Arterial Pressure Research Articles

TCT-467 Prolonged Occlusion of the Superior Vena Cava Using the PreCardia System Reduces Cardiac Filling and Renal Venous Pressures Without Causing Cerebral Injury in a Preclinical Model of Systemic Congestion

TCT-467 Prolonged Occlusion of the Superior Vena Cava Using the PreCardia System Reduces Cardiac Filling and Renal Venous Pressures Without Causing Cerebral Injury in a Preclinical Model of Systemic Congestion

Predictive value of hepatic venous pressure gradient in cirrhotic portal vein thrombosis development

Background & AimsThere are lots of risk factors reported for cirrhotic portal vein thrombosis (PVT) development, however, the relationship between hepatic venous pressure gradient (HVPG) and PVT development remains unclear. MethodsThe clinical outcomes of cirrhotic patients who had no PVT and underwent HVPG measurement at baseline between March 2018 and March 2022 were analyzed retrospectively. Screening for non-tumoral PVT development was implemented by contrast-enhanced computed tomography and/or magnetic resonance imaging every 6-12 months. ResultsEighty-two cirrhotic patients were evaluated over a follow-up period. Of these, 12 patients (14.6%) experienced the development of PVT. The occurrence of non-tumoral PVT at one, two, and three years were 6.6%, 11.7%, and 22.2% respectively. HVPG (p=0.038;HR 1.07;95%CI 1.00-1.14) and alcohol liver disease (ALD) (p=0.019;HR 4.20;95%CI 1.27-13.89) were independently associated with a high PVT risk. The cutoff value of HVPG was 17.52 mmHg. The cumulative incidence of PVT differed significantly among groups stratified by HVPG thresholds of 16mmHg (P=0.011). The sensitivity and specificity of HVPG≥16mmHg in predicting PVT development were 100.0% and 35.7%. ConclusionsIn patients with liver cirrhosis, the value of HVPG was the independent predictive factor of PVT development. Screening for PVT was recommended during follow-up in patients with HVPG≥16 mmHg.

In silico data-based comparison of the accuracy and error source of various methods for noninvasively estimating central aortic blood pressure

Background and objectivesThe higher clinical significance of central aortic blood pressure (CABP) compared to peripheral blood pressures has been extensively demonstrated. Accordingly, many methods for noninvasively estimating CABP have been proposed. However, there still lacks a systematic comparison of existing methods, especially in terms of how they differ in the ability to tolerate individual differences or measurement errors. The present study was designed to address this gap. MethodsA large-scale ‘virtual subject’ dataset (n = 600) was created using a computational model of the cardiovascular system, and applied to examine several classical CABP estimation methods, including the direct method, generalized transfer function (GTF) method, n-point moving average (NPMA) method, second systolic pressure of periphery (SBP2) method, physical model-based wave analysis (MBWA) method, and suprasystolic cuff-based waveform reconstruction (SCWR) method. The errors of CABP estimation were analyzed and compared among methods with respect to the magnitude/distribution, correlations with physiological/hemodynamic factors, and sensitivities to noninvasive measurement errors. ResultsThe errors of CABP estimation exhibited evident inter-method differences in terms of the mean and standard deviation (SD). Relatively, the estimation errors of the methods adopting pre-trained algorithms (i.e., the GTF and SCWR methods) were overall smaller and less sensitive to variations in physiological/hemodynamic conditions and random errors in noninvasive measurement of brachial arterial blood pressure (used for calibrating peripheral pulse wave). The performances of all the methods worsened following the introduction of random errors to peripheral pulse wave (used for deriving CABP), as characterized by the enlarged SD and/or increased mean of the estimation errors. Notably, the GTF and SCWR methods did not exhibit a better capability of tolerating pulse wave errors in comparison with other methods. ConclusionsClassical noninvasive methods for estimating CABP were found to differ considerably in both the accuracy and error source, which provided theoretical evidence for understanding the specific advantages and disadvantages of each method. Knowledge about the method-specific error source and sensitivities of errors to different physiological/hemodynamic factors may contribute as theoretical references for interpreting clinical observations and exploring factors underlying large estimation errors, or provide guidance for optimizing existing methods or developing new methods.

Systemic reviews and meta-analysis of the use of midodrine in hepatorenal syndrome

Aims. This study analyzes the effectiveness of midodrine in reducing or managing Hepatorenal Syndrome (HRS). Design. A systematic review and meta-analysis were conducted to gather and assess relevant literature. The review included evaluating study aims, methodologies, outcomes, and implications, with data presented in a tabular format for clarity. The protocol specified the search strategy, selection criteria, and data extraction methods for transparency. Data sources. Articles were sourced from Google Scholar and PubMed using inclusion and exclusion criteria. Quality assessment data were extracted, synthesized, analyzed, and reported. Review methods. The systematic review focused on peer-reviewed journals, considering factors such as time, language, and full-length article availability. Studies were excluded if they were duplicates, abstracts only, or non-English. Results. Midodrine was found to improve arterial pressure and renal function in HRS patients, suggesting a link between circulatory and renal functions. Sample sizes varied across studies, with some involving small patient groups. Terlipressin appeared more effective than midodrine and octreotide in improving renal function due to its impact on mean arterial pressure (MAP). Specific findings included significant increases in arterial pressure and renal function improvement in both treatment and control groups. Conclusion. Midodrine shows potential in managing HRS, decreasing nitrite and nitrate levels in ascites patients, and improving renal function. However, significant, well-designed clinical trials are needed to determine optimal dosage, duration, and pharmacological side effects. The meta-analysis highlights opportunities for further research on midodrine in combination treatments and cost-effectiveness evaluations. Impact. This study opens avenues for future research on midodrine's role in HRS treatment, particularly in combination therapies and cost-effectiveness studies.

Low-intensity blood flow restriction (LI-BFR) and moderate-intensity improves quadriceps strength and thigh circumference in older women

Background and objectives. Weakness and atrophy in the quadriceps femoris lead to decreased functional capacity, heightened fall risk, and increased mortality among older women. While moderate-intensity strength training is generally recommended for the elderly, higher-intensity exercises carry a greater risk of injury. Low-intensity exercises with blood flow restriction offer an alternative, providing comparable benefits to high-intensity training. This study aims to evaluate the effects of moderate-intensity and low-intensity blood flow restriction exercises on quadriceps femoris strength and thigh circumference in healthy elderly women. Materials and methods. The sample size was of 88 subjects equally randomized into a moderate-intensity group and a blood-flow restriction group. The moderate-intensity group performed strengthening exercises with a load of ≥40–60% of 1RM, 3 sets, 36 repetitions. The blood-flow restriction group conducted exercises at 20–30% of 1RM, completing 75 repetitions across 4 sets, using a pressure cuff applied to the upper thigh at 50 mmHg or 40% of the Arterial Occlusion Pressure (AOP). Both groups exercised twice a week over a 6-week period. Muscle strength (assessed via dynamometer and 1RM) and thigh circumference were recorded before and after the intervention. Results. After six weeks of intervention, both groups showed a significant increase in muscle strength and thigh circumference (p <0.001). However, no notable differences were observed between the moderate intensity group and the blood flow restriction group regarding quadriceps strength (dynamometer), quadriceps 1RM strength, or thigh circumference (p >0.05). Muscle soreness was reported in 18% of participants in the moderate intensity group. Conclusion. Low-intensity resistance exercises with blood flow restriction in older women can promote strength gains and muscle hypertrophy comparable to moderate-intensity training, while offering a safer alternative.

8-Aminoguanine and its actions in the metabolic syndrome.

The metabolic syndrome is characterized by obesity, insulin resistance, dyslipidemia and hypertension and predisposes to cardiorenal injury. Here, we tested our hypothesis that 8-aminoguanine, an endogenous purine, exerts beneficial effects in Zucker Diabetic-Sprague Dawley (ZDSD) rats, a preclinical model of the metabolic syndrome. ZDSD rats were instrumented for blood pressure radiotelemetry and randomized to vehicle or 8-aminoguanine (10mg/kg/day, po). The protocol was divided into four phases: Phase 1: 17days of tap water/normal diet; Phase 2: 30days of 1% saline/normal diet; Phase 3: 28days of 1% saline/diabetogenic diet; Phase 4: acute/terminal measurements. 8-Aminoguanine: (1) decreased mean arterial blood pressure (P = 0.0004; 119.5 ± 1.0 (vehicle) versus 116.3 ± 1.0 (treated) mmHg) throughout all three phases of the radiotelemetry study; (2) rebalanced the purine metabolome away from hypoxanthine (pro-inflammatory) and towards inosine (anti-inflammatory); (3) reduced by 71% circulating IL-1β, a cytokine that contributes to hypertension-induced adverse cardiovascular events and type 2 diabetes; (4) attenuated renovascular responses to angiotensin II; (5) improved cardiac and renal histopathology; (6) attenuated diet-induced polydipsia/polyuria; and (7) reduced HbA1c. In the metabolic syndrome, 8-aminoguanine lowers blood pressure, improves diabetes and reduces organ damage, likely by rebalancing the purine metabolome leading to reductions in injurious cytokines such as IL-1β.

Comparison study between Sevoflurane/Remifentanil with Isoflurane/Remifentanil to induce hypotension in Rhinoplasty Operations

Background: Answering the question of “which modality and combination is having the upper handy?” in bleeding control during rhinoplasty surgery through controlled hypotension achieved by administering anesthesia with two different inhalation agents: sevoflurane or isoflurane, both in combination with remifentanil. Numerous studies and articles are published annually, yet the wider question regarding the efficacy of each formula has remained unaddressed. Methods: This prospective observational study utilized convenient sampling with a total of 100 patients undergoing rhinoplasty. Participants were divided into two groups: one receiving remifentanil combined with sevoflurane and the other receiving remifentanil combined with isoflurane. Controlled hypotension was achieved and monitored throughout the procedure. Results: Both anesthesia combinations effectively achieved controlled hypotension and created a dry operative field. Notably, the sevoflurane/remifentanil combination resulted in a faster onset of decreased heart rate and mean arterial blood pressure (MAP) within the first 40 minutes of the procedure compared to the isoflurane/remifentanil combination. Conclusion: The study demonstrated that both sevoflurane/remifentanil and isoflurane/remifentanil combinations are effective in controlling bleeding during rhinoplasty. Sevoflurane/remifentanil showed a quicker initial effect on cardiovascular parameters, but both protocols successfully met the primary goal of minimizing bleeding and enhancing surgical visibility.

Traditional Chinese Medicine (TCM)-Inspired Fully Printed Soft Pressure Sensor Array with Self-Adaptive Pressurization for Highly Reliable Individualized Long-Term Pulse Diagnostics.

Reliable, non-invasive, continuous monitoring of pulse and blood pressure is essential for the prevention and diagnosis of cardiovascular diseases. However, the pulse wave varies drastically among individuals or even over time in the same individual, presenting significant challenges for the existing pulse sensing systems. Inspired by pulse diagnosis methods in traditional Chinese medicine (TCM), this work reports a self-adaptive pressure sensing platform (PSP) that combines the fully printed flexible pressure sensor array with an adaptive wristband-style pressure system can identify the optimal pulse signal. Besides the detected pulse rate/width/length, "Cun, Guan, Chi" position, and "floating, moderate, sinking" pulse features, the PSP combined with a machine learning-based linear regression model can also accurately predict blood pressure such as systolic, diastolic, and mean arterial pressure values. The developed diagnostic platform is demonstrated for highly reliable long-term monitoring and analysis of pulse and blood pressure across multiple human subjects over time. The design concept and proof-of-the-concept demonstrations also pave the way for the future developments of flexible sensing devices/systems for adaptive individualized monitoring in the complex practical environments for personalized medicine, along with the support for the development of digital TCM.

Renal Medulla in Hypertension.

Studies have found that blood flow to the renal medulla is an important determinant of pressure-natriuresis and the long-term regulation of arterial pressure. First, a brief review of methods developed enabling the study of the medullary circulation is presented. Second, studies performed in rats are presented showing medullary blood flow plays a vital role in the pressure-natriuresis relationship and thereby in hypertension. Third, it is shown that chronic reduction of medullary blood flow results in hypertension and that enhancement of medullary blood flow reduces hypertension hereditary models of both salt-sensitive rats and salt-resistant forms of hypertension. The key role that medullary nitric oxide production plays in protecting this region from ischemic injury associated with circulating vasoconstrictor agents and reactive oxygen species is presented. The studies cited are largely the work of my students, research fellows, and colleagues with whom I have performed these studies dating from the late 1980s to more recent years.

Decreasing the pressure of endotracheal tube cuff slowly with a constant speed can decrease coughing incidence during extubation: a randomized clinical trial

BackgroundTo discuss whether decreasing the pressure of endotracheal tube cuff slowly with a constant speed can decrease the incidence of coughing during extubation.MethodsNinety patients undergoing elective noncardiac surgery under general anesthesia with endotracheal intubation were randomly divided into two groups: group P, the pilot balloon was connected to a syringe and an aneroid manometer through a three-way stopcock, respectively, and the decrease of cuff pressure was controlled at 3 cmH2O/s during deflating before extubation; group C, the pressure in endotracheal tube cuff was decreased suddenly with a syringe extracting the air from the cuff rapidly at once exactly before extubation. The incidence of coughing during extubation period was recorded. Mean arterial pressure (MAP) and heart rate (HR) were recorded before general anesthesia induction (T0), just before cuff deflation (T1), immediately after deflation (T2), at 1 min (T3), 3 min (T4), and 5 min after extubation (T5). The occurrence of adverse reactions was also recorded.ResultsThe initiation of coughing during extubation period occurs at immediately the time of balloon deflation. Compared with group C, the incidence of coughing was significantly decreased (P = 0.001), MAP and HR were significantly decreased at T2-T4 and T2-T5, respectively (P < 0.05 for all), and the incidence of pharyngolaryngeal discomfort after extubation was significantly reduced (P = 0.021) in group P.ConclusionsDecreasing the pressure of endotracheal tube cuff slowly with a constant speed can significantly reduce the incidence of coughing during extubating period, stabilize hemodynamics, and reduce the incidence of adverse reactions.

Targeting Kidney Inflammation After Brain Death and Cold Storage: Investigating the Potential of an NLRP3 Inflammasome Inhibitor (MCC950) for Preconditioning Donor Kidneys.

Brain death (BD) and cold storage (CS) are critical factors that induce inflammation in donor kidneys, compromising organ quality. We investigated whether treating kidneys from BD rats with an inflammasome Nod-like receptor family pyrin domain containing 3 (NLRP3) inhibitor (MCC950) followed by CS could reduce kidney inflammation. BD rats were assigned to MCC950-treated or nontreated (NT) groups. Kidneys were evaluated immediately before CS (T0) and after 12 h (T12) and 24 h (T24) of CS. Mean arterial pressure, serum creatinine, gene/protein expression, and histology were evaluated. At T0, MCC950 treatment did not affect mean arterial pressure but tended to reduce serum creatinine and ameliorated the histological score of acute tubular necrosis. However, MCC950 reduced NLRP3, caspase-1, interleukin (IL)-1β, IL-6, Kim-1, nuclear factor kappa B, tumor necrosis factor alpha, and caspase-3 gene expression while increasing IL-10 cytokine gene expression. After 12 h of CS, only the expression of the NLRP3 and caspase-1 genes decreased, and after 24 h of CS, no further changes in the gene expression profile were observed. The levels of the inflammasome proteins NLRP3, caspase-1, and IL-1β consistently decreased across all time points (T0, T12, and T24). These findings suggest that MCC950 treatment holds promise for mitigating the proinflammatory state observed in kidneys after BD and CS.

Effects of an 8-week intervention of anulom vilom pranayama combined with heartfulness meditation on psychological stress, autonomic function, inflammatory biomarkers, and oxidative stress in healthcare workers during COVID-19 pandemic: a randomized controlled trial.

Health care workers were exposed to huge stress during COVID-19 pandemic affecting their physical and mental health. Practice of anulom vilom pranayama andheartfulness meditation (AVPHFN) can improve mental and physical health and counter stress. The present study explored the effect of 8-week AVPHFN intervention on autonomic functions, emotional stress, oxidative stress, andinflammation markers in the nurse group of health-care givers. This was a randomized controlled trial where 50 nurses underwent AVPHFN and 50 participated as controls. At baseline and after 8week intervention of AVPHFN anthropometric parameters, cardiovascular parameters, autonomic function including time and frequency domain parameters, biochemical parameters, and psychological stress using the questionnaire were assessed. Forty nurses in AVPHFN group and 46 in control group completed the study. AVPHFN intervention resulted ina significant reduction in cardiovascular parameters heart rate, systolic blood pressure, diastolic blood pressure, mean arterial pressure and rate pressure product (p<0.001,p<0.001, p<0.001, p<0.001, and p<0.001, respectively), perceived stress score and depression, anxiety, andstress scale psychological variables of depression, andstress compared to the control group. Total power, ratioof low frequency to high frequency and change in successive normal sinus (NN) intervals exceeds 50 ms (p<0.01, p=0.05, and p<0.01 respectively) suggesting parasympathodominance due to higher vagal efferent activity. Serum cortisol, high-sensitivity C-reactive protein (hs-CRP), tumor necrosis factor-alpha, interleukin (IL)-1, IL-6 and telomerase significantly decreased in AVPHFN group post intervention. Eighty-week intervention of AVPHFN improved psychophysiological, autonomic and biochemistry profile of nurse group of health-care workers. AVPHFN module may be beneficial for curtailing stress and improving well-being.

The relation between socioeconomic status and invasive haemodynamics at evaluation for advanced heart failure.

Socioeconomic deprivation is a risk marker for worse prognosis in patients with heart failure (HF), and a potential barrier to referral for advanced HF evaluation. The relationship between socioeconomic status (SES) and invasive haemodynamics in patients undergoing evaluation for advanced HF therapies is unknown. We combined a consecutive clinical registry of patients evaluated for advanced HF with patient-level data on SES (household income, education, workforce status, cohabitant status and distance from home to tertiary HF centre) derived from nationwide registries. Using this information, the cohort was divided into groups of low-, medium- and high degree of socioeconomic deprivation. The associations between SES and invasive haemodynamics were explored with multiple linear regression adjusted for age and sex. A total of 631 patients were included. The median age was 53years, and 23% were women. Patients in the highest income quartile versus the lowest (Q4 vs. Q1) were older (median age 57 vs. 50years) and more often male (83% vs. 67%), both P<0.001. Increasing household income (per 100000 Danish kroner,1 EUR=7.4 DKK) was associated with lower pulmonary capillary wedge pressure (PCWP)[-0.18mmHg, 95% confidence interval (CI) -0.36 to -0.01, P=0.036] but not significantly associated with central venous pressure (CVP) (-0.07mmHg, 95% CI -0.21 to 0.06, P=0.27), cardiac index (-0.004L/min/m2, 95% CI -0.02 to 0.01, P=0.60), or pulmonary vascular resistance (PVR) (-0.003 Wood units, 95% CI -0.37 to 0.16, P=0.84). Comparing the most deprived with the least deprived group, adjusted mean PVR was higher (0.35 Wood units, 95% CI 0.02 to 0.68, P=0.04), but PCWP (0.66mmHg, 95% CI -1.49 to 2.82, P=0.55), CVP (-0.26mmHg, 95% CI -1.76 to 1.24, P=0.73) and cardiac index (-0.03L/min/m2, 95% CI -0.22 to 0.17, P=0.78) were similar. Most haemodynamic measurements were similar across layers of SES. Nevertheless, there were some indications of worse haemodynamics in patients with lower household income or a high accumulated burden of socioeconomic deprivation. Particular attention may be warranted in socioeconomically deprived patients to ensure timely referral for advanced HF evaluation.

Functional hemodynamic monitoring

Critically ill patients in the intensive care unit require intensified monitoring to control the treatment with volume and/or vasoactive substances. What role does functional hemodynamic monitoring play in controlling treatment and what techniques are used to manage this? Review of the current literature. Precise knowledge of the physiology of the cardiovascular system as well as the pathophysiology of individual clinical pictures and the possibilities of invasive and noninvasive monitoring are the prerequisites for the indications, implementation and interpretation of functional hemodynamic monitoring. An understanding of the heart-lung interaction and the influence of invasive ventilation on the volumetric target parameters, such as stroke volume variation, systolic pressure variation and pulse pressure variation as well as sonography of the inferior vena cava are indispensable prerequisites for the question of volume responsiveness. Other maneuvers, such as the passive leg raising test, can be very helpful when deciding on volume administration in everyday clinical practice. Static parameters such as central venous pressure generally play no role and if any only a subordinate one.

Discrepancy between pulmonary arterial wedge pressure and left ventricular end diastolic pressure in patients with interstitial lung disease

BackgroundRight heart catheterization (RHC) is the gold standard for diagnosing pulmonary hypertension (PH) in patients with interstitial lung disease (ILD). However, discrepancies between pulmonary arterial wedge pressure (PAWP) and left ventricular end-diastolic pressure (LVEDP) remain understudied in this population. MethodsWe conducted a retrospective analysis of data from ILD patients who underwent RHC and had concomitant LVEDP measurements. Pulmonary vascular resistance (PVR) was calculated using both PAWP and LVEDP. Patients were categorized based on PAWP and LVEDP values using a threshold of 15 mmHg and PVR values using a threshold of 2 or 3 Wood Units. After that patients were categorized as concordant or discordant if both values were on the same or opposite sides of these thresholds, respectively. A discordantly higher PAWP group (left atrial dysfunction, LAD) was defined as patients with a PAWP-LVEDP difference of more than 3mmHg. ResultsAmong 87 ILD patients, 9 patients (10.3%) showed discordance between PAWP and LVEDP. LAD was observed in 12 patients (13.8%) and was associated with lower forced vital capacity (Odd ratio [OR]: 0.956, p = 0.049) and a larger left atrium diameter (OR: 3.205, p = 0.033). Discordance in PVR values was also noted, with potential treatment targets for PH-specific therapy differing in 9 patients (22.0%) depending on whether PAWP or LVEDP was used. ConclusionsThis study highlights the clinical significance of PAWP-LVEDP discrepancies in suspected PH-ILD patients, emphasizing the need for comprehensive assessments incorporating LVEDP and clinical context for accurate diagnosis, risk stratification, and treatment decisions.

Audit of Geriatric Emergency Medicine-Unit staff compliance in providing care in line with the Age Friendly Health Systems Conceptual Framework

Abstract Background The Geriatric Emergency Medicine Unit (GEMU) in University Hospital Limerick (UHL) is in the Emergency Department for the assessment of those over the age of 75. The unit is staffed by a multi-disciplinary team with specialist skills in older person’s care. The aim of this audit was to determine assessment and documentation compliance with the Age Friendly Health Systems conceptual framework for older persons who present to GEMU. Methods A retrospective documentation review took place from patients who attended GEMU between January-March 2023. Medical record numbers were selected at random from the Health and Social Care Professionals (HSCP) team data management system with individual patient records subsequently retrieved from the Therefore Emergency Medicine (EM) patient management system. Patient records were reviewed by SW, which included Nursing, EM Doctors documentation and HSCP documentation. Results 15 charts were reviewed. Compliance varied across all areas from 0-100%. Compliance was greatest in the domains of the EWS score, mobility assessments, falls history and 4AT. Hydration and the documentation of ‘What Matters’/patient care preference were both 0%. Otherwise, compliance broadly was &amp;gt;50%. The first re-audit of 15 charts took place from December 2023-January 2024. Improvements were noted across all assessments, with 100% compliance additionally achieved in CFS, cognitive status, co-morbidities and nutritional intake. A second re-audit of 15 charts took place from March-April 2024, with further improvements seen in terms of lying and standing blood pressures and polypharmacy assessments. Conclusion Results demonstrate the continued improvements made amongst the team in adhering to the Age Friendly Health Systems Framework. Efforts are ongoing to focus specifically on the care preference component, with structured QIPs in place and a view to re-auditing in Q4 2024.

Acute effects of empagliflozin on open-loop baroreflex function and urine output in streptozotocin-induced type 1 diabetic rats

Although sympathetic suppression is considered one of the mechanisms for cardioprotection afforded by sodium–glucose cotransporter 2 (SGLT2) inhibitors, whether SGLT2 inhibition acutely modifies sympathetic arterial pressure (AP) regulation remains unclear. We examined the acute effect of an SGLT2 inhibitor, empagliflozin (10 mg/kg), on open-loop baroreflex static characteristics in streptozotocin (STZ)-induced type 1 diabetic and control (CNT) rats (n = 9 each). Empagliflozin significantly increased urine flow [CNT: 25.5 (21.7–31.2) vs. 55.9 (51.0–64.5), STZ: 83.4 (53.7–91.7) vs. 121.2 (57.0–136.0) μL·min−1·kg−1, median (1st–3rd quartiles), P < 0.001 for empagliflozin and STZ]. Empagliflozin decreased the minimum sympathetic nerve activity (SNA) [CNT: 15.7 (6.8–18.4) vs. 10.5 (2.9–19.0), STZ: 36.9 (25.7–54.9) vs. 32.8 (15.1–37.5) %, P = 0.021 for empagliflozin and P = 0.003 for STZ], but did not significantly affect the peripheral arc characteristics assessed by the SNA–AP relationship. Despite the significant increase in urine flow and changes in several baroreflex parameters, empagliflozin preserved the overall sympathetic AP regulation in STZ-induced diabetic rats. The lack of a significant change in the peripheral arc may minimize reflex sympathetic activation, thereby enhancing a cardioprotective benefit of empagliflozin.

GLP-1 Receptor Agonists and SGLT2 Inhibitors in Type 2 Diabetes: Pleiotropic Cardiometabolic Effects and Add-on Value of a Combined Therapy.

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter 2 inhibitors (SGLT2is) have proven efficacy and safety in randomized clinical trials and observational real-life studies. Besides improving glucose control, reducing body weight, and lowering arterial blood pressure (surrogate endpoints), the breakthroughs were the demonstration of a significant reduction in cardiovascular and renal events in patients with type 2 diabetes at high risk. GLP-1RAs reduce events linked to atherogenic cardiovascular disease (especially ischemic stroke) and also renal outcomes (FLOW trial with semaglutide), with a limited effect on heart failure. The most striking protective effects of SGLT2is were a marked reduction in hospitalization for heart failure and a remarkable reduced progression of chronic kidney disease. These benefits have been attributed to numerous pleiotropic effects beyond glucose-lowering action. Underlying mechanisms contributing to cardiovascular and renal protection are at least partially different between GLP-1RAs (mainly anti-atherogenic and vascular effects) and SGLT2is (mainly systemic and intrarenal hemodynamic changes). Thus, patients at high risk may benefit from complementary actions when being treated with a GLP-1RA/SGLT2i combination. Such combination has proven its efficacy on surrogate endpoints. Furthermore, posthoc subgroup analyses of cardiovascular outcome trials have suggested a greater cardiorenal protection in patients treated with a combination versus either monotherapy. The benefits of a combined therapy have been confirmed in a few retrospective cohort studies. A dedicated prospective trial comparing a combined therapy versus either monotherapy is ongoing (PRECIDENTD); however, several challenges still remain, especially the higher cost of a combined therapy and the worldwide underuse of either GLP-1RAs or SGLT2is in clinical practice, even in patients at high cardiorenal risk.

Capillary Refill Time as a Part of Routine Physical Examination in Critically Ill Patients Undergoing Vasoactive Therapy: A Prospective Study.

Background/Objectives: In critically ill patients, achieving a mean arterial pressure (MAP) of 65 mmHg is a recommended resuscitation goal to ensure proper tissue oxygenation. Unfortunately, some patients do not benefit from providing such a value, suggesting that other indices are needed for better hemodynamic assessment. Capillary refill time (CRT) has emerged as an established marker for peripheral perfusion and a therapeutic target in critical illness, but its relationship with other exponents of hypoperfusion during vasopressor support after resuscitation period still warrants further research. This study aimed to investigate whether in critically ill patients after initial resuscitation, CRT would provide information independent of other, readily accessible hemodynamic variables. Methods: Critically ill patients who were mechanically ventilated after the resuscitation period and receiving vasopressors were prospectively studied between December 2022 and June 2023. Vasopressor support was measured using norepinephrine equivalent doses (NEDs). CRT, MAP and NED were assessed simultaneously and analyzed using Spearman's rank correlation. Results: A total of 92 patients were included and 210 combined MAP-CRT-NED-Lactate records were obtained. There was no correlation between CRT and MAP (R = -0.1, p = 0.14) or lactate (R = 0.11, p = 0.13), but there was a positive weak correlation between CRT and NED (R = 0.25, p = 0.0005). In patients with hypotension, in 83% of cases (15/18), CRT was within normal range, despite different doses of catecholamines. When assessing patients with high catecholamine doses, in 58% cases (11/19), CRT was normal and MAP was usually above 65 mmHg. Conclusions: Capillary refill time provides additional hemodynamic information that is not highly related with the values of mean arterial pressure, lactate level and vasopressor doses. It could be incorporated into routine physical examination in critically ill patients who are beyond initial resuscitation.

Akkermansia muciniphila improve cognitive dysfunction by regulating BDNF and serotonin pathway in gut-liver-brain axis

BackrgroundAkkermansia muciniphila, a next-generation probiotic, is known as a cornerstone regulating the gut-organ axis in various diseases, but the underlying mechanism remains poorly understood. Here, we revealed the neuronal and antifibrotic effects of A. muciniphila on the gut-liver-brain axis in liver injury.ResultsTo investigate neurologic dysfunction and characteristic gut microbiotas, we performed a cirrhosis cohort (154 patients with or without hepatic encephalopathy) and a community cognition cohort (80 participants in one region for three years) and validated the existence of cognitive impairment in a 3,5-diethoxycarbonyl-1,4-dihydrocollidine-induced hepatic injury mouse model. The effects of the candidate strain on cognition were evaluated in animal models of liver injury. The expression of brain-derived neurotrophic factor (BDNF) and serotonin receptors was accessed in patients with fibrosis (100 patients) according to the fibrosis grade and hepatic venous pressure gradient. The proportion of A. muciniphila decreased in populations with hepatic encephalopathy and cognitive dysfunction. Tissue staining techniques confirmed gut-liver-brain damage in liver injury, with drastic expression of BDNF and serotonin in the gut and brain. The administration of A. muciniphila significantly reduced tissue damage and improved cognitive dysfunction and the expression of BDNF and serotonin. Isolated vagus nerve staining showed a recovery of serotonin expression without affecting the dopamine pathway. Conversely, in liver tissue, the inhibition of injury through the suppression of serotonin receptor (5-hydroxytryptamine 2A and 2B) expression was confirmed. The severity of liver injury was correlated with the abundance of serotonin, BDNF, and A. muciniphila.ConclusionsA. muciniphila, a next-generation probiotic, is a therapeutic candidate for alleviating the symptoms of liver fibrosis and cognitive impairment.Graphical