Psychodynamic psychotherapy for complex trauma: targets, focus, applications, and outcomes

Complex trauma describes that category of severe, chronic interpersonal trauma usually originating in the formative years of a child. In the adult, this can result in global dissociative difficulties across areas of cognitive, affective, somatic, and behavioral functions. Targeting this field of traumatic pathology, this article reviews the contributions and developments within one broad approach: psychodynamic theory and practice. Brief descriptions of aspects of analytical, Jungian, relational, object relations, and attachment therapeutic approaches are given, along with understandings of pathology and the formulation of therapeutic goals. Major practices within client sessions are canvassed and the issues of researching treatment outcomes are discussed

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Complex Trauma, Dissociation, and the Use of Symbolism in Therapy

As therapists are confronted with clients who have childhood histories of severe interpersonal trauma, the challenge is to understand how this trauma affects individuals developmentally and how healing might be facilitated. This article explores how integration might be understood in the context of complex posttraumatic stress disorder. It is proposed that the symbolic function is central both to the fracturing of selfhood due to early trauma and to its resolution. The article provides a detailed discussion of symbolism and therapeutic possibilities for the use of symbolism as an adjunct to therapy with sufferers of complex posttraumatic stress disorder. It is argued that symbols provide a potentially powerful means of assisting reintegration and that this can be used within a range of therapeutic traditions, including cognitive-behavioral, psychodynamic, psychopharmacological, and neurophysiological approaches. The work of the first author in this regard is illustrated by means of a case study

Presentations at the UK National Immunisation Conference.

Funder: NIHR Oxford Biomedical Research CentreFunder: Meningitis Research Foundatio

Dairy matrix effects: response to consumption of dairy fat differs when eaten within the cheese matrix—a randomized controlled trial

peer-reviewedBackground Dairy fat consumed as cheese has different effects on blood lipids than that consumed as butter. It is unknown whether the effect is specific to fat interaction with other cheese nutrients (calcium, casein proteins), or to the cheese matrix itself. Objective We aimed to test the effect of 6 wk daily consumption of ∼40 g dairy fat, eaten within macronutrient-matched food matrices, on markers of metabolic health, in overweight adults aged ≥50 y. Design The study was a 6-wk randomized parallel intervention; 164 volunteers (75 men) received ∼40 g of dairy fat/d, in 1 of 4 treatments: (A) 120 g full-fat Irish cheddar cheese (FFCC) (n = 46); (B) 120 g reduced-fat Irish cheddar cheese + butter (21 g) (RFC + B) (n = 45); (C) butter (49 g), calcium caseinate powder (30 g), and Ca supplement (CaCO3) (500 mg) (BCC) (n = 42); or (D) 120 g FFCC, for 6 wk (as per A) (n = 31). Group D first completed a 6-wk “run-in” period, where they excluded all dietary cheese before commencing the intervention. Results There was no difference in anthropometry, fasting glucose, or insulin between the groups at pre- or postintervention. However, a stepwise-matrix effect was observed between the groups for total cholesterol (TC) (P = 0.033) and LDL cholesterol (P = 0.026), with significantly lower postintervention TC (mean ± SD) (5.23 ± 0.88 mmol/L) and LDL cholesterol (2.97 ± 0.67 mmol/L) when all of the fat was contained within the cheese matrix (Group A), compared with Group C when it was not (TC: 5.57 ± 0.86 mmol/L; LDL cholesterol: 3.43 ± 0.78 mmol/L). Conclusion Dairy fat, eaten in the form of cheese, appears to differently affect blood lipids compared with the same constituents eaten in different matrices, with significantly lower total cholesterol observed when all nutrients are consumed within a cheese matrix This trial was registered at ISRCTN as ISRCTN86731958.Enterprise Irelan

Cytokine expression in the placenta of pregnant cattle after inoculation with Neospora caninum

13 páginas, 4 tablas, 2 figuras.Neospora caninum is recognized as a major cause of reproductive losses worldwide but its pathogenesis is not completely understood. Immune mediated placental pathology has been reported as being responsible for compromising pregnancy probably due to the adverse effects of exacerbated Th1 type response at the maternal-foetal interface. Different clinical outcomes are known to occur following experimental infections of cattle at different stages of gestation, with foetal death being the most common finding during early gestation, and the birth of live congenitally infected calves following infection later in gestation. The aim of the current study was to characterize the cytokine expression in the placenta of cattle experimentally challenged with tachyzoites of the Nc-1 strain during early, mid and late gestation. Moderate to severe infiltration of IL-12, IFN-γ and TNF-α expressing cells was observed in the placentas collected at early gestation and this infiltration was more pronounced in the samples collected from challenged dams carrying non-viable foetuses, compared with the mothers carrying viable foetuses. In contrast, the infiltration of Th1 cytokine expressing-cells was mild following N. caninum infection in mid gestation and scarce during infection in late gestation. Scarce expression of IL-4 was observed in the placentas from N. caninum-challenged and negative control animals throughout gestation. The milder Th1 immune response observed during later stages of gestation following Nc-1 infection could partially explain the less severe clinical outcome when compared to early pregnancy. © 2014 Elsevier B.V.The authors acknowledge the Scottish Government's Rural and Environment Science and Analytical Services Division (RESAS), UK, and Instituto Nacional de Tecnología Agropecuaria (INTA), Argentina.Peer Reviewe

A Bayesian reanalysis of the Standard versus Accelerated Initiation of Renal-Replacement Therapy in Acute Kidney Injury (STARRT-AKI) trial

Background Timing of initiation of kidney-replacement therapy (KRT) in critically ill patients remains controversial. The Standard versus Accelerated Initiation of Renal-Replacement Therapy in Acute Kidney Injury (STARRT-AKI) trial compared two strategies of KRT initiation (accelerated versus standard) in critically ill patients with acute kidney injury and found neutral results for 90-day all-cause mortality. Probabilistic exploration of the trial endpoints may enable greater understanding of the trial findings. We aimed to perform a reanalysis using a Bayesian framework. Methods We performed a secondary analysis of all 2927 patients randomized in multi-national STARRT-AKI trial, performed at 168 centers in 15 countries. The primary endpoint, 90-day all-cause mortality, was evaluated using hierarchical Bayesian logistic regression. A spectrum of priors includes optimistic, neutral, and pessimistic priors, along with priors informed from earlier clinical trials. Secondary endpoints (KRT-free days and hospital-free days) were assessed using zero–one inflated beta regression. Results The posterior probability of benefit comparing an accelerated versus a standard KRT initiation strategy for the primary endpoint suggested no important difference, regardless of the prior used (absolute difference of 0.13% [95% credible interval [CrI] − 3.30%; 3.40%], − 0.39% [95% CrI − 3.46%; 3.00%], and 0.64% [95% CrI − 2.53%; 3.88%] for neutral, optimistic, and pessimistic priors, respectively). There was a very low probability that the effect size was equal or larger than a consensus-defined minimal clinically important difference. Patients allocated to the accelerated strategy had a lower number of KRT-free days (median absolute difference of − 3.55 days [95% CrI − 6.38; − 0.48]), with a probability that the accelerated strategy was associated with more KRT-free days of 0.008. Hospital-free days were similar between strategies, with the accelerated strategy having a median absolute difference of 0.48 more hospital-free days (95% CrI − 1.87; 2.72) compared with the standard strategy and the probability that the accelerated strategy had more hospital-free days was 0.66. Conclusions In a Bayesian reanalysis of the STARRT-AKI trial, we found very low probability that an accelerated strategy has clinically important benefits compared with the standard strategy. Patients receiving the accelerated strategy probably have fewer days alive and KRT-free. These findings do not support the adoption of an accelerated strategy of KRT initiation