Anti-PD-1 therapy in advanced sarcomas: is cutaneous primary site a stronger predictor of response than histologic subtype?

BACKGROUND: Immune checkpoint inhibitors (ICIs) have shown modest antitumor activity in unselected advanced sarcomas. Histology driven approach to patient selection is the current standard for off-label anti-programmed cell death 1 (PD1) immunotherapy use. METHODS: We retrospectively reviewed the clinical characteristics and outcomes of patients with advanced sarcoma who were treated with off label anti-PD1 immunotherapy at our center. RESULTS: A total of 84 patients with 25 histological subtypes were included. Nineteen patients (23%) had a cutaneous primary tumor site. Eighteen patients (21%) were classified as having clinical benefit, including 1 patient with complete response, 14 with partial response, and 3 with stable disease lasting over 6 months with previously progressive disease. Cutaneous primary site location was associated with higher clinical benefit rate (58% vs. 11%, p < 0.001), longer median PFS (8.6 vs. 2.5 months, p = 0.003) and OS (19.0 vs. 9.2 months, p = 0.011), compared to non-cutaneous primary. Patients with histological subtypes that pembrolizumab is indicated per current National Comprehensive Cancer Network guidelines had modestly higher rate of clinical benefit versus other histologies, however, the difference was statistically insignificant (29% vs. 15%, p = 0.182) and no statistically significant difference in PFS or OS was observed between these groups. Immune-related adverse events were more frequently seen among patients with clinical benefit (72% vs. 35%, p = 0.007). CONCLUSIONS: Anti-PD1-based immunotherapy is highly efficacious in advanced sarcomas of cutaneous primary site. Cutaneous primary site location is a stronger predictor of ICI response than histologic subtype and should be accounted for in treatment guidelines and clinical trial design.

Evaluation of Broad Skill Repertoire Changes Over 3 Months of PEAK Implementation in a Special Education Classroom.

The Promoting the Emergence of Advanced Knowledge (PEAK) Relational Training System provides a comprehensive language and cognition training strategy for use with children with disabilities. In the present study, we conducted PEAK within a special education classroom over the course of 3 months, and language and cognitive skills were assessed using the PEAK Comprehensive Assessment (PCA). On average, each of the five participants mastered 11.2 target programs across PEAK modules with an average of 186.4 new verbal behaviors or supporting behaviors. All participants showed an increase on the PCA following the intervention, with an average increase of 39.6 correct responses, and parents and staff reported improvements in participants' use of language at home and at school relative to prior semesters. Supplementary Information: The online version contains supplementary material available at 10.1007/s40617-021-00657-6.

A Rare Case of Bullous Pemphigoid Secondary to Checkpoint Inhibitor Immunotherapy: A Tense Situation.

Bullous pemphigoid is a serious and rare complication of immunotherapy. Here, we present a case of bullous pemphigoid secondary to ipilimumab/nivolumab checkpoint inhibitor therapy in a patient with metastatic melanoma. Immune checkpoint inhibitor therapy is more widely used now to treat cancer patients, bringing more challenging cases of adverse events associated with their use. Bullous pemphigoid can be a difficult diagnosis to make in the initial stages as the rash is similar to other red rashes before transforming into the typical appearance of a blister. As bullous pemphigoid can be a life-threatening adverse event, early identification is key to increasing patient survival.

Developing Remote Delivery of Language and Cognitive Training for Use With Children With Autism: A Technological Report.

Remote delivery of language and cognitive training is becoming increasingly prevalent within special education settings, and the recent COVID-19 pandemic has challenged many providers to pivot to telehealth models. This technical article outlines a procedure for developing computerized discrete-trial training programs using commonly available software, as well as a description of how to adapt this strategy to teach chained tasks remotely. Within this article, we describe how to establish unidirectional and bidirectional remote interfaces to work directly with learners. Finally, we conducted a field test of these approaches with programs adapted from two standardized curricula: PEAK and PRISM. We conclude the article by discussing barriers and potential solutions that we observed while field-testing these procedures within special education settings in response to the wide-scale emigration to remote teaching due to the COVID-19 pandemic. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40617-020-00544-6.

Synthesizing the Multiple-Probe Experimental Design With the PEAK Relational Training System in Applied Settings.

The scientist-practitioner model necessitates embedding experimental designs within applied practice. This technical report describes a procedure for embedding a multiple-probe experimental design within the PEAK Relational Training System across all four PEAK modules. Baseline probes provide a direct test of target skills negatively endorsed within the PEAK assessment battery and can provide an estimate of skill acquisition in the absence of direct training. Temporal staggering of the probes maintains the fidelity of the experimental design and allows for the design to evolve along with learner skill acquisition. Achievement of mastery criteria demonstrates the efficacy of programming, and failure to achieve mastery can be remedied through programming adjustments that can be captured within the design. We additionally conducted a field test of the design with a child with disabilities, supporting the viability of this procedure within applied settings.

Feeding Infants with Neonatal Abstinence Syndrome: Finding the Sweet Spot.

PURPOSE: The purpose of this study is to learn how caregivers who are expert in feeding infants with neonatal abstinence syndrome (NAS) successfully feed these infants during withdrawal. DESIGN/SAMPLE: Focus group methodology was used to gather information from self-identified experts from three large regional NICUs. Twelve NICU nurses and speech therapists participated in open-ended, recorded discussions. Detailed flip chart notes were taken, reviewed, and verified by the participants before the group ended. RESULTS: Four major themes emerged verified by the participants: (1) optimal medication management, (2) follow the baby's cues, (3) calm and comfortable, and (4) nurture the relationship. Participants reported using both common and creative techniques. Keeping the infant calm was crucial to being successful, as well as maintaining good control of withdrawal signs. Feeding the infant facing away from them to avoid eye contact was used, as well as vertical rocking, continuous butt patting, bundling, "shhing" sound, and a novel feeding position.

Long-Term Outcomes of Infants with Neonatal Abstinence Syndrome.

Parents of infants with neonatal abstinence syndrome (NAS) in the NICU may have questions about the long-term consequences of prenatal exposure to methadone, both asked and unasked. Although the signs of withdrawal will abate relatively quickly, parents should be aware of potential vision, motor, and behavioral/cognitive problems, as well as sleeping disturbances and ear infections so their infants can be followed closely and monitored by their pediatrician with appropriate referrals made. Furthermore, this knowledge may inspire parents to enroll their infants in an early intervention program to help optimize their outcomes. There are still many unanswered questions about epigenetic consequences, risk for child abuse/neglect, and risk of future substance abuse in this population.

Predicting emergency room visits and hospitalizations among hospice patients with cardiac disease.

BACKGROUND: One goal of quality palliative care in hospice is to limit emergency room visits and/or hospitalizations (ERVH). PURPOSE: The purpose of this study was to determine predisposing factors that contribute to ERVH and devise a model to predict the probability of hospice cardiac disease patients having ERVH after hospice admission. METHODS: The study was a retrospective chart review of hospice cardiac patients comparing those with ERVH (n = 65) and those who died in their homes (n = 80). Data reduction strategy included bivariate tests and model-building analyses using logistic regression analysis. RESULTS: Some factors were associated with decreased odds of having ERVH: older patients (odds ratio [OR] = 0.94; p = 0.001), increased nursing visits (OR = 0.79; p = 0.001) and chaplain visits (OR = 0.48; p = 0.040), patients' medication compliance (OR = 0.27; p = 0.029), patients treated with morphine sulfate (OR = 0.15; p = 0.001), patients with caregiver(s) (OR = 0.09; p = 0.012), patients with hospice emergency kits (OR = 0.33; p = 0.004), interaction of the latter two variables (OR = 0.26; p = 0.001), patients with do-not-resuscitate orders (OR = 0.29; p = 0.001), Caucasian patients (OR = 0.22; p = 0.001), and the interaction of the latter two variables (OR = 0.22; p = 0.001). Other factors were associated with increased odds of having ERVH: patients with diabetes (OR = 2.64; p = 0.009), peripheral vascular disease (OR = 5.30; p = 0.003), hyperlipidemia (OR = 4.52; p = 0.013), chronic pulmonary disease/asthma (OR = 2.83; p = 0.003) as comorbidities; palpitations (OR = 6.61; p = 0.010), and chest pain (OR = 3.78; p = 0.006). The best fitting forecasting model had six independent variables decreasing and two increasing the odds of having ERVH. The final model chosen was: Z = 7.817 + 2.929 (peripheral vascular disease) + 1.513 (diabetes mellitus) - 3.306 (Caucasian) - 1.824 (caregiver presence x hospice emergency kit at home) - 0.212 (frequency of nursing visits) - 3.275 (on morphine) - 4.422 (medication compliance). CONCLUSION: The forecasting model predicted the probability of ERVH correctly in 87.7% of the patients. The model is simple to use to predict hospice cardiac patients having ERVH. Future studies should validate this model. Interventions should utilize these factors and be evaluated to determine their ability to decrease ERVH in hospice cardiac patients.

Spirituality and job satisfaction among hospice interdisciplinary team members.

As a continuing effort to enhance the quality of palliative care for the dying, this study examined (1) the prevalence of spirituality among hospice interdisciplinary team (IDT) members; (2) whether spirituality is related to job satisfaction; and (3) the structural path relationships among four variables: spiritual belief, integration of spirituality at work, self actualization and job satisfaction. The study surveyed 215 hospice IDT members who completed the Jarel Spiritual Well-Being Scale, the Chamiec-Case Spirituality Integration and Job Satisfaction Scales. Multiple regression and structural path modeling methods were applied to explain the path relationships involving all four variables. The IDT members surveyed were: nurses, 46.4%; home health aids, 24.9%; social workers, 17.4%; chaplains, 4.2%; physicians, 2.3%; and other, 4.8%. Ninety-eight percent of the respondents viewed themselves as having spiritual well-being. On a 0-100 scale, IDT staff reported high spiritual belief (mean = 89.4) and they were self-actualizing (mean = 82.6). Most reported high job satisfaction (mean = 79.3) and spiritual integration (mean = 67.9). In multiple regression, spirituality, integration and self-actualization explained 22% of the variation in job satisfaction (R = 0.48; adjusted R(2) = 0.218; df = 3,175; F = 17.2; p = 0.001). Structural path models revealed that job satisfaction is more likely to be realized by a model that transforms one's spirituality into processes of integrating spirituality at work and self actualization (chi(2) = 0.614; df = 1; p = 0.433) than a model that establishes a direct path from spirituality to job satisfaction (chi(2) = 1.65; df = 1; p = 0.199). Hospice IDT member's integration of their spirituality at work and greater self actualization significantly improve job satisfaction.

Effect of subfornical organ lesion on the development of mineralocorticoid-salt hypertension.

Accumulating evidence suggests that structures within the lamina terminalis; the organum vasculosm of the lamina terminalis (OVLT), the median preoptic nucleus (MnPO) and/or the subfornical organ (SFO); are required for the development of DOCA-salt hypertension. Lesion of the anteroventral tissue lining the third ventricle (AV3V), which destroys cell bodies in the OVLT and MnPO, as well as efferent projections from the SFO to the OVLT and MnPO, abolishes DOCA-salt hypertension in the rat. However, the individual contribution of these structures to DOCA-salt hypertension is unknown. The present study was designed to determine whether an intact SFO is required for hypertension development in the DOCA-salt model. In uninephrectomized SFO lesioned (SFOx; n=6) and SHAM (n=8) Sprague-Dawley rats, 24-h mean arterial pressure (MAP) and heart rate (HR) were continuously recorded telemetrically 4 days before and 36 days after DOCA implantation (100 mg/rat; s.c.); 24-h sodium and water balances were measured throughout the protocol. No differences in control MAP, HR, sodium and water balances were observed between groups. Following DOCA implantation, the magnitude of the elevation of MAP was similar between groups (approximately 40 mm Hg) so that by Day 40, MAP was 148+/-5 mm Hg in SFOx and 145+/-4 mm Hg in SHAM rats. The magnitude of decrease in HR from control values was similar in both groups. Differences in sodium and water balances were not observed between groups. We conclude that the SFO alone does not play a significant role in the development of mineralocorticoid-salt hypertension.

Role of renal nerves in development of hypertension in DOCA-salt model in rats: a telemetric approach.

Centrally mediated hyperactivity of the autonomic nervous system contributes to DOCA hypertension; however, the targeted peripheral vascular bed(s) remain unclear. We propose that if renal sympathetic activity is a factor in the development of DOCA-salt hypertension, then renal denervation (RDNX) should attenuate the hypertensive response. In protocol 1, uninephrectomized RDNX (n = 9) and sham-denervated (n = 6) Sprague-Dawley rats were allowed free access to 0.9% NaCl solution and 0.1% NaCl diet. Mean arterial pressure (MAP) and heart rate were telemetrically recorded for 4 days before and 36 days after DOCA (100 mg/rat) implantation; sodium and water balances were recorded daily. Protocol 2 was similar except that saline intake in sham rats (n = 7) was matched to that observed in RDNX rats of protocol 1 for 30 days; for the last 10 days, the rats were allowed free access to saline. Before DOCA in protocol 1, MAP was lower (P < 0.05) in RDNX rats (99 +/- 1 mmHg) compared with sham rats (111 +/- 3 mmHg); however, heart rate and sodium and water balances were similar between groups. RDNX attenuated the MAP response to DOCA by approximately 50% (DeltaMAP = 22 +/- 3 mmHg, where Delta is change in MAP) when compared with sham rats (DeltaMAP = 38 +/- 6). RDNX rats consumed significantly less saline than sham rats, and cumulative sodium and water balances were reduced by 33% and 23%, respectively. In protocol 2, a similar pattern in MAP elevation was observed in RDNX and saline-restricted, sham-denervated rats even when saline restriction was removed. These results indicate that the renal sympathetic nerves are important in hypertension development but that other factors are also involved.