Light-mediated intracellular polymerization.

The synthesis of synthetic intracellular polymers offers groundbreaking possibilities in cellular biology and medical research, allowing for novel experiments in drug delivery, bioimaging and targeted cancer therapies. These macromolecules, composed of biocompatible monomers, are pivotal in manipulating cellular functions and pathways due to their bioavailability, cytocompatibility and distinct chemical properties. This protocol details two innovative methods for intracellular polymerization. The first one uses 2-hydroxy-4'-(2-hydroxyethoxy)-2-methylpropiophenone (Irgacure 2959) as a photoinitiator for free radical polymerization under UV light (365 nm, 5 mW/cm2). The second method employs photoinduced electron transfer-reversible addition-fragmentation chain-transfer polymerization with visible light (470 nm, 100 mW/cm2). We further elaborate on isolating these intracellular polymers by streptavidin/biotin interaction or immobilized metal ion affinity chromatography for polymers tagged with biotin or histidine. The entire process, from polymerization to isolation, takes ~48 h. Moreover, the intracellular polymers thus generated demonstrate significant potential in enhancing actin polymerization, in bioimaging applications and as a novel avenue in cancer treatment strategies. The protocol extends to animal models, providing a comprehensive approach from cellular to systemic applications. Users are advised to have a basic understanding of organic synthesis and cell biology techniques.

Amphiphilic Block Copolymers Containing Benzenesulfonyl Azide Groups as Visible Light-Responsive Drug Carriers for Image-Guided Delivery.

Nanoparticles (NPs) containing light-responsive polymers and imaging agents show great promise for controlled drug delivery. However, most light-responsive NPs rely on short-wavelength excitation, resulting in poor tissue penetration and potential cytotoxicity. Moreover, excessively sensitive NPs may prematurely release drugs during storage and circulation, diminishing their efficacy and causing off-target toxicity. Herein, we report visible-light-responsive NPs composed of an amphiphilic block copolymer containing responsive 4-acrylamide benzenesulfonyl azide (ABSA) and hydrophilic N,N'-dimethylacrylamide (DMA) units. The polymer pDMA-ABSA was loaded with the chemotherapy drug dasatinib and zinc tetraphenylporphyrin (ZnTPP). ZnTPP acted as an imaging reagent and a photosensitizer to reduce ABSA upon visible light irradiation, converting hydrophobic units to hydrophilic units and disrupting NPs to trigger drug release. These NPs enabled real-time fluorescence imaging in cells and exhibited synergistic chemophotodynamic therapy against multiple cancer cell lines. Our light-responsive NP platform holds great promise for controlled drug delivery and cancer theranostics, circumventing the limitations of traditional photosensitive nanosystems.

A meta-analysis evaluating wound infections and other complications following distal versus complete gastrectomy for gastric cancer.

A meta-analysis investigation was carried out to measure the wound infections (WIs) and other postoperative problems (PPs) of distal gastrectomy (DG) compared with total gastrectomy (TG) for gastric cancer (GC). A comprehensive literature investigation till February 2023 was used and 1247 interrelated investigations were reviewed. The 12 chosen investigations enclosed 2896 individuals with GC in the chosen investigations' starting point, 1375 of them were TG, and 1521 were DG. Odds ratio (OR) in addition to 95% confidence intervals (CIs) were utilized to compute the value of the WIs and other PPs of DG compared with TG for GC by the dichotomous approaches and a fixed or random model. TG had significantly higher overall PP (OR, 1.58; 95% CI, 1.15-2.18, p = 0.005), WIs (OR, 1.69; 95% CI, 1.07-2.67, p = 0.02), peritoneal abscess (PA) (OR, 2.99; 95% CI, 1.67-5.36, p < 0.001), anastomotic leakage (AL) (OR, 1.90; 95% CI, 1.21-2.97, p = 0.005) and death (OR, 2.26; 95% CI, 1.17-4.37, p = 0.02) compared to those with DG in individuals with GC. TG had significantly higher overall PP, WIs, PA, AL and death compared to those with DG in individuals with GC. However, care must be exercised when dealing with its values because of the low sample size of some of the nominated investigations for the meta-analysis.

Application of different counseling strategies for better adult asthma control.

OBJECTIVE: We aimed to compare the effectiveness of three distinct counseling methods to determine the most effective approach. METHODS: In this prospective cohort study with a two-month follow-up, A group of non-smoking adults, aged 19-60 years, were randomly collected at outpatients clinic with prior asthma diagnosis, based on the forced expiratory volume in one seconds to forced vital capacity ratio (FEV1/FVC) and the guidelines outlined by the Global Initiative for Asthma (GINA), At the baseline assessment, all patients, underwent FEV1/FVC measurements, asthma symptom evaluations using Asthma Control Test (ACT), Asthma Control Questionnaire (ACQ), and GINA symptoms control assessment questionnaire, and assessment of pressurized metered-dose inhaler (pMDI) usage. The patients were divided into three groups, each assigned a distinct counseling strategy: traditional verbal counseling, advanced counseling utilizing the Asthma smartphone-application, and a combination of advanced-verbal counseling. We conducted a two-month monitoring period for all three groups. RESULTS: Significant differences (p < .001) were observed among the three counseling groups in ACT, FEV1/FVC ratio, and GINA symptoms control assessment scores from the first month to the second month visit. Regarding ACQ, the study unveiled a noteworthy disparity in ACQ scores during the second week, with a significant difference (p = .025) observed between the verbal and advanced-verbal counseling groups. Similarly, a significant difference (p = .016) was noted between the advanced counseling group and the advanced-verbal counseling groups. CONCLUSION: The study findings indicate that the combining advanced-verbal counseling by incorporating the Asthma smartphone-application alongside traditional verbal counseling is a more effective approach for improving asthma control in adults.

Prevalence of surgical site wound infection after spine surgery in nasal colonization of methicillin-resistant Staphylococcus aureus: A meta-analysis.

The purpose of the meta-analysis was to evaluate and compare the prevalence of surgical site infection (SSI) after spine surgery (SS) in nasal colonization of methicillin-resistant Staphylococcus aureus (MRSA). The results of this meta-analysis were analysed, and the odds ratio (OR) and mean difference (MD) with 95% confidence intervals (CIs) were calculated using dichotomous or contentious random- or fixed-effect models. For the current meta-analysis, 14 examinations spanning from 2014 to 2022 were included, encompassing 18 410 people who were tested for nasal colonization after SS. MRSA-positive had a significantly higher SSI (OR, 3.65; 95% CI, 2.48-5.37, p < 0.001) compared with MRSA-negative in SS subjects. However, no significant difference was found between methicillin-susceptible Staphylococcus aureus and Staphylococcus aureus negative (OR, 0.94; 95% CI, 0.32-2.79, p = 0.91), and Staphylococcus aureus positive and negative (OR, 2.13; 95% CI, 0.26-17.41, p = 0.48) in SS subjects. The examined data revealed that MRSA colonization had a significant effect on SSI; however, methicillin-susceptible Staphylococcus aureus and Staphylococcus aureus had no significant effect on SSI in SS subjects. However, given that some comparisons included a small number of chosen studies, attention should be given to their values.

Intra-surgical optimized identification of masseteric nerve for central facial nerve neurorrhaphy: A retrospective study.

It is the aim of the study to provide a detailed intraoperative assessment of the masseteric nerve and the facial branch of the smiling muscles complex through the same superficial musculoaponeurotic system (SMAS) incision. This observational retrospective study aimed to define the straightest and safest surgical route to identify the facial nerve for the smiling muscles complex and the masseteric nerve, using distance from the tragus and zygomatic arch as anatomical landmarks. 30 patients were included in the study. The mean distance from the tragus to the masseteric nerve was 40.03 mm, the mean distance from the zygomatic arch was 12.24 mm, and the mean depth from the SMAS was 10.84 mm. Data were consistent, with little variation. The distance from the zygoma was found to be higher in male patients. There was a positive correlation between the depth to the nerve and the distance from the zygoma, but no correlation between body mass index and the other parameters studied. Within the limitations of the study it seems that the proposed standardized direct approach to the masseteric nerve is a reproducible technique that may be used to increase the safety of the procedure, reduce the operating time, and decrease the amount of dissection and related postoperative scarring, thereby fostering positive results.

Cytotoxic flavone-C-glycosides from the leaves of Dypsis pembana (H.E.Moore) Beentje & J.Dransf., Arecaceae: in vitro and molecular docking studies.

BACKGROUND: Cancer poses a health threat, with an increased incidence worldwide. Thus, it is essential to develop new natural anticancer agents. Dypsis pembana (H.E.Moore) Beentje & J.Dransf (DP) is an ornamental plant belonging to the family Arecaceae. This study aimed to isolate and identify phytoconstituents from the leaves of this plant and evaluate their in vitro cytotoxic activities. METHODS: Different chromatographic techniques were applied to fractionate the hydro-alcoholic extract of DP and separate the major phytoconstituents. The isolated compounds were structurally elucidated based on their physical and spectroscopic data. The in vitro cytotoxic activities of the crude extract and fractions thereof were evaluated against human colon carcinoma (HCT-116), human breast carcinoma (MCF-7), and human hepatocellular carcinoma (HepG-2) cell lines via MTT assay. Moreover, selected isolates were tested against HepG-2 cell line. Molecular docking analysis was performed to investigate the interactions of these compounds with two potential targets, the human topoisomerase IIα and cyclin-dependent kinase 2 enzymes. RESULTS: Thirteen diverse compounds were reported for the first time from DP, providing significant chemotaxonomic biomarkers. Among tested compounds, vicenin-II (7) was the most cytotoxic against HepG-2 cell line, with an IC50 value of 14.38 µg/mL, followed by isovitexin (13) (IC50 of 15.39 µg/mL). These experimental findings were complemented by molecular docking, which demonstrated that vicenin-II exhibited superior enzyme-binding affinities to the studied vital targets and shed light on the structure-activity relationships among the investigated flavone-C-glycosides members. CONCLUSION: The phytochemical profile of DP was characterized for the first time, reflecting chemotaxonomic data about the concerned species, genus, or even the family. Biological and computational findings revealed that vicenin-II and isovitexin are possible lead structures as inhibitors of the human topoisomerase IIα and cyclin-dependent kinase 2 enzymes.

Predictors of long-term outcomes of endoscopic submucosal dissection of early gastric neoplasia in the West: a multicenter study.

BACKGROUND: This study aimed to determine long-term outcomes of gastric endoscopic submucosal dissection (ESD) in Western settings based on the latest Japanese indication criteria, and to examine predictors of outcomes and complications. METHODS: Data were collected from consecutive patients undergoing gastric ESD at four participating centers from 2009 to 2021. Retrospective analysis using logistic regression and survival analysis was performed. RESULTS: 415 patients were included (mean age 71.7 years; 56.4 % male). Absolute indication criteria (2018 guideline) were met in 75.3 % of patients. Median follow-up was 52 months. Post-resection histology was adenocarcinoma, high grade dysplasia, and low grade dysplasia in 49.9 %, 22.7 %, and 17.1 %, respectively. Perforation, early and delayed bleeding occurred in 2.4 %, 4.3 %, and 3.4 %, respectively. Rates of en bloc and R0 resection, and recurrence on first endoscopic follow-up were 94.7 %, 83.4 %, and 2.7 %, respectively. Relative indication (2018 guideline) for ESD was associated with R1 outcome (P = 0.02). Distal location (P = 0.002) and increased procedure time (P = 0.04) were associated with bleeding, and scarring (P = 0.009) and increased procedure duration (P = 0.003) were associated with perforation. Recurrence-free survival at 2 and 5 years was 94 % and 83 %, respectively. CONCLUSION: This is the largest Western multicenter cohort and suggests that gastric ESD is safe and effective in the Western setting. A quarter of patients fell outside the new absolute indications for ESD, suggesting that Western practice involves more advanced lesions. We identified the predictors of complications, which should help to inform future Western practice and research.

Impact of negative pressure wound drainage compared with natural wound drainage after thyroid tumour surgery: A meta-analysis.

We conducted a meta-analysis to compare the effectiveness of negative pressure wound drainage to that of spontaneous wound drainage after thyroid tumour surgery. A thorough analysis of the literature up to July 2022 revealed that, of the 1234 patients who used surgery for thyroid tumours, 615 used negative pressure wound drainage and 619 used natural wound drainage. To measure the influence of negative pressure wound drainage in comparison to natural wound drainage following thyroid tumour surgery, mean difference (MD) and odds ratio (OR) with 95% confidence intervals (CIs) were measured using the contentious and dichotomous approaches with a random or fixed-effect model. Subjects who used negative pressure wound drainage had significantly higher averages for drained material (OR, 12.52; 95% CI, 6.78-18.26, P = 0.001), shorter drain placement times (MD, -1.06; 95% CI, 1.57 to -0.55, P = .001), lower rates of infection at the surgical site (OR, 0.17; 95% CI, 0.05-0.60, P = .006), higher rates of wound healing (OR, 5.91; 95% CI, 1.56-22.34, P = .009), and lower rate of wound seroma (OR, 0.21; 95% CI, 0.10-0.42, P < .001) in subjects after thyroid tumour surgery in comparison to subjects who used natural wound drainage after thyroid tumour surgery. Those who used negative pressure wound drainage had significantly higher averages of drained material, shorter drain placement times, lower rates of wound infection at the surgical site, higher rates of wound healing, and lower rates of wound seroma. Care must be used when analysing the results because of the small sample size of 7 of the 13 studies included in the meta-analysis and the lack of studies in several comparisons.

Development and validation of artificial neural networks model for detection of Barrett's neoplasia: a multicenter pragmatic nonrandomized trial (with video).

BACKGROUND AND AIMS: The aim of this study was to develop and externally validate a computer-aided detection (CAD) system for the detection and localization of Barrett's neoplasia and assess its performance compared with that of general endoscopists in a statistically powered multicenter study by using real-time video sequences. METHODS: In phase 1, the hybrid visual geometry group 16-SegNet model was trained by the use of 75,198 images and videos (96 patients) of neoplastic and 1,014,973 images and videos (65 patients) of nonneoplastic Barrett's esophagus. In phase 2, image-based validation was performed on a separate dataset of 107 images (20 patients) of neoplastic and 364 images (14 patients) of nonneoplastic Barrett's esophagus. In phase 3 (video-based external validation) we designed a real-time video-based study with 32 videos (32 patients) of neoplastic and 43 videos (43 patients) of nonneoplastic Barrett's esophagus from 4 European centers to compare the performance of the CAD model with that of 6 nonexpert endoscopists. The primary endpoint was the sensitivity of CAD diagnosis of Barrett's neoplasia. RESULTS: In phase 2, CAD detected Barrett's neoplasia with sensitivity, specificity, and accuracy of 95.3%, 94.5%, and 94.7%, respectively. In phase 3, the CAD system detected Barrett's neoplasia with sensitivity, specificity, negative predictive value, and accuracy of 93.8%, 90.7%, 95.1%, and 92.0%, respectively, compared with the endoscopists' performance of 63.5%, 77.9%, 74.2%, and 71.8%, respectively (P < .05 in all parameters). The CAD system localized neoplastic lesions with accuracy, mean precision, and mean intersection over union of 100%, 0.62, and 0.54, respectively, when compared with at least 1 of the expert markings. The processing speed of the CAD detection and localization were 5 ms/image and 33 ms/image, respectively. CONCLUSION: To our knowledge, this is the first study describing external (multicenter) validation of AI algorithms for the detection of Barrett's neoplasia on real-time endoscopic videos. The CAD system in this study significantly outperformed nonexpert endoscopists on real-time video-based assessment, achieving >90% sensitivity for neoplasia detection. This result needs to be validated during real-time endoscopic assessment.

Performance of a novel computer-aided diagnosis system in the characterization of colorectal polyps, and its role in meeting Preservation and Incorporation of Valuable Endoscopic Innovations standards set by the American Society of Gastrointestinal Endoscopy.

Background and aims: There has been an increasing role of artificial intelligence (AI) in the characterization of colorectal polyps. Recently, a novel AI algorithm for the characterization of polyps was developed by NEC Corporation (Japan). The aim of our study is to perform an external validation of this algorithm. Methods: The study was a video-based evaluation of the computer-aided diagnosis (CADx) system. Patients undergoing colonoscopy were recruited to record videos of colonic polyps. The frozen polyp images extracted from these videos were used for real-time histological prediction by the endoscopists and by the CADx system, and the results were compared. Results: A total of 115 polyp images were extracted from 66 patients. Sensitivity, negative predictive value and accuracy for diminutive polyps on white light imaging (WLI) and image-enhanced endoscopy (IEE) when assessed by CADx was 90.9% [95% confidence interval (CI) 77.3-100] and 95.8% [95% CI 87.5-100], 80% [95% CI 44.4-97.5] and 90.9% [95% CI 58.7-99.8], 84.8% [95% CI 72.7-97] and 84.6% [95%CI 71.8-94.9], respectively, compared to 48.1% [95%CI 37.7-59.1] and 72% [95% CI 62.5-81], 37.5% [95% CI 28.8-46.8] and 55% [95% CI 44.7-65.0], 53.7% [95% CI 44.2-63.2] and 66.7% [95% CI 59.7-73.3] when assessed by endoscopists. Concordance between histology and CADx-based post-polypectomy surveillance intervals was 93.02% on WLI and 96% on IEE. Conclusion: AI-based optical diagnosis is promising and has the potential to be better than the performance of general endoscopists. We believe that AI can help make real-time optical diagnoses of polyps meeting the Preservation and Incorporation of Valuable endoscopic Innovations standards set by the American Society of Gastrointestinal Endoscopy.

A novel PGPF Penicillium olsonii isolated from the rhizosphere of Aeluropus littoralis promotes plant growth, enhances salt stress tolerance, and reduces chemical fertilizers inputs in hydroponic system.

The hydroponic farming significantly enhances the yield and enables multiple cropping per year. These advantages can be improved by using plant growth-promoting fungi (PGPF) either under normal or stress conditions. In this study, the fungal strain (A3) isolated from the rhizosphere of the halophyte plant Aeluropus littoralis was identified as Penicillium olsonii based on sequence homology of its ITS region. The A3 fungus was shown to be halotolerant (up to 1 M NaCl) and its optimal growth was at 27°C, but inhibited at 40°C. In liquid culture medium, the A3 produced indole acetic acid (IAA) especially in the presence of L-tryptophan. Tobacco plants grown under hydroponic farming system were used to evaluate the promoting activity of the direct effect of A3 mycelium (DE) and the indirect effect (IDE) of its cell-free culture filtrate (A3CFF). The results showed that for the two conditions (DE or IDE) the tobacco seedlings exhibited significant increase in their height, leaf area, dry weight, and total chlorophyll content. Interestingly, the A3CFF (added to the MS liquid medium or to nutrient solution (NS), prepared from commercial fertilizers) induced significantly the growth parameters, the proline concentration, the catalase (CAT) and the superoxide dismutase (SOD) activities of tobacco plants. The A3CFF maintained its activity even after extended storage at 4°C for 1 year. Since the A3 is a halotolerant fungus, we tested its ability to alleviate salt stress effects. Indeed, when added at 1:50 dilution factor to NS in the presence of 250 mM NaCl, the A3CFF enhanced the plant salt tolerance by increasing the levels of total chlorophyll, proline, CAT, and SOD activities. In addition, the treated plants accumulated less Na+ in their roots but more K+ in their leaves. The A3CFF was also found to induce the expression of five salt stress related genes (NtSOS1, NtNHX1, NtHKT1, NtSOD, and NtCAT1). Finally, we proved that the A3CFF can reduce by half the chemical fertilizers inputs. Indeed, the tobacco plants grown in a hydroponic system using 0.5xNS supplemented with A3CFF (1:50) exhibited significantly higher growth than those grown in 0.5xNS or 1xNS. In an attempt to explain this mechanism, the expression profile of some growth related genes (nitrogen metabolism (NR1, NRT1), auxin (TRYP1, YUCCA6-like), and brassinosteroid (DET2, DWF4) biosynthesis) was performed. The results showed that all these genes were up-regulated following plant treatment with A3CFF. In summary the results revealed that the halotolerant fungus P. olsonii can stimulates tobacco plant growth, enhances its salt tolerance, and reduces by half the required chemical fertilizer inputs in a hydroponic farming system.

Expected value of artificial intelligence in gastrointestinal endoscopy: European Society of Gastrointestinal Endoscopy (ESGE) Position Statement.

This ESGE Position Statement defines the expected value of artificial intelligence (AI) for the diagnosis and management of gastrointestinal neoplasia within the framework of the performance measures already defined by ESGE. This is based on the clinical relevance of the expected task and the preliminary evidence regarding artificial intelligence in artificial or clinical settings. MAIN RECOMMENDATIONS:: (1) For acceptance of AI in assessment of completeness of upper GI endoscopy, the adequate level of mucosal inspection with AI should be comparable to that assessed by experienced endoscopists. (2) For acceptance of AI in assessment of completeness of upper GI endoscopy, automated recognition and photodocumentation of relevant anatomical landmarks should be obtained in ≥90% of the procedures. (3) For acceptance of AI in the detection of Barrett's high grade intraepithelial neoplasia or cancer, the AI-assisted detection rate for suspicious lesions for targeted biopsies should be comparable to that of experienced endoscopists with or without advanced imaging techniques. (4) For acceptance of AI in the management of Barrett's neoplasia, AI-assisted selection of lesions amenable to endoscopic resection should be comparable to that of experienced endoscopists. (5) For acceptance of AI in the diagnosis of gastric precancerous conditions, AI-assisted diagnosis of atrophy and intestinal metaplasia should be comparable to that provided by the established biopsy protocol, including the estimation of extent, and consequent allocation to the correct endoscopic surveillance interval. (6) For acceptance of artificial intelligence for automated lesion detection in small-bowel capsule endoscopy (SBCE), the performance of AI-assisted reading should be comparable to that of experienced endoscopists for lesion detection, without increasing but possibly reducing the reading time of the operator. (7) For acceptance of AI in the detection of colorectal polyps, the AI-assisted adenoma detection rate should be comparable to that of experienced endoscopists. (8) For acceptance of AI optical diagnosis (computer-aided diagnosis [CADx]) of diminutive polyps (≤5 mm), AI-assisted characterization should match performance standards for implementing resect-and-discard and diagnose-and-leave strategies. (9) For acceptance of AI in the management of polyps ≥ 6 mm, AI-assisted characterization should be comparable to that of experienced endoscopists in selecting lesions amenable to endoscopic resection.

The effect of Green green tea consumption on body mass index, lipoprotein, liver enzymes, and liver cancer: An updated systemic review incorporating a meta-analysis.

INTRODUCTION: Green tea is related to the reduction of liver enzymes, lipoprotein, and body mass index. However, some reports related green tea to the risk of developing liver cancer, but their outcomes were conflicting. Hence, the present study aimed to determine the relationship between green tea intake and lipoprotein, liver enzymes, body mass index, and liver cancer. METHODS: A systematic literature search up to January 2022 was performed and 22 studies with a total of 169599 subjects participated in the studies with 97316 subjects of them used green tea intake. Odds ratio (OR) or standardized mean difference (MD) with 95% confidence intervals (CIs) was calculated to evaluate the relationship between green tea intake and lipoprotein, liver enzymes, body mass index, and liver cancer using the dichotomous or the contentious method with a random effect model. RESULTS: Green tea intake significantly lowered the risk of developing liver cancer (OR, 0.85; 95% CI, 0.74 to 0.97, p = 0.02), and body mass index (MD, -0.69; 95% CI, -0.95to -0.42, p < 0.001) compared to no green tea intake. Also, there was a significant lowering effect of green tea intake on liver enzymes including alanine aminotransferase (MD, -0.65; 95% CI, -0.92 to -0.38, p < 0.001), and aspartate aminotransferase (MD, -0.77; 95% CI, -1.40 to -0.14, p = 0.02) compared to no green tea intake. There was also a significant lowering effect of green tea intake on lipoprotein including triglycerides (MD, -0.70; 95% CI, -1.35 to -0.04, p = 0.04), total cholesterol (MD, -0.39; 95% CI, -0.74 to -0.04, p = 0.03) and law-density lipoprotein (MD, -0.44; 95% CI, -0.69- -0.19, p < 0.001) compared to no green tea intake. However, no significant different was found between green tea intake and no green tea intake on high-density lipoprotein (MD, 0.16; 95% CI, -0.11 to 0.44, p = 0.24). CONCLUSIONS: Based on this meta-analysis, green tea intake had a significant lowering effect on the risk of developing liver cancer and had a significantly improving effect on body mass index, liver enzymes, and lipoprotein compared to no green tea intake. These results suggest that green tea may be added to the daily dietary program to improve cardiovascular status with no possible risk of liver cancer. It even may have a protecting effect against liver cancer in the usual daily number of cups.

Characterizing the Heart Rate Effects From Administration of Sugammadex to Reverse Neuromuscular Blockade: An Observational Study in Patients.

BACKGROUND: Reversal of neuromuscular blockade (NMB) with sugammadex can cause marked bradycardia and asystole. Administration of sugammadex typically occurs in a dynamic period when anesthetic adjuvants and gas concentrations are being titrated to achieve emergence. This evaluation examined the heart rate (HR) responses to sugammadex to reverse moderate to deep NMB during a steady-state period and sought mechanisms for HR changes. METHODS: Patients with normal sinus rhythm, who were undergoing elective surgery that included rocuronium for NMB, were evaluated. After surgery, while at steady-state surgical depth anesthesia with sevoflurane and mechanical ventilation, patients received either placebo or 2 or 4 mg/kg of sugammadex to reverse moderate to deep NMB. Study personnel involved in data analysis were blinded to treatment. Continuous electrocardiogram (ECG) was recorded from the 5 minutes before and 5 minutes after sugammadex/placebo administration. R-R intervals were converted to HR and averaged in 1-minute increments. The maximum prolongation of an R-R interval after sugammadex was converted to an instantaneous HR. RESULTS: A total of 63 patients were evaluated: 8 received placebo, and 38 and 17 received 2 and 4 mg/kg sugammadex. Age, body mass index, and patient factors were similar in groups. Placebo did not elicit HR changes, whereas sugammadex caused maximum instantaneous HR slowing (calculated from the longest R-R interval), ranging from 2 to 19 beats/min. There were 7 patients with maximum HR slowing >10 beats/min. The average HR change and 95% confidence interval (CI) during the 5 minutes after 2 mg/kg sugammadex were 3.1 (CI, 2.3-4.1) beats/min, and this was not different from the 4 mg/kg sugammadex group (4.1 beats/min [CI, 2.5-5.6]). HR variability derived from the standard deviation of consecutive R-R intervals increased after sugammadex. CONCLUSIONS: Sugammadex to reverse moderate and deep NMB resulted in a fast onset and variable magnitude of HR slowing in patients. A difference in HR slowing as a function of dose did not achieve statistical significance. The observational nature of the investigation prevented a full understanding of the mechanism(s) of the HR slowing.