Optimization of kidney function in cardiac surgery patients with intra-abdominal hypertension: expert opinion.

Cardiac surgery-associated acute kidney injury (CSA-AKI) affects up to 42% of cardiac surgery patients. CSA-AKI is multifactorial, with low abdominal perfusion pressure often overlooked. Abdominal perfusion pressure is calculated as mean arterial pressure minus intra-abdominal pressure (IAP). IAH decreases cardiac output and compresses the renal vasculature and renal parenchyma. Recent studies have highlighted the frequent occurrence of IAH in cardiac surgery patients and have linked the role of low perfusion pressure to the occurrence of AKI. This review and expert opinion illustrate current evidence on the pathophysiology, diagnosis, and therapy of IAH and ACS in the context of AKI.

Continuous Urine Output-Based Alert Identifies Cardiac Surgery-associated Acute Kidney Injury Earlier Than Serum Creatinine: A Prospective and Retrospective Observational Study.

OBJECTIVE(S): Acute kidney injury (AKI) is defined and staged by reduced urine output (UO) and increased serum creatinine (SCr). UO is typically measured manually and documented in the electronic health record, making early and reliable detection of oliguria-based AKI and electronic data extraction challenging. The authors investigated the diagnostic performance of continuous UO, enabled by active drain line clearance-based alerts (Accuryn AKI Alert), compared with AKI stage 2 SCr criteria and their associations with length of stay, need for continuous renal replacement therapy, and 30-day mortality. DESIGN: This study was a prospective and retrospective observational study. SETTING: Nine tertiary centers participated. PARTICIPANTS: Cardiac surgery patients were enrolled. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 522 patients were analyzed. AKI stages 1, 2, and 3 were diagnosed in 32.18%, 30.46%, and 3.64% of patients based on UO, compared with 33.72%, 4.60%, and 3.26% of patients using SCr, respectively. Continuous UO-based alerts diagnosed stage ≥1 AKI 33.6 (IQR =15.43, 95.68) hours before stage ≥2 identified by SCr criteria. A SCr-based diagnosis of AKI stage ≥2 has been designated a Hospital Harm by the Centers for Medicare & Medicaid Services. Using this criterion as a benchmark, AKI alerts had a discriminative power of 0.78. The AKI Alert for stage 1 was significantly associated with increased intensive care unit and hospital length of stay and continuous renal replacement therapy, and stage ≥2 alerts were associated with mortality. CONCLUSIONS: AKI Alert, based on continuous UO and enabled by active drain line clearance, detected AKI stages 1 and 2 before SCr criteria. Early AKI detection allows for early kidney optimization, potentially improving patient outcomes.

Efficient synthesis of indole-chalcones based glycohybrids and their anticancer activity.

Indole based glycosides belong to the class of pharmacologically active molecules and found in diverse natural compounds. Herein, we report the synthesis of 1,2,3-triazole bridged chirally enriched diverse indole-chalcones based glycohybrids. Three series of glycohybrids were designed and efficiently synthesized using d-glucose, d-galactose and d-mannose derived 1-azido glycosides. The reactions sequence involved were, the synthesis of indole derived chalcones which were formed via Claisen-Schmidt condensation reaction and subsequently N-propargylation which leads to the production of N-propargylated indole-chalcones. The N-propargylated indole-chalcones get transformed into 1,2,3-triazole bridged indole-chalcone based glycohybrids by reacting with 1-azido sugar glycosides under click-chemistry reaction conditions. Further, the biological activity of synthesized glycohybrids (n = 27) was assessed in-vitro against MDA-MB231, MCF-7, MDA-MB453 cancer, and MCF-10A normal cell lines. The selected compounds showed potent anti-oncogenic properties against MCF-7 and MDA-MB231 breast cancer cell line with IC50 values of 1.05 µM and 11.40 µM respectively, with very good selectivity index (SI > 161). The active compounds show better binding affinity as compared to co-crystallized inhibitor 1-(tert-butyl)-3-(p-tolyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine (PP1) with HCK (PTKs) proteins in molecular docking studies.

Sustainability of the Subspecialty of Anesthesiology Critical Care: An Expert Consensus and Review of the Literature.

While considerable literature exists with respect to clinical aspects of critical care anesthesiology (CCA) practice, few publications have focused on how anesthesiology-based critical care practices are organized and the challenges associated with the administration and management of anesthesiology critical care units. Currently, numerous challenges are affecting the sustainability of CCA practice, including decreased applications to fellowship positions and decreased reimbursement for critical care work. This review describes what is known about the subspecialty of CCA and leverages the experience of administrative leaders in adult critical care anesthesiologists in the United States to describe potential solutions.

Comparison of Central and Peripheral Arterial Blood Pressure Gradients in Critically Ill Patients: A Systematic Review and Meta-Analysis.

OBJECTIVES: Measurement of blood pressure taken from different anatomical sites, are often perceived as interchangeable, despite them representing different parts of the systemic circulation. We aimed to perform a systematic review and meta-analysis on blood pressure differences between central and peripheral arterial cannulation in critically ill patients. DATA SOURCES: We searched MEDLINE, Cochrane Central Register of Controlled Trials, and Embase from inception to December 26, 2023, using Medical Subject Headings (MeSH) terms and keywords. STUDY SELECTION: Observation study of adult patients in ICUs and operating rooms who underwent simultaneous central (femoral, axillary, or subclavian artery) and peripheral (radial, brachial, or dorsalis pedis artery) arterial catheter placement in ICUs and operating rooms. DATA EXTRACTION: We screened and extracted studies independently and in duplicate. We assessed risk of bias using the revised Quality Assessment for Studies of Diagnostic Accuracy tool. DATA SYNTHESIS: Twenty-four studies that enrolled 1598 patients in total were included. Central pressures (mean arterial pressure [MAP] and systolic blood pressure [SBP]) were found to be significantly higher than their peripheral counterparts, with mean gradients of 3.5 and 8.0 mm Hg, respectively. However, there was no statistically significant difference in central or peripheral diastolic blood pressure (DBP). Subgroup analysis further highlighted a higher MAP gradient during the on-cardiopulmonary bypass stage of cardiac surgery, reperfusion stage of liver transplant, and in nonsurgical critically ill patients. SBP or DBP gradient did not demonstrate any subgroup specific changes. CONCLUSIONS: SBP and MAP obtained by central arterial cannulation were higher than peripheral arterial cannulation; however, clinical implication of a difference of 8.0 mm Hg in SBP and 3.5 mm Hg in MAP remains unclear. Our current clinical practices preferring peripheral arterial lines need not change.

Pressure injury treatment by intermittent electrical stimulation (PROTECT-2): protocol for a multicenter randomized clinical trial.

BACKGROUND: Pressure ulcers account for a substantial fraction of hospital-acquired pathology, with consequent morbidity and economic cost. Treatments are largely focused on preventing further injury, whereas interventions that facilitate healing remain limited. Intermittent electrical stimulation (IES) increases local blood flow and redistributes pressure from muscle-bone interfaces, thus potentially reducing ulcer progression and facilitating healing. METHODS: The Pressure Injury Treatment by Intermittent Electrical Stimulation (PROTECT-2) trial will be a parallel-arm multicenter randomized trial to test the hypothesis that IES combined with routine care reduces sacral and ischial pressure injury over time compared to routine care alone. We plan to enroll 548 patients across various centers. Hospitalized patients with stage 1 or stage 2 sacral or ischial pressure injuries will be randomized to IES and routine care or routine care alone. Wound stage will be followed until death, discharge, or the development of an exclusion criteria for up to 3 months. The primary endpoint will be pressure injury score measured over time. DISCUSSION: Sacral and ischial pressure injuries present a burden to hospitalized patients with both clinical and economic consequences. The PROTECT-2 trial will evaluate whether IES is an effective intervention and thus reduces progression of stage 1 and stage 2 sacral and ischial pressure injuries. TRIAL REGISTRATION: ClinicalTrials.gov NCT05085288 Registered October 20, 2021.

Renin in critically ill patients.

The renin-angiotensin system (RAS) constitutes one of the principal mechanisms to maintain hemodynamic and fluid homeostasis. However, most research until now on RAS primarily focuses on its relationship with hypertension and its role in critically ill hypotensive populations is not well understood. With the approval of angiotensin II (Ang II) in the United States and Europe, following a phase 3 randomized controlled trial showing efficacy in catecholamine-resistant vasodilatory shock, there is growing interest in RAS in critically ill patients. Among the fundamental components of RAS, renin acts as the initial stimulus for the entire system. In the context of hypotension, its release increases in response to low blood pressure sensed by renal baroreceptors and attenuated negative Ang II feedback loop. Thus, elevated renin could reflect disease severity and predict poor outcomes. Studies investigating this hypothesis have validated the prognostic accuracy of renin in various critically ill populations, with several reports indicating its superiority to lactate for mortality prediction. Accordingly, renin reduction has been used to assess the effectiveness of Ang II administration. Furthermore, renin holds potential to identify patients who might benefit from Ang II treatment, potentially paving the way for personalized vasopressor management. Despite these promising data, most available evidence is derived from retrospective analysis and necessitates prospective confirmation. The absence of a rapid, point-of-care and reliable renin assay presents another hurdle to its integration into routine clinical practice. This narrative review aims to describe the current understanding and future directions of renin as a biomarker during resuscitation of critically ill patients.

Incidence and Risk Factors of Chronic Postoperative Pain in Same-day Surgery: A Prospective Cohort Study.

BACKGROUND: The amount of same-day surgery has increased markedly worldwide in recent decades, but there remains limited evidence on chronic postsurgical pain in this setting. METHODS: This study assessed pain 90 days after ambulatory surgery in an international, multicenter prospective cohort study of patients at least 45 yr old with comorbidities or at least 65 yr old. Pain was assessed using the Brief Pain Inventory. Chronic postsurgical pain was defined as a change of more than 1 point in self-rated average pain at the surgical site between baseline and 90 days, and moderate to severe chronic postsurgical pain was defined as a score greater than 4 in self-rated average pain at the surgical site at 90 days. Risk factors for chronic postsurgical pain were identified using multivariable logistic regression. RESULTS: Between November 2021 and January 2023, a total of 2,054 participants were included, and chronic postsurgical pain occurred in 12% of participants, of whom 93.1% had new chronic pain at the surgical site (i.e., participants without pain before surgery). Moderate to severe chronic postsurgical pain occurred in 9% of overall participants. Factors associated with chronic postsurgical pain were active smoking (odds ratio, 1.82; 95% CI, 1.20 to 2.76), orthopedic surgery (odds ratio, 4.7; 95% CI, 2.24 to 9.7), plastic surgery (odds ratio, 4.3; 95% CI, 1.97 to 9.2), breast surgery (odds ratio, 2.74; 95% CI, 1.29 to 5.8), vascular surgery (odds ratio, 2.71; 95% CI, 1.09 to 6.7), and ethnicity (i.e., for Hispanic/Latino ethnicity, odds ratio, 3.41; 95% CI, 1.68 to 6.9 and for First Nations/native persons, odds ratio, 4.0; 95% CI, 1.05 to 15.4). CONCLUSIONS: Persistent postsurgical pain after same-day surgery is common, is usually moderate to severe in nature, and occurs mostly in patients without chronic pain before surgery.

Robot-Assisted Video Endoscopic Inguinal Lymph Node Dissection for Penile Cancer: An Indian Multicenter Experience.

Objective: To report outcomes of multicenter series of penile cancer patients undergoing robot-assisted video endoscopic inguinal lymph node dissection (RA-VEIL). Materials and Methods: In this retrospective analysis from 3 tertiary care centers in India, consecutive intermediate-/high-risk carcinoma penis (CaP) patients with nonpalpable inguinal lymphadenopathy and/or nonbulky (<3 cm) mobile inguinal lymphadenopathy undergoing RA-VEIL were included. Patients with matted/bulky (>3 cm) and fixed lymphadenopathy were excluded. Demographic, clinical, and intraoperative data were recorded. Perioperative complications were graded by the Clavien-Dindo classification (CDC). The International Society of Lymphology (ISL) {0-III} grading was used for the assessment of lymphedema. Incidence and pattern of recurrences were assessed on follow-up. Results: From January 1, 2011, to September 30, 2023, 115 patients (230 groins) underwent bilateral RA-VEIL for CaP. The median age of the cohort was 60 (50-69) years. Clinically palpable (either unilateral or bilateral) inguinal lymphadenopathy was seen in 54 patients (47%). The "per groin" median operative time was 120 (100-140) minutes with median lymph node yield of 12 (9-16). No complications were recorded in 87.8% groins operated, with major complications (CDC 3) seen in 2.6% groins. At a median follow-up of 13.5 months, 13 patients had documented recurrences and there were 10 cancer-related deaths. No port-site recurrences were observed. No/minimal lymphedema (ISL 0/I) was seen in 94% legs. Conclusion: RA-VEIL demonstrates safety and oncologic efficacy in penile cancer patients presenting with clinically nonpalpable and/or nonbulky inguinal lymphadenopathy, with favorable functional outcomes.

ACE inhibitors and angiotensin receptor blockers differentially alter the response to angiotensin II treatment in vasodilatory shock.

BACKGROUND: Angiotensin-converting enzyme inhibitor (ACEi) and angiotensin receptor blockers (ARB) medications are widely prescribed. We sought to assess how pre-admission use of these medications might impact the response to angiotensin-II treatment during vasodilatory shock. METHODS: In a post-hoc subgroup analysis of the randomized, placebo-controlled, Angiotensin Therapy for High Output Shock (ATHOS-3) trial, we compared patients with chronic angiotensin-converting enzyme inhibitor (ACEi) use, and patients with angiotensin receptor blocker (ARB) use, to patients without exposure to either ACEi or ARB. The primary outcome was mean arterial pressure after 1-h of treatment. Additional clinical outcomes included mean arterial pressure and norepinephrine equivalent dose requirements over time, and study-drug dose over time. Biological outcomes included baseline RAS biomarkers (renin, angiotensin-I, angiotensin-II, and angiotensin-I/angiotensin-II ratio), and the change in renin from 0 to 3 h. RESULTS: We included n = 321 patients, of whom, 270 were ACEi and ARB-unexposed, 29 were ACEi-exposed and 22 ARB-exposed. In ACEi/ARB-unexposed patients, angiotensin-treated patients, compared to placebo, had higher hour-1 mean arterial pressure (9.1 mmHg [95% CI 7.6-10.1], p < 0.0001), lower norepinephrine equivalent dose over 48-h (p = 0.0037), and lower study-drug dose over 48-h (p < 0.0001). ACEi-exposed patients treated with angiotensin-II showed similarly higher hour-1 mean arterial pressure compared to ACEi/ARB-unexposed (difference in treatment-effect: - 2.2 mmHg [95% CI - 7.0-2.6], pinteraction = 0.38), but a greater reduction in norepinephrine equivalent dose (pinteraction = 0.0031) and study-drug dose (pinteraction < 0.0001) over 48-h. In contrast, ARB-exposed patients showed an attenuated effect of angiotensin-II on hour-1 mean arterial pressure versus ACEi/ARB-unexposed (difference in treatment-effect: - 6.0 mmHg [95% CI - 11.5 to - 0.6], pinteraction = 0.0299), norepinephrine equivalent dose (pinteraction < 0.0001), and study-drug dose (pinteraction = 0.0008). Baseline renin levels and angiotensin-I/angiotensin-II ratios were highest in ACEi-exposed patients. Finally, angiotensin-II treatment reduced hour-3 renin in ACEi/ARB-unexposed and ACEi-exposed patients but not in ARB-exposed patients. CONCLUSIONS: In vasodilatory shock patients, the cardiovascular and biological RAS response to angiotensin-II differed based upon prior exposure to ACEi and ARB medications. ACEi-exposure was associated with increased angiotensin II responsiveness, whereas ARB-exposure was associated with decreased responsiveness. These findings have clinical implications for patient selection and dosage of angiotensin II in vasodilatory shock. Trial Registration ClinicalTrials.Gov Identifier: NCT02338843 (Registered January 14th 2015).

Overview and Clinical Applications of Artificial Intelligence and Machine Learning in Cardiac Anesthesiology.

Artificial intelligence- (AI) and machine learning (ML)-based applications are becoming increasingly pervasive in the healthcare setting. This has in turn challenged clinicians, hospital administrators, and health policymakers to understand such technologies and develop frameworks for safe and sustained clinical implementation. Within cardiac anesthesiology, challenges and opportunities for AI/ML to support patient care are presented by the vast amounts of electronic health data, which are collected rapidly, interpreted, and acted upon within the periprocedural area. To address such challenges and opportunities, in this article, the authors review 3 recent applications relevant to cardiac anesthesiology, including depth of anesthesia monitoring, operating room resource optimization, and transthoracic/transesophageal echocardiography, as conceptual examples to explore strengths and limitations of AI/ML within healthcare, and characterize this evolving landscape. Through reviewing such applications, the authors introduce basic AI/ML concepts and methodologies, as well as practical considerations and ethical concerns for initiating and maintaining safe clinical implementation of AI/ML-based algorithms for cardiac anesthesia patient care.

Sepsis-associated acute kidney injury: recent advances in enrichment strategies, sub-phenotyping and clinical trials.

Acute kidney injury (AKI) often complicates sepsis and is associated with high morbidity and mortality. In recent years, several important clinical trials have improved our understanding of sepsis-associated AKI (SA-AKI) and impacted clinical care. Advances in sub-phenotyping of sepsis and AKI and clinical trial design offer unprecedented opportunities to fill gaps in knowledge and generate better evidence for improving the outcome of critically ill patients with SA-AKI. In this manuscript, we review the recent literature of clinical trials in sepsis with focus on studies that explore SA-AKI as a primary or secondary outcome. We discuss lessons learned and potential opportunities to improve the design of clinical trials and generate actionable evidence in future research. We specifically discuss the role of enrichment strategies to target populations that are most likely to derive benefit and the importance of patient-centered clinical trial endpoints and appropriate trial designs with the aim to provide guidance in designing future trials.

Synthesis of Chirally Enriched Pyrazolylpyrimidinone-Based Glycohybrids via Annulation of Glycals with 2-Hydrazineylpyrimidin-4(3H)-ones.

A new strategy for synthesizing chirally enriched pyrazolylpyrimidinone-based glycohybrids has been achieved, employing an annulation approach in ethanol without any additives or catalysts under microwave conditions. The designed compounds were obtained within a short reaction time (5 min). This method offers several advantages, including mild reaction conditions, a green solvent, and a metal-free approach. Furthermore, the protocol demonstrated a broad substrate scope, successfully incorporating various functional groups with stereochemical diversity and furnishing chirally enriched molecules.

Dysfunction of the renin-angiotensin-aldosterone system in human septic shock.

Sepsis and septic shock are global healthcare problems associated with mortality rates of up to 40% despite optimal standard-of-care therapy and constitute the primary cause of death in intensive care units worldwide. Circulating biomarkers of septic shock severity may represent a clinically relevant approach to individualize those patients at risk for worse outcomes early in the course of the disease, which may facilitate early and more precise interventions to improve the clinical course. However, currently used septic shock biomarkers, including lactate, may be non-specific and have variable impact on prognosis and/or disease management. Activation of the renin-angiotensin-aldosterone system (RAAS) is likely an early event in septic shock, and studies suggest that an elevated level of renin, the early and committed step in the RAAS cascade, is a better predictor of worse outcomes in septic shock, including mortality, than the current standard-of-care measure of lactate. Despite a robust increase in renin, other elements of the RAAS, including endogenous levels of Ang II, may fail to sufficiently increase to maintain blood pressure, tissue perfusion, and protective immune responses in septic shock patients. We review the current clinical literature regarding the dysfunction of the RAAS in septic shock and potential therapeutic approaches to improve clinical outcomes.

Recent developments on the synthesis of biologically active glycohybrids.

The exploration of hybridization emerges as a potent tool in advancing drug discovery research, with a significant emphasis on carbohydrate-containing hybrid scaffolds. Evidence indicates that linking carbohydrate molecules to privileged bioactive scaffolds enhances the bioactivity of drug molecules. This synergy results in a diverse range of activities, making carbohydrate scaffolds pivotal for synthesizing compound libraries with significant functional and structural diversity. Beyond their synthesis utility, these scaffolds offer applications in screening bioactive molecules, presenting alternative avenues for drug development. This comprehensive review spanning 2015 to 2023 focuses on synthesized glycohybrid molecules, revealing their bioactivity in areas such as anti-microbial, anti-cancer, anti-diabetic, anti-inflammatory activities, enzyme inhibition and pesticides. Numerous novel glycohybrids surpass positive control drugs in biological activity. This focused study not only highlights the diverse bioactivities of glycohybrids but also underscores their promising role in innovative drug development strategies.

A Pilot Study of Renin-Guided Angiotensin-II Infusion to Reduce Kidney Stress After Cardiac Surgery.

BACKGROUND: Vasoplegia is common after cardiac surgery, is associated with hyperreninemia, and can lead to acute kidney stress. We aimed to conduct a pilot study to test the hypothesis that, in vasoplegic cardiac surgery patients, angiotensin-II (AT-II) may not increase kidney stress (measured by [TIMP-2]*[IGFBP7]). METHODS: We randomly assigned patients with vasoplegia (cardiac index [CI] > 2.1l/min, postoperative hypotension requiring vasopressors) and Δ-renin (4-hour postoperative-preoperative value) ≥3.7 µU/mL, to AT-II or placebo targeting a mean arterial pressure ≥65 mm Hg for 12 hours. The primary end point was the incidence of kidney stress defined as the difference between baseline and 12 hours [TIMP-2]*[IGFBP7] levels. Secondary end points included serious adverse events (SAEs). RESULTS: We randomized 64 patients. With 1 being excluded, 31 patients received AT-II, and 32 received placebo. No significant difference was observed between AT-II and placebo groups for kidney stress (Δ-[TIMP-2]*[IGFBP7] 0.06 [ng/mL] 2 /1000 [Q1-Q3, -0.24 to 0.28] vs -0.08 [ng/mL] 2 /1000 [Q1-Q3, -0.35 to 0.14]; P = .19; Hodges-Lehmann estimation of the location shift of 0.12 [ng/mL] 2 /1000 [95% confidence interval, CI, -0.1 to 0.36]). AT-II patients received less fluid during treatment than placebo patients (2946 vs 3341 mL, P = .03), and required lower doses of norepinephrine equivalent (0.19 mg vs 4.18mg, P < .001). SAEs were reported in 38.7% of patients in the AT-II group and in 46.9% of patients in the placebo group. CONCLUSIONS: The infusion of AT-II for 12 hours appears feasible and did not lead to an increase in kidney stress in a high-risk cohort of cardiac surgery patients. These findings support the cautious continued investigation of AT-II as a vasopressor in hyperreninemic cardiac surgery patients.