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.

Update on Anticoagulation Strategies in Patients with ECMO-A Narrative Review.

The use of extracorporeal membrane oxygenation (ECMO) has recently increased exponentially. ECMO has become the preferred mode of organ support in refractory respiratory or circulatory failure. The fragile balance of haemostasis physiology is massively altered by the patient's critical condition and specifically the aetiology of the underlying disease. Furthermore, an application of ECMO conveys another disturbance of haemostasis due to blood-circuit interaction and the presence of an oxygenator. The purpose of this review is to summarise current knowledge on the anticoagulation management in patients undergoing ECMO therapy. The unfractionated heparin modality with monitoring of activated partial thromboplastin tests is considered to be a gold standard for anticoagulation in this specific subgroup of intensive care patients. However, alternative modalities with other agents are comprehensively discussed. Furthermore, other ways of monitoring can represent the actual state of coagulation in a more complex fashion, such as thromboelastometric/graphic methods, and might become more frequent. In conclusion, the coagulation system of patients with ECMO is altered by multiple variables, and there is a significant lack of evidence in this area. Therefore, a highly individualised approach is the best solution today.

Morphine Analgesia, Cannabinoid Receptor 2, and Opioid Growth Factor Receptor Cancer Tissue Expression Improve Survival after Pancreatic Cancer Surgery.

Pancreatic cancer (PDAC) has a poor prognosis despite surgical removal and adjuvant therapy. Additionally, the effects of postoperative analgesia with morphine and piritramide on survival among PDAC patients are unknown, as are their interactions with opioid/cannabinoid receptor gene expressions in PDAC tissue. Cancer-specific survival data for 71 PDAC patients who underwent radical surgery followed by postoperative analgesia with morphine (n = 48) or piritramide (n = 23) were therefore analyzed in conjunction with opioid/cannabinoid receptor gene expressions in the patients' tumors. Receptor gene expressions were determined using the quantitative real-time polymerase chain reaction. Patients receiving morphine had significantly longer cancer-specific survival (CSS) than those receiving piritramide postoperative analgesia (median 22.4 vs. 15 months; p = 0.038). This finding was supported by multivariate modelling (p < 0.001). The morphine and piritramide groups had similar morphine equipotent doses, receptor expression, and baseline characteristics. The opioid/cannabinoid receptor gene expression was analyzed in a group of 130 pancreatic cancer patients. Of the studied receptors, high cannabinoid receptor 2 (CB2) and opioid growth factor receptor (OGFR) gene expressions have a positive influence on the length of overall survival (OS; p = 0.029, resp. p = 0.01). Conversely, high delta opioid receptor gene expression shortened OS (p = 0.043). Multivariate modelling indicated that high CB2 and OGFR expression improved OS (HR = 0.538, p = 0.011, resp. HR = 0.435, p = 0.001), while high OPRD receptor expression shortened OS (HR = 2.264, p = 0.002). Morphine analgesia, CB2, and OGFR cancer tissue gene expression thus improved CSS resp. OS after radical PDAC surgery, whereas delta opioid receptor expression shortened OS.

Internal jugular vein collapsibility does not predict fluid responsiveness in spontaneously breathing patients after cardiac surgery.

PURPOSE: The objective of our study was to evaluate the diagnostic accuracy of internal jugular vein (IJV) collapsibility as a predictor of fluid responsiveness in spontaneously breathing patients after cardiac surgery. METHODS: In this prospective observational study, spontaneously breathing patients were enrolled on the first postoperative day after coronary artery bypass grafting. Hemodynamic data coupled with simultaneous ultrasound assessment of the IJV were collected at baseline and after passive leg raising test (PLR). Continuous cardiac index (CI), stroke volume (SV), and stroke volume variation (SVV) were assessed with FloTracTM/EV1000™. Fluid responsiveness was defined as an increase in CI ≥ 10% after PLR. We compared the differences in measured variables between fluid responders and non-responders and tested the ability of ultrasonographic IJV indices to predict fluid responsiveness. RESULTS: Fifty-four patients were included in the study. Seventeen (31.5%) were fluid responders. The responders demonstrated significantly lower inspiratory and expiratory diameters of the IJV at baseline, but IJV collapsibility was comparable (P = 0.7). Using the cut-off point of 20%, IJV collapsibility predicted fluid responsiveness with a sensitivity of 76.5% and specificity of 38.9%, ROC AUC 0.55. CONCLUSION: In spontaneously breathing patients after surgical coronary revascularisation, collapsibility of the internal jugular vein did not predict fluid responsiveness.

A Prospective Comparative Study of Laryngeal Glottic View Using the Vie Scope® versus Standard Macintosh Laryngoscope in Morbidly Obese Patients.

Background: The visualization of the glottis may be inadequate in morbidly obese patients when a standard Macintosh blade laryngoscope (MCL) is used. The Vie Scope® (VS) is a novel type laryngoscope consisting of a straight, enclosed, illuminated tube that offers intubation via a bougie using the paraglossal technique. In this prospective, nonrandomized comparative study, we tested the research hypothesis that the VS may improve visualization of the glottic larynx in comparison to the MCL. Materials and Methods: After obtaining institutional ethics committee approval, 60 morbidly obese patients (BMI >40 kg/m2) undergoing elective non-head and neck surgery were included in the study. After induction of general anesthesia (GA), the glottic visualization was performed using the two laryngoscopes in succession, first MCL size 3 or 4 followed by the VS and was assessed using the modified Cormack-Lehane scale. Tracheal intubation was performed using the VS The first pass intubation success and the total success rate was recorded only for the VS Intubation time was not measured because of the paired study design. Results and Discussion: Mean demographic data included: age 41.9±8.2 years, height 171.2±10.2 cm, weight 129.9±21.6 kg, BMI 44.95±3.85 kg/m2. Using MCL, Cormack-Lehane grade 1 was observed in 36 (60%) cases; grade 2 in 7/60 (11.6%); grade 3 in 13/60 (21.7%); and grade 4 in 4/60 (6.7%). Poor laryngeal views represented by grades 3 and 4 were observed in 28.4% of patients with the MCL. Grades obtained with the VS were all grade 1 (100%). The first attempt intubation success was in 58/60 (96.7%) with the VS. No complications were observed. Conclusion: The Vie Scope® laryngoscope, using the paraglossal technique of tracheal intubation, significantly improves visualization of the vocal cords in morbidly obese patients compared to the standard Macintosh laryngoscope.

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.

Using the national electronic prescription system to determine the primary non-adherence to medication in the Czech Republic.

The primary medication non-adherence occurs when a patient does not collect his or her newly prescribed medication. Various studies give estimates that this occurs between 0.2 percent and 74 percent. Recently, this topic has been researched by analyzing data in national electronic prescription systems. The database of the Czech electronic prescription system was used to obtain the number of all prescriptions issued and collected in 2021 for fifty particular substances (associated with six medication groups). Additionally, a similar query was performed with an additional criterion that the same substance had not been prescribed within the last 365 days. The data were obtained separately in five age categories. The total number of prescriptions analyzed in this study was over 21 million, which represents almost 30 percent of all prescriptions issued in the Czech Republic in 2021. The primary medication non-adherence in the selected substances was 4.56 percent, which negatively correlates (rxy = 0.707) with the age of a patient. There is a higher primary non-adherence in the Psychoanaleptics and Lipid modifying medication groups than in the whole studied sample (p < 0.05). Lipid-modifying medication group and several other particular substances showed a larger difference between primary non-adherence and overall non-adherence, indicating issues in the initiation of these drugs. The results of our study are following earlier studies with similar methodologies from other countries. However, the difference between primary non-adherence and overall non-adherence had not been observed in other studies before. The electronic prescription system proved to be a valuable tool for conducting this type of research.

Prediction of Fluid Responsiveness Using Combined End-Expiratory and End-Inspiratory Occlusion Tests in Cardiac Surgical Patients.

End-expiratory occlusion (EEO) and end-inspiratory occlusion (EIO) tests have been successfully used to predict fluid responsiveness in various settings using calibrated pulse contour analysis and echocardiography. The aim of this study was to test if respiratory occlusion tests predicted fluid responsiveness reliably in cardiac surgical patients with protective ventilation. This single-centre, prospective study, included 57 ventilated patients after elective coronary artery bypass grafting who were indicated for fluid expansion. Baseline echocardiographic measurements were obtained and patients with significant cardiac pathology were excluded. Cardiac index (CI), stroke volume and stroke volume variation were recorded using uncalibrated pulse contour analysis at baseline, after performing EEO and EIO tests and after volume expansion (7 mL/kg of succinylated gelatin). Fluid responsiveness was defined as an increase in cardiac index by 15%. Neither EEO, EIO nor their combination predicted fluid responsiveness reliably in our study. After a combined EEO and EIO, a cut-off point for CI change of 16.7% predicted fluid responsiveness with a sensitivity of 61.8%, specificity of 69.6% and ROC AUC of 0.593. In elective cardiac surgical patients with protective ventilation, respiratory occlusion tests failed to predict fluid responsiveness using uncalibrated pulse contour analysis.

Influence of opioid analgesia type on circulating tumor cells in open colorectal cancer surgery (POACC-1): study protocol for a prospective randomized multicenter controlled trial.

BACKGROUND: Opioids and epidural analgesia are a mainstay of perioperative analgesia but their influence on cancer recurrence remains unclear. Based on retrospective data, we found that cancer recurrence following colorectal cancer surgery correlates with the number of circulating tumor cells (CTCs) in the early postoperative period. Also, morphine- but not piritramide-based postoperative analgesia increases the presence of CTCs and shortens cancer-specific survival. The influence of epidural analgesia on CTCs has not been studied yet. METHODS: We intend to enroll 120 patients in four centers in this prospective randomized controlled trial. The study protocol has been approved by Ethics Committees in all participating centers. Patients undergoing radical open colorectal cancer surgery are randomized into epidural, morphine, and piritramide groups for perioperative analgesia. The primary outcome is the difference in the number of CTCs in the peripheral blood before surgery, on the second postoperative day, and 2-4 weeks after surgery. The number of CTCs is measured using molecular biology methods. Perioperative care is standardized, and relevant data is recorded. A secondary outcome, if feasible, would be the expression and activity of various receptor subtypes in cancer tissue. We intend to perform a 5-year follow-up with regard to metastasis development. DISCUSSION: The mode of perioperative analgesia favorably affecting cancer recurrence would decrease morbidity/mortality. To identify such techniques, trials with long-term follow-up periods seem suboptimal. Given complex oncological therapeutic strategies, such trials likely disable the separation of perioperative analgesia effects from other factors. We believe that early postoperative CTCs presence/dynamics may serve as a sensitive marker of various perioperative interventions´ influences on cancer recurrence. Importantly, it is unbiased to the influence of long-term factors and minimally invasive. Analysis of opioid/cannabinoid receptor subtypes in cancer tissue would improve understanding of underlying mechanisms and promote personalization of treatment. We are not aware of any similar ongoing studies. TRIAL REGISTRATION NUMBER: NCT03700411, registration date: October 3, 2018. STUDY STATUS: recruiting.

Population Pharmacokinetic Analysis Proves Superiority of Continuous Infusion in PK/PD Target Attainment with Oxacillin in Staphylococcal Infections.

Considering its very short elimination half-life, the approved oxacillin dosage might not be sufficient to maintain the pharmacokinetic/pharmacodynamics (PK/PD) target of time-dependent antibiotics. This study aimed to describe the population pharmacokinetics of oxacillin and to explore the probability of PK/PD target attainment by using various dosing regimens with oxacillin in staphylococcal infections. Both total and unbound oxacillin plasma concentrations retrieved as a part of routine therapeutic drug-monitoring practice were analyzed using nonlinear mixed-effects modeling. Monte Carlo simulations were used to generate the theoretical distribution of unbound oxacillin plasma concentration-time profiles at various dosage regimens. Data from 24 patients treated with oxacillin for staphylococcal infection have been included into the analysis. The volume of distribution of oxacillin in the population was 11.2 L, while the elimination rate constant baseline of 0.73 h-1 increased by 0.3 h-1 with each 1 mL/s/1.73 m2 of the estimated glomerular filtration rate (eGFR). The median value of oxacillin binding to plasma proteins was 86%. The superiority of continuous infusion in achieving target PK/PD values was demonstrated and dosing according to eGFR was proposed. Daily oxacillin doses of 9.5 g, 11 g, or 12.5 g administered by continuous infusion have been shown to be optimal for achieving target PK/PD values in patients with moderate, mild, or normal renal function, respectively.

Fibrinogenolysis in Venom-Induced Consumption Coagulopathy after Viperidae Snakebites: A Pilot Study.

Envenomations that are caused by Viperidae snakebites are mostly accompanied by venom-induced consumption coagulopathy (VICC) with defibrination. The clinical course of VICC is well described; however, reports about its detailed effects in the hemocoagulation systems of patients are sparse. In this pilot study, we prospectively analyzed the changes in plasma fibrinogen that were caused by the envenomation of six patients by five non-European Viperidae snakes. Western blot analysis was employed and fibrinogen fragments were visualized with the use of specific anti-human fibrinogen antibodies. All of the studied subjects experienced hypo- or afibrinogenemia. The western blot analysis demonstrated fibrinogenolysis of the fibrinogen chains in all of the cases. Fibrinogenolysis was considered to be a predominant cause of defibrination in Crotalus, Echis, and Macrovipera envenomation; while, in the cases of VICC that were caused by Atheris and Calloselasma envenomation, the splitting of the fibrinogen chains was present less significantly.

CZecking heart failure in patients with advanced chronic kidney disease (Czech HF-CKD): Study protocol.

BACKGROUND: Heart failure (HF) is a frequent cause of morbidity and mortality of end-stage kidney disease (ESKD) patients on hemodialysis. It is not easy to distinguish HF from water overload. The traditional HF definition has low sensitivity and specificity in this population. Moreover, many patients on hemodialysis have exercise limitations unrelated to HF. Therefore, we postulated two new HF definitions ((1) Modified definition of the Acute Dialysis Quality Improvement working group; (2) Hemodynamic definition based on the calculation of the effective cardiac output). We hypothesize that the newer definitions will better identify patients with higher number of endpoints and with more advanced structural heart disease. METHODS: Cohort, observational, longitudinal study with recording predefined endpoints. Patients (n = 300) treated by hemodialysis in six collaborating centers will be examined centrally in a tertiary cardiovascular center every 6-12 months lifelong or till kidney transplantation by detailed expert echocardiography with the calculation of cardiac output, arteriovenous dialysis fistula flow volume calculation, bio-impedance, and basic laboratory analysis including NTproBNP. Effective cardiac output will be measured as the difference between measured total cardiac output and arteriovenous fistula flow volume and systemic vascular resistance will be also assessed non-invasively. In case of water overload during examination, dry weight adjustment will be recommended, and the patient invited for another examination within 6 weeks. A composite major endpoint will consist of (1) Cardiovascular death; (2) HF worsening/new diagnosis of; (3) Non-fatal myocardial infarction or stroke. The two newer HF definitions will be compared with the traditional one in terms of time to major endpoint analysis. DISCUSSION: This trial will differ from others by: (1) detailed repeated hemodynamic assessment including arteriovenous access flow and (2) by careful assessment of adequate hydration to avoid confusion between HF and water overload.

The diagnostic performance of CT pulmonary angiography in the detection of chronic thromboembolic pulmonary hypertension-systematic review and meta-analysis.

OBJECTIVES: To examine the diagnostic performance of CT of the pulmonary artery (CTPA) as a potential first-choice imaging modality in patients with pulmonary arterial hypertension and suspected chronic thromboembolic pulmonary hypertension (CTEPH). METHODS: A systematic review and meta-analysis were conducted in accordance with the PRISMA reporting checklist. Six scientific databases and registers (PubMed, EMBASE, Scopus, Web of Science, Cochrane, ClinicalTrials.gov ) were searched for studies evaluating the diagnostic performance of CTPA in suspected CTEPH in adult patients. Results were pooled separately for studies based on the evaluation of the pulmonary artery and those that relied solely on changes in parenchymal perfusion. RESULTS: Ten single-center studies with 734 patients were eligible for pooling of the diagnostic performance of CTPA by evaluation of the pulmonary artery. The pooled sensitivity, specificity, PPV, NPV, accuracy, and diagnostic odds ratio (DOR) estimates for CTPA in the detection of CTEPH were 0.98, 0.99, 0.94, 1.00, 0.96, 0.96, and 292. Evaluation of perfusion changes yielded pooled estimates for sensitivity, specificity, PPV, NPV, accuracy, and DOR of 0.99, 0.84, 0.79, 0.98, 0.89, 0.89, and 98 across four studies with 278 patients. Scintigraphy, SPECT, digital subtraction angiography, right heart catheterization, pulmonary endarterectomy, and international guidelines were used to establish the diagnosis. CONCLUSION: CTPA has high sensitivity and specificity in the detection of CTEPH when the examination is evaluated by expert radiologists. Evaluation of parenchymal perfusion alone is associated with slightly lower specificity. Further research is needed to determine the diagnostic performance of CTPA in excluding CTEPH in general radiology departments. KEY POINTS: • CT pulmonary angiography (CTPA) is recommended in the diagnostic workup of chronic thromboembolic pulmonary hypertension (CTEPH). • CTPA has high sensitivity and specificity in the detection of CTEPH when evaluated by an expert radiologist. • Evaluation of changes in parenchymal perfusion alone is associated with slightly lower specificity. • Little is known about the diagnostic performance of CTPA in the detection of CTEPH in general radiology departments.

The diagnostic performance of whole-body MRI in the staging of lymphomas in adult patients compared to PET/CT and enhanced reference standard-systematic review and meta-analysis.

BACKGROUND: Morphology highlighted by diffusion weighted imaging (DWI) is the basis of whole-body MRI (wbMRI). The aim of this study was to analyze current knowledge on the diagnostic performance of wbMRI in the pretreatment staging of patients with lymphoma. METHODS: A search for original articles reporting the diagnostic performance (sensitivity, specificity) of pretreatment (first staging or staging in relapsed patients after complete remission) wbMRI in nodal and extranodal involvement by extracranial lymphoma and the agreement of stage by the Cotswolds-modified Ann Arbor classification in adult patients compared to the reference standard (PET/CT or enhanced reference standard) was conducted in PubMed, EMBASE, Cochrane Library, ClinicalTrials.gov. RESULTS: Altogether 15 studies with 519 patients were included in the meta-analysis. The pooled sensitivity and specificity for nodal involvement were 0.93 (95% CI: 0.90 to 0.96) and 0.99 (95% CI: 0.98 to 1.00). For nodal staging, most studies used the size criterion of 10 mm in the short diameter (n=10) and the absence of prominent fatty hilum (n=4). Restricted diffusion on diffusion-weighted imaging as a sign of nodal involvement was either not used (n=5), used for detection (n=4), semi-quantitatively (n=4), or quantitatively (n=1). Only one study (7) relied solely on restricted diffusion as the main criterion for nodal involvement. The pooled sensitivity and specificity for extranodal involvement were 0.89 (95% CI: 0.79 to 0.98) and 0.99 (95% CI: 0.99 to 1.00). Seven studies considered diffuse splenic involvement when its long or vertical axis was greater than 13 cm regardless of the patient's physiognomy. The pooled agreement in staging (Cohen's kappa) was almost perfect (0.90, 95% CI: 0.84 to 0.95). DISCUSSION: The sensitivity and specificity of wbMRI in the assessment of the nodal and extranodal involvement by lymphoma is high. The agreement of wbMRI with the reference standard is almost perfect.

Novel Methods for Predicting Fluid Responsiveness in Critically Ill Patients-A Narrative Review.

In patients with acute circulatory failure, fluid administration represents a first-line therapeutic intervention for improving cardiac output. However, only approximately 50% of patients respond to fluid infusion with a significant increase in cardiac output, defined as fluid responsiveness. Additionally, excessive volume expansion and associated hyperhydration have been shown to increase morbidity and mortality in critically ill patients. Thus, except for cases of obvious hypovolaemia, fluid responsiveness should be routinely tested prior to fluid administration. Static markers of cardiac preload, such as central venous pressure or pulmonary artery wedge pressure, have been shown to be poor predictors of fluid responsiveness despite their widespread use to guide fluid therapy. Dynamic tests including parameters of aortic blood flow or respiratory variability of inferior vena cava diameter provide much higher diagnostic accuracy. Nevertheless, they are also burdened with several significant limitations, reducing the reliability, or even precluding their use in many clinical scenarios. This non-systematic narrative review aims to provide an update on the novel, less employed dynamic tests of fluid responsiveness evaluation in critically ill patients.

Evaluation of the insertion parameters and complications of the i-gel Plus airway device for maintaining patent airway during planned procedures under general anaesthesia: a protocol for a prospective multicentre cohort study.

INTRODUCTION: Supraglottic airway devices represent a less invasive method of airway management than tracheal intubation during general anaesthesia. Their continued development is focused mainly on improvements in the insertion success rate and minimalisation of perioperative and postoperative complications. The i-gel Plus is a novel, anatomically preshaped supraglottic airway device which achieves a perilaryngeal seal due to a non-inflatable cuff made of a soft thermoplastic elastomer. The purpose of this cohort study is to assess the success rate of the i-gel Plus use during elective procedures under general anaesthesia, its intraoperative performance, and the degree of postoperative complications. METHODS AND ANALYSIS: This is a multicentre, prospective, interventional cohort study. The enrolment will take place in seven centres in four European countries. We plan to enrol 2000 adult patients in total, who are scheduled for elective surgery under general anaesthesia, and with an indication for use of a supraglottic airway device for management of their airway. The study is projected to run over a period of 18 months. The primary outcome of the study is the total success rate of the i-gel Plus insertion in terms of successful ventilation and oxygenation through the device. Secondary outcomes include perioperative parameters, such as insertion time, seal/leak pressures, number of insertion attempts and postoperative adverse events and complications. Postoperative follow-up will be performed at 1 hour, 24 hours in all patients, and for selected patients at 3 and 6 months. ETHICS AND DISSEMINATION: The cohort study has received the following ethical approvals: General University Hospital Prague, University Hospital Olomouc, University Military Hospital Prague, University Hospital Barcelona, University Hospital Lodz, Antrim Area Hospital, Craigavon Area Hospital, Office for Research Ethics Committees Northern Ireland. The results will be published in peer-reviewed journals and presented at relevant anaesthesia conferences. TRIAL REGISTRATION NUMBER: ISRCTN86233693;Pre-results.

Pancreatic Injury in Patients with SARS-Cov-2 (COVID-19) Infection: A Retrospective Analysis of CT Findings.

OBJECTIVE: To determine the association between COVID-19 infection and peripancreatic changes on CT as a sign of acute pancreatic injury. METHODS: Retrospective analysis of CT examinations in patients with confirmed COVID-19 infection yielded 103 instances. An age- and gender-matched cohort of patients without COVID-19 was found. CT examinations were evaluated for peripancreatic stranding or edema, fluid collection, or necrosis, without any other explanation. Depicted pulmonary parenchyma was evaluated for possible COVID-19-related changes. Clinical and laboratory data were retrieved from the clinical database. RESULTS: Peripancreatic fat stranding (n = 8) or fluid collection (n = 2) without any other cause was found in 10 (10%) patients. Abdominal complaints were reported in 4 (40%) patients. Elevated serum amylase or lipase levels were documented in 5 (50%) patients who also satisfied the diagnostic criteria for acute pancreatitis. From the study sample of 103 patients with COVID-19, pulmonary parenchyma was depicted in 102 (99%), and from these, 57 (55%) had an evidence of pulmonary changes compatible with COVID-19 pneumonia. This proportion was not significantly different between patients with and without peripancreatic changes (p = 0.35). In the matched cohort, we found peripancreatic changes in 2 (2%, p = 0.033) patients. Patients with pancreatic injury and elevated amylase levels were more likely to require orotracheal intubation (35% vs. 12%, p = 0.021). CONCLUSIONS: We showed that the prevalence of peripancreatic stranding or fluid collection is higher in patients diagnosed with COVID-19 infection compared to an age- and gender-matched cohort. Patients with pancreatic injury and elevated amylase levels are more likely to require orotracheal intubation. Our findings corroborate the link between COVID-19 infection and pancreatic injury from the perspective of imaging.

Indications for venous access in oncology - recommendations of national professional societies and current state in the Czech Republic.

BACKGROUND: The aim of the paper is to present the current recommendations and indications of venous access in oncology which reflect and recognize the opinions of national and international professional societies. It focuses exclusively on the indications of intravenous catheter placement for anticancer treatment, such as medium-term and long-term venous accesses. MATERIALS AND METHODS: The survey results obtained from a national questionnaire of 24 oncology centers identified the current situation in the Czech Republic. There were evaluated relevant data on the number of and the criteria for the introduction of venous accesses provided by physicians. Comparisons were made between current oncological practice and recommendations provided by evidence-based medicine. RESULTS: At each center surveyed in the Czech Republic, an average of 130 ports and 80 permanent implanted central catheters are introduced annually. The ports are increasingly indicated, with over a half of the centers surveyed introducing ports to more than 100 patients a year, with four centers introducing a total of 1,600 ports annually. In all centers, the decision for venous access is made by an oncologist. However, most procedures are performed by a doctor of another specialization, most often by a surgeon, a radiologist or an anesthesiologist. More than a half of the indications for venous access placement result from poor peripheral venous system or complications of parenteral therapy, not from comprehensive assessment prior to the initiation of the therapy. CONCLUSION: Based on our findings, we developed general indications and recommendations for venous access to cancer patients which represent the consensus of an interdisciplinary team of specialists, predominantly from the committee of professional societies - the Society for Ports and Permanent Catheters, the Working Group of Nutritional Care in Oncology of the Czech Oncological Society and the Society of Clinical Nutrition and Intensive Metabolic Care. The number of introduced venous access catheters remains insufficient to meet the needs in the Czech Republic, which necessitates increased awareness and possibilities for safe drug administration.