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Managing cancer and living meaningfully (CALM) is a brief, semi-structured individual and couple-based intervention designed to alleviate distress and promote well-being in individuals living with advanced cancer. CALM emerged from a longitudinal program of research and the theoretical traditions of relational, attachment, and existential theory. Through a therapeutic process that supports affect regulation, attachment security, and reflective functioning, CALM addresses four content domains: symptom management and communication with healthcare providers; changes in self and relations with close others; spiritual well-being, sense of meaning and purpose; and preparing for the future, sustaining hope, and facing mortality. Caregivers are invited to participate to provide an additional perspective and help address strains and strengths in the spousal relationship, the impact of the illness on the family, and planning for the future. Qualitative research demonstrates that CALM provides the experience of a safe place to explore fears, feel more fully seen in human terms, and face the challenges and threats of advancing disease. Quantitative research demonstrates that CALM is effective in reducing and preventing depressive symptoms, alleviating death anxiety, and facilitating communication of patients with healthcare providers, preparation for the end of life, and clarification of feelings and values. Healthcare providers from multiple disciplines in more than 20 countries have been successfully trained in CALM through didactic and experiential workshops and ongoing supervision. The semi-structured nature of CALM has allowed its adaptation and delivery in diverse cultural and clinical contexts.

Background The ability to identify genetic alterations in cancers is essential for precision medicine; however, surgical approaches to obtain brain tumor tissue are invasive. Profiling circulating tumor DNA (ctDNA) in liquid biopsies has emerged as a promising approach to avoid invasive procedures. Here, we systematically evaluated the feasibility of profiling pediatric brain tumors using ctDNA obtained from plasma, cerebrospinal fluid (CSF), and urine. Methods We prospectively collected 564 specimens (257 blood, 240 urine, and 67 CSF samples) from 258 patients across all histopathologies. We performed ultra-low-pass whole-genome sequencing (ULP-WGS) to assess copy number variations and estimate tumor fraction and developed a pediatric CNS tumor hybrid capture panel for deep sequencing of specific mutations and fusions. Results ULP-WGS detected copy number alterations in 9/46 (20%) CSF, 3/230 (1.3%) plasma, and 0/153 urine samples. Sequencing detected alterations in 3/10 (30%) CSF, 2/74 (2.7%) plasma, and 0/2 urine samples. The only positive results were in high-grade tumors. However, most samples had insufficient somatic mutations (median 1, range 0-39) discoverable by the sequencing panel to provide sufficient power to detect tumor fractions of greater than 0.1%. Conclusions Children with brain tumors harbor very low levels of ctDNA in blood, CSF, and urine, with CSF having the most DNA detectable. Molecular profiling is feasible in a small subset of high-grade tumors. The level of clonal aberrations per genome is low in most of the tumors, posing a challenge for detection using whole-genome or even targeted sequencing methods. Substantial challenges therefore remain to genetically characterize pediatric brain tumors from liquid biopsies.

Isolated orbital periphlebitis in the context of nonspecific orbital inflammation is rare. This case series describes 3 patients with periphlebitis of the superior ophthalmic vein, 2 of which were confirmed with pathology. All 3 cases had a history of Graves hyperthyroidism. Superior ophthalmic vein periphlebitis is a rare form of orbital inflammation presenting with proptosis and motility restriction yet few inflammatory signs. It may be associated with autoimmune hyperthyroidism and represent a rare feature of thyroid eye disease, or perhaps could be an overlap syndrome between thyroid eye disease and nonspecific orbital inflammation. Treatment response is variable and may require a prolonged course of steroids or other immunosuppressive medications.

Purpose To describe a novel surgical technique for implanting eyelid weights via a sutureless transconjunctival approach. In comparison to the traditional supratarsal crease approach, this technique does not involve any external incisions or suture placement. The procedure can reduce surgical time and complications associated with the traditional external approach. Methods This case series includes 13 patients who underwent eyelid weight placement via the transconjunctival approach for paralytic lagophthalmos secondary to facial nerve paralysis (12 patients had unilateral paralysis and 1 patient had bilateral) with a total of 14 eyelid weights placed. The procedures were performed at an outpatient office-based surgical center. All procedures were performed or supervised by the same surgeon. Patients were followed for an average 6-month postoperative period for postoperative complications. Results The sutureless transconjunctival approach to eyelid weight insertion was successful in achieving the desired functional and aesthetic outcomes. Patients undergoing this technique avoided the discomfort of postoperative suture removal. All patients achieved comparable outcomes postoperatively. There were no complications reported across the 13 patients throughout the 6-month postoperative period. Conclusions This case series demonstrates that the transconjunctival approach for metal eyelid weight insertion is practical, relatively easy to perform, and associated with functional outcomes that are comparable to those achieved with the traditional approach, however, without external incision or placement of sutures.

The purpose is to understand the natural history and physical findings in thyroid eye disease (TED) patients with severe dry eye symptoms (DES).Prospective cohort study, studying DES in TED patients over two years. Baseline data included clinical activity score (CAS), time since disease onset, punctate epithelial erosions (PEE), lagophthalmos, superior limbic keratoconjunctivitis (SLK), and marginal reflex distance 1 (MRD1). Ocular Surface Disease Index (OSDI) was utilized to measure symptomatology and scores33 (severe) were the primary outcome measure. Multivariate logistic regression was performed on two groups (9 months,9 months) to assess if variables change in early versus late disease.88 met the inclusion criteria. 80.7% (n = 71) were female. There were 42 patients in the group with onset of symptoms under nine months and 46 patients over nine months. Mean CAS score was greater under nine months (2.45) than over nine months (1.29) (Severe DES correlate with inflammatory features within the first nine months. Afterward, presence of PEE became more important. DES in TED tends to be a manifestation of orbital inflammation early in disease and exposure later.

The purpose of this study is to report cases of choroidal melanoma that developed extrascleral tumour recurrence after treatment with iodine-125 brachytherapy.In this single-institution retrospective observational case series, all instances of biopsy-confirmed orbital melanoma after known intraocular melanoma were reviewed. Tumour characteristics, clinical course, time to recurrence, cytogenetics of initial tumour and recurrence, and presence of intraocular recurrence were documented.Five cases of orbital melanoma following treatment with plaque radiotherapy are described. Tumour staging was Ia (1), IIa (2), and IIb (2). The primary lesion in four of the five appeared to have undergone complete regression for an average of 2 years, with the orbital melanoma developing after this interval. Recurrence of the intraocular tumour was seen in conjunction with an extrascleral component in two cases. Four cases ultimately underwent enucleation or exenteration; three had evidence of direct extension of tumour through the sclera. Four cases in this series had molecular characteristics associated with high metastatic risk (three patients with monosomy 3, one with BAP1 mutation).High-risk tumour biology may predispose to late appearance of extrascleral melanoma despite optimal treatment and adequate control of the intraocular tumour. Extended follow-up with detailed orbital examination and imaging is recommended for this population.

Anti-adhesion therapies interfere with the bacterial adhesion to the host and thus avoid direct disruption of bacterial cycles for killing, which may alleviate resistance development. Herein, an anti-adhesion nanomedicine platform is made by wrapping synthetic polymeric cores with bacterial outer membranes. The resulting bacterium-mimicking nanoparticles (denoted "OM-NPs") compete with source bacteria for binding to the host. The "top-down" fabrication of OM-NPs avoids the identification of the adhesins and bypasses the design of agonists targeting these adhesins. In this study, OM-NPs are made with the membrane of Helicobacter pylori and shown to bind with gastric epithelial cells (AGS cells). Treatment of AGS cells with OM-NPs reduces H. pylori adhesion and such anti-adhesion efficacy is dependent on OM-NP concentration and its dosing sequence.

Background Pancreatic cancer has one of the highest mortality rates of any malignancy, placing a substantial burden on patients and families with high unmet informational and supportive care needs. Nevertheless, access to psychosocial and palliative care services for the individuals affected is limited. There is a need for standardized approaches to facilitate adjustment and to improve knowledge about the disease and its anticipated impact. In this intervention-development paper guided by implementation science principles, we report the rationale, methods, and processes employed in developing an interdisciplinary group psychoeducational intervention for people affected by pancreatic cancer. The acceptability and feasibility of implementation will be evaluated as a part of a subsequent feasibility study. Methods The Schofield and Chambers framework for designing sustainable self-management interventions in cancer care informed the development of the intervention content and format. The Consolidated Framework for Implementation Research served as an overarching guide of the implementation process, including the development phase and the formative evaluation plan of implementation. Results A representative team of stakeholders collaboratively developed and tailored the intervention content and format with attention to the principles of implementation science, including available resourcing. The final intervention prototype was designed as a single group-session led by an interdisciplinary clinical team with expertise in caring for patients with pancreatic cancer and their families and in addressing nutrition guidelines, disease and symptom management, communication with family and health care providers, family impact of cancer, preparing for the future, and palliative and supportive care services. Conclusions The present paper describes the development of a group psychoeducational intervention to address the informational and supportive care needs of people affected by pancreatic cancer. Consideration of implementation science during intervention development efforts can optimize uptake and sustainability in the clinical setting. Our approach may be utilized as a framework for the design and implementation of similar initiatives to support people affected by diseases with limited prognoses. Electronic supplementary material The online version of this article (10.1186/s40814-019-0466-x) contains supplementary material, which is available to authorized users.

This study was to determine the degree of posttraumatic enophthalmos that is detectable by lay observers. In this case-control study, 60 photographs (frontal and oblique angles) of patients from an oculoplastics registry at the authors' institution were reviewed by lay observers. Patients were included if they had between 1 and 5 mm of unilateral enophthalmos, at least 6 months following trauma. They were divided into five groups of 10 and each group was separated by increments of 1 mm. Controls were selected from the same database and had 0 mm difference between each eye. Patients were excluded if they had any medical condition that might cause enophthalmos (including use of prostaglandin analogues). Participants were also excluded if they had any medical or surgical condition affecting the contralateral side. Lay observers were randomly selected from a pool of volunteers in nonmedical programs at our affiliated university. The primary outcome measure was the asymmetry cut-off (in millimeters) in which more than 50% of the cases (chance) were identified correctly. The generalized mixed model predicts that 66% of lay observers would correctly identify a difference between both eyes at a rate greater than would be predicted by chance, if at least a 5 mm difference existed between them (95% confidence interval [CI] 55.5–75%). This study shows that lay observers only reliably detect unilateral enophthalmos when there is at least a 5 mm difference between the eyes. This study used two-dimensional (2D) photographs and, therefore, results with three-dimensional (3D) observation may be different. In this study of 2D photographs, unilateral posttraumatic enophthalmos is only reliably detected by lay observers when a 5 mm difference exists between the eyes.

We designed a novel, manualized intervention called Emotion And Symptom-focused Engagement (EASE) for acute leukemia (AL) and report here on a phase II randomized controlled trial (RCT) to assess its feasibility and preliminary efficacy. Patients were recruited within 1 month of hospital admission and randomized to EASE plus usual care (UC) or UC alone. EASE includes (1) EASE-psy, a tailored psychotherapy delivered over 8 weeks, and (2) EASE-phys, weekly physical symptom screening over 8 weeks to trigger early palliative care. The primary outcome was traumatic stress symptoms; secondary outcomes included physical symptom burden and quality of life. Assessments were conducted at baseline and at 4, 8, and 12 weeks. Between-group differences were evaluated using multilevel modeling. Forty-two patients were randomized to EASE (n = 22) or UC (n = 20), with 76% retention at 12 weeks. Predefined feasibility outcomes were met: 86% (19/22) of EASE participants completed ≥ 50% of EASE-psy sessions (goal ≥ 64%); 100% received Edmonton Symptom Assessment System (ESAS, modified for AL) screenings, 64% (14/22) of whom completed ≥ 50% of planned screenings (goal ≥50%); and 100% with scores ≥ 4/10 on any physical ESAS-AL item had ≥ 1 meeting with the EASE-phys team (goal 100%). Significant treatment-group differences favoring EASE were observed in traumatic stress symptoms at 4 and 12 weeks, and pain intensity and interference at 12 weeks (all p

PURPOSE: Mentalization has been clearly defined in the literature as a relational concept and yet in surveys and transcript-based measures it is almost universally treated as an individual capacity. That approach has value but may not capture the emergent nature of mentalization, as it is jointly constructed within a relational context. // METHODS: We report here on a critical evaluation of measurement approaches commonly used to conceptualize and assess mentalization and argue for the value of conversation analysis (CA) as an alternative approach. // RESULTS: A variety of approaches have been shown to have utility in assessing mentalization as an individual capacity. We illustrate how conversation analysis allows for an in-depth-analysis of mentalization as it is co-created across different contexts in real-life therapy sessions. This method of analysis shifts the focus from content to process. // CONCLUSIONS: Conversation analysis is a potentially valuable tool to support training, to assess treatment integrity, and to improve outcomes with mentalization-based interventions.

Objective: Death acceptance may indicate positive adaptation in cancer patients. Little is known about what characterizes patients with different levels of death acceptance or its impact on psychological distress. We aimed to broaden the understanding of death acceptance by exploring associated demographic, medical, and psychological characteristics. Methods: At baseline, we studied 307 mixed cancer patients attending the University Cancer Center Hamburg and a specialized lung cancer center (age M = 59.6, 69% female, 69% advanced cancer). At 1-year follow-up, 153 patients participated. We assessed death acceptance using the validated Life Attitude Profile–Revised. Patients further completed the Memorial Symptom Assessment Scale, the Demoralization Scale, the Patient Health Questionnaire, and the Generalized Anxiety Disorder Questionnaire. Statistical analyses included multinomial and hierarchical regression analyses. Results: At baseline, mean death acceptance was 4.33 (standard deviation [SD] = 1.3, range 1-7). There was no change to follow-up (P = 0.26). When all variables were entered simultaneously, patients who experienced high death acceptance were more likely to be older (odds ratio [OR] = 1.04; 95% confidence interval [CI], 1.01-1.07), male (OR = 3.59; 95% CI, 1.35-9.56), widowed (OR = 3.24; 95% CI, 1.01-10.41), and diagnosed with stage IV (OR = 2.44; 95% CI, 1.27-4.71). They were less likely to be diagnosed with lung cancer (OR = 0.20; 95% CI, 0.07-0.58), and their death acceptance was lower with every month since diagnosis (OR = 0.99; 95% CI, 0.98-0.99). High death acceptance predicted lower demoralization and anxiety at follow-up but not depression. Conclusions: High death acceptance was adaptive. It predicted lower existential distress and anxiety after 1 year. Advanced cancer did not preclude death acceptance, supporting the exploration of death-related concerns in psychosocial interventions.

Objective To identify how therapists invite patients with advanced cancer to engage with alternative perspectives about their illness trajectory and their end of life. Methods Sequences of talk in which a therapist introduced a patient to alternative perspectives, were transcribed and analysed using the method of conversation analysis. Results The analysis identifies one subtle way a patient is invited to consider an alternative perspective relating to their disease progression. Meaning expansion enquiries invite the patient to expand on the meaning of an utterance and in doing so, implicitly problematize the singularity of the patient’s assumptions, without directly challenging them. The questions work as preliminary moves, providing the patient with the opportunity to expand on their assumptions. This enables the therapist to subsequently present an alternative perspective in a way that incorporates the patient’s expanded perspective. Conclusion The analysis reveals a skilful way in which therapists can cautiously and collaboratively introduce a patient to alternative perspectives concerning end-of-life, without invalidating the patient’s perspective in this particularly delicate context. Practice Implications Whilst mentalization is considered an important therapeutic process, the present study reveals precisely how this phenomenon can be enacted in therapy and within the particularly challenging context of end-of-life.

RATIONALE: Pulmonary arterial hypertension (PAH) is a progressive disease that can compromise quality of life and potentially raise existential distress about its meaning and value. Such distress h...

Purpose This perspective explores the term "Asian blepharoplasty" and its socioemotional meaning to some patients. Methods N/A. Results Words have power. The term "Asian blepharoplasty" makes some patients uncomfortable. To our knowledge, it is the only medical descriptor that uses race. Conclusions The use of the term "Asian Blepharoplasty" may unwittingly make patients uncomfortable and pathologize Asian features. Therefore, we suggest replacing the term "Asian Blepharoplasty" with "Double Eyelid Surgery." For the subset of procedures which do not include the creation of an eyelid crease, "Blepharoplasty" is appropriate.

Purpose:Existing cell-free DNA (cfDNA) methods lack the sensitivity needed for detecting minimal residual disease (MRD) following therapy. We developed a test for tracking hundreds of patient-specific mutations to detect MRD with a 1,000-fold lower error rate than conventional sequencing.Experimental Design:We compared the sensitivity of our approach to digital droplet PCR (ddPCR) in a dilution series, then retrospectively identified two cohorts of patients who had undergone prospective plasma sampling and clinical data collection: 16 patients with ER+/HER2− metastatic breast cancer (MBC) sampled within 6 months following metastatic diagnosis and 142 patients with stage 0 to III breast cancer who received curative-intent treatment with most sampled at surgery and 1 year postoperative. We performed whole-exome sequencing of tumors and designed individualized MRD tests, which we applied to serial cfDNA samples.Results:Our approach was 100-fold more sensitive than ddPCR when tracking 488 mutations, but most patients had fewer identifiable tumor mutations to track in cfDNA (median = 57; range = 2–346). Clinical sensitivity was 81% (n = 13/16) in newly diagnosed MBC, 23% (n = 7/30) at postoperative and 19% (n = 6/32) at 1 year in early-stage disease, and highest in patients with the most tumor mutations available to track. MRD detection at 1 year was strongly associated with distant recurrence [HR = 20.8; 95% confidence interval, 7.3–58.9]. Median lead time from first positive sample to recurrence was 18.9 months (range = 3.4–39.2 months).Conclusions:Tracking large numbers of individualized tumor mutations in cfDNA can improve MRD detection, but its sensitivity is driven by the number of tumor mutations available to track.

We examined patterns of avoidance when existential emotional topics were raised during conversations with patients with pulmonary arterial hypertension (PAH), an incurable life-limiting disease. 30 adult outpatients with PAH were recruited for a 20 to 60-minute interview about their illness experience. Qualitative content analysis was used to identify avoidance strategies that patients employed. Participants averaged 58 years in age (SD = 18), 77% were female, and mean length of illness was 6.3 years (SD = 5.3). We found four avoidance strategies: (1) Reversal, when individuals would begin discussing a negative concern and then backtrack to more positive sentiments; (2) Diversion for when patients would sidetrack the conversation to a different and less uncomfortable topic; (3) Diminishment for when a concern is raised and then made to seem unimportant; and (4) Obstruction, when patients refuse to discuss a concern further. Exploration of existential concerns can elicit distress but may be necessary to promote adaptation to progressive illness and to the foreseeable challenges that may affect the sense of life meaning and value. By recognizing when existential concerns may be present but not adequately discussed, clinicians may be better able to assist patients to cope and prepare for the future.

Fiber textiles worn by some athletes and basketball and volleyball players experience higher than usual thermomechanical stresses compared to everyday garments because these athletes slide and dive on hardwood courts. Common textile testing procedures, such as the Martindale abrasion tester, effectively test textiles under modest loads and thousands of cycles, but this methodology does not suffice for athletic textiles. In addition, there is not a robust model nor a repeatable test that mimics high thermomechanical stress on fabrics and provides insights on fabric abrasion resistance. We present a model to calculate the temperatures and strain rates that are seen by fabrics undergoing thermomechanical deformation. To enable validation of the model, a fabric pendulum abrasion tester, an adaptation of the Cooper pendulum skid tester, was developed. The tester characterizes high-strain fabric abrasion deformation. This adaptation is statistically reliable and induces repeatable and realistic fabric failure within tens to hundreds of cycles, proving to be analogous to the loads athletes place on their textiles. Analog electronics on the pendulum abrasion tester generate real-time temperature and velocity profiles. A series of 11 unique athletic fabrics were abrasion tested, and it was found that fabrics with macroporosity experience the largest abrasion degradation. Significant degradation sites were further explored using scanning electron microscopy and X-ray diffraction analysis, and it was shown that thermomechanical loading’s effect on fiber microstructure is a function of the fabric construction. This novel abrasion tester and quantitative relationships between fabric structure and degradation mechanisms will enable more data-driven decisions when designing textiles for thermomechanical loads.

The confrontation with death imposed by advanced cancer or other illness can trigger existential concerns about the meaning and value of life. - From an Eriksonian perspective, the ability to come to terms with the end of life is influenced by one's developmental history and life stage prior to illness. - The experience of advanced disease may re-awaken for some patients developmental issues that they had thought long resolved, as physical deterioration removes functional capacities in a manner reminiscent of a reversal of early development. - The threat of mortality may accelerate individuals through the latter stages of human development to engage in a process of life review, for whom those at earlier stages of psychosocial development are less prepared to undergo. - Generativity may offer protection against existential distress, because the sense of meaning in life may often reside in feelings of nurturance and contribution to others.

Purpose Individuals with advanced cancer experience substantial distress in response to disease burden and impending mortality. Managing Cancer And Living Meaningfully (CALM) is a novel, brief, manualized psychotherapeutic intervention intended to treat and prevent depression and end-of-life distress in patients with advanced cancer. We conducted a randomized controlled trial to compare CALM with usual care (UC) in this population. Methods Patients with advanced cancer were recruited from outpatient oncology clinics at a comprehensive cancer center into an unblinded randomized controlled trial. Permuted block randomization stratified by Patient Health Questionnaire-9 depression score allocated participants to CALM plus UC or to UC alone. Assessments of depressive symptoms (primary outcome), death-related distress, and other secondary outcomes were conducted at baseline, 3 months (primary end point), and 6 months (trial end point). Analyses were by intention to treat. Analysis of covariance was used to test for outcome differences between groups at follow-up, controlling for baseline. Mixed-model results are reported. Results Participants (n = 305) were recruited between February 3, 2012, and March 4, 2016, and randomly assigned to CALM (n = 151) or UC (n = 154). CALM participants reported less-severe depressive symptoms than UC participants at 3 months (Δ = 1.09; P = .04; Cohen’s d = 0.23; 95% CI, 0.04 to 2.13) and at 6 months (Δ = 1.29; P = .02; d = 0.29; 95% CI, 0.24 to 2.35). Significant findings for greater end-of-life preparation at 6 months also favored CALM versus UC. No adverse effects were identified. Conclusion Findings suggest that CALM is an effective intervention that provides a systematic approach to alleviating depressive symptoms in patients with advanced cancer and addresses the predictable challenges these patients face.

T- and NK-cell lymphomas (TCL) are a heterogenous group of lymphoid malignancies with poor prognosis. In contrast to B-cell and myeloid malignancies, there are few preclinical models of TCLs, which has hampered the development of effective therapeutics. Here we establish and characterize preclinical models of TCL. We identify multiple vulnerabilities that are targetable with currently available agents (e.g., inhibitors of JAK2 or IKZF1) and demonstrate proof-of-principle for biomarker-driven therapies using patient-derived xenografts (PDXs). We show that MDM2 and MDMX are targetable vulnerabilities within TP53-wild-type TCLs. ALRN-6924, a stapled peptide that blocks interactions between p53 and both MDM2 and MDMX has potent in vitro activity and superior in vivo activity across 8 different PDX models compared to the standard-of-care agent romidepsin. ALRN-6924 induced a complete remission in a patient with TP53-wild-type angioimmunoblastic T-cell lymphoma, demonstrating the potential for rapid translation of discoveries from subtype-specific preclinical models., T- and NK-cell lymphomas (TCL) are a group of lymphoid malignancies characterized by poor prognosis, but the absence of appropriate pre-clinical models has hampered the development of effective therapies. Here the authors establish several pre-clinical models and identify vulnerabilities that could be further exploited to treat patients afflicted by these diseases.

Objective Acute leukemia (AL) is associated with an immediate threat to life, an unpredictable clinical course, and substantial physical suffering. Traumatic stress symptoms that may meet criteria for acute stress disorder (ASD) may be common and disabling in this context, but have received little clinical attention. We investigated the incidence over time and risk factors for traumatic stress symptoms and ASD in the 3 months following diagnosis or relapse of AL. Methods Individuals with AL were recruited at a tertiary cancer center in Canada within one month of diagnosis or relapse. Participants (N = 230) completed self-report measures, including the Stanford Acute Stress Reaction Questionnaire, at baseline and monthly over 3 months. The incidence of traumatic stress symptoms over time was examined, and a generalized logistic model was used to identify factors associated with ASD. Results Participants were 60% male, with a mean age of 48.9 ± 15.2 years. Symptoms of ASD were identified on ≥1 assessment over the study period in 24.4% of participants at baseline and in an additional 12.6% at a subsequent follow-up. Of these, 55.3% reported symptoms on ≥2 assessments. ASD was associated with having young children, being unmarried, acute lymphocytic leukemia, and greater physical symptom burden. Persistent or recurrent ASD was associated with female sex, acute lymphocytic leukemia, greater attachment anxiety, less spiritual well-being, and less satisfactory patient-clinician communication. Conclusions Symptoms of ASD are common and often persist or recur following diagnosis or relapse of AL. Research is urgently needed to determine the impact of interventions to prevent and treat psychological distress in this population.

Objectives Fear of death and dying is common in patients with advanced cancer, but can be difficult to address in clinical conversations. We aimed to show that the experience of death anxiety may be deconstructed into a network of specific concerns and to provide a map of their interconnections to aid clinical exploration. Methods We studied a sample of 382 patients with advanced cancer recruited from outpatient clinics at the Princess Margaret Cancer Centre, Toronto, Canada. Patients completed the 15-item Death and Dying Distress Scale (DADDS). We used item ratings to estimate a regularised partial correlation network of death and dying-related concerns. We calculated node closeness-centrality, clustering and global network characteristics. Results Death-related anxieties were highly frequent, each associated with at least moderate distress in 22%–55% of patients. Distress about ‘Running out of time’ was a central concern in the network. The network was organised into two areas: one about more practical fears concerning the process of dying and another about more psychosocial or existential concerns including relational problems, uncertainty about the future and missed opportunities. Both areas were yet closely connected by bridges which, for example, linked fear of suffering and a prolonged death to fear of burdening others. Conclusions Patients with advanced cancer may have many interconnected death-related fears that can be patterned in individual ways. The bridging links between more practical and more psychosocial concerns emphasise that the alleviation of death anxiety may require interventions that integrate symptom management, advance care planning and psychological treatment approaches.

BACKGROUND Demoralization refers to a state in which there is a perceived inability to cope, that is associated with a sense of disheartenment and a loss of hope and meaning. This study investigated the co-occurrence versus independence of demoralization with mental disorders and suicidal ideation to evaluate its features as a concept of distress in the context of severe illness. METHODS In a cross-sectional sample of 430 mixed cancer patients, we assessed demoralization with the Demoralization Scale (DS); the 4-week prevalence of mood, anxiety, and adjustment disorders and suicidal ideation with the standardized Composite International Diagnostic Interview–Oncology (CIDI-O); and depressive symptoms with the Patient Health Questionnaire-9 (PHQ-9). We compared the relative risk (RR) for mental disorders associated with demoralization to that associated with self-reported depression. RESULTS Clinically relevant levels of demoralization were present in 21% of the patients. Demoralization co-occurred with a mood/anxiety disorder in 7%; 14% were demoralized in absence of any mood/anxiety disorder. Demoralization and adjustment disorders co-occurred in 2%. The RR for any mood/anxiety disorder was 4.0 in patients with demoralization (95% confidence interval [CI], 2.5-6.2) and 3.0 in those with depression (95% CI, 1.9-4.6). Demoralization, but not depression, was associated with a significantly increased risk for suicidal ideation after controlling for mental disorders (RR, 2.0; 95% CI, 1.1-3.5). CONCLUSIONS Clinically relevant demoralization frequently occurs independently of a mental disorder in patients with cancer and has a unique contribution to suicidal ideation. Demoralization is a useful concept to identify profiles of psychological distress symptoms amenable to interventions improving psychological well-being in this population. Cancer 2017. © 2017 American Cancer Society.

Context Distress and anxiety about issues related to death and dying is commonly experienced in patients with advanced disease and a limited life expectancy. Objectives To evaluate the psychometric properties of the German version of the Death and Dying Distress Scale (DADDS-G) in advanced cancer patients. Methods We recruited advanced patients with mixed tumor entities (Union for International Cancer Control [UICC] Stage III/IV) treated in two German University Medical Centers during their outpatient treatment. After testing a preliminary version of the state-of-the-art translated original Death and Dying Distress Scale, we analyzed the psychometric properties of the shortened nine-item adapted DADDS-G using validated instruments measuring distress, anxiety, depression, fear of progression, and quality of life. Results We obtained complete questionnaires from 77 of 93 patients with advanced cancer (response rate: 83%). Participants were mostly married or cohabiting (75%), well-educated, and both sexes were almost equally represented (52% men; mean age 58 years, SD = 12). The total mean DADDS-G score was 13.3 (SD = 8.5). Patients reported to be most distressed by the feeling of being a burden to others. The exploratory factor analysis led to one factor that accounted for more than 59% of the variance. The DADDS-G's internal consistency was excellent with Cronbach alpha = 0.91. The confirmatory factor analysis demonstrated a very good model fit. Death-related anxiety was significantly associated with distress, depression, anxiety, fear of progression, and lower quality of life ( P Conclusion Results provide further evidence that the DADDS-G is a valid and reliable instrument of high clinical relevance for use in patients with advanced cancer.

Large panels of comprehensively characterized human cancer models, including the Cancer Cell Line Encyclopedia (CCLE), have provided a rigorous framework with which to study genetic variants, candidate targets, and small-molecule and biological therapeutics and to identify new marker-driven cancer dependencies. To improve our understanding of the molecular features that contribute to cancer phenotypes, including drug responses, here we have expanded the characterizations of cancer cell lines to include genetic, RNA splicing, DNA methylation, histone H3 modification, microRNA expression and reverse-phase protein array data for 1,072 cell lines from individuals of various lineages and ethnicities. Integration of these data with functional characterizations such as drug-sensitivity, short hairpin RNA knockdown and CRISPR-Cas9 knockout data reveals potential targets for cancer drugs and associated biomarkers. Together, this dataset and an accompanying public data portal provide a resource for the acceleration of cancer research using model cancer cell lines.

PURPOSE To investigate the safety and efficacy of direct, intralesional doxycycline hyclate injection for improving the appearance of cosmetically significant lower eyelid festoons and malar edema. METHODS An Institutional Review Board approved, retrospective review was performed of 15 consecutive patients with malar edema and/or festoons injected with doxycycline hyclate at a concentration of 10 mg/ml. Pre- and postinjection photographs were reviewed and graded on a scale of 0 to 3 (0: no festoon; 1: small festoon; 2: medium festoon; 3: large festoon) by 2 masked physician observers. Patients were excluded from the final analysis if they received an alternate dose concentration, had incomplete photographic records, or did not follow up. Student t test was used for statistical analysis. RESULTS Twenty consecutive treatment areas of 11 patients were included in the analysis. Final follow up ranged from 3 to 104 weeks, with a mean follow up of 22.5 weeks. The average (standard deviation) initial festoon grade of 2.5 (0.58) decreased to 0.9 (0.82) with a p value of

There is an expanding role for nonsurgical techniques in periorbital and facial rejuvenation. While these treatments can sometimes replace surgery, they more often play an adjunctive role. First, this chapter presents an approach to evaluating patients and reviews the current understanding of the aging face. While new products are entering the market at lightning speed, we present an overview of the current classes of products and techniques available. Furthermore, the underlying philosophy behind successful aesthetic rejuvenation is introduced. There is a synergy to these techniques, which should be capitalized upon for the benefit of the patient.

Tumor content in circulating cell-free DNA (cfDNA) is a promising biomarker, but longitudinal dynamics of tumor-derived and non-tumor-derived cfDNA through multiple courses of therapy have not been well described.CfDNA from 663 plasma samples from 140 patients with castration-resistant prostate cancer (CRPC) was subject to sparse whole genome sequencing. Tumor fraction (TFx) estimated using the computational tool ichorCNA was correlated with clinical features and responses to therapy.TFx associated with the number of bone metastases (median TFx = 0.014 with no bone metastases, 0.047 with 1-3 bone metastases, 0.190 for 4+ bone metastases; P0.0001) and with visceral metastases (P0.0001). In multivariable analysis, TFx remained associated with metastasis location (P = 0.042); TFx was positively correlated with alkaline phosphatase (P = 0.0227) and negatively correlated with hemoglobin (Hgb) (P0.001), but it was not correlated with prostate specific antigen (PSA) (P = 0.75). Tumor-derived and non-tumor-derived cfDNA track together and do not increase with generalized tissue damage from chemotherapy or radiation at the time scales examined. All new treatments that led to ≥30% PSA decline at 6 weeks were associated with TFx decline when baseline TFx was7%; however, TFx in patients being subsequently maintained on secondary hormonal therapy was quite dynamic.TFx correlates with clinical features associated with overall survival in CRPC, and TFx decline is a promising biomarker for initial therapeutic response.Dana-Farber/Harvard Cancer Center (DF/HCC) protocol no. 18-135.Wong Family Award in Translational Oncology, Dana Farber Cancer Institute Medical Oncology grant, Gerstner Family Foundation, Janssen Pharmaceuticals Inc., and Koch Institute Support (core) grant P30-CA14051 from the National Cancer Institute (NCI).

We designed a novel, manualized intervention called Emotion And Symptom-focused Engagement (EASE) for acute leukemia (AL) and report here on a phase II randomized controlled trial (RCT) to assess its feasibility and preliminary efficacy.Patients were recruited within 1 month of hospital admission and randomized to EASE plus usual care (UC) or UC alone. EASE includes (1) EASE-psy, a tailored psychotherapy delivered over 8 weeks, and (2) EASE-phys, weekly physical symptom screening over 8 weeks to trigger early palliative care. The primary outcome was traumatic stress symptoms; secondary outcomes included physical symptom burden and quality of life. Assessments were conducted at baseline and at 4, 8, and 12 weeks. Between-group differences were evaluated using multilevel modeling.Forty-two patients were randomized to EASE (n = 22) or UC (n = 20), with 76% retention at 12 weeks. Predefined feasibility outcomes were met: 86% (19/22) of EASE participants completed ≥ 50% of EASE-psy sessions (goal ≥ 64%); 100% received Edmonton Symptom Assessment System (ESAS, modified for AL) screenings, 64% (14/22) of whom completed ≥ 50% of planned screenings (goal ≥50%); and 100% with scores ≥ 4/10 on any physical ESAS-AL item had ≥ 1 meeting with the EASE-phys team (goal 100%). Significant treatment-group differences favoring EASE were observed in traumatic stress symptoms at 4 and 12 weeks, and pain intensity and interference at 12 weeks (all p .05).EASE is feasible in patients newly diagnosed with AL and shows promise of effectiveness. These results warrant a larger RCT to provide evidence for its more routine use as a standard of care.

BackgroundManaging Cancer And Living Meaningfully (CALM) is a brief individual psychotherapy for patients with advanced cancer. In an intervention-only phase 2a trial, CALM showed promising results, leading to the present 2b pilot, which introduces procedures for randomisation and improved rigour in preparation for a phase 3 randomised controlled trial (RCT).AimsTo test trial methodology and assess feasibility of a confirmatory RCT.DesignA parallel-arm RCT (intervention vs usual care) with 3 and 6-month follow-ups. Assessment of feasibility included rates of consent, randomisation, attrition, intervention non-compliance and usual care contamination. Primary outcome: depressive symptoms (Patient Health Questionnaire-9; PHQ-9). Secondary outcomes: major depressive disorder (MDD), generalised anxiety, death anxiety, spiritual well-being, attachment anxiety and avoidance, self-esteem, experiential avoidance, quality of life and post-traumatic growth. Bayesian conjugate analysis was used in this low-powered setting.Setting/participants60 adult patients with advanced cancer from the Princess Margaret Cancer Centre.ResultsRate of consent was 32%, randomisation 78%, attrition 25%, non-compliance 37% and contamination 17%. There was support for potential treatment effects on: PHQ-9, OR=1.48, 95% Credible Interval (CRI.95) (0.65, 3.38); MDD, OR=1.56, CRI.95(0.50, 4.84); attachment anxiety, OR=1.72, CRI.95(0.73, 4.03); and attachment avoidance, OR=1.58, CRI.95(0.67, 3.71). There was no support for effects on the seven remaining secondary outcomes.ConclusionsA phase 3 CALM RCT is feasible and should aim to detect effect sizes of d=0.40, with greater attention to issues of compliance and contamination.Trial registration numberNCT02353546.

Objective Acute leukemia (AL) is a life-threatening cancer associated with substantial morbidity and mortality, particularly in older adults. Given that there has been little research on the psychological impact of such malignancies with acute onset, we assessed the prevalence and correlates of depression and hopelessness in patients with AL. Methods Three hundred forty-one participants were recruited within 1 month of diagnosis or relapse and completed the Beck Depression Inventory-II (BDI-II), Beck Hopelessness Scale (BHS), Memorial Symptom Assessment Scale, and other psychosocial measures. Multivariate regression analyses identified correlates of depression and hopelessness. Results 17.8% reported clinically significant depressive symptoms (BDI-II ≥ 15), 40.4% of which were in the moderate-severe range (BDI-II ≥ 20). 8.5% reported significant symptoms of hopelessness (BHS ≥ 8). Depression was associated with greater physical symptom burden (adjusted R2 = 48.4%), while hopelessness was associated with older age and lower self-esteem (adjusted R2 = 45.4%). Both were associated with poorer spiritual well-being. Conclusions Clinically significant depressive symptoms were common early in the course of AL and related to physical symptom burden. Hopelessness was less common and associated with older age and lower self-esteem. The results suggest that whereas depression in AL may be related to disease burden, the preservation of hope may be linked to individual resilience, life stage, and realistic prognosis. Copyright © 2015 John Wiley & Sons, Ltd.

A raised erythematous eyelid lesion that appeared in a 31-year-old man was diagnosed as an arteriovenous malformation (AVM), with confirmatory Doppler ultrasound demonstrating high arterial flow. Surgical excision, aided by electrocautery for extensive hemorrhage, resulted in an acceptable cosmetic result. Histopathology of the excised lesion showed collapsed capillary channels lined by endothelium. AVM is rarely encountered in the eyelid.

Background: Breast cancer (BC) may recur years to decades after initial treatment, leading to incurable, metastatic disease. Prior studies have shown blood biopsy can detect minimal residual disease (MRD), but not in all patients and often with very short lead time. Most efforts thus far have focused on tracking one or a few mutations via ctDNA, which may limit sensitivity. Here we sought to maximize the detection sensitivity of blood biopsies by tracking up to hundreds of individualized tumor mutations in cell-free DNA (cfDNA). Doing so enables us to break the detection ceiling imposed by the limited copies of each gene in the cell-free DNA in a blood draw. Methods: cfDNA was extracted from archival plasma samples (n=271) from 142 patients with stage 0-III BC enrolled prospectively onto two IRB-approved studies. We applied whole-exome sequencing (WES) to define up to several hundred mutations from each patient’s tumor. To limit potential errors, we employed strict criteria to select somatic SNVs to track using duplex sequencing in cfDNA. We required detection of ≥ 2 mutations for a cfDNA sample to be MRD+ and excluded any mutations also found in a patient’s own germline DNA. Results: We identified 142 patients treated for stage 0-III BC, who had postoperative blood and plasma samples available, and were monitored for distant recurrences for up to thirteen years. All patients had biopsy-proven BC, with 86 (61%) having HR+/HER2- BC, 31 (22%) having HR-/HER2-, or “triple negative” BC (TNBC), and 25 (18%) having HER2-positive disease. Three (2%) patients had stage 0 disease, 32 (23%) had stage I, 68 (42%) had stage II, and 39 (27%) had stage III BC at diagnosis. Archived plasma samples were collected post-operatively, at year 1, and at year 4. We created individualized assays targeting a median of 57 mutations (range 2 - 346) per patient. Reasoning that MRD status after completion of all local therapy and chemotherapy might best predict for distant recurrence, we conducted a landmark analysis at one year following surgery, and found all patients (n=6/6) with detectable MRD experienced recurrence (HR=21.2 (7.43-60.35)) in a median of 6.7 (range 3.4 - 15.8) months. Median lead time including all timepoints from first positive blood sample to recurrence was 18.9 (range: 3.4 - 39.2) months. Finally, in a multivariate model, MRD remained highly statistically significant independent of stage, subtype, and age at diagnosis. Conclusions: We present a novel approach to MRD tracking based on the premise that tracking many - rather than one or a handful of - mutations inherently increases sensitivity and that assay personalization maximizes sensitivity in a disease without multiple, recurrent mutations. To our knowledge, the lead time we show here is significantly longer than that seen in prior investigations, and if confirmed, could offer an opportunity to treat MRD long before the development of clinically apparent metastatic disease. Prospective studies are needed to determine whether earlier detection of MRD is clinically meaningful for patients. Citation Format: Heather A Parsons, Justin Rhoades, Sarah C. Reed, Greg Gydush, Priyanka Ram, Pedro Exman, Kan Xiong, Christopher Lo, Tianyu Li, Mark Fleharty, Greg Kirkner, Denisse Rotem, Ofir Cohen, Melissa Hughes, Shoshanna Rosenberg, Laura Collins, Kathy Miller, Brendan Blumenstiel, Carrie Cibulskis, Donna Neuberg, Samuel S. Freeman, Niall Lennon, Nikhil Wagle, Gavin Ha, Daniel G. Stover, Atish D. Choudhury, Gad Getz, Matthew Meyerson, Nancy U. Lin, Ian E. Krop, J. Christopher Love, G. Mike Makrigiorgos, Ann Partridge, Erika Mayer, Todd R. Golub, Viktor A. Adalsteinsson. Ultrasensitive detection of minimal residual disease in patients treated for breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-01-03.

Background Felt security in close relationships may affect individual adaptation responses to existential threat in severe illness. We examined the contribution of attachment security to demoralization, a state of existential distress involving perceived pointlessness and meaninglessness in advanced cancer. Method A mixed cross-sectional sample of 382 patients with advanced cancer (mean age 59, 60% female) was recruited from outpatient oncology clinics. Participants completed self-report measures of attachment security, demoralization, depression, and physical symptom burden. We used multiple linear regression to analyze the association between attachment security and demoralization, controlling for demographic factors and symptom burden and tested whether attachment security moderated the association of symptom burden with demoralization. Separate analyses compared the contribution of the dimensions of attachment anxiety and attachment avoidance. Results The prevalence of clinically relevant demoralization was 35%. Demoralization was associated with lower attachment security (β = −0.54, 95%CI: −0.62 to 0.46). This effect was empirically stronger for attachment anxiety (β = 0.52, 95%CI: 0.44 to 0.60) compared to attachment avoidance (β = 0.36, 95%CI: 0.27 to 0.45). Attachment security also significantly moderated the association of physical symptom burden with demoralization, such that with less attachment security, there was a stronger association between symptom burden and demoralization. Conclusion Attachment security may protect from demoralization in advanced cancer. Its relative lack, particularly on the dimension of attachment anxiety, may limit adaptive capacities to deal with illness burden and to sustain morale and purpose in life. An understanding of individual differences in attachment needs can inform existential interventions for severely ill individuals.

A broad understanding of the different imaging modalities used to assess the physiologic changes seen in Graves' orbitopathy complement clinical examination. Subtle applications of radiographic imaging techniques allow for a better understanding of the overall physiology of the orbit, quantify progression of disease, and differentiate it from orbital diseases with overlapping features. A nuanced approach to interpreting imaging features may allow us to delineate inactive from active thyroid eye disease, and advances within this field may arm clinicians with the ability to better predict and prevent dysthyroid optic neuropathy.

The occurrence of an accessory palpebral fissure and eyelid is an extremely rare phenomenon. An isolated accessory palpebral fissure and eyelid have been reported only twice in the literature, and in one case as an extension of Delleman syndrome, or oculocerebrocutaneous syndrome. The authors report a case of a full-term newborn who presented with an accessory palpebral fissure and eyelid associated with microcornea, skin polyps and tags, cutis dysplasia, and hypoplasia of the corpus callosum with an otherwise normal systemic workup and negative genetic screening. Detailed surgical management and histopathological analysis of the accessory findings are also described.

Amyloidosis is a disorder characterized by the deposition of insoluble abnormal proteins in the extracellular space. It may occur as a localized lesion or as a systemic disease involving multiple organs and systems. Localized conjunctival amyloidosis is rare and is less frequently associated with systemic involvement. Although amyloidosis itself is a benign lesion involvement of multiple organs and systems is associated with poor prognosis. Diagnosis of amyloidosis is made on biopsy specimens with Congo red staining for the appearance of apple-green birefringence under polarized light microscopy. Liquid chromatography tandem-mass spectrometry (LC-MS/MS) is much more sensitive in diagnosing amyloidosis and can determine the type of amyloid deposit. Here we reported a case of conjunctival amyloidosis in a 52 year-old male patient who was presented with left lower eyelid swelling to our medical center. He has a complicated past medical history of anti-phospholipid antibody syndrome, Buerger's disease (thromboangitis obliterans), and small cell lymphoma (SLL) of the right orbit/eyelid. The patient received radiation to the right orbit to treat SLL with therapy completed one and a half years prior to presentation. Physical examination revealed a firm, raised yellowish colored lesion in the left lower conjunctiva. The conjunctival lesion was biopsied, and tissue sections were examined with Congo red stains and LC-MS/MS analysis. The biopsy showed amyloid deposits without evidence of malignancy, and the type of proteins in the deposit was immunoglobulin light chain (AL) of kappa type. A complete work up was taken for possible systemic involvement of amyloidosis and results were all negative. To our knowledge, this is the first case of localized conjunctival amyloidosis with a history of contralateral orbit/eyelid SLL.

PURPOSE To study whether ethmoidectomy predisposes the orbit to medial wall fracture with lesser trauma. METHODS An interventional cadaver study of 5 heads (10 orbits); the left or right orbit was randomized to undergo endoscopic complete ethmoidectomy with the fellow orbit as control. Fractures were induced with direct globe trauma, and heads underwent CT scanning. Energy to induce fracture, peak orbital pressure at time of fracture, fracture pattern, and volume of herniated tissue were measured and analyzed. RESULTS Fractures were induced in both orbits of all cadavers. Experimental orbits after ethmoidectomy sustained orbital fracture at less energy required (2.14 ± 0.66 vs. 3.10 ± 0.19 J, mean difference: -0.96 ± 0.33 J, p < 0.05). Similarly, peak orbital pressure was lower for ethmoidectomized orbits than for controls (11.8 ± 8.42 vs. 28.4 ± 13.2 mm Hg, mean difference: -16.5 ± 6.9 mm Hg, p < 0.05). Orbits after ethmoidectomy were more likely to sustain medial wall involvement in fracture (100%) compared with controls (20%, p < 0.05) and pure medial wall fracture (80%) compared with controls (0%, p < 0.05). Overall volume of herniated orbital contents was not significantly different between groups (p = 0.25); volume of herniated tissue from the medial wall only was significantly greater in orbits after ethmoidectomy (mean difference: 1.01 ± -0.39 cm, p < 0.05). CONCLUSION Endoscopic ethmoidectomy in fresh cadavers reduces impact energy necessary to induce orbital fracture and increases the prevalence of medial wall involvement. Clinicians may wish to counsel patients undergoing endoscopic sinus surgery about these relative risks.