Neuroendocrine (NE) cancers are a diverse group of neoplasms typically diagnosed and treated on the basis of their site of origin. This Perspective focuses on advances in our understanding of the ...tumorigenesis and treatment of poorly differentiated neuroendocrine tumors. Recent evidence from sequencing indicates that, although neuroendocrine tumors can arise de novo, they can also develop as a result of lineage plasticity in response to pressure from targeted therapies. We discuss the shared genomic alterations of these tumors independently of their site of origin, and we explore potential therapeutic strategies on the basis of recent biological findings.
Berlin Electropolisties the German discourse on nervousness in the late nineteenth and early twentieth centuries to Berlin's transformation into a capital of the second industrial revolution. ...Focusing on three key groups-railway personnel, soldiers, and telephone operators-Andreas Killen traces the emergence in the 1880s and then later decline of the belief that modernity caused nervous illness. During this period, Killen explains, Berlin became arguably the most advanced metropolis in Europe. A host of changes, many associated with breakthroughs in technologies of transportation, communication, and leisure, combined to radically alter the shape and tempo of everyday life in Berlin. The resulting consciousness of accelerated social change and the shocks and afflictions that accompanied it found their consummate expression in the discourse about nervousness. Wonderfully researched and clearly written, this book offers a wealth of new insights into the nature of the modern metropolis, the psychological aftermath of World War I, and the operations of the German welfare state. Killen also explores cultural attitudes toward electricity, the evolution of psychiatric thought and practice, and the status of women workers in Germany's rapidly industrializing economy. Ultimately, he argues that the backlash against the welfare state that occurred during the late Weimar Republic brought about the final decoupling of modernity and nervous illness.
BACKGROUND:The population-based Surveillance, Epidemiology, and End Results (SEER) registries collect information on first-course treatment, including surgery, chemotherapy, radiation therapy, and ...hormone therapy. However, the SEER program does not release data on chemotherapy or hormone therapy due to uncertainties regarding data completeness. Activities are ongoing to investigate the opportunity to supplement SEER treatment data with other data sources.
METHODS:Using the linked SEER-Medicare data, we examined the validity of the SEER data to identify receipt of chemotherapy and radiation therapy among those aged 65 and older diagnosed from 2000 to 2006 with bladder, female breast, colorectal, lung, ovarian, pancreas, or prostate cancer and hormone therapy among men diagnosed with prostate cancer at age 65 or older. Treatment collected by SEER was compared with treatment as determined by Medicare claims, using Medicare claims as the gold standard. The κ, sensitivity, specificity, positive predictive values, and negative predictive values were calculated for the receipt of each treatment modality.
RESULTS:The overall sensitivity of SEER data to identify chemotherapy, radiation, and hormone therapy receipt was moderate (68%, 80%, and 69%, respectively) and varied by cancer site, stage, and patient characteristics. The overall positive predictive value was high (>85%) for all treatment types and cancer sites except chemotherapy for prostate cancer.
CONCLUSIONS:SEER data should not generally be used for comparisons of treated and untreated individuals or to estimate the proportion of treated individuals in the population. Augmenting SEER data with other data sources will provide the most accurate treatment information.
Purpose
Talimogene laherparepvec (T-VEC) is an oncolytic immunotherapy designed to induce tumor regression of injected lesions through direct lytic effects, and of uninjected lesions through ...induction of systemic antitumor immunity. In this study, we describe the patterns and time course of response to T-VEC from the phase III OPTiM trial of 436 patients with unresected stages IIIB–IV melanoma.
Methods
Lesion-level response analyses were performed based on the type of lesion (injected or uninjected cutaneous, subcutaneous, or nodal lesions; or visceral lesions uninjected), and the best percentage change from baseline of the sum of products of the longest diameters was calculated. Patients randomized to T-VEC (
n
= 295) who experienced a durable response (continuous partial or complete response for ≥6 months) were evaluated for progression prior to response (PPR), defined as the appearance of a new lesion or >25 % increase in total baseline tumor area.
Results
T-VEC resulted in a decrease in size by ≥50 % in 64 % of injected lesions (
N
= 2116), 34 % of uninjected non-visceral lesions (
N
= 981), and 15 % of visceral lesions (
N
= 177). Complete resolution of lesions occurred in 47 % of injected lesions, 22 % of uninjected non-visceral lesions, and 9 % of visceral lesions. Of 48 patients with durable responses, 23 (48 %) experienced PPR, including 14 who developed new lesions only. No difference in overall survival was observed, and median duration of response was not reached in patients with PPR versus those without PPR.
Conclusions
Responses in uninjected lesions provide validation of T-VEC-induced systemic immunotherapeutic effects against melanoma. PPR did not negatively impact the clinical effectiveness of T-VEC.
Pine bark (Pinus spp.) extract is rich in bioflavonoids, predominantly proanthocyanidins, which are antioxidants. Commercially-available extract supplements are marketed for preventing or treating ...various chronic conditions associated with oxidative stress. This is an update of a previously published review.
To assess the efficacy and safety of pine bark extract supplements for treating chronic disorders.
We searched three databases and three trial registries; latest search: 30 September 2019. We contacted the manufacturers of pine bark extracts to identify additional studies and hand-searched bibliographies of included studies.
Randomised controlled trials (RCTs) evaluating pine bark extract supplements in adults or children with any chronic disorder.
Two authors independently assessed trial eligibility, extracted data and assessed risk of bias. Where possible, we pooled data in meta-analyses. We used GRADE to evaluate the certainty of evidence. Primary outcomes were participant- and investigator-reported clinical outcomes directly related to each disorder and all-cause mortality. We also assessed adverse events and biomarkers of oxidative stress.
This review included 27 RCTs (22 parallel and five cross-over designs; 1641 participants) evaluating pine bark extract supplements across 10 chronic disorders: asthma (two studies; 86 participants); attention deficit hyperactivity disorder (ADHD) (one study; 61 participants), cardiovascular disease (CVD) and risk factors (seven studies; 338 participants), chronic venous insufficiency (CVI) (two studies; 60 participants), diabetes mellitus (DM) (six studies; 339 participants), erectile dysfunction (three studies; 277 participants), female sexual dysfunction (one study; 83 participants), osteoarthritis (three studies; 293 participants), osteopenia (one study; 44 participants) and traumatic brain injury (one study; 60 participants). Two studies exclusively recruited children; the remainder recruited adults. Trials lasted between four weeks and six months. Placebo was the control in 24 studies. Overall risk of bias was low for four, high for one and unclear for 22 studies. In adults with asthma, we do not know whether pine bark extract increases change in forced expiratory volume in one second (FEV
) % predicted/forced vital capacity (FVC) (mean difference (MD) 7.70, 95% confidence interval (CI) 3.19 to 12.21; one study; 44 participants; very low-certainty evidence), increases change in FEV
% predicted (MD 7.00, 95% CI 0.10 to 13.90; one study; 44 participants; very low-certainty evidence), improves asthma symptoms (risk ratio (RR) 1.85, 95% CI 1.32 to 2.58; one study; 60 participants; very low-certainty evidence) or increases the number of people able to stop using albuterol inhalers (RR 6.00, 95% CI 1.97 to 18.25; one study; 60 participants; very low-certainty evidence). In children with ADHD, we do not know whether pine bark extract decreases inattention and hyperactivity assessed by parent- and teacher-rating scales (narrative synthesis; one study; 57 participants; very low-certainty evidence) or increases the change in visual-motoric coordination and concentration (MD 3.37, 95% CI 2.41 to 4.33; one study; 57 participants; very low-certainty evidence). In participants with CVD, we do not know whether pine bark extract decreases diastolic blood pressure (MD -3.00 mm Hg, 95% CI -4.51 to -1.49; one study; 61 participants; very low-certainty evidence); increases HDL cholesterol (MD 0.05 mmol/L, 95% CI -0.01 to 0.11; one study; 61 participants; very low-certainty evidence) or decreases LDL cholesterol (MD -0.03 mmol/L, 95% CI -0.05 to 0.00; one study; 61 participants; very low-certainty evidence). In participants with CVI, we do not know whether pine bark extract decreases pain scores (MD -0.59, 95% CI -1.02 to -0.16; one study; 40 participants; very low-certainty evidence), increases the disappearance of pain (RR 25.0, 95% CI 1.58 to 395.48; one study; 40 participants; very low-certainty evidence) or increases physician-judged treatment efficacy (RR 4.75, 95% CI 1.97 to 11.48; 1 study; 40 participants; very low-certainty evidence). In type 2 DM, we do not know whether pine bark extract leads to a greater reduction in fasting blood glucose (MD 1.0 mmol/L, 95% CI 0.91 to 1.09; one study; 48 participants;very low-certainty evidence) or decreases HbA1c (MD -0.90 %, 95% CI -1.78 to -0.02; 1 study; 48 participants; very low-certainty evidence). In a mixed group of participants with type 1 and type 2 DM we do not know whether pine bark extract decreases HbA1c (MD -0.20 %, 95% CI -1.83 to 1.43; one study; 67 participants; very low-certainty evidence). In men with erectile dysfunction, we do not know whether pine bark extract supplements increase International Index of Erectile Function-5 scores (not pooled; two studies; 147 participants; very low-certainty evidence). In women with sexual dysfunction, we do not know whether pine bark extract increases satisfaction as measured by the Female Sexual Function Index (MD 5.10, 95% CI 3.49 to 6.71; one study; 75 participants; very low-certainty evidence) or leads to a greater reduction of pain scores (MD 4.30, 95% CI 2.69 to 5.91; one study; 75 participants; very low-certainty evidence). In adults with osteoarthritis of the knee, we do not know whether pine bark extract decreases composite Western Ontario and McMaster Universities Osteoarthritis Index scores (MD -730.00, 95% CI -1011.95 to -448.05; one study; 37 participants; very low-certainty evidence) or the use of non-steroidal anti-inflammatory medication (MD -18.30, 95% CI -25.14 to -11.46; one study; 35 participants; very low-certainty evidence). We do not know whether pine bark extract increases bone alkaline phosphatase in post-menopausal women with osteopenia (MD 1.16 ug/L, 95% CI -2.37 to 4.69; one study; 40 participants; very low-certainty evidence). In individuals with traumatic brain injury, we do not know whether pine bark extract decreases cognitive failure scores (MD -2.24, 95% CI -11.17 to 6.69; one study; 56 participants; very low-certainty evidence) or post-concussion symptoms (MD -0.76, 95% CI -5.39 to 3.87; one study; 56 participants; very low-certainty evidence). For most comparisons, studies did not report outcomes of hospital admissions or serious adverse events.
Small sample sizes, limited numbers of RCTs per condition, variation in outcome measures, and poor reporting of the included RCTs mean no definitive conclusions regarding the efficacy or safety of pine bark extract supplements are possible.
Summary Objectives To describe the natural course of distant metastases (DMs) following radiotherapy (RT) or chemoradiotherapy (CRT) in HPV(+) oropharyngeal carcinoma (OPC). Methods OPC treated with ...RT/CRT from 1/1/2000 to 5/31/2010 were reviewed. The natural course of DM were compared between HPV(+) and HPV(−) cohorts. Results Median follow-up was 3.9 years. The DM rate were similar (11% vs. 15% at 3-years, p = 0.25) between the HPV(+) ( n = 457) vs. the HPV(−) ( n = 167) cases. While almost all (24/25) HPV(−) DM occurred within 2-years following RT (1 was at 2.1 years), 7/54 (13%) of HPV(+) DM were detected beyond 3 years (up to 5.3 years). Disseminating to >2 organs occurred in 18 (33%) HPV(+) vs. none in HPV(−). Post-DM survival rates were 11% vs. 4% at 2-years ( p = 0.02) for the HPV(+) vs. HPV(−) cases respectively. 5/6 HPV(+) with lung oligo-metastasis were still alive with stable disease beyond 2-years after salvage procedures for DM (chemotherapy: 3; surgical resection: 2; radiotherapy: 1). Conclusions Although DM rates are similar, the natural course of HPV(+) DM differs from that of HPV(−) patients: it may occur after a longer interval, often with a “disseminating” phenotype, and a small number may have prolonged survival after salvage for DM.
Systematic literature review.
To assess the toxicity, common radiation doses, and local control (LC) rates of radiation therapy for chordoma of the spine and sacrum and identify the difference in LC ...and toxicity between adjuvant, salvage, and primary therapy using radiation.
Chordoma of the spine is typically a low-grade malignant tumor thought to be relatively radioresistant with a high rate of local recurrence and the potential for metastases. Improved results of modern radiation therapy in the treatment of chordoma support exploration of its role in the management of primary/de novo chordoma or recurrent chordoma.
We conducted a systematic literature review using PubMed and Embase databases to assess information available regarding the toxicity, LC rates, and overall survival (OS) rates for adjuvant, salvage, and primary radiation therapy for spinal and sacral chordoma.
A total of 40 articles were reviewed. Evidence quality was low or very low. The highest rates of LC and OS were with early adjuvant RT for primary/de novo disease. Salvage RT for recurrent disease has very small cohorts and thus strong conclusions were not able be made.
The use of pre- and/or post-operative photon image-guided radiotherapy (IGRT), proton or carbon ion therapy should be considered for patients undergoing surgery for the treatment of primary and recurrent chordomas in the mobile spine and sacrum, since these RT modalities may improve local control. Preoperative evaluation by the surgeon and radiation oncologist should be used to formulate a cohesive treatment plan.The use of photon IGRT or carbon ion therapy as the primary treatment of chordoma, when currently in its developmental stage, shows promise and requires clear delineation of toxicity profile and long-term local control.
2.
The aim of this updated statement is to provide comprehensive and timely evidence-based recommendations on the prevention of ischemic stroke among survivors of ischemic stroke or transient ischemic ...attack. Evidence-based recommendations are included for the control of risk factors, interventional approaches for atherosclerotic disease, antithrombotic treatments for cardioembolism, and the use of antiplatelet agents for noncardioembolic stroke. Further recommendations are provided for the prevention of recurrent stroke in a variety of other specific circumstances, including arterial dissections; patent foramen ovale; hyperhomocysteinemia; hypercoagulable states; sickle cell disease; cerebral venous sinus thrombosis; stroke among women, particularly with regard to pregnancy and the use of postmenopausal hormones; the use of anticoagulation after cerebral hemorrhage; and special approaches to the implementation of guidelines and their use in high-risk populations.
•Virtual reality exposure therapy shows a large effect size compared to control conditions.•Virtual reality exposure therapy did not show significant differences from in vivo exposure therapy.•Effect ...sizes for disorder types were relatively consistent.
Trials of virtual reality exposure therapy (VRET) for anxiety-related disorders have proliferated in number and diversity since our previous meta-analysis that examined 13 total trials, most of which were for specific phobias (Powers & Emmelkamp, 2008). Since then, new trials have compared VRET to more diverse anxiety and related disorders including social anxiety disorder (SAD), posttraumatic stress disorder (PTSD), and panic disorder (PD) with and without agoraphobia. With the availability of this data, it is imperative to re-examine the efficacy of VRET for anxiety. A literature search for randomized controlled trials of VRET versus control or in vivo exposure yielded 30 studies with 1057 participants. Fourteen studies tested VRET for specific phobias, 8 for SAD or performance anxiety, 5 for PTSD, and 3 for PD. A random effects analysis estimated a large effect size for VRET versus waitlist (g = 0.90) and a medium to large effect size for VRET versus psychological placebo conditions (g = 0.78). A comparison of VRET and in vivo conditions did not show significantly different effect sizes (g = −0.07). These findings were relatively consistent across disorders. A meta-regression analysis revealed that larger sample sizes were associated with lower effect sizes in VRET versus control comparisons (β = −0.007, p < 0.05). These results indicate that VRET is an effective and equal medium for exposure therapy.
PDF
