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Background: Pelvic organ prolapse (POP) affects many women and is often managed with pessary treatment, yet predicting the success of fitting remains challenging. This study aims to identify anatomical parameters associated with successful and unsuccessful pessary treatment using dynamic magnetic resonance imaging (dMRI). Methods: A cross-sectional study in Maastricht University Medical Centre (MUMC+), the Netherlands. Sixteen women with a cystocele and/or descensus uteri minimal POP-Q stage 2, using pessary treatment, were included. All women underwent a dynamic MRI of the pelvic floor at rest, during contraction and on Valsalva. The anatomical parameters evaluated included various lengths and angles. The association between the anatomical parameters and pessary fitted is assessed using partial least squares regression. The predictive accuracy was tested using cross-validation based on the partial least squares model with the most important variables. Results: Seven of the sixteen women (43.8%) were in the non-fitting group (due to movement, rotation or expulsion of the pessary), and nine women (56.3%) were in the fitting group. Participants in the non-fitting group had a significantly lower body mass index (BMI). Variables such as total vaginal length (TVL) and certain angles were highly predictive of pessary fitting success, with variable importance of projection (VIP) scores indicating their importance. The prediction models showed accuracies ranging from 53.3% to 80.0%. Conclusions: In this explorative study, TVL, cervical length (CL), sacrococcygeal angle and pubococcygeal angle were key variables associated with pessary fitting success. These findings offer valuable insights for optimizing pessary fitting procedures and the development of new pessaries. [ABSTRACT FROM AUTHOR]

Atrioventricular conduction disturbance leading to permanent pacemaker (PM) implantation is a frequent and relevant complication after transcatheter aortic valve implantation (TAVI). We aimed to evaluate the rate of post-TAVI permanent PM implantation over time and to identify the predictive factors for post-TAVI PM. The data were retrospectively collected by the Netherlands Heart Registration (NHR). In total, 7489 isolated TAVI patients between 2013 and 2019 were included in the final analysis. The primary endpoint was a permanent PM implantation within 30 days following TAVI. The incidence of the primary endpoint was 12%. Post-TAVI PM showed a stable rate over time. Using multivariable logistic regression analysis, age (OR 1.01, 95% CI 1.00–1.02), weight (OR 1.00, 95% CI 1.00–1.01), creatinine serum level (OR 1.15, 95% CI 1.01–1.31), transfemoral TAVI approach (OR 1.34, 95% CI 1.11–1.61), and TAVI post-dilatation (OR 1.58, 95% CI 1.33–1.89) were shown to be independent predictors of PM. Male sex (OR 0.80, 95% CI 0.68–0.93) and previous aortic valve surgery (OR 0.42, 95% CI 0.26–0.69) had a protective effect on post-TAVI PM. From a large national TAVI registry, some clinical and procedural factors have been identified as promoting or preventing post-TAVI PM. Further efforts are required to identify high-risk patients for post-TAVI PM and to reduce the incidence of this important issue. [ABSTRACT FROM AUTHOR]

Cardiac surgery is regularly associated with postoperative delirium (POD), affected by neuro-inflammation and changes in cholinergic activity. Therefore, this prospective observational study aimed to evaluate whether pre- and perioperative changes in blood acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) activity were associated with POD development in patients undergoing isolated elective coronary artery bypass graft (CABG) surgery. It included 93 patients. Pre- and postoperative blood AChE and BChE activities were measured with photometric rapid-point-of-care-testing. The Intensive Care Delirium Screening Checklist and the Confusion Assessment Method for the Intensive Care Unit were used to screen patients for POD. POD developed in 20 patients (21.5%), who were older ( p = 0.003), had higher EuroSCOREs ( p ≤ 0.001), and had longer intensive care unit stays ( p < 0.001). On postoperative day one, BChE activity decreased from preoperative values more in patients with (31.9%) than without (23.7%) POD (group difference p = 0.002). Applying a cutoff of ≥32.0% for BChE activity changes, receiver operating characteristic analysis demonstrated a moderate prediction capability for POD (area under the curve = 0.72, p = 0.002). The risk of developing POD was 4.31 times higher with a BChE activity change of ≥32.0% ( p = 0.010). Monitoring the pre- to postoperative reduction in BChE activity might be a clinically practicable biomarker for detecting patients at risk of developing POD after CABG surgery.

Several predictive biomarkers for coronavirus disease (COVID-19)-associated mortality in critically ill patients have been described. Although mitochondrial DNA (mtDNA) is elevated in patients with COVID-19, the association with coagulation function and its predictive power for mortality is unclear. Accordingly, this study investigates the predictive power of mtDNA for in-hospital mortality in critically ill patients with COVID-19, and whether combining it with thromboelastographic parameters can increase its predictive performance. This prospective explorative study included 29 patients with COVID-19 and 29 healthy matched controls. mtDNA encoding for NADH dehydrogenase 1 (ND1) was quantified using a quantitative polymerase chain reaction analysis, while coagulation function was evaluated using thromboelastometry and impedance aggregometry. Receiver operating characteristic (ROC) curves were used for the prediction of in-hospital mortality. Within the first 24 h, the plasma levels of mtDNA peaked significantly (controls: 65 (28-119) copies/µL; patients: 281 (110-805) at t 0 , 403 (168-1937) at t 24 , and 467 (188-952) copies/µL at t 72 ; controls vs. patients: p = 0.02 at t 0 , p = 0.03 at t 24 , and p = 0.44 at t 72 ). The mtDNA levels at t 24 showed an excellent predictive performance for in-hospital mortality (area under the ROC curve: 0.90 (0.75-0.90)), which could not be improved by the combination with thromboelastometric or aggregometric parameters. Critically ill patients with COVID-19 present an early increase in the plasma levels of ND1 mtDNA, lasting over 24 h. They also show impairments in platelet function and fibrinolysis, as well as hypercoagulability, but these do not correlate with the plasma levels of fibrinogen. The peak plasma levels of mtDNA can be used as a predictive biomarker for in-hospital mortality; however, the combination with coagulation parameters does not improve the predictive validity.

Background: Intraoperative hypotension is common in patients having non-cardiac surgery and associated with postoperative acute myocardial injury, acute kidney injury, and mortality. Avoiding intraoperative hypotension is a complex task for anesthesiologists. Using artificial intelligence to predict hypotension from clinical and hemodynamic data is an innovative and intriguing approach. The AcumenTM Hypotension Prediction Index (HPI) software (Edwards Lifesciences; Irvine, CA, USA) was developed using artificial intelligence—specifically machine learning—and predicts hypotension from blood pressure waveform features. We aimed to describe the incidence, duration, severity, and causes of intraoperative hypotension when using HPI monitoring in patients having elective major non-cardiac surgery. Methods: We built up a European, multicenter, prospective, observational registry including at least 700 evaluable patients from five European countries. The registry includes consenting adults (≥18 years) who were scheduled for elective major non-cardiac surgery under general anesthesia that was expected to last at least 120 min and in whom arterial catheter placement and HPI monitoring was planned. The major objectives are to quantify and characterize intraoperative hypotension (defined as a mean arterial pressure [MAP] < 65 mmHg) when using HPI monitoring. This includes the time-weighted average (TWA) MAP < 65 mmHg, area under a MAP of 65 mmHg, the number of episodes of a MAP < 65 mmHg, the proportion of patients with at least one episode (1 min or more) of a MAP < 65 mmHg, and the absolute maximum decrease below a MAP of 65 mmHg. In addition, we will assess causes of intraoperative hypotension and investigate associations between intraoperative hypotension and postoperative outcomes. Discussion: There are only sparse data on the effect of using HPI monitoring on intraoperative hypotension in patients having elective major non-cardiac surgery. Therefore, we built up a European, multicenter, prospective, observational registry to describe the incidence, duration, severity, and causes of intraoperative hypotension when using HPI monitoring in patients having elective major non-cardiac surgery.

Chronic Lung Allograft Dysfunction (CLAD) is a life-threatening complication that limits the long-term survival of lung transplantation patients. Early diagnosis remains the basis of efficient management of CLAD, making the need for distinctive biomarkers critical. This explorative study aimed to investigate the predictive power of mitochondrial DNA (mtDNA) derived from bronchoalveolar lavages (BAL) to detect CLAD. The study included 106 lung transplant recipients and analyzed 286 BAL samples for cell count, cell differentiation, and inflammatory and mitochondrial biomarkers, including mtDNA. A receiver operating curve analysis of mtDNA levels was used to assess its ability to detect CLAD. The results revealed a discriminatory pro-inflammatory cytokine profile in the BAL fluid of CLAD patients. The concentration of mtDNA increased in step with each CLAD stage, reaching its highest concentration in stage 4, and correlated significantly with decreasing FEV1. The receiver operating curve analysis of mtDNA in BAL revealed a moderate prediction of CLAD when all stages were grouped together (AUROC 0.75, p-value < 0.0001). This study has found the concentration mtDNA in BAL to be a potential predictor for the early detection of CLAD and the differentiation of different CLAD stages, independent of the underlying pathology.

The use of minimized extracorporeal circulation (MiECC) during cardiac surgery is associated with a reduced inflammatory reaction compared to conventional cardiopulmonary bypass (cCPB). Since it is unknown if MiECC also reduces the amount of free-circulating mitochondrial DNA (mtDNA), this study aims to compare MiECC-induced mtDNA release to that of cCPB as well as to identify potential relations between the plasma levels of mtDNA and an adverse outcome. Overall, 45 patients undergoing cardiac surgery with either cCPB or MiECC were included in the study. MtDNA encoding for NADH dehydrogenase 1 was quantified with quantitative polymerase chain reaction. The plasma amount of mtDNA was significantly lower in patients undergoing cardiac surgery with MiECC compared to cCPB (MiECC: 161.8 (65.5−501.9); cCPB 190.8 (82−705.7); p < 0.001). Plasma levels of mtDNA showed comparable kinetics independently of the study group and peaked during CPB (MiECC preoperative: 68.2 (26.5−104.9); MiECC 60 min after start of CPB: 536.5 (215.7−919.6); cCPB preoperative: 152.5 (80.9−207.6); cCPB 60 min after start of CPB: 1818.0 (844.2−3932.2); all p < 0.001). Patients offering an mtDNA blood concentration of >650 copies/µL after the commencement of CPB had a 5-fold higher risk for postoperative atrial fibrillation independently of the type of cardiopulmonary bypass. An amount of mtDNA being higher than 650 copies/µL showed moderate predictive power (AUROC 0.71 (0.53−071)) for the identification of postoperative atrial fibrillation. In conclusion, plasma levels of mtDNA were lower in patients undergoing cardiac surgery with MiECC compared to cCPB. The amount of mtDNA at the beginning of the CPB was associated with postoperative atrial fibrillation independent of the type of cardiopulmonary bypass.

Transcatheter aortic valve implantation (TAVI) has emerged as an alternative to surgical aortic valve replacement. The aim of this study was to evaluate whether a relevant alteration in cerebral tissue oxygen saturation (rSO2) could be detected following TAVI. Retrospective data analysis included 275 patients undergoing TAVI between October 2016 and December 2020. Overall, rSO2 significantly increased following TAVI (64.6 ± 10% vs. 68.1 ± 10%, p < 0.01). However, a significant rise was only observed in patients with a preoperative rSO2 < 60%. Of the hemodynamic confounders studied, hemoglobin, mean arterial pressure and blood pH were lowered, while central venous pressure and arterial partial pressure of carbon dioxide (PaCO2) were slightly elevated (PaCO2: 39 (36−43) mmHg vs. 42 (37−47) mmHg, p = 0.03; pH: 7.41 (7.3−7.4) vs. 7.36 (7.3−7.4), p < 0.01). Multivariate linear regression modeling identified only hemoglobin as a predictor of altered rSO2. Patients with a EuroScore II above 4% and an extended ICU stay were found to have lower rSO2, while no difference was observed in patients with postoperative delirium or between the implanted valve types. Further prospective studies that eliminate differences in potential confounding variables are necessary to confirm the rise in rSO2. Future research should provide more information on the value of cerebral oximetry for identifying high-risk patients who will require further clinical interventions in the setting of the TAVI procedure.

Background: Cardiac surgery patients represent a high-risk cohort in intensive care units (ICUs). Central venous pressure (CVP) measurement seems to remain an integral part in hemodynamic monitoring, especially in cardio-surgical ICUs. However, its value as a prognostic marker for organ failure is still unclear. Therefore, we analyzed postoperative CVP values after adult cardiac surgery in a large cohort with regard to its prognostic value for morbidity and mortality., Methods: All adult patients admitted to our ICUs between 2006 and 2019 after cardiac surgery were eligible for inclusion in the study ( n = 11,198). We calculated the median initial CVP (miCVP) after admission to the ICU, which returned valid values for 9802 patients. An ROC curve analysis for optimal cut-off miCVP to predict ICU mortality was conducted with consecutive patient allocation into a (a) low miCVP (LCVP) group (≤11 mmHg) and (b) high miCVP (HCVP) group (>11 mmHg). We analyzed the impact of high miCVP on morbidity and mortality by propensity score matching (PSM) and logistic regression., Results: ICU mortality was increased in HCVP patients. In addition, patients in the HCVP group required longer mechanical ventilation, had a higher incidence of acute kidney injury, were more frequently treated with renal replacement therapy, and showed a higher risk for postoperative liver dysfunction, parametrized by a postoperative rise of ≥ 10 in MELD Score. Multiple regression analysis confirmed HCVP has an effect on postoperative ICU-mortality and intrahospital mortality, which seems to be independent., Conclusions: A high initial CVP in the early postoperative ICU course after cardiac surgery is associated with worse patient outcome. Whether or not CVP, as a readily and constantly available hemodynamic parameter, should promote clinical efforts regarding diagnostics and/or treatment, warrants further investigations.

Background: Etomidate is typically used as an induction agent in cardiac surgery because it has little impact on hemodynamics. It is a known suppressor of adrenocortical function and may increase the risk for post-operative infections, sepsis, and mortality. The aim of this study was to evaluate whether etomidate increases the risk of postoperative sepsis (primary outcome) and infections (secondary outcome) compared to propofol., Methods: This was a retrospective before-after trial (IRB EA1/143/20) performed at a tertiary medical center in Berlin, Germany, between 10/2012 and 01/2015. Patients undergoing cardiac surgery were investigated within two observation intervals, during which etomidate and propofol were the sole induction agents., Results: One-thousand, four-hundred, and sixty-two patients, and 622 matched pairs, after caliper propensity-score matching, were included in the final analysis. Sepsis rates did not differ in the matched cohort (etomidate: 11.5% vs. propofol: 8.2%, p = 0.052). Patients in the etomidate interval were more likely to develop hospital-acquired pneumonia (etomidate: 18.6% vs. propofol: 14.0%, p = 0.031)., Conclusion: Our study showed that a single-dose of etomidate is not statistically associated with higher postoperative sepsis rates after cardiac surgery, but is associated with a higher incidence of hospital-acquired pneumonia. However, there is a notable trend towards a higher sepsis rate.

The early administration of fibrinogen has gained wide acceptance for the treatment of major hemorrhage, whereas the substitution of coagulation factor XIII (FXIII) is only supported by a low level of evidence. This study aimed to answer the question of whether a combined therapy of fibrinogen/FXIII substitution performs superiorly to sole fibrinogen administration in the treatment of dilutional coagulopathy. An in-vitro model of massive transfusion was used to compare the effect of combined fibrinogen/FXIII administration to that of sole fibrinogen therapy for the treatment of dilutional coagulopathy. For this purpose, the blood of red blood cell concentrates, fresh frozen plasma, and platelet concentrates were reconstituted in a ratio of 4:4:1, and then diluted with gelatin by 20% and 40%, respectively. Clot formation and stability were analyzed by thrombelastography. Both sole fibrinogen therapy (equivalent to 50 mg/kg) and the combined administration of fibrinogen (equivalent to 50 mg/kg) and FXIII (equivalent to 75 International Units (IU)/kg) increased fibrinogen-dependent mean clot firmness independently of the degree of dilution (20% dilution: 7 (6.3-7.8) mm; 20% dilution fibrinogen: 13.5 (13-17.3) mm; 20% dilution fibrinogen/FXIII: 16.5 (15.3-18.8) mm; 40% dilution: 3 (2-3.8) mm; 40% dilution fibrinogen: 8 (7-11.3) mm; 40% dilution fibrinogen/FXIII: 10 (8.3-11.8) mm; all p < 0.01). However, no differences were identified between the two treatment arms. Compared to fibrinogen therapy, no beneficial effect of the combined administration of fibrinogen and FXIII for the treatment of dilutional coagulopathy was detected in this in-vitro massive transfusion model. The result was independent of the degree of dilution.

Major surgery is regularly associated with clinical signs of systemic inflammation, which potentially affects the rapid identification of sepsis. Therefore, this secondary analysis of an observational study aims to determine whether NADH dehydrogenase 1 (ND1) mitochondrial DNA (mtDNA) could be used as a potential biomarker for the discrimination between septic shock and postsurgical systemic inflammation. Overall, 80 patients were included (septic shock ( n = 20), cardiac artery bypass grafting (CABG, n = 20), major abdominal surgery (MAS, n = 20), and matched controls (CTRL, n = 20)). Quantitative PCR was performed to measure ND1 mtDNA. Thromboelastography was used to analyze the coagulatory system. Free-circulating ND1 mtDNA levels were significantly higher in septic shock patients compared to patients suffering from post-surgical inflammation ({copies/µL}: CTRL: 1208 (668-2685); septic shock: 3823 (2170-7318); CABG: 1272 (417-2720); and MAS: 1356 (694-2845); CTRL vs. septic shock: p < 0.001; septic shock vs. CABG: p < 0.001; septic shock vs. MAS: p = 0.006; CABG vs. MAS: p = 0.01). ND1 mtDNA levels in CABG patients showed a strong positive correlation with fibrinogen (correlation coefficient [ r ]= 0.57, p < 0.001) and fibrinogen-dependent thromboelastographic assays (maximum clot firmness, EXTEM: r = 0.35, p = 0.01; INTEM: r = 0.31, p = 0.02; FIBTEM: r = 0.46, p < 0.001). In conclusion, plasma levels of free-circulating ND1 mtDNA were increased in septic shock patients and were discriminative between sepsis and surgery-induced inflammation. Furthermore, this study showed an association between ND1 mtDNA and a fibrinogen-dependent pro-coagulatory shift in cardiac surgical patients.

Patients undergoing esophageal cancer surgery are at high risk of developing severe pulmonary complications. Beneficial effects of minimally invasive esophagectomy had been discussed recently, but the incidence of perioperative respiratory impairment remains unclear. This is a retrospective single-center cohort study of patients, who underwent open (OE) or laparoscopically assisted, hybrid minimally invasive abdomino-thoracic esophagectomy (LAE) for cancer regarding respiratory impairment (PaO 2 /FiO 2 ratio (P/FR) < 300 mmHg) and pneumonia. No differences were observed in the cumulative incidence of reduced P/FR between OE and LAE patients. Of note, until postoperative day (POD) 2, P/FR did not differ among both groups. Thereafter, the rate of patients with respiratory impairment was higher after OE on POD 3, 5, and 10 ( p ≤ 0.05) and tended being higher on POD 7 and 9 ( p ≤ 0.1). Although the duration of LAE procedure was slightly longer (total: p = 0.07, thoracic part: p = 0.004), the duration of surgery (Spearman's rank correlation coefficient (r sp ) = -0.267, p = 0.006), especially of laparotomy (r sp = -0.242, p = 0.01) correlated inversely with respiratory impairment on POD 3 after OE. Pneumonia occurred on POD 5 (1-25) and 8.5 (3-14) after OE and LAE, respectively, with the highest incidence after OE ( p = 0.01). In conclusion, respiratory impairment and pulmonary complications occur frequently after esophagectomy. Although early respiratory impairment is independent of the surgical approach, postoperative pneumonia rate is reduced after LAE.

This proof-of-concept study aimed to evaluate a novel method of flow cytometry-based quantification of neutrophil extracellular traps (NETs) in septic shock patients and to identify possible interactions between the number of free-circulating NETs and alterations of the coagulatory system. Patients suffering from septic shock, a matched control group (CTRL), and patients suffering from systemic inflammation after cardiac (CABG) or major abdominal surgery (MAS) were enrolled in this prospective proof-of-concept study. Compared to the matched controls, free-circulating NETs were significantly elevated in septic shock and postsurgical patients (data are presented in median (IQR)); septic shock: (2.7 (1.9-3.9); CABG: 2.7 (2.1-3.7); MAS: 2.7 (2.1-3.9); CTRL: 1.6 (1-2); CTRL vs. septic shock: p = 0.001; CTRL vs. CABG: p < 0.001; CTRL vs. MAS: p < 0.001). NETs correlated positively with FIBTEM mean clot firmness (MCF) in septic shock patients ( r = 0.37, p < 0.01) while they correlated negatively in surgical patients (CABG: r = -0.28, p < 0.01; MAS: r = -0.25, p = 0.03). Flow-cytometric quantification of NETs showed a significant increase in free-circulating NETs under inflammatory conditions. Furthermore, this study hints to an association of the number of NETs with hypercoagulation in septic shock patients and hypocoagulation in surgery-induced inflammation., Competing Interests: The authors declare no conflict of interest.