principles for such porous materials, a chapter discussing recent examples from different fields where the formation of comparable structures has already been successfully applied, and an outlook over the future development of this field that is foreseen.

Problematic Smartphone Use, Screen Time and Chronotype Correlations in University Students.

BACKGROUND: Besides numerous advantages and commodities offered by smartphones, there are obvious unhealthy effects. The global trend of an increase in the frequency of usage of smartphones, that is, prolonged screen time, is closely related to problematic smartphone use. The aim of our study was to measure the level of problematic smartphone use in a student population through the assessment of the smartphone screen time and the determination of the student chronotype, as well as through the correlation between these variables. METHODS: The participants were students of medicine of both sexes. Problematic smartphone use was measured by the short version of the Smartphone Addiction Scale. Smartphone screen time was assessed by the free Android application Quality Time. Chronotype was established by the Morningness-Eveningness Questionnaire. RESULTS: Almost one quarter (22.7%) of students involved in our study could be classified as being "smartphone-addicted". The students with problematic smartphone use more frequently (statistical significance) belonged to the evening chronotype. Those students spent significantly more time on their phones compared to the non-addicted ones. There was no statistically significant difference between the number of male and female students with problematic smartphone use. The best predictors of problematic smartphone use were longer daily smartphone screen time and evening chronotype personality. CONCLUSIONS: The results of our study showed that a significant number of students of medicine showed problematic smartphone use. There was a strong correlation between extensive screen time and the level of problematic smartphone use in the studied population.

Caffeic acid phenethyl ester attenuates changes in pancreatic tissue damage biomarkers induced by cisplatin.

Application of cisplatin (CP) for the treatment of different cancers is known to cause pancreatitis through an increase in reactive oxygen species production and promotion of inflammation. Caffeic acid phenethyl ester (CAPE), the main activity carrier of propolis extracts, was previously found to possess numerous beneficial properties. This study aims to determine for the first time the potential of CAPE in preventing CP-induced pancreatic tissue damage by studying the changes occurring on both biochemical and microscopic levels. The levels of serum α-amylase and a panel of pancreatic tissue biomarkers related to tissue injury (reduced glutathione, xanthine oxidase, malondialdehyde, and protein carbonylated concentration) and inflammation (myeloperoxidase, nitric oxide, and umor necrosis factor alpha) were studied in male Wistar rats treated with either CP alone or with CP and CAPE. Additionally, microscopic analysis of pancreatic tissue would be conducted as well. Application of CAPE together with CP statistically significantly prevented the disturbance in all here-studied pancreatic tissue damage and inflammation-related biomarkers. The changes in pancreas biochemical status was followed by morphological disturbance. The results of the present study suggest that CAPE could act as a protective agent in pancreatic damage that arises after CP application.

Circulating levels of inflammatory parameters pentraxin-3, cyclophilin and heparin-binding epidermal growth factor-like growth factor in patients with ST-elevation myocardial infarction.

Inflammatory biomarkers - pentraxin-3 (PTX3), cyclophilin A (CypA) and heparin-binding epidermal growth factor-like growth factor (HB-EGF) were examined in patients with ST-segment elevation myocardial infarction (STEMI) undergoing revascularization with primary percutaneous coronary intervention (pPCI) and stent implanting. Investigated parameters were compared between patients with and without obstructive coronary artery disease (CAD). In addition, their changes were tested in circulation before and immediately after pPCI. The study group consisted of 81 STEMI patients. Patients were classified in the STEMI-CAD group if they had significant obstructive CAD or in MINOCA group if they had no significant stenosis. In STEMI-CAD patients inflammatory parameters were determined prior to and after pPCI intervention. Immediately after pPCI, in STEMI-CAD patients levels of PTX3 were significantly lower (1.52 vs. 2.17 µg/L, p < .001), while the levels of HB-EGF (14.61 vs. 12.03 pg/L, p < .001) and CyPA (15.95 vs. 8.62 µg/L, p < .001) were significantly higher compared to levels before pPCI. STEMI-CAD patients had lower PTX3 values 2.17 µg/L (1.55-5.10 µg/L) than MINOCA patients 5.06 µg/L (2.77-6.7 µg/L), p = .046. Diagnostic accuracy of PTX3 for discrimination MINOCA from STEMI-CAD patients was low (area under receiver operating characteristic curve = 0.770). Evaluation of PTX3 values may be helpful in the understanding of MINOCA aetiology but they couldn't distinguish stenosis severity in STEMI patients. Inflammatory biomarkers significantly changed after pPCI but the possibility of clinical use of these biomarkers needs to be evaluated in a larger prospective study.

Two different melatonin treatment regimens prevent an increase in kidney injury marker-1 induced by carbon tetrachloride in rat kidneys.

Acute kidney injury is a frequent disorder that can be mimicked by the application of different nephrotoxic agents, including carbon tetrachloride (CCl4), where kidney injury marker-1 (KIM-1) has been recognized as a highly specific marker. Melatonin is one of the most powerful natural antioxidants and has numerous beneficial properties. We evaluated the nephroprotective potential of 2 melatonin treatment regimens (pre- and post-intoxication) in a CCl4-induced acute kidney injury model based on the standard serum parameters, kidney tissue antioxidative capacity, KIM-1 levels, and kidney tissue morphological changes. The two treatment regimens were found to preserve kidney function, as judged from the evaluated standard serum parameters. Only when administered after the intoxication, melatonin preserved total kidney antioxidant capacity; pre-treatment melatonin only preserved reduced glutathione levels. An increase in tissue KIM-1 level was found to be prevented by both treatment regimens, which correlated with the morphological changes seen in the kidney tissues of animals treated with melatonin and CCl4. The findings of our study are in agreement with the known actions of melatonin in relieving kidney tissue oxidative burden, but also contribute to the understanding of its action by preventing an increase in KIM-1.

Pancreatic Polypeptide-Secreting Tumour of the Proximal Pancreas (PPoma)-Ultra Rare Pancreatic Tumour: Clinically Malign, Histologically Benign.

Background and objectives: Here we report a rare case of a pancreatic polypeptide-secreting tumour (PPoma) discovered by accident during an autopsy. These PPomas occur in less than 2% of all pancreatic neoplasms and are almost exclusively silent, i.e., they are non-functional. Symptoms arising from PPoma are due to its compression of surrounding tissue. Materials and methods: The autopsy was performed on a 68-year-old male diagnosed with multiple endocrine neoplasm type 1 (MEN1) due to the patient's sudden death. Results: A solitary, densely fibrotic, pink-brown tumour, 18 mm in size tumorous mass, was localised in the head of the pancreas. Microscopically, the tumour had a glandular structure with a tubuloacinar arrangement of the cells. Immunohistochemically, we detected strong PP (pancreatic polypeptide) intracytoplasmic activity and negative glucagon activity. The PPoma was located in the head of the pancreas, likely resulting in the obstruction of the main pancreatic and common bile duct. Conclusions: To the best of our knowledge, this is the first report suggesting the association of PPomas with MEN1. Also, the PPoma could be the cause of acute hemorrhagic pancreatitis due to its location.

Differences in Angular Photogrammetric Soft-Tissue Facial Characteristics among Parents and Their Offspring.

Background and objectives: The objective of this study was to determine if the angular photogrammetric analysis of soft-tissue characteristics can determine similarities between parents and their offspring in the Serbian population. Materials and Methods: A total of 15 families (52 participants) met the participation criteria of this study and their facial profile images were analyzed using the ImageJ software. Subjects were divided into groups of mothers and fathers and four groups of children (divided according to their age and gender). In total, twelve angular measurements were made on the standardized digital images of the profiles of the participants and the obtained data were compared using one-way ANOVA. Results: The obtained results showed that there were statistically significant differences in the values of the nasal and cervicomental angles, as well as the angle of the total facial convexity, between the group of fathers, on one side, and groups of male/female children, on the other. Conclusions: This work represents the first photogrammetric analysis of facial soft-tissue characteristics of children and adults in the Serbian population. The data suggest that there are much more similarities between the facial soft-tissue angles of fathers and their male offspring. Furthermore, mothers tend to have statistically insignificant differences in angle sizes, compared to both male and female offspring.

The Quantitative ER Immunohistochemical Analysis in Breast Cancer: Detecting the 3 + 0, 4 + 0, and 5 + 0 Allred Score Cases.

The currently used immunohistochemical approach in determining the estrogen receptor (ER) positivity of breast cancers (BCs) is inherently subjective and additionally limited by its semi-quantitative nature. The application of software in the analysis of digitized slide images may overcome some of these limitations. However, the utilization of such an approach requires that the entire staining procedure is standardized. BACKGROUND AND OBJECTIVES: We aimed to establish a procedure for the photometric and morphometric analysis of BC immunohistochemical parameters that can possibly be used for a diagnostic purpose that is in line with the current semi-quantitative scoring system. MATERIALS AND METHODS: Semi-quantitative analysis of ER-stained tissue sections was performed following the Allred scoring system guidelines. The quantitative analysis was performed in ImageJ software after color deconvolution. The quantitative analysis of 66 cases of invasive lobular BC included: Percent of ER-positive cells, average nuclear coloration intensity, and the quantitative ER score. The percent of ER-positive tumor cells was counted using a standard grid overlay, while optical density (0.0-1.0) was measured within each nucleus at the grid points. RESULTS: A statistical analysis revealed a significant positive correlation (r = 0.886, p < 0.001) between the subjective semi-quantitative and quantitative ER scores, with a large effect size (d = 3.8215). We observed strong statistically significant correlations between individual parameters of the total ER score, percentage of ER-positive nuclei, and color intensity, obtained by the two independent methods. CONCLUSIONS: Additionally, besides excluding subjectivity, the up to now unreported cases of 3 + 0, 4 + 0, and 5 + 0 Allred scores were detected only by the application of the proposed quantitative approach.

Effects of melatonin on oxidative stress parameters and pathohistological changes in rat skeletal muscle tissue following carbon tetrachloride application.

Animal models demonstrating skeletal muscle (SM) disorders are rarely investigated, although these disorders accompany liver disorders and can occur during prolonged exercise/training. In cases of SM disorders exogenous antioxidants, such as melatonin, could help by generally improving tissues antioxidant capacities. We aimed to analyze the potential of melatonin in preventing biochemical and structural changes in rat biceps muscle (BM) occurring after an acute exposure to carbon tetrachloride (CCl4). Biceps muscles obtained from male Wistar rats belonging to different experimental groups were biochemically (determination of tissue MDA, total antioxidant capacity, GSH, CAT, SOD and GPx activities) and pathologically analyzed. Also, serum levels of potassium, LHD and CK were analyzed in all experimental animals. The obtained results were statically compared with those from vehicle-treated control group. The applied melatonin prevented potassium and intracellular enzyme leakage (CK and LDH) that was induced by CCl4, as well as an increase in tissue MDA. From a panel of determined oxidative stress parameters melatonin was able to statistically significantly prevent changes in total antioxidative capacity and in CAT, SOD and GPx activities induced by CCl4. Microscopic analysis of BM from the animals exposed to CCl4 revealed significant muscle fiber disorganization and massive inflammatory cell infiltration. All these changes were significantly ameliorated in the group that received melatonin prior to CCl4. Changes in serum and tissue biochemical parameters accompanied the observed pathological changes, which demonstrated a significant influence of melatonin in preventing skeletal muscle damage induced by CCl4.

Echocardiographic predictors of outcome in patients with chronic obstructive pulmonary disease.

BACKGROUND: We aimed to assess the relationship between echocardiographic characteristics and mortality in patients with chronic obstructive pulmonary disease (COPD). METHODS: We prospectively studied 154 patients (mean age 71 ± 10 years, 71% male) with COPD. All patients underwent transthoracic Doppler echocardiography within 48 hours of hospital admission. Primary endpoint was all-cause mortality during a median period of 22 months. RESULTS: Mildly elevated tricuspid regurgitation pressure and mitral E/e' ratio were the most commonly encountered echocardiographic abnormalities, observed in 60% and 56% of patients, respectively. In Kaplan-Meier analysis of survival, left atrial enlargement, E/e' ratio > 8, right atrial enlargement, right ventricular dilation, decreased tricuspid annular plane systolic excursion, decreased tricuspid annular systolic velocity, and elevated tricuspid regurgitation velocity were associated with all-cause mortality (p < 0.05 for all). In the Cox proportional hazards analysis, the mitral E/e' ratio (hazard ratio 1.048; 95% confidence interval 1.001-1.096) remained an independent echocardiographic predictor of survival after adjustment for age, COPD severity, and other baseline echocardiographic parameters. CONCLUSIONS: Among patients with COPD, an abnormal mitral E/e' ratio was an independent echocardiographic predictor of all-cause mortality. Echocardiographic evaluation of structural and functional cardiac abnormalities provides important prognostic information and should be used routinely in the assessment of patients with COPD. © 2016 Wiley Periodicals, Inc. J Clin Ultrasound 45:211-221, 2017.

Laparotomy site implantation metastasis of carcinoma of the papilla of Vater.

Introduction Carcinomas of the papilla of Vater make up a heterogeneous group of tumours arising from different types of epithelium. Regional lymph nodes, liver and lungs are the primary sites of metastatic progression of these tumours. Case presentation We present a patient with an abdominal incision site metastasis of low-grade (mixed type) adenocarcinoma of the papilla of Vater one year after pylorus-preserving pancreaticoduodenectomy. Implantation metastasis of low-grade ampullary carcinoma in the laparotomy wound after open Whipple's procedure is unusual. Conclusion Adjuvant chemoradiation might be considered for patients with low-grade localised disease as a potentially preventative measure vs. metastatic progression.

Seven-year survey of classical and pleomorphic invasive lobular breast carcinomas in women from southeastern Serbia: Differences in clinicopathological and immunohistochemical features.

PURPOSE: The occurrence of different variants of invasive lobular carcinoma (ILC) of the breast is variable. For example, the pleomorphic variant of ILC has an incidence of around 5%; however, the number of analyzed cases of ILC is shadowed by the number of ductal type carcinoma (IDC). Thus, we aimed to analyze the classical and pleomorphic ILCs in women from southeastern Serbia. METHODS: Analyzed were 296 cases (11.91%) diagnosed with ILC, out of 2486 cases of all breast cancers (BCs), during a 7-year period (2005-2011) from southeastern Serbia. The differences in clinicopathological and immunohistochemical features (estrogen receptor/ER, progesterone receptor/ PR, HER-2, Ki-67, BRCA-1, p53 and E-cadherin) of these cases of ILCs were assessed and compared. RESULTS: Pleomorphic ILC occurred relatively rarely compared to other variants, however almost one fifth of the ILC cases were pleomorphic. No statistically significant correlation was found between patient age, tumor stage and the presence/absence of multifocality (MFC), multicentricity (MCC) and bilaterality (BL) on one side, and ILC variant on the other. Only the expression of two prognostic and predictive immunohistochemical markers, important for endocrine therapy, ER and PR, showed significant correlation with the ILC variant. CONCLUSIONS: Although higher tumor stage, incidence of multicentricity, overexpression of HER2 and higher p53 positivity were deemed to be characteristic of pleomorphic ILC, in our study that included a much larger number of cases than previous studies did, such correlations were not observed. Thus, it appears that the only two features of pleomorphic ILCs is absence of ER and PR positivity.

Differences in Histological Subtypes of Invasive Lobular Breast Carcinoma According to Immunohistochemical Molecular Classification.

The technical complexity of gene expression profiling in routine practice has necessitated the use of surrogate molecular classification of breast cancer, based on immunohistochemical analyses. BACKGROUND AND OBJECTIVES: The aim of this study was to compare the differences between histological and molecular subtypes of invasive lobular carcinoma (ILC) of the breast, in order to be able to predict the behavior and prognosis of the disease, as well as to effectively determine therapy. MATERIAL AND METHODS: This study included 263 cases of breast ILC diagnosed over a seven-year period. The diagnosis of invasive lobular carcinoma is based on the characteristic growth pattern and phenotype of cancer cells with the respective subtypes: classic, alveolar, solid, tubulolobular, pleomorphic and mixed lobular type. The examined cases were divided into five groups according to molecular classification based on the expression of ER, PR, HER2 and Ki67 immunohistochemical markers. RESULTS: It was found that the pleomorphic subtype occurred statistically significantly less often as the luminal A subtype compared to others (p = 0.00027), and the HER2-enriched subtype occurred statistically significantly more often in the pT4 stage (p = 0.024). CONCLUSIONS: The results of this study significantly singled out the luminal A subtype, and among them classic ILC, as the subtype with the most favorable expression ratio of the investigated predictive/prognostic immunohistochemical markers.

Long-term outcomes of ischaemia with no obstructive coronary artery disease (INOCA): a systematic review and meta-analysis.

BACKGROUND: The prognosis of myocardial ischaemia with no obstructive coronary artery disease (INOCA) and its underlying vasomotor disorders, vasospastic angina (VSA) and microvascular angina (MVA), is not well defined. The aim of this study was to perform a systematic review and meta-analysis of studies evaluating the long-term prognosis of patients with INOCA. METHODS: We included studies evaluating the prognosis of patients with INOCA published between January 1984 and August 2023 in Medline, Embase, Web of Science and Cochrane databases. Studies were selected if they included patients who fulfilled the Coronary Vasomotor Disorders International Study Group (COVADIS) criteria for either possible or definitive VSA or MVA. The primary outcomes were composite of all-cause death and myocardial infarction (MI), and major adverse cardiovascular event (MACE) at annual intervals up to 5-year follow-up. The incidence of primary outcomes for INOCA, each INOCA endotype and by method used to determine the diagnosis was calculated using the random effects model. RESULTS: Fifty-four studies (17 302 patients) meeting the eligibility criteria were selected. The rate of all-cause death and MI with VSA was 0.7 (95% CI 0.4 to 1.0)/100 patient-years and with MVA was 1.1 (95% CI 0.7 to 1.5)/100 patient-years (p>0.05). The rate of MACE with VSA was 1.1 (95% CI 0.5 to 1.9)/100 patient-years and with MVA was 2.5 (95% CI 1.6 to 3.6)/100 patient-years (p=0.025). Patients with reduced coronary flow reserve (CFR) had higher all-cause death and MI rates than patients whose diagnosis of MVA was established based on an abnormal exercise or imaging stress test (4.7 (95% CI 2.0 to 8.4) vs 0.5 (95% CI 0.1 to 1.1) vs 1.1 (95% CI 0.5 to 2.0)/100 patient-years, p=0.001). CONCLUSIONS: Overall, patients with INOCA have a low rate of MACEs, but patients with MVA, especially those with reduced CFR, have a significantly higher rate of MACE than other subgroups, although there is high heterogeneity among the included studies. PROSPERO REGISTRATION NUMBER: CRD42021275070.

Spontaneous coronary artery dissection in women in the generative period: clinical characteristics, treatment, and outcome-a systematic review and meta-analysis.

Introduction: Spontaneous coronary artery dissection (SCAD) is a non-traumatic and non-iatrogenic separation of the coronary arterial wall. Materials and methods: This systematic review and meta-analysis is reported following the PRISMA guidelines and is registered in the PROSPERO database. A literature search was focused on female patients in generative period (16-55 of age) with acute coronary syndrome (ACS) caused by SCAD, and comparison from that database NP-SCAD (spontaneous coronary artery dissection in non pregnant women) and P-SCAD (spontaneous coronary artery dissection in pregnant women). Results: 14 studies with 2,145 females in the generative period with ACS caused by SCAD were analyzed. The median age was 41 years (33.4-52.3 years). The most common risk factor was previous smoking history in 24.9% cases. The most common clinical presentation of ACS was STEMI in 47.4%. Conservative treatment was reported in 41.1%. PCI was performed in 32.7%, and 3.8% of patients had CABG surgery. LAD was the most frequently affected (50.5%). The prevalence of composite clinical outcomes including mortality, non-fatal MI and recurrent SCAD was 3.3% (95% CI: 1.4-5.1), 37.7% (95% CI: 1.9-73.4) and 15.2% (95% CI: 9.1-21.3) of patients. P-SCAD compared to NP-SCAD patients more frequently had STEMI (OR = 3.16; 95% CI: 2.30-4.34; I2 = 64%); with the left main and LAD more frequently affected [(OR = 14.34; 95% CI: 7.71-26.67; I2 = 54%) and (OR = 1.57; 95% CI: 1.06-2.32; I2 = 23%)]; P-SCAD patients more frequently underwent CABG surgery (OR = 6.29; 95% CI: 4.08-9.70; I2 = 0%). NP-SCAD compared to P-SCAD patients were more frequently treated conservatevly (OR = 0.61; 95% CI: 0.37-0.98; I2 = 0%). In P-SCAD compared to NP-SCAD mortality rates (OR = 1.13; 95% CI: 0.06-21.16; I2 = not applicable) and reccurence of coronary artery dissection (OR = 2.54; 95% CI: 0.97-6.61; I2 = 0%) were not more prevalent. Conclusion: The results of this meta-analysis indicated that patients with P-SCAD more frequently had STEMI, and events more frequently involved left main and LAD compared to NP-SCAD patients. Women with NP-SCAD were significantly more often treated conservatively compared to P-SCAD patients. P-SCAD compared to NP-SCAD patients did not have significantly higher mortality rates or recurrent coronary dissection.