2-Aryl-Benzoimidazoles as Type II NADH Dehydrogenase Inhibitors of Mycobacterium tuberculosis.

The nonproton pumping type II NADH dehydrogenase in Mycobacterium tuberculosis is essential for meeting the energy needs in terms of ATP under normal aerobic and stressful hypoxic environmental states. Type II NADH dehydrogenase conduits electrons into the electron transport chain in Mycobacterium tuberculosis, which results in ATP synthesis. Therefore, the inhibition of NDH-2 ensures the abolishment of the entire ATP synthesis machinery. Also, type II NADH dehydrogenase is absent in the mammalian genome, thus making it a potential target for antituberculosis drug discovery. Herein, we have screened a commercially available library of drug-like molecules and have identified a hit having a benzimidazole core moiety (6, H37Rv mc26230; minimum inhibitory concentration (MIC) = 16 µg/mL and ATP IC50 = 0.23 µg/mL) interfering with the oxidative phosphorylation pathway. Extensive medicinal chemistry optimization resulted in analogue 8, with MIC = 4 µg/mL and ATP IC50 = 0.05 µg/mL against the H37Rv mc26230 strain of Mycobacterium tuberculosis. Compounds 6 and 8 were found to be active against mono- and multidrug-resistant mycobacterium strains and demonstrated a bactericidal response. The Peredox-mCherry experiment and identification of single-nucleotide polymorphisms in mutants of CBR-5992 (a known type II NADH dehydrogenase inhibitor) were used to confirm the molecules as inhibitors of the type II NADH dehydrogenase enzyme. The safety index >10 for the test active molecules revealed the safety of test molecules.

Consequences of NICU Intubations: Incidence, Identifications, and Interventions.

OBJECTIVE: Prolonged intubation often leads to laryngeal injuries such as subglottic stenosis (SGS), especially in neonates with prematurity and congenital defects key for tissue healing. Recognizing at risk patients in the neonatal intensive care unit (NICU) is not well studied. The study's goals were to determine intubation risk factors, characterize laryngeal injuries, and calculate the incidence of intervention. STUDY DESIGN: Retrospective case review. SETTING: Quaternary pediatric referral center. METHODS: This retrospective study included all intubated patients in the NICU from April 1, 2020 to 2023. Electronic records were reviewed for demographics and intubation details. Patients were categorized to into intubation only or intervention groups, including direct laryngoscopy and bronchoscopy (DLB) and tracheostomy history. RESULTS: A total of 441 patients were identified with 94 (21%) neonates undergoing DLB. Characteristics impacting intervention included older gestational age, genetic syndromes, and congenital heart disease. Significant risk factors were older age at first intubation, recurrent intubation events, longer intubation duration, and larger endotracheal tube (ETT) diameter, but not birth weight or intubation attempts. Otolaryngology was more likely to intubate the intervention cohort. SGS overall incidence was 2.95% with balloon dilation in 6.4%. Two-thirds of neonates with DLB ultimately required tracheostomy, in which all variables remained significant risk factors except for gestational age. CONCLUSION: Older age at first intubation, more intubation events, longer intubation duration, and larger ETT increased risk for future DLB and tracheostomy but not birth weight or number of intubation attempts. Most NICU patients selected for DLB ultimately required further procedures.

Stress Echocardiography for Assessment of Diastolic Function.

PURPOSE OF REVIEW: Diastolic dysfunction is an important, though often underappreciated, cause for exertional dyspnea. Echocardiography enables noninvasive evaluation of diastolic function and filling pressure, but images acquired at rest may be insensitive for detection of exertional abnormalities. This review focuses on stress echocardiography to assess diastolic function, including traditional and novel techniques, with emphasis on specific patient sub-groups in whom this testing may be valuable. RECENT FINDINGS: Emerging data informs patient selection for diastolic stress testing. Further, increasing literature provides considerations for performance and interpretation of diastolic metrics relevant to patients with heart failure with preserved ejection fraction, hypertrophic cardiomyopathy, athletes, and those with microvascular coronary dysfunction. Methods, such as speckle-tracking and multi-modality imaging, provide additional and complementary information for non-invasive diastolic assessment. This review serves as a guide to optimally utilize existing and novel techniques of stress echocardiography for diastolic assessment across a broad range of patients.

Physiological and molecular insights into the alternate bearing in mango (Mangifera indica L.) using next-generation sequencing approaches.

India's mango productivity is hindered by many factors but more importantly due to limited understanding of the genomic complexities behind regular bearing habit. This study is the first to quantify carbohydrate fractions, protein content, and macro and micronutrient storage pools, their transportation, and contributions to regular 'Totapuri' and alternate bearer 'Bombay Green' mango varieties during the 'off' year. Deep RNA sequencing was used to assess gene expression dynamics between buds and flowers of these varieties. Differential pathway analysis showed the greatest number of differentially expressed genes in metabolic processes (1377), followed by oxido-reductase (879), hormone (80), oxidative stress (77), starvation (39), alternate bearing (8), flowering (3), meristem (3), and cellular component (2) pathways. In silico analysis showed that among 15 genes, twelve genes up-regulated in Totapuri and three in Bombay Green, confirmed by qRT-PCR. Additionally, 202 SNPs were identified in 32 alternate bearing-related genes. The study confirmed the reproductive bud's strong ability to import sugars, protein, and starch in the regular bearer variety, enhancing flowering and fruiting during off years. The mineral nutrients and biochemical constituent of the bud and leaf tissue in contrasting genotypes, showed the potential role for regular bearing in mango.

Radio-pathological characteristics of primary neuroendocrine breast carcinoma: Series of 4 cases.

Neuroendocrine breast cancers (NEBCs) are a rare and distinct subtype of breast tumors, characterized by their neuroendocrine differentiation. Despite accounting for less than 1% of all breast cancers, NEBCs present unique diagnostic and therapeutic challenges due to their heterogeneous nature and variable prognosis. Accurate imaging plays a crucial role in the diagnosis, treatment planning, and follow-up of NEBCs, yet remains a complex area due to the rarity of these tumors and overlapping features with more common breast cancers. We present a series of 4 cases of primary NEBC, emphasizing the imaging features and their histopathological correlations. All patients presented with breast lump. Diagnostic Mammography followed by Ultrasound was performed in each case. All 4 cases were categorized as Breast Imaging- Reporting and Data System (BI-RADS)-4. Trucut biopsy was performed and histopathological analysis revealed the diagnosis of NEBC. Patients underwent Surgery followed by Chemotherapy, Hormonal Therapy or Radiation therapy alone or in combination with each other depending upon the histopathological characteristics.

Glomerular injury induced by vinyl carbamate in A/J inbred mice: a novel model of membranoproliferative glomerulonephritis.

Ethyl carbamate (EC) is a process contaminant found in fermented foods and alcoholic beverages. Metabolic conversion of ethyl carbamate generates vinyl carbamate (VC), a carcinogenic metabolite. EC, as a Group 2A probable human carcinogen, and the more potent VC, are known to cause tumors in rodents. However, their effects on the kidney are unknown and were explored here. Female A/J inbred mice received an intraperitoneal injection of vehicle or VC. Beginning 5 weeks after VC injection, mice showed signs of moribund state. Mouse necropsies revealed renal glomerular injury that histopathologically recapitulated human membranoproliferative glomerulonephritis (MPGN), as evidenced by light microscopy, immunostaining for immunoglobulins and complements, and electron microscopy. To determine the molecular pathomechanisms, a post-hoc analysis was performed on a publicly available RNA-Seq transcriptome of kidneys from control rats and rats treated with fermented wine containing high concentrations of EC. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses of the differentially expressed genes revealed that the complement and coagulation cascades were a top predicted biological process involved. Furthermore, pathway-based data integration and visualization revealed that key regulators of complement activation were altered by high EC treatment. Among these, complement factors (CF) D and H, critical positive and negative regulators of the alternative pathway, respectively, were most affected, with CFD induced by 3.49-fold and CFH repressed by 5.9-fold, underscoring a hyperactive alternative pathway. Consistently, exposure of primary glomerular endothelial cells to EC or VC resulted in induction of CFD and repression of CFH, accompanied by increased fixation of C3 and C5b9. This effect seems to be mediated by Ras, one of the top genes that interact with both EC and VC, as identified by analyzing the chemical-gene/protein interactions database. Indeed, EC or VC-elicited complement activation was associated with activation of Ras signaling, but was abolished by the Ras inhibitor farnesyl thiosalicylic acid. Collectively, our findings suggest that VC, a metabolite of EC, induces glomerular injury in mice akin to human MPGN, possibly via perturbing the expression of complement regulators, resulting in an effect that favors activation of the alternative complement pathway.

Leveraging ultra-high field (7T) MRI in psychiatric research.

Non-invasive brain imaging has played a critical role in establishing our understanding of the neural properties that contribute to the emergence of psychiatric disorders. However, characterizing core neurobiological mechanisms of psychiatric symptomatology requires greater structural, functional, and neurochemical specificity than is typically obtainable with standard field strength MRI acquisitions (e.g., 3T). Ultra-high field (UHF) imaging at 7 Tesla (7T) provides the opportunity to identify neurobiological systems that confer risk, determine etiology, and characterize disease progression and treatment outcomes of major mental illnesses. Increases in scanner availability, regulatory approval, and sequence availability have made the application of UHF to clinical cohorts more feasible than ever before, yet the application of UHF approaches to the study of mental health remains nascent. In this technical review, we describe core neuroimaging methodologies which benefit from UHF acquisition, including high resolution structural and functional imaging, single (1H) and multi-nuclear (e.g., 31P) MR spectroscopy, and quantitative MR techniques for assessing brain tissue iron and myelin. We discuss advantages provided by 7T MRI, including higher signal- and contrast-to-noise ratio, enhanced spatial resolution, increased test-retest reliability, and molecular and neurochemical specificity, and how these have begun to uncover mechanisms of psychiatric disorders. Finally, we consider current limitations of UHF in its application to clinical cohorts, and point to ongoing work that aims to overcome technical hurdles through the continued development of UHF hardware, software, and protocols.

Effect of KiwiBiotic on functional constipation and related symptoms: A prospective, single-center, randomized, comparative, crossover study.

BACKGROUND: Functional constipation (FC) is a common gastrointestinal disorder characterized by abdominal pain and bloating, which can greatly affect the quality of life of patients. Conventional treatments often yield suboptimal results, leading to the exploration of alternative therapeutic approaches. AIM: To evaluate the efficacy of KiwiBiotic in the management of FC and related symptoms. METHODS: This prospective, interventional, single-center, crossover study compared the safety and effectiveness of KiwiBiotic® vs psyllium husk in managing FC, abdominal pain, and bloating. Participants diagnosed with FC were randomly assigned to receive KiwiBiotic or psyllium husk during the two treatment periods, with a 14-day washout period between them. RESULTS: Seventy participants were enrolled, 32 of whom received KiwiBiotic followed by psyllium husk, and 33 received KiwiBiotic. KiwiBiotic showed superiority over psyllium husk in alleviating abdominal pain and bloating, as evidenced by significantly lower mean scores. Furthermore, KiwiBiotic resulted in more than 90.0% of patients experiencing relief from various constipation symptoms, while psyllium husk showed comparatively lower efficacy. CONCLUSION: KiwiBiotic is an effective treatment option for FC, abdominal pain, and bloating, highlighting its potential as a promising alternative therapy for patients with FC and its associated symptoms.

Left Ventricular Wall Stress and Incident Heart Failure in Elderly Community-Dwelling Individuals.

Background: Greater left ventricular (LV) wall stress is associated with adverse outcomes among patients with prevalent heart failure (HF). Less is known about the association between LV wall stress and incident HF. Objectives: The purpose of the study was to identify clinical factors associated with wall stress and test the association between wall stress and incident HF. Methods: We studied 4,601 ARIC (Atherosclerosis Risk In Communities) study participants without prevalent HF who underwent echocardiography between 2011 and 2013. LV end systolic and diastolic wall stress (LVESWS, LVEDWS) were calculated from chamber and wall thickness, systemic blood pressure, and transmitral Doppler E/e' as a surrogate for LV end diastolic pressure. Incident HF was ascertained by International Classification of Diseases (ICD)-9/10 claims for hospitalized HF through December 31, 2016. We used Cox regression to test the association between wall stress and incident HF, adjusted for demographics, traditional cardiovascular risk factors, prevalent coronary artery disease and atrial fibrillation, creatinine, N-terminal pro-B-type natriuretic peptide, troponin, triglycerides, C-reactive protein, LV ejection fraction, and LV mass. Results: The cohort had a median age of 75 years and 58% women, with 18% identifying as Black. Median LVESWS and LVEDWS were 48.8 (25th-75th percentile: 39.3-60.1) and 18.9 (25th-75th percentile: 15.8-22.5) kdynes/cm2, respectively. LVESWS and LVEDWS were modestly related (rho = 0.30, P < 0.001). Over 4.6 years of median follow-up (156 HF events), each 1 kdyne/cm2 greater LVEDWS was significantly associated with higher risk of incident HF (HR: 1.03; 95% CI: 1.01-1.06), while LVESWS was not (HR: 1.00; 95% CI: 0.99-1.01). Conclusions: Among community-dwelling elderly individuals, greater LVEDWS is associated with a higher risk for incident HF.

Microglia and Multiple Sclerosis.

Multiple sclerosis (MS) is a devastating autoimmune disease that leads to profound disability. This disability arises from the stochastic, regional loss of myelin-the insulating sheath surrounding neurons-in the central nervous system (CNS). The demyelinated regions are dominated by the brain's resident macrophages: microglia. Microglia perform a variety of functions in MS and are thought to initiate and perpetuate demyelination through their interactions with peripheral immune cells that traffic into the brain. However, microglia are also likely essential for recruiting and promoting the differentiation of cells that can restore lost myelin in a process known as remyelination. Given these seemingly opposing functions, an overarching beneficial or detrimental role is yet to be ascribed to these immune cells. In this chapter, we will discuss microglia dynamics throughout the MS disease course and probe the apparent dichotomy of microglia as the drivers of both demyelination and remyelination.

Azacoumarin-based "turn-on" fluorescent probe for the detection and imaging of hydrogen peroxide in living cells.

Azacoumarins are a relatively unexplored group of coumarin fluorophores, despite their excellent light-emitting properties. In this report, we detail the creation and production of a fluorescent probe (PYCB) based on azacoumarin for detecting H2O2. The probe utilizes a carboxy benzyl boronic pinacol ester as the recognition unit and displays a turn-on fluorescence response at 460 nm upon exposure to H2O2. The probe shows excellent sensitivity and selectivity to H2O2, with a detection limit of 0.385 µM. PYCB also exhibited strong pH stability and selectivity for H2O2 over other reactive oxygen species (ROS). Additionally, MTT assay results demonstrated the excellent biocompatibility of PYCB in MCF-7 cell lines. Fluorescence imaging of PYCB-treated MCF-7 cells revealed enhanced blue fluorescence corresponding to varying concentrations of exogenous H2O2.

MANCR lncRNA Modulates Cell-Cycle Progression and Metastasis by Cis-Regulation of Nuclear Rho-GEF.

A significant number of the genetic alterations observed in cancer patients lie within nonprotein-coding segments of the genome, including regions coding for long noncoding RNAs (lncRNAs). LncRNAs display aberrant expression in breast cancer (BrCa), but the functional implications of this altered expression remain to be elucidated. By performing transcriptome screen in a triple negative BrCa (TNBC) isogenic 2D and 3D spheroid model, we observed aberrant expression of >1000 lncRNAs during BrCa progression. The chromatin-associated lncRNA MANCR shows elevated expression in metastatic TNBC. MANCR is upregulated in response to cellular stress and modulates DNA repair and cell proliferation. MANCR promotes metastasis as MANCR-depleted cells show reduced cell migration, invasion, and wound healing in vitro, and reduced metastatic lung colonization in xenograft experiments in vivo. Transcriptome analyses reveal that MANCR modulates expression and pre-mRNA splicing of genes, controlling DNA repair and checkpoint response. MANCR promotes the transcription of NET1A, a Rho-GEF that regulates DNA damage checkpoint and metastatic processes in cis, by differential promoter usage. Experiments suggest that MANCR regulates the expression of cancer-associated genes by modulating the association of various transcription factors and RNA-binding proteins. Our results identified the metastasis-promoting activities of MANCR in TNBC by cis-regulation of gene expression.

A Data-driven Exploration and Prediction of Deep Brain Stimulation Effects on Gait in Parkinson's Disease.

Deep brain stimulation of the subthalamic nucleus (STN-DBS) is an established treatment for motor impairment due to Parkinson's disease (PD) progression. While treated subjects mostly experience significant amelioration of symptoms, some still report adverse effects. In particular, changes in gait patterns due to the electrical stimulation have shown mixed results across studies, with overall gait velocity improvement described as the core positive outcome. This retrospective study investigates changes in the gait parameters of 50 PD patients before and 6 months after STN-DBS, by exploiting a purely data-driven approach. First, unsupervised learning identifies clusters of subjects with similar variations in the gait parameters after STN-DBS. This analysis highlights two dominant clusters (Silhouette score: 0.45, Dunn index: 0.18), with one of them associated to a worsening in walking. Then, supervised machine learning models (i.e., Support Vector Machine and Ensemble Boosting models) are trained using pre-surgery gait parameters, clinical scores, and demographic information to predict the two gait change clusters. In a Leave-One-Subject-Out validation, the best model achieves balanced accuracy 80.05 ± 3.52 %, denoting moderate predictability of both clusters. Moreover, feature importance analysis reveals the variability in the step width and in the step length asymmetry during the preoperative gait test as promising biomarkers to predict gait response to STN-DBS.

Adjuvant Everolimus in Non-Clear Cell Renal Cell Carcinoma: A Secondary Analysis of a Randomized Clinical Trial.

Importance: Clinical trial data on adjuvant therapy in patients with non-clear cell renal cell carcinoma (RCC) are scant. Objective: To evaluate the effect of adjuvant everolimus after nephrectomy on recurrence-free survival (RFS) and overall survival (OS) in patients with localized papillary and chromophobe RCC. Design, Setting, and Participants: This prespecified subgroup analysis of a phase 3 randomized clinical trial, EVEREST, included patients enrolled between April 1, 2011, and September 15, 2016. Eligible patients had fully resected RCC at intermediate-high risk (pT1 grade 3-4, N0 to pT3a grade 1-2, N0) or very-high risk (pT3a grade 3-4 to pT4 any grade or N+) for recurrence who had received radical or partial nephrectomy. Final analyses was completed in March 2022. Intervention: The intervention group received 54 weeks of everolimus (10 mg orally daily); the control group received a matching placebo. Main Outcomes and Measures: The main outcomes were RFS, OS, and rates of adverse events. For testing the hazard ratio (HR) for treatment effect, a Cox regression model was used for both OS and RFS. Results: Of 1545 adult patients with treatment-naive, nonmetastatic, fully resected RCC in EVEREST, 109 had papillary RCC (median [range] age, 60 [19-81] years; 82 [75%] male; 50 patients [46%] with very high-risk disease) and 99 had chromophobe RCC (median [range] age 51 [18-71] years; 53 [54%] male; 34 patients [34%] with very high-risk disease). Among 57 patients with papillary RCC in the intervention group, 26 (46%) completed 54 weeks of treatment, and among 53 patients with chromophobe RCC in the intervention group, 26 (49%) completed 54 weeks of treatment. With a median (IQR) follow-up of 76 (61-96) months, adjuvant everolimus did not improve RFS compared with placebo in either papillary RCC (5-year RFS: 62% vs 70%; HR, 1.19; 95% CI, 0.61-2.33; P = .61) or chromophobe RCC (5-year RFS: 79% vs 77%; HR, 0.89; 95% CI, 0.37-2.13; P = .79). In the combined non-clear RCC cohort, grade 3 or higher adverse events occurred in 48% of patients who received everolimus and 9% of patients who received placebo. Conclusions and Relevance: In this clinical trial assessing the use of adjuvant everolimus, postoperative everolimus did not show evidence of improved RFS among patients with papillary or chromophobe RCC, and results from the study do not support adjuvant everolimus for this cohort. However, since the lower bounds of the 95% CIs were 0.61 and 0.89, respectively, potential treatment benefit in these subgroups cannot be ruled out. Trial Registration: ClinicalTrials.gov Identifier: NCT01120249.

The clinical relevance of the new criteria for cirrhotic cardiomyopathy and future directions.

Cardiac dysfunction in patients with liver disease has been recognized since the 1950s. Initially attributed to shared risk factors, it is now evident that cardiac dysfunction in patients with cirrhosis can occur in the absence of known cardiac, that is, coronary artery and valvular heart disease, and across all etiologies for cirrhosis. In 1996, this myocardial dysfunction was termed cirrhotic cardiomyopathy (CCM). The pathophysiologic mechanisms underlying CCM include impaired beta-adrenergic membrane function and circulating proinflammatory and cardiotoxic substances. In 2005, the first diagnostic criteria for CCM were introduced enabling greater sensitivity and accuracy of diagnosis. Since 2005, advancements in echocardiographic methods and a better understanding of the pathophysiology of cardiac dysfunction in patients with cirrhosis necessitated a revision of CCM criteria. Changes in CCM criteria included the removal of blunted contractile or heart rate response on stress testing and the addition of global longitudinal systolic strain. The refinement of criteria for diastolic dysfunction was also incorporated into the new diagnostic approach. Since 2020, the prevalence of the disorder and clinical considerations for pretransplant, peritransplant, and posttransplant patients with cirrhosis have been further evaluated, and CCM was found to adversely impact clinical outcomes during all 3 phases of care. Future research considerations should address the timing of universal echocardiographic screening for patients with cirrhosis, the utility of biomarkers in aiding CCM diagnosis, the impact of CCM on right heart function, and the role of anti-remodeling agents after liver transplant.

Pathological concordance rate and outcomes by subtype in advanced papillary renal cell carcinoma.

OBJECTIVE: To evaluate the clinical significance of subtyping (type 1 vs 2) of papillary renal cell carcinoma (PRCC) in patients treated with targeted therapy, as well as the concordance, sensitivity and positive predictive value (PPV) of local review pathology review. METHODS: Patients with advanced refractory PRCC were randomised to receive sunitinib or cabozantinib, crizotinib or savolitinib, stratified by PRCC subtype (type 1, type 2, or not otherwise specified [NOS]/mixed) by local review. Central review was retrospectively conducted by three expert genitourinary pathologists who independently reviewed cases. The sensitivity and PPV of local review were estimated and outcomes [objective response rate (ORR), progression-free survival (PFS)] were summarised for treatment groups stratified by subtypes by central review. RESULTS: Amongst the 147 patients reviewed, the prevalence of individual subtypes varied by local or central review (type 1: 17.7% vs 29.3%; type 2: 53.1% vs 45.6%; NOS/mixed: 29.3% vs 25.2%), respectively. Individual cases were frequently reclassified and local pathology review demonstrated low sensitivity (type 1: 48%, 95% confidence interval [CI] 33, 65; type 2: 67%, 95% CI 55, 78; NOS/mixed: 43%, 95% CI 27, 61). The PPVs of local review were 80%, 57.7% and 37% for type 1, 2 and NOS/mixed, respectively. Compared to sunitinib, cabozantinib demonstrated improved PFS for both type 1 and type 2 PRCC subgroups (7.4 vs 9.0 and 2.9 vs 5.6 months, respectfully) as well as higher ORR. CONCLUSIONS: The PRCC subtype assignment did not identify a subset of patients with greater clinical benefit from cabozantinib, with significant discordance between local and central review. Our findings confirm the limited clinical value of pathological subtyping of metastatic PRCC, in line with the recent World Health Organisation 2022 guidelines. PATIENT SUMMARY: In this study, categorising papillary renal cell carcinoma into type 1 or 2 subtypes showed limited concordance between central and local pathological review and did not enrich for patients more likely to benefit from cabozantinib in the S1500 PAPMET trial.

A Comparison of Analgesic and Recovery Profiles of Ketamine, Lignocaine, and Dexmedetomidine (KeLiDex) Versus Fentanyl-Based Anesthesia in Laparoscopic Nephrectomies: A Randomized, Single-Blind, Pilot Study.

BACKGROUND: In the search for opioid-free anesthesia, notable numbers of drugs, singly or in combinations, have been tested with variable results. However, most of the drugs used are not as strong as opioids. Even if some non-opioid drugs are potent enough, they cause significant untoward effects, necessitating the use of lower effective dosages of multiple drugs as a substitute. The present pilot study evaluated low-dose combinations of ketamine, lignocaine, and dexmedetomidine (KeLiDex) against fentanyl-based anesthesia for analgesia and recovery profiles in laparoscopic nephrectomies. METHODS: Twenty patients (10 in each group) randomly received KeLiDex or fentanyl infusion as an analgesic component for balanced general anesthesia. Entire patients also received paracetamol and quadratus lumborum block-2. Anesthesia depth, neuromuscular blockade, and reversal were standardized. Intraoperative hemodynamic variation, time to extubation after reversal (T-tEAR) administration, postanesthesia care unit (PACU) discharge readiness assessed using modified Aldrete score, sedations using Richmond Agitation Sedation Scale, postoperative pain, and rescue analgesia consumptions were compared using different validated scales. P-value <0.05 was considered significant. RESULTS: The KeLiDex group had a significantly lower heart rate (HR) between 45-90 minutes and at the time of reversal. Mean arterial pressure (MAP) (mean ± standard deviation (SD)) differed significantly at only a 60-minute interval (KeLiDex group 80.90 ± 9.50 versus fentanyl group 92.60 ± 16.13 mmHg, p-value 0.041). The Friedman test for change in HR and MAP over time within each group was also insignificant. The mean ± SD of T-tEAR was 6.37 ± 2.13 in KeLiDex, and 8.18 ± 2.92 minutes in the fentanyl group, p-value 0.27. Sedation scores, Modified Alderette scores, pain scores, and rescue analgesic requirements were also comparable. CONCLUSION: KeLiDex could effectively control hemodynamics and pain both at rest and in movements in line with fentanyl-based anesthesia for laparoscopic nephrectomies. Further, recovery from the anesthesia, sedation, and PACU discharge readiness were similar.