Oral as compared to intravenous tranexamic acid to limit peri-operative blood loss associated with primary total hip arthroplasty: A randomised noninferiority trial.

BACKGROUND: Oral as compared to intravenous tranexamic acid (TXA) is an attractive option, in terms of cost and safety, to reduce blood loss and transfusion in total hip arthroplasty. Exclusion criteria applied in the most recent randomised trials may have limited the generalisability of oral tranexamic acid in this indication. Larger and more inclusive studies are needed to definitively establish oral administration as a credible alternative to intravenous administration. OBJECTIVES: To assess the noninferiority of oral to intravenous TXA at reducing intra-operative and postoperative total blood loss (TBL) in primary posterolateral approached total hip arthroplasty (PLTHA). DESIGN: Noninferiority, single centre, randomised, double-blind controlled study. SETTING: Patients scheduled for primary PLTHA. Data acquisition occurred between May 2021 and November 2022 at the University Hospital of Liège, Belgium. PATIENTS: Two hundred and twenty-eight patients, randomised in a 1 : 1 ratio from a computer-generated list, completed the trial. INTERVENTIONS: Administration of 2 g of oral TXA 2 h before total hip arthroplasty and 4 h after incision (Group oral) was compared to the intravenous administration of 1 g of TXA 30 min before surgery and 4 h after incision (Group i.v.). MAIN OUTCOME MEASURES: TBL (measured intra-operative and drainage blood loss up to 48 h after surgery, primary outcome), decrease in haemoglobin concentration, D-Dimer at day 1 and day 3, transfusion rate (secondary outcomes). RESULTS: Analyses were performed on 108 out of 114 participants (Group i.v.) and 104 out of 114 participants (Group oral). Group oral was noninferior to Group i.v. with regard to TBL, with a difference between medians (95% CI) of 35 ml (-103.77 to 33.77) within the noninferiority margins. Median [IQR] of estimated TBL was 480 ml [350 to 565] and 445 ml [323 to 558], respectively. No significant interaction between group and time was observed regarding the evolution of TBL and haemoglobin over time. CONCLUSIONS: TXA as an oral premedication before PLTHA is noninferior to its intravenous administration regarding peri-operative TBL. TRIAL REGISTRATION: European Clinical Trial Register under EudraCT-number 2020-004167-29 ( https://www.clinicaltrialsregister.eu/ctr-search/trial/2020-004167-29/BE ).

Comparison between supra-inguinal fascia iliaca and pericapsular nerve group blocks on postoperative pain and functional recovery after total hip arthroplasty: A noninferiority randomised clinical trial.

BACKGROUND: Pain after a posterolateral approach for total hip arthroplasty (THA) may affect early functional recovery. Supra-inguinal fascia iliaca (SFIB) and pericapsular nerve group (PENG) blocks have been proposed as promising analgesia techniques. OBJECTIVES: This trial was conducted to compare a PENG with a SFIB for controlling postoperative pain and for providing functional recovery. DESIGN: Noninferiority monocentric randomised controlled study. SETTING: One hundred and two patients scheduled for a total hip arthroplasty via the posterolateral approach under spinal anaesthesia were prospectively allocated to two groups. Data acquisition occurred between October 2021 and July 2022 at the University Hospital of Liege. PATIENTS: One hundred and two patients completed the trial. INTERVENTIONS: Group SFIB received supra-inguinal fascia iliaca block (SFIB) (40 ml ropivacaine 0.375%), whereas group PENG received a PENG block (20 ml ropivacaine 0.75%). MAIN OUTCOME MEASURES: Rest and mobilisation pain on a 0 to 10 numeric rating scale at fixed time points: 1 and 6 h after surgery, on day-1 and day-2 at 8 a.m.,1 p.m. and 6 p.m. On day-1 and day-2, evolution of quality-of-recovery-15 score was assessed, and timed-up-and-go, 2 and 6 min-walking tests. The noninferiority margin was set as 1 numeric rating scale point 6 h after surgery. RESULTS: Six hours after surgery, pain scores in group PENG were noninferior to those of group SFIB, with a difference between medians at 0 (95% CI -0.93 to 0.93). There were no significant differences between the groups regarding rest and dynamic pain trajectories during the first 48 postoperative hours, with no significant effects of group (rest P  = 0.800; dynamic P  = 0.708) or interaction between group and time (rest P  = 0.803; dynamic P  = 0.187). Similarly, no significant differences were observed regarding motor and functional recovery as assessed by timed-up-and-go ( P  = 0.197), 2 min ( P  = 0.364), and 6 min walking ( P  = 0.347) tests and quality-of-recovery-15 ( P  = 0.417) score. CONCLUSION: Following a total hip arthroplasty via the posterolateral approach, a PENG block is noninferior to SFIB regarding postoperative pain control 6 h after surgery, and functional recovery. TRIAL REGISTRATION: European Clinical Trial Register under EudraCT-number 2020-005126-28 ( https://www.clinicaltrialsregister.eu/ctr-search/trial/2020-005126-28/BE ).

Dose-dense ABVD as first-line therapy in early-stage unfavorable Hodgkin lymphoma: results of a prospective, multicenter double-step phase II study by Fondazione Italiana Linfomi.

We investigated the feasibility and activity of an intensified dose-dense ABVD (dd-ABVD) regimen in patients with early-stage unfavorable Hodgkin lymphoma (HL). This prospective, multicenter, phase II study enrolled 96 patients with newly diagnosed, unfavorable stage I or II classical HL. The patients received four cycles of dd-ABVD followed by radiotherapy. Interim PET (PET-2) was mandatory after two courses. Primary endpoints were the evaluation of dd-ABVD feasibility and activity (incidence of PET-2 negativity). The feasibility endpoint was achieved with 48/52 (92.3%) patients receiving > 85% of the programmed dose. The mean dose intensity in the overall patient population (n = 96) was 93.7%, and the median duration of dd-ABVD was 85 days (range, 14-115) versus an expected duration of 84 days. PET-2 was available for 92/96 (95.8%) patients, of whom 79 were PET-2 negative (85.9%). In total, 90 (93.8%) patients showed complete response at the end of treatment. With a follow-up of 80.9 months (3.3-103.2), the median progression-free survival (PFS) and overall survival (OS) were not reached. At 84 months, PFS and OS rates were 88.4% and 95.7%, respectively. No evidence for a difference in PFS or OS was observed for PET-2-negative and PET-2-positive patients. Infections were documented in 8.3% and febrile neutropenia in 6.2% of cases. Four patients died: one had alveolitis at cycle 3, one death was unrelated to treatment, and two died from a secondary cancer. dd-ABVD is feasible and demonstrates activity in early-stage unfavorable HL. The predictive role of PET-2 positivity in early-stage unfavorable HL remains controversial. The study was registered in the EudraCT (reference number, 2011-003,191-36) and the ClinicalTrials.gov (reference number, NCT02247869) databases.

Influence of Levobupivacaine Regional Scalp Block on Hemodynamic Stability, Intra- and Postoperative Opioid Consumption in Supratentorial Craniotomies: A Randomized Controlled Trial.

BACKGROUND: The anesthetic management of supratentorial craniotomy (CR) necessitates tight intraoperative hemodynamic control. This type of surgery may also be associated with substantial postoperative pain. We aimed at evaluating the influence of regional scalp block (SB) on hemodynamic stability during the noxious events of supratentorial craniotomies and total intravenous anesthesia, its influence on intraoperative anesthetic agents' consumption, and its effect on postoperative pain control. METHODS: Sixty patients scheduled for elective CR were prospectively enrolled. Patient, anesthesiologist, and neurosurgeon were blind to the random performance of SB with either levobupivacaine 0.33% (intervention group [group SB], n = 30) or the same volume of saline (control group [group CO], placebo group, n = 30). General anesthesia was induced and maintained using target-controlled infusions of remifentanil and propofol that were adjusted according to hemodynamic parameters and state entropy of the electroencephalogram (SE), respectively. Mean arterial blood pressure (MAP), heart rate (HR), SE, and propofol and remifentanil effect-site concentrations (Ce) were recorded at the time of scalp block performance (Baseline), and 0, 1, 3, and 5 minutes after skull-pin fixation (SP), skin incision (SI), CR, and dura-mater incision (DM). Morphine consumption and postoperative pain intensity (0-10 visual analog scale [VAS]) were recorded 1, 3, 6, 24, and 48 hours after surgery. Propofol and remifentanil overall infusion rates were also recorded. Data were analyzed using 2-tailed Student unpaired t tests, 2-way mixed-design analysis of variance (ANOVA), and Tukey's honestly significant difference (HSD) tests for post hoc comparisons as appropriate. RESULTS: Demographics and length of anesthetic procedure of group CO and SB were comparable. SP, SI, and CR were associated with a significantly higher MAP in group CO than in group SB, at least at one of the time points of recording surrounding those noxious events. This was not the case at DM. Similarly, HR was significantly higher in group CO than in group SB during SP and SI, at least at 1 of the points of recording, but not during CR and DM. Propofol and remifentanil Ce and overall infusion rates were significantly higher in group CO than in group SB, except for propofol Ce during SP. Postoperative pain VAS and cumulative morphine consumption were significantly higher in group CO than in group SB. CONCLUSIONS: In supratentorial craniotomies, SB improves hemodynamic control during noxious events and provides adequate and prolonged postoperative pain control as compared to placebo.

Comparison of several methods for pain management after video-assisted thoracic surgery for pneumothorax: an observational study.

BACKGROUND: There is no defined gold standard for pain management after video-assisted thoracic surgery (VATS) for pneumothorax. In addition to systemic analgesia, various loco-regional analgesic techniques have been proposed but remain poorly evaluated in this context. We aimed to assess the analgesic efficacy of several of these techniques for the management of postoperative pain. METHODS: We conducted a monocentric prospective observational cohort study from February 2017 to April 2018 in patients suffering from spontaneous pneumothorax and scheduled for VATS (n = 59). Patients received systemic analgesia (i) alone (n = 15); (ii) combined with a continuous paravertebral block (n = 9); (iii) combined with a continuous serratus plane block (n = 19); or (iv) single-shot serratus plane block (n = 16) as decided by the attending physician. Pain scores and analgesic-related side effects were prospectively collected by an independent observer during the first postoperative 72 h. The primary endpoint criterion was the cumulative oral morphine consumption at the end of the third postoperative day. Statistical analysis used univariate and multivariate step-by-step forward logistic regression models to determine risk factors associated with the main criteria. RESULTS: Mean pain scores and morphine consumption were not significantly different between the 4 groups. In the multivariate analysis, the use of a continuous serratus plane block through a catheter was the only technique associated with a reduced incidence of high-dose oral morphine consumption (OR 0.09-95%CI [0.01-0.79], p = 0.03). CONCLUSION: This study suggests that serratus plane block combined with continuous infusion through a catheter may have some benefits, although further studies are needed to confirm these results and determine the true place of the serratus plane block in pain management after VATS for pneumothorax.

STEMI patients and nonculprit lesions: To treat or not to treat? and when? A review of most recent literature.

Patients with ST segment elevation myocardial infarction and multivessel disease represent a high percentage of ischemic patient with a worse outcome than patient with single coronary artery disease. Therefore, initial management of these patients is of high importance, but unfortunately this is not clarified yet. We analyze the available literature trying to afford current doubts to determine which way of revascularization is to be preferred. © 2015 Wiley Periodicals, Inc.

Effect of preoperative warming on intraoperative hypothermia and postoperative functional recovery in total hip arthroplasty: a randomized clinical trial.

BACKGROUND: Intraoperative hypothermia is associated with increased morbidity and impaired postoperative recovery. Direct anterior-approached total hip arthroplasty (ATHA) may lead to significant thermal loss. We aimed to assess whether preoperative warming had an impact on intraoperative hypothermia and postoperative functional recovery after ATHA. METHODS: In this prospective randomized controlled clinical trial 40 patients scheduled for ATHA were randomly divided into two groups of 20 patients each. Group W received, prior to the induction of general anesthesia, a 30 minutes 43 °C forced-air preoperative warming. Group C did not receive any preoperative warming. A blinded observer noted the core body temperature at the time of induction and at fixed time points, i.e. every five minutes during the first hour of surgery. The evolution of postoperative patient perceived thermal comfort (TC) and functional recovery (QoR-15) was assessed 24, 48 and 72 hours after surgery. Length of stay in the post-anesthesia care unit (PACU) was noted. RESULTS: The temperature drop was significantly faster and of higher amplitude in group C than in group W, during first hour of surgery (P<0.001). Evolution of QoR-15 and TC was significantly better in group W than in group C (P<0.001 for QoR-15 and P<0.001 for thermal comfort), with shorter length of stay (median [IQR]) in the PACU (minutes; 73 [61-79] for group C and 98 [83-129] for group W, P<0.001). CONCLUSIONS: In ATHA, pre-warming delays and reduces intraoperative heat loss, impacting patient comfort and postoperative functional recovery.

Effect of virtual reality hypnosis on intraoperative sedation needs and functional recovery in knee arthroplasty: a prospective randomized clinical trial.

BACKGROUND AND OBJECTIVES: Perioperative psychological stress and pharmacological anxiolysis can negatively affect the quality of recovery after total knee arthroplasty. We aimed to assess whether hypnosis combined with virtual reality could reduce intraoperative pharmacological sedation and improve quality of recovery after total knee arthroplasty surgery. METHODS: In this prospective randomized clinical trial, 60 patients scheduled for total knee arthroplasty with spinal anesthesia were randomly divided into 2 groups of 30 patients each. Intraoperatively, intermittent boluses of midazolam 1 mg were administered at 5 min intervals at the patient's request, with a maximum driven by the clinical assessment of sedation depth. During surgery, patients received standard care (group control) or virtual reality hypnosis (group VRH). An unblinded observer recorded the total dose of midazolam administered during surgery, and changes in the Quality-of-Recovery 15-item score, comfort, fatigue, pain and anxiety before and 1, 3 and 7 days after surgery. RESULTS: Patients in the VRH group required a lower dose of midazolam (mg; median (range)) intraoperatively (group VRH: 0 (0-4) and group control: 2 (0-9), p<0.001). Quality-of-Recovery 15-item, anxiety, and pain were similar between groups. CONCLUSIONS: In total knee arthroplasty with spinal anesthesia, VRH reduces the requirement for intraoperative pharmacological sedation, without a change in the quality of recovery. TRIAL REGISTRATION NUMBER: NCT05707234.

Pericapsular nerve group block: a 3D CT scan imaging study to determine the spread of injectate.

BACKGROUND: Current understanding of the mechanism of action of the pericapsular nerve group (PENG) block is primarily based on cadaver studies. We performed an imaging study in patients undergoing hip surgery to enhance the understanding of the analgesic mechanisms following a PENG block. MATERIALS AND METHODS: 10 patients scheduled for hip surgery received an ultrasound-guided PENG block with 18 mL of 0.5% ropivacaine mixed with 2 mL of a contrast agent. After completion of the block, a high-resolution CT scan was performed to obtain a three-dimensional reconstruction of the injectate's dispersion. RESULTS: The CT imaging revealed that injectate was mainly confined to the epimysium of the iliacus and the psoas muscle, with a minor spread to the hip capsule. Contrast dye was detected within the iliacus and/or the psoas muscle in all patients. No observed spread to either the subpectineal plane or the obturator foramen was detected. CONCLUSION: Our study suggests that the analgesic effect of the PENG block may be related to the block of the branches of the femoral nerve traveling within the iliopsoas muscle without a spread pattern commensurate with the block of the obturator nerve. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Registry (NCT06062134).

Effect of suprainguinal fascia iliaca compartment block on postoperative opioid consumption and functional recovery in posterolateral-approached total hip arthroplasty: a single-blind randomized controlled trial.

INTRODUCTION: Posterolateral-approached total hip arthroplasty (PLTHA) is followed by moderate to severe postoperative pain. Suprainguinal fascia iliaca compartment block (SFICB) has been proposed as a promising analgesia technique. METHODS: Data from 86 patients scheduled for PLTHA with spinal anesthesia were analyzed in this prospective randomized controlled trial. Patients were randomly divided into two groups of 43 patients each. As opposed to the control group (group C), ropivacaine group (group R) received additional SFICB using 40 mL of 0.375% ropivacaine. As primary endpoint, blind observers noted total morphine consumption at postoperative 48 hours. Secondary endpoints were pain at rest and mobilization on 0-10 Numeric Rating Scale (rest and dynamic NRS) at fixed time points (1 hour and 6 hours after surgery, and at day 1 and day 2 at 8:00, 13:00 and 18:00 hours), walking performance at day 1 and day 2; postoperative complications including morphine-related side effects or orthostatic intolerance symptoms such as dizziness, nausea, blurred vision or vasovagal syncope. RESULTS: A 48-hour morphine consumption (mg; median (IQR)) was significantly lower in group R than in group C (11 (8.5-15.5)) vs 26 (21-33.5), p<0001), as well as incidence of morphine-related side effects such as nausea at day 1 (p=0.04) and day 2 (p<0.01). Rest and dynamic NRS were globally significantly lower in group R than in group C (p<0.01). Group R showed less orthostatic intolerance at day 1 (p<0.001) and day 2 (p<0.01) and better functional walking performance at day 1 (<0.001) and day 2 (<0.001). DISCUSSION: In PLTHA, SFICB provides opioid sparing, improved postoperative pain control, and enhanced functional recovery. TRIAL REGISTRATION NUMBER: NCT04574479.

Impact of second-degree related donor on the outcomes of T cell-replete haploidentical transplantation with post-transplant cyclophosphamide.

Donor selection may contribute to improve clinical outcomes of T cell-replete haploidentical stem cell transplantation (Haplo-SCT) with post-transplant cyclophosphamide (PT-Cy). Impact of second-degree related donor (SRD) was not fully elucidated in this platform. We retrospectively compared the outcome of patients receiving Haplo-SCT either from a SRD (n = 31) or a first-degree related donor (FRD, n = 957). Median time to neutrophil and platelet recovery did not differ between a SRD and a FRD transplant (p = 0.599 and 0.587). Cumulative incidence of grade II-IV acute graft-versus host disease (GVHD) and moderate-severe chronic GVHD was 13% and 19% after SRD vs 24% (p = 0.126) and 13% (p = 0.395) after FRD transplant. One-year cumulative incidence of non-relapse mortality (NRM) was 19% for SRD and 20% for FRD (p = 0.435) cohort. The 3-year probability of overall survival (OS) and progression-free survival (PFS) was 42% vs 55% (p = 0.273) and 49% vs 35% (p = 0.280) after SRD and FRD transplant, respectively. After propensity score adjustment or matched pair analysis, the outcome of patients receiving Haplo-SCT from a SRD or a FRD did not differ in terms of NRM, OS, PFS, acute and chronic GVHD. Our results suggest that a SRD is a viable option for Haplo-SCT with PT-Cy when a FRD is not available.

Endothelial dysfunction and carotid lesions are strong predictors of clinical events in patients with early stages of atherosclerosis: a 24-month follow-up study.

BACKGROUND: The purpose of this study was to investigate whether the vasodilator response to brachial artery and the presence of carotid lesions may have a prognostic significance in patients with early stages of atherosclerosis. METHODS AND RESULTS: Vascular echography was performed to analyze flow-mediated vasodilatation (FMD) at the brachial artery and intima-media thickness (IMT) of carotid arteries in 84 asymptomatic patients. At baseline, we evaluated all the established traditional cardiovascular risk factors. Transient ischemic attack, stroke, effort or unstable angina, acute myocardial infarction, peripheral arterial disease and cerebrovascular and cardiovascular death served as outcome variables over a follow-up period of 24 months. Brachial FMD was correlated inversely with carotid IMT (P=0.003), systolic blood pressure (P=0.0001) and age (P=0.0001). IMT was positively correlated with systolic blood pressure (P=0.0001), waist circumference (P=0.004) and age (P=0.01). At the end of the follow-up cardiovascular and cerebrovascular events were registered in 29% of the patients and in a multivariate analysis, including all the variables evaluated at baseline, male sex [odds ratio (OR) 1.6, P=0.005], the presence of baseline carotid lesions (OR 3.5, P=0.02) and FMD below the median (OR 3.2, P=0.03) were the only variables predictive of clinical events. CONCLUSION: In this study, endothelial dysfunction and carotid lesions significantly increased the risk of vascular events in asymptomatic patients with early stages of atherosclerosis. Assessment of systemic vasoreactivity and carotid IMT evaluation may provide, in this category of patients, important prognostic information in addition to that derived from traditional established cardiovascular risk factors.

Haploidentical transplantation is associated with better overall survival when compared to single cord blood transplantation: an EBMT-Eurocord study of acute leukemia patients conditioned with thiotepa, busulfan, and fludarabine.

BACKGROUND: Thiotepa-busulfan-fludarabine (TBF) is a widely used conditioning regimen in single umbilical cord blood transplantation (SUCBT). More recently, it was introduced in the setting of non-T cell depleted haploidentical stem cell transplantation (NTD-Haplo). Whether TBF based conditioning provides additional benefit in transplantation from a particular alternative donor type remains to be established. METHODS: This was a retrospective study based on an international European registry. We compared outcomes of de-novo acute myeloid leukemia patients in complete remission receiving NTD-Haplo (n = 186) vs. SUCBT (n = 147) following myeloablative conditioning (MAC) with TBF. Median follow-up was 23 months. Treatment groups resembled in baseline characteristics. RESULTS: SUCBT was associated with delayed engraftment and higher graft failure. In multivariate analysis no statistically significant differences were observed between the two groups in terms of acute or chronic graft-versus-host disease (GvHD) (HR = 1.03, p = 0.92 or HR = 1.86, p = 0.21) and relapse incidence (HR = 0.8, p = 0.65). Non-relapse mortality (NRM) was significantly higher in SUCBT as compared to NTD-Haplo (HR = 2.63, p = 0.001); moreover, SUCBT did worse in terms of overall survival (HR = 2.18, p = 0.002), leukemia-free survival (HR = 1.94, p = 0.007), and GvHD relapse-free survival (HR = 2.38, p = 0.0002). CONCLUSIONS: Our results suggest that TBF-MAC might allow for a potent graft-versus-leukemia, regardless of the alternative donor type. Furthermore, in patients receiving TBF-MAC, survival with NTD-Haplo may be better compared to SUCBT due to decreased NRM.