Prostate high dose-rate brachytherapy as monotherapy for low and intermediate-risk prostate cancer: Efficacy results from a randomized phase II clinical trial of one fraction of 19 Gy or two fractions of 13.5 Gy: A 9-year update.

BACKGROUND AND PURPOSE: High dose-rate (HDR) brachytherapy as a monotherapy is an accepted treatment for localized prostate cancer, but the optimal dose and fractionation schedule remain unknown. We report on the efficacy of a randomized Phase II trial comparing HDR monotherapy delivered as 27 Gy in 2 fractions vs. 19 Gy in 1 fraction with a median follow-up of 9 years. MATERIALS AND METHODS: Enrolled patients had low or intermediate-risk disease, <60 cc prostate volume and no androgen deprivation use. Patients were randomized to 27 Gy in 2 fractions delivered one week apart vs a single fraction of 19 Gy. RESULTS: 170 patients were randomized: median age 65 years, median follow-up 107 months and median baseline PSA 6.35 ng/ml. NCCN risk categories comprised low (19 %), favourable (51 %), and unfavourable intermediate risk (30 %). The median PSA at 8 years was 0.08 ng/ml in the 2-fraction arm vs. 0.89 ng/ml in the single-fraction arm. The cumulative incidence of local failure at 8 years was 11.2 % in the 2-fraction arm vs. 35.9 % in the single-fraction arm (p < 0.001). The incidence of distant failure at 8 years was 3.8 % in the 2-fraction arm and 2.5 % in the single-fraction arm (p = 0.6). CONCLUSIONS: HDR monotherapy delivered in two fractions of 13.5 Gy demonstrated a persistent cancer control rate at 8 years and was well-tolerated. Single-fraction monotherapy yielded poor oncologic control and is not recommended. These findings contribute to the ongoing discourse on optimal HDR monotherapy strategies for low and intermediate-risk prostate cancer.

Radical Spin Polarization and Magnetosensitivity from Reversible Energy Transfer.

Molecular spins provide potential building units for future quantum information science and spintronic technologies. In particular, doublet (S = 1/2) and triplet (S = 1) molecular spin states have the potential for excellent optical and spin properties for these applications if useful photon-spin mechanisms at room temperature can be devised. Here we explore the potential of exploiting reversible energy transfer between triplet and doublet states to establish magnetosensitive luminescence and spin polarization. We investigate the dependence of the photon-spin mechanism on the magnitude and sign of the exchange interaction between the doublet and triplet spin components in amorphous and crystalline model systems. The design of a magnetic field inclination sensor is proposed from understanding the required "structure" (spin interactions) to "function" (magnetosensitivity).

Presentation and Outcome of Patients with Multiple Myeloma (MM), Single Centre Experience from Windsor Essex Regional Cancer Centre.

Introduction: Outcomes for patients with multiple myeloma has significantly improved through the years. This is mainly related to the use of novel agents. Methods: This is a retrospective study that reviewed presentation and outcome of 139 patients with multiple myeloma at the Windsor Essex Regional Cancer Centre from Jan. 1, 2015 to Dec. 31, 2019. Median age was 71 years and most patients had higher risk disease (65.5% either R ISS stage II or III). 30% had high risk FISH for myeloma including del.17P, t (4:14), t (14:16) and Gain (1q21). In terms of presentation, 38.8% had anemia (hemoglobin <100g/L), 18.7% had hypercalcemia, 74.1% had skeletal lytic lesions, 38.8% had pathologic fracture and 17.3% had plasmacytoma. Results: Almost all (92%) of the patients were treated using at least one novel agent (proteasome inhibitor or immunomodulators [ImiDs]). Cyclophosphamide, bortezomib, and dexamethasone (CyBorD) was the most used treatment regimen (48.9%) followed by bortezomib, melphalan and prednisone (BMP) at 28.8% and lenalidomide, dexamethasone (LenDex) at 14.4%. With respect to response to therapy, 51.8% had at least Very good partial response (VGPR), while 9.4% had progressive disease. 33% had autologous stem cell transplant. After a median follow up of 2.4 years, median overall survival was 3.7 years. 2 years overall survival and relapse-free survival were 70% and 83%, respectively. Discussion: Our study showed comparable outcome for patients with multiple myeloma despite older age and higher risk disease. Outcome is expected to improve with the introduction of more novel agents.

Technical note: The migration distance - a unidirectional distance metric for region-of-interest comparisons.

BACKGROUND: The radiotherapy process relies on several metrics in determining a notion of "distance" from one three-dimensional region-of-interest (ROI) to another. The majority are symmetric (or commutative) and do not contain information pertaining to directionality. Growth versus regression, for example, is not inherently distinguished by these metrics. PURPOSE: The purpose of this work was to formalize a unidirectional distance metric, motivated by radiotherapy margin concepts, which we term the migration distance. Informally, the migration distance from ROI X to Y is the minimum isotropic expansion of X such that Y is completely encompassed by the expansion. If Y is contained within X, the migration distance is negative with magnitude equal to the maximum isotropic contraction of X such that Y remains contained within contraction. The metric is demonstrated by quantifying glioblastoma interfraction target changes. METHODS: An explicit mathematical formulation of the migration distance is presented and contrasted with the related Hausdorff distance. The results are demonstrated for the gross tumor volume (GTV) dynamics of a glioblastoma cohort consisting of 111 patients that underwent standard chemoradiotherapy with offline MR imaging at planning, fraction 10, fraction 20, and 1-month post radiotherapy. RESULTS: The mean ± SD of the GTV migration distance relative to planning was 5.9 ± 3.9 mm at fraction 10, 6.2 ± 4.4 mm at fraction 20, and 7.9 ± 7.1 mm at 1-month post radiotherapy. The maximum GTV migration distance across all patients at the same timepoints was 20.4, 20.7, and 45.5 mm, respectively. CONCLUSIONS: We have proposed and demonstrated a unidirectional distance metric. The migration distance may have applications in the quantification of anatomical changes, planning target volume designs, and dosimetric radiotherapy plan assessment.

Blood pH Analysis in Combination with Molecular Medical Tools in Relation to COVID-19 Symptoms.

The global outbreak of SARS-CoV-2/COVID-19 provided the stage to accumulate an enormous biomedical data set and an opportunity as well as a challenge to test new concepts and strategies to combat the pandemic. New research and molecular medical protocols may be deployed in different scientific fields, e.g., glycobiology, nanopharmacology, or nanomedicine. We correlated clinical biomedical data derived from patients in intensive care units with structural biology and biophysical data from NMR and/or CAMM (computer-aided molecular modeling). Consequently, new diagnostic and therapeutic approaches against SARS-CoV-2 were evaluated. Specifically, we tested the suitability of incretin mimetics with one or two pH-sensitive amino acid residues as potential drugs to prevent or cure long-COVID symptoms. Blood pH values in correlation with temperature alterations in patient bodies were of clinical importance. The effects of biophysical parameters such as temperature and pH value variation in relation to physical-chemical membrane properties (e.g., glycosylation state, affinity of certain amino acid sequences to sialic acids as well as other carbohydrate residues and lipid structures) provided helpful hints in identifying a potential Achilles heel against long COVID. In silico CAMM methods and in vitro NMR experiments (including 31P NMR measurements) were applied to analyze the structural behavior of incretin mimetics and SARS-CoV fusion peptides interacting with dodecylphosphocholine (DPC) micelles. These supramolecular complexes were analyzed under physiological conditions by 1H and 31P NMR techniques. We were able to observe characteristic interaction states of incretin mimetics, SARS-CoV fusion peptides and DPC membranes. Novel interaction profiles (indicated, e.g., by 31P NMR signal splitting) were detected. Furthermore, we evaluated GM1 gangliosides and sialic acid-coated silica nanoparticles in complex with DPC micelles in order to create a simple virus host cell membrane model. This is a first step in exploring the structure-function relationship between the SARS-CoV-2 spike protein and incretin mimetics with conserved pH-sensitive histidine residues in their carbohydrate recognition domains as found in galectins. The applied methods were effective in identifying peptide sequences as well as certain carbohydrate moieties with the potential to protect the blood-brain barrier (BBB). These clinically relevant observations on low blood pH values in fatal COVID-19 cases open routes for new therapeutic approaches, especially against long-COVID symptoms.

The Cognitive Daisy (COG-D) for improving care for residents with dementia in care homes: protocol of a feasibility RCT.

BACKGROUND: Cognitive problems associated with dementia affect a large proportion of older adults living in residential care. Knowledge of cognitive impairments is important for providing person-centred care (PCC). The impact of specific cognitive impairments on residents' needs is often overlooked in dementia training and information about residents' individual cognitive profiles are frequently underspecified in care-plans, potentially undermining the delivery of PCC. This can lead to reduced resident quality of life and increased distressed behaviours-a major cause of staff stress and burnout. The COG-D package was developed to fill this gap. Daisies provide a visual representation of a resident's individual cognitive strengths and weaknesses in a colourful flower (Daisy) representing five cognitive domains. By viewing a resident's Daisy, care-staff can flexibly adjust in-the-moment care-decisions and can consult Daisies in care-plans for longer-term planning. The primary aim of this study is to assess the feasibility of implementing the COG-D package in residential care homes for older adults. METHODS/DESIGN: This 24-month feasibility cluster randomized controlled trial involves a 6-month intervention of the use of Cognitive Daisies in 8-10 residential care homes for older adults after training of care staff on the use of Cognitive Daisies in daily care (basic training) and on conducting the COG-D assessments with residents (advanced training). The key feasibility outcomes include % residents recruited, % COG-D assessments completed, and % staff completing the training. Candidate outcome measures for residents and staff will be obtained at baseline, and at 6 and 9 months post-randomization. COG-D assessments of residents will be repeated 6 months after the first assessment. A process evaluation will assess intervention implementation and barriers and facilitators to this through care-plan audits, interviews and focus groups with staff, residents, and relatives. Feasibility outcomes will be analysed against progression criteria to a full trial. DISCUSSION: The results of this study will provide important information about the feasibility of using COG-D in care homes and will inform the design of a future large-scale cluster RCT to assess the effectiveness and cost-effectiveness of the COG-D intervention in care homes. TRIAL REGISTRATION: This trial was registered on 28/09/2022 (ISRCTN15208844) and is currently open to recruitment.

Testing the relationship between lateralization on sequence-based motor tasks and language laterality using an online battery.

ABSTRACTStudies have highlighted an association between motor laterality and speech production laterality. It is thought that common demands for sequential processing may underlie this association. However, most studies in this area have relied on relatively small samples and have infrequently explored the reliability of the tools used to assess lateralization. We, therefore, established the validity and reliability of an online battery measuring sequence-based motor laterality and language laterality before exploring the associations between laterality indices on language and motor tasks. The online battery was completed by 621 participants, 52 of whom returned to complete the battery a second time. The three motor tasks included in the battery showed good between-session reliability (r ≥ .78) and were lateralized in concordance with hand preference. The novel measure of speech production laterality was left lateralized at population level as predicted, but reliability was less satisfactory (r = .62). We found no evidence of an association between sequence-based motor laterality and language laterality. Those with a left-hand preference were more strongly lateralized on motor tasks requiring midline crossing; this effect was not observed in right-handers. We conclude that there is little evidence of the co-lateralization of language and sequence-based motor skill on this battery.

Dynamic Contrast-enhanced CT to Evaluate Early Response in Neuroendocrine Liver Metastases Treated With Everolimus and Radiation.

BACKGROUND/AIM: The optimal method to evaluate response of neuroendocrine liver metastases (NELM) to radiation treatment (RT) is unknown; tumor perfusion parameters were evaluated by using dynamic contrast-enhanced computed tomography (DCE-CT) to correlate with efficacy in a prospective pilot study utilizing everolimus with radiotherapy for NELM. PATIENTS AND METHODS: Fourteen patients with progressive NELM received everolimus for 28 days prior to, concurrent with, and 14 days following radiation. Patients had a DCE-CT at baseline (t0), prior to radiation (t1) and 7 days after radiation (t2). Per lesion response was evaluated per standard response evaluation criteria (RECIST v1.1). Median statistics of the perfusion parameters were tabulated and included: blood flow (BF), blood volume (BV), and permeability (PS). Correlations between the parameters and the maximum percent change in size of the NELM at 12-months were explored. NELM not treated with radiation served as an internal control. RESULTS: Twenty-one treated NELM in 10 patients were evaluable. Compared to t0, BV increased at t1 (median 11%, range -15 to +37%, p=0.59), and then decreased significantly at t2 (median -8.4%, range -29 to +5.4%, p<0.03). A trend of increased BV in internal controls at each time point supports that the observed effect is due to radiation. Conventional objective response rate was 33%; no progression was seen within 12-months. CONCLUSION: Changes in DCE-CT were observed in patients receiving everolimus and radiation for NELM, with BV decreasing significantly following radiotherapy. Given the challenges in assessing response in NELM using traditional response evaluation criteria in any context, DCE-CT appears to be a promising modality.

Inconsistent language lateralisation - Testing the dissociable language laterality hypothesis using behaviour and lateralised cerebral blood flow.

BACKGROUND: Most people have strong left-brain lateralisation for language, with a minority showing right- or bilateral language representation. On some receptive language tasks, however, lateralisation appears to be reduced or absent. This contrasting pattern raises the question of whether and how language laterality may fractionate within individuals. Building on our prior work, we postulated (a) that there can be dissociations in lateralisation of different components of language, and (b) these would be more common in left-handers. A subsidiary hypothesis was that laterality indices will cluster according to two underlying factors corresponding to whether they involve generation of words or sentences, versus receptive language. METHODS: We tested these predictions in two stages: At Step 1 an online laterality battery (Dichotic listening, Rhyme Decision and Word Comprehension) was given to 621 individuals (56% left-handers); At Step 2, functional transcranial Doppler ultrasound (fTCD) was used with 230 of these individuals (51% left-handers). 108 left-handers and 101 right-handers gave useable data on a battery of three language generation and three receptive language tasks. RESULTS: Neither the online nor fTCD measures supported the notion of a single language laterality factor. In general, for both online and fTCD measures, tests of language generation were left-lateralised. In contrast, the receptive tasks were at best weakly left-lateralised or, in the case of Word Comprehension, slightly right-lateralised. The online measures were only weakly correlated, if at all, with fTCD measures. Most of the fTCD measures had split-half reliabilities of at least .7, and showed a distinctive pattern of intercorrelation, supporting a modified two-factor model in which Phonological Decision (generation) and Sentence Decision (reception) loaded on both factors. The same factor structure fitted data from left- and right-handers, but mean scores on the two factors were lower (less left-lateralised) in left-handers. CONCLUSIONS: There are at least two factors influencing language lateralization in individuals, but they do not correspond neatly to language generation and comprehension. Future fMRI studies could help clarify how far they reflect activity in specific brain regions.

Effects of onabotulinumtoxin A in patients concurrently diagnosed with chronic migraine encephalalgia and temporomandibular disorders: A retrospective case series.

OBJECTIVE: Chronic migraine encephalalgia (CME) with concomitant temporomandibular disorder (TMD) is a serious illness with limited effective treatment options. This study explores the effectiveness of onabotulinumtoxinA (BtxA) as an adjunct therapeutic to TMJ arthroscopy in the relief of CME. METHODS: A retrospective cohort study of patients receiving TMJ arthroscopy, with or without BtxA injections for CME, was conducted. Variables assessed include pain using a visual analog scale (VAS), maximal incisal opening (MIO), muscle soreness, and headache frequency and duration. RESULTS: Sixty patients (44 BtxA, 16 Control), consisting of 56 (93.3%) females, met inclusion criteria. A significant reduction in pain is reported with patients receiving BtxA (p < 0.0001) on VAS as compared to Control group. BtxA treatment also significantly reduced headache frequency and duration (p < 0.05). CONCLUSION: These results support the use of adjunctive BtxA treatment with arthroscopy for the treatment of CME in the context of TMD.

Stereotactic Ablative Radiotherapy for the Management of Liver Metastases from Neuroendocrine Neoplasms: A Preliminary Study.

INTRODUCTION: Liver metastases are common in patients with neuroendocrine neoplasms. The role of stereotactic ablative radiotherapy (SABR) is not well understood in this population. OBJECTIVE: The objective of this study was to evaluate the safety and efficacy of SABR in treating well-differentiated neuroendocrine liver metastases (WD-NELM). METHODS: A retrospective review of patients with WD-NELM treated with SABR was conducted between January 2015 and July 2019. Demographic, treatment, and clinical/radiographic follow-up data were abstracted. RECIST 1.1 criteria were applied to each individual target to evaluate the response to treatment. Local control (LC) and progression-free survival (PFS) were determined using the Kaplan-Meier methodology. Toxicity was reported according to the CTCAE v5.0. RESULTS: Twenty-five patients with a total of 53 liver metastases treated with SABR were identified. Most patients (68%) had midgut tumors, were grade 2 (80%), and had high-volume intrahepatic and/or extrahepatic disease (76%). The median number of liver metastases treated was 2, with a median size of 2.5 cm. The median radiation dose delivered was 50 Gy/5 fractions. The median follow-up was 14 months; 24 of the 25 patients were alive at the time of analysis. The objective response rate was 32%, with improvement or stability in 96% of lesions treated. The median time to best response was 9 months. The 1-year LC and PFS were 92 and 44%, respectively. No grade 3/4 acute or late toxicity was identified. CONCLUSIONS: Liver SABR is a safe and promising means of providing LC for WD-NELM. This treatment modality should be evaluated in selected patients in concert with strategies to manage systemic disease.

Hypofractionated Stereotactic Radiation Therapy for Intact Brain Metastases in 5 Daily Fractions: Effect of Dose on Treatment Response.

PURPOSE: Multileaf collimator (MLC) linear accelerator (Linac)-based hypofractionated stereotactic radiation therapy (HSRT) is increasingly used not only for large brain metastases or those adjacent to critical structures but also for those metastases that would otherwise be considered for single-fraction radiosurgery (SRS). However, data on outcomes in general are limited, and there is a lack of understanding regarding optimal dosing. Our aim was to report mature image-based outcomes for MLC-Linac HSRT with a focus on clinical and dosimetric factors associated with local failure (LF). METHODS AND MATERIALS: A total of 220 patients with 334 brain metastases treated with HSRT were identified. All patients were treated using a 5-fraction daily regimen and were followed with clinical evaluation and volumetric magnetic resonance imaging every 2 to 3 months. Overall survival and progression-free survival were calculated using the Kaplan-Meier method, with LF determined using Fine and Gray's competing risk method. Predictive factors were identified using Cox regression multivariate analysis. RESULTS: Median follow-up was 10.8 months. Median size of treated metastasis was 1.9 cm; 60% of metastases were <2 cm in size. The median total dose was 30 Gy in 5 fractions; 36% of the cohort received <30 Gy. The median time to LF and 12-month cumulative incidence of LF was 8.5 months and 23.8%, respectively. Median time to death and 12-month overall survival rates were 11.8 months and 48.2%, respectively. Fifty-two metastases (15.6%) had an adverse radiation effect, of which 32 (9.5%) were symptomatic necrosis. Multivariable analysis identified worse LF in patients who received a total dose of <30 Gy (hazard ratio, 1.62; P = .03), with LF at 6 and 12 months of 13% and 33% for patients treated with <30 Gy versus 5% and 19% for patients treated with >30 Gy. Exploratory analysis demonstrated a dose-response effect observed in all histologic types, including among breast cancer subtypes. CONCLUSION: Optimal local control is achieved with HSRT of ≥30 Gy in 5 daily fractions, independent of tumor volume and histology, with an acceptable risk of radiation necrosis.

Implementation of a standardized robotic assistant surgical training curriculum.

Since 2000, robotic-assisted surgery has rapidly expanded into almost every surgical sub-specialty. Despite the popularity of robotic surgery across the United States, a national consensus for standardized training and education of robotic surgeons or surgical teams remains absent. In this quality improvement initiative, a novel, stepwise iterative Robotic Assistant Surgical Training (RAST) curriculum was developed to broaden and standardize robotic bedside assistant training. Thirteen voluntary participants, capable of fulfilling the bedside assistant role, were evaluated to determine if RAST enhanced the learner's self-perceived level of confidence and comfort in their role as bedside assistant. A pre- and post-RAST training survey and a between-stages repeated-measures survey were conducted. All learner participants reported statistically significant increases in confidence and comfort after RAST training, (p = < 0.001), and between each stage, F (2, 24 = 60.47, p < .001; [Formula: see text] = 0.834). Participant feedback regarding curriculum improvement was obtained, suggesting the desire for more training and practice, in smaller groups of 2-3 participants. One hundred percent of participants felt RAST was beneficial and that it should be implemented as standardized training during onboarding for all robotic bedside assistants. Thus, a standardized, stepwise iterative robotic bedside assistant curriculum increases learner preparedness, comfort, and confidence, safely away from the patient bedside.

Efficacy of Chondroprotective Food Supplements Based on Collagen Hydrolysate and Compounds Isolated from Marine Organisms.

Osteoarthritis belongs to the most common joint diseases in humans and animals and shows increased incidence in older patients. The bioactivities of collagen hydrolysates, sulfated glucosamine and a special fatty acid enriched dog-food were tested in a dog patient study of 52 dogs as potential therapeutic treatment options in early osteoarthritis. Biophysical, biochemical, cell biological and molecular modeling methods support that these well-defined substances may act as effective nutraceuticals. Importantly, the applied collagen hydrolysates as well as sulfated glucosamine residues from marine organisms were strongly supported by both an animal model and molecular modeling of intermolecular interactions. Molecular modeling of predicted interaction dynamics was evaluated for the receptor proteins MMP-3 and ADAMTS-5. These proteins play a prominent role in the maintenance of cartilage health as well as innate and adapted immunity. Nutraceutical data were generated in a veterinary clinical study focusing on mobility and agility. Specifically, key clinical parameter (MMP-3 and TIMP-1) were obtained from blood probes of German shepherd dogs with early osteoarthritis symptoms fed with collagen hydrolysates. Collagen hydrolysate, a chondroprotective food supplement was examined by high resolution NMR experiments. Molecular modeling simulations were used to further characterize the interaction potency of collagen fragments and glucosamines with protein receptor structures. Potential beneficial effects of collagen hydrolysates, sulfated glycans (i.e., sulfated glucosamine from crabs and mussels) and lipids, especially, eicosapentaenoic acid (extracted from fish oil) on biochemical and physiological processes are discussed here in the context of human and veterinary medicine.

Connectivity and Neuronal Synchrony during Seizures.

There is uncertainty regarding when and which groups of neurons fire synchronously during seizures. While several studies found heterogeneous firing during seizures, others suggested synchronous neuronal firing in the seizure core. We tested whether neuronal activity during seizures is orderly in the direction of the excitatory neuronal connections in the circuit. There are strong excitatory connections laterally within the septotemporally organized lamella and inhibitory trans-lamellar connections in the hippocampus, which allow testing of the connectivity hypothesis. We further tested whether epileptogenesis enhances synchrony and antiseizure drug administration disrupts it. We recorded local field potentials from CA1 pyramidal neurons using a small microelectrode array and kindled rats by a rapid, recurrent hippocampal stimulation protocol. We compared cross-correlation, theta phase synchronization, entropy, and event synchronization. These analyses revealed that the firing pattern was correlated along the lamellar, but not the septotemporal, axis during evoked seizures. During kindling, neuronal synchrony increased along the lamellar axis, while synchrony along the septotemporal axis remained relatively low. Additionally, the theta phase distribution demonstrated that CA1 pyramidal cell firing became preferential for theta oscillation negative peak as kindling progressed in the lamellar direction but not in the trans-lamellar direction. Last, event synchronization demonstrated that neuronal firings along the lamellar axis were more synchronized than those along the septotemporal axis. There was a marked decrease in synchronization and phase preference after treatment with phenytoin and levetiracetam. The synchrony structure of CA1 pyramidal neurons during seizures and epileptogenesis depends on anatomic connectivity and plasticity.SIGNIFICANCE STATEMENT We could improve the efficacy of brain stimulation to treat seizures by understanding the structure of synchrony. Electrical stimulation may disrupt seizures by desynchronizing neurons, but there is an uncertainty on which groups of neurons fire synchronously or chaotically during seizures. Here, we demonstrate that neurons linked by excitatory connections fire synchronously during seizures, and this synchrony is modulated by epileptogenesis and antiseizure drugs. Closed-loop brain stimulation carefully targeted to disrupt synchrony may improve the treatment of seizures.

A pilot study of everolimus and radiation for neuroendocrine liver metastases.

Liver metastases are common in patients with neuroendocrine tumours. For patients, management must balance disease control with consideration of toxicity, given limited treatment options. Everolimus has demonstrated effectiveness in neuroendocrine neoplasms. Given emerging data of a synergistic effect with radiation therapy, we evaluated combined everolimus and radiation for neuroendocrine liver metastases. This single-arm, single-centre prospective pilot study evaluated the safety and efficacy of combined everolimus and radiotherapy for well-differentiated neuroendocrine liver metastases. Patients with unresectable liver metastases received everolimus for 30 days, followed by concurrent everolimus and liver radiotherapy, then a further 14 days of everolimus. Tolerability was evaluated using the CTCAE v.4.03. Individual metastasis response rate and local control were measured by RECIST v1.1. Overall survival, progression-free survival and freedom from a change in systemic therapy were estimated by the Kaplan-Meier method. Forty metastases were treated in 14 patients. No grade 3 or higher toxicities were identified in the concurrent treatment phase; one patient developed grade 3 toxicity in the post-radiation phase. Overall response rate was 38%. One- and 2-year local control were 97% and 71%. Median progression-free survival was 12 months. One- and 2-year overall survival were 100% and 92%. In conclusion, combined everolimus and radiation are well-tolerated for neuroendocrine liver metastases and are associated with excellent local control. The approach of selective local ablation of oligometastatic or oligoprogressive disease warrants further evaluation in this patient population.

The relationship between lateralization patterns from sequence based motor tasks and hemispheric speech dominance.

Objective: Skilled motor praxis and speech production display marked asymmetries at the individual and the population level, favoring the right hand and the left hemisphere, respectively. Theories suggesting a common processing mechanism between praxis and speech are supported by evidence that shared neural architecture underlies both functions. Despite advances in understanding the neurobiology of this left-hemisphere specialization the cortical networks linking these 2 functions are rarely investigated on a behavioral level. Method: This study deploys functional transcranial doppler (fTCD) ultrasound to directly measure hemispheric activation during skilled manual praxis tasks shown to be correlated to hemispheric speech lateralization indices. In a new paradigm we test the hypothesis that praxis tasks are highly dependent on the left hemisphere's capacity for processing sequential information will be better correlated with direction and strength of hemispheric speech lateralization. Results: Across 2 experiments we first show that only certain praxis tasks (pegboard and coin-rotation) correlated with direct measurements of speech lateralization despite shared properties across all tasks tested. Second, through novel imaging of hemispheric activation during praxis, results showed that the pegboard differed in the lateralization pattern created and furthermore that it was significantly related to speech laterality indices, which was not the case for either of the other two tasks. Conclusion: These results are discussed in terms of a lateralized speech-praxis control mechanism and demonstrates that measurements of motor paradigms through the use of fTCD are reliable enough to provide a new insight to the behavioral relationship been speech and handedness. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

A Systematic Review of Job Demands and Resources Associated with Compassion Fatigue in Mental Health Professionals.

Psychosocial hazards in mental healthcare contribute to the development of compassion fatigue in mental health professionals. Compassion fatigue has a negative impact on the mental health and wellbeing of professionals that can impair the quality of services provided to clients. The majority of research on compassion fatigue has focused on individual-level variables such as gender, history of trauma and age, among others. It is also imperative to understand the role played by alterable work-related characteristics in contributing to the development of compassion fatigue in order to attenuate its impact on mental health professionals and their clients. The present review examined articles exploring work-related factors associated with compassion fatigue. Fifteen quantitative studies were included and their quality was assessed using a checklist. An inductive content-analysis approach was adopted to synthesise the themes emerging from the data. The results suggested a theoretical model consistent with the Job Demands-Resources model, wherein job demands (such as workplace trauma, workload and therapeutic settings) are associated with compassion fatigue, and job resources (such as supervisors', coworkers' and organisational support) mitigate the impact of job demands. In addition to person-oriented factors, work-related factors are critical for the prevention of compassion fatigue.

A Multidisciplinary Approach to Synovial Chondromatosis of the Temporomandibular Joint With Cranial Base Involvement: A Brief Review of the Literature and Case Report.

Synovial chondromatosis (SC) is an infrequent, benign condition of unknown etiology affecting the synovium within articular joints. Often considered a metaplastic process, multiple cartilaginous nodules develop in the confines of the synovial membrane. In time, these cartilage nodules develop into fragments, sometimes detaching from the synovium and, thus, become loose in an adjacent synovial cavity. The temporomandibular joint (TMJ) is an unusual site of involvement, with the extracapsular compromise of the cranial base exceedingly rare. A 68-year-old woman presented with a tender mass to the left TMJ that later proved to be SC. Computed tomography illustrated a rare extension of the lesion into the middle cranial fossa. The multidisciplinary effort to remove the mass in its entirety included both oral and maxillofacial surgical and neurosurgical teams. We have reviewed the presentation, diagnosis, surgical treatment, and outcomes of the present case, with diagnostic images and photomicrographs of the lesion included. We also briefly reviewed the reported studies.

Effects of Solriamfetol on Quality-of-Life Measures from a 12-Week Phase 3 Randomized Controlled Trial.

Rationale: Excessive daytime sleepiness in patients with obstructive sleep apnea is associated with substantial burden of illness.Objectives: To assess treatment effects of solriamfetol, a dopamine/norepinephrine reuptake inhibitor, on daily functioning, health-related quality of life, and work productivity in participants with obstructive sleep apnea and excessive daytime sleepiness as additional outcomes in a 12-week phase 3 trial (www.clinicaltrials.gov identifier NCT02348606).Methods: Participants (N = 476) were randomized to solriamfetol 37.5, 75, 150, or 300 mg or to placebo. Outcome measures included the Functional Outcomes of Sleep Questionnaire short version, Work Productivity and Activity Impairment Questionnaire: Specific Health Problem, and 36-item Short Form Health Survey version 2. A mixed-effects model with repeated measures was used for comparisons with placebo.Results: Demographics, baseline disease characteristics, daily functioning, health-related quality of life, and work productivity were similar across groups. At Week 12, increased functioning and decreased impairment were observed with solriamfetol 150 and 300 mg (mean difference from placebo [95% confidence interval]) on the basis of Functional Outcomes of Sleep Questionnaire total score (1.22 [0.57 to 1.88] and 1.47 [0.80 to 2.13], respectively), overall work impairment (-11.67 [-19.66 to -3.69] and -11.75 [-19.93 to -3.57], respectively), activity impairment (-10.42 [-16.37 to -4.47] and -10.51 [-16.59 to -4.43], respectively), physical component summary (2.07 [0.42 to 3.72] and 1.91 [0.22 to 3.59], respectively), and mental component summary (150 mg only, 2.05 [0.14 to 3.96]). Common adverse events were headache, nausea, decreased appetite, and anxiety.Conclusions: Solriamfetol improved measures of functioning, quality of life, and work productivity in participants with obstructive sleep apnea and excessive daytime sleepiness. Safety was consistent with previous studies.Clinical trial registered with www.clinicaltrials.gov (NCT02348606).