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Trauma-Focused mentalization-based treatment (MBT-TF) is an adaptation of mentalization-based treatment (MBT) specifically developed for patients suffering from attachment or complex trauma, with the possibility of co-occurring borderline personality pathology. The creation of MBT-TF was driven by previous research and observations that interventions centered on mentalizing could be significantly improved by directly addressing the impact of trauma. MBT-TF aims to mitigate symptoms that arise post-trauma, such as hyperarousal, hypervigilance, intrusions, flashbacks, avoidance behaviors, dissociative experiences, negative perceptions of self and others, and ensuing relational difficulties. Implemented as a group intervention, MBT-TF typically spans 6-12 months. From a mentalizing perspective, trauma, particularly attachment trauma, leads to a failure in processing the effects of trauma through and with others. Stress and attachment behavioral systems are disrupted, which undermines the capacity for epistemic trust, and impairs mentalizing abilities. This paper offers a concise summary of the reasoning for MBT-TF's creation, its theoretical underpinnings, and its clinical strategy for addressing the adverse impacts of trauma. It further details the treatment phases, their main goals, and their interventions, supplemented by clinical case examples that underscore MBT-TF's distinctive attributes and frequent clinical hurdles., Competing Interests: AB, PF, PL, MS, LN, TN, JV, and LS are involved in the development, training, and/or dissemination of mentalization-based treatments. The remaining author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Smits, de Vos, Rüfenacht, Nijssens, Shaverin, Nolte, Luyten, Fonagy and Bateman.)

Background: Although clinical guidelines prioritize the treatment of depression and anxiety in young persons, there is accumulating evidence that the presence of symptoms of borderline personality disorder (BPD) is associated with the limited effectiveness of these standard treatments. These findings stress the need for interventions addressing early-stage BPD in young people with presenting symptoms of anxiety and depressive disorders. The aim of this study is to investigate the (cost-)effectiveness of an early intervention programme for BPD (MBT-early) compared to first-choice psychological treatment for depression and anxiety according to Dutch treatment guidelines (CBT), in adolescents with either depression, anxiety, or both, in combination with early-stage BPD., Methods: This study is a multi-centre randomized controlled trial. A total of 132 adolescents, presenting with either depression, anxiety, or both and significant BPD features will be randomized to either MBT-early or CBT. The severity of BPD, symptoms of depression and anxiety, personality, social and academic functioning, and quality of life will be assessed at baseline, end of treatment, and at 12-, 18-, and 24-month follow-up, along with medical costs and costs of productivity losses for cost-effectiveness analyses., Discussion: This study will provide an empirical evaluation of the potential surplus value of early intervention in young people for whom treatment oriented at common mental disorders like anxiety and depression may be insufficient given their underlying personality problems., Trial Registration: Netherlands Trial Register, NL9569. Registered on June 15, 2021., (© 2024. The Author(s).)

Background & Aims: High-dose unilobar radioembolization, or 'radiation lobectomy' (RL), is an induction therapy that achieves contralateral future liver remnant hypertrophy while simultaneously irradiating the tumor. As such, it may prevent further growth, but it is unknown whether RL affects intrahepatic lymphatics, a major route via which liver tumors disseminate., Methods: This was a case-control study conducted at University Medical Center Utrecht. The study compared lymph vessels in livers that had undergone RL (cases) with those in livers that had not undergone RL (controls). Histological samples were acquired from patients diagnosed with hepatocellular carcinoma (HCC) or colorectal liver metastases (CRLM) between 2017 and 2022. Lymph vessel morphology was analyzed by two researchers using podoplanin, a protein that is expressed in lymphatic endothelium. In vivo liver lymph drainage of radioembolized livers was assessed using intraoperative liver lymphangiography (ILL): during liver surgery, patent blue dye was injected into the liver parenchyma, followed by inspection for staining of perihepatic lymph structures. ILL results were compared to a previously published cohort., Results: Immunohistochemical analysis on post-RL tumor tissues from ten patients with CRLM and nine patients with HCC revealed aberrant morphology of irradiated liver lymphatics when compared to controls (n = 3 per group). Irradiated lymphatics were tortuous ( p <0.05), thickened ( p <0.05) and discontinuous ( p <0.05). Moreover, post-RL lymphatics had larger lumens (1.5-1.7x, p <0.0001), indicating lymph stasis. ILL revealed diminished lymphatic drainage to perihepatic lymph nodes and vessels in irradiated livers when compared to non-radioembolized controls ( p  = 1.0x10 -4 )., Conclusions: Radioembolization impairs peritumoral lymph vessel function. Further research is needed to evaluate if radioembolization impairs tumor dissemination via this route., Impact and Implications: Unilobar radioembolization can serve as an alternative to portal venous embolization for patients who are considered unresectable due to an insufficient future liver remnant. This research suggests that radioembolization impairs the function of peritumoral liver lymph vessels, potentially hindering dissemination via this route. These findings provide support for considering unilobar radioembolization over standard portal venous embolization., Competing Interests: Marnix Lam is a consultant for Boston Scientific and Terumo. Maarten Smits is consultant for Philips and Terumo/Quierem Medical and has served as speakers for SirTex, BTG, Swedisch Orphan Biovitrum, Terumo and Metronic. The Department of Radiology and Nuclear Medicine of the UMC Utrecht receives royalties from Quirem Medical. No other potential conflict of interest relevant to this article was reported. Please refer to the accompanying ICMJE disclosure forms for further details., (© 2023 The Authors.)

Background: Two types of mentalisation-based treatment (MBT) have been developed and empirically evaluated for borderline personality disorder (BPD): day hospital MBT (MBT-DH) and intensive out-patient MBT (MBT-IOP). No trial has yet compared their efficacy., Aims: To compare the efficacy of MBT-DH and MBT-IOP 18 months after start of treatment. MBT-DH was hypothesised to be superior to MBT-IOP because of its higher treatment intensity., Method: In a multicentre randomised controlled trial (Nederlands Trial Register: NTR2292) conducted at three sites in the Netherlands, patients with BPD were randomly assigned to MBT-DH (n = 70) or MBT-IOP (n = 44). The primary outcome was symptom severity (Brief Symptom Inventory). Secondary outcome measures included borderline symptomatology, personality functioning, interpersonal functioning, quality of life and self-harm. Patients were assessed every 6 months from baseline to 18 months after start of treatment. Data were analysed using multilevel modelling based on intention-to-treat principles., Results: Significant improvements were found on all outcome measures, with moderate to very large effect sizes for both groups. MBT-DH was not superior to MBT-IOP on the primary outcome measure, but MBT-DH showed a clear tendency towards superiority on secondary outcomes., Conclusions: Although MBT-DH was not superior to MBT-IOP on the primary outcome measure despite its greater treatment intensity, MBT-DH showed a tendency to be more effective on secondary outcomes, particularly in terms of relational functioning. Patients receiving MBT-DH and MBT-IOP, thus, seem to follow different trajectories of change, which may have important implications for clinical decision-making. Longer-term follow-up and cost-effectiveness considerations may ultimately determine the optimal intensity of specialised treatments such as MBT for patients with BPD.

Background: The borderline personality disorder (BPD) population is notably heterogeneous, and this has potentially important implications for intervention. Identifying distinct subtypes of patients may represent a first step in identifying which treatments work best for which individuals., Methods: A cluster-analysis on dimensional personality disorder (PD) features, as assessed with the SCID-II, was performed on a sample of carefully screened BPD patients ( N  = 187) referred for mentalization-based treatment. The optimal cluster solution was determined using multiple indices of fit. The validity of the clusters was explored by investigating their relationship with borderline pathology, symptom severity, interpersonal problems, quality of life, personality functioning, attachment, and trauma history, in addition to demographic and clinical features., Results: A three-cluster solution was retained, which identified three clusters of BPD patients with distinct profiles. The largest cluster ( n  = 145) consisted of patients characterized by "core BPD" features, without marked elevations on other PD dimensions. A second "Extravert/externalizing" cluster of patients ( n  = 27) was characterized by high levels of histrionic, narcissistic, and antisocial features. A third, smaller "Schizotypal/paranoid" cluster ( n  = 15) consisted of patients with marked schizotypal and paranoid features. Patients in these clusters showed theoretically meaningful differences in terms of demographic and clinical features., Conclusions: Three meaningful subtypes of BPD patients were identified with distinct profiles. Differences were small, even when controlling for severity of PD pathology, suggesting a strong common factor underlying BPD. These results may represent a stepping stone toward research with larger samples aimed at replicating the findings and investigating differential trajectories of change, treatment outcomes, and treatment approaches for these subtypes., Trial Registration: The study was retrospectively registered 16 April 2010 in the Nederlands Trial Register , no. NTR2292.

Radioembolization is an established treatment modality that has been subjected to many improvements over the last decade. Developments are occurring at a high pace, affecting patient selection and treatment. The aim of this review is therefore to provide an overview of current practice, with a focus on recent developments in the field of radioembolization. Several practical issues and recommendations in the application of radioembolization will be discussed, ranging from patient selection to treatment response and future applications., (© 2015 by the Society of Nuclear Medicine and Molecular Imaging, Inc.)

Background: Borderline personality disorder (BPD) is associated with a high socioeconomic burden. Although a number of evidence-based treatments for BPD are currently available, they are not widely disseminated; furthermore, there is a need for more research concerning their efficacy and cost-effectiveness. Such knowledge promises to lead to more efficient use of resources, which will facilitate the effective dissemination of these costly treatments. This study focuses on the efficacy and cost-effectiveness of Mentalization-Based Treatment (MBT), a manualized treatment for patients with BPD. Studies to date have either investigated MBT in a day hospitalization setting (MBT-DH) or MBT offered in an intensive outpatient setting (MBT-IOP). No trial has compared the efficacy and cost-effectiveness of these MBT programmes. As both interventions differ considerably in terms of intensity of treatment, and thus potentially in terms of efficacy and cost-effectiveness, there is a need for comparative trials. This study therefore sets out to investigate the efficacy and cost-effectiveness of MBT-DH versus MBT-IOP in patients with BPD. A secondary aim is to investigate the association between baseline measures and outcome, which might improve treatment selection and thus optimize efficacy and cost-effectiveness., Methods/design: A multicentre randomized controlled trial comparing MBT-DH versus MBT-IOP in severe BPD patients. Patients are screened for BPD using the Structured Clinical Interview for DSM-IV Axis II Personality Disorders, and are assessed before randomization, at the start of treatment and 6, 12, 18, 24, 30 and 36 months after the start of treatment. Patients who refuse to participate will be offered care as usual in the same treatment centre. The primary outcome measure is symptom severity as measured by the Brief Symptom Inventory. Secondary outcome measures include parasuicidal behaviour, depression, substance use, social, interpersonal, and personality functioning, attachment, mentalizing capacities, and quality of life. All analyses will be conducted based on the intention-to-treat principle. Cost-effectiveness will be calculated based on costs per quality-adjusted life-year., Discussion: This multisite randomized trial will provide data to refine criteria for treatment selection for severe BPD patients and promises to optimize (cost-)effectiveness of the treatment of BPD patients., Trial Registration: NTR2292 . Registered 16 April 2010.

Purpose: Treatment efficacy of intra-arterial radioembolization for liver tumors depends on the selective targeting of tumorous tissue. Recent investigations have demonstrated that tumors may receive inadequate doses of radioactivity after radioembolization, due to unfavorable tumor to non-tumor (T/N) uptake ratios of radioactive microspheres. Hepatic arterial infusion of the vasoconstrictor angiotensin II (AT-II) is reported to increase the T/N blood flow ratio. The purpose of this systematic review was to provide a comprehensive overview of the effect of hepatic arterial AT-II on T/N blood flow ratio in patients with hepatic malignancies, and determine its clinical value for radioembolization., Methods: This review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A structured search was performed in the PubMed, EMBASE and Cochrane databases. Only studies that presented data on T/N ratios before and after infusion of AT-II into the hepatic artery, in human patients with hepatic malignancies, were selected. Median T/N ratios before, during and after AT-II infusion, and the median T/N ratio improvement factor were extracted from the selected articles. All data on systemic blood pressure measurements and clinical symptoms were also extracted., Results: The search identified 524 titles of which 5 studies, including a total of 71 patients were considered relevant. Median T/N ratios before infusion of AT-II ranged from 0.4 to 3.4. All studies observed a substantial improvement of the T/N ratio after AT-II infusion, with median improvement factors ranging from 1.8 to 3.1. A transitory increase of systemic blood pressure was observed during AT-II infusion., Conclusions: Infusion of AT-II into the hepatic artery leads to an increase of the tumor to non-tumor blood flow ratio, as measured by T/N uptake ratios. Clinical trials are warranted to assess safety aspects, optimal administration strategy and impact on treatment efficacy during radioembolization.

Unlabelled: (166)Ho-poly(l-lactic acid) microspheres allow for quantitative imaging with MR imaging or SPECT for microsphere biodistribution assessment after radioembolization. The purpose of this study was to evaluate SPECT- and MR imaging-based dosimetry in the first patients treated with (166)Ho radioembolization., Methods: Fifteen patients with unresectable, chemorefractory liver metastases of any origin were enrolled in this phase 1 study and were treated with (166)Ho radioembolization according to a dose escalation protocol (20-80 Gy). The contours of all liver segments and all discernible tumors were manually delineated on T2-weighted posttreatment MR images and registered to the posttreatment SPECT images (n = 9) or SPECT/CT images (n = 6) and MR imaging-based R2* maps (n = 14). Dosimetry was based on SPECT (n = 15) and MR imaging (n = 9) for all volumes of interest, tumor-to-nontumor (T/N) activity concentration ratios were calculated, and correlation and agreement of MR imaging- and SPECT-based measurements were evaluated., Results: The median overall T/N ratio was 1.4 based on SPECT (range, 0.9-2.8) and 1.4 based on MR imaging (range, 1.1-3.1). In 6 of 15 patients (40%), all tumors had received an activity concentration equal to or higher than the normal liver (T/N ratio ≥ 1). Analysis of SPECT and MR imaging measurements for dose to liver segments yielded a high correlation (R(2) = 0.91) and a moderate agreement (mean bias, 3.7 Gy; 95% limits of agreement, -11.2 to 18.7)., Conclusion: With the use of (166)Ho-microspheres, in vivo dosimetry is feasible on the basis of both SPECT and MR imaging, which enables personalized treatment by selective targeting of inadequately treated tumors.

Unlabelled: Currently, there is no consensus on the use of (90)Y radioembolization for salvage patients with colorectal cancer liver metastases. The purpose of this study was to provide a comprehensive overview of the available data on tumor response and survival after (90)Y radioembolization for this group of patients., Methods: A systematic literature search was conducted in PubMed (Medline), Excerpta Medica (EMBASE), and the Cochrane Library (September 2012) with synonyms for "radioembolization" and "colorectal cancer liver metastases." Results were described separately for patient cohorts treated with (90)Y radioembolization as monotherapy and with (90)Y radioembolization in combination with chemotherapy., Results: The search yielded 13 relevant articles for systematic review on (90)Y radioembolization as monotherapy and 13 relevant articles on (90)Y radioembolization combined with chemotherapy. Disease control rates (i.e., complete response, partial response, and stable disease) ranged from 29% to 90% for (90)Y radioembolization as monotherapy and from 59% to 100% for (90)Y radioembolization combined with chemotherapy. Heterogeneity in the data prohibited pooling of response rates. Survival proportions at 12 mo ranged from 37% to 59% for (90)Y radioembolization as monotherapy and from 43% to 74% for (90)Y radioembolization combined with chemotherapy., Conclusion: In the studies included in this systematic review, approximately 50% of salvage patients with colorectal cancer liver metastases survive more than 12 mo after treatment with (90)Y radioembolization, either as monotherapy or in combination with chemotherapy. Heterogeneity between studies has unfortunately prohibited pooling of data. Future research will discern the precise role of (90)Y radioembolization in general clinical practice in comparison with chemotherapy.

Aim: To assess the technical feasibility and clinical outcome of percutaneous transluminal angioplasty (PTA) with and without stent placement for treatment of buttock claudication caused by internal iliac artery (IIA) stenosis., Methods: Between September 2001 and July 2011, thirty-four patients with buttock claudication underwent endovascular treatment. After angiographic lesion evaluation PTA with or without stent placement was performed. Technical success was recorded. Clinical outcome post-treatment was assessed at three months post-intervention and was classified as: 1) complete relief of symptoms, 2) partial relief, or 3) no relief of symptoms. Complications during follow-up were recorded., Results: Forty-four lesions in 34 symptomatic patients were treated with PTA. Eight lesions were treated with additional stent placement. Technical success was achieved in 40/44 lesions (91%). Three procedure-related minor complications occurred, i.e. asymptomatic conservatively treated intimal dissections. After a median of 2.9 months, patients experienced no relief of symptoms in 7/34 cases (21%), partial relief in 14/34 cases (41%), and complete relief in 13/34 cases (38%). Six patients required a reintervention during follow-up., Conclusion: Endovascular treatment of IIA stenosis has a high technical success rate and a low complication rate. Complete or partial relief of symptoms is achieved in the majority (79%) of patients.

Unlabelled: In hepatic (90)Y radioembolization, pretreatment (99m)Tc-macroaggregated albumin ((99m)Tc-MAA) nuclear imaging is used for lung shunt analysis, evaluation of extrahepatic deposition, and sometimes for treatment planning, using a partition model. A high level of agreement between pretreatment (99m)Tc-MAA distribution and final (90)Y-microsphere distribution is assumed. The aim of this study was to investigate the value of pretreatment (99m)Tc-MAA SPECT to predict intrahepatic posttreatment (90)Y-microsphere distribution., Methods: Volumes of interest (VOIs) were delineated on pretreatment contrast-enhanced CT or MR images according to Couinaud liver segmentation. All VOIs were registered to the (99m)Tc-MAA SPECT and (90)Y SPECT images. The (99m)Tc-MAA SPECT and (90)Y SPECT activity counts were normalized to the total administered activity of (90)Y. For each VOI, this practice resulted in a predictive amount of (90)Y (MBq/cm(3)) based on (99m)Tc-MAA SPECT in comparison with an actual amount of (90)Y based on (90)Y SPECT. Bland-Altman analysis was used to investigate the agreement of the activity distribution between (99m)Tc-MAA SPECT and (90)Y SPECT., Results: A total of 39 procedures (225 VOIs) in 31 patients were included for analysis. The overall mean difference between pretreatment and posttreatment distribution of activity concentration for all segments was -0.022 MBq/cm(3) with 95% limits of agreement of -0.581 to 0.537 MBq/cm(3) (-28.9 to 26.7 Gy absorbed dose). A difference of >10%, >20%, and >30% of the mean activity per milliliter was found in, respectively, 153 (68%), 97 (43%), and 72 (32%) of the 225 segments. In every (99m)Tc-MAA procedure, at least 1 segment showed an under- or overestimation of >10%. The position of the catheter tip during administrations, as well as the tumor load of the liver segments, significantly influenced the disagreement., Conclusion: In current clinical practice, (99m)Tc-MAA distribution does not accurately predict final (90)Y activity distribution. Awareness of the importance of catheter positioning and adherence to specific recommendations may lead to optimization of individualized treatment planning based on pretreatment imaging.

Objective: To investigate clinical and laboratory toxicity in patients with unresectable liver metastases, treated with yttrium-90 radioembolization ((90)Y-RE)., Methods: Patients with liver metastases treated with (90)Y-RE, between February 1(st) 2009 and March 31(st) 2012, were included in this study. Clinical toxicity assessment was based on the reporting in patient's charts. Laboratory investigations at baseline and during a four-month follow-up were used to assess laboratory toxicity according to the Common Terminology Criteria for Adverse Events version 4.02. The occurrence of grade 3-4 laboratory toxicity was stratified according to treatment strategy (whole liver treatment in one session versus sequential sessions). Response assessment was performed at the level of target lesions, whole liver and overall response in accordance with RECIST 1.1 at 3- and 6 months post-treatment. Median time to progression (TTP) and overall survival were calculated by Kaplan-Meier analysis., Results: A total of 59 patients, with liver metastases from colorectal cancer (n = 30), neuroendocrine tumors (NET) (n = 6) and other primary tumors (n = 23) were included. Clinical toxicity after (90)Y-RE treatment was confined to grade 1-2 events, predominantly post-embolization symptoms. No grade 3-4 clinical toxicity was observed, whereas laboratory toxicity grade 3-4 was observed in 38% of patients. Whole liver treatment in one session was not associated with increased laboratory toxicity. Three-months disease control rates for target lesions, whole liver and overall response were 35%, 21% and 19% respectively. Median TTP was 6.2 months for target lesions, 3.3 months for the whole liver and 3.0 months for overall response. Median overall survival was 8.9 months., Conclusion: The risk of severe complications or grade 3-4 clinical toxicity in patients with liver metastases of various primary tumors undergoing (90)Y-RE is low. In contrast, laboratory toxicity grade 3-4 can be expected to occur in more than one-third of patients without any clinical signs of radiation induced liver disease.

Patients with malignant tumors originating from the biliary tree have a poor prognosis, since only a minority of tumors can be resected and most palliative regimens have shown only limited success. We present two patients with unresectable tumors, who were treated with trans-arterial (90)yttrium radioembolization: a patient with an infiltrating gallbladder carcinoma and a patient with an extensive intrahepatic cholangiocarcinoma. In both cases the treatment was technically feasible, effective in controlling tumor growth, and without significant side effects. In conclusion, the presented cases demonstrate the potential of (90)yttrium radioembolization as a palliative treatment option for malignant tumors of the biliary tree.

Background: Intra-arterial radioembolization with yttrium-90 microspheres ( 90Y-RE) is an increasingly used therapy for patients with unresectable liver malignancies. Over the last decade, radioactive holmium-166 poly(L-lactic acid) microspheres ( 166Ho-PLLA-MS) have been developed as a possible alternative to 90Y-RE. Next to high-energy beta-radiation, 166Ho also emits gamma-radiation, which allows for imaging by gamma scintigraphy. In addition, Ho is a highly paramagnetic element and can therefore be visualized by MRI. These imaging modalities are useful for assessment of the biodistribution, and allow dosimetry through quantitative analysis of the scintigraphic and MR images. Previous studies have demonstrated the safety of 166Ho-PLLA-MS radioembolization ( 166Ho-RE) in animals. The aim of this phase I trial is to assess the safety and toxicity profile of 166Ho-RE in patients with liver metastases., Methods: The HEPAR study (Holmium Embolization Particles for Arterial Radiotherapy) is a non-randomized, open label, safety study. We aim to include 15 to 24 patients with liver metastases of any origin, who have chemotherapy-refractory disease and who are not amenable to surgical resection. Prior to treatment, in addition to the standard technetium-99m labelled macroaggregated albumin ( 99mTc-MAA) dose, a low radioactive safety dose of 60-mg 166Ho-PLLA-MS will be administered. Patients are treated in 4 cohorts of 3-6 patients, according to a standard dose escalation protocol (20 Gy, 40 Gy, 60 Gy, and 80 Gy, respectively). The primary objective will be to establish the maximum tolerated radiation dose of 166Ho-PLLA-MS. Secondary objectives are to assess tumour response, biodistribution, performance status, quality of life, and to compare the 166Ho-PLLA-MS safety dose and the 99mTc-MAA dose distributions with respect to the ability to accurately predict microsphere distribution., Discussion: This will be the first clinical study on 166Ho-RE. Based on preclinical studies, it is expected that 166Ho-RE has a safety and toxicity profile comparable to that of 90Y-RE. The biochemical and radionuclide characteristics of 166Ho-PLLA-MS that enable accurate dosimetry calculations and biodistribution assessment may however improve the overall safety of the procedure.