Longitudinal profile of estrogen-related thrombotic biomarkers after cessation of combined hormonal contraceptives.

ABSTRACT: The persistence of risk of venous thromboembolism (VTE) due to combined hormonal contraceptives (CHCs), after their cessation, is unknown but important to guide clinical practice. The objective of this prospective cohort study was to define the time until normalization of estrogen-related thrombotic biomarkers after CHC cessation. We enrolled women aged 18 to 50 years who had decided to stop their CHC, excluding those with a personal history of VTE, anticoagulation, or pregnancy. The study started before cessation of CHC, with 6 visits afterwards (at 1, 2, 4, 6, and 12 weeks after cessation). Primary outcomes were normalized sensitivity ratios to activated protein C (nAPCsr) and to thrombomodulin (nTMsr), with sex hormone-binding globulin (SHBG) as a secondary end point. We also included control women without CHC. Among 66 CHC users, from baseline until 12 weeks, average levels of nAPCsr, nTMsr, and SHBG decreased from 4.11 (standard deviation [SD], 2.06), 2.53 (SD, 1.03), and 167 nmol/L (SD, 103) to 1.27 (SD, 0.82), 1.11 (SD, 0.58), and 55.4 nmol/L (SD, 26.7), respectively. On a relative scale, 85.8%, 81.3%, and 76.2% of the decrease from baseline until 12 weeks was achieved at 2 weeks and 86.7%, 85.5%, and 87.8% at 4 weeks after CHC cessation, respectively. Levels were not meaningfully modified throughout the study period among 28 control women. In conclusion, CHC cessation is followed by a rapid decrease in estrogen-related thrombotic biomarkers. Two to 4 weeks of cessation before planned major surgery or withdrawal of anticoagulants in patients with VTE appears sufficient for the majority of women. The trial is registered at www.clinicaltrials.gov as #NCT03949985.

Reliability and Accuracy of the Pediatric Swiss Emergency Triage Scale-the SETSped Study.

BACKGROUND AND IMPORTANCE: The Swiss Emergency Triage Scale (SETS) is an adult triage tool used in several emergency departments. It has been recently adapted to the pediatric population but, before advocating for its use, performance assessment of this tool is needed. OBJECTIVES: The purpose of this study was to assess the reliability and the accuracy of the pediatric version of the SETS for the triage of pediatric patients. DESIGN, SETTING, AND PARTICIPANTS: This study was a cross-sectional study among a sample of emergency triage nurses (ETNs) exposed to 17 clinical scenarios using a computerized simulator. OUTCOME MEASURES AND ANALYSIS: The primary outcome was the reliability of the triage level performed by the ETNs. It was assessed using an intraclass correlation coefficient.Secondary outcomes included accuracy of triage compared with expert-based triage levels and factors associated with accurate triage. MAIN RESULTS: Eighteen ETNs participated in the study and completed the evaluation of all scenarios, for a total of 306 triage decisions. The intraclass correlation coefficient was 0.80 (95% confidence interval, 0.69-0.91), with an agreement by scenario ranging from 61.1% to 100%. The overall accuracy was 85.8%, and nurses were more likely to undertriage (16.0%) than to overtriage (4.3%). No factor for accurate triage was identified. CONCLUSIONS: This simulator-based study showed that the SETS is reliable and accurate among a pediatric population. Future research is needed to confirm these results, compare this triage scale head-to-head with other recognized international tools, and study the SETSped in real-life setting.

Limitation of life-sustaining therapies in critically ill patients with COVID-19: a descriptive epidemiological investigation from the COVID-ICU study.

BACKGROUND: Limitations of life-sustaining therapies (LST) practices are frequent and vary among intensive care units (ICUs). However, scarce data were available during the COVID-19 pandemic when ICUs were under intense pressure. We aimed to investigate the prevalence, cumulative incidence, timing, modalities, and factors associated with LST decisions in critically ill COVID-19 patients. METHODS: We did an ancillary analysis of the European multicentre COVID-ICU study, which collected data from 163 ICUs in France, Belgium and Switzerland. ICU load, a parameter reflecting stress on ICU capacities, was calculated at the patient level using daily ICU bed occupancy data from official country epidemiological reports. Mixed effects logistic regression was used to assess the association of variables with LST limitation decisions. RESULTS: Among 4671 severe COVID-19 patients admitted from February 25 to May 4, 2020, the prevalence of in-ICU LST limitations was 14.5%, with a nearly six-fold variability between centres. Overall 28-day cumulative incidence of LST limitations was 12.4%, which occurred at a median of 8 days (3-21). Median ICU load at the patient level was 126%. Age, clinical frailty scale score, and respiratory severity were associated with LST limitations, while ICU load was not. In-ICU death occurred in 74% and 95% of patients, respectively, after LST withholding and withdrawal, while median survival time was 3 days (1-11) after LST limitations. CONCLUSIONS: In this study, LST limitations frequently preceded death, with a major impact on time of death. In contrast to ICU load, older age, frailty, and the severity of respiratory failure during the first 24 h were the main factors associated with decisions of LST limitations.

Nontuberculous Mycobacteria under Scrutiny in the Geneva Area (2015-2020).

BACKGROUND: Nontuberculous mycobacteria (NTM) are increasingly identified in industrialized countries, and their role as pathogens is more frequently recognized. The relative prevalence of NTM strains shows an important geographical variability. Thus, establishing the local relative prevalence of NTM strains is relevant and useful for clinicians. METHODS: Retrospective analysis (2015-2020) of a comprehensive database was conducted including all results of cultures for mycobacteria in a University Hospital (Geneva, Switzerland), covering a population of approximately 500,000 inhabitants. All NTM culture-positive patients were included in the analyses. Patients' characteristics, NTM strains, and time to culture positivity were reported. RESULTS: Among 38,065 samples analyzed during the study period, 411 were culture-positive for NTM, representing 236 strains, and 231 episodes of care which occurred in 222 patients. Patients in whom NTM were identified were predominantly female (55%), with a median age of 62 years, and a low BMI (median: 22.6 kg/m2). The Mycobacterium avium complex (MAC) was the most frequently identified group (37% of strains) followed by Mycobacterium gordonae (25%) and Mycobacterium xenopi (12%) among the slowly growing mycobacteria (SGM), while the Mycobacterium chelonae/abscessus group (11%) were the most frequently identified rapidly growing mycobacteria (RGM). Only 19% of all patients were treated, mostly for pulmonary infections: the MAC was the most frequently treated NTM (n = 19, 43% of cases in patients treated) followed by RGM (n = 15, 34%) and M. xenopi (n = 6, 14%). Among those treated, 23% were immunosuppressed, 12% had pulmonary comorbidities, and 5% systemic comorbidities. Cultures became positive after a median of 41 days (IQR: 23; 68) for SGM and 28 days (14; 35) for RGM. CONCLUSIONS: In Western Switzerland, M. avium and M. gordonae were the most prevalent NTM identified. Positive cultures for NTM led to a specific treatment in 19% of subjects. Patients with a positive culture for NTM were mostly female, with a median age of 62 years, a low BMI, and a low prevalence of immunosuppression or associated severe comorbidities.

Limping and patient satisfaction after primary total hip arthroplasty: a registry-based cohort study.

BACKGROUND AND PURPOSE: The influence of postoperative limping on patient satisfaction and amount of limping reduction following THA are not well documented. We (1) assessed if postoperative limping is associated with satisfaction 5 years after THA performed via the lateral or anterior approach; (2) evaluated the influence of surgical approach on amount of limping reduction following THA. PATIENTS AND METHODS: We conducted a prospective cohort study of primary elective THAs performed in 2002-2013. Limping was assessed before and 5 years after surgery using the Harris Hip limping sub-score. Satisfaction was assessed at 5 years on a 5-point Likert scale. We compared proportions of satisfied patients among groups of limping. Evolution of limping before and after surgery was noted. Analyses were performed overall and stratified by pain and surgical approach. We used univariate and multivariate logbinomial regression models. RESULTS: 1,257 patients were included (mean age 70 years). 81% had surgery via a lateral and 19% via an anterior approach. Before THA, 60% had moderate to severe limping and all reported pain. After THA, limping and pain improved; 9% of patients were dissatisfied. In multivariate analysis stratified on pain level, limping was associated with higher dissatisfaction. Similar results were obtained after lateral vs. anterior approach. INTERPRETATION: Postoperative limping impacts patient satisfaction after THA. The association varied by degree of limping and absence or presence of pain. It was independent of surgical approach. 5 years after THA occurrence of limping was largely reduced after both a lateral and an anterior approach, with low evidence of a greater reduction under an anterior approach.

Rapid Sequence Induction With a Standard Intubation Dose of Rocuronium After Magnesium Pretreatment Compared With Succinylcholine: A Randomized Clinical Trial.

BACKGROUND: Succinylcholine remains the muscle relaxant of choice for rapid sequence induction (RSI) but has many adverse effects. High-dose rocuronium bromide may be an alternative to succinylcholine for RSI but recovery times are nearly doubled compared with a standard intubating dose of rocuronium. Magnesium sulfate significantly shortens the onset time of a standard intubating dose of rocuronium. We set out to investigate whether intravenous (IV) pretreatment with MgSO4 followed by a standard intubating dose of rocuronium achieved superior intubation conditions compared with succinylcholine. METHODS: Adults were randomized to receive a 15-minute IV infusion of MgSO4 (60 mg·kg-1) immediately before RSI with propofol 2 mg·kg-1, sufentanil 0.2 µg·kg-1 and rocuronium 0.6 mg·kg-1, or a matching 15-minute IV infusion of saline immediately before an identical RSI, but with succinylcholine 1 mg·kg-1. Primary end point was the rate of excellent intubating conditions 60 seconds after administration of the neuromuscular blocking agent and compared between groups using multivariable log-binomial regression model. Secondary end points were blood pressure and heart rate before induction, before and after intubation, and adverse events up to 24 hours postoperatively. RESULTS: Among 280 randomized patients, intubating conditions could be analyzed in 259 (133 MgSO4-rocuronium and 126 saline-succinylcholine). The rate of excellent intubating conditions was 46% with MgSO4-rocuronium and 45% with saline-succinylcholine. The analysis adjusted for gender and center showed no superiority of MgSO4-rocuronium compared with saline-succinylcholine (relative risk [RR] 1.06, 95% confidence interval [CI], 0.81-1.39, P = .659). The rate of excellent intubating conditions was higher in women (54% [70 of 130]) compared with men (37% [48 of 129]; adjusted RR 1.42, 95% CI, 1.07-1.91, P = .017). No significant difference between groups was observed for systolic and diastolic blood pressures. Mean heart rate was significantly higher in the MgSO4-rocuronium group. The percentage of patients with at least 1 adverse event was lower with MgSO4-rocuronium (11%) compared with saline-succinylcholine (28%) (RR 0.38, 95% CI, 0.22-0.66, P < .001). With saline-succinylcholine, adverse events consisted mainly of postoperative muscle pain (n = 26 [19%]) and signs of histamine release (n = 13 [9%]). With MgSO4-rocuronium, few patients had pain on injection, nausea and vomiting, or skin rash during the MgSO4-infusion (n = 5 [4%]). CONCLUSIONS: IV pretreatment with MgSO4 followed by a standard intubating dose of rocuronium did not provide superior intubation conditions to succinylcholine but had fewer adverse effects.

Longitudinal Timed Up and Go Assessment in Amyotrophic Lateral Sclerosis: A Pilot Study.

Progressive loss of walking ability in amyotrophic lateral sclerosis (ALS) has been scarcely studied as a potential predictive factor for survival in motor neuron disease. We aimed to assess the progression of gait decline and its association with mortality in ALS using the Timed Up and Go test (TUG). Patients were followed up prospectively at the Centre for ALS and Related Disorders in Geneva University Hospitals between 2012 and 2016. The TUG was performed at baseline and subsequent evaluations occurred every 3 months. At inclusion, patients were classified as unable to perform the TUG, "slow TUG" (>10.6 s), and "fast TUG" (≤10.6 s). In total, 68 patients with ALS (mean ± SD age: 68.6 ± 11.9 years; 50% female) were included. Baseline TUG was negatively correlated with the total ALSFRS-R score (r = -0.63, p < 0.001). At baseline, ALS patients with bulbar onset performed the TUG faster (9.9 ± 3.7 s) than the non-bulbar ones (17.3 ± 14.9 s, p = 0.008). Thirty of 68 (44%) patients died by the end of the follow-up period. The TUG performance at the first visit did not predict mortality. While we did not find any association with mortality in ALS and gait quantification, the TUG was feasible in a majority of ALS patients, was correlated with functional status, and could be of interest in the follow-up of non-bulbar ALS patients.

Feasibility and safety of high-intensity interval training for the rehabilitation of geriatric inpatients (HIITERGY) a pilot randomized study.

BACKGROUND: High-intensity interval training (HIIT) has been shown to be more effective than moderate-intensity continuous training (MICT) for the physical rehabilitation. However, data on its suitability for older hospitalized patients is scarce. METHODS: Randomized controlled trial in a hospital setting. Inclusion of 100 patients, ≥65 years old, hospitalized for rehabilitation after an acute medical condition, in a two-week rehabilitation program of either four HIIT or three MICT sessions per week. Completion was defined as participation in all but two planned sessions accomplishing ≥50% of each session. We assessed: upper-limb muscle strength (handgrip isometric strength test), lower-limb muscle strength (quadriceps and ankle flexion and extension tests); gait speed and spatio-temporal parameters (instrumented walkway), and exercise capacity (6-min walk test). All adverse events were recorded as safety endpoints. RESULTS: An intention-to-treat analysis showed a 44% completion rate for the HIIT group (95% CI, 30-59) and 77% for MICT (95% CI, 55-82). A modified intention-to-treat analysis restricted to patients who participated in ≥1 session showed an 88% completion rate in the HIIT group (95%CI, 69-97) and an 80% completion rate in MICT (95%CI, 65-90). The exercises most frequently undertaken were the pedal exerciser (54%) and the NuStep (32%). There were no significant differences in the various measures. No serious adverse events occurred. CONCLUSION: A HIIT rehabilitation program for this population was feasible, safe and had a high adherence rate. TRIAL REGISTRATION NUMBER: Clinicatrials.gov ID: NCT02318459. Trial registration date: November 7th, 2014. Retrospectively registered. This study adheres to the CONSORT guidelines.

Walking Speed and Maximal Knee Flexion During Gait After Total Knee Arthroplasty: Minimal Clinically Important Improvement Is Not Determinable; Patient Acceptable Symptom State Is Potentially Useful.

BACKGROUND: Total knee arthroplasty (TKA) is the operation of choice in patients with end-stage knee osteoarthritis (OA). Up to 1 in 5 patients still encounter functional limitations after TKA, partly explaining patient dissatisfaction. Which gait ability to target after TKA remains unclear. To determine whether Minimal Clinical Important Improvement (MCII) or Patient Acceptable Symptom State (PASS) values could be derived from gait parameters recorded in patients with TKA. And, if so, to define those values. METHODS: In this ancillary study, we retrospectively analyzed gait parameters of patients scheduled for a unilateral TKA between 2011 and 2013. We investigated MCII and PASS values for walking speed and maximal knee flexion using anchor-based methods: 5 anchoring questions based on perceived body function and patients' satisfaction. RESULTS: Over the study period, 79 patients performed a clinical gait analysis the week before and 1 year after surgery, and were included in the present study. All clinical and gait parameters improved 1 year after TKA. Nevertheless, changes in gait outcomes were not associated with perceived body function or patients' satisfaction, precluding any MCII estimation in gait parameters. PASS values, however, could be determined as 1.2 m/s for walking speed and 50° for maximal knee flexion. CONCLUSION: In this study, we found that MCII and PASS values are not necessarily determinable for gait parameters after TKA in patients with end-stage OA. Using anchor questions based on perceived body function and patient's satisfaction, MCII could not be defined while PASS values were potentially useful. LEVEL OF EVIDENCE: Level III.

Cost-effectiveness of HLA-DQB1/HLA-B pharmacogenetic-guided treatment and blood monitoring in US patients taking clozapine.

Less than 1% of adult patients with schizophrenia taking clozapine develop agranulocytosis, and most of these cases occur within the first weeks of treatment. The human leukocyte antigen (HLA) region has been associated with genetic susceptibility to clozapine-induced agranulocytosis (single amino acid changes in HLA-DQB1 (126Q) and HLA-B (158T)). The current study aimed to evaluate the cost-effectiveness, from a healthcare provider's perspective, of an HLA genotype-guided approach in patients with treatment-resistant schizophrenia who were taking clozapine and to compare the results with the current absolute neutrophil count monitoring (ANCM) schemes used in the USA. A semi-Markovian model was developed to simulate the progress of a cohort of adult men and women who received clozapine as a third-line antipsychotic medication. We compared current practices using two genotype-guided strategies: (1) HLA genotyping followed by clozapine, with ANCM only for patients who tested positive for one or both alleles (genotype-guided blood sampling); (2) HLA genotyping followed by clozapine for low-risk patients and alternative antipsychotics for patients who tested positive (clozapine substitution scheme). Up to a decision threshold of $3.9 million per quality-adjusted life-year (90-fold the US gross domestic product per capita), the base-case results indicate that compared with current ANCM, genotype-guided blood sampling prior to clozapine initiation appeared cost-effective for targeted blood monitoring only in patients with HLA susceptibility alleles. Sensitivity analysis demonstrated that at a cost of genotype testing of up to USD700, HLA genotype-guided blood monitoring remained a cost-effective strategy compared with either current ANCM or clozapine substitution.

Cost-effectiveness evaluation of HPV self-testing offered to non-attendees in cervical cancer screening in Switzerland.

OBJECTIVE: About 30% of women who are eligible for cervical cancer (CC) screening remain un-screened or under-screened in Switzerland. HPV testing on self-collected vaginal samples (Self-HPV) has shown to be more sensitive than cytology while also reaching non-attendees. The objective of this study was to explore the cost-effectiveness of offering Self-HPV to non-attendees in Switzerland. METHODS: A recursive decision-tree with one-year cycles was used to model the life-long natural HPV history. Markov cohort simulations were used to assess the expected outcomes from the model. The outcomes of three strategies were compared with the absence of screening: Self-HPV and triage with colposcopy (Self-HPV/colpo), Self-HPV and triage with Pap cytology (Self-HPV/PAP), cytological screening and triage with HPV (PAP/HPV). Sensitivity analyses for the key parameters of the model were conducted to check the robustness of findings. RESULTS: Offering a Self-HPV screening to non-attendees could prevent 90% of CC and 94% of CC-related deaths in the study population. The current cytology-based program could reduce by 83% the number of CC cases and by 88% the number of CC-related deaths over the population's lifetime. Compared to the absence of screening, incremental cost-effectiveness ratios (ICER) were estimated to be, per saved Quality Adjusted Life Year (QALY), 12413US$ for the strategy Self-HPV/colpo, 11138US$ for the strategy Self-HPV/Pap and 22488US$ for the strategy PAP/HPV. CONCLUSIONS: Offering Self-HPV as a CC screening strategy to non-attendees in Switzerland is a cost-effective solution that is associated with a reduction of CC cases and related deaths. Self-HPV is more cost-effective than the currently used cytology-based screening.

Assessing Inspiratory Muscle Strength for Early Detection of Respiratory Failure in Motor Neuron Disease: Should We Use MIP, SNIP, or Both?

BACKGROUND: Motor neuron disease (MND) invariably impacts on inspiratory muscle strength leading to respiratory failure. Regular assessment of sniff nasal inspiratory pressure (SNIP) and/or maximal mouth inspiratory pressure (MIP) contributes to early detection of a requirement for ventilatory support. OBJECTIVES: The aim of this study was to compare the feasibility, agreement, and performance of both tests in MND. METHODS: Patients with MND followed by a multidisciplinary consultation were prospectively included. Pulmonary follow-up included forced expiratory volumes, vital capacity (VC) seated and supine, MIP, SNIP, pulse oximetry, and daytime arterial blood gases. RESULTS: A total of 61 patients were included. SNIP and MIP could not be performed in 14 (21%) subjects; 74% of the subjects showed a decrease in MIP or SNIP at inclusion versus 31% for VC. Correlation between MIP and SNIP (Pearson's rho: 0.68, p < 0.001) was moderate, with a non-significant bias in favor of SNIP (3.6 cm H2O) and wide limits of agreement (-34 to 41 cm H2O). Results were similar in "bulbar" versus "non-bulbar" patients. At different proposed cut-off values for identifying patients at risk of respiratory failure, the agreement between MIP and SNIP (64-79%) and kappa values (0.29-0.53) was moderate. CONCLUSIONS: MIP and SNIP were equally feasible. There was no significant bias in favor of either test, but a considerable disparity in results between tests, suggesting that use of both tests is warranted to screen for early detection of patients at risk of respiratory failure and avoid over diagnoses. SNIP, MIP, and VC all follow a relatively linear downhill course with a steeper slope for "bulbar" versus "non-bulbar" patients.

Determinants of the calibration of SAPS II and SAPS 3 mortality scores in intensive care: a European multicenter study.

BACKGROUND: The aim of the Simplified Acute Physiology Score (SAPS) II and SAPS 3 is to predict the mortality of patients admitted to intensive care units (ICUs). Previous studies have suggested that the calibration of these scores may vary across countries, centers, and/or characteristics of patients. In the present study, we aimed to assess determinants of the calibration of these scores. METHODS: We assessed the calibration of the SAPS II and SAPS 3 scores among 5266 patients admitted to ICUs during a 4-week period at 120 centers in 17 European countries. We obtained calibration curves, Brier scores, and standardized mortality ratios. Points attributed to SAPS items were reevaluated and compared with those of the original scores. Finally, we tested associations between the calibration and center characteristics. RESULTS: The mortality was overestimated by both scores: The standardized mortality ratios were 0.75 (95% CI 0.71-0.79) for the SAPS II score and 0.91 (95% CI 0.86-0.96) for the SAPS 3 score. This overestimation was partially explained by changes in associations between some items of the scores and mortality, especially the heart rate, Glasgow Coma Scale score, and diagnosis of AIDS for SAPS II. The calibration of both scores was better in countries with low health expenditures. The between-center variability in calibration curves was much greater than expected by chance. CONCLUSIONS: Both scores overestimate current mortality among European ICU patients. The magnitude of the miscalibration of SAPS II and SAPS 3 scores depends not only on patient characteristics but also on center characteristics. Furthermore, much between-center variability in calibration remains unexplained by these factors. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01422070 . Registered 19 August 2011.

Respiratory weakness after mechanical ventilation is associated with one-year mortality - a prospective study.

BACKGROUND: Diaphragm dysfunction in mechanically ventilated patients is associated with poor outcome. Maximal inspiratory pressure (MIP) can be used to evaluate inspiratory muscle function. However, it is unclear whether respiratory weakness is independently associated with long-term mortality. The aim of this study was to determine if low MIP is independently associated with one-year mortality. METHODS: We conducted a prospective observational cohort study in an 18-bed ICU. Adults requiring at least 24 hours of mechanical ventilation with scheduled extubation and no evidence of pre-existing muscle weakness underwent MIP evaluation just before extubation. Patients were divided into two groups: low MIP (MIP ≤30 cmH2O) and high MIP (MIP >30 cmH2O). Mortality was recorded for one year after extubation. For the survival analysis, the effect of low MIP was assessed using the log-rank test. The independent effect of low MIP on post mechanical ventilation mortality was analyzed using a multivariable Cox regression model. RESULTS: One hundred and twenty-four patients underwent MIP evaluation (median age 66 years (25(th)-75(th) percentile 56-74), Simplified Acute Physiology Score (SAPS) 2 = 45 (33-57), duration of mechanical ventilation 7 days (4-10)). Fifty-four percent of patients had low MIP. One-year mortality was 31 % (95 % CI 0.21, 0.43) in the low MIP group and 7 % (95 % CI 0.02, 0.16) in the high MIP group. After adjustment for SAPS 2 score, body mass index and duration of mechanical ventilation, low MIP was independently associated with one-year mortality (hazard ratio 4.41, 95 % CI 1.5, 12.9, p = 0.007). Extubation failure was also associated with low MIP (relative risk 3.0, 95 % CI 1, -9.6; p = 0.03) but tracheostomy and ICU length of stay were not. CONCLUSION: Low MIP is frequent in patients on mechanical ventilation and is an independent risk factor for long-term mortality in ICU patients requiring mechanical ventilation. MIP is easily evaluated at the patient's bedside. TRIAL REGISTRATION: This study was retrospectively registered in www.clinicaltrials.gov (NCT02363231) in February 2015.

The influence of FRCs reinforcement on marginal adaptation of CAD/CAM composite resin endocrowns after simulated fatigue loading.

To evaluate the marginal adaptation of endodontically treated molars restored with CAD/CAM composite resin endocrowns either with or without reinforcement by fibre reinforced composites (FRCs), used in different configurations. 32 human endodontically treated molars were cut 2 mm over the CEJ. Two interproximal boxes were created with the margins located 1 mm below the CEJ (distal box) and 1 mm over the CEJ (mesial box). All specimens were divided in four groups (n = 8). The pulp chamber was filled with: group 1 (control), hybrid resin composite (G-aenial Posterior, GC); group 2, as group 1 but covered by 3 meshes of E-glass fibres (EverStick NET, Stick Tech); group 3, FRC resin (EverX Posterior, GC); group 4, as group 3 but covered by 3 meshes of E-glass fibres. The crowns of all teeth were restored with CAD/CAM composite resin endocrowns (LAVA Ultimate, 3M). All specimens were thermo-mechanically loaded in a computer-controlled chewing machine (600,000 cycles, 1.6 Hz, 49 N and simultaneously 1500 thermo-cycles, 60 s, 5-55 °C). Marginal analysis before and after the loading was carried out on epoxy replicas by SEM at 200× magnification. For all the groups, the percentage values of perfect marginal adaptation after loading were always significantly lower than before loading (p < 0.05). The marginal adaptation before and after loading was not significantly different between the experimental groups (p > 0.05). Within the limitations of this in vitro study, the use of FRCs to reinforce the pulp chamber of devitalized molars restored with CAD/CAM composite resin restorations did not significantly influenced their marginal quality.

Donor hypernatremia before procurement and early outcomes following pediatric liver transplantation.

The demand for transplantable organs far outweighs the supply. Recently, efforts have been made to increase the donor pool by adopting extended criteria for livers, including those from hypernatremic donors. Currently, there is no clear evidence that the use of organs from hypernatremic donors has detrimental effects on pediatric liver transplantation (LT) recipients. Our aim was to use the Scientific Registry of Transplant Recipients database to evaluate the effects of donor hypernatremia on 30-day outcomes in pediatric LT recipients. We performed an analysis of 2325 children who underwent whole or partial LT between 2005 and 2010. First, we sought to determine a donor sodium threshold for increased mortality following pediatric LT. Second, we examined rates of mortality and graft failure at 30 days after LT in patients receiving grafts from hypernatremic donors compared to patients receiving grafts from normonatremic donors. Hypernatremia was defined as a donor sodium level of ≥160 µmol/L. The primary outcome measure was mortality at 30 days after transplant. The secondary outcome measure was graft failure at 30 days after transplant. There was no threshold sodium level for increased 30-day mortality following pediatric LT. Mean recipient ages/weights, Pediatric End-Stage Liver Disease/Model for End-Stage Liver Disease scores, and mean cold and warm ischemia times were similar between the 2 study groups. There were no significant differences in mortality rates (3.9% versus 4.5%; P = 0.87) and graft failure rates (2.2% versus 1.9%; P = 1.00) in patients receiving grafts from hypernatremic donors compared to patients receiving grafts from normonatremic donors at 30 days after LT. In conclusion, donor hypernatremia just before procurement does not appear to have negative effects on mortality and graft failure rates at 30 days following pediatric LT.

Impact of non-inhibited platelet supplementation on platelet reactivity in patients treated with prasugrel or ticagrelor for an acute coronary syndrome: An ex vivo study.

Managing bleeding in patients receiving P2Y12 inhibitors is challenging. Few data are available regarding the efficacy of platelet transfusion in patients treated with prasugrel or ticagrelor. The aim of this study was to evaluate the minimal amount of platelet supplementation (in terms of ratio of non-inhibited platelets to inhibited platelets) necessary to restore platelet reactivity in platelet-rich plasma (PRP) of patients treated with aspirin and a prasugrel or ticagrelor loading dose for an acute coronary syndrome. PRP samples from patients were mixed ex vivo with increasing proportions of pooled PRP from healthy volunteers. Platelet reactivity was challenged with adenosine diphosphate (ADP), arachidonic acid, collagen or thrombin receptor activating peptide using light transmission aggregometry. The primary endpoint was the proportion of patient samples recovering an ADP-induced maximal aggregation (ADP-Aggmax) value above 40%. In patients treated with prasugrel (n = 32), ADP-Aggmax increased progressively with supplements of pooled PRP, with an average increase of 7.9% (95% CI [7.1; 8.8], p < 0.001) per each 20% increase in the ratio of non-inhibited platelets to inhibited platelets. A ratio of 60% was associated with 90% of patients reaching the primary endpoint. In patients treated with ticagrelor (n = 15), ADP-Aggmax did not significantly increase with any level of supplements. In conclusions, ex vivo addition of non-inhibited platelets significantly improved ADP-Aggmax in patients treated with prasugrel with a dose-dependent effect. There was no evidence of such a reversal in patients treated with ticagrelor. These results suggest that platelet transfusion may be more effective in blunting bleeding in patients treated with prasugrel, than those treated with ticagrelor.

Accurate computed tomography-based portal pressure assessment in patients with hepatocellular carcinoma.

BACKGROUND & AIMS: Liver resection is generally restricted to patients without clinically significant portal hypertension (Hepatic Venous Pressure Gradient - HVPG - ⩽10mmHg) and several teams perform transjugular HVPG measurements as part of the pre-operative work-up. The present study investigates whether a non-invasive Computed Tomography (CT)-based assessment could be as accurate as the invasive transjugular measurement. METHODS: A cohort of patients with hepatocellular carcinoma (HCC) treated by resection (n=36) or transplantation (n=39) was selected (mean age: 61±9.2years, male/female ratio: 4/1). Pre-operative CTs were read by two independent investigators, and potential CT-based HVPG predictors were compared to the transjugular HVPG measurements. A validation was conducted on another cohort of 70 non-surgical patients. RESULTS: The invasive HVPG values were significantly correlated to liver/spleen volume ratio, spleen volume, platelet count, and peri-hepatic ascites (p<0.001), which all showed high inter-observer agreements (intra-class correlation coefficients ⩾0.927, Kappa ⩾0.945). The presence of a HVPG >10mmHg was best predicted by the liver/spleen volume ratio (AUC: 0.883 [0.805-0.960]) and the peri-hepatic ascites (p<0.001). These two variables were combined into an accurate model for predicting HVPG >10mmHg (AUC: 0.911 [0.847-0.975]), with sensitivity, specificity, and positive and negative predictive values of 92%, 79%, 91%, and 81%. The model was also accurate in the validation cohort with an AUC of 0.820 [0.719-0.921]. The computed formula was: CONCLUSIONS: The proposed CT-based model showed a high accuracy in the prediction of HVPG and, if further confirmed by prospective validation, could replace the invasive transjugular assessment in patients not requiring a biopsy of the non-tumoral liver.

Detection and quantification of focal uptake in head and neck tumours: (18)F-FDG PET/MR versus PET/CT.

PURPOSE: Our objectives were to assess the quality of PET images and coregistered anatomic images obtained with PET/MR, to evaluate the detection of focal uptake and SUV, and to compare these findings with those of PET/CT in patients with head and neck tumours. METHODS: The study group comprised 32 consecutive patients with malignant head and neck tumours who underwent whole-body (18)F-FDG PET/MR and PET/CT. PET images were reconstructed using the attenuation correction sequence for PET/MR and CT for PET/CT. Two experienced observers evaluated the anonymized data. They evaluated image and fusion quality, lesion conspicuity, anatomic location, number and size of categorized (benign versus assumed malignant) lesions with focal uptake. Region of interest (ROI) analysis was performed to determine SUVs of lesions and organs for both modalities. Statistical analysis considered data clustering due to multiple lesions per patient. RESULTS: PET/MR coregistration and image fusion was feasible in all patients. The analysis included 66 malignant lesions (tumours, metastatic lymph nodes and distant metastases), 136 benign lesions and 470 organ ROIs. There was no statistically significant difference between PET/MR and PET/CT regarding rating scores for image quality, fusion quality, lesion conspicuity or anatomic location, number of detected lesions and number of patients with and without malignant lesions. A high correlation was observed for SUVmean and SUVmax measured on PET/MR and PET/CT for malignant lesions, benign lesions and organs (ρ = 0.787 to 0.877, p < 0.001). SUVmean and SUVmax measured on PET/MR were significantly lower than on PET/CT for malignant tumours, metastatic neck nodes, benign lesions, bone marrow, and liver (p < 0.05). The main factor affecting the difference between SUVs in malignant lesions was tumour size (p < 0.01). CONCLUSION: In patients with head and neck tumours, PET/MR showed equivalent performance to PET/CT in terms of qualitative results. Comparison of SUVs revealed an excellent correlation for measurements on both modalities, but underestimation of SUVs measured on PET/MR as compared to PET/CT.