Assessment of Surgeons' Stress Levels with Digital Sensors during Robot-Assisted Surgery: An Experimental Study.

Robot-Assisted Minimally Invasive Surgery (RAMIS) marks a paradigm shift in surgical procedures, enhancing precision and ergonomics. Concurrently it introduces complex stress dynamics and ergonomic challenges regarding the human-robot interface and interaction. This study explores the stress-related aspects of RAMIS, using the da Vinci XI Surgical System and the Sea Spikes model as a standard skill training phantom to establish a link between technological advancement and human factors in RAMIS environments. By employing different physiological and kinematic sensors for heart rate variability, hand movement tracking, and posture analysis, this research aims to develop a framework for quantifying the stress and ergonomic loads applied to surgeons. Preliminary findings reveal significant correlations between stress levels and several of the skill-related metrics measured by external sensors or the SURG-TLX questionnaire. Furthermore, early analysis of this preliminary dataset suggests the potential benefits of applying machine learning for surgeon skill classification and stress analysis. This paper presents the initial findings, identified correlations, and the lessons learned from the clinical setup, aiming to lay down the cornerstones for wider studies in the fields of clinical situation awareness and attention computing.

Pacemaker Channels and the Chronotropic Response in Health and Disease.

Loss or dysregulation of the normally precise control of heart rate via the autonomic nervous system plays a critical role during the development and progression of cardiovascular disease-including ischemic heart disease, heart failure, and arrhythmias. While the clinical significance of regulating changes in heart rate, known as the chronotropic effect, is undeniable, the mechanisms controlling these changes remain not fully understood. Heart rate acceleration and deceleration are mediated by increasing or decreasing the spontaneous firing rate of pacemaker cells in the sinoatrial node. During the transition from rest to activity, sympathetic neurons stimulate these cells by activating ß-adrenergic receptors and increasing intracellular cyclic adenosine monophosphate. The same signal transduction pathway is targeted by positive chronotropic drugs such as norepinephrine and dobutamine, which are used in the treatment of cardiogenic shock and severe heart failure. The cyclic adenosine monophosphate-sensitive hyperpolarization-activated current (If) in pacemaker cells is passed by hyperpolarization-activated cyclic nucleotide-gated cation channels and is critical for generating the autonomous heartbeat. In addition, this current has been suggested to play a central role in the chronotropic effect. Recent studies demonstrate that cyclic adenosine monophosphate-dependent regulation of HCN4 (hyperpolarization-activated cyclic nucleotide-gated cation channel isoform 4) acts to stabilize the heart rate, particularly during rapid rate transitions induced by the autonomic nervous system. The mechanism is based on creating a balance between firing and recently discovered nonfiring pacemaker cells in the sinoatrial node. In this way, hyperpolarization-activated cyclic nucleotide-gated cation channels may protect the heart from sinoatrial node dysfunction, secondary arrhythmia of the atria, and potentially fatal tachyarrhythmia of the ventricles. Here, we review the latest findings on sinoatrial node automaticity and discuss the physiological and pathophysiological role of HCN pacemaker channels in the chronotropic response and beyond.

Atrial fibrillation incidence after coronary artery bypass graft surgery and percutaneous coronary intervention: the prospective AFAF cohort study.

Objectives. Atrial fibrillation is a common arrhythmia in patients with ischemic heart disease. This study aimed to determine the cumulative incidence of new-onset atrial fibrillation after percutaneous coronary intervention or coronary artery bypass grafting surgery during 30 days of follow-up. Design. This was a prospective multi-center cohort study on atrial fibrillation incidence following percutaneous coronary intervention or coronary artery bypass grafting for stable angina or non-ST-elevation acute coronary syndrome. Heart rhythm was monitored for 30 days postoperatively by in-hospital telemetry and handheld thumb ECG recordings after discharge were performed. The primary endpoint was the cumulative incidence of atrial fibrillation 30 days after the index procedure. Results. In-hospital atrial fibrillation occurred in 60/123 (49%) coronary artery bypass graft and 0/123 percutaneous coronary intervention patients (p < .001). The cumulative incidence of atrial fibrillation after 30 days was 56% (69/123) of patients undergoing coronary artery bypass grafting and 2% (3/123) of patients undergoing percutaneous coronary intervention (p < .001). CABG was a strong predictor for atrial fibrillation compared to PCI (OR 80.2, 95% CI 18.1-354.9, p < .001). Thromboembolic stroke occurred in-hospital in one coronary artery bypass graft patient unrelated to atrial fibrillation, and at 30 days in two additional patients, one in each group. There was no mortality. Conclusion. New-onset atrial fibrillation during 30 days of follow-up was rare after percutaneous coronary intervention but common after coronary artery bypass grafting. A prolonged uninterrupted heart rhythm monitoring strategy identified additional patients in both groups with new-onset atrial fibrillation after discharge.

The role of heart rate variability in predicting delirium: A systematic review and meta-analysis.

Brain and heart interact through multiple ways. Heart rate variability, a non-invasive measurement is studied extensively as a predicting model for various health conditions including subarachnoid hemorrhage, cancer, and diabetes. There is limited evidence to predict delirium, an acute fluctuating disorder of brain dysfunction, as it poses a significant challenge in the intensive care unit (ICU) and post-operative setting. In this systematic review of 9 articles, heart rate variability indices were used to investigate the occurrence of post-operative and ICU delirium. This systematic review and meta-analysis reveal evidence of a strong predilection between postoperative and intensive care unit delirium and alterations in the heart rate variability, measured by mean differences for standard deviation of NN-intervals. Other heart rate variability indices [root mean squares of successive differences, low-frequency (LF), high-frequency (HF), and LF:HF ratio] showed lack of or very weak association. A non-invasive tool of brain and heart interaction may refine diagnostic predictions for acute brain dysfunctions like delirium in such population and would be an important step in delirium research.

Effects of Vitamin D Supplementation on Central Hemodynamic Parameters and Autonomic Nervous System in Obese or Overweight Individuals. / Efeitos da Suplementação de Vitamina D sobre Parâmetros Hemodinâmicos Centrais e Sistema Nervoso Autônomo em Indivíduos com Obesidade ou Sobrepeso.

BACKGROUND: Previous studies have been inconsistent in demonstrating beneficial cardiovascular effects of vitamin D supplementation. OBJECTIVE: To evaluate the effects of vitamin D3 supplementation on central hemodynamic parameters and autonomic activity in obese/overweight individuals with low vitamin D levels (<30ng/dl). METHODS: Adults 40-65 years old with body mass index ≥25<40 kg/m2 were enrolled in this prospective, randomized, double-blind clinical trial (NCT05689632). Central hemodynamics was assessed using the oscillometric method (Mobil-O-Graph®), and heart rate variability using a Polar heart rate monitor (Kubios® software). Patients (n=53) received a placebo in the control group (CO, n=25) or vitamin D3 (VD, n=28) 7000 IU/day, and were evaluated before (W0) and after 8 weeks (W8) with a significance level of 0.05. RESULTS: The groups were homogeneous regarding age (51±6 vs 52±6 years, p=0.509) and vitamin D levels (22.8±4.9 vs 21.7±4.5ng/ml, p=0.590). At W8, the VD group had significantly higher levels of vitamin D (22.5 vs 35.6ng/ml, p<0.001). Only the VD group showed a significant reduction in systolic blood pressure (SBP; 123±15 vs 119±14mmHg, p=0.019) and alkaline phosphatase (213±55 vs 202±55mg/dl, p=0.012). The CO group showed an increase in augmentation pressure (AP: 9 vs 12 mmHg, p=0.028) and augmentation index (AIx: 26 vs 35%, p=0.020), which was not observed in the VD group (AP: 8 vs 8 mmHg, AIx: 26 vs 25%, p>0.05). VD group showed an increase in the parasympathetic nervous system index (PNSi) (-0.64±0.94 vs -0.16±1.10, p=0.028) and the R-R interval (866±138 vs 924±161 ms, p= 0.026). CONCLUSION: In this sample, eight weeks of daily vitamin D supplementation resulted in an improvement in blood pressure levels and autonomic balance.

FUNDAMENTO: Estudos prévios têm sido inconsistentes em demonstrar efeitos cardiovasculares benéficos da suplementação de vitamina D. OBJETIVO: Avaliar efeitos da suplementação de vitamina D3 sobre parâmetros hemodinâmicos centrais e atividade autonômica em indivíduos obesos/sobrepeso e baixos níveis de vitamina D (<30ng/dl). MÉTODOS: Ensaio clínico prospectivo, randomizado, duplo-cego (NCT05689632), adultos 40-65 anos com índice de massa corporal ≥25<40 kg/m2. Hemodinâmica central avaliada por método oscilométrico (Mobil-O-Graph®), variabilidade da frequência cardíaca utilizando frequencímetro Polar (software Kubios®). Os pacientes (n=53) receberam placebo no grupo controle (CO, n=25) ou vitamina D3 (VD, n=28) 7000 UI/dia, avaliados antes (S0) e após 8 semanas (S8) com nível de significância de 0,05. RESULTADOS: Os grupos foram homogêneos na idade (51±6 vs. 52±6 anos, p=0,509) e níveis de vitamina D (22,8±4,9 vs. 21,7±4,5ng/ml, p=0,590). Na S8, o grupo VD apresentou níveis significativamente maiores de vitamina D (22,5 vs. 35,6ng/ml, p<0,001). Apenas o grupo VD mostrou redução significativa da pressão arterial sistólica (PAS; 123±15 vs. 119±14mmHg, p=0,019) e fosfatase alcalina (213±55 vs. 202±55mg/dl, p=0,012). O grupo CO mostrou elevação da pressão de aumento (AP: 9 vs. 12mmHg, p=0,028) e do índice de incremento (Aix: 26 vs. 35%, p=0,020), o que não foi observado no grupo VD (AP: 8 vs. 8mmHg, Aix: 26 vs. 25%, p>0,05). Grupo VD apresentou aumento no índice do sistema nervoso (iSN) parassimpático (-0,64±0,94 vs. -0,16±1,10, p=0,028) e no intervalo R-R (866±138 vs. 924±161ms, p=0,026). CONCLUSÃO: Nesta amostra, a suplementação diária de vitamina D durante oito semanas resultou em melhora dos níveis pressóricos, parâmetros hemodinâmicos centrais e do equilíbrio autonômico.

Concentration-QTc modeling of sitravatinib in patients with advanced solid malignancies.

Sitravatinib (MGCD516) is an orally available, small molecule, tyrosine kinase inhibitor that has been evaluated in patients with advanced solid tumors. Concentration-corrected QT interval (QTc; C-QTc) modeling was undertaken, using 767 matched concentration-ECG observations from 187 patients across two clinical studies in patients with advanced solid malignancies, across a dose range of 10-200 mg, via a linear mixed-effects (LME) model. The effect on heart rate (HR)-corrected QT interval via Fridericia's correction method (QTcF) at the steady-state maximum concentration (Cmax,ss) for the sitravatinib proposed therapeutic dosing regimen (100 mg malate once daily [q.d.]) without and with relevant intrinsic and extrinsic factors were predicted. No significant changes in HR from baseline were observed. Hysteresis between sitravatinib plasma concentration and change in QTcF from baseline (ΔQTcF) was not observed. There was no significant relationship between sitravatinib plasma concentration and ΔQTcF. The final C-QTc model predicted a mean (90% confidence interval [CI]) ΔQTcF of 3.92 (1.95-5.89) ms and 2.94 (0.23-6.10) ms at the proposed therapeutic dosing regimen in patients with normal organ function (best case scenario) and patients with hepatic impairment (worst-case scenario), respectively. The upper bounds of the 90% CIs were below the regulatory threshold of concern of 10 ms. The results of the described C-QTc analysis, along with corroborating results from nonclinical safety pharmacology studies, indicate that sitravatinib has a low risk of QTc interval prolongation at the proposed therapeutic dose of 100 mg malate q.d.

Novel predictive approaches for drug-induced convulsions in non-human primates using machine learning and heart rate variability analysis.

Drug-induced convulsions are a major challenge to drug development because of the lack of reliable biomarkers. Using machine learning, our previous research indicated the potential use of an index derived from heart rate variability (HRV) analysis in non-human primates as a biomarker for convulsions induced by GABAA receptor antagonists. The present study aimed to explore the application of this methodology to other convulsants and evaluate its specificity by testing non-convulsants that affect the autonomic nervous system. Telemetry-implanted males were administered various convulsants (4-aminopyridine, bupropion, kainic acid, and ranolazine) at different doses. Electrocardiogram data gathered during the pre-dose period were employed as training data, and the convulsive potential was evaluated using HRV and multivariate statistical process control. Our findings show that the Q-statistic-derived convulsive index for 4-aminopyridine increased at doses lower than that of the convulsive dose. Increases were also observed for kainic acid and ranolazine at convulsive doses, whereas bupropion did not change the index up to the highest dose (1/3 of the convulsive dose). When the same analysis was applied to non-convulsants (atropine, atenolol, and clonidine), an increase in the index was noted. Thus, the index elevation appeared to correlate with or even predict alterations in autonomic nerve activity indices, implying that this method might be regarded as a sensitive index to fluctuations within the autonomic nervous system. Despite potential false positives, this methodology offers valuable insights into predicting drug-induced convulsions when the pharmacological profile is used to carefully choose a compound.

Effects of intrarenal pelvic infusion of tumour necrosis factor-α and interleukin 1-ß on reno-renal reflexes in anaesthetised rats.

OBJECTIVE: Reno-renal reflexes are disturbed in cardiovascular and hypertensive conditions when elevated levels of pro-inflammatory mediators/cytokines are present within the kidney. We hypothesised that exogenously administered inflammatory cytokines tumour necrosis factor alpha (TNF-α) and interleukin (IL)-1ß modulate the renal sympatho-excitatory response to chemical stimulation of renal pelvic sensory nerves. METHODS: In anaesthetised rats, intrarenal pelvic infusions of vehicle [0.9% sodium chloride (NaCl)], TNF-α (500 and 1000 ng/kg) and IL-1ß (1000 ng/kg) were maintained for 30 min before chemical activation of renal pelvic sensory receptors was performed using randomized intrarenal pelvic infusions of hypertonic NaCl, potassium chloride (KCl), bradykinin, adenosine and capsaicin. RESULTS: The increase in renal sympathetic nerve activity (RSNA) in response to intrarenal pelvic hypertonic NaCl was enhanced during intrapelvic TNF-α (1000 ng/kg) and IL-1ß infusions by almost 800% above vehicle with minimal changes in mean arterial pressure (MAP) and heart rate (HR). Similarly, the RSNA response to intrarenal pelvic adenosine in the presence of TNF-α (500 ng/kg), but not IL-1ß, was almost 200% above vehicle but neither MAP nor HR were changed. There was a blunted sympatho-excitatory response to intrapelvic bradykinin in the presence of TNF-α (1000 ng/kg), but not IL-1ß, by almost 80% below vehicle, again without effect on either MAP or HR. CONCLUSION: The renal sympatho-excitatory response to renal pelvic chemoreceptor stimulation is modulated by exogenous TNF-α and IL-1ß. This suggests that inflammatory mediators within the kidney can play a significant role in modulating the renal afferent nerve-mediated sympatho-excitatory response.

Effects of interval training on haemodynamic variables after coronary artery bypass graft: A meta-analysis.

Objective: To assess the combined impact of interval training programme on haemodynamic variables, specifically blood pressure and heart rate, in patients having undergone coronary artery bypass graft surgery. METHODS: The meta-analysis was conducted from October to December 2022, and comprised search on PubMed, MEDLINE, Web of Science, PeDro, EMBASE, Science Direct, Cochrane Central Register of Controlled Clinical Trials, Google Scholar and Scopus electronic databases by two researchers independently for literature published between 2009 and 2020 related to the effects of interval training on coronary artery bypass graft patients. Meta-analysis was then performed to analyse the effects of an interval training on systolic blood pressure, diastolic blood pressure, and heart rate. The meta-analysis was performed in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. RESULTS: Of the 122 studies initially located, 7 were related to the effects of different forms of interval trainings and their impact on systolic and diastolic blood pressure of the patients, and 5 studies analysing the effects of interval trainings on heart rate. Interval training showed mild improvement in decreasing SBP compared to control groups. Standardized mean difference suggested an effect size of -0.226 in random effect model (I2=52.01; p=0.064). Similarly, a small effect size of 0.136 (I2=39.19%, p=0.14) was observed for diastolic blood pressure. Also, there was a small effect size of 0.155 (I2= 28.08, p=0.23) observed for heart rate. Conclusion: Interval training programmes, including high-intensity interval training, low-volume interval training, and aerobic interval training, had a small effect on systolic blood pressure, whereas continuous training protocols had a similarly small effect size on diastolic blood pressure and heart rate.

Stress responses in surgical trainees during simulation-based training courses in laparoscopy.

BACKGROUND: Simulation-based training courses in laparoscopy have become a fundamental part of surgical training programs. Surgical skills in laparoscopy are challenging to master, and training in these skills induces stress responses in trainees. There is limited data on trainees' stress levels, the stress responses related to training on different laparoscopic simulators, and how previous experiences influence trainees' stress response during a course. This study investigates physiologic, endocrine and self-reported stress responses during simulation-based surgical skills training in a course setting. METHODS: We conducted a prospective observational study of trainees attending basic laparoscopic skills training courses at a national training centre. During the three-day course, participants trained on different laparoscopic simulators: Two box-trainers (the D-box and P.O.P. trainer) and a virtual reality simulator (LAPMentor™). Participants' stress responses were examined through heart rate variability (HRV), saliva cortisol, and the State Trait Anxiety Inventory-6 (STAI-6). The correlation between previous laparoscopic experiences and stress response measurements was explored. RESULTS: Twenty-four surgical trainees were included in the study. Compared to resting conditions, stress measures were significantly higher during simulation-training activity (the D-box (SDNN = 58.5 ± 23.4; LF/HF-ratio = 4.58 ± 2.71; STAI-6 = 12.3 ± 3.9, P < 0.05), the P.O.P trainer (SDNN = 55.7 ± 7.4; RMSSD = 32.4 ± 17.1; STAI-6 = 12.1 ± 3.9, P < 0.05), and the LAPMentor™ (SDNN = 59.1 ± 18.5; RMSSD = 34.3 ± 19.7; LF/HF-ratio = 4.71 ± 2.64; STAI-6 = 9.9 ± 3.0, P < 0.05)). A significant difference in endocrine stress response was seen for the simulation-training activity on the D-box (saliva cortisol: 3.48 ± 1.92, P < 0.05), however, no significant differences were observed between the three simulators. A moderate correlation between surgical experience, and physiologic and endocrine stress response was observed (RMSSD: r=-0.31; SDNN: r=-0.42; SD2/SD1 ratio: r = 0.29; Saliva cortisol: r = 0.46; P < 0.05), and a negative moderate correlation to self-reported stress (r=-0.42, P < 0.05). CONCLUSION: Trainees have a significant higher stress response during simulation-training compared to resting conditions, with no difference in stress response between the simulators. Significantly higher cortisol levels were observed on the D-box, indicating that simulation tasks with time pressure stress participants the most. Trainees with more surgical experience are associated with higher physiologic stress measures, but lower self-reported stress scores, demonstrating that surgical experience influences trainees' stress response during simulation-based skills training courses.

Defining Ultra-Massive Transfusion through a Systematic Review.

Background: Despite the widespread use of ultra-massive transfusion (UMT) as an intervention for trauma patients in hemorrhagic shock, no standard definition exists. We performed a systematic review to determine a consensus definition for UMT. Methods: A search was performed from 1979-2022. The authors screened studies defining UMT and associated outcomes as defined by our prespecified PICO questions. The PRISMA guidelines were used. Results: 1662 articles met criteria for eligibility assessment, 17 for full-text review and eight for data extraction. Only two studies demonstrated a consensus definition of UMT, which used ≥20 units of red blood cell product within 24hrs. Parameters associated with increased mortality included lower blood pressure, lower pulse and lower Glasgow Coma Score at the time of presentation and a higher injury severity score and undergoing a resuscitative thoracotomy. Conclusions: The absence of a consensus definition for UMT raises challenges from clinical, research and ethical perspectives. Based on our findings, the authors advocate for the feasibility of standardizing the definition of UMT as ≥20 units of red blood cell product within 24hrs.

Association of chronotropic incompetence with reduced cardiorespiratory fitness in older adults with HIV.

OBJECTIVE: Understanding the physiological drivers of reduced cardiorespiratory fitness in people with HIV (PWH) will inform strategies to optimize healthspan. Chronotropic incompetence is common in heart failure and associated with low cardiorespiratory fitness yet is understudied in PWH. The objective was to determine the prevalence of chronotropic incompetence and its relationship with cardiorespiratory fitness. DESIGN: Participants were PWH at least 50 years of age with no prior history of heart failure or coronary heart disease who were enrolled in a randomized exercise trial. Baseline cardiopulmonary exercise testing (CPET) was used to measure cardiorespiratory fitness as peak oxygen consumption (VO2peak) and calculate the chronotropic index from heart rate values. Chronotropic incompetence was defined as an index less than 80%. RESULTS: The 74 participants were on average 61 years old, 80% Black or African American, and 93% men. Chronotropic incompetence was present in 31.1%. VO2peak was significantly lower among participants with chronotropic incompetence compared with participants without chronotropic incompetence [mean (SD) ml/min/kg: 20.9 (5.1) vs. 25.0 (4.5), P = 0.001]. Linear regression showed that chronotropic incompetence and age were independent predictors of VO2peak, but smoking and comorbidity were not. The chronotropic index correlated with VO2peak (r = 0.48, P < 0.001). CONCLUSION: Among older PWH without heart failure or coronary heart disease, chronotropic incompetence was present in approximately one-third of individuals and was associated with clinically relevant impaired cardiorespiratory fitness. Investigation of chronotropic incompetence in large cohorts which includes PWH and heart failure may contribute to strategies that promote healthy aging with HIV infection and offer a preclinical window for intervention.

[Afferent baroreflex failure with hyponatremia: A case report].

Afferent baroreflex failure (ABF) is a rare disease. It refers to the clinical syndrome caused by the impairment of the afferent limb of the baroreflex or its central connections at the level of the medulla. The recognized causes include trauma, surgery in related areas (radical neck tumor surgery, carotid endarterectomy), neck radiotherapy, brain stem stroke, tumor growth paraganglioma and hereditary diseases, among which the most common cause is extensive neck surgery or radiotherapy for neck cancer. The main manifestations are fluctuating hypertension, orthostatic hypotension, paroxysmal tachycardia and bradycardia. This case is a young man, whose main feature is blood pressure fluctuation, accom-panied by neurogenic orthostatic hypotension (nOH). After examination, the common causes of hypertension and nOH were ruled out. Combined with the previous neck radiotherapy and neck lymph node dissection, it was considered that the blood pressure regulation was abnormal due to the damage of carotid sinus baroreceptor after radiotherapy for nasopharyngeal carcinoma and neck lymph node dissection, which was called ABF. At the same time, the patient was complicated with chronic hyponatremia. Combined with clinical and laboratory examination, the final consideration was caused by syndrome of in- appropriate antidiuretic hormone (SIADH). Baroreceptors controlled the secretion of heart rate, blood pressure and antidiuretic hormone through the mandatory "inhibition" signal. We speculate that the carotid sinus baroreceptor was damaged after neck radiotherapy and surgery, which leads to abnormal blood pressure regulation and nOH, while the function of inhibiting ADH secretion was weakened, resulting in higher ADH than normal level and mild hyponatremia. The goal of treating ABF patients was to reduce the frequency and amplitude of sudden changes in blood pressure and heart rate, and to alleviate the onset of symptomatic hypotension. At present, drug treatment is still controversial, and non-drug treatment may alleviate some patients' symptoms, but long-term effective treatment still needs further study. The incidence of ABF is not high, but it may lead to serious cardiovascular and cerebrovascular events, and the mechanism involved is extremely complicated, and there are few related studies. The reports of relevant medical records warn that patients undergoing neck radiotherapy or surgery should minimize the da-mage to the baroreceptor in the carotid sinus in order to reduce the adverse prognosis caused by complications.

Independent and interactive associations of heart rate and obesity with type 2 diabetes mellites: A population-based study.

BACKGROUND: Although obesity and heart rate (HR) were closely related to the prevalence and development of type 2 diabetes mllitus (T2DM), few studies have shown a co-association effect of them on T2DM. We aimed at assessing the interactive effects of HR and obesity with prevalence of T2DM in Chinese population, providing the exact cutpoint of the risk threshold for blood glucose with high HR. MATERIALS AND METHODS: In the Risk Evaluation of cAncers in Chinese diabeTic Individuals: a lONgitudinal study (REACTION) cohorts (N = 8398), the relationship between HR and T2DM was explored by linear regression, logistic regression, and restricted cubic spline, and odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Interaction terms between HR and body mass index (BMI) and HR and waist circumference (WC) were introduced into the logistic regression model. RESULTS: In those with HR > 88.0 beats/min, fasting plasma glucose and oral glucose tolerance tests were significantly correlated with HR, and the prevalence of T2DM was highly correlated with HR (all p < .05). There were interactive associations of HR and obesity in patients with T2DM with HR < 74 beats/min. CONCLUSION: High HR was in interaction with obesity, associating with prevalence of T2DM. The newly subdivided risk threshold for HR with T2DM might be HR > 88 beats/minute.

A simple and rapid pre-clinical in vivo model reveals comparative cardiotoxicity profiles of kinase inhibitors.

Despite significant success, targeted therapeutics such as kinase inhibitors (KIs) still pose adverse events such as the cardiotoxicity. There is a lot of variation in the type and intensity of cardiotoxicity caused by different KIs and current pre-clinical models are inadequate to predict it. Thus, there is a need to develop more simple and rapid models for screening of novel KIs at the pre-clinical step itself. We thus aimed to establish a rapid and robust pre-clinical animal model for predicting cardiotoxicity of KIs and identify comparative cardiotoxicity profiles of a panel of FDA-approved KIs. Heart rate measurement and survival analysis of Daphnia was performed at regular intervals following treatment with ten KIs that were approved for the treatment of various cancers. The heart rates of Daphnia as well as the survival varied between KIs in a dose and time dependent manner suggesting differential cardiotoxicity profiles of various KIs. Further, the correlation between the cardiotoxicity and survival also varied among the ten KIs. Importantly, sorafenib and vemurafenib displayed maximum and least cardiotoxicity, respectively. The comparative cardiotoxicity profiles also are in conformity with the previous studies indicating the utility of Daphnia as a valuable and relevant animal model to rapidly predict the cardiotoxicity of novel KIs at a pre-clinical stage.

One-lung ventilation with fixed and variable tidal volumes on oxygenation and pulmonary outcomes: A randomized trial.

OBJECTIVE: Test the hypothesis that one-lung ventilation with variable tidal volume improves intraoperative oxygenation and reduces postoperative pulmonary complications after lung resection. BACKGROUND: Constant tidal volume and respiratory rate ventilation can lead to atelectasis. Animal and human ARDS studies indicate that oxygenation improves with variable tidal volumes. Since one-lung ventilation shares characteristics with ARDS, we tested the hypothesis that one-lung ventilation with variable tidal volume improves intraoperative oxygenation and reduces postoperative pulmonary complications after lung resection. DESIGN: Randomized trial. SETTING: Operating rooms and a post-anesthesia care unit. PATIENTS: Adults having elective open or video-assisted thoracoscopic lung resection surgery with general anesthesia were randomly assigned to intraoperative ventilation with fixed (n = 70) or with variable (n = 70) tidal volumes. INTERVENTIONS: Patients assigned to fixed ventilation had a tidal volume of 6 ml/kgPBW, whereas those assigned to variable ventilation had tidal volumes ranging from 6 ml/kg PBW ± 33% which varied randomly at 5-min intervals. MEASUREMENTS: The primary outcome was intraoperative oxygenation; secondary outcomes were postoperative pulmonary complications, mortality within 90 days of surgery, heart rate, and SpO2/FiO2 ratio. RESULTS: Data from 128 patients were analyzed with 65 assigned to fixed-tidal volume ventilation and 63 to variable-tidal volume ventilation. The time-weighted average PaO2 during one-lung ventilation was 176 (86) mmHg in patients ventilated with fixed-tidal volume and 147 (72) mmHg in the patients ventilated with variable-tidal volume, a difference that was statistically significant (p < 0.01) but less than our pre-defined clinically meaningful threshold of 50 mmHg. At least one composite complication occurred in 11 (17%) of patients ventilated with variable-tidal volume and in 17 (26%) of patients assigned to fixed-tidal volume ventilation, with a relative risk of 0.67 (95% CI 0.34-1.31, p = 0.24). Atelectasis in the ventilated lung was less common with variable-tidal volumes (4.7%) than fixed-tidal volumes (20%) in the initial three postoperative days, with a relative risk of 0.24 (95% CI 0.01-0.8, p = 0.02), but there were no significant late postoperative differences. No other secondary outcomes were both statistically significant and clinically meaningful. CONCLUSION: One-lung ventilation with variable tidal volume does not meaningfully improve intraoperative oxygenation, and does not reduce postoperative pulmonary complications.

Adult vasovagal syncope with abdominal pain diagnosed by head-up tilt combined with transcranial doppler: a preliminary study.

BACKGROUND: Syncope is a common condition that increases the risk of injury and reduces the quality of life. Abdominal pain as a precursor to vasovagal syncope (VVS) in adults is rarely reported and is often misdiagnosed.​. METHODS: We present three adult patients with VVS and presyncopal abdominal pain diagnosed by synchronous multimodal detection (transcranial Doppler [TCD] with head-up tilt [HUT]) and discuss the relevant literature. RESULTS: Case 1: A 52-year-old man presented with recurrent decreased consciousness preceded by six months of abdominal pain. Physical examinations were unremarkable. Dynamic electrocardiography, echocardiography, head and neck computed tomography angiography, magnetic resonance imaging (MRI), and video electroencephalogram showed no abnormalities. Case 2: A 57-year-old woman presented with recurrent syncope for 30 + years, accompanied by abdominal pain. Physical examination, electroencephalography, and MRI showed no abnormalities. Echocardiography showed large right-to-left shunts. Case 3: A 30-year-old woman presented with recurrent syncope for 10 + years, with abdominal pain as a precursor. Physical examination, laboratory analysis, head computed tomography, electrocardiography, and echocardiography showed no abnormalities. Syncope secondary to abdominal pain was reproduced during HUT. Further, HUT revealed vasovagal syncope, and synchronous TCD showed decreased cerebral blood flow; the final diagnosis was VVS in all cases. CONCLUSIONS: Abdominal pain may be a precursor of VVS in adults, and our findings enrich the clinical phenotypic spectrum of VVS. Prompt recognition of syncopal precursors is important to prevent incidents and assist in treatment decision-making. Abdominal pain in VVS may be a sign of sympathetic overdrive. Synchronous multimodal detection can help in diagnosing VVS and understanding hemodynamic mechanisms.

High Anxiety Levels before Elective Cesarean Section Can Negatively Affect the Mother and Fetus.

BACKGROUND: Both pregnancy and surgery cause anxiety. This situation may negatively affect the health of the mother and baby. AIM: The effect of anxiety level before cesarean section (CS) on feto-maternal outcomes was investigated. METHODS: The preoperative anxiety score was determined with the State-Trait Anxiety Inventory (STAI) in 224 pregnant women who were planned for elective CS. RESULTS: Among patients, 33.5% were in the low anxiety group, 27.2% in the moderate, and 39.3% in the high anxiety group. The average birth weight in the low anxiety group was noticeably higher than that of the high anxiety group (P = 0.018). The mean heart rate at postop 1st and 24th hour in the high anxiety group was higher than the moderate anxiety group (P < 0.028). In addition, diastolic blood pressure (DBP) at the sixth hour in the low anxiety group was found to be lower than in the moderate anxiety group (P < 0.05). CONCLUSION: According to these results, it was found that an increased anxiety score before CS is associated with low birth weight in the baby, higher heart rate, and DBP in the mother.

Wild Blueberry Extract Intervention in Healthy Older Adults: A Multi-Study, Randomised, Controlled Investigation of Acute Cognitive and Cardiovascular Effects.

BACKGROUND: Circadian and homeostatic declines in cognitive performance are observed during the day, most commonly at 14:00. Additionally, postprandial reductions in cognitive ability have been widely demonstrated 1 h after lunch consumption, affecting domains of executive functioning (EF), episodic memory (EM), and attention. Existing evidence shows that anthocyanin-rich foods such as berries may improve or attenuate the decline in EF and EM in ageing adults. Further research is required to assess whether extracts such as wild blueberry extract (WBE) may be beneficial for cognitive function across an acute timeframe, including known periods of reduced functioning. OBJECTIVES: (1) Study 1: ROAB: To investigate the efficacy of WBE in maintaining EF and EM throughout the day alongside measures of cardiovascular outcomes in healthy older adults. A range of WBE doses were utilised to identify the optimal dose at which cognitive and cardiovascular effects occur. (2) Study 2: BEAT: To replicate alleviation of cognitive decline during a predicted post-lunch dip whilst also improving cardiovascular outcomes following acute WBE 222 mg supplementation. METHODS: Both studies employed a randomised, double-blind, cross-over, placebo-controlled design to explore the effects of WBE intervention versus placebo on several outcomes, including EM, EF, blood pressure, and heart rate in a healthy older adult population (aged 68-75). In ROAB, 28 participants received a single dose of WBE 111 mg, 222 mg, 444 mg, or 888 mg or placebo over a 5-week period, each separated by a 1-week washout. Outcomes were measured at 0 h, 2 h, 4 h, and 6 h post intervention, with intervention occurring immediately after baseline (0 h). In BEAT, 45 participants received WBE 222 mg and placebo (1-week washout). Outcomes were measured at 0 h and 6 h (14:00) when a post-lunch dip was anticipated. This was further enhanced by consumption of lunch 1 h prior to cognitive testing. The WBE 222 mg intervention aligned with known peaks in plasma blueberry polyphenol metabolites at 2 h post dosing, which would coincide with a predicted drop in post-lunch performance. RESULTS: ROAB: A significant dip in executive function was apparent at the 4 h timepoint for placebo only, indicating attenuation for WBE doses. Strikingly, WBE 222 mg produced acute reductions in both systolic and diastolic blood pressure compared with placebo. BEAT: EF reaction time was found to be significantly faster for WBE 222 compared to placebo at the predicted post-lunch dip (14:00), with no other notable benefits on a range of cognitive and cardiovascular outcomes. CONCLUSION: These two studies indicate that WBE may have cardiovascular benefits and attenuate the natural cognitive decline observed over the course of the day, particularly when a decline is associated with a circadian rhythm-driven postprandial dip. However, it is important to acknowledge that effects were subtle, and benefits were only observed on a small number of outcomes. Further research is required to explore the utility of WBE in populations already experiencing mild cognitive impairments.

To Compare the Anesthetic Effect of Remimazolam and Propofol in Painless Hysteroscopic Minimally Invasive Surgery.

OBJECTIVE: Hysteroscopic surgery will stimulate the autonomic nerves innervating the uterus, causing intense discomfort and pain in the examined person, and in severe cases, it will cause blood pressure drop, heart rate slowing, arrhythmia and even cardiac arrest, so most patients need anesthetic intervention. This study to retrospectively compare the anesthetic effect of remimazolam and propofol in minimally invasive painless hysteroscopic surgery and to explore the safety and efficacy of remimazolam. METHODS: The clinical data of 110 female patients who underwent painless hysteroscopic minimally invasive surgery in our hospital from January 2023 to June 2023 were collected. The patients were divided into the remimazolam group (group R, n = 55) and the propofol group (group P, n = 55) according to the main anesthetic drugs used during the operation. The changes in heart rate (HR), mean arterial pressure (MAP), blood oxygen saturation (SpO2), and respiratory rate (RR) at the time of entry (T0), modified vigilance/sedation score (MOAA/S) 0 (T1), cervical dilation (T2), end of the operation (T3) and anesthesia recovery (T4) were compared between the two groups. Anesthesia induction time, operation time, and anesthesia recovery time were compared between the two groups, and the incidence of intraoperative and postoperative adverse reactions was compared between the two groups. RESULTS: HR, MAP, and SpO2 in group R were significantly higher than those in group P at T1, T2, T3, and T4 (p < 0.05), and there was no significant difference in RR between the two groups (p > 0.05). HR, MAP, and SpO2 at T1 and T2 were significantly lower than those at T0 in group R (p < 0.05), and RR at different time points in the group had no significant difference (p > 0.05). HR, MAP, and SpO2 at T1, T2, T3, and T4 were significantly lower than those at T0 in group P (p < 0.01), and RR at different time points in the same group had no significant difference (p > 0.05). The anesthesia induction time in group R was more prolonged than in group P, and the anesthesia recovery time in group R was shorter than in group P (p < 0.05). The incidences of hypotension, bradycardia, low oxygen saturation, respiratory depression, and injection pain in group R were significantly lower than those in group P (p < 0.05). CONCLUSION: Intravenous induction of remimazolam at 6 mg·kg-1·h-1 and maintenance of anesthesia at 1-2 mg·kg-1·h-1 have less effect on hemodynamics, faster recovery time and lower incidence of adverse reactions compared with propofol when used in minimally invasive hysteroscopic surgery. Remimazolam can be safely and effectively used in this kind of surgery.