Short- and long-term outcomes of critically ill patients with cancer and prolonged ICU length of stay

BACKGROUND: Data on patients with cancer who have a prolonged length of stay (LOS) in the ICU are scarce. The aim of the present study was to evaluate the characteristics and the outcomes of cancer patients with life-threatening complications with an ICU stay >/= 21 days. METHODS: A cohort study performed at a 10-bed oncology medical-surgical ICU from May 2000 to December 2005. Prolonged ICU LOS was defined as an ICU stay >/= 21 days. RESULTS: During the period, 1,090 patients were admitted to the ICU and 163 patients (15%) had a prolonged ICU LOS. These patients, however, accounted for 48% (5,828/12,224) of the total ICU bed-days. The hospital and 6-month mortality rates were 50% and 60%, respectively, and similar to patients with ICU LOS < 21 days (51% and 61%, respectively). ICU-acquired events and complications were common, and the most frequent were infections (90%), mechanical ventilation (99%), and need for vasopressors (88%). The number of organ failures, older age, and poor performance status were the main outcome predictors. The median long-term follow-up after hospital discharge was 537 days (range, 193 to 1,119 days), and 29 patients (18%) were alive. CONCLUSIONS: Fifteen percent of critically ill patients with cancer had a prolonged ICU LOS. Short- and long-term survival rates were reasonable, and the prognosis was better than expected a priori. In our opinion, the length of ICU admission per se should not be used in the clinical decisions regarding the continuation of treatment in these patients.     

Clathrin light chains function in mannose phosphate receptor trafficking via regulation of actin assembly

Clathrin-coated vesicles (CCVs) are major carriers for endocytic cargo and mediate important intracellular trafficking events at the trans-Golgi network (TGN) and endosomes. Whereas clathrin heavy chain provides the structural backbone of the clathrin coat, the role of clathrin light chains (CLCs) is poorly understood. We now demonstrate that CLCs are not required for clathrin-mediated endocytosis but are critical for clathrin-mediated trafficking between the TGN and the endosomal system. Specifically, CLC knockdown (KD) causes the cation-independent mannose-6 phosphate receptor (CI-MPR) to cluster near the TGN leading to a delay in processing of the lysosomal hydrolase cathepsin D. A recently identified binding partner for CLCs is huntingtin-interacting protein 1-related (HIP1R), which is required for productive interactions of CCVs with the actin cytoskeleton. CLC KD causes mislocalization of HIP1R and overassembly of actin, which accumulates in patches around the clustered CI-MPR. A dominant-negative CLC construct that disrupts HIP1R/CLC interactions causes similar alterations in CI-MPR trafficking and actin assembly. Thus, in mammalian cells CLCs function in intracellular membrane trafficking by acting as recruitment proteins for HIP1R, enabling HIP1R to regulate actin assembly on clathrin-coated structures.     

Evaluation of the quality of different endodontic obturation techniques by digital radiography

Objectives

This study was aimed to evaluate different endodontic obturation techniques (Thermafil, lateral condensation, and Tagger’s hybrid technique) regarding the homogeneity of the obturation radiopacity.

Materials and methods

Seventy roots of human upper central incisors were filled using the Thermafil system, lateral condensation. and Tagger’s hybrid technique. Radiopacity of the filling was evaluated based on mean of grey levels, and its homogeneity was assessed by the coefficient of variation (CV), analyzing the histograms obtained of digitized and digital radiographs.

Results

The increase in mean grey levels (p?<?0.001) and reduction in the CV (p?<?0.05) were higher for Tagger’s hybrid technique compared with other methods.

Conclusions

Tagger’s hybrid technique provided better homogeneity of the obturation radiopacity and better apical sealing compared with lateral condensation technique.

Clinical relevance

The results suggest that Tagger’s hybrid technique provided the best compaction of the root canal filling material, an important factor for the sealing of obturations and, consequently, for the effectiveness of treatment.     

Inclusion of CYP3A5 genotyping in a nonparametric population model improves dosing of tacrolimus early after transplantation

Following organ engraftment, initial dosing of tacrolimus is based on recipient weight and adjusted by measured C₀ concentrations. The bioavailability and elimination of tacrolimus are affected by the patients CYP3A5 genotype. Prospective data of the clinical advantage of knowing patient's CYP3A5 genotype prior to transplantation are lacking. A nonparametric population model was developed for tacrolimus in renal transplant recipients. Data from 99 patients were used for model development and validation. A three‐compartment model with first‐order absorption and lag time from the dosing compartment described the data well. Clearances and volumes of distribution were allometrically scaled to body size. The final model included fat‐free mass, body mass index, hematocrit, time after transplantation, and CYP3A5 genotype as covariates. The bias and imprecision were 0.35 and 1.38, respectively, in the external data set. Patients with functional CYP3A5 had 26% higher clearance and 37% lower bioavailability. Knowledge of CYP3A5 genotype provided an initial advantage, but only until 3‐4 tacrolimus concentrations were known. After this, a model without CYP3A5 genotype predicted just as well. The present models seem applicable for clinical individual dose predictions but need a prospective evaluation.