The Role of Radiation Therapy on Postmastectomy Breast Reconstruction Patients

https://openworks.mdanderson.org/sumexp22/1071/thumbnail.jp

Deficits in attention to emotional stimuli distinguish youth with severe mood dysregulation from youth with bipolar disorder.

Studying attention in the context of emotional stimuli may aid in differentiating pediatric bipolar disorder (BD) from severe mood dysregulation (SMD). SMD is characterized by chronic irritability, arousal, and hyper-reactivity; SMD youth frequently receive a BD diagnosis although they do not meet DSM-IV criteria for BD because they lack manic episodes. We compared 57 BD (14.4 +/- 2.9 years old, 56% male), 41 SMD (12.6 +/- 2.6 years old, 66% male), and 33 control subjects (13.7 +/- 2.5 years old, 52% male) using the Emotional Interrupt task, which examines how attention is impacted by positive, negative, or neutral distracters. We compared reaction time (RT) and accuracy and calculated attention interference scores by subtracting performance on neutral trials from emotional trials. Between-group analyses indicated that SMD subjects had significantly reduced attention interference from emotional distracters relative to BD and control subjects. Thus, attention in SMD youth was not modulated by emotional stimuli. This blunted response in SMD youth may contribute to their affective and behavioral dysregulation

Analysis of eligibility criteria in Alzheimer’s and related dementias clinical trials

Overly restrictive clinical trial eligibility criteria can reduce generalizability, slow enrollment, and disproportionately exclude historically underrepresented populations. The eligibility criteria for 196 Alzheimer’s Disease and Related Dementias (AD/ADRD) trials funded by the National Institute on Aging were analyzed to identify common criteria and their potential to disproportionately exclude participants by race/ethnicity. The trials were categorized by type (48 Phase I/II pharmacological, 7 Phase III/IV pharmacological, 128 non-pharmacological, 7 diagnostic, and 6 neuropsychiatric) and target population (51 AD/ADRD, 58 Mild Cognitive Impairment, 25 at-risk, and 62 cognitively normal). Eligibility criteria were coded into the following categories: Medical, Neurologic, Psychiatric, and Procedural. A literature search was conducted to describe the prevalence of disparities for eligibility criteria for African Americans/Black (AA/B), Hispanic/Latino (H/L), American Indian/Alaska Native (AI/AN) and Native Hawaiian/Pacific Islander (NH/PI) populations. The trials had a median of 15 criteria. The most frequent criterion were age cutoffs (87% of trials), specified neurologic (65%), and psychiatric disorders (61%). Underrepresented groups could be disproportionately excluded by 16 eligibility categories; 42% of trials specified English-speakers only in their criteria. Most trials (82%) contain poorly operationalized criteria (i.e., criteria not well defined that can have multiple interpretations/means of implementation) and criteria that may reduce racial/ethnic enrollment diversity.</p

“Build a Bridge So You Can Cross It:” A Photo-Elicitation Study of Health and Wellness Among Homeless and Marginally Housed Veterans

As part of a photo-elicitation interview study, we aimed to describe homeless and marginally housed Veterans’ experiences with health and wellness, health decisions, and health-related behaviors. Twenty Veterans receiving Veterans Affairs Homeless Patient-Aligned Care Team care took photographs depicting health and wellness, then used their photographs to discuss the same topics in 30-60 minute audio-recorded, semi-structured photo-elicitation interviews. Transcripts were analyzed using template analysis. Veterans described eight dimensions related to their health and wellness; physical, social, and environmental were most commonly discussed, followed by emotional, intellectual, spiritual, occupational, and financial wellness. Photographs contained literal and metaphorical depictions that were positively-oriented, comprehensive, and reflective. Of central importance was overcoming external and internal obstacles to wellness. Photo-narratives may be helpful in educating health care providers and advocating for the needs of homeless and marginally housed Veterans. Integrated primary care services should address the multi-faceted aspects of health and wellness for Veterans

Dose-finding study of a 90-day contraceptive vaginal ring releasing estradiol and segesterone acetate.

ObjectiveTo evaluate serum estradiol (E2) concentrations during use of 90-day contraceptive vaginal rings releasing E2 75, 100, or 200&nbsp;mcg/day and segesterone acetate (SA) 200&nbsp;mcg/day to identify a dose that avoids hypoestrogenism.Study designWe conducted a multicenter dose-finding study in healthy, reproductive-aged women with regular cycles with sequential enrollment to increasing E2 dose groups. We evaluated serum E2 concentrations twice weekly for the primary outcome of median E2 concentrations throughout initial 30-day use (target ≥40&nbsp;pg/mL). In an optional 2-cycle extension substudy, we randomized participants to 2- or 4-day ring-free intervals per 30-day cycle to evaluate bleeding and spotting based on daily diary information.ResultsSixty-five participants enrolled in E2 75 (n&nbsp;=&nbsp;22), 100 (n&nbsp;=&nbsp;21), and 200 (n&nbsp;=&nbsp;22)&nbsp;mcg/day groups; 35 participated in the substudy. Median serum E2 concentrations in 75 and 100&nbsp;mcg/day groups were &lt;40&nbsp;pg/mL. In the 200&nbsp;mcg/day group, median E2 concentrations peaked on days 4-5 of CVR use at 194&nbsp;pg/mL (range 114-312&nbsp;pg/mL) and remained &gt;40&nbsp;pg/mL throughout 30&nbsp;days; E2 concentrations were 37&nbsp;pg/mL (range 28-62&nbsp;pg/mL) on days 88-90 (n&nbsp;=&nbsp;11). Among the E2 200&nbsp;mcg/day substudy participants, all had withdrawal bleeding following ring removal. The 2-day ring-free interval group reported zero median unscheduled bleeding and two (range 0-16) and three (range 0-19) unscheduled spotting days in extension cycles 1 and 2, respectively. The 4-day ring-free interval group reported zero median unscheduled bleeding or spotting days.ConclusionsEstradiol concentrations with rings releasing E2 200&nbsp;mcg/day and SA 200&nbsp;mcg/day avoid hypoestrogenism over 30-day use.ImplicationsA 90-day contraceptive vaginal ring releasing estradiol 200&nbsp;mcg/day and segesterone acetate 200&nbsp;mcg/day achieves estradiol concentrations that should avoid hypoestrogenism and effectively suppresses ovulation

Maintenance of Sertoli Cell Number and Function in Immature Human Testicular Tissues Exposed to Platinum-Based Chemotherapy-Implications for Fertility Restoration

Background: Retrospective studies in adult survivors of childhood cancer show long-term impacts of exposure to alkylating chemotherapy on future fertility. We recently demonstrated germ cell loss in immature human testicular tissues following exposure to platinum-based chemotherapeutic drugs. This study investigated the effects of platinum-based chemotherapy exposure on the somatic Sertoli cell population in human fetal and pre-pubertal testicular tissues. Methods: Human fetal (n = 23; 14–22 gestational weeks) testicular tissue pieces were exposed to cisplatin (0.5 or 1.0 μg/ml) or vehicle for 24 h in vitro and analysed 24–240 h post-exposure or 12 weeks after xenografting. Human pre-pubertal (n = 10; 1–12 years) testicular tissue pieces were exposed to cisplatin (0.5 μg/ml), carboplatin (5 μg/ml) or vehicle for 24 h in vitro and analysed 24–240 h post-exposure; exposure to carboplatin at 10-times the concentration of cisplatin reflects the relative clinical doses given to patients. Immunohistochemistry was performed for SOX9 and anti-Müllerian hormone (AMH) expression and quantification was carried out to assess effects on Sertoli cell number and function respectively. AMH and inhibin B was measured in culture medium collected post-exposure to assess effects on Sertoli cell function. Results: Sertoli cell (SOX9(+ve)) number was maintained in cisplatin-exposed human fetal testicular tissues (7,647 ± 459 vs. 7,767 ± 498 cells/mm(2); p > 0.05) at 240 h post-exposure. No effect on inhibin B (indicator of Sertoli cell function) production was observed at 96 h after cisplatin (0.5 and 1.0 μg/ml) exposure compared to control (21 ± 5 (0.5 μg/ml cisplatin) vs. 23 ± 7 (1.0 μg/ml cisplatin) vs. 25 ± 7 (control) ng/ml, p > 0.05). Xenografting of cisplatin-exposed (0.5 μg/ml) human fetal testicular tissues had no long-term effect on Sertoli cell number or function (percentage seminiferous area stained for SOX9 and AMH, respectively), compared with non-exposed tissues. Sertoli cell number was maintained in human pre-pubertal testicular tissues following exposure to either 0.5 μg/ml cisplatin (6,723 ± 1,647 cells/mm(2)) or 5 μg/ml carboplatin (7,502 ± 627 cells/mm(2)) compared to control (6,592 ± 1,545 cells/mm(2)). Conclusions: This study demonstrates maintenance of Sertoli cell number and function in immature human testicular tissues exposed to platinum-based chemotherapeutic agents. The maintenance of a functional Sertoli cell environment following chemotherapy exposure suggests that fertility restoration by spermatogonial stem cell (SSC) transplant may be possible in boys facing platinum-based cancer treatment

Homeless and marginally housed Veteran perspectives on participating in a photo-elicitation research study

Photo-elicitation interviewing (PEI) seems a valuable tool for engaging marginalized populations in research despite documented challenges. Given limited data on acceptability of PEI among homeless and marginally housed Veterans, this evaluation aimed to characterize their research experience. Veterans took photographs about health, health behaviors, and health care which facilitated semi-structured interviews. Their research study experience was assessed via a modified Reactions to Research Participation Questionnaire-Revised (RRPQ-R), along with additional survey and open-ended questions. Of the 20 participants who consented and participated, 16 (80%) completed the exit surveys. Most participants (\u3e88%) indicated favorable experiences and limited drawbacks. Respondents disagreed that participation was difficult or overly time consuming. Many indicated intense or unexpected emotionality. Open-ended responses indicated appreciation of photography, interview experiences, and connection with study staff. Transportation was the most cited barrier. Overall, experiences were reportedly emotionally challenging, but positive. PEI appears to be acceptable to homeless and marginally housed Veterans for eliciting their perspectives

Nutritional and metabolic status of children with autism vs. neurotypical children, and the association with autism severity

<p>Abstract</p> <p>Background</p> <p>The relationship between relative metabolic disturbances and developmental disorders is an emerging research focus. This study compares the nutritional and metabolic status of children with autism with that of neurotypical children and investigates the possible association of autism severity with biomarkers.</p> <p>Method</p> <p>Participants were children ages 5-16 years in Arizona with Autistic Spectrum Disorder (n = 55) compared with non-sibling, neurotypical controls (n = 44) of similar age, gender and geographical distribution. Neither group had taken any vitamin/mineral supplements in the two months prior to sample collection. Autism severity was assessed using the Pervasive Development Disorder Behavior Inventory (PDD-BI), Autism Treatment Evaluation Checklist (ATEC), and Severity of Autism Scale (SAS). Study measurements included: vitamins, biomarkers of vitamin status, minerals, plasma amino acids, plasma glutathione, and biomarkers of oxidative stress, methylation, sulfation and energy production.</p> <p>Results</p> <p>Biomarkers of children with autism compared to those of controls using a t-test or Wilcoxon test found the following statistically significant differences (p < 0.001): Low levels of biotin, plasma glutathione, RBC SAM, plasma uridine, plasma ATP, RBC NADH, RBC NADPH, plasma sulfate (free and total), and plasma tryptophan; also high levels of oxidative stress markers and plasma glutamate. Levels of biomarkers for the neurotypical controls were in good agreement with accessed published reference ranges. In the Autism group, mean levels of vitamins, minerals, and most amino acids commonly measured in clinical care were within published reference ranges.</p> <p>A stepwise, multiple linear regression analysis demonstrated significant associations between several groups of biomarkers with all three autism severity scales, including vitamins (adjusted R²of 0.25-0.57), minerals (adj. R²of 0.22-0.38), and plasma amino acids (adj. R²of 0.22-0.39).</p> <p>Conclusion</p> <p>The autism group had many statistically significant differences in their nutritional and metabolic status, including biomarkers indicative of vitamin insufficiency, increased oxidative stress, reduced capacity for energy transport, sulfation and detoxification. Several of the biomarker groups were significantly associated with variations in the severity of autism. These nutritional and metabolic differences are generally in agreement with other published results and are likely amenable to nutritional supplementation. Research investigating treatment and its relationship to the co-morbidities and etiology of autism is warranted.</p

Prediction of Breast Cancer-Related Lymphedema By Dermal Backflow Detected With Near-infrared Fluorescence Lymphatic Imaging

PURPOSE: Mild breast cancer-related lymphedema (BCRL) is clinically diagnosed as a 5%-10% increase in arm volume, typically measured no earlier than 3-6 months after locoregional treatment. Early BCRL treatment is associated with better outcomes, yet amid increasing evidence that lymphedema exists in a latent form, treatment is typically delayed until arm swelling is obvious. In this study, we investigated whether near-infrared fluorescence lymphatic imaging (NIRF-LI) surveillance could characterize early onset of peripheral lymphatic dysfunction as a predictor of BCRL. METHODS: In a prospective, longitudinal cohort/observational study (NCT02949726), subjects with locally advanced breast cancer who received axillary lymph node dissection and regional nodal radiotherapy (RT) were followed serially, between 2016 and 2021, before surgery, 4-8 weeks after surgery, and 6, 12, and 18 months after RT. Arm volume was measured by perometry, and lymphatic (dys) function was assessed by NIRF-LI. RESULTS: By 18 months after RT, 30 of 42 study subjects (71%) developed mild-moderate BCRL (i.e., ≥ 5% arm swelling relative to baseline), all manifested by dermal backflow of lymph into lymphatic capillaries or interstitial spaces. Dermal backflow had an 83% positive predictive value and 86% negative predictive value for BCRL, with a sensitivity of 97%, specificity of 50%, accuracy of 83%, positive likelihood ratio of 1.93, negative likelihood ratio of 0.07, and odds ratio of 29.00. Dermal backflow appeared on average 8.3 months, but up to 23 months, before the onset of mild BCRL. CONCLUSION: BCRL can be predicted by dermal backflow, which often appears months before arm swelling, enabling early treatment before the onset of edema and irreversible tissue changes