Abstract Background Desmoid tumours describe a rare monoclonal, fibroblastic proliferation characterised by an often unpredictable clinical course. Surgery is one therapeutic option for progressing ...patients, except if mutilating and associated with considerable function loss. Different systemic treatment approaches have been investigated and promising results could be demonstrated using imatinib. Patients and methods We initiated a phase II trial within the German Interdisciplinary Sarcoma Group (GISG) evaluating imatinib to induce progression arrest in desmoid tumour patients being Response Evaluation Criteria in Solid Tumours (RECIST) progressive, not amenable to surgical resection with R0 intent or accompanied by unacceptable function loss (NCT01137916). Thirty-eight patients (median age 44 years range: 19–80; 68% female; 90% Eastern Cooperative Oncology Group (ECOG) performance status 0) were treated with a daily dose of 800 mg imatinib planned over 2 years. The progression arrest rate after 6 months of imatinib treatment (PAR6mo ) was the primary end-point. Patients showing disease progression under imatinib could be treated with nilotinib 800 mg daily. Accrual started in July 2010 in four GISG centres and finalised in September 2013. Results The final analysis for the primary end-point in the evaluable patients of the full analysis set revealed a PAR6mo of 65%. Subsequent progression arrest rates at 9, 12, 15, 18, 21 and 24 months were 65%, 59%, 53%, 53%, 50% and 45%, respectively. None of the patients died within the study observational period. Best reported response was seven partial responses at 21 months revealing an overall response rate of 19%. Eight patients treated with nilotinib demonstrated a PAR at 3 months of 88% (7/8); no more disease progressions occurred until end of study. In general imatinib adverse events were mild to moderate. Conclusions Imatinib induces sustained progression arrest in RECIST progressive desmoid tumour patients. In addition, nilotinib had the potential to stabilise desmoid tumour growth after treatment failure with imatinib.
Depression is a common, disabling condition for which psychological treatments, in particular cognitive behavioural therapies are recommended. Promising results in recent randomized trials have ...renewed interest in behavioural therapy. This systematic review sought to identify all randomized trials of behavioural therapy for depression, determine the effect of such interventions and examine any moderators of such effect.
Randomized trials of behavioural treatments of depression versus controls or other psychotherapies were identified using electronic database searches, previous reviews and reference lists. Data on symptom-level, recovery/dropout rate and study-level moderators (study quality, number of sessions, severity and level of training) were extracted and analysed using meta-analysis and meta-regression respectively.
Seventeen randomized controlled trials including 1109 subjects were included in this meta-analysis. A random-effects meta-analysis of symptom-level post-treatment showed behavioural therapies were superior to controls standardized mean difference (SMD) -0.70, 95% CI -1.00 to -0.39, k=12, n=459, brief psychotherapy (SMD -0.56, 95% CI -1.0 to -0.12, k=3, n=166), supportive therapy (SMD -0.75, 95% CI -1.37 to -0.14, k=2, n=45) and equal to cognitive behavioural therapy (SMD 0.08, 95% CI -0.14 to 0.30, k=12, n=476).
The results in this study indicate behavioural therapy is an effective treatment for depression with outcomes equal to that of the current recommended psychological intervention. Future research needs to address issues of parsimony of such interventions.
Although elevated plasma interleukin-8 (pIL-8) has been associated with poor outcome to immune checkpoint blockade
, this has not been comprehensively evaluated in large randomized studies. Here we ...analyzed circulating pIL-8 and IL8 gene expression in peripheral blood mononuclear cells and tumors of patients treated with atezolizumab (anti-PD-L1 monoclonal antibody) from multiple randomized trials representing 1,445 patients with metastatic urothelial carcinoma (mUC) and metastatic renal cell carcinoma. High levels of IL-8 in plasma, peripheral blood mononuclear cells and tumors were associated with decreased efficacy of atezolizumab in patients with mUC and metastatic renal cell carcinoma, even in tumors that were classically CD8
T cell inflamed. Low baseline pIL-8 in patients with mUC was associated with increased response to atezolizumab and chemotherapy. Patients with mUC who experienced on-treatment decreases in pIL-8 exhibited improved overall survival when treated with atezolizumab but not with chemotherapy. Single-cell RNA sequencing of the immune compartment showed that IL8 is primarily expressed in circulating and intratumoral myeloid cells and that high IL8 expression is associated with downregulation of the antigen-presentation machinery. Therapies that can reverse the impacts of IL-8-mediated myeloid inflammation will be essential for improving outcomes of patients treated with immune checkpoint inhibitors.
Objective: To examine the efficacy of a modular cognitive-behavioral therapy (CBT) protocol relative to treatment as usual (TAU) among children with high-functioning autism spectrum disorders (ASD) ...and clinically significant anxiety. Method: A total of 45 children (7-11 years of age) with high-functioning ASD and clinically significant anxiety were randomized to receive 16 sessions of weekly CBT or TAU for an equivalent duration. After screening, assessments were conducted at baseline, post-treatment, and 3-month follow-up. Raters were blind to treatment condition. Results: Youth receiving CBT showed substantial improvement relative to TAU on primary anxiety outcomes. Of 24 children randomized to the CBT arm, 18 (75%) were treatment responders, versus only 3 of 21 children (14%) in the TAU arm. Gains were generally maintained at 3-month follow-up for CBT responders. Conclusions: Relative to usual care, CBT adapted for anxious youth with high-functioning ASD demonstrates large effects in reducing anxiety symptoms. This study contributes to the growing literature supporting adapted CBT approaches for treating anxiety in youth with ASD. Clinical trial registration information--Cognitive-Behavioral Treatment for Anxiety Disorders in Children With Autism Spectrum Disorders; http://clinicaltrials.gov; NCT01178385. (Contains 1 figure and 3 tables.)
Janus kinase inhibitors (JAKi) have been approved for use in various immune-mediated inflammatory diseases. With five agents licensed, it was timely to summarise the current understanding of JAKi use ...based on a systematic literature review (SLR) on efficacy and safety.
Existing data were evaluated by a steering committee and subsequently reviewed by a 29 person expert committee leading to the formulation of a consensus statement that may assist the clinicians, patients and other stakeholders once the decision is made to commence a JAKi. The committee included patients, rheumatologists, a gastroenterologist, a haematologist, a dermatologist, an infectious disease specialist and a health professional. The SLR informed the Task Force on controlled and open clinical trials, registry data, phase 4 trials and meta-analyses. In addition, approval of new compounds by, and warnings from regulators that were issued after the end of the SLR search date were taken into consideration.
The Task Force agreed on and developed four general principles and a total of 26 points for consideration which were grouped into six areas addressing indications, treatment dose and comedication, contraindications, pretreatment screening and risks, laboratory and clinical follow-up examinations, and adverse events. Levels of evidence and strengths of recommendations were determined based on the SLR and levels of agreement were voted on for every point, reaching a range between 8.8 and 9.9 on a 10-point scale.
The consensus provides an assessment of evidence for efficacy and safety of an important therapeutic class with guidance on issues of practical management.
This document outlines recommendations for physiotherapy management for COVID-19 in the acute hospital setting. It includes: recommendations for physiotherapy workforce planning and preparation; a ...screening tool for determining requirement for physiotherapy; and recommendations for the selection of physiotherapy treatments and personal protective equipment. It is intended for use by physiotherapists and other relevant stakeholders in the acute care setting caring for adult patients with confirmed or suspected COVID-19.
The aim of the study was to compare 6-month efficacy and safety for treatment of vaginal dryness/genitourinary syndrome of menopause in women undergoing fractionated CO2 vaginal laser therapy to ...women using estrogen vaginal cream.
This multicenter, randomized trial compared fractionated CO2 laser to estrogen cream at 6 institutions. We included menopausal women with significant vaginal atrophy symptoms and we excluded women with prolapse below stage 2, recent pelvic surgery, prior mesh surgery, active genital infection, history of estrogen sensitive malignancy, and other autoimmune conditions. The primary outcome was the visual analog scale vaginal dryness score. Secondary outcomes included evaluation of vaginal atrophy, quality of life symptoms, assessment of sexual function, and urinary symptoms. Adverse events (AEs) and patient global impression of improvement (PGI-I) and satisfaction were also assessed.
Sixty-nine women were enrolled in this trial before enrollment was closed due to the Federal Drug Administration requiring the sponsor to obtain and maintain an Investigational Device Exemption. Of the 69 participants enrolled, 62 completed the 6-month protocol; 30 women were randomized to the laser and 32 to estrogen cream from June 2016 to September 2017. Demographics did not differ between groups except the laser group was less parous (0 range 0-4 vs 2 0-6, P = 0.04). On patient global impression, 85.8% of laser participants rated their improvement as "better or much better" and 78.5% reported being either "satisfied or very satisfied" compared to 70% and 73.3% in the estrogen group; this was not statistically different between groups. On linear regression, mean difference in female sexual function index scores was no longer statistically significant; and, vaginal maturation index scores remained higher in the estrogen group (adj P value 0.02); although, baseline and 6-month follow-up vaginal maturation index data were only available for 34 participants (16 laser, 18 estrogen).
At 6 months, fractionated CO2 vaginal laser and vaginal estrogen treatment resulted in similar improvement in genitourinary syndrome of menopause symptoms as well as urinary and sexual function. Overall, 70% to 80% of participants were satisfied or very satisfied with either treatment and there were no serious adverse events. : Video Summary:http://links.lww.com/MENO/A470.
Background
Cancer stem cells are associated with metastatic potential, treatment resistance, and poor patient prognosis. Distant recurrence remains the major cause of mortality in rectal cancer ...patients with preoperative chemoradiotherapy (CRT). We investigated the role of three stem cell markers (
CD133
,
OCT4
, and
SOX2
) in rectal cancer and evaluated the association between these gene levels and clinical outcome in rectal cancer patients with preoperative CRT.
Methods
Thirty-three patients with rectal cancer underwent preoperative CRT. Total RNAs of rectal cancer cells before and after CRT were isolated. Residual cancer cells after CRT were obtained from formalin-fixed paraffin-embedded (FFPE) specimens using microdissection. The expression levels of three stem cell genes were measured using real-time reverse-transcription polymerase chain reaction (RT-PCR). The association between these gene levels and radiation was evaluated using colon cancer cell lines. Immunohistochemical staining of these markers after CRT was also investigated.
Results
There were significant positive correlations among the three genes after CRT. Patients who developed distant recurrence had higher levels of the three genes compared with those without recurrence in residual cancer after CRT. These elevated gene levels were significantly associated with poor disease-free survival. The radiation caused upregulation of these gene levels in LoVo and SW480 in vitro. Immunohistochemically, CD133 staining was observed in not only luminal surface but also cytoplasm.
Conclusions
Expression of CD133, OCT4, and SOX2 may predict distant recurrence and poor prognosis of rectal cancer patients treated with preoperative CRT. Correlations among these genes may be associated with tumor regrowth and metastatic relapse after CRT.
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