Masataka Kamei

Unblinded Pilot Study of Autologous Transplantation of Bone Marrow Mononuclear Cells in Patients With Thromboangiitis Obliterans

Background— The short-term clinical benefits of bone marrow mononuclear cell transplantation have been shown in patients with critical limb ischemia. The purpose of this study was to assess the long-term safety and efficacy of bone marrow mononuclear cell transplantation in patients with thromboangiitis obliterans. Methods and Results— Eleven limbs (3 with rest pain and 8 with an ischemic ulcer) of 8 patients were treated by bone marrow mononuclear cell transplantation. The patients were followed up for clinical events for a mean of 684±549 days (range 103 to 1466 days). At 4 weeks, improvement in pain was observed in all 11 limbs, with complete relief in 4 (36%). Pain scale (visual analog scale) score decreased from 5.1±0.7 to 1.5±1.3. An improvement in skin ulcers was observed in all 8 limbs with an ischemic ulcer, with complete healing in 7 (88%). During the follow-up, however, clinical events occurred in 4 of the 8 patients. The first patient suffered sudden death at 20 months after transplantation at 30 years of age. The second patient with an incomplete healing of a skin ulcer showed worsening of the lesion at 4 months. The third patient showed worsening of rest pain at 8 months. The last patient developed an arteriovenous shunt in the foot at 7 months, which spontaneously regressed by 1 year. Conclusions— In the present unblinded and uncontrolled pilot study, long-term adverse events, including death and unfavorable angiogenesis, were observed in half of the patients receiving bone marrow mononuclear cell transplantation. Given the current incomplete knowledge of the safety and efficacy of this strategy, careful long-term monitoring is required for future patients receiving this treatment.

Venous thromboembolism after total joint arthroplasty: results from a Japanese multicenter cohort study

IntroductionReal-world evidence of the effectiveness of pharmacological thromboprophylaxis for venous thromboembolism (VTE) is limited. Our objective was to assess the effectiveness and safety of thromboprophylactic regimens in Japanese patients undergoing joint replacement in a real-world setting.MethodOverall, 1,294 patients (1,073 females and 221 males) who underwent total knee arthroplasty (TKA) and 868 patients (740 females and 128 males) who underwent total hip arthroplasty (THA) in 34 Japanese national hospital organization (NHO) hospitals were enrolled. The primary efficacy outcome was the incidence of deep vein thrombosis (DVT) detected by mandatory bilateral ultrasonography up to post-operative day (POD) 10 and pulmonary embolism (PE) up to POD28. The main safety outcomes were bleeding (major or minor) and death from any cause up to POD28.ResultsPatients undergoing TKA (n = 1,294) received fondaparinux (n = 360), enoxaparin (n = 223), unfractionated heparin (n = 72), anti-platelet agents (n = 45), or no medication (n = 594). Patients undergoing THA (n = 868) received fondaparinux (n = 261), enoxaparin (n = 148), unfractionated heparin (n = 32), anti-platelet agents (n = 44), or no medication (n = 383). The incidence rates of sonographically diagnosed DVTs up to POD10 were 24.3% in patients undergoing TKA and 12.6% in patients undergoing THA, and the incidence rates of major bleeding up to POD28 were 1.2% and 2.3%, respectively. Neither fatal bleeding nor fatal pulmonary embolism occurred. Significant risk factors for postoperative VTE identified by multivariate analysis included gender (female) in both TKA and THA groups and use of a foot pump in the TKA group. Only prophylaxis with fondaparinux reduced the occurrence of VTE significantly in both groups. Propensity score matching analysis (fondaparinux versus enoxaparin) showed that the incidence of DVT was lower (relative risk 0.70, 95% confidence interval (CI) 0.58 to 0.85, P = 0.002 in TKA and relative risk 0.73, 95% CI 0.53 to 0.99, P = 0.134 in THA) but that the incidence of major bleeding was higher in the fondaparinux than in the enoxaparin group (3.4% versus 0.5%, P = 0.062 in TKA and 4.9% versus 0%, P = 0.022 in THA).ConclusionsThese findings indicate that prophylaxis with fondaparinux, not enoxaparin, reduces the risk of DVT but increases bleeding tendency in patients undergoing TKA and THA.Trial registrationUniversity Hospital Medical Information Network Clinical Trials Registry: UMIN000001366. Registered 11 September 2008.

Mechanical prophylaxis is a heparin-independent risk for anti-platelet factor 4/heparin antibody formation after orthopedic surgery

Platelet-activating antibodies, which recognize platelet factor 4 (PF4)/heparin complexes, induce spontaneous heparin-induced thrombocytopenia (HIT) syndrome or fondaparinux-associated HIT without exposure to unfractionated heparin (UFH) or low-molecular-weight heparin (LMWH). This condition mostly occurs after major orthopedic surgery, implying that surgery itself could trigger this immune response, although the mechanism is unclear. To investigate how surgery may do so, we performed a multicenter, prospective study of 2069 patients who underwent total knee arthroplasty (TKA) or hip arthroplasty. Approximately half of the patients received postoperative thromboprophylaxis with UFH, LMWH, or fondaparinux. The other half received only mechanical thromboprophylaxis, including dynamic (intermittent plantar or pneumatic compression device), static (graduated compression stockings [GCSs]), or both. We measured anti-PF4/heparin immunoglobulins G, A, and M before and 10 days after surgery using an immunoassay. Multivariate analysis revealed that dynamic mechanical thromboprophylaxis (DMT) was an independent risk factor for seroconversion (odds ratio [OR], 2.01; 95% confidence interval [CI], 1.34-3.02; P = .001), which was confirmed with propensity-score matching (OR, 1.99; 95% CI, 1.17-3.37; P = .018). For TKA, the seroconversion rates in patients treated with DMT but no anticoagulation and in patients treated with UFH or LMWH without DMT were similar, but significantly higher than in patients treated with only GCSs. The proportion of patients with ≥1.4 optical density units appeared to be higher among those treated with any anticoagulant plus DMT than among those not treated with DMT. Our study suggests that DMT increases risk of an anti-PF4/heparin immune response, even without heparin exposure. This trial was registered to www.umin.ac.jp/ctr as #UMIN000001366.

Accuracy and Trending Ability of the Fourth-Generation FloTrac/Vigileo System in Patients With Low Cardiac Index.

OBJECTIVES To determine the accuracy and trending ability of the fourth-generation FloTrac/Vigileo in patients with low cardiac index by comparing FloTrac/Vigileo-derived cardiac index with that measured by 3-dimensional echocardiography. DESIGN Prospective clinical study. SETTING Cardiac surgery operating room in a single cardiovascular center. PARTICIPANTS Twenty-five patients undergoing elective cardiac resynchronization therapy lead implantation. INTERVENTIONS FloTrac/Vigileo-derived cardiac index and 3-dimensional echocardiography-derived cardiac index were determined simultaneously before and after phenylephrine bolus and cardiac resynchronization therapy using 3-dimensional echocardiography-derived cardiac index as the reference method. MEASUREMENTS AND MAIN RESULTS Cardiac index measured by the fourth-generation FloTrac/Vigileo had a wide limit of agreement with that measured by 3-dimensional echocardiography, with a percentage error of 59.1%. The tracking ability of the unit after both phenylephrine administration and cardiac resynchronization therapy were measured by concordance rate, and both were below the acceptable limit (72.7% and 85%, respectively). CONCLUSIONS The degree of accuracy of the fourth-generation FloTrac/Vigileo in patients with low cardiac index was not acceptable, and high systemic vascular resistance in patients with low cardiac index may have contributed to this inaccuracy. The tracking ability of the fourth-generation FloTrac/Vigileo after phenylephrine administration or cardiac resynchronization therapy was below acceptable limits.

Spinal anesthesia increases the risk of venous thromboembolism in total arthroplasty: Secondary analysis of a J-PSVT cohort study on anesthesia

Abstract Clinical guidance on the choice of anesthetic modality vis-à-vis the risk of perioperative venous thromboembolism (VTE) is largely lacking because of a paucity of recent evidence. A comparative effect of general anesthesia and neuraxial blockade on the perioperative incidence of VTE has not been well-investigated. We compared the effects of different types of anesthetic modalities on the risk of VTE after total hip arthroplasty (THA) and total knee arthroplasty (TKA). This is a secondary analysis of the Japanese Study of Prevention and Actual Situation of Venous Thromboembolism after Total Arthroplasty (J-PSVT). Data pertaining to a total of 2162 patients who underwent THA and TKA at 34 hospitals were included in this analysis. We compared the different anesthetic modalities with respect to the incidence of VTE. The composite end-point was asymptomatic/symptomatic deep vein thrombosis detected using scheduled bilateral ultrasonography up to postoperative day (POD) 10 and fatal/non-fatal pulmonary embolism up to POD 10. The study groups were as follows: general anesthesia (n = 646), combined epidural/general anesthesia (n = 1004), epidural anesthesia (n = 87), and spinal anesthesia (n = 425). On multivariate analysis, only spinal anesthesia was associated with a significant increase in the risk of VTE as compared with that associated with general anesthesia. Propensity score-matched analysis for “combined epidural/general anesthesia group” versus “spinal anesthesia group” demonstrated a 48% higher incidence of VTE (relative risk = 1.48, 95% confidence interval [CI] 1.18–1.85) in the latter. Spinal anesthesia was associated with a higher risk of postoperative VTE, as compared with that associated with combined epidural/general anesthesia, in patients undergoing total arthroplasty.