In SARS-CoV-2 patients with severe acute respiratory distress syndrome (ARDS), Veno-Venous Extracorporeal Membrane Oxygenation (V-V ECMO) was shown to provide valuable treatment with reasonable survival in large multi-centre investigations. However, in some patients, conversion to modified ECMO support forms may be needed. In this single-centre retrospective registry, all consecutive patients receiving V-V ECMO between 1 March 2020 to 1 May 2021 were included and analysed. The patient cohort was divided into two groups: those who remained on V-V ECMO and those who required conversion to other modalities. Seventy-eight patients were included, with fourteen cases (18%) requiring conversions to veno-arterial (V-A) or hybrid ECMO. The reasons for the ECMO mode configuration change were inadequate drainage (35.7%), inadequate perfusion (14.3%), myocardial infarction (7.1%), hypovolemic shock (14.3%), cardiogenic shock (14.3%) and septic shock (7.1%). In multivariable analysis, the use of dobutamine (p = 0.007) and a shorter ICU duration (p = 0.047) predicted the conversion. The 30-day mortality was higher in converted patients (log-rank p = 0.029). Overall, only 19 patients (24.4%) survived to discharge or lung transplantation. Adverse events were more common after conversion and included renal, cardiovascular and ECMO-circuit complications. Conversion itself was not associated with mortality in the multivariable analysis. In conclusion, as many as 18% of patients undergoing V-V ECMO for COVID-19 ARDS may require conversion to advanced ECMO support.

Aims Because reported mortality on veno-arterial (V-A) extracorporeal life support (ECLS) substantially varies between centres, the aim of the current analysis was to assess the outcomes between units performing heart transplantation and/or implanting ventricular assist device (HTx/VAD) vs. non-HTx/VAD units in patients undergoing V-A ECLS for cardiogenic shock. Methods and results Systematic search according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses was performed using PubMed/MEDLINE databases until 30 November 2019. Articles reporting in-hospital/ 30-day mortality and centre's HTx/VAD status were included. In-hospital outcomes and long-term survival were analysed in subgroup meta-analysis. A total of 174 studies enrolling n = 13 308 patients were included with 20 series performed in non-HTx/VAD centres (1016 patients, 7.8%). Majority of patients underwent V-A ECLS for post-cardiotomy shock (44.2%) and acute myocardial infarction (20.7%). Estimated overall in-hospital mortality was 57.2% (54.9-59.4%). Mortality rates were higher in non-HTx/VAD [65.5% (59.8-70.8%)] as compared with HTx/VAD centres [55.8% (53.3-58.2%)], P < 0.001. Estimated late survival was 61.8% (55.7-67.9%) without differences between non-HTx/VAD and HTx/VAD centres: 66.5% (30.3-1.02%) vs. 61.7% (55.5-67.8%), respectively (P = 0.797). No differences were seen with respect to ECLS duration, limb complications, and reoperations for bleeding, kidney injury, and sepsis. Yet, weaning rates were higher in HTx/VAD vs. non-HTx/VAD centres: 58.7% (56.2-61.1%) vs. 48.9% (42.0-55.9%), P = 0.010. Estimated rate of bridge to heart transplant was 6.6% (5.2-8.3%) with numerical, yet not statistically significant, difference between non-HTx/VAD [2.7% (0.8-8.3%)] as compared with HTx/VAD [6.7% (5.3-8.6%)] (P = 0.131). Conclusions Survival after V-A ECLS differed according to centre's HTx/VAD status. Potentially different risk profiles of patients must be taken account for before definite conclusions are drawn.

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Capsaicin is a natural compound found in chili peppers and is used in the diet of many countries. The important mechanism of action of capsaicin is its influence on TRPV1 channels in nociceptive sensory neurons. Furthermore, the beneficial effects of capsaicin in cardiovascular and oncological disorders have been described. Many recent publications show the positive effects of capsaicin in animal models of brain disorders. In Alzheimer’s disease, capsaicin reduces neurodegeneration and memory impairment. The beneficial effects of capsaicin in Parkinson’s disease and depression have also been described. It has been found that capsaicin reduces the area of infarction and improves neurological outcomes in animal models of stroke. However, both proepileptic and antiepileptic effects of capsaicin in animal models of epilepsy have been proposed. These contradictory results may be caused by the fact that capsaicin influences not only TRPV1 channels but also different molecular targets such as voltage-gated sodium channels. Human studies show that capsaicin may be helpful in treating stroke complications such as dysphagia. Additionally, this compound exerts pain-relieving effects in migraine and cluster headaches. The purpose of this review is to discuss the mechanisms of the beneficial effects of capsaicin in disorders of the central nervous system.

Background: Frequent occurrence of paravalvular leak (PVL) after transcatheter aortic valve replacement (TAVR) was the main concern with early-generation devices and focused technological improvements.Current systematic review and meta-analysis sought to compare outcomes of TAVR for severe native valve stenosis with next-generation devices: Lotus and Sapien 3. Methods: Electronic databases were screened for studies comparing outcomes of TAVR with Lotus and Sapien 3. In a random-effects meta-analysis, the pooled incidence rates of procedural, clinical and functional outcomes according to VARC-2 definitions were assessed.Results: Eleven observational studies including 2,836 patients (Lotus N=862 vs. Sapien 3 N=1,974) met inclusion criteria. No differences were observed regarding composite endpoints-device success and early safety. Similarly, 30-day mortality, major vascular complications, acute kidney injury and serious bleeding events were similar with both devices. Lotus valve demonstrated 35% reduction of the risk for mild PVL: risk ratio (RR) 0.65, 95% confidence interval (CI): 0.49-0.85, P=0.002; but there were no statistical differences with regard to moderate/severe PVL (RR 0.56, 95% CI: 0.18-1.77, P=0.320). Lotus valves produced significantly higher mean transaortic gradients: mean difference (MD) 0.88 mmHg, 95% CI, 0.24-1.53 mmHg, P=0.007; however, without translation into higher rate of prosthesis-patient mismatch (RR 1.10, 95% CI: 0.82-1.47, P=0.540). As compared to Sapien 3, Lotus device placement was associated with significantly higher rate of permanent pacemaker implantation (RR 2.30, 95% CI: 1.95-2.71, P<0.

No abstract

Frequent occurrence of paravalvular leak (PVL) after transcatheter aortic valve replacement (TAVR) was the main concern with earlier-generation devices. Current meta-analysis compared outcomes of TAVR with next-generation devices: ACURATE neo and SAPIEN 3. In random-effects meta-analysis, the pooled incidence rates of procedural, clinical and functional outcomes according to VARC-2 definitions were assessed. One randomized controlled trial and five observational studies including 2818 patients (ACURATE neo n = 1256 vs. SAPIEN 3 n = 1562) met inclusion criteria. ACURATE neo was associated with a 3.7-fold increase of moderate-to-severe PVL (RR (risk ratio): 3.70 (2.04–6.70); P < 0.0001), which was indirectly related to higher observed 30-day mortality with ACURATE valve (RR: 1.77 (1.03–3.04); P = 0.04). Major vascular complications, acute kidney injury, periprocedural myocardial infarction, stroke and serious bleeding events were similar between devices. ACURATE neo demonstrated lower transvalvular pressure gradients both at discharge (P < 0.00001) and at 30 days (P < 0.00001), along with lower risk of patient–prosthesis mismatch (RR: 0.29 (0.10–0.87); P = 0.03) and pacemaker implantation (RR: 0.64 (0.50–0.81); P = 0.0002), but no differences were observed regarding composite endpoints early safety and device success. In conclusion, ACURATE neo, as compared with SAPIEN 3, was associated with higher rates of moderate-to-severe PVL, which were indirectly linked with increased observed 30-day all-cause mortality.

There are two types of voltage-gated sodium channels: tetrodotoxin (TTX)-sensitive and TTX-resistant channels. TTX-sensitive sodium currents are widely present in both the central and peripheral nervous systems. 1 On the other hand, TTX-resistant sodium currents are extensively described in peripheral neurons, where they play an important role in nociception, including allodynia and hyperalgesia. [2][3][4][5][6][7][8][9][10] Neuronal TTX-resistant sodium currents are carried by two types of sodium channels, Nav1.8 and Nav1.9, which are localized in small diameter peripheral neurons. 9 In the sciatic nerve ligation model, upregulation of Nav1.8 along uninjured nerve fibres was observed, and its blockade with antisense oligodeoxynucleotides reversed neuropathic pain. 5 Moreover, pharmacological agents targeting Nav1.8 showed significant antinociception in animal models of neuropathic pain. 6,11