Neutrophils have been implicated as central mediators in myocardial and skeletal muscle ischemia-reperfusion injury. This study tests whether these cellular elements and the chemoattractant leukotriene (LTB4) play a role in postischemic renal failure. Anesthetized rats underwent 45 min of left renal pedicle clamping. Five minutes after reperfusion, LTB4 levels were elevated to 1.42 ng/ml (P less than 0.05); thromboxane (Tx)B2 was 2,840 pg/ml, higher than 503 pg/ml in sham controls (P less than 0.05); renal artery blood flow was 67% of preclamping values at 1 min of reperfusion compared with 111% in sham (P less than 0.05). At 24 h, creatinine levels were 4.6 mg/dl (P less than 0.05). At 24 h, creatinine levels were 4.6 mg/dl (P less than 0.05); histology showed acute tubular necrosis (ATN). Neutrophil depletion by rabbit antiserum (n = 8) led during reperfusion to reduced LTB4 and TxB2 levels, 1.04 ng/ml and 1.043 pg/ml (P less than 0.05); increased renal blood flow of 174% (P less than 0.05); reduced creatinine levels of 1.8 mg/dl (P less than 0.05); and limited ATN. Pretreatment with diethycarbamazine prevented the increases in LTB4 and TxB2 (P less than 0.05), increased renal blood flow (P less than 0.05), minimized creatinine increase to 1.7 mg/dl (P less than 0.05), and reduced ATN. These data indicate that neutrophils and LTB4 play a role in ischemia-induced Tx synthesis and mediate postischemic renal injury.
In endemic regions, coccidioidomycosis causes substantial morbidity and mortality for patients receiving solid organ transplants. We aimed to demonstrate the effect of antifungal coccidioidal prophylaxis in heart transplant (HT) recipients. We retrospectively reviewed the electronic health records of all patients who received HTs between October 19, 2005, and December 13, 2014. We collected information regarding antifungal regimens and determined whether patients subsequently developed infections. Our 174-person cohort all received antifungal prophylaxis for at least 6 months (mean follow-up, 53.8 months). One proven and one probable coccidioidal infection (each, 0.6%) occurred during the study period. The incidence of coccidioidomycosis was 0.6% at 1 year and 2.3% at 5 years. No cases of proven coccidioidomycosis occurred within 2 years after transplantation. No patients developed disseminated disease, and no sentinel events were attributed to coccidioidomycosis. Both fluconazole and voriconazole were well tolerated. In the absence of intolerance or contraindication, we suggest continuing a universal antifungal prophylactic regimen with fluconazole for at least 6-12 months in HT recipients residing in a coccidioidomycosis-endemic area.
Introduction Patients with sickle cell disease (SCD) are at increased risk for venous thromboembolism (VTE). By age 40, 11-12% of SCD patients have experienced a VTE. VTE confers nearly a three-fold increase in mortality risk for individuals with SCD. We hypothesized that VTE increases subsequent SCD severity which may increase acute care utilization. We investigated the association between VTE and rates of vaso-occlusive events (VOE) and acute care utilization for individuals with SCD. Methods We performed a retrospective longitudinal chart review of 239 adults with SCD who received care at our institution between 2003 and 2018. VTE was defined as deep venous thrombosis (DVT) diagnosed by Duplex ultrasound or pulmonary embolism (PE) diagnosed by either ventilation-perfusion scanning or computed tomography angiography. Medical histories, laboratories and medication use for all subjects were obtained. For VTE patients, clinical data for 1- and 5- years post-VTE were obtained and compared to 1 year prior to the VTE. For non-VTE patients, data were obtained at baseline and compared to five years later. We evaluated all acute care visits for the presence of a SCD-related problem, specifically assessing if a VOE or acute chest syndrome (ACS) occurred. We calculated rates of VOE, ACS, Emergency Department (ED) visits and hospitalizations prior to and subsequent to a VTE and compared these to occurrence rates among those without VTE. Data were analyzed using Stata 14.2. Results In our cohort of 239 individuals with SCD, 153 (64%) were HbSS/HbSβ0 and 127(53%) were female. Fifty-six individuals (23%) had a history of VTE; 20 had a DVT (36%), 33 had a PE (59%), and 3 had both (5%). Patients with VTE had a higher frequency of prior history of ACS (p<0.001), stroke (p=0.013), splenectomy (p=0.033), and avascular necrosis (p<0.001) than those without a VTE. Prior to their VTE, these patients had higher white blood cell (11.8 x103 [9-15 x 103] vs 9.7 x103 [7-12 x 103], p=0.047) and platelet counts (378 x 103 [272-485 x 103] vs 322 x 103 [244-400 x 103], p=0.007) than those without a VTE. During five years of follow-up after a VTE, these patients had 6.32 (SD 14.97) ED visits per year compared to 2.84 (SD 5.93, p<0.03) ED visits per year in those without a VTE. Ninety two percent of these ED visits were SCD-related; 73% were for VOE and 4% for ACS. Additionally, SCD patients with a VTE had an increase in all-cause hospital admissions (2.84 [SD 3.26] vs 1.43 [SD 2.86], p=0.003) and SCD-related hospital admissions (2.61 [SD 3.13] vs 1.23 [SD 2.74], p=0.001) per year compared to those without VTE. Conclusion VTE is a frequent complication in patients with SCD. Our study suggests that patients who experience a VTE have greater SCD severity as evidenced by increased VOE, ED and hospital utilization. These data suggest that VTE is not merely an isolated event in SCD patients and that it may either serve as an indicator of disease severity or contribute to overall disease pathophysiology. Disclosures Sloan: Abbvie: Other: Endpoint Review Committee; Stemline: Consultancy; Merck: Other: endpoint review commitee.
Patients with sickle cell disease (SCD) experience accelerated morbidity and mortality. Venous thromboembolism (VTE), a risk factor for early mortality in SCD, occurs in 11-12% of patients with SCD by the age of 40. While indefinite anticoagulation is indicated in the SCD population, there is limited understanding of comparative efficacy and hemorrhagic risk of individual anticoagulation agents in this population. We reviewed the use of anticoagulation for treatment of VTE in patients with SCD at our institution to begin to address these questions. A retrospective chart review of all patients with SCD 18 years of age and older (currently alive or deceased) who received care at Boston Medical Center/Boston University between 2003 and 2018 was performed. VTE was defined as deep venous thrombosis (DVT) diagnosed by duplex ultrasound or pulmonary embolism (PE) diagnosed by either ventilation-perfusion scanning or computed tomography angiography. The primary efficacy outcome was the number of VTE events which occurred while the patient was receiving anticoagulation. The primary safety outcome was major bleeding as defined by the International Society on Thrombosis and Hemostasis 2005 guidelines. The medical records of 233 patients with SCD were reviewed; VTE was identified in 55 (23.6%) patients. Sixty-five percent were female. In these 55 patients, a total of 94 VTE events occurred. Fifteen (16.0%) were catheter-associated upper extremity DVTs. For the first event, initial outpatient treatment consisted of warfarin in 56%, low-molecular-weight heparin (LMWH) in 18.2%, rivaroxaban in 9.1%, apixaban in 5.5%, and fondaparinux in 3.6%. The median length of treatment was 7.3 (median: 6, IQR: 3-12) months. Recurrent VTEs occurred in 27 (49%) patients with a total of 39 recurrent events. Among the recurrent events, thirteen (33.0%) were treatment failures occurring during anticoagulation therapy (see Table 1): 7 of 37 (18.9%) on warfarin, 2 of 20 (10.0%) on LMWH, and 4 of 15 (26.7%) on rivaroxaban. Death from recurrent VTE occurred in two patients; one occurred while a patient was therapeutic on warfarin. Major bleeding occurred in two patients (3.6%); in both cases, this was intracranial hemorrhage while on warfarin. In this retrospective study, there was a high rate of VTE recurrence despite anticoagulation in patients with SCD. Treatment failure was highest with warfarin and rivaroxaban, although adherence was difficult to assess. Risk of hemorrhage and death appears higher in those prescribed warfarin. These data affirm the need for long-term anticoagulation in most patients with SCD with a VTE and support the use of direct oral anticoagulants as a first-line agent. Disclosures Sloan: Abbvie: Other: Endpoint Review Committee; Stemline: Consultancy; Merck: Other: endpoint review commitee.
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