We explored early trajectories of psychosocial risk levels (i.e., Universal, Targeted, or Clinical) in families of children and adolescents newly diagnosed with cancer using the Psychosocial ...Assessment Tool (PAT) in secondary analysis of data from a randomized trial assessing the effects of psychosocial screening. Families were allocated to an intervention group (IG, PAT summary provided to patient treating team) or a control group (CG, no PAT summary provided to treating team) in two pediatric cancer centers. Primary caregivers (
N
= 122) of newly diagnosed children and adolescents completed the PAT along with outcome measures for the trial at 2–4 weeks post-diagnosis (T1) and 6 months post-diagnosis (T2). The CG and IG were not significantly different, in terms of PAT risk levels at T1 and T2, but at T1, the PAT total and parent stress scores were higher in the CG (
p
’s < .05). The distribution of families across PAT risk levels did not differ significantly between T1 and T2 (
p
> .05) with 63% of families remaining within the same PAT risk level at T2. A subgroup of families in the Targeted risk level at T1 moved to the Universal (34%) or Clinical (13%) levels of risk at T2 (
p
’s < .01). Another subgroup with Universal risk at T1 trended to Targeted (28%) or Clinical (2%) at T2. While psychosocial risk remained relatively consistent for the majority of families, a smaller number of families experienced changes in risk level over time. Further investigation of these exploratory trends in psychosocial trajectories is needed to guide psychosocial support during child’s cancer treatment.
Clinical Trial Registration Number:
NCT02788604 (registered with ClinicalTrials.gov).
Nipple-sparing mastectomy is appropriate for selected patients with early-stage breast cancer or high breast cancer risk. However, the postoperative rate of nipple necrosis is relatively high (10 to ...30 percent). This study analyzed the impact of clinicopathologic and surgical variables on partial and total nipple necrosis rates after nipple-sparing mastectomy and compared overall complication rates between nipple-sparing and skin-sparing mastectomy.
The study included 233 cases; 113 had nipple-sparing mastectomy and immediate breast reconstruction and 120 were matched cases of skin-sparing mastectomy and immediate reconstruction performed at the authors' institution from September of 2003 through May of 2011.
The overall complication rate was 28 percent for nipple-sparing mastectomy and 27 percent for skin-sparing mastectomy (p > 0.99). In patients who did not have axillary surgery (those undergoing risk-reducing mastectomy), the overall rate was significantly higher in the nipple-sparing group (26 percent versus 9 percent; p = 0.06). However, in patients who had axillary surgery (either sentinel lymph node biopsy or axillary lymphadenectomy), the rate did not differ between the two groups. For nipple-sparing mastectomy, the overall incidence of any (partial or total) nipple necrosis was 20 percent. Only two cases (2 percent) had total necrosis. Larger breasts (C cup or larger) were associated with a higher rate of nipple necrosis (p = 0.003).
The authors found no significant difference in the overall incidence of complications in patients who had nipple-sparing mastectomy or skin-sparing mastectomy. Exclusion of axillary lymphatic surgery in nipple-sparing mastectomy patients did not decrease the incidence of complications.
BACKGROUND: The use of clinical aromatherapy for managing pain has been studied in surgical patients and in women during childbirth. However, there are limited data on the use of aromatherapy for ...alleviating cancer-related pain, particularly at the end of life. OBJECTIVES: This pilot study identifies the preand postimplementation effects of aromatherapy on pain level, pain perception, and the use of oral morphine equivalent among patients with cancer at the end of life. METHODS: A survey was conducted to assess participant pain levels preimplementation of aromatherapy. Participants were then asked to rate their pain and describe how they felt 15 minutes postimplementation of aromatherapy. A chart review comparing oral morphine equivalent use pre- and postimplementation of aromatherapy was also performed. FINDINGS: Postimplementation of aromatherapy, mean pain scores and 24-hour oral morphine equivalent use decreased. Participants also described an improved pain experience and found aromatherapy to be soothing. KEYWORDS aromatherapy; cancer; pain; essential oils; end of life; pain management
Background
Risk assessment for breast cancer–related lymphedema has emphasized upper‐limb symptoms and treatment‐related risk factors. This article examined breast cancer–related lymphedema after ...surgery, overall and in association with broader demographic and clinical features.
Methods
The Carolina Breast Cancer Study phase 3 followed participants for breast cancer–related lymphedema from baseline (on average, 5 months after breast cancer diagnosis) to 7 years after diagnosis. Among 2645 participants, 552 self‐reported lymphedema cases were identified. Time‐to‐lymphedema curves and inverse probability weighted conditional Cox proportional hazards model were used to evaluate whether demographics and clinical features were associated with breast cancer–related lymphedema.
Results
Point prevalence of breast cancer–related lymphedema was 6.8% at baseline, and 19.9% and 23.8% at 2 and 7 years after diagnosis, respectively. Most cases had lymphedema in the arm (88%‐93%), whereas 14% to 27% presented in the trunk and/or breast. Beginning approximately 10 months after diagnosis, younger Black women had the highest risk of breast cancer–related lymphedema and older non‐Black women had the lowest risk. Positive lymph node status, larger tumor size (>5 cm), and estrogen receptor–negative breast cancer, as well as established risk factors such as higher body mass index, removal of more than five lymph nodes, mastectomy, chemotherapy, and radiation therapy, were significantly associated with increased hazard (1.5‐ to 3.5‐fold) of lymphedema.
Conclusions
Findings highlight that hazard of breast cancer–related lymphedema differs by demographic characteristics and clinical features. These factors could be used to identify those at greatest need of lymphedema prevention and early intervention.
Lay summary
In this study, the aim was to investigate breast cancer–related lymphedema (BCRL) burden.
This study found that risk of BCRL differs by race, age, and other characteristics.
A population‐based racially diverse cohort of women with breast cancer was used to assess burden of lymphedema as well as related demographic and clinical features. The findings could be used to identify those at greatest need of lymphedema prevention and early intervention after breast cancer diagnosis.
X-linked myotubular myopathy (XLMTM) results from MTM1 gene mutations and myotubularin deficiency. Most XLMTM patients develop severe muscle weakness leading to respiratory failure and death, ...typically within 2 years of age. Our objective was to evaluate the efficacy and safety of systemic gene therapy in the p.N155K canine model of XLMTM by performing a dose escalation study. A recombinant adeno-associated virus serotype 8 (rAAV8) vector expressing canine myotubularin (cMTM1) under the muscle-specific desmin promoter (rAAV8-cMTM1) was administered by simple peripheral venous infusion in XLMTM dogs at 10 weeks of age, when signs of the disease are already present. A comprehensive analysis of survival, limb strength, gait, respiratory function, neurological assessment, histology, vector biodistribution, transgene expression, and immune response was performed over a 9-month study period. Results indicate that systemic gene therapy was well tolerated, prolonged lifespan, and corrected the skeletal musculature throughout the body in a dose-dependent manner, defining an efficacious dose in this large-animal model of the disease. These results support the development of gene therapy clinical trials for XLMTM.
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Mack and colleagues conducted a gene therapy dose-finding study in a dog model of X-linked myotubular myopathy (XLMTM), a severe monogenic muscle disease. A single systemic treatment prolonged lifespan and corrected skeletal musculature throughout the body in a dose-dependent manner. These data support development of gene therapy clinical trials for XLMTM.
Background Data mining of electronic health records to identify patients suspected of familial hypercholesterolemia (FH) has been limited by absence of both phenotypic and genomic data in the same ...cohort. Methods and Results Using the Geisinger MyCode Community Health Initiative cohort (n=130 257), we ran 2 screening algorithms (Mayo Clinic Mayo and flag, identify, network, deliver FIND FH) to determine FH genetic and phenotypic diagnostic yields. With 29 243 excluded by Mayo (for secondary causes of hypercholesterolemia, no lipid value in electronic health records), 52 034 excluded by FIND FH (insufficient data to run the model), and 187 excluded for prior FH diagnosis, a final cohort of 59 729 participants was created. Genetic diagnosis was based on presence of a pathogenic or likely pathogenic variant in FH genes. Charts from 180 variant-negative participants (60 controls, 120 identified by FIND FH and Mayo) were reviewed to calculate Dutch Lipid Clinic Network scores; a score ≥5 defined probable phenotypic FH. Mayo flagged 10 415 subjects; 194 (1.9%) had a pathogenic or likely pathogenic FH variant. FIND FH flagged 573; 34 (5.9%) had a pathogenic or likely pathogenic variant, giving a net yield from both of 197 out of 280 (70%). Confirmation of a phenotypic diagnosis was constrained by lack of electronic health record data on physical findings or family history. Phenotypic FH by chart review was present by Mayo and/or FIND FH in 13 out of 120 versus 2 out of 60 not flagged by either (
<0.09). Conclusions Applying 2 recognized FH screening algorithms to the Geisinger MyCode Community Health Initiative identified 70% of those with a pathogenic or likely pathogenic FH variant. Phenotypic diagnosis was rarely achievable due to missing data.
Chimeric antigen receptor (CAR) T cell therapy has been highly successful in hematological malignancies leading to their US Food and Drug Administration (FDA) approval. However, the efficacy of CAR ...T cells in solid tumors is limited by tumor-induced immunosuppression, leading to the development of combination approaches, such as adjuvant programmed cell death 1 (PD-1) blockade. Current FDA-approved methods for generating CAR T cells utilize either anti-CD3 and interleukin (IL)-2 or anti-CD3/CD28 beads, which can generate a T cell product with an effector/exhausted phenotype. Whereas different cytokine preconditioning milieu, such as IL-7/IL-15, have been shown to promote T cell engraftment, the impact of this approach on CAR T cell responses to adjuvant immune-checkpoint blockade has not been assessed. In the current study, we reveal that the preconditioning of CAR T cells with IL-7/IL-15 increased CAR T cell responses to anti-PD-1 adjuvant therapy. This was associated with the emergence of an intratumoral CD8+CD62L+TCF7+IRF4– population that was highly responsive to anti-PD-1 therapy and mediated the vast majority of transcriptional and epigenetic changes in vivo following PD-1 blockade. Our data indicate that preservation of CAR T cells in a TCF7+ phenotype is crucial for their responsiveness to adjuvant immunotherapy approaches and should be a key consideration when designing clinical protocols.
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ABSTRACT
Introduction
X‐linked myotubular myopathy (XLMTM), a devastating pediatric disease caused by the absence of the protein myotubularin, results from mutations in the MTM1 gene. While there is ...no cure for XLMTM, we previously reported effects of MTM1 gene therapy using adeno‐associated virus (AAV) vector on muscle weakness and pathology in MTM1‐mutant dogs. Here, we followed 2 AAV‐infused dogs over 4 years.
Methods
We evaluated gait, strength, respiration, neurological function, muscle pathology, AAV vector copy number (VCN), and transgene expression.
Results
Four years following AAV‐mediated gene therapy, gait, respiratory performance, neurological function and pathology in AAV‐infused XLMTM dogs remained comparable to their healthy littermate controls despite a decline in VCN and muscle strength.
Conclusions
AAV‐mediated gene transfer of MTM1 in young XLMTM dogs results in long‐term expression of myotubularin transgene with normal muscular performance and neurological function in the absence of muscle pathology. These findings support a clinical trial in patients. Muscle Nerve 56: 943–953, 2017
Three genetic conditions-hereditary breast and ovarian cancer syndrome, Lynch syndrome, and familial hypercholesterolemia-have tier 1 evidence for interventions that reduce morbidity and mortality, ...prompting proposals to screen unselected populations for these conditions. We examined the impact of genomic screening on risk management and early detection in an unselected population.
Observational study of electronic health records (EHR) among individuals in whom a pathogenic/likely pathogenic variant in a tier 1 gene was discovered through Geisinger's MyCode project. EHR of all eligible participants was evaluated for a prior genetic diagnosis and, among participants without such a diagnosis, relevant personal/family history, postdisclosure clinical diagnoses, and postdisclosure risk management.
Eighty-seven percent of participants (305/351) did not have a prior genetic diagnosis of their tier 1 result. Of these, 65% had EHR evidence of relevant personal and/or family history of disease. Of 255 individuals eligible to have risk management, 70% (n = 179) had a recommended risk management procedure after results disclosure. Thirteen percent of participants (41/305) received a relevant clinical diagnosis after results disclosure.
Genomic screening programs can identify previously unrecognized individuals at increased risk of cancer and heart disease and facilitate risk management and early cancer detection.
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