Effect of bivalirudin on coagulation in neonatal (cord) and adult human blood in vitro.

INTRODUCTION: Bivalirudin is recommended as an alternative to heparin in cardiac surgery with cardiopulmonary bypass. Although it has been used in infants and children for this indication, there is a paucity of data on the pharmacologic effects of bivalirudin in neonates. Given the immaturity of the hemostatic system in neonates, we hypothesized that coagulation responses to bivalirudin in this population would be different than in adults. METHODS: Blood samples were drawn from placenta-cord units and from healthy adult donors. The study was carried out in two steps. First, bivalirudin was added to cord and adult blood samples at concentrations of 0, 5, 10, 15, and 20 µg/mL. Activated clotting time and thromboelastographic variables were recorded. Next, we used a Chandler loop system to assess the efficacy of bivalirudin in a simple model of cardiopulmonary bypass. The loops were primed with cord or adult blood and were run until thrombus was detected. Plasma bivalirudin concentrations were measured at 1, 15, 30, 45, 60, and 75 min after initiating rotation of the loops using liquid chromatography/mass spectrometry. RESULTS: Bivalirudin elicited a dose-dependent prolongation inhibition of coagulation in both cord and adult blood samples with greater potency in cord blood in comparison to adult blood (activated clotting time: 627 ± 50 vs. 452 ± 22 s at 15 µg/mL bivalirudin, p < .0001). This relative potency was also demonstrated in the Chandler loop system, but interestingly, cord blood appeared to inactivate bivalirudin more rapidly than adult blood with earlier clotting in loops containing cord blood. CONCLUSIONS: This study demonstrates that bivalirudin has greater potency in cord blood in vitro than in adult blood. Plasma degradation appears to proceed more rapidly in cord blood than in adults. Both of these findings should be considered when planning dosing regimens in neonatal patients.

A comparison of alveolar ridge mucosa thickness in completely edentulous patients.

PURPOSE: The purpose of this cross-sectional clinical study was to determine and compare alveolar ridge mucosa thickness at crestal, buccal, and lingual locations of the maxillary and mandibular arches in completely edentulous patients using a dedicated, ultrasonic gingival scanner. MATERIALS AND METHODS: Thirty-eight completely edentulous subjects were included in the study. In each subject, soft tissue thickness was measured at 28 sites of the edentulous ridge by a single calibrated examiner. Intra-observer reliability was calculated with Intraclass Correlation Coefficients by measuring 10 subjects twice, after 1 week. Measurements (mm) were taken at the buccal, lingual, and crestal aspects of the ridge with a dedicated ultrasonic scanner. Repeated measures ANOVA and paired t-tests were used to compare the mean buccal, lingual, and crestal soft tissue thicknesses at each site. The Generalized Estimating Equations model was used to study the effects of age, sex, and race. Confidence level was set to 95%. RESULTS: Mean tissue thickness ranged from 0.96  to 1.98 mm with a mean of 1.63 ± 0.25 mm. Intraclass Correlation Coefficients were > 0.97. No significant differences between buccal, crestal, and lingual sites were noted for the mandibular arch as well as at 4 sites on the maxillary arch (maxillary right second molar, maxillary right canine, maxillary left first premolar, maxillary left second molar). However, significant differences in soft tissue thickness were noted for all remaining maxillary sites. Race was found to be positively correlated with tissue thickness, with Black individuals showing a significantly greater thickness than White individuals at 4 sites (maxillary right first molar, maxillary left canine, mandibular right second premolar, mandibular right first molar). Age was found to be positively correlated with tissue thickness at 4 sites (maxillary left central incisor, maxillary left first molar, maxillary left second molar, mandibular left second premolar) and negatively correlated at 2 sites (mandibular right canine, mandibular right second molar). Female sex was positively (maxillary left second premolar, maxillary left second molar) and negatively (mandibular right canine) correlated, respectively, with tissue thickness at 3 sites. When data for anterior and posterior sites were respectively pooled, tissue thickness was significantly less at anterior sextant lingual and crestal sites, while no difference was seen for buccal sites. CONCLUSION: Statistically significant differences for alveolar ridge mucosa thickness were found at several sites in the maxilla and between anterior and posterior sextants for lingual and crestal sites in the maxillary and mandibular arches. Tissue thickness differences were also noted for race with Black individuals showing greater tissue thickness at some sites. Age and sex did not show a clear effect on tissue thickness. Recorded differences in tissue thickness were however small and appear of uncertain clinical significance.

Intravenous Dabigatran Provides Adequate Anticoagulation for Cardiopulmonary Bypass Using a Rabbit Model.

BACKGROUND: Heparin anticoagulation has been used successfully for cardiopulmonary bypass (CPB). However, an alternative anticoagulant approach is desirable due to the cases of heparin-induced thrombocytopenia. Dabigatran provides anticoagulation for an in vitro model of simulated CPB. The current analysis tests the hypothesis that dabigatran provides sufficient anticoagulation for CPB in intact rabbits. METHODS: Nonlinear mixed effects models were used to estimate dabigatran parameters for a two-compartment pharmacokinetic model in 10 New Zealand White rabbits. A dabigatran infusion designed to maintain a plasma concentration of 90 µg/ml was run throughout CPB based on the pharmacokinetics. Animals were subjected to sternotomy and anticoagulated with IV dabigatran (six animals) or heparin (four animals). Rabbits were cannulated centrally using the right atrium and ascending aorta and CPB was maintained for 120 min. Measurement of activated clotting time, thromboelastometric reaction time, and blood gases were performed during CPB. Then, the animals were euthanized, and the brain and one kidney were removed for histology. Sections of the arterial filters were inspected using electron microscopy. RESULTS: The observed dabigatran concentrations during CPB were greater than the target concentration, ranging from 137 ± 40 µg/ml at 5 min of CPB to 428 ± 150 µg/ml at 60 min, and 295 ± 35 µg/ml at 120 min. All rabbits completed 2 h of CPB without visible thrombosis. In the two groups, reaction time values were elevated, reaching 10,262 ± 4,198 s (dabigatran group) and 354 ± 141 s (heparin group) at 120 min of CPB. Brains and kidneys showed no evidence of thrombosis or ultrastructural damage. Sections of the arterial line filter showed minimal or no fibrin. There was no significant difference in outcomes between dabigatran- and heparin-treated animals. CONCLUSIONS: In this first-use, proof-of-concept study, the authors have shown that dabigatran provides acceptable anticoagulation similar to heparin to prevent thrombosis using a rabbit CPB model.

Is Recreational Marijuana Use Associated With Changes in the Vital Signs or Anesthetic Requirements During Intravenous Sedation?

PURPOSE: The prevalence of tetrahydrocannabinol (THC) use is increasing in the general population due to its increased availability, legality, and cultural acceptability. The purpose of the current study was to measure the association of THC use on the vital signs and anesthetic requirements during intravenous (IV) sedation procedures in recreational marijuana users. METHODS: A retrospective cohort study was performed. A study sample was chosen from July 2018 to May 2022 based on the following inclusion criteria: patients who underwent toxicology screening due to their history of recent drug use and received IV sedation. The predictor variable of the present study is THC status grouped into THC+ and THC-. THC status was established using urine toxicology. Patients who screened positive for THC were coded THC+. Patients who screened negative for THC were coded THC-. Primary outcome variable was changes in vital signs, including mean arterial pressure (MAP), heart rate (HR), and respiratory rate (RR) during IV sedation procedures in THC+ and THC- groups. Secondary outcome variable was difference in medication (midazolam, fentanyl, propofol, and ketamine) requirements in THC+ and THC- groups. Covariates included age, gender, race, weight, duration of surgery, smoking history, and alcohol use, data on psychiatric diagnosis and psychiatric medications. Descriptive statistics and 2-sample t test were calculated. Statistical significance was set at P < .05. RESULTS: In total, 53 patients met the inclusion criteria and were included in the study, with 27 patients in the THC+ group and 26 patients in the THC- group. There were no significant statistical differences in the MAP%, HR%, and RR% at T5, T10, T20, and T30 between the THC+ and THC- groups. When comparing THC+ and THC- groups, in bivariate analyses, the THC+ group required, on average, higher doses of fentanyl [83.82 mcg compared to 65 mcg (P = .02)] and propofol [70 mg compared to 45.26 mg (P = .03)] during IV sedation. However, after adjusting the effect of age, gender, and weight, THC had no significant effect on midazolam (P-value = .28), fentanyl (P-value = .12), propofol (P-value = .06) and ketamine (P-value = .86) requirements. CONCLUSIONS: These findings suggest there are no differences in vital signs or anesthetic requirements between the THC+ and THC- groups.

Accuracy of Telemedicine Consultations in Oral and Maxillofacial Surgery During the COVID-19 Pandemic.

PURPOSE: Telemedicine has been an emerging trend over the past few years and has seen an exponential rise due to the COVID-19 pandemic. The purpose of the present study was to determine the accuracy of planned oral and maxillofacial surgery (OMS) procedures for patients seen initially by telemedicine in the department of OMS during the pandemic. METHODS: This was a retrospective cohort study. Record review of all patients who received telemedicine consultations during the pandemic time frame of March 1, 2020, to March 1, 2021, was performed. The primary outcome was the accuracy of the planned OMS procedure. Accuracy was defined as the ability to conduct the planned surgery with chosen anesthesia (local anesthesia, diazepam + local anesthesia, intravenous sedation, general anesthesia) at the immediate follow-up appointment without the need for further preoperative testing, evaluation, and consultation. The secondary outcomes were to determine the change in surgical plan, anesthesia plan, and medical plan. Predictor variables included age at the time of telemedicine consultation, gender, race, ethnicity, and the type of consult. Descriptive statistics and logistic regression analysis were executed. RESULTS: The study sample comprised 286 (64.56%) females and 157 (35.44%) males. The age range of the study population was 9 to 92 years, with a mean age of 33.88 years (standard deviation = 16.29 years). In the cohort of 443 patients who obtained telemedicine consultations, 98.19% were successfully treated at the following appointment. Four hundred thirty-one (97.3%) out of the 443 telemedicine consults pertained to dentoalveolar concerns. Logistic regression analysis showed that neither age nor gender had significant effects on the change of surgical and anesthesia plans. CONCLUSIONS: Telemedicine can be effectively utilized in performing consultations for routine OMS procedures, especially dentoalveolar surgeries. Telemedicine consultation can also be used to conduct a preoperative assessment to determine anesthesia and setting of care. However, given the lack of control group and the observational nature of this study, the results must be interpreted with caution.

Effect of implant angulation and patrice on the retention of overdenture attachment systems: An in vitro study.

PURPOSE: To test the retention of two different overdenture attachment matrices and straight abutments when implants are placed at 0-, 15-, and 30-degree diverging angulations as well as the retention of 15-degree-angled abutments to correct the overall angulation to 0-degrees. MATERIALS AND METHODS: Matching aluminum blocks were machined to incorporate two dental implants at 0-degree, 15-degree, and 30-degree relative angulations and overdenture attachments to simulate a two-implant overdenture. At 0-degree, 15-degree, and 30-degree implant angulation, straight abutments were studied. At 30-degree implant angulation, an additional group was compared utilizing 15-degree angulated abutments that corrected the overall implant angulation to 0-degrees. A custom-designed testing apparatus that allowed automated insertion and removal of the simulated overdenture was designed, with three independent testing stations, each consisting of one simulated arch and one simulated overdenture base. The baseline and residual retention forces after 30,000 dislodging cycles of the simulated overdenture were measured. One-way ANOVA was used to compare retention differences among different color patrices within the 0-, 15-, and 30-degree implant angulation groups followed by Tukey's multiple comparison test. Two sample t-tests were used to compare 0-degree versus 15-degree implant groups with straight abutments and 30-degree implant groups with straight abutments versus 30-degree implant groups with angulated abutments. RESULTS: Regardless of implant angulation or abutment correction, the change in retention exhibited by the Novaloc system after testing was not statistically significant for all patrice types (p > 0.05); however, the change in retention exhibited by the Locator system was statistically significant for the tested group (p = 0.0272). In both the Novaloc and Locator systems, the baseline and final retention values provided by the different patrices were significantly different except for the white and green Novaloc patrices in the 15-degree divergent implant group which did not meet the specified level of significance (p = 0.0776). CONCLUSION: Within the limitations of this study, implant angulations upto 15 degrees do not affect differential change in retention of Novaloc patrices. There is no difference between Novaloc white inserts (light retention value) and green inserts (strong retention values) when implants diverge upto 15 degrees. When Novaloc straight abutments were placed on implants diverging by 30 degrees, blue extra-strong retention inserts outperformed yellow medium retention inserts by maintaining a higher retention value after 30,000 cycles. When utilizing Novaloc 15-degree angulated abutments that correct the overall implant angulation to zero degrees, the red light retentive patrice provides steady retention. Finally, the Locator-green patrice system provides greater retention than the comparable Novaloc-blue patrice combination; however, it also loses more retention after 30,000 cycles.

Rivaroxaban Reduces the Dabigatran Dose Required for Anticoagulation During Simulated Cardiopulmonary Bypass.

BACKGROUND: Heparin is the standard anticoagulant for cardiopulmonary bypass (CPB); however, there are problems with its use that make the development of suitable alternatives desirable. Currently, no ideal alternative exists. We have previously reported that the direct thrombin inhibitor dabigatran can prevent coagulation in simulated CPB at high concentrations. These high concentrations may cause difficulties in achieving the reversal of dabigatran with idarucizumab, given the markedly different pharmacokinetics of the 2 drugs. Herein, we test the hypothesis that the addition of the anti-Xa drug rivaroxaban would provide suitable anticoagulation at a lower concentration of dabigatran given likely synergy between the 2 classes of drugs. The primary goal of the study was to investigate whether the addition of rivaroxaban reduces the concentration of dabigatran necessary to allow 2 hours of simulated CPB. METHODS: The study was performed in sequential steps. Blood collected from consenting healthy donors was used throughout. First, we added graded concentrations of dabigatran and rivaroxaban alone and in combination and assessed inhibition of anticoagulation using thromboelastometry. Using results from this step, combinations of dabigatran and rivaroxaban were tested in both Chandler loop and simulated CPB circuits. Dabigatran and rivaroxaban were added before recalcification, and the circuits were run for 120 minutes. In both models of CPB, 120 minutes of circulation without visible thrombus was considered successful. In the Chandler loop system, idarucizumab was added to reverse anticoagulant effects. In the CPB circuits, the arterial line filters were examined using scanning electron microscope (SEM) to qualitatively assess for fibrin deposition. RESULTS: In vitro analysis of blood samples treated with dabigatran and rivaroxaban showed that dabigatran and rivaroxaban individually prolonged clotting time (CT) in a dose-dependent manner. However, when combined, the drugs behaved synergistically. In the Chandler loop system, dabigatran 2400 and 4800 ng/mL plus rivaroxaban (150 ng/mL) effectively prevented clot formation and reduced the dynamics of clot propagation for 120 minutes. Idarucizumab (250-1000 µg/mL) effectively reversed anticoagulation. In the CPB circuits, dabigatran (2500 ng/mL) and rivaroxaban (200 ng/mL) were successful in allowing 120 minutes of simulated CPB and prevented fibrin deposition. Biomarkers of coagulation activation did not increase during simulated CPB. Heparin controls performed similarly to dabigatran and rivaroxaban. CONCLUSIONS: The dual administration of oral anticoagulant drugs (dabigatran and Rivaroxaban) with different pharmacologic mechanisms of action produced synergistic inhibition of coagulation in vitro and successfully prevented clotting during simulated CPB.

Clinical Evaluation of Pink Esthetic Score of Immediately Impressed Posterior Dental Implants.

PURPOSE: While comparative outcome results for peri-implant crestal bone levels, mucosal margin position, and peri-implant indices have been reported, no studies are available that evaluate and compare the esthetic result of impressions performed immediately at implant placement with that of impressions performed on healed implants. The purpose of this cross-sectional study was to evaluate the pink esthetic score of posterior implants restored with an immediate impression workflow compared to implants restored with a delayed impression workflow. MATERIAL AND METHODS: Twenty-eight eligible participants who had received a single implant crown either in the premolar or molar regions at least 4 months before the study, were identified by an electronic health record review and scheduled for a single-visit study appointment. Esthetic outcomes were measured using the pink esthetic score. Several local- and prosthesis-related factors were recorded and their association with the selected outcome was assessed. Two-sample t-test was used for comparisons between the groups. RESULTS: Pink esthetic score ranged between 4 and 12 (mean: 8). No significant difference between immediate (8.36 ±1.12) and delayed (7.76 ±2.14) impression workflow groups were seen for the total PES (p = 0.25). In addition, individual comparisons between immediately and delayed impressed implants for mesial papilla (1.27 ±0.47; 0.88 ±0.78), distal papilla (0.73 ±0.65; 0.76 ±0.83), tissue margin (1.73 ±0.47; 1.47 ±0.51), tissue contour (1.27 ±0.65; 0.82 ±0.64), alveolar process (0.82 ±0.60; 1.00 ±0.87), color (1.27 ±0.65; 1.29 ±0.69), and texture (1.36 ±0.50; 1.53 ±0.62) did not show significant differences. CONCLUSIONS: The current study suggests that the pink esthetic score is not significantly different between single posterior implants impressed with immediate and delayed implant workflows.

A Live Attenuated Influenza Vaccine Elicits Enhanced Heterologous Protection When the Internal Genes of the Vaccine Are Matched to Those of the Challenge Virus.

Influenza A virus (IAV) causes significant morbidity and mortality, despite the availability of viral vaccines. The efficacy of live attenuated influenza vaccines (LAIVs) has been especially poor in recent years. One potential reason is that the master donor virus (MDV), on which all LAIVs are based, contains either the internal genes of the 1960 A/Ann Arbor/6/60 or the 1957 A/Leningrad/17/57 H2N2 viruses (i.e., they diverge considerably from currently circulating strains). We previously showed that introduction of the temperature-sensitive (ts) residue signature of the AA/60 MDV into a 2009 pandemic A/California/04/09 H1N1 virus (Cal/09) results in only 10-fold in vivo attenuation in mice. We have previously shown that the ts residue signature of the Russian A/Leningrad/17/57 H2N2 LAIV (Len LAIV) more robustly attenuates the prototypical A/Puerto Rico/8/1934 (PR8) H1N1 virus. In this work, we therefore introduced the ts signature from Len LAIV into Cal/09. This new Cal/09 LAIV is ts in vitro, highly attenuated (att) in mice, and protects from a lethal homologous challenge. In addition, when our Cal/09 LAIV with PR8 hemagglutinin and neuraminidase was used to vaccinate mice, it provided enhanced protection against a wild-type Cal/09 challenge relative to a PR8 LAIV with the same attenuating mutations. These findings suggest it may be possible to improve the efficacy of LAIVs by better matching the sequence of the MDV to currently circulating strains.IMPORTANCE Seasonal influenza infection remains a major cause of disease and death, underscoring the need for improved vaccines. Among current influenza vaccines, the live attenuated influenza vaccine (LAIV) is unique in its ability to elicit T-cell immunity to the conserved internal proteins of the virus. Despite this, LAIV has shown limited efficacy in recent years. One possible reason is that the conserved, internal genes of all current LAIVs derive from virus strains that were isolated between 1957 and 1960 and that, as a result, do not resemble currently circulating influenza viruses. We have therefore developed and tested a new LAIV, based on a currently circulating pandemic strain of influenza. Our results show that this new LAIV elicits improved protective immunity compared to a more conventional LAIV.

Oncological and functional outcomes in patients over 70 years of age treated with robotic radical prostatectomy: a propensity-matched analysis.

PURPOSE: The aim of this study was to report on the safety (complications) and efficacy (oncological and functional outcomes) of robot-assisted radical prostatectomy (RARP), performed at our institution, in patients aged over 70. PATIENTS AND METHODS: Review of our prospectively collected database [Cancer Information Systems (CAISIS)] identified two hundred and fifteen (215) patients, aged > 70, who underwent RARP for localized prostate cancer between July 2003 and August 2017. A propensity score-matched analysis, with multiple covariates, was performed to stratify the patients into Age ≤ 70 and Age > 70 comparison groups. RESULTS: Apart from Age (mean ± SD years: 73.5 ± 2.1 vs 59.5 ± 5.9, p < 0.0001) and nerve-sparing status, the two groups were evenly matched for all covariates (p values > 0.05). Median follow-up was 10.6 years. There were no 90-day mortalities in either group. Minor complications (Clavien ≤ 2) were more common in the Age > 70 group (p = 0.0002). Operating room time (p = 0.83), length of hospital stay (p = 0.06) and catheterization duration (p = 0.13) were similar. On final pathology, a higher pT stage (p < 0.0001) and pN1 (p = 0.003) were observed in the Age > 70 group. However, this did not translate adversely into higher rates of positive surgical margin (p = 0.41) or biochemical relapse (p = 0.72). Allowing for the follow-up duration (median 10.6 years), cancer-specific survival was marginally significant (p = 0.05) with an observed lower rate in the Age > 70 group. In terms of functional outcomes, post-operative erectile dysfunction and pad-free continence were significantly better in the younger cohort (p < 0.0001). CONCLUSIONS: Robot-assisted radical prostatectomy should not be denied to those over 70 years solely on the basis of age. Older men need to be counseled about the likelihood of encountering higher-risk features on final pathology and that their functional outcomes may be worse compared to a younger person.

Survey of Practice Pattern in Patients With Heparin-Induced Thrombocytopenia Requiring Cardiopulmonary Bypass.

BACKGROUND: Heparin-induced thrombocytopenia (HIT) is an immune-mediated adverse reaction to heparin. Patients undergoing cardiac surgery with cardiopulmonary bypass (CPB) are routinely anticoagulated with heparin before the initiation of bypass. Heparin is contraindicated, however, in patients with acute HIT, and alternatives to routine practice are often used. While guidelines have recently been published addressing this topic 10, there remains variance between institutions in how these cases are treated. Our goal was to better delineate practice trends in the diagnosis and management of HIT patients requiring CPB. METHODS: We surveyed members of the Society of Cardiovascular Anesthesiologists (SCA) and the American Society for Extracorporeal Technology (AmSECT) using an online survey tool. RESULTS: We received 304 completed surveys (5.8% response rate), 75% completed by an anesthesiologist, and 24% by a perfusionist. The majority of respondents used clinical history and/or antibody testing (71% and 63%, respectively) to diagnose HIT. Seventy-five percent of respondents reported using an institutional protocol for HIT-CPB cases. Most respondents (89%) reported having at least 1 case in the last 3 years, with a total case experience of at least 785 cases (785 = the minimum number of cases in each case volume category × the number of respondents choosing that category). The strategy recommended in published guidelines, bivalirudin, was the most commonly reported alternative anticoagulation strategy (75%) used by respondents in HIT cases, with most (83%) using the activated clotting time (ACT) to monitor anticoagulation. CONCLUSIONS: Most responding SCA and AmSECT members reported that their institution used a protocol or guideline for HIT/CPB cases, and most guidelines directed the use of bivalirudin as an alternative anticoagulant. Various other methods such as plasmapheresis are also being used with success in this patient population. Further research, including comparison studies of alternative anticoagulant strategies, is required to elucidate the best approach to these difficult cases.

High-Dose Dabigatran Is an Effective Anticoagulant for Simulated Cardiopulmonary Bypass Using Human Blood.

BACKGROUND: Currently no ideal alternative exists for heparin for cardiopulmonary bypass (CPB). Dabigatran is a direct thrombin inhibitor for which a reversal agent exists. The primary end point of the study was to explore whether Dabigatran was an effective anticoagulant for 120 minutes of simulated CPB. METHODS: The study was designed in 2 sequential steps. Throughout, human blood from healthy donors was used for each experimental step. Initially, increasing concentrations of Dabigatran were added to aliquots of fresh whole blood, and the anticoagulant effect measured using kaolin/tissue factor-activated thromboelastography (rapidTEG). The dynamics of all thromboelastography (TEG) measurements were studied with repeated measures analysis of variance (ANOVA). Based on these data, aliquots of blood were treated with high-concentration Dabigatran and placed in a Chandler loop as a simple ex vivo bypass model to assess whether Dabigatran had sufficient anticoagulant effects to maintain blood fluidity for 2 hours of continuous contact with the artificial surface of the PVC tubing. Idarucizumab, humanized monoclonal antibody fragment, was used to verify the reversibility of Dabigatran effects. Finally, 3 doses of Dabigatran were tested in a simulated CPB setup using a heart-lung machine and a commercially available bypass circuit with an arteriovenous (A-V) loop. The primary outcome was the successful completion of 120 minutes of simulated CPB with dabigatran anticoagulation, defined as lack of visible thrombus. Thromboelastographic reaction (R) time was measured repeatedly in each bypass simulation, and the circuits were continuously observed for clot. Scanning Electron Microscopy (SEM) was used to visualize fibrin formation in the filters meshes during CPB. RESULTS: In in vitro blood samples, Dabigatran prolonged R time and reduced the dynamics of clot propagation (as measured by speed of clot formation [Angle], maximum rate of thrombus generation [MRTG], and time to maximum rate of thrombus generation [TMRTG]) in a dose-dependent manner. In the Chandler Loop, high doses of Dabigatran prevented clot formation for 120 minutes, but only at doses higher than expected. Idarucizumab decreased R time and reversed anticoagulation in both in vitro and Chandler Loops settings. In the A-V loop bypass simulation, Dabigatran prevented gross thrombus generation for 120 minutes of simulated CPB. CONCLUSIONS: Using sequential experimental approaches, we showed that direct thrombin inhibitor Dabigatran in high doses maintained anticoagulation of blood for simulated CPB. Idarucizumab reduced time for clot formation reversing the anticoagulation action of Dabigatran.

Patients' and parents' expectations of orthodontic treatment in university settings.

INTRODUCTION: The primary aim was to compare patients' and parents' orthodontic treatment expectations at the Eastman Institute for Oral Health, University of Rochester, Rochester, NY (UR) in the United States. Secondary aims were to assess the association between sociodemographic factors and UR participants' expectations; and compare participants' expectations between UR, Academic Centre for Dentistry Amsterdam (ACTA) and King's College Dental Hospital, London, United Kingdom (KC) (previously published data). METHODS: One hundred and forty participants [70 patients and one of their parents (n = 70)] completed a validated questionnaire (10 questions) to measure orthodontic treatment expectations before screening at the Orthodontic Department at UR. Various sociodemographic factors were assessed. The paired t test (for continuous responses) and the Fisher exact test (for categorical responses) were used to compare UR patients' and parents' responses. Two-sample t test and the Fisher exact test were used to compare participants' responses among sociodemographic groups. One-way analysis of variance followed by the Tukey test, and the Fisher exact test were used to compare participants' responses between UR, and ACTA and KC (data collected from previous publications). A multiplicity correction was performed to control the false discovery rate. RESULTS: Patients at UR expected less check-up and diagnosis, and less discussion about treatment at the initial visit, more dietary restrictions, and less improvement in smile esthetics and social confidence with orthodontic treatment than parents. Participants' responses differed by sociodemographic factors at UR and between UR, ACTA, and KC. CONCLUSIONS: Expectations of orthodontic treatment differ between patients and their parents, are associated with sociodemographic factors, and vary among United States and European University centers.

Clinical Evaluation of Crestal Bone Levels, Peri-Implant Indices, and Mucosal Margin Position of Immediately Impressed Posterior Dental Implants: A Cross-Sectional Study.

PURPOSE: This is a cross-sectional clinical study to evaluate crestal bone levels, mucosal margin position, probing depths, bleeding on probing, and plaque and bleeding indices of implants restored with an immediate impression workflow compared to implants restored with a delayed impression workflow. MATERIALS AND METHODS: Patients who had received a posterior single implant crown in the premolar and molar regions were identified and scheduled for a single-visit study appointment. Outcome measurements included soft tissues peri-implant indices, peri-implant mucosal margin position, and crestal bone levels. Several systemic-, local-, and prosthesis-related factors were recorded. Bitewing radiographs were used to assess crestal bone levels. Wilcoxon rank sum test was used to compare the medians of continuous measurements and Pearson chi-square test (or Fisher's exact test) was used to compare the distributions of categorical variables between the two groups. RESULTS: Twenty eight patients were included. Crestal bone levels, peri-implant mucosal margin position and peri-implant soft tissue parameters for the immediately impressed group were not statistically different from the delayed impressed group, except for probing depth for the immediately impressed buccal site, which was less than that of the delayed group. Mesial bone level for cement-retained crowns was significantly more coronal than for screw-retained ones. CONCLUSIONS: While an isolated statistical difference was found in probing depth, the current study suggests that there is no clinically significant difference between implants impressed with immediate and delayed implant workflows when considering crestal bone levels, peri-implant mucosal margin position, and most peri-implant indices.

Dimensional stability of double-processed complete denture bases fabricated with compression molding, injection molding, and CAD-CAM subtraction milling.

STATEMENT OF PROBLEM: Studies evaluating the dimensional stability of denture bases fabricated by the double processing method are lacking. PURPOSE: The purpose of this in vitro study was to evaluate the dimensional stability of denture bases fabricated by 3 different techniques: compression molding, injection molding, and computer-aided design and computer-aided manufacturing (CAD-CAM) subtraction milling. MATERIAL AND METHODS: Forty-five mandibular denture bases were fabricated from a master cast by a standardized process. A double processing protocol was used with 3 methods: compression molding (PRESS), injection molding (INJECT), or CAD-CAM (CAD). The bases were compared with the titanium master cast after the first processing. By a digital subtraction process, the dimensional stability of the bases was measured at 22 different locations on the intaglio surface. Denture teeth were then positioned according to a standardized protocol, and the denture was processed a second time and finished. The dimensional discrepancy was reassessed after the second processing and compared with the titanium master cast. RESULTS: In all groups, most of the dimensional changes occurred during the first processing (P<.05), with no statistically significant deformation occurring during the second processing (P>.05). The CAD group presented significantly smaller dimensional changes than PRESS (P<.05) and INJECT (P<.05) groups. No significant difference was found in the dimensional stability in the PRESS and INJECT groups (P>.05). CONCLUSIONS: Denture bases fabricated by a CAD-CAM methodology exhibit fewer dimensional changes than either compression or injection molding. Distortion occurred during the fabrication of the denture base, and a second processing did not significantly affect the dimensional stability of the denture base.

The relations among three popular indices of risks.

The relative risk, risk difference, and odds ratio are three major indices of differences in risks of diseases between different groups. Although widely used in research and practice in biomedical and epidemiologic research, misconceptions are not uncommon about their relationships. Many publications offer contradicting advices in how to use them in studies. Some biomedical researchers believe that these indices are related in a monotone fashion, and, thus, changes in one direction in one of the indices can be interpreted as same directional changes in the other two. Misconceptions about these three indices such as the monotone relationship are so prevalent in the biomedical and epidemiologic research that clarifications of such popular beliefs are warranted. In this paper, we take a systematic approach to characterize the relationships among the indices. We develop key results to elucidate the intricate relationships between the indices. Our findings speak to the need for investigators to carefully consider the different indices before using them in their studies, since they are not interchangeable and results based on one index are generally not translatable into any of the others.

Multi-institutional nomogram predicting benign prostate pathology on magnetic resonance/ultrasound fusion biopsy in men with a prior negative 12-core systematic biopsy.

BACKGROUND: Prostate multiparametric magnetic resonance imaging (mpMRI) may be recommended for patients with a prior negative systematic biopsy (SB). However, a proportion of these patients will continue to have no prostate cancer (PCa) identified on magnetic resonance/ultrasound fusion biopsy (FB) despite abnormal mpMRI findings. METHODS: In this multi-institutional, retrospective study, clinical and mpMRI parameters were assessed for 285 consecutive patients with at least 1 prior negative biopsy who underwent FB for a Prostate Imaging Reporting and Data System (PI-RADS) score of 3 to 5 at the University of Rochester Medical Center from December 2014 to December 2016, or at the University of Alabama at Birmingham from February 2014 to February 2017. Nomograms were generated for predicting benign prostate pathology on both the targeted biopsy and the concurrent SB. RESULTS: Benign pathology was found in 132 of 285 patients (46.3%). In a multivariate analysis, the predictors of benign prostate pathology on FB were age, prostate-specific antigen, prostate volume, and PI-RADS score. The predicted probabilities were plotted on a receiver operating characteristic curve, and the area under the curve was 0.825. The nomogram demonstrated excellent calibration and a high net benefit in a decision curve analysis. With a theoretical cutoff probability of ≥0.7 used to recommend deferment of FB, 61 of 285 patients (21.4%) would have avoided an unnecessary biopsy, and only 4 of 285 patients (1.4%) with PCa with a Gleason score ≥ 3 + 4 would have been missed. CONCLUSIONS: False-positive mpMRI examinations may occur in up to 46.3% of patients with a prior negative biopsy. Thus, a multi-institutional nomogram has been developed and validated for predicting benign pathology after FB in patients with a prior negative biopsy, and this may help to reduce the number of unnecessary biopsies in the setting of abnormal mpMRI findings. Cancer 2018;124:278-85. © 2017 American Cancer Society.

A Comprehensive Analysis of Cribriform Morphology on Magnetic Resonance Imaging/Ultrasound Fusion Biopsy Correlated with Radical Prostatectomy Specimens.

PURPOSE: Recently a large body of evidence has emerged indicating that cribriform morphology is an aggressive prostate cancer morphological pattern associated with higher cancer specific mortality. In a comprehensive analysis we compared traditional and contemporary prostate biopsy techniques to detect prostate cancer with cribriform morphology with radical prostatectomy serving as the reference standard. MATERIALS AND METHODS: We queried a retrospectively maintained, single institution, multiparametric magnetic resonance imaging database of 1,001 patients to identify 240 who underwent magnetic resonance imaging-ultrasound fusion targeted biopsy and concurrent systematic biopsy from December 2014 to December 2016. Of the 3,978 biopsy cores obtained 694 positive cores were rereviewed by a genitourinary pathologist for pattern 4 subtype (cribriform, fused and poorly formed glands). Using paired analysis pathological results among 3 biopsy methods (systematic biopsy, targeted biopsy and systematic plus targeted biopsy) were compared. Prostatectomy specimens were also pathologically reviewed. RESULTS: Systematic plus targeted biopsy was superior to systematic biopsy alone or targeted biopsy alone to detect cribriform morphology (all p <0.0001). On final histopathology cribriform tumor foci were associated with an increased percent of pattern 4 involvement and extraprostatic extension (p <0.0001 and 0.003, respectively). Only 17.4% of cribriform tumors in pure form were visible on multiparametric magnetic resonance imaging. Based on final histopathology the sensitivity of systematic biopsy, targeted biopsy and systematic plus targeted biopsy for cribriform morphology was 20.7%, 28.6% and 37.1%, respectively. CONCLUSIONS: Although systematic plus targeted biopsy was the most accurate biopsy method to detect cribriform morphology, biopsy sensitivity and specificity remained poor.

Variability in Case Durations for Common Surgical Procedures.

BACKGROUND: Under the Merit-based Incentive Payment System, physician payment will be adjusted using a composite performance score that has 4 components, one of which is resource use. The objective of this exploratory study is to quantify the facility-level variation in surgical case duration for common surgeries to examine the feasibility of using surgical case duration as a performance metric. METHODS: We used data from the National Anesthesia Clinical Outcomes Registry on 404,987 adult patients undergoing one of 6 general surgical or orthopedic procedures: laparoscopic appendectomy, laparoscopic cholecystectomy, laparoscopic cholecystectomy with intraoperative cholangiogram, knee arthroscopy, laminectomy, and total hip replacement. We constructed separate mixed-effects multivariable time-to-event models (survival analysis) for each of the 6 procedures to model surgical case duration. RESULTS: We identified performance outliers, based on surgical case duration, using 2013 data and then quantified the gap between high- and low-performance outliers using 2014 data. After adjusting for patient risk, patients undergoing surgery at high-performance facilities were between 54% and 79% more likely to exit the operating room (OR) per unit time compared to average-performing facilities, depending on the procedure. For example, patients undergoing a laparoscopic appendectomy at high-performance facilities were 68% more likely to exit the OR per unit time (hazard ratio, 1.68; 95% CI, 1.40-2.02; P < .001) compared to average-performing facilities. Patients undergoing a laparoscopic appendectomy at low-performance facilities were 41% less likely to exit the OR per unit time (hazard ratio, 0.59; 95% CI, 0.47-0.74; P < .001) compared to average-performing facilities. The adjusted median surgical case duration for patients undergoing laparoscopic appendectomy was 69 minutes at high-performance centers and 92 minutes at low-performance centers. Similar results were obtained for the other procedures. CONCLUSIONS: There was wide variation in surgery case duration for patients undergoing common general surgical and orthopedic surgeries. This variability in care delivery may represent an important opportunity to promote more efficient use of health care resources.

Dendritic Cell-Specific Transmembrane Protein (DC-STAMP) Regulates Osteoclast Differentiation via the Ca2+ /NFATc1 Axis.

DC-STAMP is a multi-pass transmembrane protein essential for cell-cell fusion between osteoclast precursors during osteoclast (OC) development. DC-STAMP-/- mice have mild osteopetrosis and form mononuclear cells with limited resorption capacity. The identification of an Immunoreceptor Tyrosine-based Inhibitory Motif (ITIM) on the cytoplasmic tail of DC-STAMP suggested a potential signaling function. The absence of a known DC-STAMP ligand, however, has hindered the elucidation of downstream signaling pathways. To address this problem, we engineered a light-activatable DC-STAMP chimeric molecule in which light exposure mimics ligand engagement that can be traced by downstream Ca2+ signaling. Deletion of the cytoplasmic ITIM resulted in a significant elevation in the amplitude and duration of intracellular Ca2+ flux. Decreased NFATc1 expression in DC-STAMP-/- cells was restored by DC-STAMP over-expression. Multiple biological phenotypes including cell-cell fusion, bone erosion, cell mobility, DC-STAMP cell surface distribution, and NFATc1 nuclear translocation were altered by deletion of the ITIM and adjacent amino acids. In contrast, mutations on each of the tyrosine residues surrounding the ITIM showed no effect on DC-STAMP function. Collectively, our results suggest that the ITIM on DC-STAMP is a functional motif that regulates osteoclast differentiation through the NFATc1/Ca2+ axis. J. Cell. Physiol. 232: 2538-2549, 2017. © 2016 Wiley Periodicals, Inc.