D-lactate is a promising biomarker for the diagnosis of periprosthetic joint infection.

Introduction: Reliable biomarkers for the diagnosis of periprosthetic joint infection (PJI) are of paramount clinical value. To date, synovial fluid leukocyte count is the standard surrogate parameter indicating PJI. As D-lactate is almost solely produced by bacteria, it represents a promising molecule in the diagnostic workflow of PJI evaluation. Therefore, the purpose of this study was to assess the performance of synovial fluid D-lactate for diagnosing PJI of the hip and knee. Materials and Methods: These are preliminary results of a prospective multicenter study from one academic center. Seventy-two consecutive patients after total hip arthroplasty (THA) or total knee arthroplasty (TKA) were prospectively included. All patients received a joint aspiration in order to rule out or confirm PJI, which was diagnosed according to previously published institutional criteria. Synovial fluid D-lactate was determined spectrophotometrically at 450 nm. Receiver operating characteristic (ROC) analysis was performed to assess the diagnostic performance. Results: Eighteen patients (25%) were diagnosed with PJI and 54 patients (75%) were classified as aseptic. Synovial fluid D-lactate showed a sensitivity of 90.7% (95% CI: 79.7%-96.9%) and specificity of 83.3% (95% CI: 58.6%-96.4%) at a cut-off of 0.04 mmol/L. The median concentration of D-lactate was significantly higher in patients with PJI than in those with aseptic conditions (0.048 mmol/L, range, 0.026-0.076 mmol/L vs. 0.024 mmol/L, range, 0.003-0.058 mmol/L, p < 0.0001). The predominat microogranisms were staphylococci, followed by streptococci and gram-negative bacteria. Conclusion: D-lactate bears a strong potential to act as a valuable biomarker for diagnosing PJI of the hip and knee. In our study, a cutoff of 0.04 mmol/L showed a comparable sensitivity to synovial fluid leukocyte count. However, its specificity was higher compared to conventional diagnostic tools. The additional advantages of D-lactate testing are requirement of low synovial fluid volume, short turnaround time and low cost.

Clinical factors predicting treatment resistant depression: affirmative results from the European multicenter study.

OBJECTIVES: Clinical variables were investigated in the 'treatment resistant depression (TRD)- III' sample to replicate earlier findings by the European research consortium 'Group for the Study of Resistant Depression' (GSRD) and enable cross-sample prediction of treatment outcome in TRD. EXPERIMENTAL PROCEDURES: TRD was defined by a Montgomery and Åsberg Depression Rating Scale (MADRS) score ≥22 after at least two antidepressive trials. Response was defined by a decline in MADRS score by ≥50% and below a threshold of 22. Logistic regression was applied to replicate predictors for TRD among 16 clinical variables in 916 patients. Elastic net regression was applied for prediction of treatment outcome. RESULTS: Symptom severity (odds ratio (OR) = 3.31), psychotic symptoms (OR = 2.52), suicidal risk (OR = 1.74), generalized anxiety disorder (OR = 1.68), inpatient status (OR = 1.65), higher number of antidepressants administered previously (OR = 1.23), and lifetime depressive episodes (OR = 1.15) as well as longer duration of the current episode (OR = 1.022) increased the risk of TRD. Prediction of TRD reached an accuracy of 0.86 in the independent validation set, TRD-I. CONCLUSION: Symptom severity, suicidal risk, higher number of lifetime depressive episodes, and comorbid anxiety disorder were replicated as the most prominent risk factors for TRD. Significant predictors in TRD-III enabled robust prediction of treatment outcome in TRD-I.

International Union of Basic and Clinical Pharmacology CIV: The Neurobiology of Treatment-resistant Depression: From Antidepressant Classifications to Novel Pharmacological Targets.

Major depressive disorder is one of the most prevalent and life-threatening forms of mental illnesses and a major cause of morbidity worldwide. Currently available antidepressants are effective for most patients, although around 30% are considered treatment resistant (TRD), a condition that is associated with a significant impairment of cognitive function and poor quality of life. In this respect, the identification of the molecular mechanisms contributing to TRD represents an essential step for the design of novel and more efficacious drugs able to modify the clinical course of this disorder and increase remission rates in clinical practice. New insights into the neurobiology of TRD have shed light on the role of a number of different mechanisms, including the glutamatergic system, immune/inflammatory systems, neurotrophin function, and epigenetics. Advances in drug discovery processes in TRD have also influenced the classification of antidepressant drugs and novel classifications are available, such as the neuroscience-based nomenclature that can incorporate such advances in drug development for TRD. This review aims to provide an up-to-date description of key mechanisms in TRD and describe current therapeutic strategies for TRD before examining novel approaches that may ultimately address important neurobiological mechanisms not targeted by currently available antidepressants. All in all, we suggest that drug targeting different neurobiological systems should be able to restore normal function but must also promote resilience to reduce the long-term vulnerability to recurrent depressive episodes.

Clinical correlates of augmentation/combination treatment strategies in major depressive disorder.

OBJECTIVE: This multicenter, multinational, cross-sectional study aimed to investigate clinical characteristics and treatment outcomes associated with augmentation/combination treatment strategies in major depressive disorder (MDD). METHOD: Sociodemographic, clinical, and treatment features of 1410 adult MDD patients were compared between MDD patients treated with monotherapy and augmentation/combination medication using descriptive statistics, analyses of covariance (ancova), and Spearman's correlation analyses. RESULTS: 60.64% of all participants received augmentation and/or combination strategies with a mean number of 2.18 ± 1.22 simultaneously prescribed psychiatric drugs. We found male gender, older age, Caucasian descent, higher weight, low educational status, absence of occupation, psychotic symptoms, melancholic and atypical features, suicide risk, in-patient treatment, longer duration of hospitalization, some psychiatric comorbidities (panic disorder, agoraphobia, obsessive-compulsive disorder, and bulimia nervosa), comorbid somatic comorbidity in general and concurrent hypertension, thyroid dysfunction, diabetes, and heart disease in particular, higher current and retrospective Montgomery and Åsberg Depression Rating Scale total scores, treatment resistance, and higher antidepressant dosing to be significantly associated with augmentation/combination treatment. These findings were corroborated when examining the number of concurrently administered psychiatric drugs in the statistical analyses. CONCLUSION: Our findings suggest a clear association between augmentation/combination strategies and treatment-resistant/difficult-to-treat MDD conditions characterized by severe symptomatology and high amount of psychiatric and somatic comorbidities.

[Efficacy of antipsychotic augmentation therapy in treatment-resistant obsessive-compulsive disorder: a meta-analysis of double-blind, randomised, placebo-controlled trials]. / Effektivität einer Augmentationstherapie mit Antipsychotika bei therapieresistenten Zwangsstörungen - eine Metaanalyse doppelblinder, randomisierter, placebokontrollierter Studien.

Only 40 - 60 % of all patients with obsessive-compulsive disorder (OCD) respond to serotonin reuptake inhibitors (SRIs). Therefore, the evaluation of additive treatment in the presence of treatment resistance has high clinical relevance. All double-blind, randomised, placebo-controlled trials that evaluated the efficacy of a combination therapy of SRIs and antipsychotics in treatment-resistant OCD were identified by systematic literature searches and combined in a meta-analysis. 11 studies with a total of 356 treatment-resistant patients were included. After the augmentation, significantly more subjects in the intervention groups (SRI + antipsychotic) fulfilled the response criterion (reduction in the Yale-Brown obsessive compulsive scale [Y-BOCS] ≥ 35 %) than in the control groups (SRI + placebo) (relative risk = 2.16). The subgroup analysis showed significant efficacy only for risperidone. Further significant differences have been found regarding the antipsychotic dosage and the SRI-treatment duration before the augmentation.