Effect of sugammadex on processed EEG parameters in patients undergoing robot-assisted radical prostatectomy.

BACKGROUND: Sugammadex has been associated with increases in the bispectral index (BIS). We evaluated the effects of sugammadex administration on quantitative electroencephalographic (EEG) and electromyographic (EMG) measures. METHODS: We performed a prospective observational study of adult male patients undergoing robot-assisted radical prostatectomy. All patients received a sevoflurane-based general anaesthetic and a continuous infusion of rocuronium, which was reversed with 2 mg kg-1 of sugammadex i.v. BIS, EEG, and EMG measures were captured with the BIS Vista™ monitor. RESULTS: Twenty-five patients were included in this study. Compared with baseline, BIS increased at 4-6 min (ß coefficient: 3.63; 95% confidence interval [CI]: 2.22-5.04; P<0.001), spectral edge frequency 95 (SEF95) increased at 2-4 min (ß coefficient: 0.29; 95% CI: 0.05-0.52; P=0.016) and 4-6 min (ß coefficient: 0.71; 95% CI: 0.47-0.94; P<0.001), and EMG increased at 4-6 min (ß coefficient: 1.91; 95% CI: 1.00-2.81; P<0.001) after sugammadex administration. Compared with baseline, increased beta power was observed at 2-4 min (ß coefficient: 93; 95% CI: 1-185; P=0.046) and 4-6 min (ß coefficient: 208; 95% CI: 116-300; P<0.001), and decreased delta power was observed at 4-6 min (ß coefficient: -526.72; 95% CI: -778 to -276; P<0.001) after sugammadex administration. Neither SEF95 nor frequency band data analysis adjusted for EMG showed substantial differences. None of the patients showed clinical signs of awakening. CONCLUSIONS: After neuromuscular block reversal with 2 mg kg-1 sugammadex, BIS, SEF95, EMG, and beta power showed small but statistically significant increases over time, while delta power decreased.

Development and Performance Evaluation of a Clinical Predictive Model to Estimate the Risk of Red Blood Cell Requirements in Brain Tumor Surgery.

BACKGROUND: The identification of factors associated with perioperative red blood cell (RBC) transfusion provides an opportunity to optimize the patient and surgical plan, and to guide perioperative crossmatch and RBC orders. We examined the association among potential bleeding risk factors and RBC requirements to develop a novel predictive model for RBC transfusion in patients undergoing brain tumor surgery. METHODS: This retrospective study included 696 adults who underwent brain tumor surgery between 2008 and 2018. Multivariable logistic regression with backward stepwise selection for predictor selection was used during modeling. Model performance was evaluated using area under the receiver operating characteristic curve, and calibration was evaluated with Hosmer-Lemeshow goodness-of-fit χ 2 -estimate. RESULTS: Preoperative hemoglobin level was inversely associated with the probability of RBC transfusion (odds ratio [OR]: 0.50; 95% confidence interval [CI]: 0.39-0.63; P <0.001). The need for RBC transfusion was also greater in patients who had a previous craniotomy (OR: 2.71; 95% CI: 1.32-5.57; P =0.007) and in those with larger brain tumor volume (OR: 1.01; 95% CI: 1.00-1.02; P =0.009). The relationship between number of planned craniotomy sites and RBC transfusion was not statistically significant (OR: 2.11; 95% CI: 0.61-7.32; P =0.238). A predictive model for RBC requirements was built using these 4 variables. The area under the receiver operating characteristic curve was 0.79 (95% CI: 0.70-0.87; P <0.001) showing acceptable calibration for predicting RBC transfusion requirements. CONCLUSIONS: RBC requirements in patients undergoing brain tumor surgery can be estimated with acceptable accuracy using a predictive model based on readily available preoperative clinical variables. This predictive model could help to optimize both individual patients and surgical plans, and to guide perioperative crossmatch orders.

Associations of wrong surgery with other critical healthcare quality and patient safety challenges: a cross-sectional nationwide study of 100 general hospitals in Spain.

Wrong surgery (wrong-site, wrong-procedure, or wrong-patient surgery) is among the most feared patient safety problems in hospitals. We aimed to evaluate associations between numeric assessment of risk assigned to wrong surgery with that of other healthcare quality and patient safety challenges. This nationwide study collected information from healthcare quality experts in charge of a clinical quality and/or patient safety department in general hospitals of ≥ 150 beds in Spain. Out of the 100 included hospitals, the highest strength of associations were observed with risk priority number (RPN) for hospital-acquired pressure ulcers, RPN for venous thromboembolism in hospitalized patients, RPN for incorrect patient identification, RPN for lack of informed consent for diagnostic or therapeutic procedures, RPN for catheter-related bacteremia, and RPN for adverse events and injuries due to medical devices related to use and/or design. These results are of potential interest for designing combined and coordinated strategies to improve patient safety in hospitals.

Cardiometabolic characterization in metabolic dysfunction-associated fatty liver disease.

Background: To better understand the patient's heterogeneity in fatty liver disease (FLD), metabolic dysfunction-associated fatty liver disease (MAFLD) was proposed by international experts as a new nomenclature for nonalcoholic fatty liver disease (NAFLD). We aimed to evaluate the cardiovascular risk, assessed through coronary artery calcium (CAC) and epicardial adipose tissue (EAT), of patients without FLD and patients with FLD and its different subtypes. Methods: Cross sectional study of 370 patients. Patients with FLD were divided into 4 groups: FLD without metabolic dysfunction (non-MD FLD), MAFLD and the presence of overweight/obesity (MAFLD-OW), MAFLD and the presence of two metabolic abnormalities (MAFLD-MD) and MAFLD and the presence of T2D (MAFLD-T2D). MAFLD-OW included two subgroups: metabolically healthy obesity (MHO) and metabolically unhealthy obesity (MUHO). The patients without FLD were divided into 2 groups: patients without FLD and without MD (non-FLD nor MD; reference group) and patients without FLD but with MD (non-FLD with MD). EAT and CAC (measured through the Agatston Score) were determined by computed tomography. Results: Compared with the reference group (non-FLD nor MD), regarding EAT, patients with MAFLD-T2D and MAFLD-MUHO had the highest risk for CVD (OR 15.87, 95% CI 4.26-59.12 and OR 17.60, 95% CI 6.71-46.20, respectively), patients with MAFLD-MHO were also at risk for CVD (OR 3.62, 95% CI 1.83-7.16), and patients with non-MD FLD did not have a significantly increased risk (OR 1.77; 95% CI 0.67-4.73). Regarding CAC, patients with MAFLD-T2D had an increased risk for CVD (OR 6.56, 95% CI 2.18-19.76). Patients with MAFLD-MUHO, MAFLD-MHO and non-MD FLD did not have a significantly increased risk compared with the reference group (OR 2.54, 95% CI 0.90-7.13; OR 1.84, 95% CI 0.67-5.00 and OR 2.11, 95% CI 0.46-9.74, respectively). Conclusion: MAFLD-T2D and MAFLD-OW phenotypes had a significant risk for CVD. MAFLD new criteria reinforced the importance of identifying metabolic phenotypes in populations as it may help to identify patients with higher CVD risk and offer a personalized therapeutic management in a primary prevention setting.

11C-Methionine PET/CT in Assessment of Multiple Myeloma Patients: Comparison to 18F-FDG PET/CT and Prognostic Value.

Multiple myeloma (MM) is the second most common haematological malignancy and remains incurable despite therapeutic advances. 18F-FDG (FDG) PET/CT is a relevant tool MM for staging and it is the reference imaging technique for treatment evaluation. However, it has limitations, and investigation of other PET tracers is required. Preliminary results with L-methyl-[11C]- methionine (MET), suggest higher sensitivity than 18F-FDG. This study aimed to compare the diagnostic accuracy and prognostic value of 1FDG and MET in MM patients. We prospectively compared FDG and MET PET/CT for assessment of bone disease and extramedullary disease (EMD) in a series of 52 consecutive patients (8 smoldering MM, 18 newly diagnosed MM and 26 relapsed MM patients). Bone marrow (BM) uptake patterns and the detection of focal lesions (FLs) and EMD were compared. Furthermore, FDG PET parameters with known MM prognostic value were explored for both tracers, as well as total lesion MET uptake (TLMU). Median patient age was 61 years (range, 37-83 years), 54% were male, 13% of them were in stage ISS (International Staging System) III, and 31% had high-risk cytogenetics. FDG PET/CT did not detect active disease in 6 patients, while they were shown to be positive by MET PET/CT. Additionally, MET PET/CT identified a higher number of FLs than FDG in more than half of the patients (63%). For prognostication we focussed on the relapsed cohort, due to the low number of progressions in the two other cohorts. Upon using FDG PET/CT in relapsed patients, the presence of more than 3 FLs (HR 4.61, p = 0.056), more than 10 FLs (HR 5.65, p = 0.013), total metabolic tumor volume (TMTV) p50 (HR 4.91, p = 0.049) or TMTV p75 (HR 5.32, p = 0.016) were associated with adverse prognosis. In MET PET/CT analysis, TMTV p50 (HR 4.71, p = 0.056), TMTV p75 (HR 6.27, p = 0.007), TLMU p50 (HR 8.8, p = 0.04) and TLMU p75 (HR 6.3, p = 0.007) adversely affected PFS. This study confirmed the diagnostic and prognostic value of FDG in MM. In addition, it highlights that MET has higher sensitivity than FDG PET/CT for detection of myeloma lesions, including FLs. Moreover, we show, for the first time, the prognostic value of TMTV and TLMU MET PET/CT in the imaging evaluation of MM patients.

Oncolytic DNX-2401 Virus for Pediatric Diffuse Intrinsic Pontine Glioma.

BACKGROUND: Pediatric patients with diffuse intrinsic pontine glioma (DIPG) have a poor prognosis, with a median survival of less than 1 year. Oncolytic viral therapy has been evaluated in patients with pediatric gliomas elsewhere in the brain, but data regarding oncolytic viral therapy in patients with DIPG are lacking. METHODS: We conducted a single-center, dose-escalation study of DNX-2401, an oncolytic adenovirus that selectively replicates in tumor cells, in patients with newly diagnosed DIPG. The patients received a single virus infusion through a catheter placed in the cerebellar peduncle, followed by radiotherapy. The primary objective was to assess the safety and adverse-event profile of DNX-2401. The secondary objectives were to evaluate the effect of DNX-2401 on overall survival and quality of life, to determine the percentage of patients who have an objective response, and to collect tumor-biopsy and peripheral-blood samples for correlative studies of the molecular features of DIPG and antitumor immune responses. RESULTS: A total of 12 patients, 3 to 18 years of age, with newly diagnosed DIPG received 1×1010 (the first 4 patients) or 5×1010 (the subsequent 8 patients) viral particles of DNX-2401, and 11 received subsequent radiotherapy. Adverse events among the patients included headache, nausea, vomiting, and fatigue. Hemiparesis and tetraparesis developed in 1 patient each. Over a median follow-up of 17.8 months (range, 5.9 to 33.5), a reduction in tumor size, as assessed on magnetic resonance imaging, was reported in 9 patients, a partial response in 3 patients, and stable disease in 8 patients. The median survival was 17.8 months. Two patients were alive at the time of preparation of the current report, 1 of whom was free of tumor progression at 38 months. Examination of a tumor sample obtained during autopsy from 1 patient and peripheral-blood studies revealed alteration of the tumor microenvironment and T-cell repertoire. CONCLUSIONS: Intratumoral infusion of oncolytic virus DNX-2401 followed by radiotherapy in pediatric patients with DIPG resulted in changes in T-cell activity and a reduction in or stabilization of tumor size in some patients but was associated with adverse events. (Funded by the European Research Council under the European Union's Horizon 2020 Research and Innovation Program and others; EudraCT number, 2016-001577-33; ClinicalTrials.gov number, NCT03178032.).

Transient elastography and serum markers of liver fibrosis associate with epicardial adipose tissue and coronary artery calcium in NAFLD.

Non-alcoholic fatty liver disease (NAFLD) is associated with cardiovascular disease morbimortality. However, it is not clear if NAFLD staging may help identify early or subclinical markers of cardiovascular disease. We aimed to evaluate the association of liver stiffness and serum markers of liver fibrosis with epicardial adipose tissue (EAT) and coronary artery calcium (CAC) in an observational cross-sectional study of 49 NAFLD patients that were seen at Clínica Universidad de Navarra (Spain) between 2009 and 2019. Liver elastography and non-invasive fibrosis markers were used to non-invasively measure fibrosis. EAT and CAC, measured through visual assessment, were determined by computed tomography. Liver stiffness showed a direct association with EAT (r = 0.283, p-value = 0.049) and CAC (r = 0.337, p-value = 0.018). NAFLD fibrosis score was associated with EAT (r = 0.329, p-value = 0.021) and CAC (r = 0.387, p-value = 0.006). The association of liver stiffness with CAC remained significant after adjusting for metabolic syndrome features (including carbohydrate intolerance/diabetes, hypertension, dyslipidaemia, visceral adipose tissue, and obesity). The evaluation of NAFLD severity through liver elastography or non-invasive liver fibrosis biomarkers may contribute to guide risk factor modification to reduce cardiovascular risk in asymptomatic patients. Inversely, subclinical cardiovascular disease assessment, through Visual Scale for CAC scoring, may be a simple and effective measure for patients with potential liver fibrosis, independently of the existence of other cardiovascular risk factors.

SUCCOR cone study: conization before radical hysterectomy.

OBJECTIVE: To evaluate disease-free survival of cervical conization prior to radical hysterectomy in patients with stage IB1 cervical cancer (International Federation of Gynecology and Obstetrics (FIGO) 2009). METHODS: A multicenter retrospective observational cohort study was conducted including patients from the Surgery in Cervical Cancer Comparing Different Surgical Aproaches in Stage IB1 Cervical Cancer (SUCCOR) database with FIGO 2009 IB1 cervical carcinoma treated with radical hysterectomy between January 1, 2013, and December 31, 2014. We used propensity score matching to minimize the potential allocation biases arising from the retrospective design. Patients who underwent conization but were similar for other measured characteristics were matched 1:1 to patients from the non-cone group using a caliper width ≤0.2 standard deviations of the logit odds of the estimated propensity score. RESULTS: We obtained a weighted cohort of 374 patients (187 patients with prior conization and 187 non-conization patients). We found a 65% reduction in the risk of relapse for patients who had cervical conization prior to radical hysterectomy (hazard ratio (HR) 0.35, 95% confidence interval (CI) 0.16 to 0.75, p=0.007) and a 75% reduction in the risk of death for the same sample (HR 0.25, 95% CI 0.07 to 0.90, p=0.033). In addition, patients who underwent minimally invasive surgery without prior conization had a 5.63 times higher chance of relapse compared with those who had an open approach and previous conization (HR 5.63, 95% CI 1.64 to 19.3, p=0.006). Patients who underwent minimally invasive surgery with prior conization and those who underwent open surgery without prior conization showed no differences in relapse rates compared with those who underwent open surgery with prior cone biopsy (reference) (HR 1.94, 95% CI 0.49 to 7.76, p=0.349 and HR 2.94, 95% CI 0.80 to 10.86, p=0.106 respectively). CONCLUSIONS: In this retrospective study, patients undergoing cervical conization before radical hysterectomy had a significantly lower risk of relapse and death.

Therapeutic versus Prophylactic Bemiparin in Hospitalized Patients with Nonsevere COVID-19 Pneumonia (BEMICOP Study): An Open-Label, Multicenter, Randomized, Controlled Trial.

Thromboprophylaxis with low molecular weight heparin in hospitalized patients with COVID-19 is mandatory, unless contraindicated. Given the links between inflammation and thrombosis, the use of higher doses of anticoagulants could improve outcomes. We conducted an open-label, multicenter, randomized, controlled trial in adult patients hospitalized with nonsevere COVID-19 pneumonia and elevated D-dimer. Patients were randomized to therapeutic-dose bemiparin (115 IU/kg daily) versus standard prophylaxis (bemiparin 3,500 IU daily), for 10 days. The primary efficacy outcome was a composite of death, intensive care unit admission, need of mechanical ventilation support, development of moderate/severe acute respiratory distress, and venous or arterial thrombosis within 10 days of enrollment. The primary safety outcome was major bleeding (International Society on Thrombosis and Haemostasis criteria). A prespecified interim analysis was performed when 40% of the planned study population was reached. From October 2020 to May 2021, 70 patients were randomized at 5 sites and 65 were included in the primary analysis; 32 patients allocated to therapeutic dose and 33 to standard prophylactic dose. The primary efficacy outcome occurred in 7 patients (22%) in the therapeutic-dose group and 6 patients (18%) in the prophylactic-dose (absolute risk difference 3.6% [95% confidence interval [CI], -16% -24%]; odds ratio 1.26 [95% CI, 0.37-4.26]; p = 0.95). Discharge in the first 10 days was possible in 66 and 79% of patients, respectively. No major bleeding event was registered. Therefore, in patients with COVID-19 hospitalized with nonsevere pneumonia but elevated D-dimer, the use of a short course of therapeutic-dose bemiparin does not appear to improve clinical outcomes compared with standard prophylactic doses. Trial Registration: ClinicalTrials.gov NCT04604327.

Pattern of relapse in patients with stage IB1 cervical cancer after radical hysterectomy as primary treatment. Minimally invasive surgery vs. open approach. Systematic review and meta-analysis.

BACKGROUND: After the LACC trial, the SUCCOR study, and other studies, we know that patients who have undergone minimally invasive surgery for cervical cancer have worse outcomes, but today, we do not know if the surgical approach can be a reason to change the pattern of relapses on these patients. We evaluated the relapse pattern in patients with stage IB1 cervical cancer (FIGO, 2009) who underwent radical hysterectomy with different surgical approaches. METHODS: A systematic review of literature was performed in PubMed, Cochrane Library, Clinicaltrials.gov, and Web of science. Inclusion criteria were prospective or retrospective comparative studies of different surgical approaches that described patterns or locations of relapse in patients with stage IB1 cervical cancer. Heterogeneity was assessed by calculating I2. RESULTS: The research resulted in 782 eligible citations from January 2010 to October 2020. After filtering, nine articles that met all inclusion criteria were analyzed, comprising data from 1663 patients who underwent radical hysterectomy for IB1 cervical cancer, and the incidence of relapse was 10.6%. When we compared the pattern of relapse (local, distant, and both) of each group (open surgery and minimally invasive surgery), we did not see statistically significant differences, (OR 0.963; 95% CI, 0.602-1.541; p = 0.898), (OR 0.788; 95% CI, 0.467-1.330; p = 0.542), and (OR 0.683; 95% CI, 0.331-1.407; p = 0.630), respectively. CONCLUSION: There are no differences in patterns of relapse across surgical approaches in patients with stage IB1 cervical cancer undergoing radical hysterectomy as primary treatment.

Endobronchial autologous bone marrow-mesenchymal stromal cells in idiopathic pulmonary fibrosis: a phase I trial.

RATIONALE: Idiopathic pulmonary fibrosis (IPF) has a dismal prognosis. Mesenchymal stromal cells (MSCs) have shown benefit in other inflammatory diseases. OBJECTIVES: To evaluate the safety and feasibility of endobronchial administration of bone marrow autologous MSCs (BM-MSC) in patients with mild-to-moderate IPF. METHODS: A phase I multicentre clinical trial (ClinicalTrials.gov NCT01919827) with a single endobronchial administration of autologous adult BM-MSCs in patients diagnosed with mild-to-moderate IPF. In a first escalating-dose phase, three patients were included sequentially in three dose cohorts (10×106, 50×106 and 100×106 cells). In a second phase, nine patients received the highest tolerated dose. Follow-up with pulmonary function testing, 6-min walk test and St George's Respiratory Questionnaire was done at 1, 2, 3, 6 and 12 months, and with computed tomography at 3, 6 and 12 months. RESULTS: 21 bone marrow samples were obtained from 17 patients. Three patients were excluded from treatment due to chromosome aberrations detected in MSCs after culture, and one patient died before treatment. Finally, 13 patients received the BM-MSC infusion. No treatment-related severe adverse events were observed during follow-up. Compared to baseline, the mean forced vital capacity showed an initial decline of 8.1% at 3 months. The number of patients without functional progression was six (46%) at 3 months and three (23%) at 12 months. CONCLUSIONS: The endobronchial infusion of BM-MSCs did not cause immediate serious adverse events in IPF patients, but a relevant proportion of patients suffered clinical and/or functional progression. Genomic instability of BM-MSCs during culture found in three patients may be troublesome for the use of autologous MSCs in IPF patients.

Factors Associated with Headache and Nausea During Magnetic Resonance-Guided Focused Ultrasound for Tremor.

BACKGROUND: During magnetic resonance-guided focused ultrasound for essential or parkinsonian tremor, adverse events (headache, nausea/vomiting, or anxiety) may alter the outcome of the procedure despite being mostly transient and mild. OBJECTIVES: Our aim was to analyze the relationship between demographic, procedural, and anesthetic characteristics with magnetic resonance/ultrasound-related events. METHODS: This was a retrospective study at the Clinica Universidad de Navarra of patients undergoing thalamotomy with magnetic resonance-guided focused ultrasound between September 2018 and October 2019. The anesthesia protocol included headache and nausea/vomiting prophylaxis and rescue therapy. Dexmedetomidine was used for anxiolysis in some patients after thorough multidisciplinary assessment. RESULTS: A total of 123 patients were included. Headache was directly related to skull density ratio (P < 0.001) and skull thickness (P = 0.02). Patients with a skull density ratio less than 0.48 had 3 times the odds of experiencing moderate or severe headache (odds ratio [OR], 3.08; 95% confidence interval [CI], 1.21-7.82) and had a higher odds of aborting sonication due to pain. Sex was associated with increased nausea (P = 0.007). Women had 4 times the odds of nausea than men (OR, 4.4; 95% CI, 1.61-12.11). Dexmedetomidine did not reduce headache or nausea incidence. Patients who received dexmedetomidine had a higher number (P = 0.01) and total minutes of sonication (P = 0.01). CONCLUSIONS: Patients with lower skull density ratios and higher skull thicknesses could benefit from an aggressive analgesic prophylaxis. Women are more likely to experience nausea. Dexmedetomidine did not reduce headache and nausea, but increased the number and duration of sonications. Its exact effect on tremor is still unclear.

Effects of dexmedetomidine on subthalamic local field potentials in Parkinson's disease.

BACKGROUND: Dexmedetomidine is frequently used for sedation during deep brain stimulator implantation in patients with Parkinson's disease, but its effect on subthalamic nucleus activity is not well known. The aim of this study was to quantify the effect of increasing doses of dexmedetomidine in this population. METHODS: Controlled clinical trial assessing changes in subthalamic activity with increasing doses of dexmedetomidine (from 0.2 to 0.6 µg kg-1 h-1) in a non-operating theatre setting. We recorded local field potentials in 12 patients with Parkinson's disease with bilateral deep brain stimulators (24 nuclei) and compared basal activity in the nuclei of each patient and activity recorded with different doses. Plasma levels of dexmedetomidine were obtained and correlated with the dose administered. RESULTS: With dexmedetomidine infusion, patients became clinically sedated, and at higher doses (0.5-0.6 µg kg-1 h-1) a significant decrease in the characteristic Parkinsonian subthalamic activity was observed (P<0.05 in beta activity). All subjects awoke to external stimulus over a median of 1 (range: 0-9) min, showing full restoration of subthalamic activity. Dexmedetomidine dose administered and plasma levels showed a positive correlation (repeated measures correlation coefficient=0.504; P<0.001). CONCLUSIONS: Patients needing some degree of sedation throughout subthalamic deep brain stimulator implantation for Parkinson's disease can probably receive dexmedetomidine up to 0.6 µg kg-1 h-1 without significant alteration of their characteristic subthalamic activity. If patients achieve a 'sedated' state, subthalamic activity decreases, but they can be easily awakened with a non-pharmacological external stimulus and recover baseline subthalamic activity patterns in less than 10 min. CLINICAL TRIAL REGISTRATION: EudraCT 2016-002680-34; NCT-02982512.