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Background and Purpose-Decompressive surgery (hemicraniectomy) for life-threatening massive cerebral infarction represents a controversial issue in neurocritical care medicine. We report here the 30-day mortality and 6-and 12-month functional outcomes from the DESTINY trial. Methods-DESTINY (ISRCTN01258591) is a prospective, multicenter, randomized, controlled, clinical trial based on a sequential design that used mortality after 30 days as the first end point. When this end point was reached, patient enrollment was interrupted as per protocol until recalculation of the projected sample size was performed on the basis of the 6-month outcome (primary end pointϭmodified Rankin Scale score, dichotomized to 0 to 3 versus 4 to 6). All analyses were based on intention to treat. Results-A statistically significant reduction in mortality was reached after 32 patients had been included: 15 of 17 (88%) patients randomized to hemicraniectomy versus 7 of 15 (47%) patients randomized to conservative therapy survived after 30 days (Pϭ0.02). After 6 and 12 months, 47% of patients in the surgical arm versus 27% of patients in the conservative treatment arm had a modified Rankin Scale score of 0 to 3 (Pϭ0.23). Conclusions-DESTINY showed that hemicraniectomy reduces mortality in large hemispheric stroke. With 32 patients included, the primary end point failed to demonstrate statistical superiority of hemicraniectomy, and the projected sample size was calculated to 188 patients. Despite this failure to meet the primary end point, the steering committee decided to terminate the trial in light of the results of the joint analysis of the 3 European hemicraniectomy trials.

The pattern recognition receptor, RAGE (receptor for advanced glycation endproducts), propagates cellular dysfunction in several inflammatory disorders and diabetes. Here we show that RAGE functions as an endothelial adhesion receptor promoting leukocyte recruitment. In an animal model of thioglycollate-induced acute peritonitis, leukocyte recruitment was significantly impaired in RAGE-deficient mice as opposed to wild-type mice. In diabetic wild-type mice we observed enhanced leukocyte recruitment to the inflamed peritoneum as compared with nondiabetic wild-type mice; this phenomenon was attributed to RAGE as it was abrogated in the presence of soluble RAGE and was absent in diabetic RAGE-deficient mice. In vitro, RAGE-dependent leukocyte adhesion to endothelial cells was mediated by a direct interaction of RAGE with the β2-integrin Mac-1 and, to a lower extent, with p150,95 but not with LFA-1 or with β1-integrins. The RAGE–Mac-1 interaction was augmented by the proinflammatory RAGE-ligand, S100-protein. These results were corroborated by analysis of cells transfected with different heterodimeric β2-integrins, by using RAGE-transfected cells, and by using purified proteins. The RAGE–Mac-1 interaction defines a novel pathway of leukocyte recruitment relevant in inflammatory disorders associated with increased RAGE expression, such as in diabetes, and could provide the basis for the development of novel therapeutic applications.

In a prospective, multicenter, open-label study, de novo liver transplant patients were randomized at day 30±5 to (i) everolimus initiation with tacrolimus elimination (TAC Elimination) (ii) everolimus initiation with reduced-exposure tacrolimus (EVR+Reduced TAC) or (iii) standard-exposure tacrolimus (TAC Control). Randomization to TAC Elimination was terminated prematurely due to a higher rate of treated biopsy-proven acute rejection (tBPAR). EVR+Reduced TAC was noninferior to TAC Control for the primary efficacy endpoint (tBPAR, graft loss or death at 12 months posttransplantation): 6.7% versus 9.7% (−3.0%; 95% CI −8.7, 2.6%; p<0.001 for noninferiority [12% margin]). tBPAR occurred in 2.9% of EVR+Reduced TAC patients versus 7.0% of TAC Controls (p = 0.035). The change in adjusted estimated GFR from randomization to month 12 was superior with EVR+Reduced TAC versus TAC Control (difference 8.50 mL/min/1.73 m2, 97.5% CI 3.74, 13.27 mL/min/1.73 m2, p<0.001 for superiority). Drug discontinuation for adverse events occurred in 25.7% of EVR+Reduced TAC and 14.1% of TAC Controls (relative risk 1.82, 95% CI 1.25, 2.66). Relative risk of serious infections between the EVR+Reduced TAC group versus TAC Controls was 1.76 (95% CI 1.03, 3.00). Everolimus facilitates early tacrolimus minimization with comparable efficacy and superior renal function, compared to a standard tacrolimus exposure regimen 12 months after liver transplantation.

Background: Diagnosing and monitoring depression in primary care remains an issue of significant public health concern. Clinicians and researchers need to know if any one screening instrument is superior to the others in diagnosing ICD-10 depressive episodes. This study aimed to examine the criterion validity for diagnosing ICD-10 depressive episodes of the Patient Health Questionnaire (PHQ) in comparison with 2 well-established instruments, the Hospital Anxiety and Depression Scale (HADS), and the WHO Well-Being Index 5 (WBI-5). Methods: Five hundred and one medical outpatients completed the questionnaires and had a clinical interview. The presence of a depressive episode was determined with the International Diagnostic Checklists (IDCL) for ICD-10 as the criterion standard. Coefficient kappa (ĸ), sensitivities and specificities were calculated and a statistical comparison of the areas under the receiver operating characteristic curves was performed. Results: Diagnostic agreement between the questionnaires and the IDCL was moderate (ĸ = 0.34–0.56), with the highest values for the PHQ. While all 3 questionnaires had reasonable sensitivity and specificity, the operating characteristics for the PHQ were significantly superior to both the HADS and the WBI-5 (p = 0.02). Conclusions: Any of the 3 screening instruments can be recommended for clinical use. However, this is the first comparative study to demonstrate the diagnostic advantage of a particular depression-screening instrument using the ICD-10 diagnostic criteria. The superior criterion validity of the PHQ is likely attributable to its closer representation of the current concept of depressive disorders.

Compared with physiotherapy and as-needed anti-inflammatory drugs, addition of either TCA or sham acupuncture led to greater improvement in WOMAC score at 26 weeks. No statistically significant difference was observed between TCA and sham acupuncture, suggesting that the observed differences could be due to placebo effects, differences in intensity of provider contact, or a physiologic effect of needling regardless of whether it is done according to TCA principles.

Background and aims: Despite occasional positive reports on the efficacy of acupuncture (AC) on functions of the gastrointestinal tract, there is no conclusive evidence that AC is effective in the treatment of irritable bowel syndrome (IBS). Patients and methods: Forty three patients with IBS according to the Rome II criteria were randomly assigned to receive either AC (n = 22) or sham acupuncture (SAC) (n = 21) using the so-called ''Streitberger needle''. Treatment duration was 10 sessions with an average of two AC sessions per week. The primary end point was improvement in quality of life (QOL) using the functional digestive diseases quality of life questionnaire (FDDQL) and a general quality of life questionnaire (SF-36), compared with baseline assessments. QOL measurements were repeated three months after treatment. Results: Both the AC and SAC groups improved significantly in global QOL, as assessed by the FDDQL, at the end of treatment (p = 0.022), with no differences between the groups. SF-36 was insensitive to these changes (except for pain). This effect was partially reversed three months later. Post hoc comparison of responders and non-responders in both groups combined revealed a significant prediction of the placebo response by two subscales of the FDDQL (sleep, coping) (F = 6.746, p = 0.003) in a stepwise regression model. Conclusions: Acupuncture in IBS is primarily a placebo response. Based on the small differences found between the AC and SAC groups, a study including 566 patients would be necessary to prove the efficacy of AC over SAC. The placebo response may be predicted by high coping capacity and low sleep quality in individual patients.

Recall is an active reconstruction process likely to distort past experiences. This distortion, known as recall bias, seems to manifest itself differently in sick and healthy people. A recall bias has been documented in several disorders, but never investigated in borderline personality disorder (BPD). To determine recall bias in BPD, we assessed momentary and retrospective ratings of specific emotions in 50 patients with BPD and 50 healthy controls (HCs), using the methodology of 24-hour ambulatory monitoring. Our data reveal a group-specific valence-dependent recall bias of retrospective self-report, indicated by a different overall recall pattern in HCs and BPD. BPD patients show an overall negative recall pattern, whereas HCs show a positive recall pattern. A traditional questionnaire approach does not distinguish between symptoms of the disorder and recall bias, although the pathological mechanisms underlying them as well as the appropriate treatment strategies may be different.