Effects of age and sex on single-dose pharmacokinetics of tigecycline in healthy subjects

The pharmacokinetics of tigecycline was evaluated in 46 healthy young and elderly men and women. Except for the volumes of distribution at steady state (approximately 350 liters in women versus 500 liters in men), there were no significant differences in tigecycline pharmacokinetic parameters. Based on pharmacokinetics, no dosage adjustment is warranted based on age or sex.     

Multiple patients with revertant mosaicism in a single Wiskott-Aldrich syndrome family

We previously reported on a 43-year-old patient with Wiskott-Aldrich syndrome (WAS) who experienced progressive clinical improvement and revertant T-cell mosaicism. Deletion of the disease-causing 6-bp insertion was hypothesized to have occurred by DNA polymerase slippage. We now describe 2 additional patients from the same family who also had revertant T lymphocytes that showed selective in vivo advantage. Somatic mosaicism was demonstrated on leukocytes cryopreserved in the first patient when he was 22 years old, 11 years before his death from kidney failure. The second patient is now 16 years old, has a moderate clinical phenotype, and developed revertant cells after the age of 14 years. These results support DNA polymerase slippage as a common underlying mechanism, and they indicate that T-cell mosaicism may have different clinical effects in WAS.     

Associations of Soluble CD14 and Endotoxin with Mortality,Cardiovascular Disease,and Progression of Kidney Disease among Patients with CKD

Background and objectives

CD14 plays a key role in the innate immunity as pattern-recognition receptor of endotoxin. Higher levels of soluble CD14 (sCD14) are associated with overall mortality in hemodialysis patients. The influence of kidney function on plasma sCD14 levels and its relationship with adverse outcomes in patients with CKD not yet on dialysis is unknown. This study examines the associations between plasma levels of sCD14 and endotoxin with adverse outcomes in patients with CKD.

Design, setting, participants, & measurements

We measured plasma levels of sCD14 and endotoxin in 495 Leuven Mild-to-Moderate CKD Study participants. Mild-to-moderate CKD was defined as presence of kidney damage or eGFR<60 ml/min per 1.73 m² for ≥3 months, with exclusion of patients on RRT. Study participants were enrolled between November 2005 and September 2006.

Results

Plasma sCD14 was negatively associated with eGFR (ρ=–0.34, P<0.001). During a median follow-up of 54 (interquartile range, 23–58) months, 53 patients died. Plasma sCD14 was predictive of mortality, even after adjustment for renal function, Framingham risk factors, markers of mineral bone metabolism, and nutritional and inflammatory parameters (hazard ratio [HR] per SD higher of 1.90; 95% confidence interval [95% CI],1.32 to 2.74; P<0.001). After adjustment for the same risk factors, plasma sCD14 was also a predictor of cardiovascular disease (HR, 1.30; 95% CI, 1.00 to 1.69; P=0.05). Although plasma sCD14 was associated with progression of CKD, defined as reaching ESRD or doubling of serum creatinine in models adjusted for CKD-specific risk factors (HR, 1.24; 95% CI, 1.01 to 1.52; P=0.04), significance was lost when adjusted for proteinuria (HR, 1.19; 95% CI, 0.96 to 1.48; P=0.11). There was neither correlation between plasma endotoxin and sCD14 (ρ=–0.06, P=0.20) nor was endotoxin independently associated with adverse outcome during follow-up.

Conclusions

Plasma sCD14 is elevated in patients with decreased kidney function and associated with mortality and cardiovascular disease in patients with CKD not yet on dialysis.     

Patient,physician, and family member understanding of living wills

This study examines understanding of living wills by patients, family members, and physicians. Questionnaires were used to examine whether each cohort understood patients' living wills regarding endotracheal intubation and cardiopulmonary rescuscitation (CPR). Of 4,800 patients admitted during the study period, 206 reported having living wills, all of which precluded intubation and CPR for "terminal conditions." Of 140 admitted to the general hospital wards, 17 (12%) wanted their living wills to preclude intubation/mechanical ventilation and 12 (8.6%) did not want resuscitation under any circumstances. Seven of 120 (6%) physicians and 4 of 108 family members would not intubate or perform CPR even if there was a chance of recovery. Of 88 patients with complete data (including physicians and family members), 29 (33%) wanted their living wills to block intubation/mechanical ventilation only if they were deemed terminal and 46 (52%) wanted the living will to block intubation even if there was a 10% chance of recovery. Thirteen (15%) wanted to block intubation even if the chance of recovery was > or = 50. Results were similar for wishes regarding CPR. These data suggest substantial differences of patient, physician, and family member understanding of living wills. Living wills did not reflect fully patients' expectations of receiving (or not receiving) life-sustaining modalities.     

Primary hepatic carcinoid tumours

BACKGROUND: Carcinoid tumours of the liver are predominantly metastases from the gastrointestinal tract. Primary hepatic carcinoids are extremely rare. DISCUSSION: In contrast to metastases, primary hepatic carcinoids are usually solitary and resectable. It is important that these tumours are differentiated from metastases. Complete surgical resection should be contemplated and is generally curative.