Search

Objective: HIV preexposure prophylaxis (PrEP) is efficacious, but uptake has been slow. In Washington State, most insurance plans, including Medicaid, pay for PrEP, and the state supports a PrEP drug assistance program. We assessed trends in PrEP awareness and use among MSM in Washington., Design and Setting: Serial cross-sectional survey conducted annually at the Seattle Pride Parade between 2009 and 2015., Methods: In a convenience sample of MSM who reside in Washington State and deny ever testing HIV positive (n = 2168), we evaluated the association between calendar year and self-report of PrEP uptake and awareness using descriptive statistics and multivariable relative risk and logistic regression. Regression models included HIV risk and demographic covariates., Results: In 2015, 23% [95% confidence interval (CI): 16%, 31%] of high-risk MSM reported currently taking PrEP. The percentage of high-risk MSM who reported ever taking PrEP increased from 5% in 2012 to 31% in 2015. PrEP use among lower-risk MSM was low and stable, between 1 and 3% in 2012-2015. In multivariable analyses, PrEP use was associated with later calendar years (2015 vs. 2012: adjusted relative risk = 2.29, 95% CI: 1.16, 4.52) and elevated HIV risk (adjusted relative risk = 2.92, 95% CI: 2.00, 4.25). The percentage of high and lower-risk MSM who had heard of PrEP increased from 13 to 86% and from 29 to 58%, respectively., Conclusion: PrEP awareness is high and the use has rapidly increased over the last year among MSM in Seattle, Washington, USA. These findings demonstrate that high levels of PrEP use can be achieved among MSM at high-risk for HIV infection.

Objective: ABT-751, a novel orally available antitubulin agent, is mainly eliminated as inactive glucuronide (ABT-751G) and sulfate (ABT-751S) conjugates. We performed a pharmacogenetic investigation of ABT-751 pharmacokinetics using in-vitro data to guide the selection of genes for genotyping in a phase I trial of ABT-751., Methods: UDP-glucuronosyltransferase (UGT) and sulfotransferase (SULT) enzymes were screened for ABT-751 metabolite formation in vitro. Forty-seven cancer patients treated with ABT-751 were genotyped for 21 variants in these genes., Results: UGT1A1, UGT1A4, UGT1A8, UGT2B7, and SULT1A1 were found to be involved in the formation of inactive ABT-751 glucuronide (ABT-751G) and sulfate (ABT-751S). SULT1A1 copy number (>2) was associated with an average 34% increase in ABT-751 clearance (P=0.044), an 18% reduction in ABT-751 AUC (P=0.045), and a 50% increase in sulfation metabolic ratios (P=0.025). UGT1A8 rs6431558 was associated with a 28% increase in glucuronidation metabolic ratios (P=0.022), and UGT1A4*2 was associated with a 65% decrease in ABT-751 C trough (P=0.009)., Conclusion: These results might represent the first example of a clinical pharmacokinetic effect of the SULT1A1 copy number variant on the clearance of a SULT1A1 substrate. A-priori selection of candidate genes guided by in-vitro metabolic screening enhanced our ability to identify genetic determinants of interpatient pharmacokinetic variability.

Background: In hepatitis C virus (HCV)-positive liver transplant recipients, infection of the allograft and recurrent liver disease are important problems. Increased donor age has emerged as an important variable affecting patient and graft survival; however, specific age cutoffs and risk ratios for poor histologic outcomes and graft survival are not clear., Methods: A longitudinal database of all HCV-positive patients transplanted at our center during an 11-year period was used to identify 111 patients who received 124 liver transplants. Graft survival and histological endpoints (severe activity and fibrosis) of HCV infection in the allografts were compared as a function of donor age at transplantation., Results: By Kaplan-Meier analyses, older allografts showed earlier failure and decreased time to severe histological activity and fibrosis as compared with allografts from younger donors. By Cox proportional hazards analysis, older allografts were at greater risk for all severe histologic features and decreased graft survival as compared with younger allografts (P< or =0.02 for all outcomes). Analysis of donor age as a dichotomous variable showed that donors greater than 60 yr were at high risk for deleterious histologic outcomes and graft failure. An age cutoff of 60 yr showed a sensitivity of 94% and specificity of 67% for worse graft survival by receiver operating characteristics curve., Conclusions: Advanced donor age is associated with more aggressive recurrent HCV and early allograft failure in HCV-positive liver transplant recipients. Consideration of donor age is important for decisions regarding patient selection, antiviral therapy, and organ allocation.

Background: Recurrent hepatitis C virus (HCV) infection in patients after liver transplantation is an important clinical problem. Because serum cryoglobulins (CG) are known to be associated with an increased incidence of cirrhosis in nontransplant patients, the authors tested the hypothesis that CG would also predict aggressive recurrent HCV in patients after liver transplantation., Methods: Using a longitudinal database, the outcomes of 105 allografts transplanted into 97 HCV-positive patients from 1991 through 2002 were analyzed on the basis of CG status using a retrospective cohort design. Fifty-nine CG-negative and 38 CG-positive patients were identified. Histologic outcomes and graft survival were analyzed using Kaplan-Meier estimates and Cox univariate and multivariate analyses. Both overall survival and HCV-specific survival (non-HVC-related deaths and graft losses censored) were analyzed., Results: By Kaplan-Meier estimates, CG-positive patients showed earlier graft failure with decreased time to severe histologic activity and fibrosis as compared with CG-negative patients (P<0.05 for all outcomes). By univariate analysis, CG-positive patients had significantly higher risk ratios for shortened HCV-specific graft survival, severe activity-free survival, and severe fibrosis-free survival as compared with CG-negative patients (P<0.05 for all outcomes). In the multivariate model, CG was an independent predictor for severe activity-free, severe fibrosis-free, and HCV-specific graft survival (P<0.05 for all outcomes)., Conclusions: CG-positivity is associated with severe recurrent HCV disease in liver transplant recipients.

Purpose: To evaluate the accuracy and clinical role of gadolinium-enhanced 3D magnetic resonance angiography (MRA) in patients with suspected hepatic arterial complications after liver transplantation., Materials and Methods: Thirty-six consecutive MRA studies were performed in 33 liver transplant recipients after transplantation. MRA image quality was assessed subjectively. Thirty-two MRA studies were retrospectively reviewed and correlated with surgery (n = 2), conventional angiography (n = 18), or clinical follow-up (n = 12). MRA findings were also correlated with those of Doppler sonography in 30 of the cases. In 20 cases, concordance between MRA and surgery or conventional angiography was evaluated for each grade of hepatic artery stenosis (normal, mild [<50%], moderate [50-75%], severe [>75%], or occluded)., Results: MRA image quality was degraded 13 of 36 cases (36.1%) studies. The sensitivity, specificity, and accuracy of MRA by consensus reading for more than 50% of hepatic artery stenosis or occlusion were 67%, 90%, and 81.3%, respectively. Of the 19 cases in which Doppler sonography was abnormal, MRA correctly characterized hepatic artery stenosis in 16 (84.2%). MRA also correctly identified all 5 occurrences of celiac artery stenosis. However, MRA overestimated the severity of hepatic arterial stenosis in 3 (15%) of 20 cases and underestimated 5 (25%) of 20 cases., Conclusion: MRA complements Doppler ultrasound to exclude significant hepatic artery stenosis. However, a substantial number of MRA studies were technically inadequate, and MRA demonstrated limited efficacy for correctly grading the severity of hepatic artery stenosis.

Bracing for adolescent scoliosis has been postulated to cause permanent loss of bone mass and to predispose to adult osteoporosis. To determine whether brace use affects the rate of bone accretion with growth, the authors conducted a prospective study of 52 girls with adolescent idiopathic scoliosis. Dual-energy x-ray absorptiometry (DEXA) showed a significant increase in spinal bone mineral density (BMD) over a 1-year period of brace wear. BMD correlated with measures of growth and pubertal status, but not average daily brace wear or severity of scoliosis. The annual rate of bone density accumulation was similar to reported normal values. The annual rate of change of volumetric bone density increased only slightly during the study period, suggesting that most of the change in BMD with time reflects growth in the dimensions of the spine. Brace treatment does not appear to inhibit bone density accumulation in girls with adolescent idiopathic scoliosis.

Neither the natural history nor the optimal treatment of cervical spine anomalies in Larsen's syndrome has been clearly defined. The authors describe two patients with Larsen's syndrome with cervical kyphosis, anteroposterior dissociation, and quadriparesis to show the variable clinical progression and offer a description of the authors' treatment. One patient has had continued neurologic and radiographic improvement with nonoperative treatment consisting of early traction. The other patient was treated with posterior fusion that failed to halt progressive kyphosis of the anterior vertebral bodies because of anteroposterior dissociation. He then was treated by resection of the posterior fusion, traction, and anterior and posterior decompression and fusion. Cervical kyphosis in patients with Larsen's syndrome is unpredictable, and both nonoperative and operative treatments have the potential to be successful. Anteroposterior dissociation of the cervical spine may be more common in Larsen's syndrome than recognized previously and may profoundly affect operative strategy and outcome.

Study Design: Case report and literature review., Objectives: Review cases and literature regarding visual loss following posterior spine fusion for scoliosis and emphasize right-to-left atrial shunt as a risk factor for paradoxical embolus resulting in a postoperative visual field defect., Summary of Background Data: The existing literature discusses various possible etiologies of postoperative visual loss including direct pressure, hypotension, blood loss, and anemia. One study shows higher rates of cerebral microemboli in patients with right-to-left atrial shunts., Methods: Chart and literature review., Results: A paradoxical embolus to a branch of the central retinal artery resulted in a unilateral quadrant defect (homonymous quadrantanopsia) in a girl with a previously undiagnosed right-to-left atrial shunt., Conclusions: Right-to-left atrial shunts may predispose to cerebral emboli during scoliosis surgery. These emboli may be a cause of postoperative visual field defects.

Slipped capital femoral epiphysis (SCFE) and Down syndrome are both uncommon in the population at large, and rarely are both conditions present in a single individual. Institutional records were searched for both Down syndrome and SCFE. At least 2 years of follow-up was required. Eight patients were identified. At presentation four patients could not walk due to pain and four could walk. Six of eight hips presented with grade III SCFE. Four hips were treated with internal fixation in situ and four were manipulatively reduced in the operating room at the time of fixation with percutaneous screws or pins. Three hips healed uneventfully. Five hips developed aseptic necrosis (three partial, two whole head). This small retrospective study suggests an extremely high rate of complications in adolescents with Down syndrome and SCFE.

Background: Cavaplasty orthotopic liver transplantation (OLT) offers advantages for hepatectomy and implantation and eliminates the risk of outflow obstruction. However, it does require clamping of the cava. This study describes the use of a vasopressor without fluid expansion or venovenous bypass (VB) for hemodynamic control during the anhepatic phase., Methods: The cavaplasty OLT technique was used routinely. A vasopressor was administered if the mean arterial blood pressure (MAP) was less than 60 mm Hg after clamping of the cava. If the MAP did not reach 60 mm Hg after adjusting the dosage of the vasopressor, femoro-axillary VB would be used. VB was also indicated for preexisting cardiac disease or for massive hemorrhage from severe portal hypertension and extensive adhesions., Results: Among all the 121 adult cavaplasty OLTs, 33 were supported with VB and 50 received a vasopressor. The remaining 38 were excluded. However, baseline variables were well matched, except that preexisting cardiac disease was more frequent in the VB group. The median dosage of epinephrine was 0.07 microg/kg/min (range 0.01-0.6). The VB and vasopressor groups were similar in the reduction in mean MAP and the accumulation in arterial lactate upon clamping as well as in the central venous pressure upon unclamping. Postreperfusion hypotension was more frequent in the VB than in the vasopressor group (27.3% vs. 4.0%, P=0.006). There was no primary graft nonfunction or intraoperative right heart failure. One patient in the vasopressor group required postoperative temporary dialysis. Ninety-day patient and graft survival for the VB and vasopressor groups were 97.0% vs. 98.0% and 97.0% vs. 94.0%, respectively., Conclusion: Modest doses of vasopressor without volume expansion or VB can maintain hemodynamic stability during the anhepatic phase of cavaplasty OLT.

This prospective study used pulsed color-flow Doppler sonography to determine differences in the presence and direction of flow through the dorsalis pedis, posterior tibial, and peroneal arteries in a group of children with clubfoot and a comparison group of controls. There was a statistically significant difference in the prevalence of deficient (absent or retrograde flow) dorsalis pedis arteries in children with clubfoot (45%) compared with controls (8%). This indicates that there is an association between some clubfeet and deficiency of the dorsalis pedis artery. There was a trend toward difference in the prevalence of deficiency of the dorsalis pedis artery in the clubfeet that required surgery (54%) compared with those that did not (20%), suggesting that dorsalis pedis artery deficiency may be more prevalent among clubfeet with greater deformity.

Purpose: Cyclophosphamide is commonly used in the treatment of children with malignant brain tumors. The purpose of this study was to develop a multicycle, high-dose intensity cyclophosphamide regimen with granulocyte-macrophage colony-stimulating factor (GM-CSF) and to assess its activity against malignant glioma and primitive neuroectodermal tumor (PNET)., Methods: Twenty-three patients with brain tumors, including 15 with malignant glioma and six with PNET, were enrolled. Cyclophosphamide (1.8-2.25 g/m2/day for 2 days i.v.; total dose 3.6-4.5 g/m2) was administered and was followed by recombinant human GM-CSF (5 micrograms/kg/day s.c.) on days 3-11 or until the absolute granulocyte count reached 1.5 x 10(9)/L., Results: With a total of 83 cycles administered, the mean dose intensity of cyclophosphamide ranged from 1.5 g/m2/week through cycle 2 (22 patients) to 0.8 g/m2/week through cycle 8 (two patients). No activity was seen against malignant glioma, and five of six patients with PNET had partial responses. The mean duration of a neutrophil count of < 0.5 x 10(9)/L was only 8 days; the platelet recovery was substantially longer. Fever during neutropenia occurred in 54 of 83 cycles. One patient died from transfusion-related graft-versus-host disease., Conclusions: A cyclophosphamide regimen equal to twice the dose intensity of that used in conventional therapy was administered. The regimen was active against PNET but inactive against malignant glioma.

We determined the feasibility and value of studying intracranial CSF flow in children with potential CSF pathway problems using a cardiac gated cine magnetic resonance (MR) format. We studied 15 consecutive patients with a variety of clinical problems that suggested possible CSF pathway problems. The diagnoses included Chiari malformation, Dandy-Walker syndrome, external hydrocephalus, cerebellar tumor, CNS histoplasmosis, and tuberculous meningitis. In addition to documenting the feasibility of the technique in children (7 of 15 were less than 2 years of age), we derived significant new information relative to pathogenesis and/or therapy. The study provides preliminary evidence supporting intracranial CSF flow studies at the time of routine MR imaging of appropriate children.

The case report of a 79-year-old woman with the histologic features of verrucous squamous cell carcinoma of the uterus is presented. The case is unusual because the characteristic exophytic lesion of verrucous squamous cell carcinoma was not visible in this patient, as the entire lesion was confined to the endocervical and endometrial cavities. The diagnosis was made by fractional dilatation and curettage in the evaluation of postmenopausal bleeding. The characteristic clinical and pathological features of verrucous carcinoma are discussed. The etiologic agent and appropriate treatment of this lesion are outlined.

We studied a family with progressive dementia, optic atrophy, and spastic paraparesis. Autopsy of one family member revealed multisystem atrophy with widespread degeneration of the thalamus and marked attenuation of hemispheric white matter to account for the dementia. This family may suffer from a unique disorder, but the findings overlap with other reported cases of thalamic dementia or familial spastic paraparesis.