Population Pharmacokinetics of Fosfomycin in Critically Ill Patients

This study describes the population pharmacokinetics of fosfomycin in critically ill patients. In this observational study, serial blood samples were taken over several dosing intervals of intravenous fosfomycin treatment. Blood samples were analyzed using a validated liquid chromatography-tandem mass spectrometry technique. A population pharmacokinetic analysis was performed using nonlinear mixed-effects modeling. Five hundred fifteen blood samples were collected over one to six dosing intervals from 12 patients. The mean (standard deviation) age was 62 (17) years, 67% of patients were male, and creatinine clearance (CL_CR) ranged from 30 to 300 ml/min. A two-compartment model with between-subject variability on clearance and volume of distribution of the central compartment (V_c) described the data adequately. Calculated CL_CR was supported as a covariate on fosfomycin clearance. The mean parameter estimates for clearance on the first day were 2.06 liters/h, V_c of 27.2 liters, intercompartmental clearance of 19.8 liters/h, and volume of the peripheral compartment of 22.3 liters. We found significant pharmacokinetic variability for fosfomycin in this heterogeneous patient sample, which may be explained somewhat by the observed variations in renal function.     

An Alternative Design to Overcome the Problem of Unfavorable Implant Angulations for a Screw‐Retained,Implant‐Supported Fixed Prosthesis: Two Clinical Reports

Two clinical reports present an alternative design to address the problem of unfavorable implant angulations if a screw‐retained prosthesis is desired. The restorations were designed as screw‐retained prostheses, except in the area with the unfavorable implant screw emergence. The frameworks in these areas were customized to receive individual cement‐retained crowns. This design offers retrievability and helps to minimize complications associated with excess cement without compromising the functional or esthetic outcome.     

ANCA-associated glomerulonephritis/systemic vasculitis in childhood: clinical features–outcome

Background

Antineutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis and systemic vasculitis (AAGNV) is uncommon in childhood.

Methods

This is a retrospective study of AAGNV cases diagnosed over a 13-year period in a tertiary pediatric nephrology department.

Results

Thirteen cases of AAGNV were identified: seven Wegener granulomatosis (WG) and six microscopic polyangiitis (MPA). Acute renal failure/nephrotic range proteinuria (NRP) was found in 77 % of the patients (4 with WG, all with MPA). Eleven (85 %) patients showed necrotizing glomerulonephritis (NGN), with ≥50 % crescents identified in nine patients (69 %) (4 with WG, 5 with MPA). Treatment with methylprednisolone, cyclophosphamide and plasma exchange resulted in extra-renal remission and antibody reduction in all patients and renal function improvement/stabilization in 77 % of the patients. Three patients, all without oliguria at presentation and few sclerotic lesions, had normal renal function at follow-up. Chronic kidney disease (CKD) stages 2 and 3–4 were observed in four (WG) and three (MPA) patients, respectively. Three patients (23 %) developed end stage renal disease: two were MPA patients with severe presentation (markedly impaired glomerular filtration rate, oliguria, NRP, crescentic NGN, glomerular sclerosis) and one was a WG patient with extensive interstitial fibrosis/tubular atrophy.

Conclusions

Severe renal involvement was more common in children with MPA than WG. Treatment with methylprednisolone, cyclophosphamide and plasma exchange induced extra-renal remission/serological response and renal function improvement/stabilization. Markedly decreased GFR, oliguria, NRP, and chronic glomerular lesions at presentation were predictors of poor outcome.     

Familial hypercholesterolemia and response to statin therapy according to LDLR genetic background.

Familial hypercholesterolemia is an autosomal dominant disease defined at the molecular level mainly by the presence of mutations in the low-density lipoprotein receptor gene and is characterized by elevated low-density lipoprotein cholesterol, tendon xanthomas and increased risk of early cardiovascular disease. The type of mutation in the low-density lipoprotein receptor gene has been associated with different phenotype expression and response to statins. Several studies have been undertaken to assess the efficacy of statins and evaluate the influence of mutations on the response to treatment with statins. Not all patients respond to statin therapy with a reduction in cardiovascular disease. In this review paper, we will discuss the results available to date that correlate the low-density lipoprotein receptor genotype to the response to statins, and the interest in developing diagnostic systems which will allow identification of patients at increased risk of adverse drug reactions or patients in which a therapeutic effect is lacking.     

Amifostine stimulates the formation of hematopoietic bone marrow progenitors from B-cell chronic lymphocytic leukemia

Amifostine is a phosphorylated aminothiol that not only protects hematopoietic progenitor cells from chemotherapy and radiotherapy, but also stimulates normal hematopoiesis. The effect of amifostine on the in vitro growth of hematopoietic progenitors derived from B-cell chronic lymphocytic leukemia(B-CLL) was investigated. The colony-forming units (CFU)-granulocyte macrophage (CFU-GM), the burst-forming units-erythroid (BFU-E) and the CFU-granulocyte erythroid macrophage megakaryocytes (CFU-GEMM) increased 38, 20 and 100%, respectively, after the incubation with amifostine. There was no statistical difference in the in vitro progenitor growth of patients grouped according to their disease stage, bone marrow lymphocytic infiltration or therapy. Our data indicate that apart from cytoprotection the parallel use of amifostine and chemotherapy in patients with B-CLL could enhance bone marrow recovery.     

Factors predicting failure of redo Nissen fundoplication in children

Recurrence of gastro-oesophageal reflux (GOR) following redo Nissen fundoplication represents a significant clinical problem. The aim of this study was to identify factors predicting failure of redo Nissen fundoplication. The notes of children who underwent redo Nissen fundoplication for recurrent GOR in a single institution between June 1994 and May 2005 were reviewed. Data are reported as median (range), or as numbers of cases. Multiple logistic regression analysis, using type of first fundoplication, neurological status, presence of gastrostomy, age–weight, retching–gas bloat after first fundoplication, associated anomalies, oesophageal atresia and length of follow-up as factors, was used to generate a model to identify factors predicting recurrent vomiting (failure) after redo. Eighty-one children underwent redo Nissen fundoplication 15.9 months (0.2–176) after the initial Nissen fundoplication. In 29, the first Nissen was laparoscopic. Age at redo Nissen fundoplication was 3.3 years (0.3–15.9) and weight 12.8 kg (5–60). Thirty-four children (42%) presented with recurrent vomiting (failure). Overall, the model successfully predicted vomiting (failure) after redo fundoplication (P = 0.009). Open surgery at first fundoplication (P = 0.011) and neurological impairment (P = 0.046) were both significant predictors of redo failure in the model, whereas presence of gastrostomy (P = 0.035) and older–heavier age–weight (P = 0.028) were associated with significantly better results. Retching–gas bloat, associated anomalies and oesophageal atresia were not significant predictors of failure. Redo Nissen fundoplication has a high failure rate. Risk factors are open fundoplication at first operation and neurological impairment. Redo fundoplication after primary laparoscopic Nissen has a lower risk of failure.