Transcranial magnetic stimulation in the treatment of adolescent depression: a systematic review and meta-analysis of aggregated and individual-patient data from uncontrolled studies

Transcranial magnetic stimulation (TMS) is a non-invasive treatment for adolescent major depressive disorder (MDD). Existing evidence on the efficacy of TMS in adolescent MDD awaits quantitative synthesis. A systematic literature search was conducted, and data from eligible studies were synthesized using random-effects models. Treatment-covariate interactions were examined in exploratory analyses of individual-patient data (IPD). Systematic search of the literature yielded 1264 hits, of which 10 individual studies (2 randomized trials) were included for quantitative synthesis of mainly uncontrolled studies. Individual patient data (IPD) were available from five trials (all uncontrolled studies). Quantitative synthesis of aggregated data revealed a statistically significant negative overall standardized mean change (pooled SMCC = 2.04, 95% CI [1.46; 2.61], SE = 0.29, p < .001), as well as a significant overall treatment response rate (Transformed Proportion = 41.30%, 95% CI [31.03; 51.57], SE = 0.05; p < 0.001), considering data from baseline to post-treatment. Exploratory IPD analyses suggests TMS might be more effective in younger individuals and individuals with more severe depression, and efficacy might be enhanced with certain treatment modality settings, including higher number of TMS sessions, longer treatment durations, and unilateral and not bilateral stimulation. Existing studies exhibit methodological shortcomings, including small-study effects and lack of control group, blinding, and randomization—compromising the credibility of the present results. To date, two randomized controlled trials on TMS in adolescent depression have been published, and the only large-scale randomized trial suggests TMS is not more effective than sham stimulation. Future large-scale, randomized, and sham-controlled trials are warranted. Future trials should ensure appropriate selection of patients for TMS treatment and guide precision medicine approaches for stimulation protocols.

     

Fehlerbedingte Harnleiterverletzungen bei operativen Eingriffen im kleinen Becken

Injuries to the ureter are still a current problem in the assessment of reproaches for treatment errors following gynecological interventions; therefore, the topic was re-examined and a comparison of own previous data from the expert commission for North-Rhine with the numbers and types of errors from the North German arbitration board was undertaken. Out of a total of 13,322 assessed cases from North-Rhine over the period 2006–2014, there were 95 cases (0.7?%) of iatrogenic ureteral injuries in gynecology. For the North German arbitration board the figures were 0.5?% of 31,504 cases from the period 2000–2011. The proportion of ureteral lesions due to technical operational errors by gynecologists in the 919 cases in gynecology from North-Rhine was 2.2?%, which was double that of the North German arbitration board with 1.1?% from 2,892 cases. In 95 cases from North-Rhine, 35 reproachable treatment errors were determined, of which 32 were made by gynecologists (34?%) and 3 by urologists. The treatment error quota for gynecologists was therefore much lower than the error quota of 47?% reported from North Germany, was due to a higher number of errors in the follow-up care in the latter case.     

Correlation between HSP-72 expression and IL-8 secretion in human mesothelial cells

BACKGROUND: Cytotoxicity of peritoneal dialysis fluid (PDF) and peritoneal inflammation are currently regarded as the two major culprits for chronic mesothelial injury and peritoneal membrane failure. In this study, we correlated induction of HSP-72, as a marker of the cellular stress response, to secretion of IL-8, as a marker for pro-inflammatory cytokines, in mesothelial cells upon sublethal PDF exposure. METHODS: Primary omental cell cultures of human mesothelial cells were subjected to sublethal PDF exposure times (CAPD2, Fresenius, Germany). At the end of a 24 hour recovery period, induction of HSP-72 in the cell homogenate and IL-8 secretion in the supernatant was assessed by immunodensitometry and ELISA, respectively. RESULTS: PDF exposure times from 15 min to 60 min resulted in progressively increased HSP-72 expression levels (267 vs 320 vs 419% of controls, p<0.05 vs controls) as well as increased IL-8 secretion (323 vs 528 vs 549% of controls, p<0.05 vs controls) with full cell viability (MTT unchanged to control). HSP-72 expression was statistically significantly correlated with IL-8 secretion. CONCLUSIONS: The significant correlation between HSP-72 expression and IL-8 secretion suggests that the regulation of pro-inflammatory pathways in mesothelial cells exposed to PDF may represent an integral part of their stress response. Future studies to investigate the cellular regulatory mechanism involved are warranted.     

Preclinical evaluation of potential infection‐imaging probe [68Ga]Ga‐DOTA‐K‐A9 in sterile and infectious inflammation

The development of bacteria‐specific infection radiotracers is of considerable interest to improve diagnostic accuracy and enabling therapy monitoring. The aim of this study was to determine if the previously reported radiolabelled 1,4,7,10‐tetraazacyclododecane‐N,N′,N″,N?‐tetraacetic acid (DOTA) conjugated peptide [⁶⁸Ga]Ga‐DOTA‐K‐A9 could detect a staphylococcal infection in vivo and distinguish it from aseptic inflammation. An optimized [⁶⁸Ga]Ga‐DOTA‐K‐A9 synthesis omitting the use of acetone was developed, yielding 93 ± 0.9% radiochemical purity. The in vivo infection binding specificity of [⁶⁸Ga]Ga‐DOTA‐K‐A9 was evaluated by micro positron emission tomography/magnetic resonance imaging of 15 mice with either subcutaneous Staphylococcus aureus infection or turpentine‐induced inflammation and compared with 2‐deoxy‐2‐[¹⁸F]fluoro‐D‐glucose ([¹⁸F]FDG). The scans showed that [⁶⁸Ga]Ga‐DOTA‐K‐A9 accumulated in all the infected mice at injected doses ≥3.6 MBq. However, the tracer was not found to be selective towards infection, since the [⁶⁸Ga]Ga‐DOTA‐K‐A9 also accumulated in mice with inflammation. In a concurrent in vitro binding evaluation performed with a 5‐carboxytetramethylrhodamine (TAMRA) fluorescence analogue of the peptide, TAMRA‐K‐A9, the microscopy results suggested that TAMRA‐K‐A9 bound to an intracellular epitope and therefore preferentially targeted dead bacteria. Thus, the [⁶⁸Ga]Ga‐DOTA‐K‐A9 uptake observed in vivo is presumably a combination of local hyperemia, vascular leakiness and/or binding to an epitope present in dead bacteria.     

Stereotyped topography of different elevated contingent negative variation components in children with migraine without aura points towards a subcortical dysfunction

Increased negativity during contingent negative variation (CNV) is thought to reflect abnormal neural activation in adult migraineurs' attention related processing. Findings in childhood and adolescence have yielded less clear results. This study characterizes the age-dependent development of CNV topography in migraine during childhood in order to elucidate the origin and cerebral generators of described CNV elevations. A large sample of children with primary headache (migraine with/without aura, tension type headache) and healthy controls aged 6-18 years was examined in a CNV paradigm using 64-channel high resolution DC-EEG. Patients were tested for diagnose-related topographic group differences of initial CNV (iCNV), late CNV (lCNV) and postimperative negative variation (PINV). All three CNV components of 6-11-year-old migraineurs without aura showed elevated negativity over the supplementary motor area (SMA) and around the vertex. Migraine children lacked age-dependent development of late CNV around Cz as previously reported. However, they showed a normal development of late CNV over pre-/primary motor cortex (MI). There was no marked elevation of iCNV amplitude over frontal areas (orienting reaction) nor specific amplitude elevations over "motor" or "sensory" areas during sustained attention (late CNV). Additional "pre-mature" activation e.g., in the locus coeruleus (leading to diffuse cortical activation summing up to a maximum over the vertex) or the basal ganglia (interacting with SMA) explained the rather stereotyped CNV elevation around the vertex better than a specific implication of the cortical systems responsible for orienting, motor preparation or sensory attention.     

On the learning of addictive behavior: Sensation-seeking propensity predicts dopamine turnover in dorsal striatum

Brain Imaging and Behavior - We asked if sensation-seeking is linked to premorbid personality characteristics in patients with addictive disorders, or the characteristics follow the...     

Differential expression of perforin in muscle-infiltrating T cells in polymyositis and dermatomyositis.

Polymyositis (PM) and dermatomyositis (DM) are the prototypical inflammatory diseases of skeletal muscle. In PM, CD8+ T cells invade and destroy muscle fibers, whereas humoral effector mechanisms prevail in DM. We studied the expression of the cytotoxic mediator perforin in inflammatory cells in PM and DM muscle by semiquantitative PCR, immunohistochemistry and confocal laser microscopy. Similar levels of perforin mRNA were expressed in PM and DM, and abundant perforin-expressing CD3+CD8+ and CD3+ CD4+ T cells were observed in both diseases. However, there was a striking difference in the intracellular localization of perforin. In DM, perforin was distributed randomly in the cytoplasm of the inflammatory T cells. In contrast, 43% of the CD8+ T cells that contacted a muscle fiber in PM showed perforin located vectorially towards the target muscle fiber. The results suggest (a) that the random distribution of perforin in the cytoplasm of muscle-infiltrating T cells observed in DM reflects nonspecific activation, and (b) that the vectorial orientation observed only in PM reflects the specific recognition via the T cell receptor of an antigen on the muscle fiber surface, pointing to a perforin- and secretion-dependent mechanism of muscle fiber injury.