Challenges of biological monitoring in a hemophilia A patient without inhibitors on emicizumab undergoing major orthopedic surgery: a case report.
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SUBMITTER: Guillaume L
PROVIDER: S-EPMC8404639 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Dysnatremia may predispose to falls and fractures, and serum sodium may influence bone health. Little is known of the association of perioperative dysnatremia and clinical outcomes in those undergoing major orthopedic surgery.We examined the association of serum sodium (corrected for glucose) with morbidity and mortality in a sample of hospitalized patients undergoing major orthopedic procedures at 2 large academic medical centers.Retrospective observational study.Adult patients admitted to major academic teaching hospitals for a major orthopedic procedure from January 2006 to January 2011.The association of serum sodium with log-transformed hospital length of stay was assessed by fitting linear regression models. The association with 30-day mortality was assessed by fitting Cox proportional hazards models.There were 16,206 unique admissions, of which 44.8% were male, with a mean age of 62.5 years. Mean corrected serum sodium was 138.5 ± 2.9 mmol/L; 1.2% had moderate/severe hyponatremia, 6.4% had mild hyponatremia, and 2.5% were hypernatremic. In adjusted models, compared with normonatremia, moderate/severe hyponatremia, mild hyponatremia, and hypernatremia were associated with a 1.6-, 1.4-, and 1.4-day-longer hospital stay, respectively, and greater risk of 30-day mortality (hazard ratio [HR]: 2.47, 95% confidence interval [CI]: 1.33-4.59 for moderate/severe hyponatremia; HR: 1.80, 95% CI: 1.21-2.66 for mild hyponatremia; and HR: 2.99, 95% CI: 1.79-4.98 for hypernatremia).Dysnatremia is relatively common in the hospitalized orthopedic population and associated with greater length of stay and 30-day mortality. Future studies should address potential mechanisms underlying these associations and whether correction of perioperative dysnatremia may improve patient outcomes.
| S-EPMC4815900 | biostudies-literature
Project description:Background:Children undergoing major orthopedic surgery of the lower extremities can experience severe postoperative pain; yet, the ideal postoperative pain management strategy is unknown. Thus, in this patient population, we investigated the effect of intraoperative epidural infusion of local anesthetic on acute postoperative pain and analgesic consumption. Patients and methods:Patients (N=50, 3-12 years) randomly received either ropivacaine 0.15% (preemptive group) or normal saline (control group) as an initial bolus of 0.2 mL/kg, followed by continuous infusion of 0.15 mL/kg/h throughout surgery. Following surgery, patient-controlled epidural analgesia with ropivacaine 0.1% was provided. The main study outcomes were the revised Face, Legs, Activity, Cry, and Consolability pain scores, epidural ropivacaine consumption, and additional analgesic requirements during the first 48 hours postoperatively. Results:Forty-seven patients completed the study, 23 in the preemptive group and 24 in the control group, respectively. The revised Face, Legs, Activity, Cry, and Consolability pain scores were significantly lower in the preemptive group only at 30 minutes after postanesthesia care unit arrival and 6 hours after surgery (median difference -1.0, 95% CI -2.0 to -1.0, P=0.001 and median difference -2.0, 95% CI -3.0 to -1.0, P=0.005, respectively). However, they were not significantly different between the groups at 12, 24, and 48 hours postoperatively. Epidural ropivacaine consumption and additional analgesic requirements throughout 48 hours postoperatively were not significantly different between the groups. Conclusion:Intraoperative epidural infusion of ropivacaine did not demonstrate preemptive analgesic efficacy within 48 hours postoperatively in children undergoing extensive lower limb orthopedic surgery.
| S-EPMC6162994 | biostudies-literature
Project description:BackgroundEmicizumab, a bispecific antibody factor VIII mimetic, is approved for prophylaxis in hemophilia, and has different risks and side effects compared to factor VIII products.ObjectiveTo better understand the early impact of emicizumab on our patients at the University of Colorado Hemophilia and Thrombosis Center (UCHTC), we evaluated adverse reactions, factor prophylaxis overlap, and bleeding rates after starting emicizumab through a quality improvement project.Patients/methodsA retrospective chart review and structured phone interview were conducted from June to September 2019 for all patients who had started emicizumab at the UCHTC. Data about emicizumab dosing, reactions, bleeding events, and bleeding treatment were collected in 68 children and adults (aged 0.55-79.8 years, on emicizumab a median 213 days; range, 51-1229 days) with hemophilia A (35.3% with past or current inhibitor).ResultsAdverse reactions were primarily skin reactions, with no anaphylactic reactions or thrombosis. Bleeding events, defined as pain or swelling treated with factor or supportive measures, demonstrated wide variability, with 25 of 68 experiencing zero bleeds and 5 of 68 experiencing >8 bleeds per year. The most prevalent bleed type was traumatic musculoskeletal bleeding. Bleeding events occurred more often in the first 10 weeks after starting emicizumab, but no time period was without bleeding events. The majority of patients were prescribed every-week or every-2-week dosing, but some had alternative dosing frequency.ConclusionsReal-world emicizumab use in our center was characterized by variations in prescribing practices and bleeding outcomes and lack of severe adverse reactions.
| S-EPMC8331949 | biostudies-literature
Project description:BackgroundMonitoring of the macrocirculation during surgery provides limited information on the quality of organ perfusion.ObjectiveWe investigated the feasibility of perioperative microcirculatory measurements in children.MethodsSublingual microvessels were visualized by handheld videomicroscopy in 11 children (19 mo - 10 yrs) undergoing surgery > 120 min at four time points: T0) after induction of anesthesia; T1) before end of anesthesia, T2) 6 h post surgery and T3) 24 h post surgery.ResultsMeasurements were feasible in all children at T0 and T1. At T2 and T3, imaging was restricted to 6 and 4 infants, respectively, due to respiratory compromise and missing cooperation. The capillary density was reduced at T1 compared to T0 (8.1 mm/mm2 [4.0-17.0] vs. 10.6 mm/mm2 [5.1-19.3]; p = 0.01), and inversely related to norepinephrine dose (Pearson r = -0.65; p = 0.04). Microvascular flow and serum glycocalyx makers Syndecan-1 and Hyaluronan increased significantly from T0 to T1.ConclusionPerioperative microcirculatory monitoring in children requires a high amount of personal and logistic resources still limiting its routine use. Major surgery is associated with microvascular alterations and glycocalyx perturbation. The possible consequences on patient outcome need further evaluation. Efforts should concentrate on the development of next generation devices designed to facilitate microcirculatory monitoring in children.
| S-EPMC10116146 | biostudies-literature
Project description:Prophylaxis with emicizumab, a subcutaneously administered bispecific humanized monoclonal antibody, promotes effective hemostasis in persons with hemophilia A (PwHAs). The primary efficacy, safety, and pharmacokinetics of emicizumab were reported previously, but long-term data were limited. Here, data from 401 pediatric and adult PwHAs with/without factor VIII (FVIII) inhibitors who were enrolled in the phase 3 HAVEN 1, HAVEN 2, HAVEN 3, and HAVEN 4 studies (NCT02622321, NCT02795767, NCT02847637, NCT03020160) have been pooled to establish a long-term efficacy, safety, and pharmacokinetics profile. Across a median efficacy period of 120.4 weeks (interquartile range, 89.0-164.4) (data cutoff 15 May 2020), the model-based treated annualized bleed rate (ABR) was 1.4 (95% confidence interval [CI], 1.1-1.7). ABRs declined and then stabilized at <1 in an analysis of 24-week treatment intervals; at weeks 121 to 144 (n = 170), the mean treated ABR was 0.7 (95% CI, 0-5.0). During weeks 121 to 144, 82.4% of participants had 0 treated bleeds, 97.6% had ≤3 treated bleeds, and 94.1% reported no treated target joint bleeds. Bleeding into target joints decreased substantially. Emicizumab was well tolerated, and no participant discontinued because of adverse events beyond the 5 previously described. This data cutoff includes the previously reported 3 thrombotic microangiopathies (one in the PwHA with fatal rectal hemorrhage) and 2 thromboembolic events, all associated with activated prothrombin complex concentrate use, as well as a myocardial infarction and a venous device occlusion. With 970.3 patient-years of exposure, emicizumab prophylaxis maintained low bleed rates in PwHAs of all ages with/without FVIII inhibitors and remains well tolerated, with no new safety concerns identified.
| S-EPMC8065240 | biostudies-literature
Project description:IntroductionSurgery in people with haemophilia and factor VIII inhibitors is typically managed with perioperative administration of haemostatic agents to prevent or control the occurrence of bleeding events. Practical experience of surgery in patients with inhibitors who are receiving treatment with emicizumab is growing; however, the novelty of the situation means that standardised guidelines are lacking with regard to the concomitant administration of haemostatic agents, including dose and laboratory monitoring.AimTo review approaches to haemostatic management during major and minor invasive procedures in patients with haemophilia A and inhibitors, and to provide recommendations for controlling bleeding events.MethodsA search was conducted, limited to the past 4 years (January 2016-April 2020), pertaining to published evidence of surgery for patients receiving emicizumab. Publications identified from the search were manually reviewed to determine studies and case reports relevant for inclusion.ResultsIdentified literature and practical experience of the authors were used to build a consensus of practical recommendations for the concomitant administration of haemostatic agents during the perioperative period for elective surgery in patients with inhibitors who are receiving emicizumab.ConclusionsThe current evidence base indicates that surgery can be successfully performed in patients with inhibitors who are receiving emicizumab and that bypassing agents can be used concomitantly. Data from prospective studies are required to further support recommendations for haemostatic management of surgery in patients receiving emicizumab.
| S-EPMC8359827 | biostudies-literature
Project description:Background and purpose - There is growing evidence that hypoproteinemia is an important risk factor for adverse events after surgery. Less is known about the impact of vitamin deficiency on postoperative outcome. Therefore we evaluated the prevalence and impact of malnutrition and vitamin deficiency in geriatric patients undergoing elective orthopedic surgery.Patients and methods - In a retrospective analysis of 599 geriatric patients who had undergone elective orthopedic surgery in 2018 and 2019, hypoproteinemia, and deficiency of vitamin D, vitamin B12, and folate were assessed. Reoperation rates, readmission rates, complication rates, and transfusion rates were compared between malnourished patients and patients with normal parameters. Multivariable logistic regression models were used to assess the relationship between malnutrition and postoperative adverse events, controlling for confounding factors such as age, sex, diabetes mellitus, and frailty.Results - Patients with malnutrition showed a higher rate of reoperation (13% vs. 5.5%; p = 0.01) and exhibited more wound-healing disorders (7.4% vs. 1.3%, p = 0.001) as well as Clavien-Dindo IV° complications (7.4% vs. 2.4%; p = 0.03). Deficiency of vitamin D led to a higher rate of falls (8.4% vs. 2.9%, p = 0.006). Deficiency of vitamin B12 and folate did not affect postoperative adverse events. Although correlated to frailty (p = 0.004), multivariable regression analysis identified malnutrition as independent risk factor for reoperation (OR 2.6, 95% CI 1.1-6.2) and wound healing disorders (OR 7.1, CI 1.9-26).Interpretation - Malnutrition is common among geriatric patients undergoing elective orthopedic surgery and represents an independent risk factor for postoperative adverse events.
| S-EPMC8231356 | biostudies-literature
Project description:Biological acceptance is one of the most important aspects of a biomaterial and forms the basis for its clinical use. The aim of this study was a comprehensive biological evaluation (cytotoxicity test, bacterial colonization test, blood platelets adhesion test and transcriptome and proteome analysis of Saos-2 cells after contact with surface of the biomaterial) of biomaterials used in spinal and orthopedic surgery, namely, Ti6Al4V ELI (Extra Low Interstitials), its modified version obtained as a result of melting by electron beam technology (Ti6Al4V ELI-EBT), polyether ether ketone (PEEK) and polished medical steel American Iron and Steel Institute (AISI) 316L (the reference material). Biological tests were carried out using the osteoblasts-like cells (Saos-2, ATCC HTB-85) and bacteria Escherichia coli (DH5α). Results showed lack of cytotoxicity of all materials and the surfaces of both Ti6Al4V ELI and PEEK exhibit a significantly higher resistance to colonization with E. coli cells, while the more porous surface of the same titanium alloy produced by electron beam technology (EBT) is more susceptible to microbial colonization than the control surface of polished medical steel. None of the tested materials showed high toxicity in relation to E. coli cells. Susceptibility to platelet adhesion was very high for polished medical steel AISI 316L, whilst much lower for the other biomaterials and can be ranked from the lowest to the highest as follows: PEEK < Ti6Al4V ELI < Ti6Al4V ELI-EBT. The number of expressed genes in Saos-2 cells exposed to contact with the examined biomaterials reached 9463 genes in total (ranging from 8455 genes expressed in cells exposed to ELI to 9160 genes in cells exposed to PEEK). Whereas the number of differentially expressed proteins detected on two-dimensional electrophoresis gels in Saos-2 cells after contact with the examined biomaterials was 141 for PEEK, 223 for Ti6Al4V ELI and 133 for Ti6Al4V ELI-EBT. Finally, 14 proteins with altered expression were identified by mass spectrometry. In conclusion, none of the tested biomaterials showed unsatisfactory levels of cytotoxicity. The gene and protein expression analysis, that represents a completely new approach towards characterization of these biomaterials, showed that the polymer PEEK causes much more intense changes in gene and protein expression and thus influences cell metabolism.
| S-EPMC7672648 | biostudies-literature
Project description:BackgroundAs the first non-factor replacement therapy for persons with congenital hemophilia A (PwcHA), emicizumab's safety profile is of particular interest to the community.ObjectivesWe applied an algorithm for categorization of fatal events contemporaneous to emicizumab using reporter-assessed causality documented in the Roche Emicizumab Global Safety Database.Patients/methodsAll fatalities in PwcHA reported to the database (from clinical trials, pre-market access, and spontaneous post-marketing reports) were categorized into: associated with hemophilia A-hemorrhagic, thrombotic, human immunodeficiency virus (HIV)/hepatitis C virus (HCV), hepatic (non-HCV); associated with general population-trauma/suicide, non-HA-associated conditions; or, unspecified. Reported cause of death was not reassessed.ResultsAs of cut-off May 15, 2020, 31 fatalities in PwcHA taking emicizumab were reported. Median age at death was 58 years; 51% had factor VIII inhibitors. Fifteen fatalities were considered associated with HA; overall, the most frequent category was hemorrhage (11/31). Of these, six had a history of life-threatening bleeds, and four had a history of intracranial hemorrhage. The remaining HA-associated fatalities were related to HIV/HCV (3/31) and other hepatic causes (1/31). No cases were categorized as thrombotic. Of 10 cases considered not associated with HA, two were categorized as cardiovascular (non-thrombotic), five as infection/sepsis, and one each of trauma/suicide, pulmonary, and malignancy. Six cases were unspecified.ConclusionsNo unique risk of death was associated with emicizumab prophylaxis in PwcHA. The data reveal that mortality in PwcHA receiving emicizumab was primarily associated with hemorrhage or non-HA-associated conditions, and was not reported by treaters to be related to emicizumab treatment.
| S-EPMC7756327 | biostudies-literature
Project description:Background and objectiveEmicizumab is a monoclonal antibody that bridges activated coagulation factor IX and factor X to restore effective hemostasis in persons with hemophilia A. It is indicated for routine prophylaxis of bleeding episodes in persons with hemophilia A. The aim of the present study is to describe the exposure-response relationship between emicizumab concentrations and bleeding frequency, and to confirm adequate bleeding control of the investigated dosing regimens 1.5 mg/kg once weekly, 3 mg/kg every 2 weeks, and 6 mg/kg every 4 weeks.MethodsTreated bleeding events were pooled from 445 persons with hemophilia A with and without inhibitors against factor VIII, participating in six clinical studies. Emicizumab concentrations were predicted using a previously developed population pharmacokinetic model. A count model was used to quantify the exposure-response relationship. These models were used to illustrate the relationship between emicizumab concentrations and cumulative count of bleeding over 1 year (annualized bleeding rate).ResultsThe final exposure-response model, based on a generalized Poisson distribution and an inhibitory Emax relationship, adequately describes the relationship between daily emicizumab concentrations and daily bleed frequency. A significant effect of factor VIII prophylaxis among persons with hemophilia A without inhibitors was found. Annualized bleeding rate simulations show that the three emicizumab dosing regimens maintain the concentrations close to the plateau of the effect. At the average steady-state concentration across all regimens (53.5 µg/mL), the predicted mean annualized bleeding rate is 1.28, corresponding to a 94.0% reduction from baseline.ConclusionsThese results confirm that average emicizumab concentrations achieved with all three emicizumab dosing regimens provide adequate bleeding control.
| S-EPMC8249270 | biostudies-literature