Pharmacokinetic and Pharmacodynamic Comparison of Once-Daily Efavirenz (400 mg vs. 600 mg) in Treatment-Naïve HIV-Infected Patients: Results of the ENCORE1 Study.

Daily efavirenz 400 mg (EFV400) was virologically noninferior to 600 mg (EFV600) at 48 weeks in treatment-naïve patients. We evaluated EFV400 and EFV600 pharmacokinetics (NONMEM v. 7.2), assessing patient demographics and genetic polymorphisms (CYP2B6, CYP2A6, CYP3A4, NR1I3) as covariates and explored relationships with efficacy (plasma HIV-RNA (pVL) <200 copies/mL) and safety outcomes at 48 weeks in 606 randomized ENCORE1 patients (female = 32%, African = 37%, Asian = 33%; EFV400 = 311, EFV600 = 295). CYP2B6 516G>T/983T>C/CYP2A6*9B/*17 and weight were associated with efavirenz CL/F. Exposure was significantly lower for EFV400 (geometric mean ratio, GMR; 90% confidence interval, CI: 0.73 (0.68-0.78)) but 97% (EFV400) and 98% (EFV600) of evaluable pVL was <200 copies/mL at 48 weeks (P = 0.802). Four of 20 patients with mid-dose concentrations <1.0 mg/L had pVL ≥200 copies/mL (EFV400 = 1; EFV600 = 3). Efavirenz exposure was similar between those with and without efavirenz-related side effects (GMR; 90% CI: 0.95 (0.88-1.02)). HIV suppression was comparable between doses despite significantly lower EFV400 exposure. Comprehensive evaluation of efavirenz pharmacokinetics/pharmacodynamics revealed important limitations in the accepted threshold concentration.

[Imaging strategies for knee injuries]. / Bildgebungsstrategie bei Kniegelenkverletzungen.

Injuries of the knees are common. The Ottawa knee rule provides decisional support to determine whether radiographs are indicated or not. With the use of ultrasound it is possible to detect defects of the extensor ligaments and the anterior cruciate ligament. Furthermore, it is possible to detect indirect signs of an intra-articular fracture, e.g. lipohemarthrosis. In complex fractures, e.g. tibial plateau fractures, further diagnostic procedures with multislice computed tomography (CT) are needed for accurate classification and preoperative planning. Multislice CT with CT angiography enables three-dimensional reconstruction of the knee and non-invasive vascular imaging for detection of vascular injury. Magnetic resonance imaging (MRI) is the gold standard for detection of occult fractures and injuries of the ligaments and menisci. Higher field strengths can be used to improve the diagnostics of cartilage lesions. Virtual MR arthrography is superior to conventional MRI for detection of cartilage lesions especially after meniscus surgery.

Population imaging as valuable tool for personalized medicine.

Personalized medicine is commonly regarded as an extension of genomic medicine. However, a personalized treatment should not [corrected] be based solely on the presence or absence of genetic factors. Complex imaging methods supplement the diagnostic picture of an individual patient. Comprehensive imaging in population-based settings provides information on reference intervals, the predictive value of subclinical findings, and the complex interrelationships among risk factors, subclinical imaging phenotypes, and diseases.

[Laser ablation. Do we still need it?]. / Laserablation. Brauchen wir sie noch?

Laser ablation (LA) is momentarily the only invasive ablation procedure besides radiofrequency ablation (RFA) which can be performed entirely under magnetic resonance imaging (MRI) guidance. The long-term outcome and morbidity profiles are broadly identical for both modalities, excluding the RFA-specific prevalence for skin burns. The technical and logistic disadvantages of LA have been overcome since the introduction of miniaturized two-component applicators. The main advantage of LA is its superior MRI compatibility. Interference-free imaging during LA allows MR thermometric real-time therapy control without the need for RF filters. High-resolution thermometry in the target zone only makes sense without the extinction artifact of a metal probe and this condition is met only by the glass fibers of LA. An independent therapy monitoring is crucial in modern scenarios of oncologic quality management.

[Thoracic aortic interventions]. / Intervention an der thorakalen Aorta.

The treatment of thoracic aortic diseases has undergone a paradigm shift due to the introduction and further development of interventional techniques in recent years. Thoracic endovascular aortic repair (TEVAR) of the descending aorta has significantly lower mortality and complication rates compared to open repair. Meanwhile this endovascular approach is the first option for the treatment of the majority of thoracic aortic diseases.

Dynamics of cognitive change in HIV-infected individuals commencing three different initial antiretroviral regimens: a randomized, controlled study.

BACKGROUND: Improvements in neurocognitive (NC) function have been associated with commencing antiretroviral therapy in HIV-infected subjects. However, the dynamics of such improvements are poorly understood. METHODS: We assessed changes in NC function via a validated computerized battery (CogState™, Melbourne, Victoria, Australia) at baseline and after 24 and 48 weeks in a subset of therapy-naïve neuro-asymptomatic HIV-infected subjects, randomized to commence three different antiretroviral regimens. RESULTS: Of 28 subjects enrolled in the study, nine, eight and 11 were randomly allocated to commence tenofovir/emtricitabine with efavirenz (arm 1), atazanavir/ritonavir (arm 2) and zidovudine/abacavir (arm 3), respectively. Overall improvements in NC function were observed at week 24 and function continued to improve at week 48 (changes in z-score for overall cognitive global score of 0.16 and 0.18 at weeks 24 and 48, respectively). Within the NC speed domains, generally greater improvements were observed in arms 2 and 3, compared with arm 1 (changes in z-score for composite speed scores at weeks 24/48 of 0.16/0.16, -0.29/-0.24 and -0.15/-0.31 in arms 1, 2 and 3, respectively; P = 0.04 for change at week 48 in arm 3 versus arm 1). Finally, improvements in executive function occurred later (only observed at week 48) and were driven by improvements in arm 3 (z-score changes of 0.23, 0.06 and -0.78 in arms 1, 2 and 3, respectively; P = 0.02 for change in arm 3 versus arm 1). CONCLUSION: Improvements in NC function continue over the first year after initiating antiretroviral therapy in neuro-asymptomatic HIV-infected subjects.

[Whole-body MRI in the study of health in Pomerania]. / Ganzkörper-MRT in der "Study of Health in Pomerania"

Population-based whole-body MRI examinations have been evaluated for the first time within the Study of Health in Pomerania (SHIP). This ongoing cohort study investigates associations of overweight (57.9% of the female and 74.1% of the male population) and obesity (25.1% and 26.0%, respectively) with cardiovascular and metabolic diseases in a population with decreased life expectancy compared to the total German average. Whole-body MRI offers the possibility to evaluate parameters, such as the amount of visceral and liver fat and can contribute to further conclusions on these common diseases.

[Clinical relevance of imaging techniques in population-based research]. / Klinische Bedeutung bildgebender Verfahren in populationsbasierter Forschung.

Similar to clinical practise, population-based studies with a clinical-epidemiological focus include imaging techniques to identify manifest disease and to assess subclinical disease. Even population-based cross-sectional studies offer various options to address scientific questions of great clinical relevance, including analysis of reference values, prevalence estimates and association analysis. Further potential values of imaging techniques in population-based studies concern additional information on incidental diseases and mortality rate, which make it possible to investigate the association between imaging findings at baseline and subsequent disease. Modern population-based designs ensure a high degree of being representative and can be generally applied to clinical practise and, as a result, may be highly relevant to daily clinical routine. When imaging techniques are integrated within population-based research, problems of quality control may have to be solved, all probands must give informed consent and a decision made on what findings have to be given to the participants.

Whole-body magnetic resonance imaging of healthy volunteers: pilot study results from the population-based SHIP study.

PURPOSE: Approximately 4000 volunteers will undergo whole-body magnetic resonance imaging (WB-MRI) within the next 3 years in the population-based Study of Health in Pomerania (SHIP). Here we present a pilot study conducted (a) to determine the feasibility of adding a WB-MRI protocol to a large-scale population-based study, (b) to evaluate the reliability of standardized MRI interpretation, and (c) to establish an approach for handling pathological findings. MATERIALS AND METHODS: The institutional review board approved the study, and oral and written informed consent was obtained from each participant. Two hundred healthy volunteers (99 women, 101 men; mean age 48.3 years) underwent a standardized WB-MRI protocol. The protocol was supplemented by contrast-enhanced cardiac MRI and magnetic resonance (MR) angiography in 61 men (60.4%) and cardiac MRI and MR mammography in 44 women (44.4%). MR scans were evaluated independently by two readers. Abnormalities were discussed by an advisory board and classified according to the need for further clinical work-up. RESULTS: One hundred ninety-four (97.0%) WB-MRI examinations were successfully completed in a mean scan time per subject of 90 minutes. There were 431 pathological findings in 176 (88%) of the participants. Of those 45 (10.4%) required further clinical work-up and 386 (89.6%) characterized as benign lesions did not. The interobserver agreement for the detection of pathological findings was excellent (kappa = 0.799). CONCLUSION: The preliminary results presented here indicate that a large prospective, population-based study using WB-MRI is feasible and that the results of image analysis are reproducible. A variety of positive findings provide valuable information regarding disease prevalence in a general adult population.

[Gastric schwannoma: a "typical" clinical course?]. / Abdominelles Schwannom : Ein "klassischer" Fallbericht?

Intra-abdominal schwannoma is a rare tumor entity. Although often detected incidentally, its diagnosis and surgical planning are difficult-as with all intramural intra-abdominal tumors. Puncturing is often not satisfying due to the inhomogeneous proliferation rates of different regions of the tumor. We describe the procedure using the example of a gastric schwannoma that was found incidentally. The leading symptom was perforation of a peptic stomach ulcer.

[Atypical vascular supply from the coeliac trunk. Recurrent bleeding from a duodenal ulcer]. / Atypische Gefässversorgung aus dem Truncus coeliacus. Rezidivblutung aus einem Ulcus duodeni.

Hemorrhagic duodenal ulcers should primarily be controlled by endoscopy. In cases of recurrent bleeding or if bleeding cannot be controlled endoscopically, open surgery is the gold standard. Rarely, atypical origin of arteries or additional atypical arteries may lead to further unexpected hemorrhagic recurrences and angiography with surgical intervention is the treatment of choice. In this article a rare case of an atypical visceral artery connecting the coeliac trunk and the gastroduodenal artery leading to recurrent bleeding from a duodenal ulcer is presented.

[Characteristics of necrosis after laser-induced thermotherapy in contrast-enhanced MRI and implications for treatment success]. / Charakteristik von Koagulationsnekrosen nach laserinduzierter Thermotherapie in der kontrastmittelverstärkten Magnetresonanztomografie und deren Einfluss auf den Therapieerfolg.

AIM: This article reports on the use of magnetic resonance imaging to access the post-interventional necrosis volume of liver metastases immediately after and 48 hours after LITT. MATERIAL AND METHODS: In this prospective study, 56 liver metastases from 39 patients (16 females, 23 males, mean age 60.4 years) underwent LITT. The 56 metastases were divided into 4 groups according to the ablation strategy (dependent on multi-applicator technique and laser duration). Groups I and II were treated with an applicator and a time of ablation greater than 15 minutes and 20 minutes, respectively. In groups III and IV the multi-applicator technology with 3 or 4 applicators and a constant ablation time of 20 minutes were used. With the help of heightened contrast MRI of the liver, the portrayal of the post-interventional necrosis was conducted immediately after LITT and 48 hours after LITT. The post-interventional controls after 48 hours were performed during the inpatient stay. The protocol was complemented by an outpatient long-term control after more than 3 months. RESULTS: The local tumor control rate was initially 96.4%. After 3 months it decreased to 92.1%. The mean necrosis volume directly after LITT was: Group I (n = 11; 1 applicator, 30 watt, 10-15 minutes) 6.69 cm(3); Group II (n = 13; 1 applicator, 30 watt, 20 minutes) 10.95 cm(3); Group III (n = 28; 2 applicator, 30 watt, 10-15 minutes) 21.47 cm(3); Group IV (n = 4; 3 applicator, 30 watt, 20 minutes) 40.20 cm(3). In comparison, the necrosis volume after 48 hours increased: Group I 10.56 cm(3); Group II 15.11 cm(3); Group III 31.33 cm(3), Group IV 55.73 cm(3)). CONCLUSION: After 48 hours a progressive increase of post-interventional necrosis volumes compared to volumes directly after LITT was able to be observed. An MRI control after 48 hours, as opposed to an MRI control directly after intervention, is a better indicator for post-interventional success after LITT.