The impact of brief intensive trauma-focused treatment for PTSD on symptoms of borderline personality disorder

Objective: To investigate the effects of a brief, intensive, direct trauma-focused treatment programme for individuals with PTSD on BPD symptom severity. Methods: Individuals (n = 72) with severe PTSD (87.5% had one or more comorbidities; 52.8% fulfilled the criteria for the dissociative subtype of PTSD) due to multiple traumas (e.g. 90.3% sexual abuse) participated in an intensive eight-day trauma-focused treatment programme consisting of eye movement desensitization and reprocessing (EMDR) and prolonged exposure (PE) therapy, physical activity, and psychoeducation. Treatment did not include any form of stabilization (e.g. emotion regulation training) prior to trauma-focused therapy. Assessments took place at pre- and post-treatment (Borderline Symptom List, BSL-23; PTSD symptom severity, Clinician Administered PTSD Scale for DSM-5, CAPS-5), and across the eight treatment days (PTSD Checklist, PCL-5). Results: Treatment resulted in significant decreases of BPD symptoms (Cohen’s d = 0.70). Of the 35 patients with a positive screen for BPD at pre-treatment, 32.7% lost their positive screen at post-treatment. No adverse events nor dropouts occurred during the study time frame, and none of the patients experienced symptom deterioration in response to treatment. Conclusion: The results suggest that an intensive trauma-focused treatment is a feasible and safe treatment for PTSD patients with clinically elevated symptoms of BPD, and that BPD symptoms decrease along with the PTSD symptoms

Exposure-response analyses of anaplastic lymphoma kinase inhibitors crizotinib and alectinib in non-small cell lung cancer patients

Crizotinib and alectinib are anaplastic lymphoma kinase (ALK)-inhibitors indicated for the treatment of ALK-positive metastatic non-small cell lung cancer (NSCLC). At the currently used fixed doses, interindividual variability in exposure is high. The aim of this study was to investigate whether minimum plasma concentrations (C-min) of crizotinib and alectinib are related to efficacy and toxicity. An observational study was performed, in which ALK-positive NSCLC patients who were treated with crizotinib and alectinib and from whom pharmacokinetic samples were collected in routine care, were included in the study. Exposure-response analyses were explored using previously proposed C(min)thresholds of 235 ng/mL for crizotinib and 435 ng/mL for alectinib. Forty-eight crizotinib and 52 alectinib patients were included. For crizotinib, median progression-free survival (mPFS) was 5.7 vs. 17.4 months for patients with C-min = 235 ng/mL, respectively (P = 0.08). In multivariable analysis, C-min = 435 ng/mL, respectively (P = 0.04). Multivariable analysis resulted in an HR of 4.29 (95% CI, 1.33-13.90,P = 0.015). In conclusion, PFS of crizotinib and alectinib treated NSCLC patients is prolonged in patients with C-min >= 235 ng/mL and 435 ng/mL, respectively. Therefore, therapeutic drug monitoring should be part of routine clinical management for these agents.Pathogenesis and treatment of chronic pulmonary disease

Liver transplantation and risk of bleeding

Purpose of review Blood loss in orthotopic liver transplantation has declined during the past decade. Recent papers addressed this issue and emphasized its importance, because there is a significant correlation between intraoperative blood transfusion requirements and postoperative morbidity. This reduced blood loss. Recent findings Many preoperative variables that predict blood loss during orthotopic liver transplantation have been found. These vary between studies. Differences in perioperative blood loss, transfusion criteria and intraoperative management of coagulation may account for the interhospital variations in transfusion of red blood cells during orthotopic liver transplantation., Therefore, a risk index developed in one centre should not be applied without evaluation in other centres. Introduction of the piggyback technique and close monitoring of coagulation with thromboelastography have led to reduced blood transfusion requirements. Use of antifibrinolytics has shown to decrease blood loss. Recombinant factor Vila is not indicated for treatment of coagulation abnormalities during orthotopic liver transplantation, and its use is justified only as rescue therapy. Summary Recent changes in blood conservation practices in orthotopic liver transplantation are presented and discussed

Liver transplantation in patients with acute liver failure - Criteria and results

Objective. Evaluation of the results of emergency liver transplantation in patients with acute liver failure. Design. Analysis of 25 patients with acute liver failure. Setting. University Hospital Rotterdam Dijkzigt. Method. Twenty-five patients with acute liver failure were admitted to the Intensive Care Unit in January 1989-May 1993. Patients were selected for emergency liver transplantation according to the Clichy criteria (presence of confusion or coma and factor V activity less than 20-30%). Results. Liver transplantation was indicated in 17 patients and performed in 13. The 1-year survival rate in patients with a liver transplant was 85%. Four patients with an indication for liver transplantation, but who could not be transplanted died. All 8 patients without an indication for emergency liver transplantation survived. Conclusion. Survival after liver transplantation for acute hepatic failure is now about 80%; the Clichy criteria appear to be helpful in selecting patients with acute hepatic failure for liver transplantation.</p

Liver transplantation in patients with acute liver failure - Criteria and results

Objective. Evaluation of the results of emergency liver transplantation in patients with acute liver failure. Design. Analysis of 25 patients with acute liver failure. Setting. University Hospital Rotterdam Dijkzigt. Method. Twenty-five patients with acute liver failure were admitted to the Intensive Care Unit in January 1989-May 1993. Patients were selected for emergency liver transplantation according to the Clichy criteria (presence of confusion or coma and factor V activity less than 20-30%). Results. Liver transplantation was indicated in 17 patients and performed in 13. The 1-year survival rate in patients with a liver transplant was 85%. Four patients with an indication for liver transplantation, but who could not be transplanted died. All 8 patients without an indication for emergency liver transplantation survived. Conclusion. Survival after liver transplantation for acute hepatic failure is now about 80%; the Clichy criteria appear to be helpful in selecting patients with acute hepatic failure for liver transplantation.</p

Asymptotic dimension of minor-closed families and Assouad-Nagata dimension of surfaces

The asymptotic dimension is an invariant of metric spaces introduced by Gromov in the context of geometric group theory. In this paper, we study the asymptotic dimension of metric spaces generated by graphs and their shortest path metric and show their applications to some continuous spaces. The asymptotic dimension of such graph metrics can be seen as a large scale generalisation of weak diameter network decomposition which has been extensively studied in computer science. We prove that every proper minor-closed family of graphs has asymptotic dimension at most 2, which gives optimal answers to a question of Fujiwara and Papasoglu and (in a strong form) to a problem raised by Ostrovskii and Rosenthal on minor excluded groups. For some special minor-closed families, such as the class of graphs embeddable in a surface of bounded Euler genus, we prove a stronger result and apply this to show that complete Riemannian surfaces have Assouad-Nagata dimension at most 2. Furthermore, our techniques allow us to prove optimal results for the asymptotic dimension of graphs of bounded layered treewidth and graphs of polynomial growth, which are graph classes that are defined by purely combinatorial notions and properly contain graph classes with some natural topological and geometric flavours.</p

Aprotinin in orthotopic liver transplantation: Evidence for a prohemostatic, but not a prothrombotic, effect

Aprotinin reduces blood transfusion requirements in orthotopic liver transplantation (OLT). Concern has been voiced about the potential risk for thrombotic complications when aprotinin is used. The aim of this study is to evaluate the effects of aprotinin on the two components of the hemostatic system (coagulation and fibrinolysis) in patients undergoing OLT. As part of a larger, randomized, double-blind, placebo-controlled study, we compared coagulation (fibrinogen level, activated partial thromboplastin time [aPTT], prothrombin time, and platelet count) and fibrinolytic variables (tissue-type plasminogen activator [tPA] antigen and activity, plasminogen activator inhibitor activity, and D-dimer), as well as thromboelastography (reaction time [r], clot formation time, and maximum amplitude) in 27 patients administered either high-dose aprotinin (2 ! 106 kallikrein inhibitor units [KIU] at induction, continuous infusion of 1 ! 106 KIU/h, and 1 ! 106 KIU before reperfusion; n " 10), regular-dose aprotinin (2 ! 106 KIU at induction and continuous infusion of 0.5 ! 106 KIU/h; n " 8), or placebo (n " 9) during OLT. Blood samples were drawn at seven standardized intraoperative times. Baseline characteristics were similar for the three groups. During the anhepatic and postreperfusion periods, fibrinolytic activity (plasma D-dimer and tPA antigen levels) was significantly lower in aprotinin-treated patients compared with the placebo group. Interestingly, coagulation times (aPTT and r) were significantly more prolonged in aprotinintreated patients than the placebo group. No difference was seen in the incidence of perioperative thrombotic complications in the entire study population (n " 137). Aprotinin has an anticoagulant rather than a procoagulant effect. Its blood-sparing (prohemostatic) effect appears to be the overall result of a strong antifibrinolytic and a weaker anticoagulant effect. These findings argue against a prothrombotic effect of aprotinin in patients undergoing OLT. (Liver Transpl 2001;7:896-903.