Joint Trajectories of Cognition and Frailty and Associated Burden of Patient-Reported Outcomes

Objectives

To evaluate joint trajectories of cognition and frailty and their association with the cumulative burden of patient-reported outcomes, including hospitalization, nursing home admission, and disability.

Albumin/Creatinine Ratio for the Detection of Significant Proteinuria of Preeclampsia in Hospitalized Hypertensive Women

ObjectivePreeclampsia is a hypertensive disorder of pregnancy associated with proteinuria detected by 24-hour urine collection (≥0.3 g/24 h) or protein/creatinine ratio (≥30 mg/mmol). The albumin/creatinine ratio (ACR) is used outside pregnancy to detect abnormal amounts of albumin in the urine, but there is little data on its value in pregnancy. Our objective was to determine the diagnostic threshold for ACR to detect significant proteinuria in women investigated for preeclampsia.MethodsA prospective observational study involving 99 hypertensive women (≥140/90 mm Hg) over 20 weeks gestation who were hospitalized at 2 Canadian tertiary centres. A 24-hour urine collection and a morning urine sample were collected. The optimal ACR threshold was determined by a receiver operating characteristic (ROC) curve using the 24-hour collection as the reference test; sensitivity and specificity analyses were performed. Maternal and perinatal characteristics were extracted from medical records.ResultsOf the 87 women who had completed urine collection, 74 (85%) had an initial diagnosis of preeclampsia and 63 (72%) had significant proteinuria confirmed by 24-hour collection. The area under the morning ROC curve was 0.92 (95% CI 0.86–0.98) and the optimal threshold obtained for the ACR was 9 mg/mmol, with a sensitivity and specificity of 84% (95% CI 73–92) and 88% (95% CI 68–97), respectively.ConclusionOur results suggest that an ACR threshold of 9 mg/mmol on a morning urine sample can be used to detect significant proteinuria of preeclampsia in hospitalized hypertensive women.     

Pharmacokinetics of nelfinavir and its active metabolite,hydroxy-tert-butylamide,in infants perinatally infected with human immunodeficiency virus type 1

BACKGROUND: In children younger than 2 years of age vertically infected with HIV-1, the recommended pediatric dosing regimen for nelfinavir (20 to 30 mg/kg three times a day) provides insufficient drug exposure. This study was conducted to determine the steady state pharmacokinetics of nelfinavir and its active metabolite, M8, in this population. METHODS: Fourteen infants (2.3 to 8.5 months) underwent 18 intensive pharmacokinetic studies of nelfinavir and M8 at steady state. Nelfinavir and M8 concentrations were measured by high performance liquid chromatography coupled with mass spectrometry, and individual pharmacokinetic values were determined. RESULTS: A mean nelfinavir daily dose of 135.7 +/- 18.8 mg/kg (twice or three times a day) resulted in median C(min), C(max), area under the plasma concentration-time curve (AUC(0-24 h)) and CL/ for nelfinavir of 0.627 mg/l, 2.39 mg/l, 30.6 mg*h/l and 4.2 liters/h/kg, respectively. When normalized for a daily dose of nelfinavir of 150 mg/kg/day, 16.7% of C(max) and 27.8% of AUC(0-24 h) values were below the tenth percentile for adult values. CONCLUSIONS: During the first year of life, nelfinavir requirement is much higher than in older children and adults to obtain similar drug exposure. The mechanisms underlying such differences may involve higher first past metabolism and/or drug interactions or might be related to feeding conditions.     

Liver transplantation and neuroendocrine tumors: lessons from a single centre experience and from the literature review

Neuroendocrine tumor (NET) metastases represent at this moment the only accepted indication of liver transplantation (LT) for liver secondaries. Between 1984–2007, nine (1.1%) of 824 adult LTs were performed because of NET. There were five well differentiated functioning NETs (four carcinoids and one gastrinoma), three well differentiated non functioning NETs and one poorly differentiated NET. Indications for LT were an invalidating unresectable tumor (4×), and/or a diffuse tumor localization (3×) and/or a refractory hormonal syndrome (5×). Median post‐LT patient survival is 60.9 months (range 4.8–119). One‐, 3‐ and 5‐year actuarial survival rates are 88%, 77% and 33%; 1, 3 and 5 years disease free survival rates are 67%, 33% and 11%. Due to a more rigorous selection procedure, results improved since 2000; three out of five patients are alive disease‐free at 78, 84 and 96 months. Review of these series together with a review of the literature reveals that results of LT for this oncological condition can be improved using better selection criteria, adapted immunosuppression and neo‐ and adjuvant surgical as well as medical tretament. LT should be considered earlier in the therapeutic algorithm of selected NET patients as it is the only therapy that can offer a cure.     

Thoracoscopic thymectomy in autoimmune myasthesia: results of left-sided approach

BACKGROUND: We undertook to analyze the results of video-assisted thoracoscopic thymectomy through a left-sided approach in patients with autoimmune myasthenia. METHODS: Between 1993 and 1997, 31 patients underwent thoracoscopic thymectomy by a uniform left-sided approach. There were 8 men and 23 women with a mean age of 34 +/- 12 years. RESULTS: Preoperative duration of disease was 14.8 +/- 11 months. There were no operative deaths or major complications. The mean hospital stay was 5.2 +/- 2.8 days. Mean follow-up was 39.6 +/- 15 months and was 100% complete. At 48 months, remission and improvement rates were 36% and 96%, respectively. Shorter duration of symptoms (< 12 months) correlated with improved outcome (13 of 13 patients versus 10 of 14 patients; p = 0.036). Age, sex, Osserman class, corticosteroid therapy, presence of ectopic thymic tissue, and temporary postoperative symptom increase (deterioration) did not affect outcome. CONCLUSIONS: Thoracoscopic thymectomy facilitated the goal of early thymectomy. Through a left-sided approach, improvement or remission was achieved in more than 95% of the patients. Thoracoscopic thymectomy should be considered a valid less invasive alternative to the most radical open approaches.     

Liver transplantation with preservation of the inferior vena cava in case of symptomatic adult polycystic disease

Adult polycystic liver disease (APLD) is a rare disorder of the liver parenchyma, the treatment of which is still controversial. Conservative surgery may have a significant morbidity and is often ineffective in the long run. Liver replacement may be indicated in case of incapacitating hepatomegaly. Patients (one male, five females) undergoing liver transplantation for symptomatic APLD is presented in this study. The particular nature of this series is the fact that successful transplantation was performed in all cases with preservation of the recipient's inferior vena cava and without use of veno-venous bypass despite massive hepatomegaly and previous extensive liver surgery (in three cases). There was minimal morbidity and no mortality. All patients have excellent quality of life with a median follow-up of 41 months (range: 12-58) as testified by a median Karnofsky score of 90% (range: 80-100%).