Prognostic thresholds of outcome predictors in severe accidental hypothermia.

Hemodynamically unstable patients with severe hypothermia and preserved circulation should be transported to dedicated extracorporeal life support (ECLS) centers, but not all are eligible for extracorporeal therapy. In this group of patients, the outcome of rewarming may sometimes be unfavorable. It is, therefore, crucial to identify potential risk factors for death. Furthermore, it is unclear what criterion for hemodynamic stability should be adopted for patients with severe hypothermia. The aim of this study is to identify pre-rewarming predictors of death and their threshold values in hypothermic patients with core temperature ≤ 28 °C and preserved circulation, who were treated without extracorporeal rewarming. We conducted a multicenter retrospective study involving patients in accidental hypothermia with core temperature 28 °C or lower, and preserved spontaneous circulation on rewarming initiation. The data were collected from the International Hypothermia Registry, HELP Registry, and additional hospital data. The primary outcome was survival to hospital discharge. We conducted a multivariable logistic regression and receiver operating characteristic curve (ROC) analysis. In the multivariate analysis of laboratory tests and vital signs, systolic blood pressure (SBP) adjusted for cooling circumstances and base excess (BE) were identified as the best predictor of death (OR 0.974 95% CI 0.952-0.996), AUC ROC 0.79 (0.70-0.88). The clinically relevant cutoff for SBP was identified at 90 mmHg with a sensitivity of 0.74 (0.54-0.89) and a specificity of 0.70 (0.60-0.79). The increased risk of death among hypothermic patients with preserved circulation occurs among those with an SBP below 90 mmHg and in those who developed hypothermia in their homes.

A retrospective assessment of the effectiveness of pulsed radiofrequency ablation in the treatment of chronic pain caused by advanced knee osteoarthritis.

INTRODUCTION: Patients suffering from severe chronic pain often have problems finding an appropriate combination of painkillers. We retrospectively evaluated the effectiveness and safety of pulsed radiofrequency ablation (pRFA) of the genicular nerves in 96 patients with knee osteoarthritis (KO). We hypothesized that age, sex, and body mass index (BMI) may influence the quality of the pRFA treatment. MATERIAL AND METHODS: A diagnostic blockade with total volume of 9 ml of 1% lidocaine (WZF, Poland) combined with 4 mg of dexamethasone with subsequent pRFA with a radio frequency of 300-500 kHz under ultrasound guidance was used during the procedure. The study participants were assessed during regular monthly visits until 12 months. RESULTS: The nerves' ultrasound identification was successful in 90.62% of the cases. According to the numeric rating scale (NRS), pain was reduced by 50% or more in 64.06% of the cases. The average pain relief period lasted just over 7 and a half months. There were no pRFA-related complications or side effects of the drugs used. CONCLUSIONS: pRFA seems to be safe and effective for the treatment of chronic pain in KO. The outcome of the treatment may be related to the patient's age (block duration increased with patient age) and sex (in women, the therapeutic effect was more effectively prolonged) in our study group. There was also higher effectiveness of pRFA in high-BMI patients, which was close to statistical significance ( P = 0.053).

Expert perspectives on ECCO2R for acute hypoxemic respiratory failure: consensus of a 2022 European roundtable meeting.

BACKGROUND: By controlling hypercapnia, respiratory acidosis, and associated consequences, extracorporeal CO2 removal (ECCO2R) has the potential to facilitate ultra-protective lung ventilation (UPLV) strategies and to decrease injury from mechanical ventilation. We convened a meeting of European intensivists and nephrologists and used a modified Delphi process to provide updated insights into the role of ECCO2R in acute respiratory distress syndrome (ARDS) and to identify recommendations for a future randomized controlled trial. RESULTS: The group agreed that lung protective ventilation and UPLV should have distinct definitions, with UPLV primarily defined by a tidal volume (VT) of 4-6 mL/kg predicted body weight with a driving pressure (ΔP) ≤ 14-15 cmH2O. Fourteen (93%) participants agreed that ECCO2R would be needed in the majority of patients to implement UPLV. Furthermore, 10 participants (majority, 63%) would select patients with PaO2:FiO2 > 100 mmHg (> 13.3 kPa) and 14 (consensus, 88%) would select patients with a ventilatory ratio of > 2.5-3. A minimum CO2 removal rate of 80 mL/min delivered by continuous renal support machines was suggested (11/14 participants, 79%) for this objective, using a short, double-lumen catheter inserted into the right internal jugular vein as the preferred vascular access. Of the participants, 14/15 (93%, consensus) stated that a new randomized trial of ECCO2R is needed in patients with ARDS. A ΔP of ≥ 14-15 cmH2O was suggested by 12/14 participants (86%) as the primary inclusion criterion. CONCLUSIONS: ECCO2R may facilitate UPLV with lower volume and pressures provided by the ventilator, while controlling respiratory acidosis. Since recent European Society of Intensive Care Medicine guidelines on ARDS recommended against the use of ECCO2R for the treatment of ARDS outside of randomized controlled trials, new trials of ECCO2R are urgently needed, with a ΔP of ≥ 14-15 cmH2O suggested as the primary inclusion criterion.

An Introduction to Ventra: A Programmable Abdominal Phantom for Training, Educational, Research, and Development Purposes.

BACKGROUND: Intra-abdominal pressure (IAP) is a critical parameter in the care of critically ill patients, as elevated IAP can lead to reduced cardiac output and organ perfusion, potentially resulting in multiple organ dysfunction and failure. The current gold standard for measuring IAP is an indirect technique via the bladder. According to the Abdominal Compartment Society's Guidelines, new measurement methods/devices for IAP must be validated against the gold standard. OBJECTIVES: This study introduces Ventra, an abdominal phantom designed to simulate different IAP levels, abdominal compliance, respiration-related IAP variations, and bladder dynamics. Ventra aims to facilitate the development and validation of new IAP measurement devices while reducing reliance on animal and cadaveric studies. Additionally, it offers potential applications in training and education for biomedical engineering students. This study provides a thorough explanation on the phantom's design and fabrication, which provides a low-cost solution for advancing IAP measurement research and education. The design concept, technical aspects, and a series of validation experiments determining whether Ventra is a suitable tool for future research are presented in this study. METHODS: Ventra's performance was evaluated through a series of validation tests using a pressure gauge and two intra-gastric (Spiegelberg and CiMON) and two intra-bladder (Accuryn and TraumaGuard) pressure measurement devices. The mean and standard deviation of IAP recordings by each device were investigated. Bland-Altman analysis was used to evaluate bias, precision, limits of agreement, and percentage error for each system. Concordance analysis was performed to assess the ability of Ventra in tracking IAP changes. RESULTS: The phantom demonstrated excellent agreement with reference pressure measurements, showing an average bias of 0.11 ± 0.49 mmHg. A concordance coefficient of 100% was observed for the phantom as well. Ventra accurately simulated different abdominal compliances, with higher IAP values resulting in lower compliance. Abdominal volume changes showed a bias of 0.08 ± 0.07 L/min, and bladder fill volume measurements showed an average difference of 0.90 ± 4.33 mL for volumes ranging from 50 to 500 mL. CONCLUSION: The validation results were in agreement with the research guidelines of the world abdominal society. Ventra is a reliable tool that will facilitate the development and validation of new IAP measurement devices. It is an effective educational tool for biomedical engineering students as well.

Fluid accumulation syndrome in sepsis and septic shock: pathophysiology, relevance and treatment-a comprehensive review.

In this review, we aimed to comprehensively summarize current literature on pathophysiology, relevance, diagnosis and treatment of fluid accumulation in patients with sepsis/septic shock. Fluid accumulation syndrome (FAS) is defined as fluid accumulation (any degree, expressed as percentage from baseline body weight) with new onset organ-failure. Over the years, many studies have described the negative impact of FAS on clinically relevant outcomes. While the relationship between FAS and ICU outcomes is well described, uncertainty exists regarding its diagnosis, monitoring and treatment. A stepwise approach is suggested to prevent and treat FAS in patients with septic shock, including minimizing fluid intake (e.g., by limiting intravenous fluid administration and employing de-escalation whenever possible), limiting sodium and chloride administration, and maximizing fluid output (e.g., with diuretics, or renal replacement therapy). Current literature implies the need for a multi-tier, multi-modal approach to de-resuscitation, combining a restrictive fluid management regime with a standardized early active de-resuscitation, maintenance fluid reduction (avoiding fluid creep) and potentially using physical measures such as compression stockings.Trial registration: Not applicable.

Urine output is an early and strong predictor of acute kidney injury and associated mortality: a systematic literature review of 50 clinical studies.

BACKGROUND: Although the present diagnosis of acute kidney injury (AKI) involves measurement of acute increases in serum creatinine (SC) and reduced urine output (UO), measurement of UO is underutilized for diagnosis of AKI in clinical practice. The purpose of this investigation was to conduct a systematic literature review of published studies that evaluate both UO and SC in the detection of AKI to better understand incidence, healthcare resource use, and mortality in relation to these diagnostic measures and how these outcomes may vary by population subtype. METHODS: The systematic literature review was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist. Data were extracted from comparative studies focused on the diagnostic accuracy of UO and SC, relevant clinical outcomes, and resource usage. Quality and validity were assessed using the National Institute for Health and Care Excellence (NICE) single technology appraisal quality checklist for randomized controlled trials and the Newcastle-Ottawa Quality Assessment Scale for observational studies. RESULTS: A total of 1729 publications were screened, with 50 studies eligible for inclusion. A majority of studies (76%) used the Kidney Disease: Improving Global Outcomes (KDIGO) criteria to classify AKI and focused on the comparison of UO alone versus SC alone, while few studies analyzed a diagnosis of AKI based on the presence of both UO and SC, or the presence of at least one of UO or SC indicators. Of the included studies, 33% analyzed patients treated for cardiovascular diseases and 30% analyzed patients treated in a general intensive care unit. The use of UO criteria was more often associated with increased incidence of AKI (36%), than was the application of SC criteria (21%), which was consistent across the subgroup analyses performed. Furthermore, the use of UO criteria was associated with an earlier diagnosis of AKI (2.4-46.0 h). Both diagnostic modalities accurately predicted risk of AKI-related mortality. CONCLUSIONS: Evidence suggests that the inclusion of UO criteria provides substantial diagnostic and prognostic value to the detection of AKI.

Soft Tissue Retraction Maneuver in Cone Beam Computed Tomography Prior to Crown-Lengthening Procedure-A Technical Note.

Background: An accurate determination of the biological width and the relationship of the cemento-enamel junction with the border of the alveolar bone is crucial during a clinical crown-lengthening (CCL) procedure. The aim of this study was to present a technical note about the retraction techniques in cone beam computed tomography (CBCT) prior to CCL, highlighting the significant enhancement in procedural accuracy and predictability that these techniques offer. Methods: Clinical and radiological examinations should be performed before a CCL procedure. It is necessary to determine the length of the tooth crowns, the periodontal pockets' depth, and the phenotype of the gingiva. The ideal CBCT examination should be performed with soft tissue retraction. This can be achieved using retractors or cotton rolls. Results: Retraction of the lips, cheeks, and tongue allows one to assess the marginal gingiva, the cemento-enamel junction, and the alveolar bone. A detailed plan of the CCL procedure, which involves retraction, ensures both the aesthetic appeal and the achievement of a newly defined gingival zenith, enhancing the overall visual harmony. Conclusions: Compared with conventional radiographic imaging, the soft tissue retraction maneuver in CBCT prior to CCL surgery offers an effective approach to the evaluation and diagnosis of soft and hard tissue. This is because of the detailed planning of the aesthetic CCL procedure. Such an approach leads to superior aesthetic outcomes in dentistry, contributing to the advancement of aesthetic dentistry through a harmonious blend of art and science.

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.