Exploring the interagency collaboration between a pediatric oncology health care setting and community schools.

Globally, approximately 400,000 youth are diagnosed with pediatric cancer each year. Treatment-related side effects, psychosocial challenges, and frequent school absences may adversely impact learning and the education experience among these youth. Efforts to enhance interagency collaboration between health care settings and community schools are imperative to facilitate school reintegration. The Standards for the Psychosocial Care of Children with Cancer and Their Families outline specific guidelines related to the continuity of education for students impacted by pediatric cancer. In particular, the Academic Continuity and School Reentry Support and Monitoring and Assessment of Neuropsychological Outcomes standards of care highlighted within this article align with extant programmatic efforts for transitioning hospitalized school-aged children back into community schools. This article aims to describe systematic programmatic efforts within hospital-based psychosocial programs that are consistent with the Standards for the Psychosocial Care of Children with Cancer and Their Families, as well as interagency collaboration with community schools to support student-centered education for youth impacted by pediatric cancer. Resources for school psychologists, teachers, hospital-based programs, and others involved in student-centered education for pediatric cancer patients and survivors are presented. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

The past, present, and future of immunotherapy for endometrial adenocarcinoma.

Incidences of endometrial adenocarcinoma are increasing in the USA with poor prognosis for patients with advanced disease. The current treatment standard is surgery including total hysterectomy and bilateral oophorectomy with surgical staging and adjunct treatment, such as chemotherapy or radiation. However, these methods do not present as an effective treatment option for poorly differentiated advanced cancers. Advancements in immunotherapy now offer a new approach for various types of cancer and specifically show promise in the treatment of endometrial adenocarcinoma. This review summarizes immunotherapeutic treatment options relevant to endometrial adenocarcinoma, such as immune checkpoint blockades, bispecific T-cell engager antibodies, vaccinations, and adoptive cell transfer. This study could be helpful for clinicians to identify treatment options more suitable for women with late-stage endometrial adenocarcinoma.

A relatively high proportion of dogs with small apocrine gland anal sac adenocarcinoma (AGASACA) primary tumours present with locoregional lymph node metastasis.

Apocrine gland anal sac adenocarcinoma (AGASACA) is a highly relevant disease in dogs, with a high rate of lymph node (LN) metastasis during the course of disease. A recent study showed that risk for death and disease progression was significantly associated with primary tumour size less than 2 and 1.3 cm, respectively. The objective of this study was to report the proportion of dogs that have primary tumours less than 2 cm in diameter, that are diagnosed with LN metastasis at presentation. This was a single site retrospective study of dogs that underwent treatment for AGASACA. Dogs were included if physical examination primary tumour measurements were available, abdominal staging was performed, and confirmation of abnormal lymph nodes by cytology or histology was done. Over a 5-year period, 116 dogs were included for review with 53 (46%) having metastatic LN at presentation. The metastatic rate for dogs with primary tumours <2 cm was 20% (9 of 46 dogs) compared to 63% (44 of 70 dogs) in dogs with primary tumours ≥2 cm. The association between tumour size group (<2 vs. ≥2 cm) and the presence of metastasis at presentation was significant (P < .0001) with an OR of 7.0 (95% CI: 2.9-15.7). Primary tumour size was significantly associated with LN metastasis at presentation but the proportion of dogs that presented with LN metastasis in the <2 cm group was relatively high. This data suggests that dogs with small tumours may still have aggressive tumour biology.

Nivolumab-induced exocrine pancreatic insufficiency.

Immune checkpoint inhibition is the standard-of-care for many advanced cancers. Side effects of therapy may prevent optimal treatment of the cancer. Management of side effects is dominated by recommendations derived from oncological, not gastroenterological practice. We report a patient who developed pancreatic insufficiency during checkpoint inhibitor therapy with a programmed cell death receptor 1 inhibitor, nivolumab, which if not diagnosed would have prevented ongoing treatment. This is a problem which affects approximately 1 in 100 patients treated with this agent but is rarely recognised. Gastroenterologists need to be aware of the spectrum of gastrointestinal disorders which occur after immunotherapy to treat cancer.

Characterization and Management of Adverse Reactions in Patients With Unresectable Hepatocellular Carcinoma Treated With Lenvatinib.

Aims: Advanced practice providers (APPs) play a vital role in monitoring for and managing adverse reactions (ARs). As lenvatinib ARs can resemble cirrhosis (commonly presenting with hepatocellular carcinoma [HCC]), APP input is important for timely detection and management of ARs and to promote medication adherence. Design: The goal of this post-hoc analysis of the REFLECT trial was to characterize key ARs associated with lenvatinib, and to discuss management strategies. Methods: In REFLECT, patients with unresectable HCC were randomized to either daily lenvatinib (12 mg/day for patients who weighed ≥ 60 kg or 8 mg/day for those < 60 kg) or sorafenib 400 mg twice daily. Adverse events in the lenvatinib arm were grouped into ARs (hypertension, fatigue, palmar-plantar erythrodysesthesia syndrome, proteinuria, and decreased appetite) per the United States Prescribing Information (USPI) for lenvatinib. Results: Key ARs in the lenvatinib arm (n = 476) generally occurred within months of starting lenvatinib. Some cases of proteinuria, decreased appetite, and diarrhea were first reported at about 2 years of treatment. Conclusions: The onset of key ARs associated with lenvatinib treatment can be predicted and generally be managed (per the lenvatinib USPI and REFLECT) by withholding lenvatinib and resuming it at a reduced dose after the severity decreases. However, lenvatinib should generally be discontinued if the AR is life-threatening.

Anxiety and Depression in Pediatric Patients with Celiac Disease: A Large Cross-Sectional Study.

Mental health is a growing concern in pediatric celiac disease (CD). This study utilized the Revised Children's Anxiety and Depression Scale (RCADS) to investigate anxiety and depression symptom rates. Participants were children ages 8 to 17 years (M = 11.7, SD = 2.7; N = 175) with biopsy-proven CD (Median = 1.1 years post-diagnosis, IQR = 0-4) categorized into groups based on the child's age, caregiver or child respondent, presence or absence of comorbidities, and gluten-free diet duration. Self-reported RCADS scores showed 39% of children having clinically significant concerns for anxiety or depression ( P < 0.0001) but only 7% of caregiver-proxy RCADS scores indicated significant concerns for the child's anxiety and 14% for the child's depression. Rates of child-reported anxiety and depression symptoms were significantly higher for those without medical comorbidities than those with ( P = 0.04). Therefore, screening for mental health concerns, particularly anxiety and depression, should be routinely performed in pediatric patients with CD.

The toll of transition: Caregiver perceptions of family adjustment during the transition off pediatric cancer therapy.

OBJECTIVE: The role of transition-focused psychology appointments in managing the transition off therapy is unclear. The objective of this research was to explore caregiver perceived familial distress and the role of psychology in preparing families for transition. METHODS: Fifty-seven caregivers of youth, who finished treatment, completed an online questionnaire through a quality improvement project on experiences of families at transition. Twenty-two percent of caregivers had children who completed a transition-focused psychology consult and 63% completed a cognitive assessment at transition. Retrospective analyses were conducted assessing the association of psychology visits on caregiver perceptions of being informed of and prepared to manage transition-related challenges. RESULTS: Most caregivers reported experiencing adjustment concerns for family members. Caregivers of children completing a transition-focused psychology consult or cognitive assessment reported feeling more informed and greater preparedness to manage difficulties. Although decreased distress was not associated with the visit, those who felt more informed and prepared reported lower distress. CONCLUSIONS: Caregivers perceive transitioning off therapy as stressful for their family, though they experience decreased familial distress when informed of and prepared to manage transition-related challenges. These findings highlight the importance of psychosocial support at transition.

Estimation of Dermal Exposure to Oil Spill Response and Clean-up Workers after the Deepwater Horizon Disaster.

The GuLF STUDY is investigating health outcomes associated with oil spill-related chemical exposures among workers involved in the spill response and clean-up following the Deepwater Horizon disaster. Due to the lack of dermal exposure measurements, we estimated dermal exposures using a deterministic model, which we customized from a previously published model. Workers provided information on the frequency of contact with oil, tar, chemical dispersants applied to the oil spill and sea water, as well as the use of protective equipment, by job/activity/task. Professional judgment by industrial hygienists served as a source of information for other model variables. The model estimated dermal exposures to total hydrocarbons (THC), benzene, ethylbenzene, toluene, xylene, n-hexane (BTEX-H), polycyclic aromatic hydrocarbons (PAHs), and dispersants in GuLF DREAM units (GDUs). Arithmetic means (AMs) of THC exposure estimates across study participants ranged from <0.02 to 5.50 GDUs for oil and <0.02 to 142.14 GDUs for tar. Statistical differences in the estimates were observed among the AMs of the estimates for some broad groups of worker activities over time and for some time periods across the broad groups of activities. N-Hexane had ranges similar to THC for oil exposures (e.g. AMs up to 2.22 GDUs) but not for tar (up to 5.56 GDUs). Benzene, ethylbenzene, toluene, and xylene, in contrast, were characterized by higher exposure levels than THC for oil (AMs up to 12.77, 12.17, 17.45, and 36.77 GDUs, respectively) but lower levels than THC to tar (AMs up to 3.69, 11.65, 42.37, and 88.18 GDUs, respectively). For PAHs, the AMs were as high as 219.31 and 587.98 for oil and tar, respectively. Correlations of these seven substances to each other were high (>0.9) for most of the substances in oil but were lower for some of the substances in tar. These data were linked to the study participants to allow investigation of adverse health effects that may be related to dermal exposures.

Beyond bones: The relevance of variants of connective tissue (hypermobility) to fibromyalgia, ME/CFS and controversies surrounding diagnostic classification: an observational study.

BACKGROUND: Fibromyalgia and myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS) are poorly understood conditions with overlapping symptoms, fuelling debate as to whether they are manifestations of the same spectrum or separate entities. Both are associated with hypermobility, but this remains significantly undiagnosed, despite impact on quality of life. OBJECTIVE: We planned to understand the relevance of hypermobility to symptoms in fibromyalgia and ME/CFS. METHOD: Sixty-three patient participants presented with a confirmed diagnosis of fibromyalgia and/or ME/CFS; 24 participants were healthy controls. Patients were assessed for symptomatic hypermobility. RESULTS: Evaluations showed exceptional overlap in patients between fibromyalgia and ME/CFS, plus 81% met Brighton criteria for hypermobility syndrome (odds ratio 7.08) and 18% met 2017 hypermobile Ehlers-Danlos syndrome (hEDS) criteria. Hypermobility scores significantly predicted symptom levels. CONCLUSION: Symptomatic hypermobility is particularly relevant to fibromyalgia and ME/CFS, and our findings highlight high rates of mis-/underdiagnosis. These poorly understood conditions have a considerable impact on quality of life and our observations have implications for diagnosis and treatment targets.

Type B lactic acidosis: a rare oncological emergency.

Type B lactic acidosis is a rare metabolic complication of malignancy, more commonly in haematological malignancies. Due to the lack of formal prospective trials, treatment of lactic acidosis associated with malignancy is based on case reports. Given the poor prognosis, early recognition of type B lactic acidosis and prompt treatment are crucial. We report the first case of type B lactic acidosis in metastatic melanoma, followed by a brief literature review on the proposed pathophysiology and treatment.

Prostate field cancerization and exosomes: Association between CD9, early growth response 1 and fatty acid synthase.

Intracapsular and well­defined adenocarcinomas of the prostate are often surrounded by tissue areas that harbor molecular aberrations, including those of genetic, epigenetic and biochemical nature. This is known as field cancerization, or a field effect and denotes a state of pre­malignancy. Such alterations in histologically normal tumor­adjacent prostatic tissues have been recognized as clinically important and are potentially exploitable as biomarkers of disease and/or targets for preventative/therapeutic intervention. The authors have previously identified and validated two protein markers of field cancerization: The expressional upregulation of the transcription factor early growth response 1 (EGR­1) and the lipogenic enzyme fatty acid synthase (FASN). However, the molecular etiology of prostate field cancerization, including EGR­1 and FASN upregulation, remains largely unknown. It was thus hypothesized that extracellular vesicles, notably exosomes, released by tumor lesions may induce molecular alterations in the surrounding tissues, resulting in field cancerization, priming the tissue, and ultimately promoting multifocal tumorigenesis, which is often observed in prostate cancer. Towards testing this hypothesis, the current study, to the best of our knowledge, for the first time, presents correlative protein expression data, generated in disease­free, tumor­adjacent and cancerous human prostate tissues by quantitative immunofluorescence, between the exosomal marker CD9, and EGR­1 and FASN. Despite the pilot character of the present study, and the static nature and heterogeneity of human tissues, the data suggest that CD9 expression itself is part of a field effect. In support of this hypothesis, the results suggest a possible contribution of exosomes to the induction of field cancerization in the prostate, particularly for EGR­1. These findings were corroborated in established cell models of cancerous (LNCaP) and non­cancerous (RWPE­1) human prostate epithelial cells. The findings of this study warrant further investigation into the functional interface between exosomes and field cancerization, as a detailed understanding of this characterization may lead to the development of clinical applications related to diagnosis and/or prognosis and targeted intervention to prevent progression from pre­malignancy to cancer.

Towards a personalized surgical margin for breast conserving surgery-Implications of field cancerization in local recurrence.

The amount of normal tissue that should be excised during breast conserving surgery is widely debated. Tissue adjacent to breast tumors, although histologically normal, possesses many of the molecular abnormalities found in tumor tissues. Here, we propose that the ideal physical distance for a surgical margin may not be universal. Rather, an adequate surgical margin likely varies from patient to patient, depending on the biology of the tissue that remains after surgery. J. Surg. Oncol. 2017;115:109-115. © 2017 Wiley Periodicals, Inc.

Association and regulation of protein factors of field effect in prostate tissues.

Field effect or field cancerization denotes the presence of molecular aberrations in structurally intact cells residing in histologically normal tissues adjacent to solid tumors. Currently, the etiology of prostate field­effect formation is unknown and there is a prominent lack of knowledge of the underlying cellular and molecular pathways. We have previously identified an upregulated expression of several protein factors representative of prostate field effect, i.e., early growth response-1 (EGR­1), platelet-derived growth factor­A (PDGF­A), macrophage inhibitory cytokine­1 (MIC­1), and fatty acid synthase (FASN) in tissues at a distance of 1 cm from the visible margin of intracapsule prostate adenocarcinomas. We have hypothesized that the transcription factor EGR­1 could be a key regulator of prostate field­effect formation by controlling the expression of PDGF­A, MIC­1, and FASN. Taking advantage of our extensive quantitative immunofluorescence data specific for EGR­1, PDGF­A, MIC­1, and FASN generated in disease­free, tumor­adjacent, and cancerous human prostate tissues, we chose comprehensive correlation as our major approach to test this hypothesis. Despite the static nature and sample heterogeneity of association studies, we show here that sophisticated data generation, such as by spectral image acquisition, linear unmixing, and digital quantitative imaging, can provide meaningful indications of molecular regulations in a physiologically relevant in situ environment. Our data suggest that EGR­1 acts as a key regulator of prostate field effect through induction of pro­proliferative (PDGF­A and FASN), and suppression of pro­apoptotic (MIC­1) factors. These findings were corroborated by computational promoter analyses and cell transfection experiments in non­cancerous prostate epithelial cells with ectopically induced and suppressed EGR­1 expression. Among several clinical applications, a detailed knowledge of pathways of field effect may lead to the development of targeted intervention strategies preventing progression from pre-malignancy to cancer.

Implementation of a care bundle and evaluation of risk factors for surgical site infection in cranial neurosurgery.

OBJECTIVES: Surgical site infection [SSI] increases mortality, morbidity and length of hospital stay. Peri-operative 'care bundles' have reduced SSI in some fields of surgery. The aim of this study was to determine the impact of bundle compliance on SSI in patients undergoing a craniotomy. PATIENTS AND METHOD: Cohort study of patients [N=1253] undergoing a craniotomy over 17 months at a single centre. SSI was defined as arising within 30days of operation or 1year where an implant(s) remains. 'Bundle compliance' required administration of antibiotics <60min of induction, maintenance of intraoperative blood sugar (BM) <11mmol and temperature at >36°C. SSI incidence was compared between bundle compliant and non-compliant groups. Case mix adjustment was performed using binary logistic regression. RESULTS: Over the study period, 1253 procedures were carried out and 66 patients (5.3%) developed a SSI. The majority (38, 57.6%) of these cultured Staphyloccoccus species. Only the use of an implant was found to be an independent risk factor for SSI [AOR 2.5, p<0.005, 95%CI 1.4, 4.3]. The use of the bundle did not reduce the occurrence of SSI. CONCLUSIONS: An evidence-based bundle did not reduce SSI in this neurosurgical series. The use of an implant was an independent risk factor of its occurrence.

Evidence for bystander signalling between human trophoblast cells and human embryonic stem cells.

Maternal exposure during pregnancy to toxins can occasionally lead to miscarriage and malformation. It is currently thought that toxins pass through the placental barrier, albeit bi-layered in the first trimester, and damage the fetus directly, albeit at low concentration. Here we examined the responses of human embryonic stem (hES) cells in tissue culture to two metals at low concentration. We compared direct exposures with indirect exposures across a bi-layered model of the placenta cell barrier. Direct exposure caused increased DNA damage without apoptosis or a loss of cell number but with some evidence of altered differentiation. Indirect exposure caused increased DNA damage and apoptosis but without loss of pluripotency. This was not caused by metal ions passing through the barrier. Instead the hES cells responded to signalling molecules (including TNF-α) secreted by the barrier cells. This mechanism was dependent on connexin 43 mediated intercellular 'bystander signalling' both within and between the trophoblast barrier and the hES colonies. These results highlight key differences between direct and indirect exposure of hES cells across a trophoblast barrier to metal toxins. It offers a theoretical possibility that an indirectly mediated toxicity of hES cells might have biological relevance to fetal development.

Prostate field cancerization: deregulated expression of macrophage inhibitory cytokine 1 (MIC-1) and platelet derived growth factor A (PDGF-A) in tumor adjacent tissue.

Prostate field cancerization denotes molecular alterations in histologically normal tissues adjacent to tumors. Such alterations include deregulated protein expression, as we have previously shown for the key transcription factor early growth response 1 (EGR-1) and the lipogenic enzyme fatty acid synthase (FAS). Here we add the two secreted factors macrophage inhibitory cytokine 1 (MIC-1) and platelet derived growth factor A (PDGF-A) to the growing list of protein markers of prostate field cancerization. Expression of MIC-1 and PDGF-A was measured quantitatively by immunofluorescence and comprehensively analyzed using two methods of signal capture and several groupings of data generated in human cancerous (n = 25), histologically normal adjacent (n = 22), and disease-free (n = 6) prostate tissues. A total of 208 digitized images were analyzed. MIC-1 and PDGF-A expression in tumor tissues were elevated 7.1x to 23.4x and 1.7x to 3.7x compared to disease-free tissues, respectively (p<0.0001 to p = 0.08 and p<0.01 to p = 0.23, respectively). In support of field cancerization, MIC-1 and PDGF-A expression in adjacent tissues were elevated 7.4x to 38.4x and 1.4x to 2.7x, respectively (p<0.0001 to p<0.05 and p<0.05 to p = 0.51, respectively). Also, MIC-1 and PDGF-A expression were similar in tumor and adjacent tissues (0.3x to 1.0x; p<0.001 to p = 0.98 for MIC-1; 0.9x to 2.6x; p<0.01 to p = 1.00 for PDGF-A). All analyses indicated a high level of inter- and intra-tissue heterogeneity across all types of tissues (mean coefficient of variation of 86.0%). Our data shows that MIC-1 and PDGF-A expression is elevated in both prostate tumors and structurally intact adjacent tissues when compared to disease-free specimens, defining field cancerization. These secreted factors could promote tumorigenesis in histologically normal tissues and lead to tumor multifocality. Among several clinical applications, they could also be exploited as indicators of disease in false negative biopsies, identify areas of repeat biopsy, and add molecular information to surgical margins.

Exploring nutrition education resources and barriers, and nutrition knowledge in teachers in California.

OBJECTIVE: To determine barriers to nutrition education, nutrition education resources used, and the relationship between nutrition knowledge and whether public school teachers in California teach nutrition in the classroom. METHODS: A total of 102 teachers in California participated in a Web-based survey about nutrition education barriers, resources used to plan nutrition lessons, and factors that would encourage inclusion of nutrition. A validated questionnaire was used to assess nutrition knowledge. Analyses included ordinary least-squares regression. RESULTS: Common barriers were lack of instructional time and unrelated subject. Teachers were unaware of many nutrition education resources. Nutrition knowledge was not associated with nutrition lessons but was positively associated with teaching high school (ß = 5.13; P < .05) and female gender (ß = 6.78; P < .05), and negatively associated with identifying as Hispanic or Latino (ß = -15.50; P < .001). CONCLUSIONS AND IMPLICATIONS: Barriers of time and lack of unrelated subject matter are difficult to address but lack of awareness of resources indicates that promotion of existing resources may encourage teachers to provide nutrition education. Larger studies are needed to determine whether this holds true in a broader sample.

Observational study of intra-abdominal pressure monitoring in acute pancreatitis.

BACKGROUND: Intra-abdominal hypertension (IAH) is predictive of adverse outcome in critically ill patients; however, its role in acute pancreatitis is unclear, and prospective studies are lacking. We aimed to determine the overall incidence and predictive value of IAH on mortality in acute pancreatitis. METHODS: Transvesical IAP was measured on admission and every 4 hours within high-dependency unit/intensive care unit. Serum biochemistry and physiologic parameters permitted calculation of Acute Physiology and Chronic Health Evaluation II, Sequential Organ Failure Assessment, Imrie, and Ranson scores. The primary end point was 30-day mortality. RESULTS: A total of 218 patients with acute pancreatitis were recruited; 30-day mortality was greater in patients with IAH (IAP ≥12 mmHg; 37%) than no IAH (2%; P < .001). A total of 14% of patients had IAH on admission; another 3% developed IAH in hospital. Mortality was greater in the latter group (37% vs 50%; P < .01). In the majority of cases IAH developed in line with other organ failure; however, there were several patients in whom the development of IAH appeared to be the sentinel event before rapid clinical decline. An IAP threshold of 9 mmHg had best predictive value for mortality (sensitivity 86%, specificity 87%; area under the ROC curve 0.91). This finding was comparable with other validated markers of severe pancreatitis (Imrie ≥3: sensitivity 51%, specificity 70%; Acute Physiology and Chronic Health Evaluation II: sensitivity 67%, specificity 96%; C-reactive protein >150: sensitivity 89%, specificity 83%). CONCLUSION: IAP is a good predictor of mortality and organ failure in acute pancreatitis and compares favorably with other validated prognostic scores. Whether IAH is a phenomenon causative of organ failure or an epiphenomenon, occurring in conjunction with other organ dysfunction, remains unclear.