Povidone Iodine vs Chlorhexidine Gluconate in Alcohol for Preoperative Skin Antisepsis: A Randomized Clinical Trial.

Importance: Preoperative skin antisepsis is an established procedure to prevent surgical site infections (SSIs). The choice of antiseptic agent, povidone iodine or chlorhexidine gluconate, remains debated. Objective: To determine whether povidone iodine in alcohol is noninferior to chlorhexidine gluconate in alcohol to prevent SSIs after cardiac or abdominal surgery. Design, Setting, and Participants: Multicenter, cluster-randomized, investigator-masked, crossover, noninferiority trial; 4403 patients undergoing cardiac or abdominal surgery in 3 tertiary care hospitals in Switzerland between September 2018 and March 2020 were assessed and 3360 patients were enrolled (cardiac, n = 2187 [65%]; abdominal, n = 1173 [35%]). The last follow-up was on July 1, 2020. Interventions: Over 18 consecutive months, study sites were randomly assigned each month to either use povidone iodine or chlorhexidine gluconate, each formulated in alcohol. Disinfectants and skin application processes were standardized and followed published protocols. Main Outcomes and Measures: Primary outcome was SSI within 30 days after abdominal surgery and within 1 year after cardiac surgery, using definitions from the US Centers for Disease Control and Prevention's National Healthcare Safety Network. A noninferiority margin of 2.5% was used. Secondary outcomes included SSIs stratified by depth of infection and type of surgery. Results: A total of 1598 patients (26 cluster periods) were randomly assigned to receive povidone iodine vs 1762 patients (26 cluster periods) to chlorhexidine gluconate. Mean (SD) age of patients was 65.0 years (39.0-79.0) in the povidone iodine group and 65.0 years (41.0-78.0) in the chlorhexidine gluconate group. Patients were 32.7% and 33.9% female in the povidone iodine and chlorhexidine gluconate groups, respectively. SSIs were identified in 80 patients (5.1%) in the povidone iodine group vs 97 (5.5%) in the chlorhexidine gluconate group, a difference of 0.4% (95% CI, -1.1% to 2.0%) with the lower limit of the CI not exceeding the predefined noninferiority margin of -2.5%; results were similar when corrected for clustering. The unadjusted relative risk for povidone iodine vs chlorhexidine gluconate was 0.92 (95% CI, 0.69-1.23). Nonsignificant differences were observed following stratification by type of surgical procedure. In cardiac surgery, SSIs were present in 4.2% of patients with povidone iodine vs 3.3% with chlorhexidine gluconate (relative risk, 1.26 [95% CI, 0.82-1.94]); in abdominal surgery, SSIs were present in 6.8% with povidone iodine vs 9.9% with chlorhexidine gluconate (relative risk, 0.69 [95% CI, 0.46-1.02]). Conclusions and Relevance: Povidone iodine in alcohol as preoperative skin antisepsis was noninferior to chlorhexidine gluconate in alcohol in preventing SSIs after cardiac or abdominal surgery. Trial Registration: ClinicalTrials.gov Identifier: NCT03685604.

Hyperacute T Wave in the Early Diagnosis of Acute Myocardial Infarction.

STUDY OBJECTIVE: The diagnostic performance of T-wave amplitudes for the detection of myocardial infarction is largely unknown. We aimed to address this knowledge gap. METHODS: T-wave amplitudes were automatically measured in 12-lead ECGs of patients presenting with acute chest discomfort to the emergency department within a prospective diagnostic multicenter study. The final diagnosis was centrally adjudicated by 2 independent cardiologists. Patients with left ventricular hypertrophy, complete left bundle branch block, or paced ventricular depolarization were excluded. The performance for lead-specific 95th-percentile thresholds were reported as likelihood ratios (lr), specificity, and sensitivity. RESULTS: Myocardial infarction was the final diagnosis in 445 (18%) of 2457 patients. In most leads, T-wave amplitudes tended to be greater in patients without myocardial infarction than those with myocardial infarction, and T-wave amplitude exceeding the 95th percentile had positive and negative lr close to 1 or with confidence intervals (CIs) crossing 1. The exceptions were leads III, aVR, and V1, which had positive lrs of 3.8 (95% CI, 2.7 to 5.3), 4.3 (95% CI, 3.1 to 6.0) and 2.0 (95% CI, 1.4 to 2.9), respectively. These leads normally have inverted T waves, so T-wave amplitude exceeding the 95th percentile reflects upright rather than increased-amplitude hyperacute T waves. CONCLUSION: Hyperacute T waves, when defined as increased T-wave amplitude exceeding the 95th percentile, did not provide useful information in diagnosing myocardial infarction in this sample.

Performance of the ESC 0/2h-algorithm using high-sensitivity cardiac troponin I in the early diagnosis of myocardial infarction.

The 2020 guidelines of the European Society of Cardiology (ESC) recommend a novel ESC 0/2h-algorithm as the preferred alternative to the ESC 0/1h-algorithm in the early triage for rule-out and/or rule-in of Non-ST-segment-elevation myocardial infarction (NSTEMI). The aim was to prospectively validate the performance of the ESC 0/2h-algorithm using the high-sensitivity cardiac troponin I (hs-cTnI) assay (ARCHITECT) in an international, multicenter diagnostic study enrolling patients presenting with acute chest discomfort to the emergency department.

Limits on the Existence of sub-MeV Sterile Neutrinos from the Decay of

Sterile neutrinos are natural extensions to the standard model of particle physics and provide a possible portal to the dark sector. We report a new search for the existence of sub-MeV sterile neutrinos using the decay-momentum reconstruction technique in the decay of ^{7}Be. The experiment measures the total energy of the ^{7}Li daughter atom from the electron capture decay of ^{7}Be implanted into sensitive superconducting tunnel junction (STJ) quantum sensors. This first experiment presents data from a single STJ operated at a low count rate for a net total of 28 days, and provides exclusion limits on sterile neutrinos in the mass range from 100 to 850 keV that improve upon previous work by up to an order of magnitude.

Long-Term Severe In Vitro Hypoxia Exposure Enhances the Vascularization Potential of Human Adipose Tissue-Derived Stromal Vascular Fraction Cell Engineered Tissues.

The therapeutic potential of mesenchymal stromal/stem cells (MSC) for treating cardiac ischemia strongly depends on their paracrine-mediated effects and their engraftment capacity in a hostile environment such as the infarcted myocardium. Adipose tissue-derived stromal vascular fraction (SVF) cells are a mixed population composed mainly of MSC and vascular cells, well known for their high angiogenic potential. A previous study showed that the angiogenic potential of SVF cells was further increased following their in vitro organization in an engineered tissue (patch) after perfusion-based bioreactor culture. This study aimed to investigate the possible changes in the cellular SVF composition, in vivo angiogenic potential, as well as engraftment capability upon in vitro culture in harsh hypoxia conditions. This mimics the possible delayed vascularization of the patch upon implantation in a low perfused myocardium. To this purpose, human SVF cells were seeded on a collagen sponge, cultured for 5 days in a perfusion-based bioreactor under normoxia or hypoxia (21% and <1% of oxygen tension, respectively) and subcutaneously implanted in nude rats for 3 and 28 days. Compared to ambient condition culture, hypoxic tension did not alter the SVF composition in vitro, showing similar numbers of MSC as well as endothelial and mural cells. Nevertheless, in vitro hypoxic culture significantly increased the release of vascular endothelial growth factor (p < 0.001) and the number of proliferating cells (p < 0.00001). Moreover, compared to ambient oxygen culture, exposure to hypoxia significantly enhanced the vessel length density in the engineered tissues following 28 days of implantation. The number of human cells and human proliferating cells in hypoxia-cultured constructs was also significantly increased after 3 and 28 days in vivo, compared to normoxia. These findings show that a possible in vivo delay in oxygen supply might not impair the vascularization potential of SVF- patches, which qualifies them for evaluation in a myocardial ischemia model.

Direct Measurement of the

We report a high-statistics measurement of the L/K orbital electron capture ratio in ^{7}Be embedded in cryogenic Ta. The thin Ta film formed part of a high-resolution superconducting tunnel junction radiation detector that was used to identify the signals from different decay channels. The measured L/K capture ratio of 0.070(7) is significantly larger than the only previous measurement of this quantity and the theoretical predictions that include in-medium effects. This value is a uniquely sensitive probe of the 1s and 2s orbital overlaps with the nucleus and is of relevance to nuclear and atomic physics, as well as Li production in novae and other astrophysical scenarios. This is the first experiment that uses superconducting tunnel junctions for nuclear-recoil detection, opening a new experimental avenue for low-energy precision measurements with rare isotopes.

Observation of the pη

Data on the beam asymmetry Σ in the photoproduction of η mesons off protons are reported for tagged photon energies from 1130 to 1790 MeV (mass range from W=1748 MeV to W=2045 MeV). The data cover the full solid angle that allows for a precise moment analysis. For the first time, a strong cusp effect in a polarization observable has been observed that is an effect of a branch-point singularity at the pη^{'} threshold [E_{γ}=1447 MeV (W=1896 MeV)]. The latest BnGa partial wave analysis includes the new beam asymmetry data and yields a strong indication for the N(1895)1/2^{-} nucleon resonance, demonstrating the importance of including all singularities for a correct determination of partial waves and resonance parameters.

Comparison of isothermal microcalorimetry and BACTEC MGIT960 for the detection of the metabolic activity of Mycobacterium tuberculosis in sputum samples.

INTRODUCTION: This study explores the uses of microcalorimetry to detect Mycobacterium tuberculosis (TB) in sputum. Microcalorimetry measures metabolic heat evolution during cellular proliferation of tuberculosis (TB) and is considered as a possible alternative to conventional diagnostic tools. OBJECTIVES: To compare the time to detection (TTD) from the BACTEC™ MGIT™ 960 and the calScreener™ calorimetric system. METHODS: Sixty-four sputa samples were selected from patients with confirmed pulmonary tuberculosis. Those sample were then decontaminated and analysed using calorimetry and BACTEC MGIT 960 system. RESULTS: The incubation period until detection of M. tuberculosis in the sample was 8·5 ± 3·7 days for the MGIT system and 10·1 ± 4·1 days (mean ± SD) for calorimetry. CONCLUSIONS: The microincubations in the 48-well format calScreener offers potential for rapid and accurate diagnostic of TB in different samples. Although TTD from calorimetry is still longer than with the MGIT, our findings suggest that several improvements are possible. Still, the instrument is ideal for continuous, real-time analysis of net metabolic heat release of limited sample numbers. SIGNIFICANCE AND IMPACT OF THE STUDY: Our result emphasizes that with further optimization, calorimetry can become an alternative detection method for tuberculosis.

Echocardiographic and Clinical Follow-up After Aortic Valve Neocuspidization Using Autologous Pericardium.

INTRODUCTION: Mid-term data from a single centre showed the safety and durability of aortic valve neocuspidization using autologous pericardium (OZAKI procedure). Since validation data from other centres are missing, aim of this study was to analyze echocardiographic and clinical results of our first patients that were operated with the OZAKI technique. METHODS: Thirty-five patients (24 males, median (IQR) age 72.0 (59.0, 76.0) years) with aortic stenosis (AS; n = 10), aortic insufficiency (AR; n = 13) or a combination of both (AS/AR; n = 12), underwent aortic valve neocuspidization in our institution between September 2015 and May 2017. Echocardiographic follow-up was performed using a standardized examination protocol. RESULTS: Clinical follow-up was completed in 97% of the patients. Median (IQR) follow-up time was 645 (430, 813) days. Mortality rate was 9% (n = 1: aspiration pneumonia; n = 1: unknown; n = 1: anaphylactic shock), and the reoperation rate was 3% (n = 1: endocarditis). No pacemaker implantation was necessary after isolated OZAKI procedures. Echocardiographic follow-up was performed in 83% of the patients (n = 29; median (IQR) time 664 (497, 815) days). Median (IQR) mean and peak gradients were 6 (5,9) mmHg and 12 (8, 17) mmHg. Moderate aortic regurgitation was seen in 2 patients (7%). No severe aortic regurgitation or moderate or severe aortic stenosis occurred within the follow-up period. CONCLUSIONS: The OZAKI procedure is reliable and reoperation due to structural valve deterioration nil within a median 645 days follow-up period. The low rate of moderate aortic regurgitation will be surveilled very closely. Further studies are required to evaluate the significance of this procedure in aortic valve surgery. CLINICAL REGISTRATION NUMBER: ClinicalTrials.gov (ID NCT03677804).

Microplegia versus Cardioplexol® in Coronary Artery Bypass Surgery with Minimal Extracorporeal Circulation: Comparison of Two Cardioplegia Concepts.

BACKGROUND: The aim of this study is to compare the combined use of the Myocardial Protection System and our microplegia (Basel Microplegia Protocol) with Cardioplexol® in coronary artery bypass grafting using the minimal extracorporeal circulation. METHODS: The analysis focused on propensity score matched pairs of patients in whom microplegia or Cardioplexol® was used. Primary efficacy endpoints were high-sensitivity cardiac troponin-T on postoperative day 1 and peak values during hospitalization. Furthermore, we assessed creatine kinase and creatinine kinase-myocardial type, as well as safety endpoints. RESULTS: A total of 56 patients who received microplegia and 155 patients who received Cardioplexol® were included. The use of the microplegia was associated with significantly lower geometric mean (confidence interval) peak values of high-sensitivity cardiac troponin-T (233 ng/L [194-280 ng/L] vs. 362 ng/L [315-416 ng/L]; p = 0.001), creatinine kinase (539 U/L [458-633 U/L] vs. 719 U/L [645-801 U/L]; p = 0.011), and creatinine kinase-myocardial type (13.8 µg/L [9.6-19.9 µg/L] vs. 21.6 µg/L [18.9-24.6 µg/L]; p = 0.026), and a shorter length of stay on the intensive care unit (1.5 days [1.2-1.8 days] vs. 1.9 days [1.7-2.1 days]; p = 0.011). Major adverse cardiac and cerebrovascular events occurred with roughly equal frequency (1.8 vs. 5.2%; p = 0.331). CONCLUSIONS: The use of the Basel Microplegia Protocol was associated with lower peak values of high-sensitivity cardiac troponin-T, creatinine kinase, and creatinine kinase-myocardial type and with a shorter length of stay on the intensive care unit, as compared with the use of Cardioplexol® in isolated coronary artery bypass surgery using minimal extracorporeal circulation.

Analysis of Myocardial Ischemia Parameters after Coronary Artery Bypass Grafting with Minimal Extracorporeal Circulation and a Novel Microplegia versus Off-Pump Coronary Artery Bypass Grafting.

BACKGROUND: To compare the performance of our institutionally refined microplegia protocol in conjunction with minimal extracorporeal circulation system (MiECC) with off-pump coronary artery bypass grafting (OPCAB). METHODS: We conducted a single center study including patients undergoing isolated CABG surgery performed either off-pump or on-pump using our refined microplegia protocol in conjunction with MiECC. We used propensity modelling to calculate the inverse probability of treatment weights (IPTW). Primary endpoints were peak values of high-sensitivity cardiac troponin T (hs-cTnT) during hospitalization, and respective first values on the first postoperative day. Endpoint analysis was adjusted for intraoperative variables. RESULTS: After IPTW, we could include 278 patients into our analyses, 153 of which had received OPCAB and 125 of which had received microplegia. Standardized differences indicated that treatment groups were comparable after IPTW. The multivariable quantile regression yielded a nonsignificant median increase of first hs-cTnT by 39 ng/L (95% CI -8 to 87 ng/L, p = 0.11), and of peak hs-cTnT by 35 ng/L (CI -13 to 84, p = 0.11), and of peak hs-cTnT by 35 ng/L (CI -13 to 84, p = 0.11), and of peak hs-cTnT by 35 ng/L (CI -13 to 84, p = 0.11), and of peak hs-cTnT by 35 ng/L (CI -13 to 84. CONCLUSION: The use of our institutionally refined microplegia in conjunction with MiECC was associated with similar results with regard to ischemic injury, expressed in hs-cTnT compared to OPCAB. MACCE was seen equally frequent. ICU discharge was earlier if microplegia was used.

Frequent Door Openings During Cardiac Surgery Are Associated With Increased Risk for Surgical Site Infection: A Prospective Observational Study.

BACKGROUND: Preliminary studies that analyzed surrogate markers have suggested that operating room (OR) door openings may be a risk factor for surgical site infection (SSI). We therefore aimed to estimate the effect of OR door openings on SSI risk in patients undergoing cardiac surgery. METHODS: This prospective, observational study involved consecutive patients undergoing cardiac surgery in 2 prespecified ORs equipped with automatic door-counting devices from June 2016 to October 2017. Occurrence of an SSI within 30 days after cardiac surgery was our primary outcome measure. Respective outcome data were obtained from a national SSI surveillance cohort. We analyzed the relationship between mean OR door opening frequencies and SSI risk by use of uni- and multivariable Cox regression models. RESULTS: A total of 301 594 OR door openings were recorded during the study period, with 87 676 eligible door openings being logged between incision and skin closure. There were 688 patients included in the study, of whom 24 (3.5%) developed an SSI within 30 days after surgery. In uni- and multivariable analysis, an increased mean door opening frequency during cardiac surgery was associated with higher risk for consecutive SSI (adjusted hazard ratio per 5-unit increment, 1.49; 95% confidence interval, 1.11-2.00; P = .008). The observed effect was driven by internal OR door openings toward the clean instrument preparation room. CONCLUSIONS: Frequent door openings during cardiac surgery were independently associated with an increased risk for SSI. This finding warrants further study to establish a potentially causal relationship between OR door openings and the occurrence of SSI.

Mechanisms of lymphatic system-specific viral replication and its potential role in autoimmune disease.

Viral infections can be fatal because of the direct cytopathic effects of the virus or the induction of a strong, uncontrolled inflammatory response. Virus and host intrinsic characteristics strongly modulate the outcome of viral infections. Recently we determined the circumstances under which enhanced replication of virus within the lymphoid tissue is beneficial for the outcome of a disease. This enforced viral replication promotes anti-viral immune activation and, counterintuitively, accelerates virus control. In this review we summarize the mechanisms that contribute to enforced viral replication. Antigen-presenting cells and CD169+ macrophages exhibit enforced viral replication after infection with the model viruses lymphocytic choriomeningitis virus (LCMV) and vesicular stomatitis virus (VSV). Ubiquitin-specific peptidase 18 (Usp18), an endogenous type I interferon blocker in CD169+ macrophages, has been identified as a proviral gene, as are B cell activating factor (BAFF) and carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1). Lymphotoxins (LT) strongly enhance viral replication in the spleen and lymph nodes. All these factors modulate splenic architecture and thereby promote the development of CD169+ macrophages. Tumor necrosis factor alpha (TNF-α) and nuclear factor kappa-light-chain-enhancer of activated B cell signaling (NF-κB) have been found to promote the survival of infected CD169+ macrophages, thereby similarly promoting enforced viral replication. Association of autoimmune disease with infections is evident from (1) autoimmune phenomena described during a chronic virus infection; (2) onset of autoimmune disease simultaneous to viral infections; and (3) experimental evidence. Involvement of virus infection during onset of type I diabetes is strongly evident. Epstein-Bar virus (EBV) infection was discussed to be involved in the pathogenesis of systemic lupus erythematosus. In conclusion, several mechanisms promote viral replication in secondary lymphatic organs. Identifying such factors in humans is a challenge for future studies.

Efficacy and safety of mirikizumab (LY3074828) in the treatment of moderate-to-severe plaque psoriasis: results from a randomized phase II study.

BACKGROUND: Inhibiting interleukin (IL)-23 in patients with psoriasis has demonstrated high levels of skin clearance. OBJECTIVES: To investigate, in a phase II (AMAF; NCT02899988), multicentre, double-blind trial, the efficacy and safety of three doses of mirikizumab (LY3074828), a p19-directed IL-23 antibody, vs. placebo in patients with moderate-to-severe plaque psoriasis. METHODS: Adult patients were randomized 1 : 1 : 1 : 1 to receive placebo (n = 52), mirikizumab 30 mg (n = 51), mirikizumab 100 mg (n = 51) or mirikizumab 300 mg (n = 51) subcutaneously at weeks 0 and 8. The primary objective was to evaluate the superiority of mirikizumab over placebo in achieving a 90% improvement in the Psoriasis Area and Severity Index (PASI 90) response at week 16. Comparisons were done using logistic regression analysis with treatment, geographical region and previous biological therapy in the model. Missing data were imputed as nonresponses. RESULTS: Ninety-seven per cent of patients completed the first 16 weeks of the study. The primary end point was met for all mirikizumab dose groups vs. placebo, with PASI 90 response rates at week 16 of 0%, 29% (P = 0·009), 59% (P < 0·001) and 67% (P < 0·001) for patients receiving placebo, and mirikizumab 30 mg, 100 mg and 300 mg, respectively. There were two (1%) serious adverse events in mirikizumab-treated patients vs. one (2%) in a placebo-group patient. CONCLUSIONS: At week 16, 67% of patients treated with mirikizumab 300 mg at 8-week intervals achieved PASI 90. The percentage of patients reporting at least one treatment-emergent adverse event was similar among patients treated with placebo or mirikizumab.

Paracrine potential of adipose stromal vascular fraction cells to recover hypoxia-induced loss of cardiomyocyte function.

Cell-based therapies show promising results in cardiac function recovery mostly through paracrine-mediated processes (as angiogenesis) in chronic ischemia. In this study, we aim to develop a 2D (two-dimensional) in vitro cardiac hypoxia model mimicking severe cardiac ischemia to specifically investigate the prosurvival paracrine effects of adipose tissue-derived stromal vascular fraction (SVF) cell secretome released upon three-dimensional (3D) culture. For the 2D-cardiac hypoxia model, neonatal rat cardiomyocytes (CM) were cultured for 5 days at < 1% (approaching anoxia) oxygen (O2 ) tension. Typical cardiac differentiation hallmarks and contractile ability were used to assess both the cardiomyocyte loss of functionality upon anoxia exposure and its possible recovery following the 5-day-treatment with SVF-conditioned media (collected following 6-day-perfusion-based culture on collagen scaffolds in either normoxia or approaching anoxia). The culture at < 1% O 2 for 5 days mimicked the reversible condition of hibernating myocardium with still living and poorly contractile CM (reversible state). Only SVF-medium conditioned in normoxia expressing a high level of the prosurvival hepatocyte-growth factor (HGF) and insulin-like growth factor (IGF) allowed the partial recovery of the functionality of damaged CM. The secretome generated by SVF-engineered tissues showed a high paracrine potential to rescue the nonfunctional CM, therefore resulting in a promising patch-based treatment of specific low-perfused areas after myocardial infarction.

Effects of low-dose intraoperative fentanyl on postoperative respiratory complication rate: a pre-specified, retrospective analysis.

BACKGROUND: Fentanyl is one of the most frequently administered intraoperative drugs and may increase the risk of postoperative respiratory complications (PRCs). METHODS: We performed a pre-specified analysis of 145 735 adult non-cardiac surgical cases under general anaesthesia. Using multivariable logistic regression, we evaluated the association of intraoperative fentanyl dose and PRCs within 3 days after surgery (defined as reintubation, respiratory failure, pneumonia, pulmonary oedema, or atelectasis). We examined effect modification by patient characteristics, surgical site, and anaesthetics used. RESULTS: PRCs within 3 days after surgery occurred in 18 839 (12.9%) patients. In comparison with high intraoperative fentanyl doses [median: 3.85; inter-quartile range (IQR): 3.42-4.50 µg kg-1, quartile 4 (Q4)], low intraoperative fentanyl dose [median: 0.80, IQR: 0.00-1.14 µg kg-1, quartile 1 (Q1)] was significantly associated with lower odds of PRCs [Q1 vs Q4: 10.9% vs 16.2%; adjusted odds ratio (aOR) 0.79; 95% confidence intervals (CI) 0.75-0.84; P<0.001; adjusted absolute risk difference (aARD) -1.7%]. This effect was augmented by thoracic surgery (P for interaction <0.001; aARD -6.2%), high doses of inhalation anaesthetics (P for interaction=0.016; aARD -2.2%) and neuromuscular blocking agents (NMBAs) (P for interaction=0.001; aARD -3.4%). Exploratory analysis demonstrated that compared with no fentanyl, low-dose fentanyl was associated with lower rates of PRCs (decile 2 vs decile 1: aOR 0.82, CI 0.75-0.89, P<0.001). CONCLUSIONS: Intraoperative low-dose fentanyl (about 60-120 µg for a 70 kg patient) was associated with lower risk of postoperative respiratory complications compared with both no fentanyl and high-dose fentanyl. Beneficial effects of low-dose fentanyl were magnified in specific patient subgroups. CLINICAL TRIAL REGISTRATION: NCT03198208.

The association of early postoperative desaturation in the operating theatre with hospital discharge to a skilled nursing or long-term care facility.

It is unclear which criteria should be used to define readiness for tracheal extubation in the operating theatre. We studied the effects of desaturation in the operating theatre immediately after tracheal extubation on long-term outcomes. Performing a pre-specified, retrospective analysis of 71,025 cases involving previously independent adults undergoing non-cardiac surgery, we evaluated the association between desaturation events (oxygen saturation < 90%) within 10 min of tracheal extubation and adverse discharge (to a skilled nursing facility or long-term care facility). A total of 404 (12.3%) cases with, and 5035 (7.4%) cases without, early postoperative desaturation had an adverse discharge. Early postoperative desaturation was associated with higher odds of being discharged to a nursing facility (adjusted odds ratio 1.36 (95%CI 1.20-1.54); p < 0.001). Increased duration of desaturation augmented the effect (p for trend < 0.001). Desaturation was associated with a higher risk of respiratory, renal and cardiovascular complications as well as increased duration of hospital stay, postoperative intensive care unit admission frequency and cost. Several modifiable factors were associated with desaturation including: high intra-operative long-acting opioid administration; high neostigmine dose; high intra-operative inspired oxygen concentration; and low oxygen delivery immediately before tracheal extubation. There was substantial provider variability between anaesthetists in the incidence of postoperative desaturation unexplained by patient- and procedure-related factors. Early postoperative desaturation is a potentially preventable complication associated with a higher risk of adverse discharge disposition. Anaesthetists may consider developing guidelines to define tracheal extubation readiness that contain postoperative desaturation as an adverse outcome after tracheal extubation.

Bretschneider (Custodiol®) and St. Thomas 2 Cardioplegia Solution in Mitral Valve Repair via Anterolateral Right Thoracotomy: A Propensity-Modelled Comparison.

BACKGROUND: Single-dose cardioplegia is preferred in minimal invasive mitral valve surgery to maintain the adjustment of the operative site without change of preset visualization. The aim of our study was to compare two widely used crystalloid cardioplegias Bretschneider (Custodiol®) versus St. Thomas 2 in patients who underwent mitral valve repair via small anterolateral right thoracotomy. MATERIAL AND METHODS: From May 2012 until February 2019, 184 isolated mitral valve procedures for mitral valve repair via anterolateral right thoracotomy were performed using Bretschneider (Custodiol®) cardioplegia (n = 123) or St. Thomas (n = 61). Primary efficacy endpoint was peak postoperative high-sensitivity cardiac troponin (hs-cTnT) during hospitalization. Secondary endpoints were peak creatine kinase-muscle brain type (CK-MB) and creatine kinase (CK) as well as safety outcomes. We used inverse probability of treatment weighting (IPTW) in order to adjust for confounding by indication. RESULTS: Peak hs-cTnT was higher after use of Bretschneider (Custodiol®) (geometric mean 716 mg/L, 95% confidence interval (CI) 605-847 mg/L) vs. St. Thomas 2 (561 mg/L, CI 467-674 mg/L, p = 0.047). Peak CK-MB (geometric mean after Bretschneider (Custodiol®): 40 µg/L, CI 35-46, St. Thomas 2: 33 µg/L, CI 27-41, p = 0.295) and CK (geometric mean after Bretschneider (Custodiol®): 1370 U/L, CI 1222-1536, St. Thomas 2: 1152 U/L, CI 972-1366, p = 0.037) showed the same pattern. We did not see any difference with respect to postoperative complications between treatment groups after IPTW. CONCLUSION: Use of St. Thomas 2 cardioplegia was associated with lower postoperative peak levels of all cardiac markers that reflect cardiac ischemia such as hs-cTnT, CK, and CK-MB as compared to Bretschneider (Custodiol®) in propensity-weighted treatment groups.

Clinical implementation of a novel myocardial protection pathway in coronary artery bypass surgery with minimal extracorporeal circulation.

INTRODUCTION: The aim of this study was to report the clinical implementation of the joint use of the Myocardial Protection System (MPS®) and the minimal extracorporeal circulation system (MiECC), in conjunction with an institutionally refined dose/volume-dependent microplegia in coronary artery bypass grafting (CABG). METHODS: Patients with isolated CABG surgery were included. The final protocol to achieve cardioplegic arrest consisted of warm blood cardioplegia with 20 mmol potassium (K), 1.6 g magnesium (Mg) and 40 mg lidocaine per liter (L) blood. We prospectively collected intra- and postoperative data to monitor and validate this novel approach. RESULTS: Eighty patients were operated accordingly. Mean (SD) aortic clamping time and extracorporeal perfusion time were 67.5 (22.6) and 101.1 (31.9) minutes, respectively. Failure to induce cardiac arrest was seen in six patients at the early stage of refinement of the formula. Median (IQR) high -sensitivity cardiac troponin T (hs-cTnT) on the first postoperative day (POD) and peak hs-cTnT were 262.5 ng/L (194.3-405.8) and 265.5 ng/L (194.3-405.8), respectively. Median (IQR) creatine kinase-myocardial type (CK-MB) on POD 1 and peak CK-MB were 14.2 µg/L (10.5-22.7) and 14.2 µg/L (10.7-23.2), respectively. Median (IQR) creatine kinase (CK) on POD 1 and peak CK were 517.5 U/L (389.3-849.8) and 597.5 U/L (455.0-943.0), respectively. No patient died during hospitalization. CONCLUSIONS: The combination of this cardioplegic formula with MPS® and MiECC in CABG was safe and feasible. With the final chemical makeup, cardiac arrest was reliably achieved. Remarkably low postoperative cardiac markers indicate shielded cardiac protection during surgery.

Association between intraoperative opioid administration and 30-day readmission: a pre-specified analysis of registry data from a healthcare network in New England.

BACKGROUND: The use of intraoperative opioids may influence the rate of postoperative complications. This study evaluated the association between intraoperative opioid dose and the risk of 30-day hospital readmission. METHODS: We conducted a pre-specified analysis of existing registry data for 153 902 surgical cases performed under general anaesthesia at Massachusetts General Hospital and two affiliated medical centres. We examined the association between total intraoperative opioid dose (categorised in quintiles) and 30-day hospital readmission, controlling for several patient-, anaesthetist-, and case-specific factors. RESULTS: Compared with low intraoperative opioid dosing [quintile 1, median (inter-quartile range): 8 (4-9) mg morphine equivalents], exposure to high-dose opioids during surgery [quintile 5: 32 (27-41) equivalents] is an independent predictor of 30-day readmission [odds ratio (OR) 1.15 (95% confidence interval 1.07-1.24); P<0.001]. Ambulatory surgery patients receiving high opioid doses were found to have the greatest adjusted risk of readmission (OR 1.75; P<0.001) with a clear dose-response effect across quintiles (P for trend <0.05), and were more likely to be readmitted early (postoperative days 0-2 vs 3-30; P<0.001). Opioid class modified the association between total opioid dose and readmission, with longer-acting opioids demonstrating a stronger influence (P<0.001). We observed significant practice variability across individual anaesthetists in the utilisation of opioids that could not be explained by patient- and case-specific factors. CONCLUSIONS: High intraoperative opioid dose is a modifiable anaesthetic factor that varies in the practice of individual anaesthetists and affects postoperative outcomes. Conservative standards for intraoperative opioid dosing may reduce the risk of postoperative readmission, particularly in ambulatory surgery.