On synergy between ultrahigh throughput screening and machine learning in biocatalyst engineering.

Protein design and directed evolution have separately contributed enormously to protein engineering. Without being mutually exclusive, the former relies on computation from first principles, while the latter is a combinatorial approach based on chance. Advances in ultrahigh throughput (uHT) screening, next generation sequencing and machine learning may create alternative routes to engineered proteins, where functional information linked to specific sequences is interpreted and extrapolated in silico. In particular, the miniaturisation of functional tests in water-in-oil emulsion droplets with picoliter volumes and their rapid generation and analysis (>1 kHz) allows screening of >107-membered libraries in a day. Subsequently, decoding the selected clones by short or long-read sequencing methods leads to large sequence-function datasets that may allow extrapolation from experimental directed evolution to further improved mutants beyond the observed hits. In this work, we explore experimental strategies for how to draw up 'fitness landscapes' in sequence space with uHT droplet microfluidics, review the current state of AI/ML in enzyme engineering and discuss how uHT datasets may be combined with AI/ML to make meaningful predictions and accelerate biocatalyst engineering.

Improved ventilation efficiency due to continuous gas flow compared to decelerating gas flow in mechanical ventilation: results of a porcine trial.

In pressure-controlled ventilation (PCV), a decelerating gas flow pattern occurs during inspiration and expiration. In contrast, flow-controlled ventilation (FCV) guarantees a continuous gas flow throughout the entire ventilation cycle where the inspiration and expiration phases are simply performed by a change of gas flow direction. The aim of this trial was to highlight the effects of different flow patterns on respiratory variables and gas exchange. Anesthetized pigs were ventilated with either FCV or PCV for 1 h and thereafter for 30 min each in a crossover comparison. Both ventilation modes were set with a peak pressure of 15 cmH2O, positive end-expiratory pressure of 5 cmH2O, a respiratory rate of 20/min, and a fraction of inspired oxygen at 0.3. All respiratory variables were collected every 15 min. Tidal volume and respiratory minute volume were significantly lower in FCV (n = 5) compared with PCV (n = 5) animals [4.6 vs. 6.6, MD -2.0 (95% CI -2.6 to -1.4) mL/kg; P < 0.001 and 7.3 vs. 9.5, MD -2.2 (95% CI -3.3 to -1.0) L/min; P = 0.006]. Notwithstanding these differences, CO2-removal as well as oxygenation was not inferior in FCV compared with PCV. Mechanical ventilation with identical ventilator settings resulted in lower tidal volumes and consecutive minute volume in FCV compared with PCV. This finding can be explained physically by the continuous gas flow pattern in FCV that necessitates a lower alveolar pressure amplitude. Interestingly, gas exchange was comparable in both groups, which is suggestive of improved ventilation efficiency at a continuous gas flow pattern.NEW & NOTEWORTHY This study examined the effects of a continuous (flow-controlled ventilation, FCV) vs. decelerating (pressure-controlled ventilation, PCV) gas flow pattern during mechanical ventilation. It was shown that FCV necessitates a lower alveolar pressure amplitude leading to reduced applied tidal volumes and consequently minute volume. Notwithstanding these differences, CO2-removal as well as oxygenation was not inferior in FCV compared with PCV, which is suggestive of improved gas exchange efficiency at a continuous gas flow pattern.

Individualised flow-controlled ventilation versus pressure-controlled ventilation in a porcine model of thoracic surgery requiring one-lung ventilation: A laboratory study.

BACKGROUND: Flow-controlled ventilation (FCV) enables precise determination of dynamic compliance due to a continuous flow coupled with direct tracheal pressure measurement. Thus, pressure settings can be adjusted accordingly in an individualised approach. OBJECTIVE: The aim of this study was to compare gas exchange of individualised FCV to pressure-controlled ventilation (PCV) in a porcine model of simulated thoracic surgery requiring one-lung ventilation (OLV). DESIGN: Controlled interventional trial conducted on 16 domestic pigs. SETTING: Animal operating facility at the Medical University of Innsbruck. INTERVENTIONS: Thoracic surgery was simulated with left-sided thoracotomy and subsequent collapse of the lung over a period of three hours. When using FCV, ventilation was performed with compliance-guided pressure settings. When using PCV, end-expiratory pressure was adapted to achieve best compliance with peak pressure adjusted to achieve a tidal volume of 6 ml kg -1 during OLV. MAIN OUTCOME MEASURES: Gas exchange was assessed by the Horowitz index (= P aO 2 /FIO 2 ) and CO 2 removal by the P aCO 2 value in relation to required respiratory minute volume. RESULTS: In the FCV group ( n  = 8) normocapnia could be maintained throughout the OLV trial despite a significantly lower respiratory minute volume compared to the PCV group ( n  = 8) (8.0 vs. 11.6, 95% confidence interval, CI -4.5 to -2.7 l min -1 ; P  < 0.001), whereas permissive hypercapnia had to be accepted in PCV ( P aCO 2 5.68 vs. 6.89, 95% CI -1.7 to -0.7 kPa; P  < 0.001). The Horowitz index was comparable in both groups but calculated mechanical power was significantly lower in FCV (7.5 vs. 22.0, 95% CI -17.2 to -11.8 J min -1 ; P  < 0.001). CONCLUSIONS: In this porcine study FCV maintained normocapnia during OLV, whereas permissive hypercapnia had to be accepted in PCV despite a substantially higher minute volume. Reducing exposure of the lungs to mechanical power applied by the ventilator in FCV offers a possible advantage for this mode of ventilation in terms of lung protection.

A case report of individualized ventilation in a COVID-19 patient - new possibilities and caveats to consider with flow-controlled ventilation.

BACKGROUND: Flow-controlled ventilation (FCV) is a novel ventilation method increasingly being used clinically, particularly during the current COVID-19 pandemic. However, the continuous flow pattern in FCV during inspiration and expiration has a significant impact on respiratory parameters and ventilatory settings compared to conventional ventilation modes. In addition, the constant flow combined with direct intratracheal pressure measurement allows determination of dynamic compliance and ventilation settings can be adjusted accordingly, reflecting a personalized ventilation approach. CASE PRESENTATION: A 50-year old women with confirmed SARS-CoV-2 infection suffering from acute respiratory distress syndrome (ARDS) was admitted to a tertiary medical center. Initial ventilation occurred with best standard of care pressure-controlled ventilation (PCV) and was then switched to FCV, by adopting PCV ventilator settings. This led to an increase in oxygenation by 30 %. Subsequently, to reduce invasiveness of mechanical ventilation, FCV was individualized by dynamic compliance guided adjustment of both, positive end-expiratory pressure and peak pressure; this intervention reduced driving pressure from 18 to 12 cm H2O. However, after several hours, compliance further deteriorated which resulted in a tidal volume of only 4.7 ml/kg. CONCLUSIONS: An individualized FCV approach increased oxygenation parameters in a patient suffering from severe COVID-19 related ARDS. Direct intratracheal pressure measurements allow for determination of dynamic compliance and thus optimization of ventilator settings, thereby reducing applied and dissipated energy. However, although desirable, this personalized ventilation strategy may reach its limits when lung function is so severely impaired that patient's oxygenation has to be ensured at the expense of lung protective ventilation concepts.

The Endothelial Glycocalyx and Organ Preservation-From Physiology to Possible Clinical Implications for Solid Organ Transplantation.

The endothelial glycocalyx is a thin layer consisting of proteoglycans, glycoproteins and glycosaminoglycans that lines the luminal side of vascular endothelial cells. It acts as a barrier and contributes to the maintenance of vascular homeostasis and microperfusion. During solid organ transplantation, the endothelial glycocalyx of the graft is damaged as part of Ischemia Reperfusion Injury (IRI), which is associated with impaired organ function. Although several substances are known to mitigate glycocalyx damage, it has not been possible to use these substances during graft storage on ice. Normothermic machine perfusion (NMP) emerges as an alternative technology for organ preservation and allows for organ evaluation, but also offers the possibility to treat and thus improve organ quality during storage. This review highlights the current knowledge on glycocalyx injury during organ transplantation, presents ways to protect the endothelial glycocalyx and discusses potential glycocalyx protection strategies during normothermic machine perfusion.

Normothermic Machine Perfusion Reduces Transfusion Requirements Even After Static Cold Storage: A 1 y Retrospective Single-center Analysis.

Background: Normothermic machine perfusion (NMP) of liver grafts has been shown to reduce intraoperative catecholamine consumption and the need for allogenic blood products after reperfusion compared with organs undergoing classical static cold storage (SCS). This study aimed to investigate the effects of an NMP phase after SCS (NMP after SCS) of liver grafts in terms of postreperfusion hemodynamics and transfusion requirements. Methods: Eighteen recipients of NMP after SCS grafts were matched according to recipient age, donor age, and model for end-stage liver disease score in a 1:2 ratio with recipients of an SCS graft. Postreperfusion hemodynamics and the need for catecholamines, blood products, and clotting factors were compared. Results: After reperfusion of the organ, patients in the NMP after SCS group showed significantly reduced transfusion requirements for packed red blood cells and platelet concentrates compared with patients of the SCS group (P < 0.001 and P = 0.018, respectively). In addition, patients in the NMP after SCS group received less fibrinogen concentrate (NMP after SCS group 0 [0-1.5] g versus SCS group 2 [0-4] g; P = 0.0163). No differences in postreperfusion hemodynamics could be detected between groups. Conclusions: This retrospective analysis shows that NMP reduces postreperfusion requirements of red blood cells, platelet concentrates, and fibrinogen concentrate even if installed after a phase of organ SCS, because it may be practiced on most centers where NMP is available.

Evaluating Representation Learning on the Protein Structure Universe.

We introduce ProteinWorkshop, a comprehensive benchmark suite for representation learning on protein structures with Geometric Graph Neural Networks. We consider large-scale pre-training and downstream tasks on both experimental and predicted structures to enable the systematic evaluation of the quality of the learned structural representation and their usefulness in capturing functional relationships for downstream tasks. We find that: (1) large-scale pretraining on AlphaFold structures and auxiliary tasks consistently improve the performance of both rotation-invariant and equivariant GNNs, and (2) more expressive equivariant GNNs benefit from pretraining to a greater extent compared to invariant models. We aim to establish a common ground for the machine learning and computational biology communities to rigorously compare and advance protein structure representation learning. Our open-source codebase reduces the barrier to entry for working with large protein structure datasets by providing: (1) storage-efficient dataloaders for large-scale structural databases including AlphaFoldDB and ESM Atlas, as well as (2) utilities for constructing new tasks from the entire PDB. ProteinWorkshop is available at: github.com/a-r-j/ProteinWorkshop.

RNA-FrameFlow: Flow Matching for de novo 3D RNA Backbone Design.

We introduce RNA-FrameFlow, the first generative model for 3D RNA backbone design. We build upon SE(3) flow matching for protein backbone generation and establish protocols for data preparation and evaluation to address unique challenges posed by RNA modeling. We formulate RNA structures as a set of rigid-body frames and associated loss functions which account for larger, more conformationally flexible RNA backbones (13 atoms per nucleotide) vs. proteins (4 atoms per residue). Toward tackling the lack of diversity in 3D RNA datasets, we explore training with structural clustering and cropping augmentations. Additionally, we define a suite of evaluation metrics to measure whether the generated RNA structures are globally self-consistent (via inverse folding followed by forward folding) and locally recover RNA-specific structural descriptors. The most performant version of RNA-FrameFlow generates locally realistic RNA backbones of 40-150 nucleotides, over 40% of which pass our validity criteria as measured by a self-consistency TM-score >= 0.45, at which two RNAs have the same global fold. Open-source code: https://github.com/rish-16/rna-backbone-design.

gRNAde: Geometric Deep Learning for 3D RNA inverse design.

Computational RNA design tasks are often posed as inverse problems, where sequences are designed based on adopting a single desired secondary structure without considering 3D geometry and conformational diversity. We introduce gRNAde, a geometric RNA design pipeline operating on 3D RNA backbones to design sequences that explicitly account for structure and dynamics. Under the hood, gRNAde is a multi-state Graph Neural Network that generates candidate RNA sequences conditioned on one or more 3D backbone structures where the identities of the bases are unknown. On a single-state fixed backbone re-design benchmark of 14 RNA structures from the PDB identified by Das et al. [2010], gRNAde obtains higher native sequence recovery rates (56% on average) compared to Rosetta (45% on average), taking under a second to produce designs compared to the reported hours for Rosetta. We further demonstrate the utility of gRNAde on a new benchmark of multi-state design for structurally flexible RNAs, as well as zero-shot ranking of mutational fitness landscapes in a retrospective analysis of a recent RNA polymerase ribozyme structure. Open source code: https://github.com/chaitjo/geometric-rna-design.

gRNAde: Geometric Deep Learning for 3D RNA inverse design.

Computational RNA design tasks are often posed as inverse problems, where sequences are designed based on adopting a single desired secondary structure without considering 3D geometry and conformational diversity. We introduce gRNAde, a geometric RNA design pipeline operating on 3D RNA backbones to design sequences that explicitly account for structure and dynamics. Under the hood, gRNAde is a multi-state Graph Neural Network that generates candidate RNA sequences conditioned on one or more 3D backbone structures where the identities of the bases are unknown. On a single-state fixed backbone re-design benchmark of 14 RNA structures from the PDB identified by Das et al. [2010], gRNAde obtains higher native sequence recovery rates (56% on average) compared to Rosetta (45% on average), taking under a second to produce designs compared to the reported hours for Rosetta. We further demonstrate the utility of gRNAde on a new benchmark of multi-state design for structurally flexible RNAs, as well as zero-shot ranking of mutational fitness landscapes in a retrospective analysis of a recent RNA polymerase ribozyme structure.

The effects of bolus compared to continuous administration of adrenaline on cerebral oxygenation during experimental cardiopulmonary resuscitation.

Background: Bolus administration of adrenaline during cardiopulmonary resuscitation (CPR) results in only short-term increases in systemic and cerebral perfusion pressure (CePP) with unclear effects on cerebral oxygenation. The aim of this study was to investigate the effects of bolus compared to continuous adrenaline administration on cerebral oxygenation in a porcine CPR model. Methods: After five minutes of cardiac arrest, mechanical CPR was performed for 15 min. Adrenaline (45 µg/kg) was administered either as a bolus every five minutes or continuously over the same period via an infusion pump. Main outcome parameter was brain tissue oxygen tension (PbtO2), secondary outcome parameters included mean arterial pressure (MAP), intracranial pressure (ICP), CePP and cerebral regional oxygen saturation (rSO2) as well as arterial and cerebral venous blood gases. Results: During CPR, mean MAP (45 ± 8 mmHg vs. 38 ± 8 mmHg; p = 0.0827), mean ICP (27 ± 7 mmHg vs. 20 ± 7 mmHg; p = 0.0653) and mean CePP (18 ± 8 mmHg vs. 18 ± 8 mmHg; p = 0.9008) were similar in the bolus and the continuous adrenaline group. Also, rSO2 (both 24 ± 6 mmHg; p = 0.9903) and cerebral venous oxygen saturation (18 ± 12% versus 27.5 ± 12%; p = 0.1596) did not differ. In contrast, relative PbtO2 reached higher values in the continuous group after five minutes of CPR and remained significantly higher than in the bolus group until the end of resuscitation. Conclusion: Continuous administration of adrenaline improved brain tissue oxygen tension compared with bolus administration during prolonged CPR.

[Anesthesia for organ transplant patients]. / Anästhesie bei organtransplantierten Patient:innen.

Organ transplant patients who must undergo nontransplant surgical interventions can be challenging for the anesthesiologists in charge. On the one hand, it is important to carefully monitor the graft function in the perioperative period with respect to the occurrence of a possible rejection reaction. On the other hand, the ongoing immunosuppression may have to be adapted to the perioperative requirements in terms of the active substance and the route of administration, the resulting increased risk of infection and possible side effects (e.g., myelosuppression, nephrotoxicity and impairment of wound healing) must be included in the perioperative treatment concept. Furthermore, possible persistent comorbidities of the underlying disease and physiological peculiarities as a result of the organ transplantation must be taken into account. Support can be obtained from the expertise of the respective transplantation center.

Interleukin-6 Levels During Normothermic Machine Perfusion Impact Postreperfusion Hemodynamics of Liver Graft Recipients: A Prospective Single-center Observational Study.

BACKGROUND: Hemodynamic instability after liver graft reperfusion increases recipient morbidity after liver transplantation. The etiologies of hemodynamic disturbances appear to be multifactorial and are poorly understood. Normothermic machine perfusion (NMP) provides an opportunity to analyze graft quality prior to transplantation. In the present study, we aim to investigate the influence of interleukin-6 (IL-6) levels during NMP on postreperfusion hemodynamics of the recipient. METHODS: Consecutive NMP-liver transplants at a single-center were prospectively analyzed. Perfusate samples were collected at the beginning, after 6 h, and at the end of perfusion and analyzed for IL-6 levels. Mean arterial pressure (MAP) and catecholamine consumption during surgery were recorded. IL-6 levels at the end of NMP were correlated to donor and perfusion characteristics as well as changes in MAP and catecholamine requirements during the anhepatic and reperfusion phase. RESULTS: IL-6 perfusate measurements were assessed in 77 livers undergoing NMP and transplantation. Donor age, sex, cold ischemic time, and NMP time did not correlate with IL-6 levels. Perfusates of donation after circulatory death grafts showed higher IL-6 levels at the end of NMP than donation after brain death grafts. However, IL-6 levels at the end of NMP correlated with catecholamine requirements and MAP in the reperfusion phase. Per log10 increase in IL-6 levels, an increase of 42% points in administered catecholamine dose was observed, despite MAP being decreased by 3.6% points compared to baseline values. CONCLUSIONS: IL-6 levels may be a predictor for recipient hemodynamic instability during liver reperfusion. Larger studies are needed to confirm this finding.

Short time effects of compliance guided flow-controlled ventilation versus standard of care pressure-controlled ventilation: a prospective porcine trial.

BACKGROUND: Flow-controlled ventilation (FCV) represents a novel ventilation method, which guarantees a continuous gas flow during inspiration and expiration. Long term comparison to volume- and pressure-controlled ventilation (PCV) after five- and ten hours have shown improved gas exchange parameters and lung tissue aeration. Aim of this porcine trial was to compare gas exchange parameters and lung tissue aeration in short time application of FCV compared to PCV to determine effects which will most probably pertain in short lasting procedures under general anesthesia. METHODS: After induction of general anesthesia nine pigs were randomly ventilated either with compliance guided FCV settings or standard of PCV with compliance titrated positive end-expiratory pressure and peak pressure set to achieve a tidal volume of 7 mL/kg. Subsequently an arterial blood gas sample was obtained, and a computed tomography scan was performed. Afterwards, each animal was extubated and on the following day the same protocol was performed again with the alternative ventilation method. RESULTS: Primary analysis of 18 datasets from nine animals (with paired comparison) revealed a significantly improved oxygenation with FCV compared to control (paO2 118 vs. 109, 95% CI 2 to 16 mm Hg; P=0.042). The required respiratory minute volume was significantly lower with FCV (7.4 vs. 10.8, 95% CI -4.0 to -2.9 L/min; P<0.001) to achieve similar levels of normocapnia. However, lung tissue aeration did not significantly differ between ventilation methods. CONCLUSIONS: In this short-term ventilation comparison FCV improved gas exchange parameters without differences in lung tissue aeration compared to PCV.

Incidence, risk factors and outcome of acute kidney injury in critically ill COVID-19 patients in Tyrol, Austria: a prospective multicenter registry study.

INTRODUCTION: Acute kidney injury is a frequent complication in critically ill patients with and without COVID-19. The aim of this study was to evaluate the incidence of, and risk factors for, acute kidney injury and its effect on clinical outcomes of critically ill COVID-19 patients in Tyrol, Austria. METHODS: This multicenter prospective registry study included adult patients with a SARS-CoV-2 infection confirmed by polymerase chain reaction, who were treated in one of the 12 dedicated intensive care units during the COVID-19 pandemic from February 2020 until May 2022. RESULTS: In total, 1042 patients were included during the study period. The median age of the overall cohort was 66 years. Of the included patients, 267 (26%) developed acute kidney injury during their intensive care unit stay. In total, 12.3% (n = 126) required renal replacement therapy with a median duration of 9 (IQR 3-18) days. In patients with acute kidney injury the rate of invasive mechanical ventilation was significantly higher with 85% (n = 227) compared to 41% (n = 312) in the no acute kidney injury group (p < 0.001). The most important risk factors for acute kidney injury were invasive mechanical ventilation (OR = 4.19, p < 0.001), vasopressor use (OR = 3.17, p < 0.001) and chronic kidney disease (OR = 2.30, p < 0.001) in a multivariable logistic regression analysis. Hospital and intensive care unit mortality were significantly higher in patients with acute kidney injury compared to patients without acute kidney injury (Hospital mortality: 52.1% vs. 17.2%, p < 0.001, ICU-mortality: 47.2% vs. 14.7%, p < 0.001). CONCLUSION: As in non-COVID-19 patients, acute kidney injury is clearly associated with increased mortality in critically ill COVID-19 patients. Among known risk factors, invasive mechanical ventilation has been identified as an independent and strong predictor of acute kidney injury.

Crystallization of ropivacaine and bupivacaine when mixed with different adjuvants: a semiquantitative light microscopy analysis.

INTRODUCTION: Amino-amide local anesthetics precipitate when mixed with some commonly used adjuvants, carrying the risk of perineural or vascular crystal deposition. The aim of this study was to evaluate whether crystallization occurs with routinely used local anesthetic-adjuvant combinations and if a relation with the solution's pH exists. METHODS: All substances used in this trial were first visually investigated undiluted under tenfold magnification. Grade of crystallization was assessed using a 6 point grading system.Ropivacaine (0.2%, 0.75% and 1%) and bupivacaine (0.25% and 0.5%) were mixed in a 1:1 solution with the following adjuvants: dexamethasone, dexmedetomidine, clonidine, fentanyl, sodium bicarbonate 8.4% and sodium chloride 0.9%. Subsequently, ropivacaine (0.2% and 0.75%) and bupivacaine (0.25% and 0.5%) were mixed with adjuvants in concentrations commonly used in clinical practice and then serially assessed at several time points up to 1 hour. pH of all substances/combinations was assessed and correlated with crystallization grade. RESULTS: All pure substances-except the reference standards sterile water and triamcinolon-showed crystallization grades ranging from grade 1 to grade 4. Addition of adjuvants lead to variable, unpredictable changes in crystal depositions. Addition of sodium bicarbonate 8.4% produced heavy crystallization in all combinations. Grade of crystallization was weakly positively related to the pH of the solution in 1:1 mixtures and clinically relevant concentrations, but not in pure substances. DISCUSSION: Our study showed that crystallization is present in pure local anesthetics and may be increased or decreased by admixture of adjuvants. Higher pH of mixtures was weakly associated with more crystallization. Further research is necessary to translate these findings into clinical practice.

Solid Organ Donation and Transplantation Activity in the Eurotransplant Area During the First Year of COVID-19.

BACKGROUND: Transplantation activity during the first wave of the coronavirus disease 2019 (COVID-19) pandemic was severely affected worldwide. This retrospective analysis aimed to assess the impact of COVID-19 on organ donations and transplantations in the Eurotransplant region during the first 12 mo of the pandemic. Specifically, we compared donor and transplantation numbers during both waves to determine whether transplant systems adapted to this new reality. METHODS: All reported organ donations and transplantations from March 1, 2015, to February 28, 2021, were collected from the Eurotransplant International Foundation registry. The observation period from 2020 to 2021 was divided into three 4-mo periods, which were then compared with the corresponding periods of the preceding 5 y. COVID-19 cases for Eurotransplant countries were retrieved from the OurWorldInData.org database. RESULTS: Overall, the number of organ donors decreased by 18.3% (P < 0.0001) and the number of organ transplantations by 12.5% (P > 0.0001) compared with previous years. Pancreas transplantation was the most affected, followed by kidney, liver, heart, and lung transplant. In detail, during period 1, the number of organ donors decreased by 26.2% (P < 0.0001) and the number of organ transplantations by 16.5% (P < 0.0001), in period 2 by 5.5% (P < 0.0091) and 4.9% (P < 0.0001), and in period 3 by 23.1% (P < 0.0001) and 16.4% (P < 0.0001), respectively. CONCLUSIONS: Organ donation and transplantation decreased drastically also during the second wave; however, despite the severity of the second wave, the decline was comparable with that of the first wave.

The impact of dexamethasone as a perineural additive to ropivacaine for PECS II blockade in patients undergoing unilateral radical mastectomy - A prospective, randomized, controlled and double-blinded trial.

STUDY OBJECTIVE: Dexamethasone is commonly used as an adjuvant to local anesthetics to prolong duration of peripheral nerve blocks with minimal side-effects. The present study investigates the efficacy of dexamethasone added to ropivacaine 0.2% as compared to ropivacaine 0.2% alone for pectoral nerves block II (PECS II) in unilateral radical mastectomy. DESIGN: A prospective, randomized, controlled and double-blinded trial. SETTING: The study was performed at Innsbruck Medical University Hospital, Austria, between January 2019 and October 2020. PATIENTS: Sixty female patients with an American Society of Anesthesiologists Score I-II (18-90 years, BMI 18-35) scheduled for unilateral radical mastectomy without one-stage immediate autologous breast reconstruction were randomly assigned to receive PECS II block with ropivacaine 0.2% with or without dexamethasone 8 mg. INTERVENTIONS: Patients were randomly assigned to receive PECS II block with ropivacaine 0.2% with or without dexamethasone 8 mg. MEASUREMENTS: Primary outcome parameter was the cumulative opioid consumption during the first 72 postoperative hours. Secondary outcome parameters were the duration of analgesia and the course of the visual analogue scale (VAS) and the area under the curve VAS (AUC-VAS). MAIN RESULTS: There was no difference in cumulative opioid consumption after 72 h between the ropivacaine 0.2% plus dexamethasone group and the ropivacaine 0.2% plus placebo group (11.89 vs 11.90 morphine milligram equivalent, respectively; p 0.831). Duration of analgesia also did not differ significantly between the ropivacaine 0.2% plus dexamethasone group and the ropivacaine 0.2% plus placebo group (12.75 versus 8.75 h, respectively; p 0.680). There also was no difference in the course of VAS and AUC-VAS. CONCLUSIONS: Dexamethasone 8 mg when added to ropivacaine 0.2% for PECS II block in unilateral radical mastectomy was not found to reduce total opioid consumption over 72 postoperative hours or to prolong duration of analgesia as compared to pure ropivacaine 0.2%.

Impact of COVID-19 Related Lockdown on the Frequency of Acute and Oncological Surgeries-Lessons Learned From an Austrian University Hospital.

Innsbruck Medical University Hospital, Austria, provides the highest level of care for a region of approximately 1.8 million people. During the early COVID-19 outbreak in spring 2020 surgical activity was drastically reduced with the prime goal of preserving hospital capacities, especially intensive care beds. We conducted a retrospective analysis of surgical activities performed at Innsbruck Medical University Hospital during the lockdown period from March 15 to April 14, 2020 and compared these activities to the same period during the previous 5 years. Total surgical activity was reduced by 65.4% compared to the same period during the previous 5 years (p < 0.001); elective surgeries were reduced by 88.7%, acute surgeries by 35.3% and oncological surgeries by 47.8% compared to the previous 5 years (all p < 0.001). This dramatic decrease in acute and oncological surgeries can most likely be ascribed to the fact that many patients avoided health care facilities because of the strict stay-at-home policy and/or the fear of contracting SARS-CoV-2 in the hospital. In view of future waves, the population should be encouraged to seek medical help for acute symptoms and to attend cancer screening programs.