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Background Short and rare episodes of atrial fibrillation (AF) are commonly detected using implanted devices (device‐detected AF) in patients with prior stroke or transient ischemic attack (TIA). The effectiveness and safety of oral anticoagulation in patients with prior stroke or TIA and device‐detected AF but with no ECG‐documented AF is unclear. Methods and Results This prespecified analysis of the NOAH‐AFNET 6 (Non‐Vitamin K Antagonist Oral Anticoagulants in Patients With Atrial High Rate Episodes) trial with post hoc elements assessed the effect of oral anticoagulation in patients with device‐detected AF with and without a prior stroke or TIA in the randomized, double‐blind, double‐dummy NOAH‐AFNET 6 trial. Outcomes were stroke, systemic embolism, and cardiovascular death (primary outcome) and major bleeding and death (safety outcome). A prior stroke or TIA was found in 253 patients with device‐detected AF randomized in the NOAH‐AFNET 6 (mean age, 78 years; 36.4% women). There was no treatment interaction with prior stroke or TIA for any of the primary and secondary time‐to‐event outcomes. In patients with a prior stroke or TIA, 14 out of 122 patients experienced a primary outcome event with anticoagulation (5.7% per patient‐year). Without anticoagulation, there were 16 out of 131 patients with an event (6.3% per patient‐year). The rate of stroke was lower than expected (anticoagulation: 4 out of 122 [1.6% per patient‐year]; no anticoagulation: 6 out of 131 [2.3% per patient‐year]). Numerically, there were more major bleeding events with anticoagulation in patients with prior stroke or TIA (8 out of 122 patients) than without anticoagulation (2 out of 131 patients). Conclusions Anticoagulation appears to have ambiguous effects in patients with device‐detected AF and a prior stroke or TIA in this hypothesis‐generating analysis of the NOAH‐AFNET 6 in the absence of ECG‐documented AF, partially due to a low rate of stroke without anticoagulation.

Abstract Background Diabetic patients are at an increased risk of cardiovascular morbidities. We aimed to examine if elevated pre-operative glycosylated hemoglobin (HbA1c) levels are associated with higher likelihood of experiencing adverse events in on-pump (ONCAB) versus off-pump (OPCAB) coronary artery bypass graft (CABG) procedures. We examined characteristics of patients undergoing CABG using our institutional STS Adult Cardiac Surgery Database (ACSD) from 2014 to 2020. Descriptive statistics and univariate analyses were used to compare postoperative outcomes between ONCAB and OPCAB based on preoperative HbA1c levels: (1) HbA1c ≤ 6.0%, (2) 6.0% < HbA1c ≤ 7.0%, (3) 7.0% < HbA1c ≤ 8.5%, (4) HbA1c > 8.5%. Multivariable models were built to assess risk factors associated with adverse events. Primary outcomes were operative mortality and stroke. Results For ONCAB, statistically significant associations were found between increasing HbA1c and new post-operative dialysis (p=0.01), rates of readmission (p=0.003) and greater lengths of stay (p=0.002). For OPCAB, statistically significant associations were found between increasing HbA1c and rates of operative mortality (p=0.04), post-operative renal failure (p=0.0001), new post-operative dialysis (p=0.0001), sternal wound infection (p=0.01), and greater lengths of stay (p=0.03). No significant relationship was noted between HbA1c and stroke, reoperation due to bleeding, or post-operative transfusion. Conclusions Increasing HbA1c positively correlated with numerous adverse patient outcomes in both ONCAB and OPCAB, and differences were noted in which outcomes were most impacted between the two techniques. Pre-operative medical optimization from a diabetes standpoint is paramount to improve CABG outcomes in both on-pump or off-pump techniques.

Atrial fibrillation (AFib), the most prevalent arrhythmia in clinical practice, presents a growing global health concern, particularly with the aging population, as it is associated with devastating complications and an impaired quality of life. Its pathophysiology is multifactorial, including the pathways of fibrosis, inflammation, and oxidative stress. MicroRNAs (miRNAs), small non-coding RNA molecules, have emerged as substantial contributors in AFib pathophysiology, by affecting those pathways. In this review, we explore the intricate relationship between miRNAs and the aforementioned aspects of AFib, shedding light on the molecular pathways as well as the potential diagnostic applications. Recent evidence also suggests a possible role of miRNA therapeutics in maintenance of sinus rhythm via the antagonism of miR-1 and miR-328, or the pharmacological upregulation of miR-27b and miR-223-3p. Unraveling the crosstalk between specific miRNA profiles and genetic predispositions may pave the way for personalized therapeutic approaches, setting the tone for precision medicine in atrial fibrillation.

Introduction: Acute pulmonary vein (PV) reconnection is frequently encountered in patients undergoing PV isolation (PVI) procedure for the treatment of atrial fibrillation. In this study, we investigated whether the identification and ablation of residual potentials (RPs), after the initial achievement of PVI, reduces acute PV reconnection rate. Methods: Following PVI in 160 patients, mapping along the ablation line was performed to identify RPs, defined as bipolar amplitude ≥0.2 mV or 0.1-0.19 mV combined with a negative component of the unipolar electrogram. Ipsilateral PV sets with RPs were randomized to either no further ablation (Group B) or to additional ablation of the identified RPs (Group C). The primary study endpoint was spontaneous or adenosine-mediated acute PV reconnection after a 30-min waiting period and was also evaluated in ipsilateral PV sets without RPs (Group A). Results: After isolation of 287 PV pairs, 135 had no RPs (Group A), whereas the remaining PV pairs were randomized to either Group B (n = 75) or Group C (n = 77). Ablation of RPs resulted in a reduction of spontaneous or adenosine-mediated PV reconnection rate (16.9% in Group C vs 48.0% in Group B; p

Background: Allergic rhinitis (AR) has a significant impact on the community as a whole with regard to quality of life and its relationship to allergic multi-morbidities. Appropriate diagnosis, treatment and review of the efficacy of interventions can ameliorate these effects. Yet, the importance of AR is often overlooked, and appropriate therapy is neglected. The availability of effective medications and knowledge as to management are often lacking in both public and private health systems. Methods: This review is based on a comprehensive literature search and detailed discussions by the South African Allergic Rhinitis Working Group (SAARWG). Results: The working group provided up-to-date recommendations on the epidemiology, pathology, diagnosis and management of AR, appropriate to the South African setting. Conclusion: Allergic rhinitis causes significant, often unappreciated, morbidity. It is a complex disease related to an inflammatory response to environmental allergens. Therapy involves education, evaluation of allergen sensitisation, pharmacological treatment, allergen immunotherapy (AIT) and evaluation of the success of interventions. Regular use of saline; the important role of intranasal corticosteroids, including those combined with topical antihistamines and reduction in the use of systemic steroids are key. Practitioners should have a thorough knowledge of associated morbidities and the need for specialist referral. Contribution: This review summarises the latest developments in the diagnosis and management of AR such that it is a resource that allows easy access for family practitioners and specialists alike.

Chronic total occlusions (CTOs) represent the most complex subset of coronary artery disease and therefore careful planning of CTO percutaneous coronary recanalization (PCI) strategy is of paramount importance aiming to achieve procedural success, and improve patient's safety and post CTO PCI outcomes. Intravascular imaging has an essential role in facilitating CTO PCΙ. First, intravascular ultrasound (IVUS), due to its higher penetration depth compared to optical coherence tomography (OCT), and the additional capacity of real-time imaging without need for contrast injection is considered the preferred imaging modality for CTO PCI. Secondly, IVUS can be used to resolve proximal cap ambiguity, facilitate wire re-entry when dissection and re-entry strategies are applied and most importantly to guide stent deployment and optimization post implantation. The role of OCT during CTO PCI is currently limited to stent sizing and optimization, however, due to its high spatial resolution, OCT is ideal for detecting stent edge dissections and strut malapposition. In this review, we describe the use of intravascular imaging for lesion crossing, plaque characterization and wire tracking, extra- or intra-plaque, and stent sizing and optimization during CTO PCI and summarize the findings of the major studies in this field.

Abstract Background Mechanical circulatory support has garnered significant popularity as both a bridge to transplant as well as a destination therapy for patients with end-stage heart failure. Right heart failure (RHF) is a devastating complication after LVAD placement and is very unpredictable. Assisted circulation of the left ventricle (LV) with an LVAD device could unmask an underlying RHF. However, otherwise healthy right ventricles (RVs) can develop RHF after LVAD placement as well due to poor adaptation to new filling pressures and altered hemodynamics. It has been proposed that preoperative volumetric measurements in the pulmonary and systemic vasculature may serve as indicators for a risk of RHF after LVAD implantation. The aim of this study is to examine a potential relationship of preoperative hemodynamic values such as pulmonary artery pulsatility index (PAPi) and the ratio of central venous pressure to pulmonary wedge pressure (CVP/PWP) as preoperative predictors for RHF post LVAD placement. Methods We retrospectively reviewed patients undergoing initially planned isolated LVAD implantation with or without concomitant procedures in our institution from January 1, 2017 to June 12, 2020. Data were gathered from hemodynamic records, echocardiographic interpretations, and clinical notes. Patients who had RHF after LVAD implantation but without hemodynamic data available within 14 days from the operation were excluded. Univariable analysis was performed. Results Of the 114 patients who received planned isolated LVAD surgery, 70 (61.4%) experienced RHF within the first 7 days postoperatively. PAPi did not correlate significantly with RHF vs non-RHF among LVAD recipients (3.1 ± 2.1 vs. 3.8 ± 3.4 P = 0.21). Pre-op CVP/PWP did not differ significantly between RHF and non-RHF patients (0.4 ± 0.2 vs. 0.5 ± 0.8 P = 0.28). There was a nonsignificant correlation between elevated pre-op PWP and those with RHF vs those without, OR = 1.05 (95% CI: 1.00, 1.10). Pre-op systolic pulmonary artery pressure (SysPAP) was elevated in patients with post-LVAD RHF compared to those without (51.3 ± 12.3 vs. 47.2 ± 13.0, P = 0.09). Conclusion Preoperative hemodynamic variables such as PAPi or CVP/PWP did not show a significant correlation predicting RHF post LVAD implantation. Acute RHF post LVAD implantation remains a complex medical entity. Several studies have devised multivariable risk scores; however, their performance has been limited. Despite the widespread use of preoperative hemodynamics measurements as risk scores, our study suggests these scores are not as accurate as their use would suggest, particularly among especially morbid patient populations. More prospective studies are needed to accurately demonstrate how preoperative hemodynamics could predict and help prevent this catastrophic complication.

Abstract Background In the setting of ST-segment elevation myocardial infarction (STEMI), the faster and stronger antiplatelet action of ticagrelor compared to clopidogrel, as well as its pleiotropic effects, could result in a greater degree of cardioprotection and final infarct size (FIS) limitation. The aim of our study was to comparatively evaluate the effect of ticagrelor and clopidogrel on myocardial salvage index (MSI) in STEMI patients undergoing thrombolysis. Methods Forty-two STEMI patients treated with thrombolysis were randomized to receive clopidogrel (n = 21) or ticagrelor (n = 21), along with aspirin. Myocardial area at risk (AAR) was calculated according to the BARI and the APPROACH jeopardy scores. FIS was quantified by cardiac magnetic resonance imaging (CMR) performed 5–6 months post-randomization. MSI was calculated as (AAR-FIS)/AAR × 100%. Primary endpoint of our study was MSI. Secondary endpoints were FIS and CMR-derived left ventricular ejection fraction (LVEF) at 5 –6 months post-randomization. Results By using the BARI score for AAR calculation, mean MSI was 52.25 ± 30.5 for the clopidogrel group and 54.29 ± 31.08 for the ticagrelor group (p = 0.83), while mean MSI using the APPROACH score was calculated at 51.94 ± 30 and 53.09 ± 32.39 (p = 0.9), respectively. Median CMR-derived FIS—as a percentage of LV—was 10.7% ± 8.25 in the clopidogrel group and 12.09% ± 8.72 in the ticagrelor group (p = 0.6). Mean LVEF at 5–6 months post-randomization did not differ significantly between randomization groups. Conclusions Our results suggest that the administration of ticagrelor in STEMI patients undergoing thrombolysis offer a similar degree of myocardial salvage, compared to clopidogrel.

Abstract Background The organizational structure of cardiothoracic surgery practices varies among different programs throughout the United States (U.S.). We aimed to investigate the characteristics of the top ranked programs within the specialty and the surgeons practicing within each. Methods The top 50 hospitals for adult cardiology and heart surgery were identified using the US News and World Report 2019–20 ranking. There were 590 hospitals reported on, with 50 top rated programs. Data was collected from each hospital’s website, analyses conducted using SAS 9.4 with statistical significance set at p ≤ 0.05. Results When comparing cardiothoracic surgery program organizational structures, 21 of the top 50 ranked programs were departments and 24 were divisions within their respective Department of Surgery. Mean number of surgeons was 11 with no statistical difference when analyzed by division versus department. Overall, 9% of practicing cardiothoracic surgeons were female. Between programs that are a department versus division, general thoracic surgery was included in 58% of divisions and 52% of departments (p = ns). Among programs that were departments, approximately 6% of surgeons had attained a Ph.D., while in divisions approximately 4% of surgeons had attained a Ph.D. Conclusions The top 50 Cardiothoracic Surgery programs in the U.S. have approximately the same number of surgeons within the group and are organized similarly. This study group had a slightly higher percentage of female surgeons than has previously been noted in cardiothoracic surgery, with general thoracic surgery trending toward higher gender diversity. The presence of physician scientists was low, though similar amongst the study groups.

Background: Patients with diabetes mellitus (DM) and coronary artery disease (CAD) represent a high-risk population, where comorbidities are common and the progression of coronary heart disease is relatively rapid and extensive. The present survey, conducted nationwide in a Eurozone country, Greece, with a properly organized national health system, aimed to record specific data from a significant number of patients with diabetes and documented stable CAD (SCAD). Methods and results: We conducted our survey across the country, in private and public primary, secondary, and tertiary care centers. A total of 1900 patients aged 71 ± 10 years old who suffered from both DM and chronic coronary syndromes were registered. Of the patients registered, 574 (30.24%) were women. It was found that 506 (26.6%) of the 1900 surveyed patients showed typical angina symptoms, while another 560 (29.5%) patients had developed angina-equivalent symptoms according to their history. Additionally, 324 (17%) patients had atypical symptoms that could not easily be attributed to existing CAD and the remaining 510 (26.8%) of the 1900 patients did not exhibit any angina symptoms during their daily activities. Functional testing for myocardial ischemia was not performed in 833 patients (43.8%). Myocardial scintigraphy was the most commonly used noninvasive technique (644 patients, 34%), while 492 patients (25.9%) had an exercise test and 159 (8.4%) underwent stress echocardiography. Conclusion: Real-world data in this specific high-risk population of diabetic patients with SCAD offer the opportunity to identify and improve diagnostic and therapeutic practice in the healthcare system of a European Union country.

Introduction Mining of electronic health record (EHRs) data is increasingly being implemented all over the world but mainly focuses on structured data. The capabilities of artificial intelligence (AI) could reverse the underusage of unstructured EHR data and enhance the quality of medical research and clinical care. This study aims to develop an AI-based model to transform unstructured EHR data into an organised, interpretable dataset and form a national dataset of cardiac patients.Methods and analysis CardioMining is a retrospective, multicentre study based on large, longitudinal data obtained from unstructured EHRs of the largest tertiary hospitals in Greece. Demographics, hospital administrative data, medical history, medications, laboratory examinations, imaging reports, therapeutic interventions, in-hospital management and postdischarge instructions will be collected, coupled with structured prognostic data from the National Institute of Health. The target number of included patients is 100 000. Natural language processing techniques will facilitate data mining from the unstructured EHRs. The accuracy of the automated model will be compared with the manual data extraction by study investigators. Machine learning tools will provide data analytics. CardioMining aims to cultivate the digital transformation of the national cardiovascular system and fill the gap in medical recording and big data analysis using validated AI techniques.Ethics and dissemination This study will be conducted in keeping with the International Conference on Harmonisation Good Clinical Practice guidelines, the Declaration of Helsinki, the Data Protection Code of the European Data Protection Authority and the European General Data Protection Regulation. The Research Ethics Committee of the Aristotle University of Thessaloniki and Scientific and Ethics Council of the AHEPA University Hospital have approved this study. Study findings will be disseminated through peer-reviewed medical journals and international conferences. International collaborations with other cardiovascular registries will be attempted.Trial registration number NCT05176769.

Background: Congenital cystic swellings involving the floor of the mouth include various lesions such as developmental cysts (e.g., dermoid and epidermoid cysts), ranulas, vascular malformations etc. However, coexistence of such conditions, possibly with a cause-and-effect- relationship, is rare. The purpose of this case report is to present a rare case of a congenital epidermoid cyst associated with a mucous retention cyst in a newborn. Methods: A 6-month-old female infant was referred to an Oral Medicine Clinic in Athens, Greece on October 2019 for evaluation of a swelling at the floor of the mouth, first noticed by her paediatrician just after birth. Clinically, a yellowish “pearly” nodule in close association with the orifice of the left submandibular duct, posteriorly transitioning to a diffuse bluish cystic swelling of the left floor of the mouth was observed. With a provisional diagnosis of a dermoid cyst and/or ranula, a surgical excision was performed under general anaesthesia. Results: Histopathologically, a well-defined, keratin-filled, cystic cavity lined by orthokeratinized stratified squamous epithelium was observed in the anterior aspect while posteriorly and in close proximity, a dilated salivary duct lined by cylindrical, cuboidal or pseudostratified epithelium was noted. A final diagnosis of an epidermoid cyst intimately associated with a mucus retention cyst (ranula) of the submandibular duct was rendered. Conclusions: The coexistence of two cystic lesions in the floor of the mouth with features of epidermoid and mucous retention cyst, respectively, is rare and its pathogenesis intriguing, especially in a newborn.

Abstract Background Anomalous left coronary artery from the pulmonary artery (ALCAPA) is a rare congenital anomaly that typically presents within the first year of life but can also sporadically present in adults. ALCAPA, if left untreated, can lead to coronary ischemia and sudden death. Case presentation We present the case of a 32-year-old male with ALCAPA with ischemic cardiomyopathy and the anomalous left main coronary originating from the non-facing sinus of the pulmonary artery (PA). A posterior reimplantation of the anomalous coronary artery was accomplished with a modified Cabrol technique using synthetic polytetrafluoroethylene (PTFE) graft. Conclusions A posterior re-implantation technique using a modified Cabrol graft, in cases where length of the native button is challenging, has excellent outcomes for this rather rare and challenging clinical entity.

Background: Aplasia of the salivary glands, either partial or involving all the major and possibly the minor salivary glands, is a very rare cause of hyposalivation. The aim of this case report is to present a case of aplasia of the major and minor salivary glands and discuss the relevant literature. Methods: A 23-year-old woman, with a non-contributory medical and family history was referred due to rampant caries, that could not be attributed to any obvious aetiology. No sicca symptoms, previous parotid gland swelling or general symptoms were reported. Clinically, oral mucosa dryness and extended dental erosions and caries were observed, while the orifices of the excretory ducts of the parotid and submandibular salivary glands were not evident. Unstimulated and stimulated saliva flow rates were severely diminished, while a diagnostic biopsy of the lower lip revealed absence of minor salivary glands. Detailed hematologic and immunological investigations to exclude systemic disorders were also within normal limits. Ultrasound and magnetic resonance imaging revealed the absence of all major salivary glands, confirming the clinical diagnosis of congenital aplasia of the salivary glands. Results: Oral hygiene instructions and dietary advice were given while dental products with fluoride and saliva substitutes were administered and appropriate dental treatment was implemented. Regular dental follow-up was also advised. Conclusions: Timely diagnosis of aplasia of the salivary glands is important, considering the detrimental effects of the absence of saliva on oral health. Management consists of the use of saliva substitutes, nutritional adaptation, maintenance of oral health and regular dental follow-ups.

Introduction: Ticagrelor has been established as the P2Y12-inhibitor of choice in ST-segment elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PCI); however, its use has not been adequately studied in the context of thrombolysis. In the present study, we sought to investigate whether the administration of ticagrelor together with thrombolysis could result in a greater degree of left ventricular systolic function recovery compared to clopidogrel, at 90 days post-STEMI, as well as to evaluate post-PCI corrected TIMI Frame Count (CTFC) as a predictive marker of myocardial recovery in thrombolysis-treated patients. Material and methods: In this pre-specified analysis of the MIRTOS trial, the degree of change in left ventricular ejection fraction (ΔLVEF) and left ventricular longitudinal strain (ΔLV-GLS) from baseline to 90 days post-randomization in all patients who underwent conventional and speckle-tracking echocardiography at both timepoints was compared between the ticagrelor and clopidogrel groups. In addition, speckle-tracking echocardiographic measurements were evaluated for any correlations to post-PCI CTFC. Results: No statistically significant differences were detected between the ticagrelor and clopidogrel groups for ΔLVEF (+3.61 ± 5.08 % versus +2.21 ± 4.78 %; P = 0.18) and ΔLV-GLS (−1.53 ± 2.7 % versus −1.21 ± 3.05 %; P = 0.73). A strong negative correlation was found between post-PCI CTFC and the absolute value of LV-GLS at 90 days post-randomization (r = −0.33, P = 0.014). Conclusions: Our work suggests that both P2Y12-inhibitors are accompanied with a similar degree of myocardial recovery in the context of lytic therapy. Importantly, post-PCI microvascular integrity is a predictor of 3-month left ventricular systolic function in STEMI patients initially treated with thrombolysis.

Metastasis, rather than the growth of the primary tumor, accounts for approximately 90% of breast cancer patient deaths. Microtentacles (McTNs) formation represents an important mechanism of metastasis. Triple-negative breast cancer (TNBC) is the most aggressive subtype with limited targeted therapies. The present study aimed to isolate viable circulating tumor cells (CTCs) and functionally analyze them in response to drug treatment. CTCs from 20 TNBC patients were isolated and maintained in culture for 5 days. Biomarker expression was identified by immunofluorescence staining and VyCap analysis. Vinorelbine-induced apoptosis was evaluated based on the detection of M30-positive cells. Our findings revealed that the CTC absolute number significantly increased using TetherChips analysis compared to the number of CTCs in patients’ cytospins (p = 0.006) providing enough tumor cells for drug evaluation. Vinorelbine treatment (1 h) on live CTCs led to a significant induction of apoptosis (p = 0.010). It also caused a significant reduction in Detyrosinated α-tubulin (GLU), programmed death ligand (PD-L1)-expressing CTCs (p < 0.001), and disruption of McTNs. In conclusion, this pilot study offers a useful protocol using TetherChip technology for functional analysis and evaluation of drug efficacy in live CTCs, providing important information for targeting metastatic dissemination at a patient-individualized level.

Skin and soft tissue infections caused by non-tuberculous mycobacteria are occurring more frequently in recent years. However, chronic skin and soft tissue lesions present a challenge for clinicians, as the diagnostic work-up and definitive diagnosis require knowledge and available laboratory resources. We present here the case of a 66-year-old male patient who presented with painful abscess-like nodules on his right hand and forearm, which worsened after treatment with an anti-TNF-a agent. The fluid specimen taken from the lesion was positive for mycobacteria according to the acid-fast stain. Mycobacterium marinum was identified, first by next-generation sequencing and finally grown on culture, after eight weeks. Acknowledging the complexity of diagnosing and managing infections by non-tuberculous mycobacteria, and especially Mycobacterium marinum, we provide a review of the current epidemiology, clinical characteristics, diagnosis and management of Mycobacterium marinum infection.

Background: Implementation of an anesthesiology-led cardiac implantable electronic device (CIED) service can be viewed to have economic and efficiency challenges. This study evaluates the cost savings of an anesthesiology-led CIED service. Methods: A total of 830 patients presented in the pre-implementation period from 1 March 2016 to 31 December 2017, and 1981 patients presented in the post-implementation period from 1 January 2018 to 31 October 2021. Interrupted time-series analysis for single-group comparisons was used to evaluate the cost savings resulting from reduction in operating room (OR) start delays for patients with CIEDs. Results: OR start-time delay was reduced by 10.6 min (95%CI: −20.5 to −0.83), comparing pre- to post-implementation. For an OR cost of USD 45/min, we estimated the direct cost to the department to be USD 1.68/min. The intervention translated into a total cost reduction during the intervention period of USD 250,000 (USD 18,000 to USD 470,000) per year for the institution and USD 9800 (USD 730 to USD 17,000) per year for the department. The yearly cost of employing a full-time team of CIED specialists would have been USD 135,456. The service triggered electrophysiology consultation on 13 device malfunctions. Conclusions: An anesthesiology-led CIED service resulted in substantial cost savings, increased OR efficiency and patient safety.

Current therapies for Head and Neck cancer treatment are extremely advanced. Though, they cause oral complications which have deleterious effects on basic life functions, affect oral and overall health, may lead to significant morbidity and treatment discontinuation and have an impact on survivorship and quality of life. As new therapies are introduced, a new spectrum of oral complications is rising, compromising the mucosal integrity and the salivary function, that may not be recognized, reported and treated properly. Oral complications, often permanent and extremely painful, may include mucositis, xerostomia, dysgeusia, infections, trismus and fibrosis, risk of dental disease and necrosis of the jaw, neurosensory disorders and when targeted therapies and immunotherapy are involved, aphthoid and lichenoid lesions can also be reported. Increased awareness is required for the prevention and management of these complications, which can be best provided by a multidisciplinary team.

Abstract Cardiac remodeling is recognized as an important aspect of cardiovascular disease (CVD) progression. Machine learning (ML) techniques were applied to basic clinical parameters and electrocardiographic features, in order to detect abnormal left ventricular geometry (LVG) even before the onset of left ventricular hypertrophy (LVH), in a population without established CVD. The authors enrolled 528 patients with and without essential hypertension, but no other indications of CVD. All patients underwent a full echocardiographic evaluation and were classified into 3 groups; normal geometry (NG), concentric remodeling without LVH (CR), and LVH. Abnormal LVG was identified as increased relative wall thickness (RWT) and/or left ventricular mass index (LVMi). The authors trained supervised ML models to classify patients with abnormal LVG and calculated SHAP values to perform feature importance and interaction analysis. Hypertension, age, body mass index over the Sokolow‐Lyon voltage, QRS‐T angle, and QTc duration were some of the most important features. Our model was able to distinguish NG from CR+LVH combined, with 87% accuracy on an unseen test set, 75% specificity, 97% sensitivity, and area under the receiver operating curve (AUC/ROC) equal to 0.91. The authors also trained our model to classify NG and CR (NG + CR) against those with LVH, with 89% test set accuracy, 93% specificity, 67% sensitivity, and an AUC/ROC value of 0.89, for a 0.4 decision threshold. Our ML algorithm effectively detects abnormal LVG even at early stages. Innovative solutions are needed to improve risk stratification of patients without established CVD, and ML may enable progress in this direction.

Abstract Sepsis is a dysregulated host response to infection related to devastating outcomes. Recently, interest has been shifted towards apoptotic and antiapoptotic pathobiology. Apoptosis is executed through the activation of caspases regulated by a number of antiapoptotic proteins, such as survivin. The survivin and caspases’ responses to sepsis have not yet been elucidated. This is a multicenter prospective observational study concerning patients with sepsis (n = 107) compared to patients with traumatic systemic inflammatory response syndrome (SIRS) (n = 75) and to healthy controls (n = 89). The expression of survivin was quantified through real-time quantitative polymerase chain reaction for the different survivin splice variants (wild type-WT, ΔEx3, 2B, 3B) in peripheral blood leukocytes. The apoptotic or antiapoptotic tendency was specified by measuring survivin-WT, caspase-3, and -9 serum protein concentrations through enzyme-linked immunosorbent assay. The survivin-WT, -2B, -ΔΕx3 mRNA, survivin protein, and caspases showed an escalated increase in SIRS and sepsis, whereas survivin-3B was repressed in sepsis (p

Remote monitoring and control of heart function are of primary importance for patient evaluation and management, especially in the modern era of precision medicine and personalized approach. Breaking technological developments have brought to the frontline a variety of smart wearable devices, such as smartwatches, chest patches/straps, or sensors integrated into clothing and footwear, which allow continuous and real-time recording of heart rate, facilitating the detection of cardiac arrhythmias. However, there is great diversity and significant differences in the type and quality of the information they provide, thus impairing their integration into daily clinical practice and the relevant familiarization of practicing physicians. This review will summarize the different types and dominant functions of cardiac smart wearables available in the market. Furthermore, we report the devices certified by official American and/or European authorities and the respective sources of evidence. Finally, we comment pertinent limitations and caveats as well as the potential answers that flow from the latest technological achievements and future perspectives.

Background: Right ventricular (RV) apex has proven to induce abnormal left ventricular (LV) activation pattern leading to pacing-induced cardiomyopathy (PICM) in a substantial percentage of paced patients. This study assessed the impact of paced QRS duration on the expression in the peripheral blood of sarcoplasmic reticulum calcium ATPase (SERCA) and investigated whether its width is related to the extend of LV remodelling. Methods: We enrolled 52 consecutive patients with preserved ejection fraction (EF) who underwent pacemaker implantation for bradycardic indications. Group A consisted of 24 patients paced for atrioventricular conduction disturbances with QRS = 142 ± 12 ms post-implant and group B of 28 patients paced for sinus node disease with QRS = 94 ± 2%ms post-implant. mRNA levels of SERCA were assesed at implantation, 3, 6 and 12 months follow-up, while echocardiographic parameters at implantation, 1, 2 and 4 years. Results: In group A, mRNA levels of SERCA decreased significantly at 3 months and remained low at 6 and 12 months' follow-up and were associated to the deterioration of LV function and geometry. Paced QRS duration was associated to both the alteration in the expression of SERCA and to the extend of LV remodelling. In group B no statistically significant change was demonstrated. Conclusions: Permanent RV pacing in patients with preserved EF and wide QRS post-implant is associated with a significant reduction of mRNA levels of SERCA. Paced QRS duration is associated to alterations in the expression of SERCA which precede adverse LV remodelling.

We aimed to assess the lipopolysaccharide (LPS), or heat shock (HS) induction, and glutamine-modulating effects on heat shock protein-90α (HSP90α) and cytokines in an ex vivo model using peripheral blood mononuclear cells (PBMCs). The PBMCs of patients with septic shock, trauma-related systemic inflammatory response syndrome (SIRS), and healthy subjects were incubated with 1 μg/mL LPS at 43 °C (HS). Glutamine 10 mM was added 1 hour before or after induction or not at all. We measured mRNA HSP90α, monocyte (m) and lymphocyte (l) HSP90α proteins, interleukin (IL)-1b, -6, -8, -10, tumor necrosis factor-α (TNF-α), and monocyte chemoattractant protein-1 (MCP-1) supernatant levels. Heat shock increased the HSP90α mRNA and mHSP90α in all groups (10-fold in sepsis, p < 0.001 and p = 0.047, respectively). LPS induced the mHSP90α and lHSP90α in healthy (p < 0.001) and mHSP90α in SIRS (p = 0.004) but not in sepsis. LPS induced the cytokines at 24 and 48 h in all groups, especially in trauma (p < 0.001); HS only induced the IL-8 in healthy (p = 0.003) and septic subjects (p = 0.05). Glutamine at 10 mM before or after stimulation did not alter any induction effect of LPS or HS on HSP90α mRNA and mHSP90α protein in sepsis. In SIRS, glutamine before LPS decreased the mHSP90α but increased it when given after HS (p = 0.018). Before or after LPS (p = 0.049) and before HS (p = 0.018), glutamine decreased the lHSP90α expression in sepsis but increased it in SIRS when given after HS (p = 0.003). Regarding cytokines, glutamine enhanced the LPS-induced MCP-1 at 48 h in healthy (p = 0.011), SIRS (p < 0.001), and sepsis (p = 0.006). In conclusion, glutamine at 10 mM, before or after LPS and HS, modulates mHSP90α and lHSP90α in sepsis and SIRS differently and unpredictably. Although it does not alter the stimulation effect on interleukins, glutamine enhances the LPS induction effect on supernatant MCP-1 in all groups. Future research should seek to elucidate better the impact of glutamine and temperature modulation on HSP90α and MCP-1 pathways in sepsis and trauma.

Pazopanib is a potent multi-kinase inhibitor that hinders angiogenesis and blocks tumor growth. It has been approved for the treatment of metastatic renal cell carcinoma (mRCC) and advanced soft tissue sarcoma. There is emerging evidence that bleeding is a common adverse effect of pazopanib and other targeted therapies in patients with mRCC. In addition, jaw osteonecrosis related to pazopanib was recently described in the literature. We report three cases of patients with mRCC who developed adverse oral events related to pazopanib. The first patient, treated with pazopanib as monotherapy, presented with gingival bleeding and oral burning sensation. The other two patients receiving pazopanib as monotherapy and pazopanib followed by sunitinib, respectively, presented complaining about mandibular pain; a diagnosis of medication-related osteonecrosis of the jaw (MRONJ) was rendered in both cases. Gingival bleeding and MRONJ may develop as oral side effects of pazopanib use. The cases presented here aim to alert and inform health care professionals about the risk of adverse oral events in patients with mRCC receiving the antiangiogenic agent pazopanib.

The present study aimed to investigate any biochemical and histological changes of the rat condyle and mandible in animals that had sustained mandibular growth restriction. Seventy-two male Wistar rats were divided into two equal groups, experimental and control. Each group consisted of three equal subgroups. The animals were sacrificed 30, 60, and 90 days after the start of the experiment. Blood samples were collected from the eye, and the osteoprotegerin (OPG), Receptor Activator of Nuclear Factor Kappa B Ligand (RANKL), and Macrophage Colony-Stimulating factor (MCSF)concentrations were measured by using enzyme-linked immunosorbent assay (ELISA) kits. A histological analysis was performed on the mandibular condyles. The blood serum values of OPG, RANKL, and MCSF did not exhibit any statistically significant difference between groups or subgroups. However, significant histological changes became evident after a histomorphometric condylar examination was performed. The Bone Surface/Total Surface ratio appeared reduced in the anterior and posterior regions of the condyle. In addition, the Posterior Condylar Cartilage Thickness was measured and determined to be significantly diminished. The present intervention that employed orthodontic/orthopedic devices did not prove to have any significant effect on the circulating proteins under study. Posterior displacement of the mandible may culminate only in local histological alterations in condylar cartilage thickness and its osseous microarchitecture.

Background and study aims Through advanced endoscopic clipping techniques, endoscopic treatment of both diagnostic and therapeutic acute iatrogenic colonic perforations has been shown effective. The main purpose of this study was to compare the management of acute iatrogenic perforations (AIPs) of the colon before and after the introduction of advanced clipping techniques. Methods We conducted a retrospective study from July 1996 to February 2020. The period was divided into two sub periods, Period 1: from July 1996 to December 2012 and Period 2: from January 2013 to March 2020. All AIPs occurring during a colonoscopy and detected during or immediately (

Aims: To evaluate the impact of lockdown during the COVID-19 pandemic on lifestyle changes of the general population, and on admissions for acute coronary syndrome (ACS).Methods and Results: All ACS admissions during the COVID-19 lockdown (10 March to 4 May, 2020), in 3 municipalities (3 spoke, and 1 hub hospital), in Southwestern Greece (411,576 inhabitants), were prospectively recorded and compared to the equivalent periods during 2018, and 2019. A telephone survey of 1014 participants was conducted to explore the lifestyle habits of citizens aged ≥35-years-old before and during lockdown. The median ACS incidence rate decreased from 19.0 cases per week in 2018 and 21.5 in 2019 down to 13.0 in 2020 (RR: 0.66 during the Covid-19 lockdown; 95%CI: 0.53–0.82; P = 0.0002). This was driven by a significant reduction of admissions for Non-ST elevation myocardial infarction (NSTEMI) (RR: 0.68; 95%CI: 0.52–0.88; P = 0.0037), mainly in patients with a lower burden of cardiovascular risk factors, as we noticed an inverse association between the reduction of the incidence of ACS during the Covid-19 lockdown period and the number of registered patient risk factors. There was no difference in the rates of STEMI and population-based all-cause mortality across the examined time periods. The telephone survey demonstrated reduction of passive smoking, working hours, alcohol, junk food and salt consumption, and an increase in sleeping hours, mainly in participants with a lower burden of cardiovascular risk factors.Conclusions: A significant decline in ACS admissions during the COVID-19 lockdown was noted, affecting mainly NSTEMI patients with a lower burden of cardiovascular risk factors. This was accompanied by significant lifestyle changes. Thus, it is tempting to speculate that to some extend the latter might be associated with the observed decline in ACS admissions.

BackgroundAlthough many studies have described patient-level risk factors for outcomes in heart failure (HF), health care structural determinants remain largely unexplored. This research reports patient-, hospital- and country-level characteristics associated with 1-year all-cause mortality among patients with chronic HF, and investigates geographic and hospital variation in mortality.Methods and findingsWe included 9,277 patients with chronic HF enrolled between May 2011 and November 2017 in the prospective cohort study European Society of Cardiology Heart Failure Long Term registry across 142 hospitals, located in 22 countries. Mean age of the selected outpatients was 65 years (sd 13.2) and 28% were female. The all-cause 1-year mortality rate per 100 person-years was 7.1 (95% confidence interval (CI) 6.6-7.7), and varied between countries (median 6.8, IQR 5.6-11.2) and hospitals (median 7.8, IQR 5.2-12.4). Mortality was associated with age (incidence rate ratio 1.03, 95% CI 1.02-1.04), diabetes mellitus (1.37, 1.15-1.63), peripheral artery disease (1.56, 1.27-1.92), New York Heart Association class III/IV (1.91, 1.60-2.30), treatment with angiotensin-converting enzyme inhibitor and angiotensin receptor antagonists (0.71, 0.57-0.87) and HF clinic (0.64, 0.46-0.89). No other hospital-level characteristics, and no country-level healthcare characteristics were associated with 1-year mortality, with case-mix standardised variance between countries being very low (1.83e-06) and higher for hospitals (0.372).ConclusionsAll-cause mortality at 1 year among outpatients with chronic HF varies between countries and hospitals, and is associated with patient characteristics and the availability of hospital HF clinics. After full adjustment for clinical, hospital and country variables, between-country variance was negligible while between-hospital variance was evident.

Silibinin/silymarin has been used in herbal medicine for thousands of years and it is well-known for its hepato-protective properties. The present comprehensive literature review aimed to critically summarize the pharmacological properties of silymarin extract and its main ingredient silibinin in relation to classical cardiovascular risk factors (e.g., diabetes mellitus, etc.). We also assessed their potential protective and/or therapeutic application in cardiovascular diseases (CVDs), based on experimental and clinical studies. Pre-clinical studies including in vitro tests or animal models have predominantly implicated the following effects of silymarin and its constituents: (1) antioxidant, (2) hypolipidemic, (3) hypoglycemic, (4) anti-hypertensive and (5) cardioprotective. On the other hand, a direct amelioration of atherosclerosis and endothelial dysfunction after silymarin administration seems weak based on scarce data. In clinical trials, the most important findings are improved (1) glycemic and (2) lipid profiles in patients with type 2 diabetes mellitus and/or hyperlipidemia, while (3) the anti-hypertensive effects of silibinin/silymarin seem very modest. Finally, the changes in clinical endpoints are not robust enough to draw a firm conclusion. There are significant limitations in clinical trial design, including the great variety in doses and cohorts, the underlying conditions, the small sample sizes, the short duration and the absence of pharmacokinetic/pharmacodynamic tests prior to study commitment. More data from well-designed and high-quality pre-clinical and clinical studies are required to firmly establish the clinical efficacy of silibinin/silymarin and its possible therapeutic application in cardiovascular diseases.

Mandibular protrusion and its treatment is challenging for the orthodontist. The aim of the present research was to identify macroscopic changes in the mandible, based on three-dimensional Cone Beam Computed Tomography analysis. Seventy-two male Wistar rats were divided into two equal groups, experimental (group A) and control (group B). Each consisted of three equal subgroups of 12 rats (A1, A2, A3, B1, B2, B3). Full-cast orthodontic intraoral devices were attached to the maxillary incisors of the experimental animals, and effected functional posterior mandibular displacement. Throughout the experimental period, all animals were fed with mashed food. Animals were sacrificed at 30 days (A1, B1), 60 days (A2, B2) and 90 days (A3, B3). At the 60th day of the experiment, the orthodontic devices were removed from the remaining experimental subgroup A3. Measurements revealed significant differences in the anteroposterior dimensions between experimental and control subgroups. However, the observed changes in the vertical dimensions, Condylion/Go’–Menton and the Intercondylar distance proved insignificant. Posterior mandibular displacement of the mandible in growing rats affects the morphology of the mandible and culminates in the development of a smaller mandible at a grown age.

Oxidative stress is considered pivotal in the pathophysiology of sepsis. Oxidants modulate heat shock proteins (Hsp), interleukins (IL), and cell death pathways, including apoptosis. This multicenter prospective observational study was designed to ascertain whether an oxidant/antioxidant imbalance is an independent sepsis discriminator and mortality predictor in intensive care unit (ICU) patients with sepsis (n = 145), compared to non-infectious critically ill patients (n = 112) and healthy individuals (n = 89). Serum total oxidative status (TOS) and total antioxidant capacity (TAC) were measured by photometric testing. IL-6, -8, -10, -27, Hsp72/90 (ELISA), and selected antioxidant biomolecules (Ζn, glutathione) were correlated with apoptotic mediators (caspase-3, capsase-9) and the central anti-apoptotic survivin protein (ELISA, real-time PCR). A wide scattering of TOS, TAC, and TOS/TAC in all three groups was demonstrated. Septic patients had an elevated TOS/TAC, compared to non-infectious critically ill patients and healthy individuals (p = 0.001). TOS/TAC was associated with severity scores, procalcitonin, IL-6, -10, -27, IFN-γ, Hsp72, Hsp90, survivin protein, and survivin isoforms -2B, -ΔΕx3, -WT (p < 0.001). In a propensity probability (age-sex-adjusted) logistic regression model, only sepsis was independently associated with TOS/TAC (Exp(B) 25.4, p < 0.001). The AUCTOS/TAC (0.96 (95% CI = 0.93–0.99)) was higher than AUCTAC (z = 20, p < 0.001) or AUCTOS (z = 3.1, p = 0.002) in distinguishing sepsis. TOS/TAC, TOS, survivin isoforms -WT and -2B, Hsp90, IL-6, survivin protein, and repressed TAC were strong predictors of mortality (p < 0.01). Oxidant/antioxidant status is impaired in septic compared to critically ill patients with trauma or surgery and is related to anti-apoptotic, inflammatory, and innate immunity alterations. The unpredicted TOS/TAC imbalance might be related to undefined phenotypes in patients and healthy individuals.

Atrial fibrillation (AF) is the most frequent arrhythmia managed in clinical practice, and it is linked to an increased risk of death, stroke, and peripheral embolism. The Global Burden of Disease shows that the estimated prevalence of AF is up to 33.5 million patients. So far, successful therapeutic techniques have been implemented, with a high health-care cost burden. As a result, identifying modifiable risk factors for AF and suitable preventive measures may play a significant role in enhancing community health and lowering health-care system expenditures. Several mechanisms, including electrical and structural remodeling of atrial tissue, have been proposed to contribute to the development of AF. This review article discusses the predisposing factors in AF including the different pathogenic mechanisms, sedentary lifestyle, and dietary habits, as well as the potential genetic burden.