Resilience in Rectal Cancer Treatment: Lessons from the COVID-19 Era in Czech Republic.

Introduction: The management of patients with COVID-19 infection has placed great pressure on the healthcare systems around the world. The aim of this study was to investigate the impact of the COVID-19 pandemic on the treatment outcomes of patients with rectal cancer by comparing them to those of patients with the same diagnosis in the pre-pandemic period. Methods: Retrospective data analysis of patients undergoing multimodal treatment for rectal cancer at the four university hospitals during the COVID-19 pandemic (2020-2021) and the 2-year pre-pandemic period (2018-2019). Results: A total of 693 patients (319 in the pre-pandemic period and 374 in the pandemic period) with rectal cancer were included in the study. The demographic and clinical characteristics of patients in both study periods were comparable, as was the spectrum of surgical procedures. Palliative surgery was more common in the pandemic period (18% vs 13%, p=0.084). The proportion of patients undergoing minimally invasive surgery was higher during the COVID-19 pandemic (p=0.025). There were no statistically significant differences between the study periods in the incidence/severity of post-operative complications, 30-day mortality and length of hospital stay. The number of positive resection margins was similar (5% vs 5%). Based on these results, COVID-19 had no effect on the postoperative morbidity and mortality in patients undergoing surgery for rectal cancer. Neoadjuvant treatment was more common in the pre-pandemic period (50% vs 45%). Long-course RT was predominantly offered in the pre-pandemic period, short-course RT during the pandemic. Significantly shorter "diagnosis-surgery" intervals were observed during the pandemic (23 days vs 33 days, p=0.0002). The "surgery-adjuvant therapy" interval was similar in both analysed study periods (p=0.219). Conclusion: Our study showed, that despite concerns about the COVID-19 pandemic, multimodal treatment of rectal cancer was associated with unchanged postoperative morbidity rates, increased frequency of short-course neoadjuvant RT administration and shorter "diagnosis-surgery" intervals.

Mitochondrially targeted tamoxifen as anticancer therapy: case series of patients with renal cell carcinoma treated in a phase I/Ib clinical trial.

Mitochondrially targeted anticancer drugs (mitocans) that disrupt the energy-producing systems of cancer are emerging as new potential therapeutics. Mitochondrially targeted tamoxifen (MitoTam), an inhibitor of mitochondrial respiration respiratory complex I, is a first-in-class mitocan that was tested in the phase I/Ib MitoTam-01 trial of patients with metastatic cancer. MitoTam exhibited a manageable safety profile and efficacy; among 37% (14/38) of responders, the efficacy was greatest in patients with metastatic renal cell carcinoma (RCC) with a clinical benefit rate of 83% (5/6) of patients. This can be explained by the preferential accumulation of MitoTam in the kidney tissue in preclinical studies. Here we report the mechanism of action and safety profile of MitoTam in a case series of RCC patients. All six patients were males with a median age of 69 years, who had previously received at least three lines of palliative systemic therapy and suffered progressive disease before starting MitoTam. We recorded stable disease in four, partial response in one, and progressive disease (PD) in one patient. The histological subtype matched clear cell RCC (ccRCC) in the five responders and claro-cellular carcinoma with sarcomatoid features in the non-responder. The number of circulating tumor cells (CTCs) was evaluated longitudinally to monitor disease dynamics. Beside the decreased number of CTCs after MitoTam administration, we observed a significant decrease of the mitochondrial network mass in enriched CTCs. Two patients had long-term clinical responses to MitoTam, of 50 and 36 weeks. Both patients discontinued treatment due to adverse events, not PD. Two patients who completed the trial in November 2019 and May 2020 are still alive without subsequent anticancer therapy. The toxicity of MitoTam increased with the dosage but was manageable. The efficacy of MitoTam in pretreated ccRCC patients is linked to the novel mechanism of action of this first-in-class mitochondrially targeted drug.

Expert consensus on difficult airway assessment.

Background: Identifying a potentially difficult airway is crucial both in anaesthesia in the operating room (OR) and non-operation room sites. There are no guidelines or expert consensus focused on the assessment of the difficult airway before, so this expert consensus is developed to provide guidance for airway assessment, making this process more standardized and accurate to reduce airway-related complications and improve safety. Methods: Seven members from the Airway Management Group of the Chinese Society of Anaesthesiology (CSA) met to discuss the first draft and then this was sent to 15 international experts for review, comment, and approval. The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) is used to determine the level of evidence and grade the strength of recommendations. The recommendations were revised through a three-round Delphi survey from experts. Results: This expert consensus provides a comprehensive approach to airway assessment based on the medical history, physical examination, comprehensive scores, imaging, and new developments including transnasal endoscopy, virtual laryngoscopy, and 3D printing. In addition, this consensus also reviews some new technologies currently under development such as prediction from facial images and voice information with the aim of proposing new research directions for the assessment of difficult airway. Conclusions: This consensus applies to anesthesiologists, critical care, and emergency physicians refining the preoperative airway assessment and preparing an appropriate intubation strategy for patients with a potentially difficult airway.

Chemotherapy versus chemoradiotherapy in borderline resectable and locally advanced pancreatic adenocarcinoma.

The role of radiotherapy in borderline resectable (BRPC) and locally advanced pancreatic carcinoma (LAPC) remains controversial. In our study, we retrospectively evaluated 48 patients with BRPC (14; 29.2%) and LAPC (34; 70. 8%) who underwent 6-8 cycles of induction mFOLFIRINOX chemotherapy alone (23; 47.9%) or 4-6 cycles of mFOLFIRINOX followed by hypofractionated radiotherapy (up to the total dose of 39.9 Gy in 15 fractions) (25; 52.1%). Survival parameters were evaluated using the Gehan-Breslow-Wilcoxon Test and compared by using the long-rank test. The addition of radiotherapy was not associated with better survival (16.9 months for chemotherapy only versus 15.9 months for the combined therapy; p=0.486), as well as for both subgroups (13.5 months vs. 18.3 months; p=0.679) and (20.7 months vs. 13.8 months; p=0.425) for BRPC and LAPC, respectively. A higher resection rate was seen in the BRPC group compared to the LAPC group (43% vs. 17.6%, respectively). Our study revealed a significantly higher rate of lung metastases in patients after the combination therapy compared to those treated by chemotherapy only (19% vs. 0%, respectively; p=0.045). Such a borderline result, however, prevents us from drawing clear conclusions about whether this is an artifact caused by the low number of patients or whether radiotherapy leads to a selection of stem cells with a predilection to the generalization to the lungs.

Mitochondrially targeted tamoxifen in patients with metastatic solid tumours: an open-label, phase I/Ib single-centre trial.

Background: Mitochondria present an emerging target for cancer treatment. We have investigated the effect of mitochondrially targeted tamoxifen (MitoTam), a first-in-class anti-cancer agent, in patients with solid metastatic tumours. Methods: MitoTam was tested in an open-label, single-centre (Department of Oncology, General Faculty Hospital, Charles University, Czech Republic), phase I/Ib trial in metastatic patients with various malignancies and terminated oncological therapies. In total, 75 patients were enrolled between May 23, 2018 and July 22, 2020. Phase I evaluated escalating doses of MitoTam in two therapeutic regimens using the 3 + 3 design to establish drug safety and maximum tolerated dose (MTD). In phase Ib, three dosing regimens were applied over 8 and 6 weeks to evaluate long-term toxicity of MitoTam as the primary objective and its anti-cancer effect as a secondary objective. This trial was registered with the European Medicines Agency under EudraCT 2017-004441-25. Findings: In total, 37 patients were enrolled into phase I and 38 into phase Ib. In phase I, the initial application of MitoTam via peripheral vein indicated high risk of thrombophlebitis, which was avoided by central vein administration. The highest dose with acceptable side effects was 5.0 mg/kg. The prevailing adverse effects (AEs) in phase I were neutropenia (30%), anaemia (30%) and fever/hyperthermia (30%), and in phase Ib fever/hyperthermia (58%) together with anaemia (26%) and neutropenia (16%). Serious AEs were mostly related to thromboembolic (TE) complications that affected 5% and 13% of patients in phase I and Ib, respectively. The only statistically significant AE related to MitoTam treatment was anaemia in phase Ib (p = 0.004). Of the tested regimens weekly dosing with 3.0 mg/kg for 6 weeks afforded the best safety profile with almost all being grade 1 (G1) AEs. Altogether, five fatalities occurred during the study, two of them meeting criteria for Suspected Unexpected Serious Adverse Events Reporting (SUSAR) (G4 thrombocytopenia and G5 stroke). MitoTam showed benefit evaluated as clinical benefit rate (CBR) in 37% patients with the largest effect in renal cell carcinoma (RCC) where four out of six patients reached disease stabilisation (SD), one reached partial response (PR) so that in total, five out of six (83%) patients showed CBR. Interpretation: In this study, the MTD was established as 5.0 mg/kg and the recommended dose of MitoTam as 3.0 mg/kg given once per week via central vein with recommended preventive anti-coagulation therapy. The prevailing toxicity included haematological AEs, hyperthermia/fever and TE complications. One fatal stroke and non-fatal G4 thrombocytopenia were recorded. MitoTam showed high efficacy against RCC. Funding: Smart Brain Ltd. Translation: For the Czech translation of the abstract see Supplementary Materials section.

Selected severe „haematological“ syndromes in adult intensive care patients.

Haemophagocytic syndrome, diffuse alveolar haemorrhage, catastrophic antiphospholipid syndrome and various types of thrombotic microangiopathies are rare conditions with significant morbidity and mortality. A common feature is late diagnosis, which can affect the success of treatment. The aim of this review article is to summarize the basic diagnostic and therapeutic steps of the present subpopulation of critically ill patients.

Epidemiology of chronic thromboembolic pulmonary hypertension (CTEPH) in the Czech Republic.

This study investigated the epidemiology and survival outcomes of chronic thromboembolic pulmonary hypertension (CTEPH) in the Czech Republic, wherein pulmonary endarterectomy (PEA) surgery was the only targeted treatment option until 2015. This study included all consecutive adults newly diagnosed with CTEPH in the Czech Republic between 2003 and 2016. Incidence/prevalence rates were calculated using general population data extracted from the Institute of Health Information and Statistics of the Czech Republic. Kaplan-Meier estimates of survival from diagnosis until 2018 were calculated. Of a total of 453 patients observed, 236 (52.1%) underwent PEA (median time from diagnosis to PEA: 2.9 months) and 71 (34.1%) had residual pulmonary hypertension (PH) post-PEA. CTEPH incidence rate (95% confidence interval [CI]) between 2006 and 2016 was 4.47 (4.05; 4.91) patients per million (ppm) per year, and the prevalence (95% CI) was 37.43 (33.46; 41.73) ppm in 2016. The rate of CTEPH-related hospitalizations (95% CI) per 100 person-years was 24.4 (22.1; 26.9) for operated patients and 34.2 (30.9; 37.7) for not-operated patients. Median overall survival (95% CI) for all patients from CTEPH diagnosis was 11.2 (9.4; not reached) years. Five-year survival probability (95% CI) was 95.3% (89.9; 97.9) for operated patients without residual PH, 86.3% (75.3; 92.7) for operated patients with residual PH and 61.2% (54.0; 67.6) for not-operated patients. This study reported epidemiological estimates of CTEPH in the Czech Republic consistent with estimates from other national systematic registries; and indicates an unmet medical need in not-operated patients and operated patients with residual PH.

No significant retinal damage induced by major orthopedic surgery - a pilot study.

BACKGROUND: Perioperative visual loss is one of the rare but devastating complications of anesthesia and surgery. The incidence of less severe or even subclinical postoperative visual dysfunction is unknown. Therefore, we decided to perform a pilot prospective observational clinical study to evaluate whether structural changes of the retina can be detected in patients undergoing elective orthopaedic surgery by optical coherence tomography (OCT). METHODS: Adult patients indicated for elective knee replacement surgery with the absence of known retinal or optic nerve disease were included. Each patient underwent baseline OCT examination of the eyes one day before surgery and it was repeated 4-7 days after the surgery. The surgery was done under general and epidural anesthesia. RESULTS: A total of 18 patients (6 men and 12 women) at the age of 70.8±7.1 years were enrolled. We found statistically significant changes in the Macular central thickness and in a few areas of the Retinal Nerve Fiber Layer between the baseline and postoperative measurements. CONCLUSIONS: Even though we found significant changes in some parameters, we did not confirm that general anesthesia and/or surgical damage causes significant damage of the retina using OCT measurement. TRIAL REGISTRATION: ClinicalTrials.gov (NCT04311801).

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.

Variations and obstacles in the use of coagulation factor concentrates for major trauma bleeding across Europe: outcomes from a European expert meeting.

PURPOSE: Trauma is a leading cause of mortality, with major bleeding and trauma-induced coagulopathy (TIC) contributing to negative patient outcomes. Treatments for TIC include tranexamic acid (TXA), fresh frozen plasma (FFP), and coagulation factor concentrates (CFCs, e.g. prothrombin complex concentrates [PCCs] and fibrinogen concentrate [FCH]). Guidelines for TIC management vary across Europe and a clear definition of TIC is still lacking. METHODS: An advisory board involving European trauma experts was held on 02 February 2019, to discuss clinical experience in the management of trauma-related bleeding and recommendations from European guidelines, focusing on CFC use (mainly FCH). This review summarises the discussions, including TIC definitions, gaps in the guidelines that affect their implementation, and barriers to use of CFCs, with suggested solutions. RESULTS: A definition of TIC, which incorporates clinical (e.g. severe bleeding) and laboratory parameters (e.g. low fibrinogen) is suggested. TIC should be treated immediately with TXA and FCH/red blood cells; subsequently, if fibrinogen ≤ 1.5 g/L (or equivalent by viscoelastic testing), treatment with FCH, then PCC (if bleeding continues) is suggested. Fibrinogen concentrate, and not FFP, should be administered as first-line therapy for TIC. Several initiatives may improve TIC management, with improved medical education of major importance; generation of new and stronger data, simplified clinical practice guidance, and improved access to viscoelastic testing are also critical factors. CONCLUSIONS: Management of TIC is challenging. A standard definition of TIC, together with initiatives to facilitate effective CFC administration, may contribute to improved patient care and outcomes.

Covidogram as a simple tool for predicting severe course of COVID-19: population-based study.

OBJECTIVES: COVID-19 might either be entirely asymptomatic or manifest itself with a large variability of disease severity. It is beneficial to identify early patients with a high risk of severe course. The aim of the analysis was to develop a prognostic model for the prediction of the severe course of acute respiratory infection. DESIGN: A population-based study. SETTING: Czech Republic. PARTICIPANTS: The first 7455 consecutive patients with COVID-19 who were identified by reverse transcription-PCR testing from 1 March 2020 to 17 May 2020. PRIMARY OUTCOME: Severe course of COVID-19. RESULT: Of a total 6.2% of patients developed a severe course of COVID-19. Age, male sex, chronic kidney disease, chronic obstructive pulmonary disease, recent history of cancer, chronic heart failure, acid-related disorders treated with proton-pump inhibitors and diabetes mellitus were found to be independent negative prognostic factors (Area under the ROC Curve (AUC) was 0.893). The results were visualised by risk heat maps, and we called this diagram a 'covidogram'. Acid-related disorders treated with proton-pump inhibitors might represent a negative prognostic factor. CONCLUSION: We developed a very simple prediction model called 'covidogram', which is based on elementary independent variables (age, male sex and the presence of several chronic diseases) and represents a tool that makes it possible to identify-with a high reliability-patients who are at risk of a severe course of COVID-19. Obtained results open clinically relevant question about the role of acid-related disorders treated by proton-pump inhibitors as predictor for severe course of COVID-19.

Levosimendan Efficacy and Safety: 20 years of SIMDAX in Clinical Use.

Levosimendan was first approved for clinic use in 2000, when authorisation was granted by Swedish regulatory authorities for the haemodynamic stabilisation of patients with acutely decompensated chronic heart failure. In the ensuing 20 years, this distinctive inodilator, which enhances cardiac contractility through calcium sensitisation and promotes vasodilatation through the opening of adenosine triphosphate-dependent potassium channels on vascular smooth muscle cells, has been approved in more than 60 jurisdictions, including most of the countries of the European Union and Latin America. Areas of clinical application have expanded considerably and now include cardiogenic shock, takotsubo cardiomyopathy, advanced heart failure, right ventricular failure and pulmonary hypertension, cardiac surgery, critical care and emergency medicine. Levosimendan is currently in active clinical evaluation in the US. Levosimendan in IV formulation is being used as a research tool in the exploration of a wide range of cardiac and non-cardiac disease states. A levosimendan oral form is at present under evaluation in the management of amyotrophic lateral sclerosis. To mark the 20 years since the advent of levosimendan in clinical use, 51 experts from 23 European countries (Austria, Belgium, Croatia, Cyprus, Czech Republic, Estonia, Finland, France, Germany, Greece, Hungary, Italy, the Netherlands, Norway, Poland, Portugal, Russia, Slovenia, Spain, Sweden, Switzerland, UK and Ukraine) contributed to this essay, which evaluates one of the relatively few drugs to have been successfully introduced into the acute heart failure arena in recent times and charts a possible development trajectory for the next 20 years.

Levosimendan Efficacy and Safety: 20 Years of SIMDAX in Clinical Use.

Levosimendan was first approved for clinical use in 2000, when authorization was granted by Swedish regulatory authorities for the hemodynamic stabilization of patients with acutely decompensated chronic heart failure (HF). In the ensuing 20 years, this distinctive inodilator, which enhances cardiac contractility through calcium sensitization and promotes vasodilatation through the opening of adenosine triphosphate-dependent potassium channels on vascular smooth muscle cells, has been approved in more than 60 jurisdictions, including most of the countries of the European Union and Latin America. Areas of clinical application have expanded considerably and now include cardiogenic shock, takotsubo cardiomyopathy, advanced HF, right ventricular failure, pulmonary hypertension, cardiac surgery, critical care, and emergency medicine. Levosimendan is currently in active clinical evaluation in the United States. Levosimendan in IV formulation is being used as a research tool in the exploration of a wide range of cardiac and noncardiac disease states. A levosimendan oral form is at present under evaluation in the management of amyotrophic lateral sclerosis. To mark the 20 years since the advent of levosimendan in clinical use, 51 experts from 23 European countries (Austria, Belgium, Croatia, Cyprus, Czech Republic, Estonia, Finland, France, Germany, Greece, Hungary, Italy, the Netherlands, Norway, Poland, Portugal, Russia, Slovenia, Spain, Sweden, Switzerland, the United Kingdom, and Ukraine) contributed to this essay, which evaluates one of the relatively few drugs to have been successfully introduced into the acute HF arena in recent times and charts a possible development trajectory for the next 20 years.

Endothelial glycocalyx in acute care surgery - what anaesthesiologists need to know for clinical practice.

The endothelial glycocalyx (EG) is the thin sugar-based lining on the apical surface of endothelial cells. It has been linked to the physiological functioning of the microcirculation and has been found to be damaged in critical illness and after acute care surgery. This review aims to describe the role of EG in severely injured patients undergoing surgery, discuss specific situations (e.G. major trauma, hemorrhagic shock, trauma induced coagulopathy) as well as specific interventions commonly applied in these patients (e.g. fluid therapy, transfusion) and specific drugs related to perioperative medicine with regard to their impact on EG.EG in acute care surgery is exposed to damage due to tissue trauma, inflammation, oxidative stress and inadequate fluid therapy. Even though some interventions (transfusion of plasma, human serum albumin, hydrocortisone, sevoflurane) are described as potentially EG protective there is still no specific treatment for EG protection and recovery in clinical medicine.The most important principle to be adopted in routine clinical practice at present is to acknowledge the fragile structure of the EG and avoid further damage which is potentially related to worsened clinical outcome.

Effect of short-term administration of lipid emulsion on endothelial glycocalyx integrity in ICU patients - A microvascular and biochemical pilot study.

BACKGROUND: Endothelial glycocalyx (EG) is a carbohydrate-rich vascular lining of the apical surface of endothelial cells. It has been proved to have an essential role in vascular homeostasis. Lipid emulsions as part of parenteral nutrition (PN) are widely used in patients in the setting of critical care and perioperative medicine. Due to their structure, lipids may potentially interact with EG. The aim of the study was to evaluate the effect of lipid emulsion on EG. OBJECTIVE: To assess the influence of lipid emulsion on EG integrity in ICU patients using a videomicroscopic and biochemical methods. METHODS: Patients in surgical ICU after major abdominal surgery or cardio surgery and in general ICU were assessed for eligibility for this pilot observational study in University Hospital. The study was performed during the first day of adding lipids as a part of their PN. The patients were given the SMOFlipid 20% for 6 hours in prescribed dose of approx. 1 g/kg of body weight. EG integrity was measured indirectly by automated sublingual videomicroscopy calculating a parameter PBR which describes the amount of lateral deviation of red blood cells from the central column and by levels of syndecan-1 and syndecan-4 in plasma as EG degradational products. Measurements were performed before lipid administration (T0) and 30 minutes after (T6) the infusion of lipid emulsion was completed. The statistical analysis was performed at the level of significance p < 0.05, data are expressed as mean ± standard deviation (SD) and for PBR as median and interquartile range (IQR). RESULTS: Fifteen patients were studied, from them 9 included in final analysis. PBR (expressed in µm) increased after the lipid infusion with no statistical significance (T0 = 2.10; 1.97-2.33 vs. 2.28; 2.11-2.45, p = 0.13). At T6 both syndecans showed statistically significant decrease in their particular levels. Syndecan-1 at T0 = 2580±1013 ng/l, resp. at T6 = 2365±1077 ng/l, p = 0.02; syndecan-4 at T0 = 134±29 ng/l, resp. at T6 = 123±43 ng/l, p = 0.04. CONCLUSION: In our study, we showed that six hours long SMOFlipid 20% infusion had no detrimental effect on the EG integrity as assessed by PBR value and by syndecan-1 and syndecan-4 plasmatic levels. Observed decrease of syndecans shortly after lipid infusion allows us to hypothesize even possibly protecting effect of lipids on EG.

How to recognize stent graft infection after endovascular aortic repair: the utility of 18F-FDG PET/CT in an infrequent but serious clinical setting.

OBJECTIVE: To evaluate the diagnostic performance of 18F-FDG PET/CT in the detection of stent graft infection (SGI). METHODS: In a retrospective study, two nuclear medicine physicians have independently analyzed 17 18F-FDG PET/CT examinations performed for clinical suspicion of SGI. The images were evaluated for the uptake pattern and intensity, and by the maximum standard uptake value (SUVmax), the target-to-background ratio with blood pool (TBRBP) and liver uptake (TBRhep) as a reference. The SGI was defined as the presence of focal hyperactivity with an intensity exceeding hepatic uptake. CT images were independently assessed for signs of SGI. Clinical review of all further patients' data served as the standard of reference. RESULTS: Nine cases were established as SGI by the clinical review. PET/CT correctly diagnosed SGI in eight and yielded a sensitivity of 89% and specificity of 100%. The mean SUVmax, TBRBP, and TBRhep values were 9.8 ± 4.0, 6.9 ± 2.6, and 4.6 ± 1.7 in the group of patients with true SGI, and 4.0 ± 1.1, 2.5 ± 0.4 (p < 0.001) and 1.9 ± 0.2 (p < 0.001) in true negative cases, respectively. CT alone showed a sensitivity of 78% and specificity of 100% and was concordant with PET/CT in 14 cases. The best performing threshold values of SUVmax, TBRBP, and TBRhep were 5.6, 3.5, and 2.2, respectively. CONCLUSION: 18F-FDG PET/CT with expert evaluation, semiquantitative and quantitative image analysis with the proposed threshold values for SUVmax, TBRBP, and TBRhep has good diagnostic accuracy in the detection of SGI. We propose that visual grading scale for SGI should use hepatic uptake as a visual reference.

Neuraxial anesthesia is less harmful to the endothelial glycocalyx during elective joint surgery compared to general anesthesia.

BACKGROUND: Damage of the endothelial glycocalyx (EG) has been described during surgery, but the effect of different anesthesia techniques remains unknown. Perfused boundary region (PBR) evaluated by side-stream dark field (SDF) imaging of the sublingual microcirculation enables in vivo EG assessment. PBR values are inversely related to the EG thickness. OBJECTIVE: The aim of the observational study was to evaluate the changes of PBR in patients undergoing elective joint surgery under general (GA) vs. neuraxial anesthesia (NA). Our hypothesis was that PBR will be lower in patients in NA. METHODS: Sixty consecutive patients (ASA 1-3) undergoing elective total knee or hip replacement under GA or NA were included in this prospective observational cohort study. PBR in the sublingual microcirculation was recorded in each patient using SDF at two time points - before surgery and 2 hours after surgery. RESULTS: Before surgery, there was no significant difference in baseline PBR between groups (NA: 1.95 µm (±0.24); GA: 2.02 µm (±0.26); p = 0.098). Postoperatively (2 hours after surgery) PBR was significantly increased in both groups with respect to baseline values (NA: 2.09 µm (±0.19), GA: 2.20 µm (±0.25); p < 0.001). In the GA group, postoperative PBR values were significantly higher than in the NA group (p = 0.006). CONCLUSION: Joint surgery led to significant increases of PBR. Patients in the GA group had significantly higher PBR values 2 hours after surgery compared to NA group. This might implicate that NA is associated with less EG damage then GA in elective hip/knee surgery.

Impact of Intravenous Fluid Challenge Infusion Time on Macrocirculation and Endothelial Glycocalyx in Surgical and Critically Ill Patients.

(i) Purpose. The fluid challenge (FC) is a well-established test of preload reserve. Only limited data exist in regard to the FC efficacy based on infusion time. Slow administration may be associated with lack of effect based on fluid redistribution and external conditions changes. On the contrary, fast administration may lead to brisk fluid overload and damage to the endothelium and endothelial glycocalyx (EG). The aim of this trial was to compare the FC infusion time on its hemodynamic effects and EG. (ii) Methods. Prospective randomized single-center trial of fast (5-10 minutes) versus slow (20-30 minutes) administration of 500ml balanced crystalloid FC in spinal surgery (cohort OR) and septic shock (cohort SEP) patients. Hemodynamic response was assessed using standard monitoring and blood flow measurements; damage to EG was assessed using the perfused boundary region (PBR) via intravital microscopy monitoring in the sublingual region within relevant time points ranging up to 120 minutes. (iii) Results. Overall, 66 FCs in 50 surgical and 16 septic patients were assessed. Fluid administration was associated with increase of PBR in general (1.9 (1.8-2.1) vs. 2.0 (1.8-2.2); p= 0.008). These changes were transient in OR cohort whereas they were long-lasting in septic fluid responders. The rate of fluid responsiveness after fast versus slow administration was comparable in global population (15 (47%) vs. 17 (50%); p=0.801) as well as in both cohorts. (iv) Conclusions. Fluid challenge administration was associated with increased PBR (and presumable EG volume changes) which normalized within the next 60 minutes in surgical patients but remained impeded in septic fluid responders. The fluid responsiveness rate after fast and slow FC was comparable, but fast administration tended to induce higher, though transient, response in blood pressure.