Veliparib monotherapy following carboplatin/paclitaxel plus veliparib combination therapy in patients with germline BRCA-associated advanced breast cancer: results of exploratory analyses from the phase III BROCADE3 trial.

BACKGROUND: In the BROCADE3 trial, addition of the poly(ADP-ribose) polymerase inhibitor, veliparib, to carboplatin/paclitaxel improved progression-free survival (PFS) (hazard ratio 0.71, 95% confidence interval 0.57-0.88; P = 0.002) in patients with advanced human epidermal growth factor receptor 2-negative, germline BRCA1/2-mutated breast cancer. A subset of patients discontinued both carboplatin and paclitaxel before progression and continued on veliparib/placebo maintenance monotherapy until progression. Analyses in this patient subgroup are reported. PATIENTS AND METHODS: Patients were randomized 2 : 1 to veliparib plus carboplatin/paclitaxel or placebo plus carboplatin/paclitaxel. Veliparib (120 mg twice daily) or placebo was given on days -2 to 5, carboplatin (area under the curve 6 mg/ml) on day 1, and paclitaxel (80 mg/m2) on days 1, 8, and 15 of 21-day cycles. Patients who discontinued both carboplatin and paclitaxel before progression received blinded study drug monotherapy at an increased dose of 300-400 mg twice daily continuously. PFS was the primary endpoint. Exploratory analyses were carried out in the subgroup of patients who received blinded study drug as monotherapy. A time-varying Cox model including data from all patients was also used to evaluate treatment effect in the combination and monotherapy phases. RESULTS: A total of 136 of 337 patients randomized to veliparib plus carboplatin/paclitaxel and 58/172 patients randomized to placebo plus carboplatin/paclitaxel discontinued both carboplatin and paclitaxel before progression and continued on blinded veliparib or placebo monotherapy. In this blinded monotherapy subgroup, investigator-assessed median PFS from randomization was 25.7 months with veliparib versus 14.6 months with placebo. Hazard ratios from a time-varying Cox model favored veliparib during both combination therapy and monotherapy. Any-grade adverse events occurring in the monotherapy phase were primarily gastrointestinal. The most common grade ≥3 adverse events were neutropenia and anemia (4% each with veliparib; 5% and 2%, respectively, with placebo). CONCLUSIONS: Veliparib maintenance monotherapy had a tolerable safety profile and may extend PFS following combination chemotherapy.

Dynamic molecular analysis and clinical correlates of tumor evolution within a phase II trial of panitumumab-based therapy in metastatic colorectal cancer.

Background: Mutations in rat sarcoma (RAS) genes may be a mechanism of secondary resistance in epidermal growth factor receptor inhibitor-treated patients. Tumor-tissue biopsy testing has been the standard for evaluating mutational status; however, plasma testing of cell-free DNA has been shown to be a more sensitive method for detecting clonal evolution. Materials and methods: Archival pre- and post-treatment tumor biopsy samples from a phase II study of panitumumab in combination with irinotecan in patients with metastatic colorectal cancer (mCRC) that also collected plasma samples before, during, and after treatment were analyzed for emergence of mutations during/post-treatment by next-generation sequencing and BEAMing. Results: The rate of emergence of tumor tissue RAS mutations was 9.5% by next-generation sequencing (n = 21) and 6.3% by BEAMing (n = 16). Plasma testing of cell-free DNA by BEAMing revealed a mutant RAS emergence rate of 36.7% (n = 39). Exploratory outcomes analysis of plasma samples indicated that patients who had emergent RAS mutations at progression had similar median progression-free survival to those patients who remained wild-type at progression. Serial analysis of plasma samples showed that the first detected emergence of RAS mutations preceded progression by a median of 3.6 months (range, -0.3 to 7.5 months) and that there did not appear to be a mutant RAS allele frequency threshold that could predict near-term outcomes. Conclusions: This first prospective analysis in mCRC showed that serial plasma biopsies are more inclusive than tissue biopsies for evaluating global tumor heterogeneity; however, the clinical utility of plasma testing in mCRC remains to be further explored. ClinicalTrials.gov Identifier: NCT00891930.

Deriving ICD-11 personality disorder domains from dsm-5 traits: initial attempt to harmonize two diagnostic systems.

OBJECTIVE: The personality disorder domains proposed for the ICD-11 comprise Negative Affectivity, Detachment, Dissociality, Disinhibition, and Anankastia, which are reasonably concordant with the higher-order trait domains in the Alternative DSM-5 Model for Personality Disorders. METHOD: We examined (i) whether designated DSM-5 trait facets can be used to describe the proposed ICD-11 trait domains, and (ii) how these ICD-11 trait features are hierarchically organized. A mixed Danish derivation sample (N = 1541) of 615 psychiatric out-patients and 925 community participants along with a US replication sample (N = 637) completed the Personality Inventory for DSM-5 (PID-5). Sixteen PID-5 traits were designated to cover features of the ICD-11 trait domains. RESULTS: Exploratory structural equation modeling (ESEM) analyzes showed that the designated traits were meaningfully organized in the proposed ICD-11 five-domain structure as well as other recognizable higher-order models of personality and psychopathology. Model fits revealed that the five proposed ICD-11 personality disorder domains were satisfactorily resembled, and replicated in the independent US sample. CONCLUSION: The proposed ICD-11 personality disorder domains can be accurately described using designated traits from the DSM-5 personality trait system. A scoring algorithm for the ICD-11 personality disorder domains is provided in appendix.

[Virus-associated arthritis]. / Virusassoziierte Arthritiden.

Epidemiological studies suggest a viral etiology in approximately 1% of patients presenting with acute arthritis. The arthritogenic effect of viral infections may be related to viral invasion of synovial cells, the cellular and humoral immune response to viral antigens or by induction of autoimmunity. Viral arthritis can mimic rheumatoid arthritis by presenting as a symmetrical polyarticular disease often accompanied by a rash and influenza-like symptoms. Serological testing for pathogen-specific IgM and IgG antibodies is frequently performed for establishing a viral etiology of arthritis. Virus isolation from the joints or detection of viral nucleic acids in the synovium or synovial fluid is only rarely successful and does not always provide proof of a viral origin of arthritis. While viral arthritis in most cases is self-limiting, protracted disease can occur.

Health-related quality of life in women with recurrent ovarian cancer receiving paclitaxel plus trebananib or placebo (TRINOVA-1).

BACKGROUND: To evaluate the influence of treatment on health-related quality of life (HRQoL) in 919 women with recurrent ovarian cancer enrolled in the TRINOVA-1 study, a randomized, placebo-controlled phase III study that demonstrated that trebananib 15 mg/kg QW plus weekly paclitaxel significantly improved progression-free survival (PFS) compared with placebo plus weekly paclitaxel (7.2 versus 5.4 months; hazard ratio, 0.66; 95% confidence interval 0.57-0.77; P < 0.001). PATIENTS AND METHODS: HRQoL was assessed with the Functional Assessment of Cancer Therapy-Ovary [FACT-O; comprising FACT-G and the ovarian cancer-specific subscale (OCS)] and EuroQOL EQ-5D instruments before treatment on day 1 of weeks 1, 5, 9, 13, 17, and every 8 weeks thereafter and at the safety follow-up visit. A pattern-mixture model was used to evaluate the influence of patient dropout on FACT-O and OCS scores over time. RESULTS: Of 919 randomized patients, 834 (91%) had a baseline and ≥1 post-baseline HRQoL assessment. At baseline, scores for all instruments were similar for both arms. At 25 weeks, mean ± SD changes from baseline were negligible, with mean ± SD changes typically <1 unit from baseline: -2.4 ± 16.6 in the trebananib arm and -1.6 ± 15.2 in the placebo arm for FACT-O, -0.71 ± 5.5 in the trebananib arm and -0.86 ± 4.9 in the placebo arm for OCS, and -0.02 ± 0.22 in the trebananib arm and 0.02 ± 0.19 in the placebo arm for EQ-5D. Distribution of scores was similar between treatment arms at baseline and over the course of the study. In pattern-mixture models, there was no evidence that patient dropout affected differences in mean FACT-O or OCS scores. Edema had limited effect on either FACT-O or OCS scores in patients with grade ≥2 edema or those with grade 1 or no edema. CONCLUSIONS: Our results demonstrate that the improvement in PFS among patients in the trebananib arm in the TRINOVA-1 study was achieved without compromising HRQoL. CLINICALTRIALSGOV IDENTIFIER: NCT01204749.

A phase 3 randomized, double-blind, placebo-controlled trial of ganitumab or placebo in combination with gemcitabine as first-line therapy for metastatic adenocarcinoma of the pancreas: the GAMMA trial.

BACKGROUND: This double-blind, phase 3 study assessed the efficacy and safety of ganitumab combined with gemcitabine as first-line treatment of metastatic pancreatic cancer. PATIENTS AND METHODS: Patients with previously untreated metastatic pancreatic adenocarcinoma were randomly assigned 2 : 2 : 1 to receive intravenous gemcitabine 1000 mg/m(2) (days 1, 8, and 15 of each 28-day cycle) plus placebo, ganitumab 12 mg/kg, or ganitumab 20 mg/kg (days 1 and 15 of each cycle). The primary end point was overall survival (OS). Secondary end points included progression-free survival (PFS), safety, and efficacy by levels of circulating biomarkers. RESULTS: Overall, 322 patients were randomly assigned to placebo, 318 to ganitumab 12 mg/kg, and 160 to ganitumab 20 mg/kg. The study was stopped based on results from a preplanned futility analysis; the final results are reported. Median OS was 7.2 months [95% confidence interval (CI), 6.3-8.2] in the placebo arm, 7.0 months (95% CI, 6.2-8.5) in the ganitumab 12-mg/kg arm [hazard ratio (HR), 1.00; 95% CI, 0.82-1.21; P = 0.494], and 7.1 months (95% CI, 6.4-8.5) in the ganitumab 20-mg/kg arm (HR, 0.97; 95% CI, 0.76-1.23; P = 0.397). Median PFS was 3.7, 3.6 (HR, 1.00; 95% CI, 0.84-1.20; P = 0.520), and 3.7 months (HR, 0.97; 95% CI, 0.77-1.22; P = 0.403), respectively. No unexpected toxicity was observed with ganitumab plus gemcitabine. The circulating biomarkers assessed [insulin-like growth factor-1 (IGF-1), IGF-binding protein-2, and -3] were not associated with a treatment effect on OS or PFS by ganitumab. CONCLUSION: Ganitumab combined with gemcitabine had manageable toxicity but did not improve OS, compared with gemcitabine alone in unselected patients with metastatic pancreatic cancer. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT01231347.

Morpheaartige Hautmanifestation einer Sarkoidose : Morpheaform skin lesions in sarcoidosis.

Sarcoidosis is an idiopathic systemic disease, which is characterized by the presence of non-caseating granulomas in the affected organs. Cutaneous manifestations are frequently the first clue to the diagnosis; however, the clinical picture of the lesions is heterogenous. Here we report on a 66-year-old woman with localized indurations of the skin on both forearms that were diagnosed as a rare morphea-like skin involvement of a systemic sarcoidosis.

RAMPVIS: Answering the challenges of building visualisation capabilities for large-scale emergency responses.

The effort for combating the COVID-19 pandemic around the world has resulted in a huge amount of data, e.g., from testing, contact tracing, modelling, treatment, vaccine trials, and more. In addition to numerous challenges in epidemiology, healthcare, biosciences, and social sciences, there has been an urgent need to develop and provide visualisation and visual analytics (VIS) capacities to support emergency responses under difficult operational conditions. In this paper, we report the experience of a group of VIS volunteers who have been working in a large research and development consortium and providing VIS support to various observational, analytical, model-developmental, and disseminative tasks. In particular, we describe our approaches to the challenges that we have encountered in requirements analysis, data acquisition, visual design, software design, system development, team organisation, and resource planning. By reflecting on our experience, we propose a set of recommendations as the first step towards a methodology for developing and providing rapid VIS capacities to support emergency responses.

[Autoinflammatory syndromes/fever syndromes]. / Autoinflammatorische Syndrome/Fiebersyndrome.

Hereditary periodic (fever) syndromes, also called autoinflammatory syndromes, are characterized by relapsing fever and additional manifestations such as skin rashes, mucosal manifestations, or joint symptoms. Some of these disorders present with organ involvement and serological signs of inflammation without fever. There is a strong serological inflammatory response with an elevation of serum amyloid A (SAA), resulting in an increased risk of secondary amyloidosis. There are monogenic disorders (familial mediterranean fever (FMF), hyper-IgD-syndrome (HIDS), cryopyrin-associated periodic syndromes (CAPS), "pyogenic arthritis, acne, pyoderma gangrenosum" (PAPA), and "pediatric granulomatous arthritis (PGA) where mutations in genes have been described, which in part by influencing the function of the inflammasome, in part by other means, lead to the induction of the production of IL-1ß. In "early-onset of enterocolitis (IBD)", a functional IL-10 receptor is lacking. Therapeutically, above all, the IL-1 receptor antagonist anakinra is used. In case of TRAPS and PGA, TNF-antagonists (etanercept) may also be used; in FMF colchicine is first choice. As additional possible autoinflammatory syndromes, PFAPA syndrome (periodic fever with aphthous stomatitis, pharyngitis and adenitis), Schnitzler syndrome, Still's disease of adult and pediatric onset, Behçet disease, gout, chronic recurrent multifocal osteomyelitis (CRMO) and Crohn's disease also are mentioned.

Mechanisms of regulation of cell-mediated immunity. III. The characterization of azobenzenearsonate-specific suppressor T-cell-derived-suppressor factors.

Delayed type hypersensitivity to the hapten azobenzenearsonate (ABA) can be induced and suppressed by the administration of hapten-coupled syngeneic spleen cells by the appropriate route. Suppressor T cells stimulated by the intravenous administration of ABA-coupled spleen cells have been shown to produce a discrete subcellular factor(s) which is capable of suppressing delayed type hypersensitivity to azobenzenearsonate in the mouse. Such suppressor factors may be produced by the mechanical disruption of suppressor cells or by placing such suppressor cells in culture for 24 h. The suppressor factor(s) (SF) derived from ABA-specific suppressor cells exhibit biological specificity for the suppression of ABA delayed type hypersensitivity (DTH), but not trinitro-phenyl DTH, as well as the capacity to bind to ABA immunoadsorbents. Passage of suppressor factor(s) over reverse immunoadsorbents utilizing a rabbit anti-mouse F(ab')2 antiserum demonstrated that the antigen-specific T-cell derived SF does not bear conventional immunoglobulin markers. The suppressor factor(s) are not immunoglobulin molecules was further demonstrated by the inability of anti-ABA antibodies to suppress ABA DTH. Gel filtration of ABA suppressor factor(s) showed that the majority of the suppressive activity was present in a fraction with molecular weight ranging between 6.8 x 10(4) and 3.3 x 10(4) daltons. We also analyzed for the presence of determinants encoded by the H-2 major histocompatibility complex (MHC) and found that immunoadsorbents prepared utilizing antisera capable of interacting with gene products of the whole or selected gene regions of H-2 MHC, i.e., B10.D2 anti-B10.A and B10 anti-B10.A immunoadsorbents, retained the suppressive activity of ABA-SF. Elution of such columns with glycine HCl buffers (pH 2.8) permitted recovery of specific suppressive activity. Taken collectively such data supports the notion that suppressor T-cell-derived ABA suppressor factors have antigen-binding specificity as well as determinants controlled by the K end of the H-2 MHC. The distribution of strains capable of making SF has also been analyzed. The relationship of the antigen-binding specificity to VH gene products is discussed in this and the companion paper.

Mechanisms of regulation of cell-mediated immunity. IV. Azobenzenearsonate-specific suppressor factor(s) bear cross-reactive idiotypic determinants the expression of which is linked to the heavy-chain allotype linkage group of genes.

T-cell derived suppressor factor(s) (SF) specific for azobenzenearsonate (ABA) were prepared by the mechanical disruption of suppressor cells. Such suppressor factors were adsorbed to and recovered from immunoadsorbents prepared from the F(ab')2 fragments of rabbit immunoglobulin directed against the cross-reactive idiotype of A/J anti-ABA antibodies. These ABA-suppressor factors were not retained on Sepharose 4B immunoadsorbent columns which had been coupled with F(ab')2 fragments or normal rabbit immunoglobulins prepared from prebleeds of rabbits used to make anti-idiotypic antiserum. The specificity of the F(ab')2 rabbit anti-idiotypic serum was established by direct idiotypic-binding assays and by affinity purification over an immunoadsorbent consisting of CRI+ anti-ABA immunoglobulin from A/J mice. ABA-suppressor factors were shown to be specifically absorbed and eluted from F(ab')2 anti-idiotypic columns. Futhermore, the eluted suppressor factor can be specifically reabsorbed and recovered from a second anti-idiotypic immunoadsorbent. The concordance between antigen-binding specificity and the presence of idiotypic determinants was demonstrated by adsorbing ABA SF to antigen columns and then fractionating the ABA-specific factor on anti-idiotypic immunoadsorbents. ABA-suppressor factors were shown to be specifically retained on immunoadsorbents directed against major histocompatibility complex (MHC) determinants. Factor eluted from anti-MHC columns could then be specifically adsorbed to anti-idiotypic immunoadsorbents. This suggests that the same molecular complex that is recognized by the H-2 alloantiserum is specifically adsorbed to an anti-idiotypic immunoadsorbent. Genetic analysis of the expression of CRI+ suppressor factor was performed using the C.AL-20 mouse strain which has the AL/N allotype and produces CRI+ anti-ABA immunoglobulins. The implication of these findings to the nature of T-cell-derived regulatory molecules is discussed.

Antigen- and receptor-driven regulatory mechanisms. I. Induction of suppressor T cells with anti-idiotypic antibodies.

Delayed-type hypersensitivity (DTH) to the azobenzenearsonate (ABA) hapten can be readily induced in A/J mice injecting ABA-coupled syngeneic spleen cells subcutaneously. To further characterize this T-cell-dependent immunological phenomenon, the effect of passively administered anti-cross-reactive idiotype common to anti-ABA antibodies of A/J mice (CRI) antibodies on the development of ABA-specific DTH was investigated. Animals given daily injections (of minute amounts) of anti-CRI antibodies subsequent to immunization with ABA-coupled cells show significant reduction of ABA specific responses. This inhibition is antigen specific and requires the intact immunoglobulin molecule, as F(ab')2 treatments were ineffective in suppressing the reaction. Investigations of the mechanism of the anti-CRI-induced suppression of ABA DTH revealed that the observed suppression is a result of the activation of suppressor cells. Spleen cells taken from animals which received anti-CRI antibodies were able to adoptively transfer suppression to naive recipients. This suppression was shown to be mediated by T cells, as anti-Thy1.2 plus complement completely abrogated the transfer of suppression. In addition, animals pretreated with low doses of cyclophosphamide were not suppressed by the administration of anti-CRI antibodies. The genetic restriction of anti-CRI-induced suppression was demonstrated. Antibodies to the major cross-reactive idiotype, (CRI) associated with anti-ABA antibodies in A/J mice were unable to suppress the development of DTH to ABA in BALB/c mice (H-2d, Igh-1a). Such antibodies were, however, fully active in suppressing ABA DTH in the allotype-congenic C.AL-20 strain which has an allotype (Igh-1d) similar to that of A/J (Igh-1e) on a BALB/c background, and which produces humoral antibodies with the CRI.

Antigen- and receptor-driven regulatory mechanisms. II. Induction of suppressor T cells with idiotype-coupled syngeneic spleen cells.

Anti-p-azobenzenearsonate (ABA) antibodies, coupled covalently to normal syngeneic spleen cells and then given intravenously to normal animals, were found to be potent tolerogens for delayed-type hypersensitivity (DTH) to ABA. The ability of the antibody-coupled cells to induce tolerance was determined to be a result of the cross-reactive idiotype (CRI+) fraction of the antibodies, because anti-ABA antibodies lacking the CRI+ components when coupled to spleen cells were unable to cause any significant inhibition. Furthermore, genetic analysis revealed that the ability of CRI-coupled cells to inhibit ABA-specific DTH is linked to Igh-1 heavy chain allotype, in as much animals which possess heavy chain allotypes similar to that of A/J were sensitive to this inhibition. Adoptive transfer experiments provided evidence that CRI-coupled cells induce suppressor cells, and spleen cells or thymocytes from animals received CRI-coupled cells were able to transfer suppression to naive recipients. In addition, treatment with anti-Thy1.2 serum plus complement completely abrogated their ability to transfer suppression. Thus, this active suppression is a T-cell-dependent phenomenon. In investigating the specificity of these suppressor T cells, it was found that they functioned in an antigen-specific manner and were unable to suppress the development of DTH to an unrelated hapten 2,4-dinitro-1-fluorobenzene.

Use and impact of point-of-care ultrasonography in general practice: a prospective observational study.

OBJECTIVES: To describe how general practitioners (GPs) use point-of-care ultrasonography (POCUS) and how it influences the diagnostic process and treatment of patients. DESIGN: Prospective observational study using an online questionnaire before and after POCUS. SETTING: Office-based general practice. PARTICIPANTS: Twenty GPs consecutively recruited all patients examined with POCUS in 1 month. PRIMARY AND SECONDARY OUTCOME MEASURES: We estimated the use of POCUS through the indication for use, the frequency of use, the time consumption, the extent of modification of the examination and the findings.The influence on the diagnostic process was estimated through change in the tentative diagnoses, change in confidence, the ability to produce ultrasound images and the relationship between confidence and organs scanned or tentative diagnoses.The influence of POCUS on patient treatment was estimated through change in plan for the patient, change in patient's treatment and the relationship between such changes and certain findings. RESULTS: The GPs included 574 patients in the study. POCUS was used in patient consultations with a median frequency of 8.6% (IQR: 4.9-12.6). Many different organs were scanned covering more than 100 different tentative diagnoses. The median time taken to perform POCUS was 5 min (IQR: 3-8). Across applications and GPs, POCUS entailed a change in diagnoses in 49.4% of patients; increased confidence in a diagnosis in 89.2% of patients; a change in the management plan for 50.9% of patients including an absolute reduction in intended referrals to secondary care from 49.2% to 25.6%; and a change in treatment for 26.5% of patients. CONCLUSIONS: The clinical utilisation of POCUS was highly variable among the GPs included in this study in terms of the indication for performing POCUS, examined scanning modalities and frequency of use. Overall, using POCUS altered the GPs' diagnostic process and clinical decision-making in nearly three out of four consultations. TRIAL REGISTRATION NUMBER: NCT03375333.

Accuracy of lung ultrasonography in the hands of non-imaging specialists to diagnose and assess the severity of community-acquired pneumonia in adults: a systematic review.

OBJECTIVES: We aimed to systematically review the published literature regarding adults with clinical suspicion of pneumonia that compares the accuracy of lung ultrasonography (LUS) performed by non-imaging specialists to other reference standards in diagnosing and evaluating the severity of community-acquired pneumonia. Moreover, we aimed to describe LUS training and the speciality of the physician performing LUS, time spent on the LUS procedure and potential harms to patients. MATERIALS AND METHODS: We searched MEDLINE, Embase, CINAHL, Web of Science and Cochrane Central Register of Controlled Trials up until May 2019. We included studies that used LUS to diagnose pneumonia, but also confirmed pneumonia by other means. Publications were excluded if LUS was performed by a sonographer or radiologist (imaging specialists) or performed on other indications than suspicion of pneumonia. Two review authors screened and selected articles, extracted data and assessed quality using Quality Assessment of Diagnostic Accuracy Studies 2. RESULTS: We included 17 studies. The sensitivity of LUS to diagnose pneumonia ranged from 0.68 to 1.00; however, in 14 studies, sensitivity was ≥0.91. Specificities varied from 0.57 to 1.00. We found no obvious differences between studies with low and high diagnostic accuracy. The non-imaging specialists were emergency physicians, internal medicine physicians, intensivists or 'speciality not described'. Five studies described LUS training, which varied from a 1-hour course to fully credentialed ultrasound education. In general, the methodological quality of studies was good, though, some studies had a high risk of bias. CONCLUSION: We found significant heterogeneity across studies. In the majority of studies, LUS in the hands of the non-imaging specialists demonstrated high sensitivities and specificities in diagnosing pneumonia. However, due to problems with methodology and heterogeneity there is a need for larger studies with uniform and clearly established criteria for diagnosis and blinding. PROSPERO REGISTRATION NUMBER: Prospectively registered in PROSPERO (CRD42017057804).

[Use of biotherapy in the management of Behçet's disease in a department of internal medicine]. / Recours à la biothérapie dans la prise en charge de la maladie de Behçet dans un service de médecine interne.

BACKGROUND: Behçet's disease (BD) is a recurrent multisystemic disease responsible for occlusive vasculitis with arterial, venous and capillary involvement. The aim of this study was to determine the frequency and the features associated with the use of biotherapy in the management of patients followed in our department for BD. METHODS: This is a retrospective study of patients medical records followed for BD in a department of internal medicine from January 2005 to August 2018. RESULTS: A total of 41 patients were included with a mean age at diagnosis of 42.5±12.1 years (range 16 to 63) and a sex ratio men/women of 1.05. Oral and/or genital aphtosis was present in 70.7% of the patients. Other lesions were: ocular (78.0%), articular (46.3%), cutaneous (41.5%), central neurological (34.1%), vascular (26.8%), digestive (7.3%), pericardial (2.4%) and epididymal (2.4%). A biotherapy, interferon α and monoclonal antibodies, was used in 15 patients (36.6%), after failure of conventional treatments. The monoclonal antibodies were anti-TNFα (infliximab, adalimumab, certolizumab and golimumab) except in one patient for whom ustekinumab was used. Biotherapy was used in 46.9% of the patients with ocular involvement and never used in those patients without ocular involvement (P=0.01). CONCLUSION: Biotherapy is effective and represents a solution to the failures of conventional treatments in severe forms of Behçet's disease with ocular involvement.

Primary care physicians' access to in-house ultrasound examinations across Europe: a questionnaire study.

OBJECTIVE: The overall objective of this study was to examine the differences in ultrasound availability in primary care across Europe. DESIGN: Cross-sectional study. SETTING: Primary care. PARTICIPANTS: Primary care physicians (PCPs). PRIMARY AND SECONDARY OUTCOMES MEASURES: The primary aim was to describe the variation in in-house primary care ultrasonography availability across Europe using descriptive statistics. The secondary aim was to explore associations between in-house ultrasonography availability and the characteristics of PCPs and their clinics using a mixed-effects logistic regression model. RESULTS: We collected data from 20 European countries. A total of 2086 PCPs participated, varying from 59 to 446 PCPs per country. The median response rate per country was 24.8%. The median (minimum-maximum) percentage of PCPs across Europe with access to in-house abdominal ultrasonography was 15.3% (0.0%-98.1%) and 12.1% (0.0%-30.8%) had access to in-house pelvic ultrasonography with large variations between countries. We found associations between in-house abdominal ultrasonography availability and larger clinics (OR 2.5, 95% CI 1.2 to 4.9) and clinics with medical doctors specialised in areas, which traditionally use ultrasonography (OR 2.1, 95% CI 1.1 to 3.8). Corresponding associations were found between in-house pelvic ultrasonography availability and larger clinics (OR 1.9, 95% CI 1.3 to 2.7) and clinics with medical doctors specialised in areas, which traditionally use ultrasonography (OR 3.0, 95% CI 1.8 to 5.1). Additionally, we found a negative association between urban clinics and in-house pelvic ultrasound availability (OR 0.5, 95% CI 0.2 to 0.9). CONCLUSIONS: Across Europe, there is a large variation in PCPs' access to in-house ultrasonography and organisational aspects of primary care seem to determine this variation. If evidence continues to support ultrasonography as a front-line point-of-care test, implementation strategies for increasing its availability in primary care are needed. Future research should focus on facilitators and barriers that may affect the implementation process.

Utility of DSM-5 section III personality traits in differentiating borderline personality disorder from comparison groups.

OBJECTIVE: Borderline Personality Disorder (BPD) is a highly prevalent diagnosis in mental health care and includes a heterogeneous constellation of symptoms. As the field of personality disorder (PD) research moves to emphasize dimensional traits in its operationalization, it is important to determine how the alternative DSM-5 Section III personality trait dimensions differentiates such features in BPD patients versus comparison groups. To date, no study has attempted such validation. METHOD: The current study examined the utility of the DSM-5 trait dimensions in differentiating patients with the categorical DSM-IV/5 diagnosis of BPD (n=101) from systematically matched samples of other PD patients (n=101) and healthy controls (n=101). This was investigated using one-way ANOVA and multinomial logistic regression analyses. RESULTS: Results indicated that Emotional Lability, Risk Taking, and Suspiciousness uniquely differentiated BPD patients from other PD patients, whereas Emotional Lability, Depressivity, and Suspiciousness uniquely differentiated BPD patients from healthy controls. CONCLUSION: Emotional Lability is in particular a key BPD feature of the proposed Section III model, whereas Suspiciousness also augments essential BPD features. Provided that these findings are replicated cross-culturally in forthcoming research, a more parsimonious traits operationalization of BPD features is warranted.

Biomechanical testing of the reconstructed ulnar collateral ligament: a systematic review of the literature.

PURPOSE: The purpose was to perform a systematic review of the literature investigating biomechanical studies of ulnar collateral ligament reconstruction (UCLR) techniques to summarize the most commonly analyzed methods of fixation (at both the ulna and humerus), the degree of elbow flexion at the time of fixation, graft characteristics, and modes of failure with these techniques. MATERIALS AND METHODS: A systematic review was performed. All cadaveric biomechanical studies that tested a reconstruction method for UCLR were included. Descriptive statistics were calculated for each study and parameter/variable analyzed. RESULTS: Twenty-three studies were included with a total of 397 elbows in 242 cadavers (mean age 54.8 ± 20 years, range 16-96). The majority of studies (65 %) used a palmaris longus graft. The docking technique (37.2 %) was the most commonly tested reconstruction method. Significant heterogeneity between studies precluded assimilation of specific techniques (each of the 23 studies utilized a unique technique). Fixation was performed at 30°-90° of elbow flexion. The most common mode of failure was suture failure (51 %), followed by midsubstance rupture (27.00 %), and bone tunnel fracture (14.00 %). No significant differences were observed amongst techniques for all measures analyzed. CONCLUSION: This study found the docking technique to be the most commonly tested technique, while the mode of reconstruction failure was most commonly at the suture interface. If the graft failed at the bone interface, it was most likely to occur at the ulna. Surgeon preference and comfort level with a specific technique should dictate choice.