A New, Safe, and Effective Technique for Percutaneous Insertion of a Peritoneal Dialysis Catheter.

A properly functioning peritoneal catheter is an essential element of effective peritoneal dialysis (PD). Currently, there are three techniques available for PD catheter placement, which include open surgery, laparoscopic surgery, and percutaneous catheter placement (PCP). Currently, no particular catheter placement approach has been proven with certainty to provide superior outcomes. We present a new modified PCP method with the use of the Veress needle covered with an intravascular catheter (IC) and preliminary clinical results of PD catheter placements with this new technique. The endpoints used in the study were 1-year technical survival of the catheter, and the incidence of early (1 month) mechanical as well as infection complications. The catheter was implanted in 24 patients. The catheter survival rate was 100%; however, in two cases, the catheters were removed due to complications not associated with PD treatment. No early mechanical complications such as bleeding, hematoma, perforations, internal organ damage, exit site leaks, or hernia in the place of insertion were observed. Similarly, no early infectious complications were observed. During the 1-year follow-up, no catheter migration occurred. Our results showed that the new PCP technique is a safe and easy procedure that minimizes the occurrence of both mechanical and infectious complications and ensures good catheter survival.

Non-invasive assessment of stroke volume and cardiovascular parameters based on peripheral pressure waveform.

Cardiovascular diseases are the leading cause of death globally, making the development of non-invasive and simple-to-use tools that bring insights into the state of the cardiovascular system of utmost importance. We investigated the possibility of using peripheral pulse wave recordings to estimate stroke volume (SV) and subject-specific parameters describing the selected properties of the cardiovascular system. Peripheral pressure waveforms were recorded in the radial artery using applanation tonometry (SphygmoCor) in 35 hemodialysis (HD) patients and 14 healthy subjects. The pressure waveforms were then used to estimate subject-specific parameters of a mathematical model of pulse wave propagation coupled with the elastance-based model of the left ventricle. Bioimpedance cardiography measurements (PhysioFlow) were performed to validate the model-estimated SV. Mean absolute percentage error between the simulated and measured pressure waveforms was 4.0% and 2.8% for the HD and control group, respectively. We obtained a moderate correlation between the model-estimated and bioimpedance-based SV (r = 0.57, p<0.05, and r = 0.58, p<0.001, for the control group and HD patients, respectively). We also observed a correlation between the estimated end-systolic elastance of the left ventricle and the peripheral systolic pressure in both HD patients (r = 0.84, p<0.001) and the control group (r = 0.70, p<0.01). These preliminary results suggest that, after additional validation and possibly further refinement to increase accuracy, the proposed methodology could support non-invasive assessment of stroke volume and selected heart function parameters and vascular properties. Importantly, the proposed method could be potentially implemented in the existing devices measuring peripheral pressure waveforms.

Predictors of cardiac arrest in severe accidental hypothermia.

STUDY OBJECTIVE: To indicate predictors of witnessed hypothermic cardiac arrest. METHODS: We conducted a retrospective analysis of 182 patients with severe accidental hypothermia (i.e., with core body temperature of ≤28 °C) who presented with preserved spontaneous circulation at first contact with medical services. We divided the study population into two groups: patients who suffered hypothermic cardiac arrest (HCA) at any time between encounter with medical service and restoration of normothermia, and those who did not sustain HCA. The analyzed outcome was the occurrence of cardiac arrest prior to achieving normothermia. Hemodynamic and biochemical parameters were analyzed with regard to their association with the outcome. RESULTS: Fifty-two (29%) patients suffered HCA. In a univariable analysis, four variables were significantly associated with the outcome, namely heart rate (p < 0.001), systolic blood pressure (p = 0.03), ventricular arrhythmia (p = 0.001), and arterial oxygen partial pressure (p = 0.002). In the multivariable logistic regression the best model predicting HCA included heart rate, PaO2, and Base Excess (AUROC = 0.78). In prehospital settings, when blood gas analysis is not available, other multivariable model including heart rate and occurrence of ventricular arrhythmia (AUROC = 0.74) can be used. In this study population, threshold values of heart rate of 43/min, temperature-corrected PaO2 of 72 mmHg, and uncorrected PaO2 of 109 mmHg, presented satisfactory sensitivity and specificity for HCA prediction. CONCLUSIONS: In patients with severe accidental hypothermia, the occurrence of HCA is associated with a lower heart rate, hypoxemia, ventricular arrhythmia, lower BE, and lower blood pressure. These parameters can be helpful in the early selection of high-risk patients and their allocation to extracorporeal rewarming facilities.

Application of New Filling Material Based on Combined Heat and Power Waste for Sewage Treatment in Constructed Wetlands.

The filling of constructed wetlands (CWs) affects the efficiency of sewage treatment and proper operation. Mineral aggregates are most often used as filling materials. Significant environmental burdens from mineral mining operations justify the search for waste fill. This study aimed to determine the possibility of increasing the efficiency of CW by using a Certyd aggregate as a new filling. Certyd is produced in the sintering process of coal ash, a waste from combined heat and power (CHP) plant operation. Comprehensive two-year studies were conducted using two real-scale subsurface vertical flow (SS VF) CWs supplied with domestic sewage. One bed was filled with a Certyd and the other was filled with appropriate fractions of a mineral aggregate. Both beds worked in parallel, and to compare their effectiveness, account seasonality was taken into account. The SS-VF Certyd-filled bed achieved an average efficiency of 88.0% for biological oxygen demand (BOD5), 80.2% for chemical oxygen demand (COD), 80.4% for suspended solids (SSs), 80.2 for ammonia nitrogen (N-NH4), 72.2% for total nitrogen (TN), and 55.3% for total phosphorus (TP), while the gravel-filled bed achieved 84.5%, 77.0%, 86.9%, 74.2%, 69.4%, and 57.8% for the whole research period, respectively. A higher effect of the removed unit load was achieved in the bed filled with Certyd (36.2 g BOD5 m-2 d-1, 50.0 g COD m-2 d-1, 5.88 g SS m-2 d-1, 7.1 g TN m-2 d-1, 7.9 g N-NH4 m-2 d-1, 0.79 g TP m-2 d-1) compared to the gravel-filled bed (34.7 g BOD5 m-2 d-1, 47.0 g COD, 6.35 g SS m-2 d-1, 6.9 g TN m-2 d-1, 7.3 g m-2 d-1 N-NH4, 0.83 g TP m-2 d-1).

Update of the European Society of Anaesthesiology and Intensive Care Medicine evidence-based and consensus-based guideline on postoperative delirium in adult patients.

Postoperative delirium (POD) remains a common, dangerous and resource-consuming adverse event but is often preventable. The whole peri-operative team can play a key role in its management. This update to the 2017 ESAIC Guideline on the prevention of POD is evidence-based and consensus-based and considers the literature between 01 April 2015, and 28 February 2022. The search terms of the broad literature search were identical to those used in the first version of the guideline published in 2017. POD was defined in accordance with the DSM-5 criteria. POD had to be measured with a validated POD screening tool, at least once per day for at least 3 days starting in the recovery room or postanaesthesia care unit on the day of surgery or, at latest, on postoperative day 1. Recent literature confirmed the pathogenic role of surgery-induced inflammation, and this concept reinforces the positive role of multicomponent strategies aimed to reduce the surgical stress response. Although some putative precipitating risk factors are not modifiable (length of surgery, surgical site), others (such as depth of anaesthesia, appropriate analgesia and haemodynamic stability) are under the control of the anaesthesiologists. Multicomponent preoperative, intra-operative and postoperative preventive measures showed potential to reduce the incidence and duration of POD, confirming the pivotal role of a comprehensive and team-based approach to improve patients' clinical and functional status.

Evaluation of the TraumaGuard Balloon-in-Balloon Catheter Design for Intra-Abdominal Pressure Monitoring: Insights from Pig and Human Cadaver Studies.

Introduction: Intra-abdominal pressure (IAP) monitoring is crucial for the detection and prevention of intra-abdominal hypertension (IAH) and abdominal compartment syndrome (ACS). In the 1970s, air-filled catheters (AFCs) for urodynamic studies were introduced as a solution to overcome the limitations of water-perfused catheters. Recent studies have shown that for correct IAP measurement with traditional AFC, the bladder needs to be primed with 25 mL of saline solution to allow pressure wave transmission to the transducer outside of the body, which limits continuous IAP monitoring. Methods: In this study, a novel triple balloon, air-filled TraumaGuard (TG) catheter system from Sentinel Medical Technologies (Jacksonville, FL, USA) with a unique balloon-in-balloon design was evaluated in a porcine and cadaver model of IAH via laparoscopy (IAPgold). Results: In total, 27 and 86 paired IAP measurements were performed in two pigs and one human cadaver, respectively. The mean IAPTG was 20.7 ± 10.7 mmHg compared to IAPgold of 20.3 ± 10.3 mmHg in the porcine study. In the cadaver investigation, the mean IAPTG was 15.6 ± 10.8 mmHg compared to IAPgold of 14.4 ± 10.4 mmHg. The correlation, concordance, bias, precision, limits of agreement, and percentage error were all in accordance with the WSACS (Abdominal Compartment Society) recommendations and guidelines for research. Conclusions: These findings support the use of the TG catheter for continuous IAP monitoring, providing early detection of elevated IAP, thus enabling the potential for prevention of IAH and ACS. Confirmation studies with the TraumaGuard system in critically ill patients are warranted to further validate these findings.

In Vitro Validation of a Novel Continuous Intra-Abdominal Pressure Measurement System (TraumaGuard).

Introduction: Intra-abdominal pressure (IAP) has been recognized as an important vital sign in critically ill patients. Due to the high prevalence and incidence of intra-abdominal hypertension in surgical (trauma, burns, cardiac) and medical (sepsis, liver cirrhosis, acute kidney injury) patients, continuous IAP (CIAP) monitoring has been proposed. This research was aimed at validating a new CIAP monitoring device, the TraumaGuard from Sentinel Medical Technologies, against the gold standard (height of a water column) in an in vitro setting and performing a comparative analysis among different CIAP measurement technologies (including two intra-gastric and two intra-bladder measurement devices). A technical and clinical guideline addressing the strengths and weaknesses of each device is provided as well. Methods: Five different CIAP measurement devices (two intra-gastric and three intra-vesical), including the former CiMON, Spiegelberg, Serenno, TraumaGuard, and Accuryn, were validated against the gold standard water column pressure in a bench-top abdominal phantom. The impacts of body temperature and bladder fill volume (for the intra-vesical methods) were evaluated for each system. Subsequently, 48 h of continuous monitoring (n = 2880) on top of intermittent IAP (n = 300) readings were captured for each device. Using Pearson's and Lin's correlations, concordance, and Bland and Altman analyses, the accuracy, precision, percentage error, correlation and concordance coefficients, bias, and limits of agreement were calculated for all the different devices. We also performed error grid analysis on the CIAP measurements to provide an overview of the involved risk level due to wrong IAP measurements and calculated the area under the curve and time above a certain IAP threshold. Lastly, the robustness of each system in tracking the dynamic variations of the raw IAP signal due to respirations and heartbeats was evaluated as well. Results: The TraumaGuard was the only technology able to measure the IAP with an empty artificial bladder. No important temperature dependency was observed for the investigated devices except for the Spiegelberg, which displayed higher IAP values when the temperature was increased, but this could be adjusted through recalibration. All the studied devices showed excellent ability for IAP monitoring, although the intra-vesical IAP measurements seem more reliable. In general, the TraumaGuard, Accuryn, and Serenno showed better accuracy compared to intra-gastric measurement devices. On average, biases of +0.71, +0.93, +0.29, +0.25, and -0.06 mm Hg were observed for the CiMON, Spiegelberg, Serenno, TraumaGuard, and Accuryn, respectively. All of the equipment showed percentage errors smaller than 25%. Regarding the correlation and concordance coefficients, the Serenno and TraumaGuard showed the best results (R2 = 0.98, p = 0.001, concordance coefficient of 99.5%). Error grid analysis based on the Abdominal Compartment Society guidelines showed a very low associated risk level of inappropriate treatment strategies due to erroneous IAP measurements. Regarding the dynamic tracings of the raw IAP signal, all the systems can track respiratory variations and derived parameters; however, the CiMON was slightly superior compared to the other technologies. Conclusions: According to the research guidelines of the Abdominal Compartment Society (WSACS), this in vitro study shows that the TraumaGuard can be used interchangeably with the gold standard for measuring continuous IAP, even in an empty artificial bladder. Confirmation studies with the TraumaGuard in animals and humans are warranted to further validate these findings.

The Effect of Potassium Canrenoate (Mineralocorticoid Receptor Antagonist) on the Markers of Inflammation in the Treatment of COVID-19 Pneumonia and Fibrosis-A Secondary Analysis of Randomized Placebo-Controlled Clinical Trial.

In March 2020, the World Health Organization (WHO) announced a global pandemic of coronavirus disease 2019 (COVID-19) that presented mainly as an acute infection of the lower respiratory tract (pneumonia), with multiple long-term consequences, including lung fibrosis. The aim of this study was to evaluate the influence of potassium canrenoate on inflammatory markers in the treatment of COVID-19 pneumonia. A randomized clinical trial (RCT) of intravenous potassium canrenoate vs. placebo was performed between December 2020 and November 2021. This study is a secondary analysis of that RCT. In the final analysis, a total of 49 hospitalized patients were included (24 allocated to the potassium canrenoate group and 25 to the placebo group). Patients were assessed by serum testing and blood cell cytometry on day 1 and day 7 of the intervention. Age, sex, and body mass index were not significantly different between the placebo group and intervention group. Although there was a significantly higher rate of ischemic heart disease in the placebo group, rates of other preexisting comorbidities were not significantly different. There were no significant differences in the inflammatory parameters between the potassium canrenoate and placebo groups on day 1 and day 7. However, the intragroup comparisons using Wilcoxon's test showed significant differences between day 1 and day 7. The CD3% for potassium canrenoate increased significantly between day 1 and day 7 (12.85 ± 9.46; 11.55 vs. 20.50 ± 14.40; 17.80; p = 0.022), while the change in the placebo group was not significant (15.66 ± 11.39; 12.65 vs. 21.16 ± 15.37; 16.40; p = 0.181). The IL-1ß total count [%] increased over time for both potassium canrenoate (0.68 ± 0.58; 0.45 vs. 1.27 ± 0.83; 1.20; p = 0.004) and placebo (0.61 ± 0.59; 0.40 vs. 1.16 ± 0.91; 1.00; p = 0.016). The TNF-α total count (%) decreased significantly between day 1 and day 7 for potassium canrenoate (0.54 ± 0.45; 0.40 vs. 0.25 ± 0.23; 0.10; p = 0.031), but not for placebo (0.53 ± 0.47; 0.35 vs. 0.26 ± 0.31; 0.20; p = 0.056). Interleukin-6 (pg/mL) showed a significant decrease between day 1 and day 7 for potassium canrenoate (64.97 ± 72.52; 41.00 vs. 24.20 ± 69.38; 5.30; p = 0.006), but not the placebo group. This RCT has shown that the administration of potassium canrenoate to patients with COVID-19-induced pneumonia may be associated with significant changes in certain inflammatory markers (interleukin-6, CD3%, TNF-α), potentially related to pulmonary fibrosis. Although some positive trends were observed in the potassium canrenoate group, none of these observations reached statistical significance. Any possible benefits from the use of potassium canrenoate as an anti-inflammatory or antifibrotic drug in COVID-19 patients require further investigation.

Extracorporeal Rewarming Is Associated With Increased Survival Rate in Severely Hypothermic Patients With Preserved Spontaneous Circulation.

Treatment recommendations for rewarming patients in severe accidental hypothermia with preserved spontaneous circulation have a weak evidence due to the absence of randomized clinical trials. We aimed to compare the outcomes of extracorporeal versus less-invasive rewarming of severely hypothermic patients with preserved spontaneous circulation. We conducted a multicenter retrospective study. The patient population was compiled based on data from the HELP Registry, the International Hypothermia Registry, and a literature review. Adult patients with a core temperature <28°C and preserved spontaneous circulation were included. Patients who underwent extracorporeal rewarming were compared with patients rewarmed with less-invasive methods, using a matched-pair analysis. The study population consisted of 50 patients rewarmed extracorporeally and 85 patients rewarmed with other, less-invasive methods. Variables significantly associated with survival included: lower age; outdoor cooling circumstances; higher blood pressure; higher PaCO 2 ; higher BE; higher HCO 3 ; and the absence of comorbidities. The survival rate was higher in patients rewarmed extracorporeally ( p = 0.049). The relative risk of death was twice as high in patients rewarmed less invasively. Based on our data, we conclude that patients in severe accidental hypothermia with circulatory instability can benefit from extracorporeal rewarming without an increased risk of complications.

Concentration of Apoptotic Factors in Bronchoalveolar Lavage Fluid, as Potential Brain-Lung Oxygen Relationship, Correspond to the Severity of Brain Injury.

BACKGROUND: The mechanism of acute brain injury initiates a cascade of consequences which can directly cause lung damage, and this can contribute to poor neurological outcomes. The aim of this study was to evaluate concentration of different apoptotic molecules in the bronchoalveolar lavage fluid (BALF) in patients after severe brain injury and to correlate them with selected clinical variables and mortality. METHODS: Patients with brain injury receiving BALF operation were included in the study. BALF samples were collected within the first 6-8 hours after traumatic brain injury (A) and at days 3 (B) and 7 (C) after admission to the intensive care unit (ICU). Changes in the BALF nuclear-encoded protein (Bax), apoptotic regulatory protein (Bcl-2), pro-apoptotic protein (p53) and its upregulated modulator (PUMA), apoptotic protease factor 1 (APAF-1), Bcl-2 associated agonist of cell death (BAD) and caspase-activated DNase (CAD) were analysed. These values were correlated with the selected oxygenation parameters, Rotterdam computed tomography (CT) score, the Glasgow Coma Score and 28-day mortality. RESULTS: We found a significant increase in the concentration of selected apoptotic factors at admission (A), at day 3 (B) and day 7 (C) after severe brain damage contrasted with baseline level A (p < 0.001, separately). That concentration of selected apoptotic factors was significantly correlated with the severity of the injury and mortality. CONCLUSIONS: Activation of different apoptotic pathways seems to be an important process occurring in the lungs of patients in the early phases after severe brain trauma. Levels of apoptotic factors in the BALF correlates with the severity of brain injury.

Synergistic Antifungal Interactions between Antibiotic Amphotericin B and Selected 1,3,4-thiadiazole Derivatives, Determined by Microbiological, Cytochemical, and Molecular Spectroscopic Studies.

In recent years, drug-resistant and multidrug-resistant fungal strains have been more frequently isolated in clinical practice. This phenomenon is responsible for difficulties in the treatment of infections. Therefore, the development of new antifungal drugs is an extremely important challenge. Combinations of selected 1,3,4-thiadiazole derivatives with amphotericin B showing strong synergic antifungal interactions are promising candidates for such formulas. In the study, microbiological, cytochemical, and molecular spectroscopy methods were used to investigate the antifungal synergy mechanisms associated with the aforementioned combinations. The present results indicate that two derivatives, i.e., C1 and NTBD, demonstrate strong synergistic interactions with AmB against some Candida species. The ATR-FTIR analysis showed that yeasts treated with the C1 + AmB and NTBD + AmB compositions, compared with those treated with single compounds, exhibited more pronounced abnormalities in the biomolecular content, suggesting that the main mechanism of the synergistic antifungal activity of the compounds is related to a disturbance in cell wall integrity. The analysis of the electron absorption and fluorescence spectra revealed that the biophysical mechanism underlying the observed synergy is associated with disaggregation of AmB molecules induced by the 1,3,4-thiadiazole derivatives. Such observations suggest the possibility of the successful application of thiadiazole derivatives combined with AmB in the therapy of fungal infections.

Humulus lupus extract rich in xanthohumol improves the clinical course in critically ill COVID-19 patients.

BACKGROUND: The systemic inflammatory response following severe COVID-19 is associated with poor outcomes. Several anti-inflammatory medications have been studied in COVID-19 patients. Xanthohumol (Xn), a natural extract from hop cones, possesses strong anti-inflammatory and antioxidative properties. The aim of this study was to analyze the effect of Xn on the inflammatory response and the clinical outcome of COVID-19 patients. METHODS: Adult patients treated for acute respiratory failure (PaO2/FiO2 less than 150) were studied. Patients were randomized into two groups: Xn - patients receiving adjuvant treatment with Xn at a daily dose of 4.5 mg/kg body weight for 7 days, and C - controls. Observations were performed at four time points: immediately after admission to the ICU and on the 3rd, 5th, and 7th days of treatment. The inflammatory response was assessed based on the plasma IL-6 concentration, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), C-reactive protein (CRP) and D-dimer levels. The mortality rate was determined 28 days after admission to the ICU. RESULTS: Seventy-two patients were eligible for the study, and 50 were included in the final analysis. The mortality rate was significantly lower and the clinical course was shorter in the Xn group than in the control group (20% vs. 48%, p < 0.05, and 9 ± 3 days vs. 22 ± 8 days, p < 0.001). Treatment with Xn decreased the plasma IL-6 concentration (p < 0.01), D-dimer levels (p < 0.05) and NLR (p < 0.01) more significantly than standard treatment alone. CONCLUSION: Adjuvant therapy with Xn appears to be a promising anti-inflammatory treatment in COVID-19 patients.

Comparison of Bioelectrical Impedance Analysis (BIA)-Derived Parameters in Healthy Volunteers and Critically Ill Patients.

OBJECTIVE: To compare bioelectrical impedance analysis (BIA)-derived parameters in healthy volunteers and critically ill patients and to assess its prognostic value in an ICU patient cohort. DESIGN: Retrospective, observational data analysis. SETTING: Single centre, tertiary-level ICU (Ziekenhuis Netwerk Antwerpen, ZNA Stuivenberg Hospital). PATIENTS: 101 patients and 101 healthy subjects, participants of International Fluid Academy Days. MEASUREMENTS AND MAIN RESULTS: Compared to healthy volunteers, both male and female ICU patients had significantly higher values for total body water (TBW), extracellular water (ECW), extracellular fluid (ECF), plasma, and interstitial fluid volumes. The phase angle was significantly lower and the malnutrition index was significantly higher in ICU patients, regardless of gender. Non-survivors in the ICU had significantly higher extracellular water content (ECW, 50.7 ± 5.1 vs. 48.9 ± 4.3%, p = 0.047) and accordingly significantly lower intracellular water (ICW, 49.2 ± 5.1 vs. 51.1 ± 4.3%, p = 0.047). The malnutrition index was also significantly higher in non-survivors compared to survivors (0.94 ± 0.17 vs. 0.87 ± 0.16, p = 0.048), as was the capillary leak index (ECW/ICW). CONCLUSIONS: Compared to healthy volunteers, this study observed a higher malnutrition index and TBW in ICU patients with an accumulation of fluids in the extracellular compartment. ICU non-survivors showed similar results, indicating that ICU patients and a fortiori non-survivors are generally overhydrated, with increased TBW and ECW, and more undernourished, as indicated by a higher malnutrition index.

Cerebral Oxygen Delivery and Consumption in Brain-Injured Patients.

Organism survival depends on oxygen delivery and utilization to maintain the balance of energy and toxic oxidants production. This regulation is crucial to the brain, especially after acute injuries. Secondary insults after brain damage may include impaired cerebral metabolism, ischemia, intracranial hypertension and oxygen concentration disturbances such as hypoxia or hyperoxia. Recent data highlight the important role of clinical protocols in improving oxygen delivery and resulting in lower mortality in brain-injured patients. Clinical protocols guide the rules for oxygen supplementation based on physiological processes such as elevation of oxygen supply (by mean arterial pressure (MAP) and intracranial pressure (ICP) modulation, cerebral vasoreactivity, oxygen capacity) and reduction of oxygen demand (by pharmacological sedation and coma or hypothermia). The aim of this review is to discuss oxygen metabolism in the brain under different conditions.

Effect of Antibiotic Amphotericin B Combinations with Selected 1,3,4-Thiadiazole Derivatives on RPTECs in an In Vitro Model.

4-(5-methyl-1,3,4-thiadiazole-2-yl) benzene-1,3-diol (C1) and 4-[5-(naphthalen-1-ylmethyl)-1,3,4-thiadiazol-2-yl] benzene1,3-diol (NTBD) are representative derivatives of the thiadiazole group, with a high antimycotic potential and minimal toxicity against normal human fibroblast cells. The present study has proved its ability to synergize with the antifungal activity of AmB. The aim of this work was to evaluate the cytotoxic effects of C1 or NTBD, alone or in combination with AmB, on human renal proximal tubule epithelial cells (RPTECs) in vitro. Cell viability was assessed with the MTT assay. Flow cytometry and spectrofluorimetric techniques were used to assess the type of cell death and production of reactive oxygen species (ROS), respectively. The ELISA assay was performed to measure the caspase-2, -3, and -9 activity. ATR-FTIR spectroscopy was used to evaluate biomolecular changes in RPTECs induced by the tested formulas. The combinations of C1/NTBD and AmB did not exert a strong inhibitory effect on the viability/growth of kidney cells, as evidenced by the negligible changes in the apoptotic/necrotic rate and caspase activity, compared to the control cells. Both NTBD and C1 displayed stronger anti-oxidant activity when combined with AmB. The relatively low nephrotoxicity of the thiadiazole derivative combinations and the protective activity against AmB-induced oxidative stress may indicate their potential use in the therapy of fungal infections.

Fluid Management, Intra-Abdominal Hypertension and the Abdominal Compartment Syndrome: A Narrative Review.

BACKGROUND: General pathophysiological mechanisms regarding associations between fluid administration and intra-abdominal hypertension (IAH) are evident, but specific effects of type, amount, and timing of fluids are less clear. OBJECTIVES: This review aims to summarize current knowledge on associations between fluid administration and intra-abdominal pressure (IAP) and fluid management in patients at risk of intra-abdominal hypertension and abdominal compartment syndrome (ACS). METHODS: We performed a structured literature search from 1950 until May 2021 to identify evidence of associations between fluid management and intra-abdominal pressure not limited to any specific study or patient population. Findings were summarized based on the following information: general concepts of fluid management, physiology of fluid movement in patients with intra-abdominal hypertension, and data on associations between fluid administration and IAH. RESULTS: We identified three randomized controlled trials (RCTs), 38 prospective observational studies, 29 retrospective studies, 18 case reports in adults, two observational studies and 10 case reports in children, and three animal studies that addressed associations between fluid administration and IAH. Associations between fluid resuscitation and IAH were confirmed in most studies. Fluid resuscitation contributes to the development of IAH. However, patients with IAH receive more fluids to manage the effect of IAH on other organ systems, thereby causing a vicious cycle. Timing and approach to de-resuscitation are of utmost importance, but clear indicators to guide this decision-making process are lacking. In selected cases, only surgical decompression of the abdomen can stop deterioration and prevent further morbidity and mortality. CONCLUSIONS: Current evidence confirms an association between fluid resuscitation and secondary IAH, but optimal fluid management strategies for patients with IAH remain controversial.

Guided Endodontics as a Personalized Tool for Complicated Clinical Cases.

The aim of this paper is to present a technique to individualize root canal localization in teeth with calcified root canals using a digitally planned, 3D-printed endodontic guide. Root canal calcification is characterized by the apposition of tertiary dentin along the canal wall. The endodontic treatment of teeth with calcified canals is often challenging. However, digital dentistry meets these challenges. Merging CBCT images with an intraoral scan allows a clinician to prepare an endodontic guide. This article describes the clinical and digital workflow of the guided endodontic access approach in teeth with difficulties in terms of root canal localization due to post-traumatic pulp canal obliteration (PCO) and canal calcification in elderly patients. The path of entry into the root canal system was planned using cone-beam computed tomography (CBCT). The template was printed on a 3D printer using transparent resin. During root canal treatment (RCT), the endodontic tool was inserted through the sleeve until the desired location was reached. The use of an endodontic guide allowed for minimally invasive RCT, avoiding the excessive loss of tooth structures. Navigated endodontics enables clinicians to perform RCT in a more predictable manner and allows clinicians to avoid iatrogenic complications, which improves the treatment prognosis.

Melatonin and the Brain-Heart Crosstalk in Neurocritically Ill Patients-From Molecular Action to Clinical Practice.

Brain injury, especially traumatic brain injury (TBI), may induce severe dysfunction of extracerebral organs. Cardiac dysfunction associated with TBI is common and well known as the brain-heart crosstalk, which broadly refers to different cardiac disorders such as cardiac arrhythmias, ischemia, hemodynamic insufficiency, and sudden cardiac death, which corresponds to acute disorders of brain function. TBI-related cardiac dysfunction can both worsen the brain damage and increase the risk of death. TBI-related cardiac disorders have been mainly treated symptomatically. However, the analysis of pathomechanisms of TBI-related cardiac dysfunction has highlighted an important role of melatonin in the prevention and treatment of such disorders. Melatonin is a neurohormone released by the pineal gland. It plays a crucial role in the coordination of the circadian rhythm. Additionally, melatonin possesses strong anti-inflammatory, antioxidative, and antiapoptotic properties and can modulate sympathetic and parasympathetic activities. Melatonin has a protective effect not only on the brain, by attenuating its injury, but on extracranial organs, including the heart. The aim of this study was to analyze the molecular activity of melatonin in terms of TBI-related cardiac disorders. Our article describes the benefits resulting from using melatonin as an adjuvant in protection and treatment of brain injury-induced cardiac dysfunction.