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Background: Bilateral cardiac sympathetic denervation (CSD) performed via video-assisted thoracoscopic (VAT) surgery shows potential in managing ventricular tachycardia (VT), thereby reducing arrhythmic burden. In this setting, the scarcity of studies addressing both perioperative and long-term outcomes creates a substantial gap in the optimal management of patients with multiple comorbidities and limited treatment options. This observational study aimed to assess the medical comorbidities, as well as the short- and long-term outcomes of patients who underwent CSD for VT refractory to catheter ablation and medical therapy at a referral tertiary teaching hospital., Materials: We retrospectively analyzed data of all patients with VT who underwent bilateral CSD-VAT surgery at a single center. Unadjusted Kaplan-Meier survival curves were generated to analyze the survival rates at 1-year and 2-years following the procedure., Results: Ten consecutive patients were unrolled between August 2014 and March 2024. Bilateral CSD-VAT surgery was successfully performed in all patients. Pre-operative ejection fraction was 33 % (26-41). Two patients (22 %) suffered cardiogenic shock and 1 vasoplegia. Half (50 %) of the patients necessitated inotrope/vasopressor support and 1 an intra-aortic balloon pump. Median hospital stay was 12 (9-19) days. Three (33 %) patients required postoperative ICU admission. All patients were alive upon hospital discharge. Neither major surgical complications nor complications typically associated with VAT-CSD (e.g., Horner's syndrome) were observed. The 1-year survival was 80 % while the survival at 24 months was 60 %., Conclusions: CSD-VAT is a feasible rescue treatment in patients with refractory VT and is associated with limited intra- and postoperative complications alongside an acceptable long-term survival rate., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: In the PROTECTION trial, intravenous amino acids (AA) decreased the occurrence of acute kidney injury (AKI) in cardiac surgery patients with cardiopulmonary bypass (CPB). Recruitment of renal functional reserve may be responsible for such protection. However, patients with chronic kidney disease (CKD) have diminished renal functional reserve, and AA may be less protective in such patients. Thus, a separate investigation of such patients is warranted., Methods: We defined CKD as an estimated glomerular filtration rate (eGFR)<60 mL·min-1·1.73 m-2 and patients with eGFR≥60 mL·min-1·1.73 m-2 served as controls. The primary outcome was the occurrence of AKI. Secondary outcomes included severity of AKI, need for and duration of renal replacement therapy, and all-cause mortality., Results: Among CKD patients (n=812), compared with placebo, AA significantly decreased the rate of AKI (43.1% vs 50.3%; RR, 0.86; 95%CI, 0.74 to 0.99; p=0.041; number needed to treat [NNT]=14) with a median percentage increase in eGFR from baseline to postoperative day three of 12.7% vs. 6.5% (p=0.002). In eGFR-based CKD subgroups (30 to 39, 40 to 49, and 50 to 59 mL·min-1·1.73 m-2) the AA effect was similar (interaction p=0.50). Finally, AA infusion decreased the occurrence of severe (stage 3) AKI (2.7% vs. 5.6%; RR 0.48; 95%CI, 0.24 to 0.98; p=0.038)., Conclusions: AA infusion protected CKD patients undergoing CPB from developing AKI, with an absolute risk reduction of 7% and a NNT of 14 in a cohort with a >45% rate of AKI. Moreover, it delivered a >50% relative risk reduction in severe AKI., Competing Interests: Conflicts of Interest: Fabio Guarracino has received consulting fees from Abbott, AOP Orphan, Chiesi farmaceutici, Edwards, Masimo, Orion pharma, Vygon, and Viatris. Luca Brazzi has received consulting fees SIARE, 3M. Mario F.L. Gaudino has received research grants from NIH, PCORI, and CIHR. All the other authors declare no competing interests., (Copyright © 2024 American Society of Anesthesiologists. All Rights Reserved.)

African swine fever virus (ASFV) is the etiological agent of African swine fever, a highly contagious hemorrhagic disease affecting both wild boars and domestic pigs with lethality rates up to 100%. Until now, the most effective measure to prevent an outbreak of ASFV was early detection. In this situation, whole genome sequencing (WGS) allows the gathering of detailed information about the identity and epidemiology of the virus. However, due to the large genome size and complex genome ends, WGS is challenging. Current WGS workflows require either elaborate enrichment methods or are based on tiled PCR approaches, which are susceptible to genetic differences between ASFV strains. To overcome this, we developed a novel approach for WGS of ASFV, using the Phi29 DNA polymerase-based multiple displacement amplification in combination with only seven primers. Furthermore, we applied an alkaline-based DNA denaturation step to significantly increase the number of viral reads, which resolves the near-full genome of ASFV. This novel isothermal WGS approach can be used in authorized laboratories for the genomic epidemiological analysis of ASFV outbreaks caused by different genotypes.

Anesthetic management of pediatric patients poses several challenges and the optimal anesthetic agent for use in this population is still a matter of debate. We systematically searched PubMed/MEDLINE and Google Scholar from their inception for studies that investigated the role and potential applications of remimazolam, a novel ultra-short-acting benzodiazepine, in pediatric patients. Furthermore, in March 2024, an update of the literature search along with an additional post-hoc search on the EMBASE database were performed. A total of fourteen pertinent studies which spanned the 2021-2023 period explored remimazolam as either the primary or adjuvant hypnotic agent for inducing and/or maintaining general anesthesia or sedation. Preliminary evidence derived from these studies highlighted that remimazolam is a safe and effective option for both sedation and general anesthesia in pediatric patients, particularly those with concurrent mitochondrial disorders, myopathic diseases, or at risk for malignant hyperthermia. Moreover, the current evidence suggested that remimazolam may contribute to reducing preoperative anxiety and postoperative delirium in children. Its favorable pharmacodynamic and pharmacokinetic profile demonstrated potential safety, effectiveness, and ease-of-use in various perioperative pediatric contexts, making it suitable for integration into specific protocols, such as intraoperative monitoring of evoked potentials and management of difficult intubation. Notwithstanding these promising findings, further research is essential to determine optimal dosages, establish conclusive evidence of its superiority over other benzodiazepines, and elucidate the impact of genetic factors on drug metabolism., (© 2024. The Author(s) under exclusive licence to Japanese Society of Anesthesiologists.)

Monkeypox virus (MPXV) is the zoonotic agent responsible for mpox, an often-self-limiting pox-like disease. Since May 2022, an outbreak characterized by increased human-to-human transmission was detected outside the endemic regions. Whole genome sequencing (WGS) has been successfully used to keep track of viral evolution during outbreaks or for surveillance of multiple pathogens of public health significance. Current WGS protocols for MPXV are either based on metagenomic sequencing or tiled-PCR amplification. The latter allows multiplexing due to the efficient enrichment of the viral DNA, however, mutations or the presence of different clades can negatively influence genome coverage yield. Here, we present the establishment of a novel isothermal WGS method for MPXV based on Phi29 DNA polymerase-based multiple displacement amplification (MDA) properties making use of only 6 primers. This approach yielded from 88% up to 100% genome coverage using either alkaline denatured extracted DNA or clinical material as starting material, with the highest coverage generated by clinical material. We demonstrate that this novel isothermal WGS protocol is suitable for monitoring viral evolution during MPXV outbreaks and surveillance in any conventional laboratory setting., (© 2024. The Author(s).)

Introduction: Minimal Invasive Extracorporeal Circulation (MiECC) has recently emerged as a more 'physiologic' alternative to conventional extracorporeal circulation. However, its adoption is still limited due to lack of robust scientific evidence and ongoing debate about its potential benefits. This bibliometric analysis aims to analyze the scientific articles on MiECC and identify current research domains and existing gaps to be addressed in future studies., Methods: Pertinent articles were retrieved from the Web of Science (WOS) database. The search string included 'minimal invasive extracorporeal circulation' and its synonyms. The VOSviewer (version 1.6.17) software was used to conduct comprehensive analyses. Semantic and research networks, bibliographic coupling and journal analysis were performed., Results: Of the 1777 articles identified in WOS, 292 were retrieved. The trend in publications increased from 1991 to date. Most articles focused on transfusion requirements, acute kidney injury, inflammatory markers and cytokines, inflammation and delirium, though the impact of intraoperative optimal fluid and hemodynamic management as far as the occurrence of postoperative complications were poorly addressed. The semantic network analysis found inter-connections between the terms "cardiopulmonary bypass", "inflammatory response", and "cardiac surgery". Perfusion contributed the highest number of published documents. The most extensive research partnerships were between Germany, Greece, Italy, and England., Conclusions: Notwithstanding the scientific community's growing interest in MiECC, crucial topics (i.e., the best anesthetic management and intraoperative need for inotropes, vasopressors and fluids) still require more comprehensive exploration. This investigation may prove to be a useful tool for clinicians, scientists, and students concerning global publication output and for the use of MiECC in cardiac surgery., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

African swine fever virus (ASFV) has been spreading through Europe, Asia, and the Caribbean after its introduction in Georgia in 2007 and, due to its particularly high mortality rate, poses a continuous threat to the pig industry. The golden standard to trace back the ASFV is whole genome sequencing, but it is a cost and time-intensive methodology. A more efficient way of tracing the virus is to amplify only specific genomic regions relevant for genotyping. This is mainly accomplished by amplifying single amplicons by PCR followed by Sanger sequencing. To reduce costs and processivity time, we evaluated a multiplex PCR based on the four primer sets routinely used for ASFV genotyping ( B646L , E183L , B602L , and intergenic I73R-I329L ), which was followed by Nanopore ligation-based amplicon sequencing. We show that with this protocol, we can genotype ASFV DNA originating from different biological matrices and correctly classify multiple genotypes and strains using a single PCR reaction. Further optimization of this method can be accomplished by adding or swapping the primer sets used for amplification based on the needs of a specific country or region, making it a versatile tool that can speed up the processing time and lower the costs of genotyping during ASFV outbreaks.

Background: Acute kidney injury (AKI) is a serious and common complication of cardiac surgery, for which reduced kidney perfusion is a key contributing factor. Intravenous amino acids increase kidney perfusion and recruit renal functional reserve. However, the efficacy of amino acids in reducing the occurrence of AKI after cardiac surgery is uncertain., Methods: In a multinational, double-blind trial, we randomly assigned adult patients who were scheduled to undergo cardiac surgery with cardiopulmonary bypass to receive an intravenous infusion of either a balanced mixture of amino acids, at a dose of 2 g per kilogram of ideal body weight per day, or placebo (Ringer's solution) for up to 3 days. The primary outcome was the occurrence of AKI, defined according to the Kidney Disease: Improving Global Outcomes creatinine criteria. Secondary outcomes included the severity of AKI, the use and duration of kidney-replacement therapy, and all-cause 30-day mortality., Results: We recruited 3511 patients at 22 centers in three countries and assigned 1759 patients to the amino acid group and 1752 to the placebo group. AKI occurred in 474 patients (26.9%) in the amino acid group and in 555 (31.7%) in the placebo group (relative risk, 0.85; 95% confidence interval [CI], 0.77 to 0.94; P = 0.002). Stage 3 AKI occurred in 29 patients (1.6%) and 52 patients (3.0%), respectively (relative risk, 0.56; 95% CI, 0.35 to 0.87). Kidney-replacement therapy was used in 24 patients (1.4%) in the amino acid group and in 33 patients (1.9%) in the placebo group. There were no substantial differences between the two groups in other secondary outcomes or in adverse events., Conclusions: Among adult patients undergoing cardiac surgery, infusion of amino acids reduced the occurrence of AKI. (Funded by the Italian Ministry of Health; PROTECTION ClinicalTrials.gov number, NCT03709264.)., (Copyright © 2024 Massachusetts Medical Society.)

Objectives: Previous studies in other settings suggested that urine output (UO) might affect NephroCheck predictive value. We investigated the correlation between NephroCheck and UO in cardiac surgery patients., Design: Post hoc analysis of a multicenter study., Setting: University hospital., Participants: Patients who underwent cardiac surgery using cardiopulmonary bypass (CPB) and crystalloid cardioplegia., Measurements and Main Results: All patients underwent NephroCheck testing 4 hours after CPB discontinuation. The primary outcome was the correlation between UO, NephroCheck results, and acute kidney injury (AKI, defined according to Kidney Disease: Improving Global Outcomes). Of 354 patients, 337 were included. Median NephroCheck values were 0.06 (ng/mL) 2 /1,000) for the overall population and 0.15 (ng/mL) 2 /1,000) for patients with moderate to severe AKI. NephroCheck showed a significant inverse correlation with UO (ρ = -0.17; p = 0.002) at the time of measurement. The area under the receiver characteristic curve (AUROC) for NephroCheck was 0.60 (95% confidence interval [CI], 0.54-0.65), whereas for serum creatinine was 0.82 (95% CI, 0.78-0.86; p < 0.001). When limiting the analysis to the prediction of moderate to severe AKI, NephroCheck had a AUROC of 0.82 (95% CI, 0.77 to 0.86; p<0.0001), while creatinine an AUROC of 0.83 (95% CI, 0.79-0.87; p = 0.001)., Conclusions: NephroCheck measured 4 hours after the discontinuation from the CPB predicts moderate to severe AKI. However, a lower threshold may be necessary in patients undergoing cardiac surgery with CPB. Creatinine measured at the same time of the test remains a reliable marker of subsequent development of renal failure., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: Remimazolam, an ultra-short-acting benzodiazepine recognized and approved as an anesthetic and sedative in multiple countries, offers a distinctive pharmacokinetic profile, boasting advantages such as rapid onset, short action duration, and rapid recovery. These attributes may contribute to enhanced hemodynamic stability and a diminished risk of respiratory depression compared to other sedatives., Evidence Acquisition: We conducted the first comprehensive systematically structured narrative review to evaluate the role and potential application of remimazolam in cardiac surgery. Twenty-one studies published from 2021 to 2023 delved into remimazolam's application in open cardiac surgery, cardiac catheterization or electrophysiology laboratories, and high-risk cardiovascular patients undergoing non-cardiac surgery., Evidence Synthesis: Overall, remimazolam usage was apparently linked to potentially superior hemodynamic stability compared to other hypnotic drugs. However, findings regarding the reduction in postoperative delirium incidence with remimazolam and the doses of remimazolam for anesthesia induction and maintenance were inconsistent across the studies., Conclusions: Though remimazolam has demonstrated potential safety, efficacy, and ease-of-use for both anesthesia induction and maintenance in cardiac surgery patients and high-risk cardiovascular patients undergoing non-cardiac surgery, further research is imperative to delve into specific patient subgroups (e.g., the elderly or emergent procedures) so as to ascertain optimal dose ranges to suit diverse clinical scenarios.

Every year, 80,000-100,000 ablation procedures take place in the United States and approximately 1% of these involve paediatric patients. As the paediatric population undergoing catheter ablation to treat dysrhythmia is constantly growing, involvement of anaesthesiologists in the cardiac electrophysiology laboratory is simultaneously increasing. Compared with the adult population, paediatric patients need deeper sedation or general anaesthesia (GA) to guarantee motionlessness and preserve comfort. As a result, the anaesthesiologist working in this setting should keep in mind heart physiopathology as well as possible interactions between anaesthetic drugs and arrhythmia. In fact, drug-induced suppression of accessory pathways (APs) conduction capacity is a major concern for completing a successful electrophysiology study (EPS). Nevertheless, the literature on this topic is scarce and the optimal type of anaesthesia in EPS and ablation procedures in children is still controversial. Thus, the main goal of the present review is to collect the literature published so far on the effects on cardiac conduction tissue of the drugs commonly employed for sedation/GA in the cath lab for EPS and ablation procedures to treat supraventricular tachycardia in patients aged <18 years., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Inc.)

Objectives: The aim of the current study was to assess the relationship among thrombin receptor activator peptide 6 (TRAP test), adenosine-5'-diphosphate (ADP test), arachidonic acid (ASPI test), and stroke/transient ischemic attack (TIA), using the multiple electrode aggregometry (Multiplate) in patients undergoing carotid thromboendarterectomy (CEA)., Design: A retrospective study., Setting: Vascular surgery operating rooms of a university hospital., Participants: One hundred thirty-one out of 474 patients undergoing CEA between November 2020 and October 2022., Interventions: None., Measurements and Main Results: A preoperative blood sample of all enrolled patients was analyzed using the Multiplate analyzer. Receiver operating characteristics curves, were generated to test the ability of TRAP, ADP, and ASPI in discriminating perioperative thromboembolic stroke/TIA. A logistic LASSO regression model was used to identify factors independently associated with stroke/TIA. Eight patients experienced a perioperative stroke/TIA. Although all the platelet functional assays showed excellent predictive performance, an ADP value exceeding 72 U showed the highest specificity (87%) and sensitivity (68%) in discriminating patients who had a perioperative thromboembolic stroke/TIA, with a negative predictive value of 99% and a positive predictive value of 15%. After LASSO regression, an ADP >72 U and the need for a shunt during CEA were the only 2 variables independently associated with perioperative stroke/TIA., Conclusion: Because the ADP test was independently associated with perioperative stroke/TIA, the assessment of platelet reactivity using Multiplate may offer potential utility in monitoring patients undergoing CEA., Competing Interests: Declaration of competing interest None, (Copyright © 2023 Elsevier Inc. All rights reserved.)

Influenza D virus (IDV) can infect various livestock animals, such as cattle, swine, and small ruminants, and was shown to have zoonotic potential. Therefore, it is important to identify viral factors involved in the broad host tropism and identify potential antiviral compounds that can inhibit IDV infection. Recombinant reporter viruses provide powerful tools for studying viral infections and antiviral drug discovery. Here we present the generation of a fluorescent reporter IDV using our previously established reverse genetic system for IDV. The mNeonGreen (mNG) fluorescent reporter gene was incorporated into the IDV non-structural gene segment as a fusion protein with the viral NS1 or NS2 proteins, or as a separate protein flanked by two autoproteolytic cleavage sites. We demonstrate that only recombinant reporter viruses expressing mNG as an additional separate protein or as an N-terminal fusion protein with NS1 could be rescued, albeit attenuated, compared to the parental reverse genetic clone. Serial passaging experiments demonstrated that the mNG gene is stably integrated for up to three passages, after which internal deletions accumulate. We conducted a proof-of-principle antiviral screening with the established fluorescent reporter viruses and identified two compounds influencing IDV infection. These results demonstrate that the newly established recombinant IDV reporter virus can be applied for antiviral drug discovery and monitoring viral replication, adding a new molecular tool for investigating IDV.

Background: Impairment of platelet responses to adenosine diphosphate (ADP) is typified by mild to severe bleeding diathesis, easy bruising, excessive mucosal and post-operative bleeding. Patients lack full platelet activation and aggregation in response to ADP. Following research of the literature in Scopus, PubMed/MEDLINE, ScienceDirect, and the Cochrane Library, we report only 18 patients described to date with impaired platelet response to ADP, none of whom in the high bleeding-risk surgical setting or exploring potential therapeutic options. Data regarding population, putative genetic mutations, modes of inheritance, functional defects, and related clinical manifestations were retrieved from case series and case reports., Case Presentation: A 40-year-old woman was scheduled for on-pump cardiac surgery. Her past medical history included episodes of spontaneous mucocutaneous hemorrhages of the mild entity since childhood. Multiple electrode aggregometry (MEA, Multiplate ® Roche Diagnostics, Rotkreuz, Switzerland) was used to evaluate platelet response to thrombin-activated peptide-6 (TRAP), arachidonic acid (ASPI), and ADP. An inadequate platelet aggregation induced using a high concentration of ADP with normal TRAP and ASPI tests was detected preoperatively. Therefore, intravenous desmopressin (DVVAP) 0.3 μg/kg body weight was administered to manage microvascular bleeding developed after weaning from cardiopulmonary bypass (CPB)., Conclusions: Proper management of impaired platelet response to ADP requires a systematic assessment. The Multiplate analyzer is a valuable tool to promptly detect the disorder when a high clinical suspect is present and obtain insights during high bleeding-risk surgical procedures. DVVAP can be beneficial as first-line therapy in bleeding patients to improve platelet function.

We compare the effect of intraoperative administration of four-factor prothrombin complex concentrates (PCCs) versus fresh frozen plasma (FFP) on major bleeding, transfusions, and complications. Out of 138 patients undergoing left ventricle assist device (LVAD) implantation, 32 received PCCs as first-line hemostatic agents and 102 FFP (standard group). The crude treatment estimates indicated that, compared with the standard group, the PCC group required more FFP units (odds ratio [OR]: 4.17, 95% confidence interval [CI]: 1.58-11; p = 0.004) intraoperatively, whereas a greater number of patients received FFP at 24 hours (OR: 3.01, 95% CI: 1.19-7.59; p = 0.021) and less packed red blood cells (RBC) at 48 hours (OR: 0.61, 95% CI: 0.01-1.21; p = 0.046). After the inverse probability of treatment weighting (IPTW) adjusted analyses, in the PCC group there was still a higher number of patients who required FFP (OR: 2.9, 95% CI: 1.02-8.25; p = 0.048) or RBC (OR: 6.23, 95% CI: 1.67-23.14; p = 0.007] at 24 hours and RBC at 48 hours (OR: 3.09, 95% CI: 0.89-10.76; p = 0.007). Adverse events and survival were similar before and after the ITPW adjustment. In conclusion, the PCCs, although relatively safe with respect to thrombotic events, were not associated with a reduction of major bleeding and blood product transfusions., Competing Interests: Disclosure: The authors have no conflicts of interest to report., (Copyright © ASAIO 2023.)

Background: Sedation protocols in patients undergoing complex endovascular aortic aneurysm repair are not fully investigated. The aim of this study was to compare a dexmedetomidine (DEX) based sedation protocol with a remifentanil-based sedation protocol., Methods: Seventy-nine consecutive patients undergoing complex endovascular aortic repair were enrolled and retrospectively analyzed. Forty-two received 0.03 mg/kg midazolam intravenous bolus with remifentanil (0.075-0.1 μg/kg/min for 10 minutes followed by continuous infusion 0.050-0.25 μg/kg/min) and 37 DEX (1 μg/kg over 10 minutes and continuous infusion 0.50-0.75 μg/kg/hour) to achieve an Observer Assessment of Alertness/Sedation Scale (OAAS) ≤4, a Richmond Agitation/Sedation Scale (RASS) ≤-2 and a Visual Analogic Scale (VAS) <4. The primary endpoint was patients' satisfaction. Secondary endpoints included assessment of sedation and pain, the incidence of perioperative hemodynamic or gas exchange imbalance, and 36 month-mortality., Results: Remifentanil group showed a higher satisfaction rate than DEX (P<0.001). Patients on DEX were more sedated than remifentanil according to OAAS (3 [2-3] vs. 4 [3-4]; P=0.001) and RASS (-2[-3/-2] vs. -2[-2/-2]; P=0.001) with no difference in VAS (2 [1-3] vs. 2 [1-3]; P=0.41). DEX provides reliable sedation with lower patient's satisfaction. A higher number of patients were discharged from the recovery room on vasopressors in the DEX group compare with the remifentanil group (5 vs. 0; P=0.045, respectively). The two groups showed a non-significant difference in the survival rate at 36-month (DEX 67% vs. remifentanil 73%; (P=0.90)., Conclusions: In this setting remifentanil provides reliable sedation with higher patient's satisfaction and less hemodynamic effect than DEX.

Introduction: Recent studies showed that balanced opioid-free anesthesia is feasible and desirable in several surgical settings. However, in thoracic surgery, scientific evidence is still lacking. Thus, we conducted the first systematic review and meta-analysis of opioid-free anesthesia in this field. Methods: The primary outcome was the occurrence of any complication. Secondary outcomes were the length of hospital stay, recovery room length of stay, postoperative pain at 24 and 48 h, and morphine equivalent consumption at 48 h. Results: Out of 375 potentially relevant articles, 6 studies (1 randomized controlled trial and 5 observational cohort studies) counting a total of 904 patients were included. Opioid-free anesthesia compared to opioid-based anesthesia, was associated with a lower rate of any complication (74 of 175 [42%] vs. 200 of 294 [68%]; RR = 0.76; 95% CI, 0.65−0.89; p < 0.001; I2 = 0%), lower 48 h morphine equivalent consumption (MD −14.5 [−29.17/−0.22]; p = 0.05; I2 = 95%) and lower pain at 48 h (MD −1.95 [−3.6/0.3]; p = 0.02, I = 98%). Conclusions: Opioid-free anesthesia in thoracic surgery is associated with lower postoperative complications, and less opioid demand with better postoperative analgesia at 48 h compared to opioid-based anesthesia.

Objective: Although endovascular repair of thoraco-abdominal aortic aneurysm (TAAA) is the treatment of choice in the high risk population that is ineligible for an open surgical approach, little is known about the association between the type of anaesthesia and complications. This study compared the short term clinical outcomes of patients undergoing the visceral step of TAAA with fenestrated endograft aortic repair (FEVAR) and branched endograft aortic repair (BEVAR) under general anaesthesia (GA) with sedation with monitored care anaesthesia (MAC)., Methods: This single centre, retrospective, observational study recruited 124 consecutive patients undergoing elective F/BEVAR from 2014 - 2021. The primary endpoint was the short term complication rate according to the type of anaesthesia. Secondary endpoints included: need for inotropes or vasopressors for hypotension, time spent in the operating room, and admission to the intensive care unit. Propensity score matching was generated to account for the between group imbalance in the pre-operative covariables., Results: After propensity score matching, 42 patients under GA were matched with 42 under MAC. The two groups showed no difference in cardiac and non-cardiac complications. Among the secondary outcomes, a higher number of patients in the GA group required inotropes or vasopressors compared with MAC (33% vs. 9%; p = .031). Although GA and MAC showed the same 30 day technical success (81% vs. 83%; p = .078), non-significant lower rates of major adverse events (10% vs. 12%; p = .72), one year re-intervention (14% vs. 21%; p = .39), and one year target vessel instability (10% vs. 21%; p = .39) were observed in the GA group. Overall, the in hospital mortality rate was 4%, with no difference between GA and MAC (2% vs. 5%; p = 1.0)., Conclusion: The type of anaesthesia seemed to have no effect on procedure success, peri-operative morbidity, or mortality in patients undergoing F/BEVAR., (Copyright © 2022 European Society for Vascular Surgery. Published by Elsevier B.V. All rights reserved.)

Robotic major lung resection for lung cancer carries a risk for intraoperative hemodynamic instability. Systolic anterior motion (SAM) of the mitral valve is a rare and often misrecognized cause of intraoperative hemodynamic instability. If not promptly recognized, SAM leads to a complicated perioperative course. Here, we report for the first time a case of a patient with SAM with a severe degree of left ventricular outflow obstruction (LVOTO) undergoing robotic lung lobectomy and its challenging intraoperative management. A 70-year-old man undergoing robotic left upper lobectomy developed immediately after the induction of general anesthesia hemodynamic instability due to SAM-related LVOTO. The diagnosis was possible, thanks to the use of transesophageal echocardiography (TEE). The treatment strategies applied were preload optimization without fluid overload, ultra-short-acting beta-blockers, and vasopressors. Peripheral nerve blockades were preferred over epidural analgesia to avoid vasodilatation. The patient reported a good quality of recovery and no pain the day after surgery. The management of patients with higher risk of SAM and LVOTO development during robotic thoracic surgery requires a dedicated and skilled team together with high-impact treatment strategies driven by TEE. Since current guidelines do not recommend the use of TEE, even for patients with higher cardiac risk undergoing noncardiac surgery, the present case report may stimulate interest in future recommendations.

Background: Postoperative acute kidney injury (AKI) is frequent in cardiac surgery patients. Its pathophysiology is complex and involves decreased renal perfusion. Preliminary clinical evidence in critically ill patients shows that amino acids infusion increases renal blood flow and may decrease the incidence and severity of AKI. We designed a study to evaluate the effectiveness of perioperative continuous infusion of amino acids in decreasing AKI., Methods: This is a phase III, multi-center, randomized, double-blind, placebo-controlled trial. Adults undergoing cardiac surgery with cardiopulmonary bypass (CPB) are included. Patients are randomly assigned to receive either continuous infusion of a balanced mixture of amino acids in a dose of 2 g/kg ideal body weight/day or placebo (balanced crystalloid solution) from the operating room up to start of renal replacement therapy (RRT), or ICU discharge, or 72 h after the first dose. The primary outcome is the incidence of AKI during hospital stay defined by KDIGO (Kidney Disease: Improving Global Outcomes). Secondary outcomes include the need for, and duration of, RRT, mechanical ventilation; ICU and hospital length of stay; all-cause mortality at ICU, hospital discharge, 30, 90, and 180 days after randomization; quality of life at 180 days. Data will be analyzed in 3500 patients on an intention-to-treat basis., Discussion: The trial is ongoing and currently recruiting. It will be one of the first randomized controlled studies to assess the relationship between amino acids use and kidney injury in cardiac surgery. If our hypothesis is confirmed, this practice could reduce morbidity in the studied population., Study Registration: This trial was registered on ClinicalTrials.gov with the trial identification NCT03709264 in October 2018., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Viral cross-species transmission is recognized to be a major threat to both human and animal health, however detailed information on determinants underlying virus host tropism and susceptibility is missing. Influenza C and D viruses (ICV, IDV) are two respiratory viruses that share up to 50% genetic similarity, and both employ 9-O-acetylated sialic acids to enter a host cell. While ICV infections are mainly restricted to humans, IDV possesses a much broader host tropism and has shown to have a zoonotic potential. This suggests that additional virus-host interactions play an important role in the distinct host spectrum of ICV and IDV. In this study, we aimed to characterize the innate immune response of the respiratory epithelium of biologically relevant host species during influenza virus infection to identify possible determinants involved in viral cross-species transmission. To this end, we performed a detailed characterization of ICV and IDV infection in primary airway epithelial cell (AEC) cultures from human, porcine, and bovine origin. We monitored virus replication kinetics, cellular and host tropism, as well as the host transcriptional response over time at distinct ambient temperatures. We observed that both ICV and IDV predominantly infect ciliated cells, independently from host and temperature. Interestingly, temperature had a profound influence on ICV replication in both porcine and bovine AEC cultures, while IDV replicated efficiently irrespective of temperature and host. Detailed time-resolved transcriptome analysis revealed both species-specific and species uniform host responses and highlighted 34 innate immune-related genes with clear virus-specific and temperature-dependent profiles. These data provide the first comprehensive insights into important common and species-specific virus-host dynamics underlying the distinct host tropism of ICV and IDV, as well as possible determinants involved in viral cross-species transmission., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Laloli, Licheri, Probst, Licheri, Gultom, Holwerda, V’kovski and Dijkman.)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread globally, and the number of worldwide cases continues to rise. The zoonotic origins of SARS-CoV-2 and its intermediate and potential spillback host reservoirs, besides humans, remain largely unknown. Because of ethical and experimental constraints and more important, to reduce and refine animal experimentation, we used our repository of well-differentiated airway epithelial cell (AEC) cultures from various domesticated and wildlife animal species to assess their susceptibility to SARS-CoV-2. We observed that SARS-CoV-2 replicated efficiently only in monkey and cat AEC culture models. Whole-genome sequencing of progeny viruses revealed no obvious signs of nucleotide transitions required for SARS-CoV-2 to productively infect monkey and cat AEC cultures. Our findings, together with previous reports of human-to-animal spillover events, warrant close surveillance to determine the potential role of cats, monkeys, and closely related species as spillback reservoirs for SARS-CoV-2.

Objective: To determine the relationship between the value of fibrinogen assessed by the FIBTEM clot amplitude at 10 minutes (A10 FIBTEM) measured on admission to the intensive care unit (ICU) and the amount of drainage output at 24 hours, to investigate whether the A10 FIBTEM predicts severe bleeding (SB), and to define A10 FIBTEM thresholds to prevent (trigger) and treat (target) severe bleeding by fibrinogen supplementation., Methods: In a single centre, retrospective observational study, 166 patients underwent elective open thoraco-abdominal aortic aneurysm (TAAA) repair between March 2016 and January 2019. Exclusion criteria were emergency, congenital, or acquired coagulopathy, or administration of P 2 Y 12 inhibitor antiplatelet agents in the five days before surgery. All patients were managed intra-operatively and post-operatively according to a rotational thromboelastometry driven transfusion protocol. The principal endpoint was a composite outcome, which included bleeding, large volume transfusion, and re-operation., Results: FIBTEM clot amplitude after 10 minutes measured on ICU admission and post-operative bleeding at 24 hours showed an inverse linear relationship (R 2  = .03; p = .026). Performance of A10 FIBTEM in predicting SB evaluated by Receiving Operating Curve analysis showed an area under the curve of 0.63 (95% CI 0.56 - 0.70; p = .026) with a best cutoff of 9 mm. An A10 FIBTEM of 3 mm was the cutoff associated with a positive predictive value of 50%, while an A10 FIBTEM of 9 mm showed a negative predictive value of 92%. On multivariable analysis, an A10 FIBTEM ≤ 3 mm remained independently associated with SB., Conclusion: The present investigation shows for the first time in a population undergoing open TAAA repair that an A10 FIBTEM ≤ 3mm on ICU admission is associated with post-operative severe bleeding. Trigger and target values for fibrinogen supplementation, based on A10 FIBTEM, have been provided. The transferability and reliability of these cutoff values require further study., (Copyright © 2021 European Society for Vascular Surgery. Published by Elsevier B.V. All rights reserved.)

Background: Organ perfusion is a factor of cardiac output and perfusion pressure. Recent evidence shows that dynamic arterial elastance is a reliable index of the interaction between the left ventricle and the arterial system and, in turn, of left ventricular mechanical efficiency. A practical approach to the assessment of dynamic arterial elastance at the bedside is the ratio between pulse pressure variation and stroke volume variation, which might predict the effect of a fluid challenge on the arterial pressure in patients undergoing cardiac surgery., Objective: To evaluate the ability of dynamic arterial elastance, measured by the pressure recording analytical method (PRAM), to predict the response of mean arterial pressure (MAP) to a fluid challenge., Design: Prospective observational study., Setting: Cardiac surgery patients in a university hospital., Patients: Preload-dependent (pulse pressure variation ≥13%), hypotensive (MAP ≤65 mmHg) patients, without right ventricular dysfunction, at the end of cardiac surgery., Interventions: A 250 ml fluid challenge infused over 3 min., Main Outcome Measures: A receiver-operating characteristic curve was generated to test the ability of the baseline (before fluid challenge) dynamic arterial elastance (primary endpoint) and all other haemodynamic variables (secondary endpoint) to predict MAP responsiveness (≥10% increase in MAP) after a fluid challenge., Results: Of 270 patients undergoing cardiac surgery, 97 (35.9%) were preload-dependent, hypotensive and received a fluid challenge. Of these 97 patients, 50 (51%) were MAP responders (≥10% increase in MAP) and 47 (48%) were MAP nonresponders (<10% increase in MAP). Baseline dynamic arterial elastance (mean ± SD) had an area under the curve of 0.64 ± 0.06 [95% confidence interval (CI), 0.53 to 0.73; P = 0.017]. A dynamic arterial elastance at least 1.07 with a grey zone ranging between 0.9 and 1.5 had 86% sensitivity (95% CI, 73 to 94) and 45% specificity (95% CI, 30 to 60) in predicting MAP increase., Conclusion: In a hypotensive preload-dependent cardiac surgery cohort without right ventricular dysfunction, dynamic arterial elastance measured by PRAM can predict pressure response for values greater than 1.5 or less than 0.9., (Copyright © 2021 European Society of Anaesthesiology and Intensive Care. Unauthorized reproduction of this article is prohibited.)

Context: Protamine is routinely administered to neutralize the anticlotting effects of heparin, traditionally at a dose of 1 mg for every 100 IU of heparin-a 1:1 ratio protamine sparing effects-but this is based more on experience and practice than literature evidence. The use of Hemostasis Management System (HMS) allows an individualized heparin and protamine titration. This usually results in a decreased protamine dose, thus limiting its side effects, including paradox anticoagulation., Aims: This study aims to assess how the use of HMS allows to reduction of protamine administration while restoring the basal activated clotting time (ACT) at the end of cardiac surgery., Settings and Design: A retrospective observational study in a tertiary care university hospital., Subjects and Methods: We analyzed data from 42 consecutive patients undergoing cardiopulmonary bypass (CPB) for cardiac surgery. For all patients HMS tests were performed before and after CPB, to determine how much heparin was needed to reach target ACT, and how much protamine was needed to reverse it., Results: At the end of cardiopulmonary bypass, 2.2 ± 0.5 mg/kg of protamine was sufficient to reverse heparin effects. The protamine-to-heparin ratio was 0.56:1 over heparin total dose (a 44% reduction) and 0.84:1 over heparin initial dose (a 16% reduction)., Conclusion: A lower dose of protamine was sufficient to revert heparin effects after cardiopulmonary bypass. While larger studies are needed to confirm these findings and detect differences in clinically relevant outcomes, the administration of a lower protamine dose is endorsed by current guidelines and may help to avoid the detrimental effects of protamine overdose, including paradox bleeding.

Objective: To assess whether the administration of the ultra-short-acting β-blocker esmolol in cardiac surgery could have a cardioprotective effect that translates into improved postoperative outcomes., Design: Single-center, double-blinded, parallel-group randomized controlled trial., Setting: A tertiary care referral center., Participants: Patients undergoing elective cardiac surgery with preoperative evidence of left ventricular end-diastolic diameter >60 mm and/or left ventricular ejection fraction <50%., Interventions: Patients were assigned randomly to receive either esmolol (1 mg/kg as a bolus before aortic cross-clamping and 2 mg/kg mixed in the cardioplegia solution) or placebo in a 1:1 allocation ratio., Measurements and Main Results: The primary composite endpoint of prolonged intensive care unit stay and/or in-hospital mortality occurred in 36/98 patients (36%) in the placebo group versus 27/102 patients (27%) in the esmolol group (p = 0.13). In the esmolol group, a reduction in the maximum inotropic score during the first 24 postoperative hours was observed (10 [interquartile range 5-15] v 7 [interquartile range 5-10.5]; p = 0.04), as well as a trend toward a reduction in postoperative low-cardiac-output syndrome (13/98 v 6/102; p = 0.08) and the rate of hospital admission at one year (26/95 v 16/96; p = 0.08). A trend toward an increase in the number of patients with ejection fraction ≥60% at hospital discharge also was observed (4/95 v 11/92; p = 0.06)., Conclusions: In the present trial, esmolol as a cardioplegia adjuvant enhanced postoperative cardiac performance but did not reduce a composite endpoint of prolonged intensive care unit stay and/or mortality., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Amphibians have been disappearing at an unprecedented rate worldwide. Among the proposed contributing factors are infectious diseases. Investigations have focused mainly on ranavirus and chytrids; however, additional agents may be relevant stressors. Two novel batrachoviruses have been discovered (ranid herpesvirus 3 [RaHV-3] and bufonid herpesvirus 1 [BfHV-1]). Their clinical role is still to be clarified; however, both have been associated with obvious skin lesions in their respective hosts. Herein we present 2 consensus PCR protocols that can be used to detect all of the known and, possibly, yet to be discovered batrachoviruses. We targeted a 200 nt long, highly conserved region of the DNA terminase gene. We established a sensitive protocol, which can detect both European batrachoviruses (European batrachovirus PCR protocol; RaHV-3 and BfHV-1) and a panbatrachovirus PCR protocol detecting all known batrachoviruses, including ranid herpesvirus 1 and 2 (RaHV-1, -2). The limit of detection (LOD) for the European batrachovirus protocol was 10 1 copies of RaHV-3 and 10 2 copies of BfHV-1 per reaction. The panbatrachovirus protocol could detect all known batrachoviruses with LODs of 10 3 (RaHV-3, BfHV-1, RaHV-1) to 10 4 copies (RaHV-2) per reaction. These novel detection tools can be used as a first line of detection when herpesviral infection in amphibians is suspected, followed by additional PCRs with herpesvirus-specific primers in the case of known viral species, or sequencing as in the case of novel batrachoviruses.