Ineffectiveness of hemoadsorption in large animals with abdominal sepsis: a randomized controlled porcine study.

OBJECTIVES: The use of hemoadsorption (HA) has become popular in the treatment of vasoplegic states associated with massive cytokine release, including septic shock. However, this approach does not seem to be based on robust evidence, and it does not follow international guidelines. To understand the pathophysiological rationale and timing of HA, we conducted a large animal septic shock experiment. DESIGN: Prospective randomized large-animal peritoneal septic shock experiment. SETTING: Laboratory investigation. SUBJECTS: Twenty-six anesthetized, mechanically ventilated, and instrumented pigs randomly assigned into (1) sham-operated group with HA (SHAM, n = 5); (2) sepsis animals without HA (SEPSIS, n = 5); (3) sepsis group with HA at norepinephrine initiation (EARLY, n = 8); and (4) sepsis group with HA initiated at norepinephrine rate reaching 0.5 µg/kg/min (LATE, n = 8). INTERVENTIONS: Peritoneal sepsis was induced by cultivated autologous feces inoculation. A CytoSorb cartridge (200 g) with a blood flow rate of 200 mL/min and heparin anticoagulation was used to perform HA. The animals received sedation and intensive organ support up to 48 h or until they experienced cardiovascular collapse. MEASUREMENTS AND MAIN RESULTS: Systemic hemodynamics, multiple-organ functions, and immune-inflammatory response were measured at predefined periods. The HA treatment was not associated with any measurable benefit in terms of systemic hemodynamics and organ support. The systemic inflammatory markers were unaffected by any of the treatment timings. In contrast, the HA resulted in higher vasopressor load and decreased 36-h survival (5 animals in SHAM (100%), 4 (80%) in SEPSIS, 4 (57%) in EARLY, and 2 (25%) in LATE; p = 0.041). The HA exposure in healthy animals was associated with hemodynamic deterioration, systemic inflammatory response, and cytopenia. CONCLUSIONS: In this large-animal-controlled fulminant sepsis study, the HA was unable to counteract the disease progression in the early or advanced septic shock phase. However, findings from the HA-exposed sham animals suggest potential safety concerns.

Pressure overload is associated with right ventricular dyssynchrony in heart failure with reduced ejection fraction.

AIMS: The determinants and relevance of right ventricular (RV) mechanical dyssynchrony in heart failure with reduced ejection fraction (HFrEF) are poorly understood. We hypothesized that increased afterload may adversely affect the synchrony of RV contraction. METHODS AND RESULTS: A total of 148 patients with HFrEF and 36 controls underwent echocardiography, right heart catheterization, and gated single-photon emission computed tomography to measure RV chamber volumes and mechanical dyssynchrony (phase standard deviation of systolic displacement timing). Exams were repeated after preload (N = 135) and afterload (N = 15) modulation. Patients with HFrEF showed higher RV dyssynchrony compared with controls (40.6 ± 17.5° vs. 27.8 ± 9.1°, P < 0.001). The magnitude of RV dyssynchrony in HFrEF correlated with larger RV and left ventricular (LV) volumes, lower RV ejection fraction (RVEF) and LV ejection fraction, reduced intrinsic contractility, increased heart rate, higher pulmonary artery (PA) load, and impaired RV-PA coupling (all P ≤ 0.01). Low RVEF was the strongest predictor of RV dyssynchrony. Left bundle branch block (BBB) was associated with greater RV dyssynchrony than right BBB, regardless of QRS duration. RV afterload reduction by sildenafil improved RV dyssynchrony (P = 0.004), whereas preload change with passive leg raise had modest effect. Patients in the highest tertiles of RV dyssynchrony had an increased risk of adverse clinical events compared with those in the lower tertile [T2/T3 vs. T1: hazard ratio 1.98 (95% confidence interval 1.20-3.24), P = 0.007]. CONCLUSIONS: RV dyssynchrony is associated with RV remodelling, dysfunction, adverse haemodynamics, and greater risk for adverse clinical events. RV dyssynchrony is mitigated by acute RV afterload reduction and could be a potential therapeutic target to improve RV performance in HFrEF.

Red Blood Cell Transfusion in the Intensive Care Unit.

Importance: Red blood cell (RBC) transfusion is common among patients admitted to the intensive care unit (ICU). Despite multiple randomized clinical trials of hemoglobin (Hb) thresholds for transfusion, little is known about how these thresholds are incorporated into current practice. Objective: To evaluate and describe ICU RBC transfusion practices worldwide. Design, Setting, and Participants: International, prospective, cohort study that involved 3643 adult patients from 233 ICUs in 30 countries on 6 continents from March 2019 to October 2022 with data collection in prespecified weeks. Exposure: ICU stay. Main Outcomes and Measures: The primary outcome was the occurrence of RBC transfusion during ICU stay. Additional outcomes included the indication(s) for RBC transfusion (consisting of clinical reasons and physiological triggers), the stated Hb threshold and actual measured Hb values before and after an RBC transfusion, and the number of units transfused. Results: Among 3908 potentially eligible patients, 3643 were included across 233 ICUs (median of 11 patients per ICU [IQR, 5-20]) in 30 countries on 6 continents. Among the participants, the mean (SD) age was 61 (16) years, 62% were male (2267/3643), and the median Sequential Organ Failure Assessment score was 3.2 (IQR, 1.5-6.0). A total of 894 patients (25%) received 1 or more RBC transfusions during their ICU stay, with a median total of 2 units per patient (IQR, 1-4). The proportion of patients who received a transfusion ranged from 0% to 100% across centers, from 0% to 80% across countries, and from 19% to 45% across continents. Among the patients who received a transfusion, a total of 1727 RBC transfusions were administered, wherein the most common clinical indications were low Hb value (n = 1412 [81.8%]; mean [SD] lowest Hb before transfusion, 7.4 [1.2] g/dL), active bleeding (n = 479; 27.7%), and hemodynamic instability (n = 406 [23.5%]). Among the events with a stated physiological trigger, the most frequently stated triggers were hypotension (n = 728 [42.2%]), tachycardia (n = 474 [27.4%]), and increased lactate levels (n = 308 [17.8%]). The median lowest Hb level on days with an RBC transfusion ranged from 5.2 g/dL to 13.1 g/dL across centers, from 5.3 g/dL to 9.1 g/dL across countries, and from 7.2 g/dL to 8.7 g/dL across continents. Approximately 84% of ICUs administered transfusions to patients at a median Hb level greater than 7 g/dL. Conclusions and Relevance: RBC transfusion was common in patients admitted to ICUs worldwide between 2019 and 2022, with high variability across centers in transfusion practices.

FGF-23 is a biomarker of RV dysfunction and congestion in patients with HFrEF.

There is no biomarker reflecting right ventricular dysfunction in HFrEF patients used in clinical practice. We have aimed to look for a circulating marker of RV dysfunction employing a quantitative proteomic strategy. The Olink Proteomics Multiplex panels (Cardiovascular Disease II, III, Cardiometabolic, and Inflammation Target Panels) identified FGF-23 to be the most differentially abundant (more than 2.5-fold) in blood plasma of HF patients with severe RV dysfunction (n = 30) compared to those with preserved RV function (n = 31). A subsequent ELISA-based confirmatory analysis of circulating FGF-23 in a large cohort of patients (n = 344, 72.7% NYHA III/IV, LVEF 22.5%, 54.1% with moderate/severe RV dysfunction), followed by multivariable regression analysis, revealed that the plasma FGF-23 level was most significantly associated with RV dysfunction grade (p = 0.0004) and congestion in the systemic circulation (p = 0.03), but not with LV-ejection fraction (p = 0.69) or estimated glomerular filtration rate (eGFR, p = 0.08). FGF-23 was associated with the degree of RV dysfunction in both sub-cohorts (i.e. in patients with and without congestion, p < 0.0001). The association between FGF-23 and RV-dysfunction remained significant after the adjustment for BNP (p = 0.01). In contrast, when adjusted for BNP, FGF-23 was no longer associated with LV dysfunction (p = 0.59). The Cox proportional hazard model revealed that circulating FGF-23 was significantly associated with adverse outcomes even after adjusting for BNP, LVEF, RV dysfunction grade and eGFR. Circulating FGF-23 is thus a biomarker of right ventricular dysfunction in HFrEF patients regardless of congestion status.

Right ventricular global dysfunction score: a new concept of right ventricular function assessment in patients with heart failure with reduced ejection fraction (HFrEF).

Background: Right ventricular (RV) function is currently being evaluated solely according to the properties of RV myocardium. We have tested a concept that in patients with heart failure with reduced ejection fraction (HFrEF), RV assessment should integrate the information about both RV function as well as size. Methods: A total of 836 stable patients with HFrEF (LVEF 23.6 ± 5.8%, 82.8% males, 68% NYHA III/IV) underwent echocardiographic evaluation and were prospectively followed for a median of 3.07 (IQRs 1.11; 4.89) years for the occurrence of death, urgent heart transplantation or implantation of mechanical circulatory support. Results: RV size (measured as RV-basal diameter, RVD1) was significantly associated with an adverse outcome independent of RV dysfunction grade (p = 0.0002). The prognostic power of RVD1 was further improved by indexing to body surface area (RVD1i, p < 0.05 compared to non-indexed value). A novel parameter named RV global dysfunction score (RVGDs) was calculated as a product of RVD1i and the degree of RV dysfunction (1-4 for preserved RV function, mild, moderate and severe dysfunction, respectively). RVGDs showed a superior prognostic role compared to RV dysfunction grade alone (ΔAUC >0.03, p < 0.0001). In every subgroup of RVGDs (<20, 20-40, 40-60, >60), patients with milder degree of RV dysfunction but more dilated RV had similar outcome as those with more severe degree of RV dysfunction but smaller RV size (all p > 0.50), independent of tricuspid regurgitation severity and degree of pulmonary hypertension. Conclusion: RV dilatation is a manifestation of RV dysfunction. The evaluation of RV performance should integrate the information about both RV size and function.

A protocol based on hypotension probability indicator vs. standard care to prevent intraoperative hypotension during supratentorial brain surgery: a prospective randomized pilot trial.

BACKGROUND: To test the hypothesis that Hypotension probability indicator (HPI) driven hemodynamic protocol use may decrease the exposition to hypotension (mean arterial pressure below 65 mmHg) during supratentorial intracranial procedures. METHODS: Patients undergoing supratentorial tumor resection under general anesthesia (ASA 1-3) were included into this randomized single center-controlled pilot trial. Patients in the control group (COV, N.=20) were managed based on the institutional standard to avoid hypotension. Patients in the intervention (INT, N.=20) group were managed using a protocol triggered by the HPI above 85 based on the stroke volume variation, dynamic elastance, and cardiac index parameters. The number of patients experiencing hypotension (mean arterial pressure below 65 mmHg) during the whole procedure and anesthesia maintenance phase was the primary outcome variable. The number of hypotensive periods, time spent in hypotension, and hypotension dose served as secondary outcome variables. Other clinically relevant parameters and postsurgical outcomes were screened. RESULTS: The number of patients who never experienced hypotension was significantly lower in the INT group during the anesthesia maintenance phase (10 (50%) vs. 16 (80%); P=0.049). In several other hemodynamic outcomes, a distinct numerical, but statistically non-significant trend towards lower hypotension exposition was observed. There were no significant differences in clinically relevant parameters. CONCLUSIONS: In this pilot trial, the HPI-based protocol decreased the incidence of hypotension during the anesthesia maintenance but non-significant trends among secondary outcomes were also documented. Larger trials are needed to confirm our findings.

Individualizing Fluid Management in Patients with Acute Respiratory Distress Syndrome and with Reduced Lung Tissue Due to Surgery-A Narrative Review.

Fluids are the cornerstone of therapy in all critically ill patients. During the last decades, we have made many steps to get fluid therapy personalized and based on individual needs. In patients with lung involvement-acute respiratory distress syndrome-finding the right amount of fluids after lung surgery may be extremely important because lung tissue is one of the most vulnerable to fluid accumulation. In the current narrative review, we focus on the actual perspectives of fluid therapy with the aim of showing the possibilities to tailor the treatment to a patient's individual needs using fluid responsiveness parameters and other therapeutic modalities.

Shock Index for Early Detection of Low Plasma Fibrinogen in Trauma: A Prospective Observational Cohort Pilot Study.

Shock index (a ratio between heart rate and systolic blood pressure) predicts transfusion requirements and the need for haemostatic resuscitation in severe trauma patients. In the present study, we aimed to determine whether prehospital and on-admission shock index values can be used to predict low plasma fibrinogen in trauma patients. Between January 2016 and February 2017, trauma patients admitted from the helicopter emergency medical service into two large trauma centres in the Czech Republic were prospectively assessed for demographic, laboratory and trauma-associated variables and shock index at scene, during transport and at admission to the emergency department. Hypofibrinogenemia defined as fibrinogen plasma level of 1.5 g·L-l was deemed as a cut-off for further analysis. Three hundred and twenty-two patients were screened for eligibility. Of these, 264 (83%) were included for further analysis. The hypofibrinogenemia was predicted by the worst prehospital shock index with the area under the receiver operating characteristics curve (AUROC) of 0.79 (95% CI 0.64-0.91) and by the admission shock index with AUROC of 0.79 (95% CI 0.66-0.91). For predicting hypofibrinogenemia, the prehospital shock index ≥ 1 has 0.5 sensitivity (95% CI 0.19-0.81), 0.88 specificity (95% CI 0.83-0.92) and a negative predictive value of 0.98 (0.96-0.99). The shock index may help to identify trauma patients at risk of hypofibrinogenemia early in the prehospital course.

Intraoperative Measurement of Endotracheal Tube Cuff Pressure and Its Change During Surgery in Correlation With Recurrent Laryngeal Nerve Palsies, Hoarseness, and Dysphagia After Anterior Cervical Discectomy and Fusion: A Prospective Randomized Controlled Trial.

STUDY DESIGN: Prospective randomized controlled trial. OBJECTIVES: Adjustment of endotracheal tube cuff pressure (ETCP) in anterior cervical discectomy and fusion (ACDF) may influence the incidence of complications such as recurrent laryngeal nerve palsy (RLNP), hoarseness, and dysphagia. METHODS: The prospective randomized controlled trial was designed to investigate the influence of ETCP on the incidence of postoperative complications. All eligible patients underwent vocal cord examination before and after ACDF and were randomized into a control group (CG) and intervention group (IG). Endotracheal tube cuff pressure was passively monitored in CG, and in IG, it was maintained at 20 mmHg. Outcomes were evaluated during hospitalization and during follow-up. RESULTS: A total of 98 patients were randomized, each group consisted of 49 patients. Statistical analysis showed that gender and age did not influence the incidence of complications. In CG, duration of retractor placement and extent of approach significantly impacted the occurrence of complications. The incidence of postoperative RLNP was 8.2% in IG and 12.2% in CG, hoarseness and dysphonia were present in 18.4% in IG and in 37.5% in CG, and dysphagia in 20.8% in IG and in 22.5% in CG. Hoarseness was significantly present more in CG (P = .018). Only one patient from CG presented with RLNP after 1 year, the remaining nine patients spontaneously recovered. CONCLUSIONS: Unregulated ETCP can lead to a significantly higher incidence of hoarseness; however, its improvement rate is 100%. The early postoperative complication rate was higher in CG, and after one year, 1 patient had RLNP and 1 patient had dysphagia.

Air gun injury to the pericardium in a 9-year-old boy.

The authors present the case of a 9-year-old boy who sustained a gunshot injury to the pericardium by an air gun. The penetrative wound to the pericardium was, according to the performed pre-operative diagnostic methods, initially believed to be a penetrative wound into the cardiophrenic angle of the left pleural cavity. The stabilized patient was indicated for an extraction of the projectile through a left anterior minithoracotomy, during which the projectile was found and successfully removed from the pericardium. The limits of pre-operative assessment, optimal treatment procedures, and surgical approaches in pediatric patients with gunshot injuries to the chest and heart are discussed.

Atypical hemolytic uremic syndrome triggered by mRNA vaccination against SARS-CoV-2: Case report.

Atypical hemolytic uremic syndrome (aHUS), also called complement-mediated hemolytic uremic syndrome (CM-HUS), is a rare disease caused by dysregulation in the alternative complement activation pathway. It is a life-threatening condition causing ischemia of a number of organs, and it typically causes acute kidney injury. This disorder may be triggered by various factors including viral or bacterial infections, pregnancy, surgery, and injuries. In about 60% of cases, the genetic origin of the disease can be identified-commonly mutations affecting complementary factor H and MCP protein. Eculizumab, a monoclonal antibody to the C5 component of the complement, represents the current effective treatment.We describe a case of a young woman with a previous history of polyvalent allergies, who developed atypical hemolytic uremic syndrome after vaccination with mRNA vaccine against SARS-CoV-2. The disease manifested by scleral bleeding, acute renal insufficiency, anemia, and thrombocytopenia. The patient was treated with plasma exchanges without sufficient effect; remission occurred only after starting treatment with eculizumab. Genetic examination showed that the patient is a carrier of multiple inherited risk factors (a rare pathogenic variant in CFH, MCPggaac haplotype of the CD46 gene, and the risk haplotype CFH H3). The patient is currently in hematological remission with persistent mild renal insufficiency, continuing treatment with eculizumab/ravulizumab. By this case report, we meant to point out the need for careful monitoring of people after vaccination, as it may trigger immune-mediated diseases, especially in those with predisposing factors.

SepsEast Registry indicates high mortality associated with COVID-19 caused acute respiratory failure in Central-Eastern European intensive care units.

The coronavirus disease (COVID-19) pandemic caused unprecedented research activity all around the world but publications from Central-Eastern European countries remain scarce. Therefore, our aim was to characterise the features of the pandemic in the intensive care units (ICUs) among members of the SepsEast (Central-Eastern European Sepsis Forum) initiative. We conducted a retrospective, international, multicentre study between March 2020 and February 2021. All adult patients admitted to the ICU with pneumonia caused by COVID-19 were enrolled. Data on baseline and treatment characteristics, organ support and mortality were collected. Eleven centres from six countries provided data from 2139 patients. Patient characteristics were: median 68, [IQR 60-75] years of age; males: 67%; body mass index: 30.1 [27.0-34.7]; and 88% comorbidities. Overall mortality was 55%, which increased from 2020 to 2021 (p = 0.004). The major causes of death were respiratory (37%), cardiovascular (26%) and sepsis with multiorgan failure (21%). 1061 patients received invasive mechanical ventilation (mortality: 66%) without extracorporeal membrane oxygenation (n = 54). The rest of the patients received non-invasive ventilation (n = 129), high flow nasal oxygen (n = 317), conventional oxygen therapy (n = 122), as the highest level of ventilatory support, with mortality of 50%, 39% and 22%, respectively. This is the largest COVID-19 dataset from Central-Eastern European ICUs to date. The high mortality observed especially in those receiving invasive mechanical ventilation renders the need of establishing national-international ICU registries and audits in the region that could provide high quality, transparent data, not only during the pandemic, but also on a regular basis.

Metformin treatment is associated with improved outcome in patients with diabetes and advanced heart failure (HFrEF).

The role of metformin (MET) in the treatment of patients with advanced HFrEF and type 2 diabetes mellitus (DM) is not firmly established. We studied the impact of MET on metabolic profile, quality of life (QoL) and survival in these patients. A total of 847 stable patients with advanced HFrEF (57.4 ± 11.3 years, 67.7% NYHA III/IV, LVEF 23.6 ± 5.8%) underwent clinical and laboratory evaluation and were prospectively followed for a median of 1126 (IQRs 410; 1781) days for occurrence of death, urgent heart transplantation or mechanical circulatory support implantation. A subgroup of 380 patients (44.9%) had DM, 87 of DM patients (22.9%) were treated with MET. Despite worse insulin sensitivity and more severe DM (higher BMI, HbA1c, worse insulin resistance), MET-treated patients exhibited more stable HF marked by lower BNP level (400 vs. 642 ng/l), better LV and RV function, lower mitral and tricuspid regurgitation severity, were using smaller doses of diuretics (all p < 0.05). Further, they had higher eGFR (69.23 vs. 63.34 ml/min/1.73 m2) and better QoL (MLHFQ: 36 vs. 48 points, p = 0.002). Compared to diabetics treated with other glucose-lowering agents, MET-treated patients had better event-free survival even after adjustment for BNP, BMI and eGFR (p = 0.035). Propensity score-matched analysis with 17 covariates yielded 81 pairs of patients and showed a significantly better survival for MET-treated subgroup (p = 0.01). MET treatment in patients with advanced HFrEF and DM is associated with improved outcome by mechanisms beyond the improvement of blood glucose control.

Global longitudinal strain and outcome after endoscopic mitral valve repair.

AIMS: Identification of heart failure (HF) patients with secondary mitral regurgitation (SMR) that benefit from mitral valve (MV) repair remains challenging. We have focused on the role of left ventricular global longitudinal strain (LV-GLS) and reservoir left atrial longitudinal strain (LASr) for the prediction of long-term survival and reverse remodelling in patients with SMR undergoing endoscopic MV repair. METHODS AND RESULTS: The study population consisted of 110 patients (age 67 ± 11 years, 66% men) with symptomatic SMR undergoing isolated MV repair using a minimally invasive surgical approach. Speckle tracking-derived LV-GLS and LASr were assessed in apical views using vendor-independent software. Over a median of 7.7 years (IQRs 2.9-11.2), 64 patients (58%) died. Significant reverse LV (↓ LVESVI >10 mL/m2 ), LA (↓ LAVI >10 mL/m2 ) remodelling or both were observed in 43 (39%), 37 (34%) and 19 (17%) patients, respectively. LV-GLS (HR 0.68, 95% CI 0.58-0.79, P < 0.001) and LASr (HR 0.93, 95% CI 0.88-0.97, P < 0.01) but not LV ejection fraction (LVEF) and LA volume index (LAVi) emerged as independent predictors of all-cause mortality in Cox regression analysis. LV-GLS was the only independent predictor of LV reverse remodelling (OR 1.24, 95% CI 1.05-1.43, P < 0.001) whereas LAVi and LASr were both independent predictors of LA reverse remodelling (both P < 0.05). In patients with atrial fibrillation at baseline, only LASr was an independent predictor (P < 0.05) of LA reverse remodelling. CONCLUSIONS: In patients with SMR undergoing endoscopic MV repair, LV-GLS and LASr are independently associated with long-term survival and reverse remodelling and may be helpful in selecting SMR patients who may benefit from this procedure.

Determination of stress and displacement on human composite pelvis under static and dynamic loading.

This case study describes the experimental determination of displacements and stresses on a composite model of a pelvis that was modified to represent a healthy intact pelvic ring. The modified model was stressed statically up to 1750 N to simulate standing on one leg and also cyclically to model walking. For two different model settings in the loading machine the values of displacements and stresses at the pelvic ring were determined. The two different settings correspond to two different loading vectors applied on the pelvic ring, boundary conditions and degrees of freedom. The experimentally determined values of displacements in both settings are very similar and in accordance with the knowledge on the behaviour of a real human pelvis. The modified model is thus suitable for testing of newly developed implants for pelvis treatment and experimental determination of displacements and stresses in pelvic ring which are caused by application of implants.

Fixed-dose enoxaparin provides efficient DVT prophylaxis in mixed ICU patients despite low anti-Xa levels: A prospective observational cohort study.

BACKGROUND: Deep vein thrombosis (DVT) is a serious but preventable complication of critical illness with a reported incidence from 4 to 17%. Anti-Xa activity in critically ill patients achieved with standard dosing of low-molecular-weight heparins (LMWH) is often below the target of 0.2-0.5 IU/mL. However, the clinical significance of this finding is unclear. The quality of thromboprophylaxis also strongly impacts the incidence of DVT. We performed a prospective observational study to evaluate the incidence of DVT in a mixed medical-surgical-trauma intensive care unit (ICU) using a thromboprophylaxis protocol with a fixed dose of enoxaparin. We also explored the relation between DVT incidence and anti-Xa activity. METHOD: All consecutive patients with expected ICU stay ≥72 hours and without evidence of DVT upon admission were included. They underwent ultrasound screening for DVT twice a week until ICU discharge, death, DVT or pulmonary embolism. Peak anti-Xa activity was measured twice a week. Patients received 40 mg of enoxaparin subcutaneously (60 mg in obese, 20 mg in case of renal failure). Graduated compression stockings were used in case of LMWH or another anticoagulant contraindication. RESULTS: A total of 219 patients were enrolled. We observed six cases of DVT (incidence of 2.7%). The agreement between expected and delivered DVT prophylaxis was 94%. Mean peak anti-Xa activity level was 0.24 (SD, 0.13) IU/mL. There was no significant difference in anti-Xa activity in DVT and non-DVT group. CONCLUSION: A low incidence of DVT was achieved with meticulous adherence to the standard prophylactic protocol. The low incidence of DVT was observed despite low levels of anti-Xa activity. Our findings suggest that enoxaparin dose adjustment based on regular monitoring of anti-Xa activity is unlikely to result in further reduction of DVT incidence in a mixed ICU population. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03286985.

Successful treatment of refractory status asthmaticus with omalizumab: a case report.

Refractory status asthmaticus is the cause of rare cases of in-hospital death due to acute bronchial asthma. The most severe cases unresponsive to first, second and next line treatment may be fatal despite aggressive organ support with invasive ventilation and extracorporeal membrane oxygenation. Omalizumab, a humanized recombinant monoclonal anti-IgE antibody, is an approved add-on biological treatment for severe asthma. However, it is not indicated in an acute setting. Here, we report the case of a young patient with status asthmaticus fully dependent on extracorporeal membrane oxygenation refractory to any therapy for six days, who was successfully treated with omalizumab.

Right versus left ventricular remodeling in heart failure due to chronic volume overload.

Mechanisms of right ventricular (RV) dysfunction in heart failure (HF) are poorly understood. RV response to volume overload (VO), a common contributing factor to HF, is rarely studied. The goal was to identify interventricular differences in response to chronic VO. Rats underwent aorto-caval fistula (ACF)/sham operation to induce VO. After 24 weeks, RV and left ventricular (LV) functions, gene expression and proteomics were studied. ACF led to biventricular dilatation, systolic dysfunction and hypertrophy affecting relatively more RV. Increased RV afterload contributed to larger RV stroke work increment compared to LV. Both ACF ventricles displayed upregulation of genes of myocardial stress and metabolism. Most proteins reacted to VO in a similar direction in both ventricles, yet the expression changes were more pronounced in RV (pslope: < 0.001). The most upregulated were extracellular matrix (POSTN, NRAP, TGM2, CKAP4), cell adhesion (NCAM, NRAP, XIRP2) and cytoskeletal proteins (FHL1, CSRP3) and enzymes of carbohydrate (PKM) or norepinephrine (MAOA) metabolism. Downregulated were MYH6 and FAO enzymes. Therefore, when exposed to identical VO, both ventricles display similar upregulation of stress and metabolic markers. Relatively larger response of ACF RV compared to the LV may be caused by concomitant pulmonary hypertension. No evidence supports RV chamber-specific regulation of protein expression in response to VO.

Mesenchymal Stromal Cell Therapy in Novel Porcine Model of Diffuse Liver Damage Induced by Repeated Biliary Obstruction.

In liver surgery, biliary obstruction can lead to secondary biliary cirrhosis, a life-threatening disease with liver transplantation as the only curative treatment option. Mesenchymal stromal cells (MSC) have been shown to improve liver function in both acute and chronic liver disease models. This study evaluated the effect of allogenic MSC transplantation in a large animal model of repeated biliary obstruction followed by partial hepatectomy. MSC transplantation supported the growth of regenerated liver tissue after 14 days (MSC group, n = 10: from 1087 ± 108 (0 h) to 1243 ± 92 mL (14 days); control group, n = 11: from 1080 ± 95 (0 h) to 1100 ± 105 mL (14 days), p = 0.016), with a lower volume fraction of hepatocytes in regenerated liver tissue compared to resected liver tissue (59.5 ± 10.2% vs. 70.2 ± 5.6%, p < 0.05). Volume fraction of connective tissue, blood vessels and bile vessels in regenerated liver tissue, serum levels of liver enzymes (AST, ALT, ALP and GGT) and liver metabolites (albumin, bilirubin, urea and creatinine), as well as plasma levels of IL-6, IL-8, TNF-α and TGF-ß, were not affected by MSC transplantation. In our novel, large animal (pig) model of repeated biliary obstruction followed by partial hepatectomy, MSC transplantation promoted growth of liver tissue without any effect on liver function. This study underscores the importance of translating results between small and large animal models as well as the careful translation of results from animal model into human medicine.