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We compared the effects of Heat-not-Burn cigarette (HNBC) to those of tobacco cigarette (Tcig), on myocardial, coronary and arterial function as well as on oxidative stress and platelet activation in 75 smokers. In the acute study, 50 smokers were randomised into smoking a single Tcig or a HNBC and after 60 min were crossed-over to the alternate smoking. For chronic phase, 50 smokers were switched to HNBC and were compared with an external group of 25 Tcig smokers before and after 1 month. Exhaled carbon monoxide (CO), pulse wave velocity (PWV), malondialdehyde (MDA) and thromboxane B2 (TxB2) were assessed in the acute and chronic study. Global longitudinal strain (GLS), myocardial work index (GWI), wasted myocardial work (GWW), coronary flow reserve (CFR), total arterial compliance (TAC) and flow-mediated dilation (FMD) were assessed in the chronic study. Acute HNBC smoking caused a smaller increase of PWV than Tcig (change 1.1 vs 0.54 m/s, p < 0.05) without change in CO and biomarkers in contrast to Tcig. Compared to Tcig, switching to HNBC for 1-month improved CO, FMD, CFR, TAC, GLS, GWW, MDA, TxB2 (differences 10.42 ppm, 4.3%, 0.98, 1.8 mL/mmHg, 2.35%, 19.72 mmHg%, 0.38 nmol/L and 45 pg/mL respectively, p < 0.05). HNBCs exert a less detrimental effect on vascular and cardiac function than tobacco cigarettes. Trial registration Registered on https://clinicaltrials.gov/ (NCT03452124, 02/03/2018).

Background Incretin-based therapies are used in the treatment of type 2 diabetes mellitus (T2DM) and obesity. We investigated the changes in arterial stiffness and left ventricular (LV) myocardial deformation after 6-month treatment with the GLP-1 analogue liraglutide in subjects with newly diagnosed T2DM. Methods We randomized 60 patients with newly diagnosed and treatment-naive T2DM to receive either liraglutide (n = 30) or metformin (n = 30) for 6 months. We measured at baseline and after 6-month treatment: (a) carotid-femoral pulse wave velocity (PWV) (b) LV longitudinal strain (GLS), and strain rate (GLSR), peak twisting (pTw), peak twisting velocity (pTwVel) and peak untwisting velocity (pUtwVel) using speckle tracking echocardiography. LV untwisting was calculated as the percentage difference between peak twisting and untwisting at MVO (%dpTw–Utw MVO ), at peak (%dpTw–Utw PEF ) and end of early LV diastolic filling (%dpTw–Utw EDF ) (c) Flow mediated dilatation (FMD) of the brachial artery and percentage difference of FMD (FMD%) (d) malondialdehyde (MDA), protein carbonyls (PCs) and NT-proBNP. Results After 6-months treatment, subjects that received liraglutide presented with a reduced PWV (11.8 ± 2.5 vs. 10.3 ± 3.3 m/s), MDA (0.92 [0.45–2.45] vs. 0.68 [0.43–2.08] nM/L) and NT-proBNP (p < 0.05) in parallel with an increase in GLS (− 15.4 ± 3 vs. − 16.6 ± 2.7), GLSR (0.77 ± 0.2 vs. 0.89 ± 0.2), pUtwVel (− 97 ± 49 vs. − 112 ± 52°, p < 0.05), %dpTw–Utw MVO (31 ± 10 vs. 40 ± 14), %dpTw–Utw PEF (43 ± 19 vs. 53 ± 22) and FMD% (8.9 ± 3 vs. 13.2 ± 6, p < 0.01). There were no statistically significant differences of the measured markers in subjects that received metformin except for an improvement in FMD. In all subjects, PCs levels at baseline were negatively related to the difference of GLS (r = − 0.53) post-treatment and the difference of MDA was associated with the difference of PWV (r = 0.52) (p < 0.05 for all associations) after 6-month treatment. Conclusions Six-month treatment with liraglutide improves arterial stiffness, LV myocardial strain, LV twisting and untwisting and NT-proBNP by reducing oxidative stress in subjects with newly diagnosed T2DM. ClinicalTrials.gov Identifier NCT03010683

AimsRemote ischemic conditioning (RIC) alleviates ischemia–reperfusion injury via several pathways, including micro-RNAs (miRs) expression and oxidative stress modulation. We investigated the effects of RIC on endothelial glycocalyx, arterial stiffness, LV remodelling, and the underlying mediators within the vasculature as a target for protection.Methods and resultsWe block-randomised 270 patients within 48 h of STEMI post-PCI to either one or two cycles of bilateral brachial cuff inflation, and a control group without RIC. We measured: (a) the perfusion boundary region (PBR) of the sublingual arterial microvessels to assess glycocalyx integrity; (b) the carotid-femoral pulse wave velocity (PWV); (c) miR-144,-150,-21,-208, nitrate-nitrite (NOx) and malondialdehyde (MDA) plasma levels at baseline (T0) and 40 min after RIC onset (T3); and (d) LV volumes at baseline and after one year. Compared to baseline, there was a greater PBR and PWV decrease, miR-144 and NOx levels increase (p < 0.05) at T3 following single- than double-cycle inflation (PBR:ΔT0–T3 = 0.249 ± 0.033 vs 0.126 ± 0.034 μm, p = 0.03 and PWV:0.4 ± 0.21 vs −1.02 ± 0.24 m/s, p = 0.03). Increased miR-150,-21,-208 (p < 0.05) and reduced MDA was observed after both protocols. Increased miR-144 was related to PWV reduction (r = 0.763, p < 0.001) after the first-cycle inflation in both protocols. After one year, single-cycle RIC was associated with LV end-systolic volume reduction (LVESV) > 15% (odds-ratio of 3.75, p = 0.029). MiR-144 and PWV changes post-RIC were interrelated and associated with LVESV reduction at follow-up (r = 0.40 and 0.37, p < 0.05), in the single-cycle RIC.ConclusionRIC evokes “vascular conditioning” likely by upregulation of cardio-protective microRNAs, NOx production, and oxidative stress reduction, facilitating reverse LV remodelling.Clinical Trial Registrationhttp://www.clinicaltrials.gov. Unique identifier: NCT03984123.

Background Paraneoplastic neurological syndromes constitute rare neurological complications of malignant disease, manifesting in <1% of patients with cancer. Opsoclonus-myoclonus syndrome (OMS) presents with chaotic ocular saccades (opsoclonus), spontaneous muscular jerking (myoclonus) that may be accompanied by ataxia, strabismus, aphasia, or mutism. Its paraneoplastic variant in the adult is most commonly associated with small-cell lung cancer, followed by breast cancer. Importantly, neurological symptoms usually precede the diagnosis of breast cancer and tend to recure after its treatment. Case presentation A 43-year-old premenopausal Caucasian woman with a medical history of hypertension was admitted following an episode of focal seizure. This progressed to generalised tonic-clonic seizures and she was subsequently loaded with phenytoin, valproate, and levetiracetam. Initial workup included whole body CT scan, viral and autoimmune serology. The CT scan revealed an enhancing right axillary lymph node, which in combination with Anti-Ri antibody positivity raised the spectre of paraneoplastic OMS. MRI of the head revealed subtle nonspecific white matter signal change within the centrum semiovale without any mass lesions, while MRI of the spine was unremarkable. An uncomplicated right mastectomy and axillary lymph node clearance was performed: histopathology revealed a 9-mm, grade 2, oestrogen receptor-positive, progesterone receptor-negative (ER8, PR0), Her2-negative invasive ductal carcinoma, and 4/6 positive lymph nodes (T1b N2 M0). Two months later, she was readmitted with vertigo, diplopia, facial weakness, and ataxia, setting the diagnosis anti-Ri syndrome recurrence. MDT recommended mammogram and ultrasound of the left breast, which were normal. Subsequently, four months after initial discharge, she suffered another neurological recurrence; due to concomitant abdominal pain, PET-CT was performed demonstrating a hypermetabolic right ovarian focus. Bilateral salpingo-oophorectomy was performed as per gynaecology MDT and final histology showed normal tubes and ovaries. She has remained on remission since then, with a negative annual mammogram follow-up. Conclusions In conclusion, we report a case of OMS associated with breast cancer anti-Ri onconeural antibody. Its manifestations preceded the diagnosis of malignancy and it persisted after cancer treatment, underlining the importance for high clinical suspicion in cases of classical paraneoplastic neurological syndromes as well as the need for long-term clinical follow-up.

Ischaemia–reperfusion injury (IRI) encompasses the deleterious effects on cellular function and survival that result from the restoration of organ perfusion. Despite their unique tolerance to ischaemia and hypoxia, afforded by their dual (pulmonary and bronchial) circulation as well as direct oxygen diffusion from the airways, lungs are particularly susceptible to IRI (LIRI). LIRI may be observed in a variety of clinical settings, including lung transplantation, lung resections, cardiopulmonary bypass during cardiac surgery, aortic cross-clamping for abdominal aortic aneurysm repair, as well as tourniquet application for orthopaedic operations. It is a diagnosis of exclusion, manifesting clinically as acute lung injury (ALI) or acute respiratory distress syndrome (ARDS). Ischaemic conditioning (IC) signifies the original paradigm of treating IRI. It entails the application of short, non-lethal ischemia and reperfusion manoeuvres to an organ, tissue, or arterial territory, which activates mechanisms that reduce IRI. Interestingly, there is accumulating experimental and preliminary clinical evidence that IC may ameliorate LIRI in various pathophysiological contexts. Considering the detrimental effects of LIRI, ranging from ALI following lung resections to primary graft dysfunction (PGD) after lung transplantation, the association of these entities with adverse outcomes, as well as the paucity of protective or therapeutic interventions, IC holds promise as a safe and effective strategy to protect the lung. This article aims to provide a narrative review of the existing experimental and clinical evidence regarding the effects of IC on LIRI and prompt further investigation to refine its clinical application.

Background The coronavirus-disease 2019 (COVID-19) pandemic imposed an unprecedented burden on the provision of cardiac surgical services. The reallocation of workforce and resources necessitated the postponement of elective operations in this cohort of high-risk patients. We investigated the impact of this outbreak on the aortic valve surgery activity at a single two-site centre in the United Kingdom. Methods Data were extracted from the local surgical database, including the demographics, clinical characteristics, and outcomes of patients operated on from March 2020 to May 2020 with only one of the two sites resuming operative activity and compared with the respective 2019 period. A similar comparison was conducted with the period between June 2020 and August 2020, when operative activity was restored at both institutional sites. The experience of centres world-wide was invoked to assess the efficiency of our services. Results There was an initial 38.2% reduction in the total number of operations with a 70% reduction in elective cases, compared with a 159% increase in urgent and emergency operations. The attendant surgical risk was significantly higher [median Euroscore II was 2.7 [1.9–5.2] in 2020 versus 2.1 [0.9–3.7] in 2019 ( p  = 0.005)] but neither 30-day survival nor freedom from major post-operative complications (re-sternotomy for bleeding/tamponade, transient ischemic attack/stroke, renal replacement therapy) was compromised ( p  > 0.05 for all comparisons). Recommencement of activity at both institutional sites conferred a surgical volume within 17% of the pre-COVID-19 era. Conclusions Our institution managed to offer a considerable volume of aortic valve surgical activity over the first COVID-19 outbreak to a cohort of higher-risk patients, without compromising post-operative outcomes. A backlog of elective cases is expected to develop, the accommodation of which after surgical activity normalisation will be crucial to monitor.

BackgroundAnakinra, an interleukin-1 receptor antagonist and tocilizumab, an interleukin-6 receptor blocker, are used for the treatment of rheumatoid arthritis. We investigated the differential effects of anakinra and tocilizumab on myocardial and vascular function in an atherosclerosis model of patients with rheumatoid arthritis.Methods120 patients with rheumatoid arthritis were randomized to anakinra (n = 40), tocilizumab (n = 40) or prednisolone (n = 40) for 3 months. Primary outcome measure was the change of left ventricular longitudinal strain after 3 months of treatment. Additionally, we measured coronary flow reserve, flow-mediated dilatation of the brachial artery, carotid-femoral pulse wave velocity, malondialdehyde and protein carbonyls as oxidative stress markers and C-reactive protein blood levels at baseline and post-treatment.ResultsAt baseline, patients among the three treatment arms had similar age, sex, disease activity score and atherosclerotic risk factors. Compared with baseline, all patients had improved longitudinal strain (− 16% vs. − 17.8%), coronary flow reserve (2.56 vs. 2.9), malondialdehyde (2.0 vs. 1.5 µM/L), protein carbonyls (0.0132 vs. 0.0115 nmol/mg), and C-reactive protein post-treatment. In all patients, the percent decrease of malondialdehyde was correlated with percent increase of longitudinal strain (p < 0.001). Compared with tocilizumab and prednisolone, anakinra treatment resulted in a greater improvement of longitudinal strain (18.7% vs. 9.7% vs. 6%) and coronary flow reserve (29% vs. 13% vs. 1%), while pulse wave velocity and brachial blood pressure were improved only after tocilizumab treatment (11 ± 3 vs. 10.3 ± 2 m/s p < 0.05 for all comparisons).ConclusionsAnakinra is associated with an improvement in cardiac function and tocilizumab with improvement in vascular function.Clinical Trial RegistrationURL: https://http://www.clinicaltrials.gov. Unique identifier: NCT03288584.

Abstract In this study an unusual combination of arterial, venous and neural variations discovered during dissection of cervical, axillary and brachial area of a cadaver is described. Variations are thoroughly described and literature is briefly reviewed. Lateral cord of brachial plexus was not formed; Eight Cervical root divided into anterior and posterior division before uniting with First Thoracic root and Upper Trunk was unusually short. Axillary artery gave origin to a superficial brachial artery and then continued as deep brachial artery. Multiple variations in typical axillary artery branches were present including existence of inferior pectoral artery. Cephalic vein was absent. A variety of interventions, from relative simple as central venous catheter placement to most complicated as brachial plexus injury repair demand thorough knowledge of area’s regional anatomy. Familiarity with anatomic variations allows more precise and careful interventions. Research on these variations is valuable for anatomists and embryologists but also for clinicians because it may provide useful information for non - typical cases but also helps in raising a high level of suspicion.

Diabetes mellitus is a major factor contributing to the development of cardiovascular disease. As morbidity and mortality rates rise dramatically, when target organ damage develops pre-symptomatic assessment is critical for the management of diabetic patients. Echocardiography is a noninvasive and reproducible method that may aid in risk stratification and in evaluation of treatment effects. The aim of this review is to analyze the echocardiographic techniques which can detect early alteration in cardiac function in patients with diabetes.

Background: Maternal vitamin D status during pregnancy has been hypothesized to influence offspring neurodevelopment; however, the evidence remains inconsistent. Methods: We studied 66 mother–child pairs from the KLOTHO cohort with serum 25-hydroxyvitamin D [25(OH)D] measurements at delivery (maternal and umbilical cord). At 10 years of age, neurodevelopment was assessed using standardized questionnaires, generating composite z-scores for cognitive (cognitive, communication, motor) and psychosocial (social–sentimental, special interests) domains. Multivariable models were adjusted for sex, maternal body mass index and education, and neonatal birth weight and gestational age. Results: Maternal 25(OH)D deficiency (<50 nmol/L) was not associated with cognitive composite scores (p = 0.77). The psychosocial composite scores showed a non-significant negative trend (p = 0.29). Neonatal deficiency showed no consistent association with cognition (p = 0.99) or psychosocial outcomes (p = 0.30). Exploratory partial correlations suggested a positive association between maternal 25(OH)D and psychosocial development (r = 0.60, p = 0.038, n = 12). Seasonal variation in maternal vitamin D was observed (autumn: 56.0 ± 24.6 vs. winter: 32.0 ± 18.3 nmol/L; p < 0.0001), but did not translate into differences in 10-year outcomes. Conclusions: In this cohort of 66 pairs, perinatal vitamin D status was not a determinant of global cognition at 10 years of age. A potential link with psychosocial development requires replication in larger longitudinal studies. Due to the limited sample size, all findings should be interpreted as exploratory.