Risk of conversion to mild cognitive impairment or dementia among subjects with amyloid and tau pathology: a systematic review and meta-analysis.

BACKGROUND: Measurement of beta-amyloid (Aß) and phosphorylated tau (p-tau) levels offers the potential for early detection of neurocognitive impairment. Still, the probability of developing a clinical syndrome in the presence of these protein changes (A+ and T+) remains unclear. By performing a systematic review and meta-analysis, we investigated the risk of mild cognitive impairment (MCI) or dementia in the non-demented population with A+ and A- alone and in combination with T+ and T- as confirmed by PET or cerebrospinal fluid examination. METHODS: A systematic search of prospective and retrospective studies investigating the association of Aß and p-tau with cognitive decline was performed in three databases (MEDLINE via PubMed, EMBASE, and CENTRAL) on January 9, 2024. The risk of bias was assessed using the Cochrane QUIPS tool. Odds ratios (OR) and Hazard Ratios (HR) were pooled using a random-effects model. The effect of neurodegeneration was not studied due to its non-specific nature. RESULTS: A total of 18,162 records were found, and at the end of the selection process, data from 36 cohorts were pooled (n= 7,793). Compared to the unexposed group, the odds ratio (OR) for conversion to dementia in A+ MCI patients was 5.18 [95% CI 3.93; 6.81]. In A+ CU subjects, the OR for conversion to MCI or dementia was 5.79 [95% CI 2.88; 11.64]. Cerebrospinal fluid Aß42 or Aß42/40 analysis and amyloid PET imaging showed consistent results. The OR for conversion in A+T+ MCI subjects (11.60 [95% CI 7.96; 16.91]) was significantly higher than in A+T- subjects (2.73 [95% CI 1.65; 4.52]). The OR for A-T+ MCI subjects was non-significant (1.47 [95% CI 0.55; 3.92]). CU subjects with A+T+ status had a significantly higher OR for conversion (13.46 [95% CI 3.69; 49.11]) than A+T- subjects (2.04 [95% CI 0.70; 5.97]). Meta-regression showed that the ORs for Aß exposure decreased with age in MCI. (beta = -0.04 [95% CI -0.03 to -0.083]). CONCLUSIONS: Identifying Aß-positive individuals, irrespective of the measurement technique employed (CSF or PET), enables the detection of the most at-risk population before disease onset, or at least at a mild stage. The inclusion of tau status in addition to Aß, especially in A+T+ cases, further refines the risk assessment. Notably, the higher odds ratio associated with Aß decreases with age. TRIAL REGISTRATION: The study was registered in PROSPERO (ID: CRD42021288100).

Evaluating the predictive value of late gadolinium enhancement assessed by cardiac magnetic resonance on sudden cardiac death in patients selected for implantable cardioverter defibrillator and cardiac resynchronization therapy implantation: a systematic review and meta-analysis.

AIMS: Late gadolinium enhancement (LGE) assessed by cardiovascular magnetic resonance (CMR) can evaluate myocardial scar associated with a higher risk of sudden cardiac death (SCD), which can guide the selection between cardiac resynchronization therapy with or without a defibrillator (CRT-P/CRT-D). Our aim was to investigate the association between LGE and SCD risk in patients with CRT using the LGE-CMR technique. METHODS AND RESULTS: We performed a systematic literature search using four databases. The target population was CRT candidates. The primary endpoint was SCD. The risk of bias was assessed using the QUIPS tool. Fifteen eligible articles were included with a total of 2494 patients, of whom 27%, 56%, and 19% had an implantable cardioverter defibrillator (ICD), CRT-D, and CRT-P, respectively. Altogether, 54.71% of the cohort was LGE positive, who had a 72% higher risk for SCD (HR 1.72; 95% CI 1.18-2.50) compared to LGE negatives. In non-ischemic patients, the proportion of LGE positivity was 46.6%, with a significantly higher risk for SCD as compared to LGE negatives (HR 2.42; 95% CI 1.99-2.94). The subgroup of CRT-only patients showed no difference between the LGE-positive vs. negative candidates (HR 1.17; 95% CI 0.82-1.68). Comparable SCD risk was observed between articles with short- (OR 7.47; 95% CI 0.54-103.12) vs. long-term (OR 6.15; 95% CI 0.96-39.45) follow-up time. CONCLUSION: LGE-CMR positivity was associated with an increased SCD risk; however, in CRT candidates, the difference in risk reduction between LGE positive vs. negative patients was statistically not significant, suggesting a role of reverse remodeling. LGE-CMR before device implantation could be crucial in identifying high-risk patients even in non-ischemic etiology.

The Effect of Preoperative Administration of Glucocorticoids on the Postoperative Complication Rate in Liver Surgery: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Background: Glucocorticoids may grant a protective effect against postoperative complications. The evidence on their efficacy, however, has been inconclusive thus far. We investigated the effects of preoperatively administered glucocorticoids on the overall postoperative complication rate, and on liver function recovery in patients undergoing major liver surgery. Methods: We performed a systematic literature search on PubMed, Embase, and CENTRAL in October 2021, and repeated the search in April 2023. Pre-study protocol was registered on PROSPERO (ID: CRD42021284559). Studies investigating patients undergoing liver resections or transplantation who were administered glucocorticoids preoperatively and reported postoperative complications were eligible. Meta-analyses were performed using META and DMETAR packages in R with a random effects model. Risk of bias was assessed using RoB2. Results: The selection yielded 11 eligible randomized controlled trials (RCTs) with 964 patients. Data from nine RCTs (n = 837) revealed a tendency toward a lower overall complication rate with glucocorticoid administration (odds ratio: 0.71; 95% confidence interval: 0.38-1.31, p = 0.23), but it was not statistically significant. Data pooled from seven RCTs showed a significant reduction in wound infections with glucocorticoid administration [odds ratio: 0.64; 95% confidence interval: 0.45-0.92 p = 0.02]. Due to limited data availability, meta-analysis of liver function recovery parameters was not possible. Conclusions: The preoperative administration of glucocorticoids did not significantly reduce the overall postoperative complication rate. Future clinical trials should investigate homogenous patient populations with a specific focus on postoperative liver recovery.

Predicting residual cholesteatoma with the Potsic staging system still lacks evidence: a systematic review and meta-analysis.

PURPOSE: To investigate the rate of residual disease in the Potsic staging system for congenital cholesteatomas. METHODS: A protocol registration was published on PROSPERO (CRD42022383932), describing residual disease as a primary outcome and hearing improvement as secondary. A systematic search was performed in four databases (PubMed, Embase, Cochrane Library, Web of Science) on December 14, 2022. Articles were included if cholesteatomas were staged according to the Potsic system and follow-up duration was documented. Risk of bias was evaluated using the Quality In Prognosis Studies (QUIPS) tool. In the statistical synthesis a random effects model was used. Between-study heterogeneity was assessed using I2. RESULTS: Thirteen articles were found to be eligible for systematic review and seven were included in the meta-analysis section. All records were retrospective cohort studies with high risk of bias. Regarding the proportions of residual disease, analysis using the χ2 test showed no statistically significant difference between Potsic stages after a follow-up of minimum one year (stage I 0.06 (confidence interval (CI) 0.01-0.33); stage II 0.20 (CI 0.09-0.38); stage III 0.06 (CI 0.00-0.61); stage IV: 0.17 (CI 0.01-0.81)). Postoperative and preoperative hearing outcomes could not be analyzed due to varied reporting. Results on cholesteatoma location and mean age at staging were consistent with those previously published. CONCLUSION: No statistically significant difference was found in the proportions of residual disease between Potsic stages, thus the staging system's applicability for outcome prediction could not be proven based on the available data. Targeted studies are needed for a higher level of evidence.

Domain-specific cognitive impairment in multiple sclerosis: A systematic review and meta-analysis.

OBJECTIVE: Methods of cognitive measurements in multiple sclerosis (MS) are not standardized. We aimed to identify the prevalence of cognitive domain-specific impairment (DSI) in MS by using subtests of the Brief Repeatable Battery of Neuropsychological Tests (BRB-N) with analyzing different cutoff values. METHODS: The systematic review and meta-analysis were registered on PROSPERO (ID: CRD42021287004). The systematic literature search was performed via PubMed, Embase, and CENTRAL on 24 October 2021. Inclusion criteria were adults of different MS subtypes (CIS, RRMS, PPMS, and SPMS) with the condition of distinct DSI measured by BRB-N. Pediatric MS, computerized versions of BRB-N, and patients receiving steroids were excluded. Primary outcome was pooled prevalence rates of impaired patients within each cutoff and MS subtype, with 95% confidence interval, I-squared statistics for heterogeneity, and chi-squared test for subgroup differences. Risk of bias was assessed using the "JBI Quality Assessment Tool for Prevalence Studies." RESULTS: In 48 eligible observational studies (n = 3431 patients), the three most prevalent thresholds were the 2.0 SD and 1.5 SD below the mean of normative values, and the score below the fifth percentile of the normative values. A progressively increasing worsening of the overall DSI was observed from CIS, moving toward RRMS, PPMS, and SPMS. INTERPRETATION: Cognitive impairment is observed in all MS phenotypes, with varying degrees. Due to several potential influencing factors, our comprehensive literature review has not revealed consistent findings, and we, therefore, recommend considering a more sophisticated, "individual referencing" approach, acknowledging the diverse clinical and sociodemographic characteristics among populations and disparities in cognitive testing.

Towards richer knowledge partnerships between ecology and ethnoecology.

Indigenous and traditional practices based on ethnoecological knowledge are fundamental to biodiversity stewardship and sustainable use. Knowledge partnerships between Indigenous Peoples, traditional local communities, and ecologists can produce richer and fairer understandings of nature. We identify key topical areas where such collaborations can positively transform science, policy, and practice.

Evidence for gait improvement with robotic-assisted gait training of children with cerebral palsy remains uncertain.

BACKGROUND: Cerebral palsy (CP) is a group of neuromotor diseases that develops as a result of damage to the developing central nervous system during the perinatal period. The condition is usually accompanied by musculoskeletal problems resulting in movement disorders. Gait improvement therefore, is an important part of its treatment. Roboticassisted gait training (RAGT) is a new potential rehabilitation tool for CP patients, however there is no clear evidence for the effectiveness of this method. RESEARCH QUESTION: Can robotic-assisted gait training improve walking function in children with CP? METHODS: A systematic search was performed in five databases: MEDLINE (via PubMed), Cochrane Central Register of Controlled Trials (CENTRAL), Embase, Scopus, and Web of Science. Eligible studies were randomized controlled trials (RCT) with CP patients under the age of 18. Gross motor function and kinematic gait parameters of patients were the main outcomes. Two authors determined the risk of bias of the RCTs independently using the revised Risk of Bias 2 (ROB 2) tool. Mean Differences (MDs) along with their 95% Confidence Interval (CI) were calculated when at least three studies were present for an outcome, subgroup analysis was performed based on the treatment of the control group. RESULTS: Of the 7363 screened articles, 13 papers met our inclusion criteria and among them, 7 studies could be used in our meta-analyses. The results related to RAGT suggest nonsignificant improvement in standing and walking function (Gross Motor Function Measure D, E), moreover changes in gait speed, step length, and in cadence were also only comparable to controls. SIGNIFICANCE: The results indicate that there is a trend in some gait parameters where the improvement was higher in the intervention group than in control group. The therapeutic effect of RAGT was probably not superior to physiotherapy combined with treadmill training.

The potential role of extracorporeal cytokine removal with CytoSorb® as an adjuvant therapy in Acute Respiratory Distress Syndrome.

Management of acute respiratory distress syndrome (ARDS) represents one of the greatest challenges in intensive care and despite all efforts mortality remains high. One common phenotype of ARDS is that of a secondary injury to a dysregulated inflammatory host response resulting in increased capillary congestion, interstitial lung edema, atelectasis, pulmonary embolism, muscle wasting, recurring infectious episodes, and multiple organ failure. In cases of hyperinflammation, immunomodulation by extracorporeal cytokine removal such as the CytoSorb hemoadsorption cartridge could conceptually enhance lung recovery during the early course of the disease. The aim of this narrative review is to summarize the currently available data in this field and to provide an overview of pathophysiology and rationale for the use of CytoSorb hemoadsorption in patients with hyperinflammatory ARDS.

Adjunctive Hemoadsorption Therapy with CytoSorb in Patients with Septic/Vasoplegic Shock: A Best Practice Consensus Statement.

A dysregulated host response is a common feature in critically ill patients due to both infectious and non-infectious origins that can lead to life-threatening organ dysfunction, which is still the primary cause of death in intensive care units worldwide. In its course, pathologic, unregulated levels of inflammatory mediators are often released into the circulation, a phenomenon also referred to as a "cytokine storm". To date, there are no approved therapies to modulate the excessive immune response and limit hyperinflammation with the goal of preventing related organ failure and death. In this context, extracorporeal blood purification therapies aiming at the alteration of the host inflammatory response through broad-spectrum, non-selective removal of inflammatory mediators have come into focus. A novel hemoadsorption device (CytoSorb®, CytoSorbents Inc., Princeton, NJ, USA) has shown promising results in patients with hyperinflammation from various origins. Although a significant body of literature exists, there is ongoing research to address many important remaining questions, including the optimal selection of patient groups who might benefit the most, optimal timing for therapy initiation, optimal schedule for adsorber exchanges and therapy duration, as well as an investigation into the potential removal of concomitant antibiotics and other medications. In this review, we discuss the existing evidence and provide a consensus-based best practice guidance for CytoSorb® hemoadsorption therapy in patients with vasoplegic shock.

Plasma Exchange versus Intravenous Immunoglobulin in Worsening Myasthenia Gravis: A Systematic Review and Meta-Analysis with Special Attention to Faster Relapse Control.

Currently used rescue interventions to prevent rapid myasthenic deterioration are plasma exchange (PLEX) and intravenous immunoglobulin (IVIG). We investigated the evidence to determine whether the two methods were interchangeable or whether one was superior to the other. This review was registered on PROSPERO (CRD42021285985). Only randomized controlled trials (RCTs) comparing the efficacy and safety of PLEX and IVIG in patients with moderate-to-severe myasthenia gravis (MG) were included. Five major databases were systematically searched (PubMed, CENTRAL, Embase, Scopus, and Web of Science). Odds ratios (OR) with 95% confidence intervals (CI) were calculated for adverse events and mean differences (MD) for changes in quantitative myasthenia gravis scores (QMG). Three RCTs met the inclusion criteria. Two investigating 114 patients in total were eligible for meta-analysis to analyze efficacy and safety. For the change in QMG score, the MD was -2.8 (95% CI: -5.614-0.113), with PLEX performing better. For adverse events, an OR of 1.04 was found (95% CI: 0.25-4.27). This study demonstrated a low risk of bias in evaluating treatment efficacy but indicated a high risk of bias in assessing procedural safety outcomes. Although the results did not show any significant difference, there was a tendency indicating faster efficacy of PLEX in the first two weeks of treatment. In such a critical clinical condition, this tendency may be clinically meaningful, but further studies should clarify this benefit.

Hemoadsorption as Adjuvant Therapy in Acute Respiratory Distress Syndrome (ARDS): A Systematic Review and Meta-Analysis.

BACKGROUND: Acute respiratory distress syndrome (ARDS) is often a consequence of a dysregulated immune response; therefore, immunomodulation by extracorporeal cytokine removal has been increasingly used as an adjuvant therapy, but convincing data are still missing. The aim of this study was to investigate the effects of adjunctive hemoadsorption (HA) on clinical and laboratory outcomes in patients with ARDS. METHODS: We performed a systematic literature search in PubMed, Embase, CENTRAL, Scopus, and Web of Science (PROSPERO: CRD42022292176). The population was patients receiving HA therapy for ARDS. The primary outcome was the change in PaO2/FiO2 before and after HA therapy. Secondary outcomes included the before and after values for C-reactive protein (CRP), lactate, interleukin-6 (IL-6), and norepinephrine (NE) doses. RESULTS: We included 26 publications, with 243 patients (198 undergoing HA therapy and 45 controls). There was a significant improvement in PaO2/FiO2 ratio following HA therapy (MD = 68.93 [95%-CI: 28.79 to 109.06] mmHg, p = 0.005) and a reduction in CRP levels (MD = -45.02 [95%-CI: -82.64; -7.39] mg/dL, p = 0.026) and NE dose (MD = -0.24 [95%-CI: -0.44 to -0.04] µg/kg/min, p = 0.028). CONCLUSIONS: Based on our findings, HA resulted in a significant improvement in oxygenation and a reduction in NE dose and CRP levels in patients treated with ARDS. Properly designed RCTs are still needed.

PADAPT 1.0 - the Pannonian Dataset of Plant Traits.

The existing plant trait databases' applicability is limited for studies dealing with the flora and vegetation of the eastern and central part of Europe and for large-scale comparisons across regions, mostly because their geographical data coverage is limited and they incorporate records from several different sources, often from regions with markedly different climatic conditions. These problems motivated the compilation of a regional dataset for the flora of the Pannonian region (Eastern Central Europe). PADAPT, the Pannonian Dataset of Plant Traits relies on regional data sources and collates data on 54 traits and attributes of the plant species of the Pannonian region. The current version covers approximately 90% of the species of the region and consists of 126,337 records on 2745 taxa. By including species of the eastern part of Europe not covered by other databases, PADAPT can facilitate studying the flora and vegetation of the eastern part of the continent. Although data coverage is far from complete, PADAPT meets the longstanding need for a regional database of the Pannonian flora.

Procalcitonin-guided antibiotic therapy may shorten length of treatment and may improve survival-a systematic review and meta-analysis.

BACKGROUND: Appropriate antibiotic (AB) therapy remains a challenge in the intensive care unit (ICU). Procalcitonin (PCT)-guided AB stewardship could help optimize AB treatment and decrease AB-related adverse effects, but firm evidence is still lacking. Our aim was to compare the effects of PCT-guided AB therapy with standard of care (SOC) in critically ill patients. METHODS: We searched databases CENTRAL, Embase and Medline. We included randomized controlled trials (RCTs) comparing PCT-guided AB therapy (PCT group) with SOC reporting on length of AB therapy, mortality, recurrent and secondary infection, ICU length of stay (LOS), hospital LOS or healthcare costs. Due to recent changes in sepsis definitions, subgroup analyses were performed in studies applying the Sepsis-3 definition. In the statistical analysis, a random-effects model was used to pool effect sizes. RESULTS: We included 26 RCTs (n = 9048 patients) in the quantitative analysis. In comparison with SOC, length of AB therapy was significantly shorter in the PCT group (MD - 1.79 days, 95% CI: -2.65, - 0.92) and was associated with a significantly lower 28-day mortality (OR 0.84, 95% CI: 0.74, 0.95). In Sepsis-3 patients, mortality benefit was more pronounced (OR 0.46 95% CI: 0.27, 0.79). Odds of recurrent infection were significantly higher in the PCT group (OR 1.36, 95% CI: 1.10, 1.68), but there was no significant difference in the odds of secondary infection (OR 0.81, 95% CI: 0.54, 1.21), ICU and hospital length of stay (MD - 0.67 days 95% CI: - 1.76, 0.41 and MD - 1.23 days, 95% CI: - 3.13, 0.67, respectively). CONCLUSIONS: PCT-guided AB therapy may be associated with reduced AB use, lower 28-day mortality but higher infection recurrence, with similar ICU and hospital length of stay. Our results render the need for better designed studies investigating the role of PCT-guided AB stewardship in critically ill patients.

Thromboelastometry-Guided Individualized Fibrinolytic Treatment for COVID-19-Associated Severe Coagulopathy Complicated by Portal Vein Thrombosis: A Case Report.

COVID-19-associated coagulopathy (CAC), mainly characterized by hypercoagulability leading to micro- and macrovascular thrombotic events due to the fibrinolysis shutdown phenomenon, is a life-threatening complication of severe SARS-CoV-2 infection. However, optimal criteria to assess patients with the highest risk for progression of severe CAC are still unclear. Bedside point-of-care viscoelastic testing (VET) appears to be a promising tool to recognize CAC, to support the appropriate therapeutic decisions, and to monitor the efficacy of the treatment. The ClotPro VET has the potential to reveal fibrinolysis resistance indicated by a clot lysis time (LT) > 300 s on the TPA-test. We present a case of severe SARS-CoV-2 infection complicated by CAC-resulting portal vein thrombosis (PVT) and subsequent liver failure despite therapeutic anticoagulation. Since fibrinolysis shutdown (LT > 755 s) caused PVT, we performed a targeted systemic fibrinolytic therapy. We monitored the efficacy of the treatment with repeated TPA assays every three hours, while the dose of recombinant plasminogen activator (rtPA) was adjusted until fibrinolysis shutdown completely resolved and portal vein patency was confirmed by an ultrasound examination. Our case report highlights the importance of VET-guided personalized therapeutic approach during the care of severely ill COVID-19 patients, in order to appropriately treat CAC.

Is there a massive glacial-Holocene flora continuity in Central Europe?

The prevailing paradigm about the Quaternary ecological and evolutionary history of Central European ecosystems is that they were repeatedly impoverished by regional extinctions of most species during the glacial periods, followed by massive recolonizations from southern and eastern refugia during interglacial periods. Recent literature partially contradicts this view and provides evidence to re-evaluate this Postglacial Recolonization Hypothesis and develop an alternative one. We examined the long-term history of the flora of the Carpathian (Pannonian) Basin by synthesising recent advances in ecological, phylogeographical, palaeoecological and palaeoclimatological research, and analysing the cold tolerance of the native flora of a test area (Hungary, the central part of the Carpathian Basin). We found that (1) many species have likely occurred there continuously since before the Last Glacial Maximum (LGM); (2) most of the present-day native flora (1404 species, about 80%) can occur in climates as cold as or colder than the LGM (mean annual temperature ≤+3.5°C); and (3) grasslands and forests can be species-rich under an LGM-like cold climate. These arguments support an alternative hypothesis, which we call the Flora Continuity Hypothesis. It states that long-term continuity of much of the flora in the Carpathian Basin is more plausible than regional extinctions during the LGM followed by massive postglacial recolonizations. The long-term continuity of the region's flora may have fundamental implications not only for understanding local biogeography and ecology (e.g. the temporal scale of processes), but also for conservation strategies focusing on protecting ancient species-rich ecosystems and local gene pools.

Cerebral Perfusion Pressure-Guided Therapy in Patients with Subarachnoid Haemorrhage-A Retrospective Analysis.

BACKGROUND: Prevention and treatment of haemodynamic instability and increased intracranial pressure (ICP) in patients with subarachnoid haemorrhage (SAH) is vital. This study aimed to evaluate the effects of protocolised cerebral perfusion pressure (CPP)-guided treatment on morbidity and functional outcome in patients admitted to the intensive care unit (ICU) with SAH. METHODS: We performed a retrospective study comparing 37 patients who received standard haemodynamic treatment (control group) with 17 individuals (CPP-guided group) who were on the CPP-guided treatment aimed at maintaining CPP > 70 mmHg using both optimisations of ICP and mean arterial pressure (MAP). RESULTS: MAP, cumulative crystalloid doses and fluid balance were similar in both groups. However, the incidence of delayed cerebral ischaemia was significantly lower in the CPP-guided group (14% vs. 64%, p < 0.01), and functional outcome as assessed by the Glasgow Outcome Scale at 30 days after SAH was improved (29.0% vs. 5.5%, p = 0.03). CONCLUSIONS: This preliminary analysis showed that implementing a CPP-guided treatment approach aimed at maintaining a CPP > 70 mmHg may reduce the occurrence of delayed cerebral ischaemia and improve functional outcomes in patients with SAH. This observation merits further prospective investigation of the use of CPP-guided treatment in patients with SAH.

Extracorporeal hemoadsorption in critically ill COVID-19 patients on VV ECMO: the CytoSorb therapy in COVID-19 (CTC) registry.

OBJECTIVES: The CytoSorb therapy in COVID-19 (CTC) registry evaluated the clinical performance and treatment parameters of extracorporeal hemoadsorption integrated with veno-venous extracorporeal membrane oxygenation (VV ECMO) in critically ill COVID-19 patients with acute respiratory distress syndrome (ARDS) and respiratory failure under US FDA Emergency Use Authorization. DESIGN: Multicenter, observational, registry (NCT04391920). SETTING: Intensive care units (ICUs) in five major US academic centers between April 2020 and January 2022. PATIENTS: A total of 100 critically ill adults with COVID-19-related ARDS requiring VV ECMO support, who were treated with extracorporeal hemoadsorption. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Baseline demographics, clinical characteristics, laboratory values and outcomes were recorded following individual ethics committee approval at each center. Detailed data on organ support utilization parameters and hemoadsorption treatments were also collected. Biomarker data were collected according to the standard practice at each participating site, and available values were compared before and after hemoadsorption. The primary outcome of mortality was evaluated using a time-to-event analysis. A total of 100 patients (63% male; age 44 ± 11 years) were included. Survival rates were 86% at 30 days and 74% at 90 days. Median time from ICU admission to the initiation of hemoadsorption was 87 h and was used to define two post hoc groups: ≤ 87 h (group-early start, GE) and > 87 h (group-late start, GL). After the start of hemoadsorption, patients in the GE versus GL had significantly shorter median duration of mechanical ventilation (7 [2-26] vs. 17 [7-37] days, p = 0.02), ECMO support (13 [8-24] vs. 29 [14-38] days, p = 0.021) and ICU stay (17 [10-40] vs 36 [19-55] days, p = 0.002). Survival at 90 days in GE was 82% compared to 66% in GL (p = 0.14). No device-related adverse events were reported. CONCLUSIONS: In critically ill patients with severe COVID-19-related ARDS treated with the combination of VV-ECMO and hemoadsorption, 90-day survival was 74% and earlier intervention was associated with shorter need for organ support and ICU stay. These results lend support to the concept of "enhanced lung rest" with the combined use of VV-ECMO plus hemoadsorption in patients with ARDS.

Monitoring Treatment, Risks and Side Effects.

Inflammation plays a key role in the pathophysiology of organ dysfunction in the critically ill patients and is triggered by an overwhelming host response resulting in the overproduction of various cytokines. Regaining immune homeostasis over the dysregulated immune response through broad removal of cytokines using extracorporeal blood purification therapies has recently gained increasing attention. Nonetheless, many questions remain regarding the appropriate monitoring treatment, its potential risks, and side effects. The CytoSorb blood purification, the most extensively investigated device, has been shown to effectively remove an array of cytokines that may lead to rapid hemodynamic stabilization as indicated by reduced vasopressor need during the treatment, as well as an improvement in vital organ function. However, reported survival benefits have been fairly inconsistent. The therapy has also been confirmed as being safe and well tolerated. Despite several questions remaining such as the right timing, duration, frequency, concomitant antibiotic use, and most appropriate patient group with the highest change of benefit, the additional use as adjuvant therapy in hyperinflammatory states and/or in patients refractory to best standard care seems reasonable. Of note, there are several randomized controlled trials currently registered and ongoing that hopefully will provide answers to some of the above questions in the not-too-distant future.

Intraoperative Hypotension Prediction-A Proactive Perioperative Hemodynamic Management-A Literature Review.

Intraoperative hypotension (IH) is a frequent phenomenon affecting a substantial number of patients undergoing general anesthesia. The occurrence of IH is related to significant perioperative complications, including kidney failure, myocardial injury, and even increased mortality. Despite advanced hemodynamic monitoring and protocols utilizing goal directed therapy, our management is still reactive; we intervene when the episode of hypotension has already occurred. This literature review evaluated the Hypotension Prediction Index (HPI), which is designed to predict and reduce the incidence of IH. The HPI algorithm is based on a machine learning algorithm that analyzes the arterial pressure waveform as an input and the occurrence of hypotension with MAP <65 mmHg for at least 1 min as an output. There are several studies, both retrospective and prospective, showing a significant reduction in IH episodes with the use of the HPI algorithm. However, the level of evidence on the use of HPI remains very low, and further studies are needed to show the benefits of this algorithm on perioperative outcomes.

Management of severe peri-operative bleeding: Guidelines from the European Society of Anaesthesiology and Intensive Care: Second update 2022.

BACKGROUND: Management of peri-operative bleeding is complex and involves multiple assessment tools and strategies to ensure optimal patient care with the goal of reducing morbidity and mortality. These updated guidelines from the European Society of Anaesthesiology and Intensive Care (ESAIC) aim to provide an evidence-based set of recommendations for healthcare professionals to help ensure improved clinical management. DESIGN: A systematic literature search from 2015 to 2021 of several electronic databases was performed without language restrictions. Grading of Recommendations, Assessment, Development and Evaluation (GRADE) was used to assess the methodological quality of the included studies and to formulate recommendations. A Delphi methodology was used to prepare a clinical practice guideline. RESULTS: These searches identified 137 999 articles. All articles were assessed, and the existing 2017 guidelines were revised to incorporate new evidence. Sixteen recommendations derived from the systematic literature search, and four clinical guidances retained from previous ESAIC guidelines were formulated. Using the Delphi process on 253 sentences of guidance, strong consensus (>90% agreement) was achieved in 97% and consensus (75 to 90% agreement) in 3%. DISCUSSION: Peri-operative bleeding management encompasses the patient's journey from the pre-operative state through the postoperative period. Along this journey, many features of the patient's pre-operative coagulation status, underlying comorbidities, general health and the procedures that they are undergoing need to be taken into account. Due to the many important aspects in peri-operative nontrauma bleeding management, guidance as to how best approach and treat each individual patient are key. Understanding which therapeutic approaches are most valuable at each timepoint can only enhance patient care, ensuring the best outcomes by reducing blood loss and, therefore, overall morbidity and mortality. CONCLUSION: All healthcare professionals involved in the management of patients at risk for surgical bleeding should be aware of the current therapeutic options and approaches that are available to them. These guidelines aim to provide specific guidance for bleeding management in a variety of clinical situations.