Post-anesthesia care unit hypotension in low-risk patients recovering from non-cardiac surgery: a prospective observational study.

Intraoperative hypotension is common and associated with organ injury. Hypotension can not only occur during surgery, but also thereafter. After surgery, most patients are treated in post-anesthesia care units (PACU). The incidence of PACU hypotension is largely unknown - presumably in part because arterial pressure is usually monitored intermittently in PACU patients. We therefore aimed to evaluate the incidence, duration, and severity of PACU hypotension in low-risk patients recovering from non-cardiac surgery. In this observational study, we performed blinded continuous non-invasive arterial pressure monitoring with finger-cuffs (ClearSight system; Edwards Lifesciences, Irvine, CA, USA) in 100 patients recovering from non-cardiac surgery in the PACU. We defined PACU hypotension as a mean arterial pressure (MAP) < 65 mmHg. Patients had continuous finger-cuff monitoring for a median (25th percentile, 75th percentile) of 64 (44 to 91) minutes. Only three patients (3%) had PACU hypotension for at least one consecutive minute. These three patients had 4, 4, and 2 cumulative minutes of PACU hypotension; areas under a MAP of 65 mmHg of 17, 9, and 9 mmHg x minute; and time-weighted averages MAP less than 65 mmHg of 0.5, 0.3, and 0.2 mmHg. The median volume of crystalloid fluid patients were given during PACU treatment was 200 (100 to 400) ml. None was given colloids or a vasopressor during PACU treatment. In low-risk patients recovering from non-cardiac surgery, the incidence of PACU hypotension was very low and the few episodes of PACU hypotension were short and of modest severity.

Hyperangulated vs. Macintosh videolaryngoscopy in adults with anticipated difficult airway management: a randomised controlled trial.

BACKGROUND: It is not certain whether the blade geometry of videolaryngoscopes, either a hyperangulated or Macintosh shape, affects glottic view, success rate and/or tracheal intubation time in patients with expected difficult airways. We hypothesised that using a hyperangulated videolaryngoscope blade would visualise a higher percentage of glottic opening compared with a Macintosh videolaryngoscope blade in patients with expected difficult airways. METHODS: We conducted an open-label, patient-blinded, randomised controlled trial in adult patients scheduled to undergo elective ear, nose and throat or oral and maxillofacial surgery, who were anticipated to have a difficult airway. All airway operators were consultant anaesthetists. Patients were allocated randomly to tracheal intubation with either hyperangulated (C-MAC D-BLADE™) or Macintosh videolaryngoscope blades (C-MAC™). The primary outcome was the percentage of glottic opening. First attempt success was designated a key secondary outcome. RESULTS: We assessed 2540 adults scheduled for elective head and neck surgery for eligibility and included 182 patients with expected difficult airways undergoing orotracheal intubation. The percentage of glottic opening visualised, expressed as median (IQR [range]), was 89 (69-99 [0-100])% with hyperangulated videolaryngoscope blades and 54 (9-90 [0-100])% with Macintosh videolaryngoscope blades (p < 0.001). First-line hyperangulated videolaryngoscopy failed in one patient and Macintosh videolaryngoscopy in 12 patients (13%, p = 0.002). First attempt success rate was 97% with hyperangulated videolaryngoscope blades and 67% with Macintosh videolaryngoscope blades (p < 0.001). CONCLUSIONS: Glottic view and first attempt success rate were superior with hyperangulated videolaryngoscope blades compared with Macintosh videolaryngoscope blades when used by experienced anaesthetists in patients with difficult airways.

Processed electroencephalography-guided general anesthesia and norepinephrine requirements: A randomized trial in patients having vascular surgery.

STUDY OBJECTIVE: Processed electroencephalography (pEEG) may help clinicians optimize depth of general anesthesia. Avoiding excessive depth of anesthesia may reduce intraoperative hypotension and the need for vasopressors. We tested the hypothesis that pEEG-guided - compared to non-pEEG-guided - general anesthesia reduces the amount of norepinephrine needed to keep intraoperative mean arterial pressure above 65 mmHg in patients having vascular surgery. DESIGN: Randomized controlled clinical trial. SETTING: University Medical Center Hamburg-Eppendorf, Hamburg, Germany. PATIENTS: 110 patients having vascular surgery. INTERVENTIONS: pEEG-guided general anesthesia. MEASUREMENTS: Our primary endpoint was the average norepinephrine infusion rate from the beginning of induction of anesthesia until the end of surgery. MAIN RESULT: 96 patients were analyzed. The mean ± standard deviation average norepinephrine infusion rate was 0.08 ± 0.04 µg kg-1 min-1 in patients assigned to pEEG-guided and 0.12 ± 0.09 µg kg-1 min-1 in patients assigned to non-pEEG-guided general anesthesia (mean difference 0.04 µg kg-1 min-1, 95% confidence interval 0.01 to 0.07 µg kg-1 min-1, p = 0.004). Patients assigned to pEEG-guided versus non-pEEG-guided general anesthesia, had a median time-weighted minimum alveolar concentration of 0.7 (0.6, 0.8) versus 0.8 (0.7, 0.8) (p = 0.006) and a median percentage of time Patient State Index was <25 of 12 (1, 41) % versus 23 (3, 49) % (p = 0.279). CONCLUSION: pEEG-guided - compared to non-pEEG-guided - general anesthesia reduced the amount of norepinephrine needed to keep mean arterial pressure above 65 mmHg by about a third in patients having vascular surgery. Whether reduced intraoperative norepinephrine requirements resulting from pEEG-guided general anesthesia translate into improved patient-centered outcomes remains to be determined in larger trials.

Psychometric evaluation of the modified quality of recovery score for the postanaesthesia care unit (QoR-PACU2)-A prospective validation study.

BACKGROUND: To date, there is no instrument to adequately assess self-reported quality of recovery (QoR) in the post-anesthesia care unit (PACU). We previously developed the QoR-PACU, a 13-item questionnaire specifically applicable to the PACU. The feasibility, acceptance, and validity of the QoR-PACU were promising. However, measures of reliability were slightly lower than expected. METHODS: We modified the QoR-PACU and evaluated its psychometric properties in a cohort of adult patients scheduled for non-cardiac surgery with general anesthesia. The modified QoR-PACU (termed QoR-PACU2) was administered before surgery and postoperatively in the PACU at the time of the decision to discharge. RESULTS: A total of 307 patients were included in the final analysis. Postoperative QoR-PACU2 sum scores differed across categories of sex, perioperative and surgical risk, and modes of airway management. The duration of anesthesia and surgery, maximum pain intensity and analgesic requirement in the PACU, and length of PACU stay were all inversely correlated with QoR in the PACU. Cronbach's alpha was 0.70 (95%CI: 0.66-0.75). The intra-class correlation coefficient was 0.86 (95%CI: 0.70-0.94, p < 0.001) for intra-rater reliability (n = 24) and 0.94 (95%CI 0.90 to 0.97, p < 0.001) for inter-rater reliability (n = 31). Cohen's effect size was 0.68 and the standardized response mean was 0.57. CONCLUSION: The QoR-PACU2 assesses self-reported QoR after surgery in the PACU. Measures of feasibility, validity, and reliability were consistently high. Measures of responsiveness were moderate, which might be attributable to the heterogeneity of the study population. Future studies should include aspects of ethnicity and cross-cultural applicability.

Comparison of ex vivo bioluminescence imaging, Alu-qPCR and histology for the quantification of spontaneous lung and bone metastases in subcutaneous xenograft mouse models.

Bioluminescence imaging (BLI) is a non-invasive state-of-the-art-method for longitudinal tracking of tumor cells in mice. The technique is commonly used to determine bone metastatic burden in vivo and also suitable ex vivo to detect even smallest bone micro-metastases in spontaneous metastasis xenograft models. However, it is unclear to which extent ex vivo BLI correlates with alternative methods for metastasis quantification. Here, we compared ex vivo BLI, human DNA-based Alu-qPCR, and histology for the quantification of bone vs. lung metastases, which are amongst the most common sites of metastasis in prostate cancer (PCa) patients and spontaneous PCa xenograft models. Data from 93 immunodeficient mice were considered, each of which were subcutaneously injected with luciferase/RGB-labeled human PCa PC-3 cells. The primary tumors were resected at ~ 0.75 cm³ and mice were sacrificed ~ 3 weeks after surgery and immediately examined by ex vivo BLI. Afterwards, the right lungs and hind limbs with the higher BLI signal (BLIHi bone) were processed for histology, whereas the left lung lobes and hind limbs with the lower BLI signal (BLILo bone) were prepared for Alu-qPCR. Our data demonstrate remarkable differences in the correlation coefficients of the different methods for lung metastasis detection (r ~ 0.8) vs. bone metastasis detection (r ~ 0.4). However, the BLI values of the BLIHi and BLILo bones correlated very strongly (r ~ 0.9), indicating that the method per se was reliable under identical limitations; the overall level of metastasis to contralateral bones was astonishingly similar. Instead, the level of lung metastasis only weakly to moderately correlated with the level of bone metastasis formation. Summarized, we observed a considerable discrepancy between ex vivo BLI and histology/Alu-qPCR in the quantification of bone metastases, which was not observed in the case of lung metastases. Future studies using ex vivo BLI for bone metastasis quantification should combine multiple methods to accurately determine metastatic load in bone samples.

Multidisciplinary survey on use of feeding tubes in head and neck cancer patients undergoing chemoradiotherapy in Germany-the SUFEETUBE project.

BACKGROUND AND OBJECTIVE: Data on enteral tube feeding in head and neck cancer (HNC) patients undergoing chemoradiotherapy vary considerably between German institutions. This survey aims to investigate the management of feeding tubes in an interdisciplinary context across Germany. MATERIALS AND METHODS: Between December 2022 and May 2023, 70 participants (42 radiation oncologists, 12 medical oncologists, 14 head and neck surgeons, and 2 physicians covering several specialties) responded to our web-based survey. In addition to the type of institution (university hospital, private practice, etc.), their age, and professional experience (in years), participants were asked several questions on the indication and institutional policy for tube placement and management (prophylactic/reactive nasogastric or gastrostomy tube). All questions were mandatory single- or multiple-choice questions, while additional comments were possible by email. RESULTS: Most participants were employed at a university hospital (n = 52; 74.3%) and came from a radiation oncology background (n = 42; 60%). Fifty-four contributors (77.1%) reported that no nutritional risk screening prior to chemoradiotherapy was routinely performed, and 71.4% (n = 50) stated that no standardized protocol was used at the institution to set the indication for tube placement. Generally, policies and methods of tube feeding vary considerably between the individual institutions and specialties. However, the majority (n = 56, 80%) recommended a prophylactic percutaneous enteral gastrostomy (PEG) tube to their patients before chemoradiotherapy. Still, there was no consistent trend regarding the approach for reactive tube feeding. CONCLUSION: The policies and methods of tube feeding vary considerably between the individual institutions and specialties in Germany. In the era of individualized medicine, uniform protocols are difficult to establish. However, a baseline nutritional risk screening could simplify decision-making in clinical practice.

Microsurgical Clipping of Unruptured Anterior Circulation Aneurysms-A Global Multicenter Investigation of Perioperative Outcomes.

BACKGROUND AND OBJECTIVES: Microsurgical aneurysm repair by clipping continues to be highly important despite increasing endovascular treatment options, especially because of inferior occlusion rates. This study aimed to present current global microsurgical treatment practices and to identify risk factors for complications and neurological deterioration after clipping of unruptured anterior circulation aneurysms. METHODS: Fifteen centers from 4 continents participated in this retrospective cohort study. Consecutive patients who underwent elective microsurgical clipping of untreated unruptured intracranial aneurysm between January 2016 and December 2020 were included. Posterior circulation aneurysms were excluded. Outcome parameters were postsurgical complications and neurological deterioration (defined as decline on the modified Rankin Scale) at discharge and during follow-up. Multivariate regression analyses were performed adjusting for all described patient characteristics. RESULTS: Among a total of 2192 patients with anterior circulation aneurysm, complete occlusion of the treated aneurysm was achieved in 2089 (95.3%) patients at discharge. The occlusion rate remained stable (94.7%) during follow-up. Regression analysis identified hypertension (P < .02), aneurysm diameter (P < .001), neck diameter (P < .05), calcification (P < .01), and morphology (P = .002) as preexisting risk factors for postsurgical complications and neurological deterioration at discharge. Furthermore, intraoperative aneurysm rupture (odds ratio 2.863 [CI 1.606-5.104]; P < .01) and simultaneous clipping of more than 1 aneurysm (odds ratio 1.738 [CI 1.186-2.545]; P < .01) were shown to be associated with an increased risk of postsurgical complications. Yet, none of the surgical-related parameters had an impact on neurological deterioration. Analyzing volume-outcome relationship revealed comparable complication rates (P = .61) among all 15 participating centers. CONCLUSION: Our international, multicenter analysis presents current microsurgical treatment practices in patients with anterior circulation aneurysms and identifies preexisting and surgery-related risk factors for postoperative complications and neurological deterioration. These findings may assist in decision-making for the optimal therapeutic regimen of unruptured anterior circulation aneurysms.

Spontaneous metastasis xenograft models link CD44 isoform 4 to angiogenesis, hypoxia, EMT and mitochondria-related pathways in colorectal cancer.

Hematogenous metastasis limits the survival of colorectal cancer (CRC) patients. Here, we illuminated the roles of CD44 isoforms in this process. Isoforms 3 and 4 were predominantly expressed in CRC patients. CD44 isoform 4 indicated poor outcome and correlated with epithelial-mesenchymal transition (EMT) and decreased oxidative phosphorylation (OxPhos) in patients; opposite associations were found for isoform 3. Pan-CD44 knockdown (kd) independently impaired primary tumor formation and abrogated distant metastasis in CRC xenografts. The xenograft tumors mainly expressed the clinically relevant CD44 isoforms 3 and 4. Both isoforms were enhanced in the paranecrotic, hypoxic tumor regions but were generally absent in lung metastases. Upon CD44 kd, tumor angiogenesis was increased in the paranecrotic areas, accompanied by reduced hypoxia-inducible factor-1α and CEACAM5 but increased E-cadherin expression. Mitochondrial genes and proteins were induced upon pan-CD44 kd, as were OxPhos genes. Hypoxia increased VEGF release from tumor spheres, particularly upon CD44 kd. Genes affected upon CD44 kd in xenografts specifically overlapped concordantly with genes correlating with CD44 isoform 4 (but not isoform 3) in patients, validating the clinical relevance of the used model and highlighting the metastasis-promoting role of CD44 isoform 4.

The Urethral Perfusion Index During Off-Pump Coronary Artery Bypass Surgery: An Observational Study.

OBJECTIVES: The IKORUS system (Vygon, Écouen, France) allows continuous monitoring of the urethral perfusion index (uPI) using a photoplethysmographic sensor mounted near the base of the balloon of a dedicated urinary catheter. We aimed to test the hypothesis that the uPI decreases during off-pump coronary artery bypass (OPCAB) surgery and to investigate the relationship between the uPI and macrocirculatory variables. DESIGN: Prospective observational study. SETTING: University Medical Center Hamburg-Eppendorf, Hamburg, Germany. PARTICIPANTS: Twenty patients having OPCAB surgery. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The primary endpoint was changes in the uPI during OPCAB surgery. We additionally investigated associations between the uPI and cardiac output, mean arterial pressure, heart rate, and point-of-care variables. Twenty patients with 24,137 uPI measurements were included. Overall, there was a high interindividual variability in the uPI. Compared with the preparation phase (during which the median [interquartile range] uPI was 7.7 [5.6-12.0]), the uPI decreased by 14% (95% CI 13%-15%) during the bypass grafting phase, by 35% (95% CI 34%-36%) during the cardiac positioning phase, and by 7% (95% CI 6%-9%) during hemostasis. There was no clinically important association between uPI and either cardiac output, mean arterial pressure, or heart rate. CONCLUSIONS: The uPI decreases during OPCAB surgery, specifically during the cardiac positioning phase. There was no clinically important association between uPI and either cardiac output, mean arterial pressure, or heart rate. It, therefore, remains to be determined whether intraoperative uPI decreases are clinically important, reflect alterations in intra-abdominal tissue perfusion that are not reflected by systemic macrohemodynamics, and can help clinicians guide therapeutic interventions.

Muscle quality, not quantity, is associated with outcome after colorectal cancer surgery.

INTRODUCTION: Emerging evidence suggests that deconditioned patients benefit most from prehabilitation before colorectal cancer surgery. So far, selecting patients with poor muscle status and high perioperative risk remains challenging. Therefore, this study evaluates the potential of the CT-derived Skeletal Muscle Index (SMI), representing muscle mass, and of the Muscle Radiation Attenuation (MRA), a measure of muscle quality, for risk stratification in colorectal cancer patients. METHODS: In this retrospective, single-center observational study, 207 patients with resection of colorectal adenocarcinoma between January 2016 and December 2020 were included. The Charlson comorbidity index (CCI), postoperative complications, length of hospital stay, and survival were recorded. Data were analyzed using multivariable linear, logistic, and Cox proportional hazards regression models adjusted for age, sex, BMI, CCI, neoadjuvant therapy, tumor stage, and surgery type. RESULTS: An increase of the MRA was associated with fewer postoperative complications (anastomotic leakage and pneumonia) and lesser severity according to the Clavien-Dindo classification, shorter hospital stays, and prolonged survival (Hazard ratio: 0.63 [95%CI: 0.49-0.81], p < 0.001). No relevant associations were found between the SMI and postoperative complications, length of hospital stay, or survival. CONCLUSION: The easy-to-raise MRA serves as a more reliable tool than the SMI for identifying high-risk patients with poor muscle status before colorectal surgery. Those patients may benefit most from prehabilitation, which has to be proven in future interventional trials.

Irradiation dose to the swallowing apparatus impacts nutritional status in head and neck cancer patients-results from the prospective randomized HEADNUT trial.

PURPOSE: To investigate the influence of radiation dose to the swallowing muscles on the nutritional status in patients with head and neck cancer undergoing primary or adjuvant (chemo)radiotherapy (C)RT. METHODS: Between 2018 and 2020, 61 patients were prospectively randomized into the so-called HEADNUT trial (head and neck cancer patients undergoing nutritional intervention). Follow-up was continued until 2022. Contouring of the swallowing apparatus included the superior (scm), middle (mcm), and inferior constrictor muscle (icm), the cricopharyngeal muscle (cphm), and the esophageal inlet. Nutritional status was assessed by bioelectrical impedance analysis (BIA) at the beginning and the end of radiotherapy. The posttherapeutic nutritional status was evaluated by the BIA-derived fat-free mass index (FFMI; kg/m2). Malnutrition was assumed at FFMI values of < 15 (women) and < 17 (men) kg/m2. To find differences between dosimetric parameters in well- and malnourished patients, Mann-Whitney U test was used. To model the association between malnutrition and its potentially influencing variables, several logistic regression models were built. RESULTS: The following parameters differed between well- and malnourished patients at the end of therapy: icm Dmean, V40Gy (%), V50Gy (%), and V60Gy (%), and sphm V40Gy (%). After entering these parameters into a multivariable logistic regression model (dosimetric model), icm Dmean (b = -0.12; Exp(b) = 0.88; 95% CI: 0.78-1.0; p = 0.06) and icm V40Gy (%; b = 0.06; Exp(b) = 1.07; 95% CI: 1-1.13; p = 0.04) proved to be independent dosimetric predictors of malnutrition. We only determined the cut-off value for predicting malnutrition for icm V40Gy (%) since it was the only parameter which met p < 0.05. The optimal cut-off value for the predictor V40Gy (%) based on the Youden Index was 85.6%. Another logistic regression model (dosimetric-clinical model) consisted of icm V40 (%) and the clinical parameters tumor localization, malnutrition before RT, gender, and combined chemotherapy. It was confirmed that both icm V40% (b = -1.9; Exp(b) = -2.7; 95% CI: 0.01-0.8; p = 0.03) and malnutrition at baseline (b = -1.9; Exp(b) = 4.4; 95% CI: 8.4-816.6; p = 0.0002) were independent predictors of subsequent malnutrition the end of RT. CONCLUSION: Establishment of a normal nutritional status before the start of RT and adherence to dose constraints for the swallowing apparatus may prevent malnutrition in head and neck cancer patients at the end of therapy. Specifically, we suggest an icm V40Gy (%) of more than 86% to be predictive for nutritional complications.

Psychometric evaluation of a quality of recovery score for the postanesthesia care unit-A preliminary validation study.

INTRODUCTION: Patients' perception of postoperative recovery is a key aspect of perioperative care. Self-reported quality of recovery (QoR) has evolved as a relevant endpoint in perioperative research. Several psychometric instruments have been introduced to assess self-reported recovery 24 hours after surgery. However, there is no questionnaire suitable for use in the postanesthesia care unit (PACU). We aimed to develop and psychometrically evaluate a QoR questionnaire for the PACU (QoR-PACU). METHODS: The QoR-PACU was developed in German language based on the 40-item QoR-40 questionnaire. Between March and November 2020, adult patients scheduled for elective urologic surgery completed the QoR-PACU preoperatively and during the PACU stay. We evaluated feasibility, validity, reliability, and responsiveness. RESULTS: We included 375 patients. After two piloting phases including 72 and 48 patients, respectively, we administered the final version of the QoR-PACU to 255 patients, with a completion rate of 96.5%. Patients completed the QoR-PACU at a median of 125.0 (83.0; 156.8) min after arrival in the PACU. Construct validity was good with postoperative QoR-PACU sum scores correlating with age (r = 0.23, 95% CI: 0.11 to 0.35, p < 0.001), length of PACU stay (r = -0.15, 95%CI: -0.27 to -0.03, p = 0.02), pain in the PACU (r = -0.48, 95% CI: -0.57 to -0.37, p < 0.001) and piritramide dose administered (r = -0.29, 95% CI: -0.40 to -0.17, p < 0.001). Cronbach's alpha was 0.67 (95% CI: 0.61-0.73) with moderate test-retest reliability (ICC of 0.67, 95% CI: 0.38 to 0.83). Cohen's effect size was 3.08 and the standardized response mean was 1.65 indicating adequate responsiveness. CONCLUSION: The assessment of QoR in the early postoperative period is feasible. We found high acceptability, good validity, adequate responsiveness, and moderate reliability. Future studies should evaluate the psychometric properties of the QoR-PACU in more heterogeneous patient populations including female and gender-diverse patients with varying degress of perioperative risk.

Glidescope Video Laryngoscopy in Patients with Severely Restricted Mouth Opening-A Pilot Study.

BACKGROUND: An inter-incisor gap <3 cm is considered critical for videolaryngoscopy. It is unknown if new generation GlideScope Spectrum™ videolaryngoscopes with low-profile hyperangulated blades might facilitate safe tracheal intubation in these patients. This prospective pilot study aims to evaluate feasibility and safety of GlideScopeTM videolaryngoscopes in severely restricted mouth opening. METHODS: Feasibility study in 30 adults with inter-incisor gaps between 1.0 and 3.0 cm scheduled for ENT or maxillofacial surgery. Individuals at risk for aspiration or rapid desaturation were excluded. RESULTS: The mean mouth opening was 2.2 ± 0.5 cm (range 1.1-3.0 cm). First attempt success rate was 90% and overall success was 100%. A glottis view grade 1 or 2a was achieved in all patients. Nasotracheal intubation was particularly difficult if Magill forceps were required (n = 4). Intubation time differed between orotracheal (n = 9; 33 (25; 39) s) and nasotracheal (n = 21; 55 (38; 94) s); p = 0.049 intubations. The airway operator's subjective ratings on visual analogue scales (0-100) revealed that tube placement was more difficult in individuals with an inter-incisor gap <2.0 cm (n = 10; 35 (29; 54)) versus ≥2.0 cm (n = 20; 20 (10; 30)), p = 0.007, while quality of glottis exposure did not differ. CONCLUSIONS: GlidescopeTM videolaryngoscopy is feasible and safe in patients with severely restricted mouth opening if given limitations are respected.

Continuous Finger-cuff versus Intermittent Oscillometric Arterial Pressure Monitoring and Hypotension during Induction of Anesthesia and Noncardiac Surgery: The DETECT Randomized Trial.

BACKGROUND: Finger-cuff methods allow noninvasive continuous arterial pressure monitoring. This study aimed to determine whether continuous finger-cuff arterial pressure monitoring helps clinicians reduce hypotension within 15 min after starting induction of anesthesia and during noncardiac surgery. Specifically, this study tested the hypotheses that continuous finger-cuff-compared to intermittent oscillometric-arterial pressure monitoring helps clinicians reduce the area under a mean arterial pressure of 65 mmHg within 15 min after starting induction of anesthesia and the time-weighted average mean arterial pressure less than 65 mmHg during noncardiac surgery. METHODS: In this single-center trial, 242 noncardiac surgery patients were randomized to unblinded continuous finger-cuff arterial pressure monitoring or to intermittent oscillometric arterial pressure monitoring (with blinded continuous finger-cuff arterial pressure monitoring). The first of two hierarchical primary endpoints was the area under a mean arterial pressure of 65 mmHg within 15 min after starting induction of anesthesia; the second primary endpoint was the time-weighted average mean arterial pressure less than 65 mmHg during surgery. RESULTS: Within 15 min after starting induction of anesthesia, the median (interquartile range) area under a mean arterial pressure of 65 mmHg was 7 (0, 24) mmHg × min in 109 patients assigned to continuous finger-cuff monitoring versus 19 (0.3, 60) mmHg × min in 113 patients assigned to intermittent oscillometric monitoring (P = 0.004; estimated location shift: -6 [95% CI: -15 to -0.3] mmHg × min). During surgery, the median (interquartile range) time-weighted average mean arterial pressure less than 65 mmHg was 0.04 (0, 0.27) mmHg in 112 patients assigned to continuous finger-cuff monitoring and 0.40 (0.03, 1.74) mmHg in 115 patients assigned to intermittent oscillometric monitoring (P < 0.001; estimated location shift: -0.17 [95% CI: -0.41 to -0.05] mmHg). CONCLUSIONS: Continuous finger-cuff arterial pressure monitoring helps clinicians reduce hypotension within 15 min after starting induction of anesthesia and during noncardiac surgery compared to intermittent oscillometric arterial pressure monitoring.

Noninferiority of Artificial Intelligence-Assisted Analysis of Ki-67 and Estrogen/Progesterone Receptor in Breast Cancer Routine Diagnostics.

Image analysis assistance with artificial intelligence (AI) has become one of the great promises over recent years in pathology, with many scientific studies being published each year. Nonetheless, and perhaps surprisingly, only few image AI systems are already in routine clinical use. A major reason for this is the missing validation of the robustness of many AI systems: beyond a narrow context, the large variability in digital images due to differences in preanalytical laboratory procedures, staining procedures, and scanners can be challenging for the subsequent image analysis. Resulting faulty AI analysis may bias the pathologist and contribute to incorrect diagnoses and, therefore, may lead to inappropriate therapy or prognosis. In this study, a pretrained AI assistance tool for the quantification of Ki-67, estrogen receptor (ER), and progesterone receptor (PR) in breast cancer was evaluated within a realistic study set representative of clinical routine on a total of 204 slides (72 Ki-67, 66 ER, and 66 PR slides). This represents the cohort with the largest image variance for AI tool evaluation to date, including 3 staining systems, 5 whole-slide scanners, and 1 microscope camera. These routine cases were collected without manual preselection and analyzed by 10 participant pathologists from 8 sites. Agreement rates for individual pathologists were found to be 87.6% for Ki-67 and 89.4% for ER/PR, respectively, between scoring with and without the assistance of the AI tool regarding clinical categories. Individual AI analysis results were confirmed by the majority of pathologists in 95.8% of Ki-67 cases and 93.2% of ER/PR cases. The statistical analysis provides evidence for high interobserver variance between pathologists (Krippendorff's α, 0.69) in conventional immunohistochemical quantification. Pathologist agreement increased slightly when using AI support (Krippendorff α, 0.72). Agreement rates of pathologist scores with and without AI assistance provide evidence for the reliability of immunohistochemical scoring with the support of the investigated AI tool under a large number of environmental variables that influence the quality of the diagnosed tissue images.

Tumor cell integrin ß4 and tumor stroma E-/P-selectin cooperatively regulate tumor growth in vivo.

BACKGROUND: The immunological composition of the tumor microenvironment has a decisive influence on the biological course of cancer and is therefore of profound clinical relevance. In this study, we analyzed the cooperative effects of integrin ß4 (ITGB4) on tumor cells and E-/P-selectin on endothelial cells within the tumor stroma for regulating tumor growth by shaping the local and systemic immune environment. METHODS: We used several preclinical mouse models for different solid human cancer types (xenograft and syngeneic) to explore the role of ITGB4 (shRNA-mediated knockdown in tumor cells) and E-/P-selectins (knockout in mice) for tumor growth; effects on apoptosis, proliferation and intratumoral signaling pathways were determined by histological and biochemical methods and 3D in vitro experiments; changes in the intratumoral and systemic immune cell composition were determined by flow cytometry and immunohistochemistry; chemokine levels and their attracting potential were measured by ELISA and 3D invasion assays. RESULTS: We observed a very robust synergism between ITGB4 and E-/P-selectin for the regulation of tumor growth, accompanied by an increased recruitment of CD11b+ Gr-1Hi cells with low granularity (i.e., myeloid-derived suppressor cells, MDSCs) specifically into ITGB4-depleted tumors. ITGB4-depleted tumors undergo apoptosis and actively attract MDSCs, well-known to promote tumor growth in several cancers, via increased secretion of different chemokines. MDSC trafficking into tumors crucially depends on E-/P-selectin expression. Analyses of clinical samples confirmed an inverse relationship between ITGB4 expression in tumors and number of tumor-infiltrating leukocytes. CONCLUSIONS: These findings suggest a distinct vulnerability of ITGB4Lo tumors for MDSC-directed immunotherapies.

Energy Expenditure Under General Anesthesia: An Observational Study Using Indirect Calorimetry in Patients Having Noncardiac Surgery.

BACKGROUND: Perioperative hemodynamic management aims to optimize organ perfusion pressure and blood flow-assuming this ensures that oxygen delivery meets cellular metabolic needs. Cellular metabolic needs are reflected by energy expenditure. A better understanding of energy expenditure under general anesthesia could help tailor perioperative hemodynamic management to actual demands. We thus sought to assess energy expenditure under general anesthesia. Our primary hypothesis was that energy expenditure under general anesthesia is lower than preoperative awake resting energy expenditure. METHODS: We conducted an observational study on patients having elective noncardiac surgery at the University Medical Center Hamburg-Eppendorf (Germany) between September 2019 and March 2020. We assessed preoperative awake resting energy expenditure, energy expenditure under general anesthesia, and energy expenditure after surgery using indirect calorimetry. We compared energy expenditure under general anesthesia at incision to preoperative awake resting energy expenditure using a Wilcoxon signed-rank test for paired measurements. RESULTS: We analyzed 60 patients. Median (95% confidence interval [CI]) preoperative awake resting energy expenditure was 953 (95% CI, 906-962) kcal d -1 m -2 . Median energy expenditure under general anesthesia was 680 (95% CI, 642-711) kcal d -1 m -2 -and thus 263 (95% CI, 223-307) kcal d -1 m -2 or 27% (95% CI, 23%-30%) lower than preoperative awake resting energy expenditure ( P < .001). CONCLUSIONS: Median energy expenditure under general anesthesia is about one-quarter lower than preoperative awake resting energy expenditure in patients having noncardiac surgery.

Endotypes of intraoperative hypotension during major abdominal surgery: a retrospective machine learning analysis of an observational cohort study.

BACKGROUND: Intraoperative hypotension is associated with myocardial injury, acute kidney injury, and death. In routine practice, specific causes of intraoperative hypotension are often unclear. A more detailed understanding of underlying haemodynamic alterations of intraoperative hypotension may identify specific treatments. We thus aimed to use machine learning - specifically, hierarchical clustering - to identify underlying haemodynamic alterations causing intraoperative hypotension in major abdominal surgery patients. Specifically, we tested the hypothesis that there are distinct endotypes of intraoperative hypotension, which may help refine therapeutic interventions. METHODS: We conducted a secondary analysis of intraoperative haemodynamic measurements from a prospective observational study in 100 patients who had major abdominal surgery under general anaesthesia. We used stroke volume index, heart rate, cardiac index, systemic vascular resistance index, and pulse pressure variation measurements. Intraoperative hypotension was defined as any mean arterial pressure ≤65 mm Hg or a mean arterial pressure between 66 and 75 mm Hg requiring a norepinephrine infusion rate exceeding 0.1 µg kg-1 min-1. To identify endotypes of intraoperative hypotension, we used hierarchical clustering (Ward's method). RESULTS: A total of 615 episodes of intraoperative hypotension occurred in 82 patients (46 [56%] female; median age: 64 [57, 73] yr) who had surgery of a median duration of 270 (195, 335) min. Hierarchical clustering revealed six distinct intraoperative hypotension endotypes. Based on their clinical characteristics, we labelled these endotypes as (1) myocardial depression, (2) bradycardia, (3) vasodilation with cardiac index increase, (4) vasodilation without cardiac index increase, (5) hypovolaemia, and (6) mixed type. CONCLUSION: Hierarchical clustering identified six endotypes of intraoperative hypotension. If validated, considering these intraoperative hypotension endotypes may enable causal treatment of intraoperative hypotension.

Effect of personalized perioperative blood pressure management on postoperative complications and mortality in high-risk patients having major abdominal surgery: protocol for a multicenter randomized trial (IMPROVE-multi).

BACKGROUND: Intraoperative hypotension is common in patients having non-cardiac surgery and is associated with serious complications and death. However, optimal intraoperative blood pressures for individual patients remain unknown. We therefore aim to test the hypothesis that personalized perioperative blood pressure management-based on preoperative automated blood pressure monitoring-reduces the incidence of a composite outcome of acute kidney injury, acute myocardial injury, non-fatal cardiac arrest, and death within 7 days after surgery compared to routine blood pressure management in high-risk patients having major abdominal surgery. METHODS: IMPROVE-multi is a multicenter randomized trial in 1272 high-risk patients having elective major abdominal surgery that we plan to conduct at 16 German university medical centers. Preoperative automated blood pressure monitoring using upper arm cuff oscillometry will be performed in all patients for one night to obtain the mean of the nighttime mean arterial pressures. Patients will then be randomized either to personalized blood pressure management or to routine blood pressure management. In patients assigned to personalized management, intraoperative mean arterial pressure will be maintained at least at the mean of the nighttime mean arterial pressures. In patients assigned to routine management, intraoperative blood pressure will be managed per routine. The primary outcome will be a composite of acute kidney injury, acute myocardial injury, non-fatal cardiac arrest, and death within 7 days after surgery. DISCUSSION: Our trial will determine whether personalized perioperative blood pressure management reduces the incidence of major postoperative complications and death within 7 days after surgery compared to routine blood pressure management in high-risk patients having major abdominal surgery. TRIAL REGISTRATION: ClinicalTrials.gov NCT05416944. Registered on June 14, 2022.

Importance of computed tomography muscle quality and continuous versus cut-off-based sarcopenia detection in major hepatic surgery.

Background: The role of the computed tomography (CT)-derived skeletal muscle index (SMI) as a parameter of muscle quantity on the outcome after major liver resection remains contradictory and that of the muscle radiodensity attenuation (MRA) as a parameter of muscle quality has not been sufficiently evaluated. This observational study aimed to investigate the influence of metric SMI and MRA values and cut-off-based CT sarcopenia detection on liver-surgery specific complications measured by the new FABIB (liver failure, ascites, biliary leakage, infection, bleeding) score and survival after hemihepatectomy. Methods: A total of 183 patients with major hepatectomy were retrospectively included. The SMI and MRA were determined from the abdominal muscle area of preoperative CT scans. Patients were classified as sarcopenic by the SMI and MRA cut-off values of Prado et al., Martin et al., and van der Werf et al. Postoperative complications were documented according to the Clavien-Dindo classification and FABIB score. The relation of the continuous, non-categoric SMI and MRA values and of the cut-off-based sarcopenia detection to the postoperative complications and survival was analyzed by multivariable linear, logistic, and Cox proportional hazards regression. Results: A higher MRA was associated with less severe postoperative complications in the Clavien-Dindo [-0.59 (95% CI: -0.95 to -0.23), P=0.002] and the FABIB score [-0.65 (95% CI: -1.19 to -0.12), P=0.017]. An increase of the SMI did not result in less severe complications in the Clavien-Dindo [0.14 (95% CI: -0.27 to 0.55), P=0.503] or FABIB score [0.17 (95% CI: -0.42 to 0.76), P=0.572]. For patients classified as sarcopenic by the cut-off-based systems no relevant relation to postoperative complications was found. Overall survival was better for a higher MRA [hazard ratio (HR): 0.75 (95% CI: 0.58-0.97), P=0.029], as long-term survival was for a higher SMI [HR: 0.68 (95% CI: 0.47-0.96), P=0.031]. Only below van der Werf's MRA cut-off the probability of overall and long-term survival was reduced [HR: 2.32 (95% CI: 1.18-4.54), P=0.015; 2.68 (95% CI: 1.25-5.74), P=0.011]. Conclusions: The MRA has a stronger influence on complications in the Clavien-Dindo classification and the liver-surgery specific FABIB score than the SMI. Continuous, non-categoric MRA and SMI values are superior to cut-off-based systems in predicting the outcome after major hepatic surgery.