Postradiation hypothyroidism in head and neck cancers: A Department of Veterans Affairs single-institution case-control dosimetry study

We performed a case-control study to characterize the dose-volume relationship and other variables leading to hypothyroidism after head and neck (H&N) cancer radiation therapy (RT) in a homogenous Veterans Affairs (VA) population. All records of patients receiving RT for various H&N cancers at a single VA medical center between 2007 and 2013 (n?=?143) were screened for post-RT thyroid stimulating hormone (TSH) levels (n?=?77). The thyroid gland was contoured on each slice of the planning computed tomography scan when available (hypothyroid: n?=?18; euthyroid >?2 years: n?=?16), and dose-volume histograms based on physical dose and biologically equivalent dose (BED) were compared systematically to find the significant dose-volume thresholds that distinguish the patients who developed clinical hypothyroidism. Dosimetric and clinical variables were considered in univariate and multivariate analysis. Preirradiation prevalence of hypothyroidism was 8 of 143 (5.6%). After RT, 36 of 77 (47%) screened patients had abnormally high TSH, of which 22 of 36 (61%) had clinical hypothyroidism after 1.29?±?0.99 years. The median follow-up durations were 3.3 years and 4.7 years for euthyroid and hypothyroid patients, respectively. Compared with the euthyroid cohort (n?=?41), these hypothyroid patients displayed no significant difference in age, gender, primary tumor site, thyroid volume, hypertension, diabetes, or use of chemotherapy, surgery, or intensity-modulated radiation therapy (IMRT). They were more likely to have had stage 3 or 4 cancer than euthyroid patients (86.5% vs 73.2%, p?=?0.01). The odds ratios of hypothyroidism for stage 3?+?4 cancers and V50Gy?<?75% were 5.0 and 0.2, respectively (p?<?0.05). Equivalent BED threshold of V75Gy₃?<?75% gave an odds ratio of 0.156 for developing hypothyroidism (p?=?0.02). The prevalence of post-RT clinical hypothyroidism was relatively high for patients with H&N cancers and warrants routine surveillance, especially in those with higher stage malignancy. V50Gy?<?75% may be a useful guideline to avoid hypothyroidism. We also show BED data which could be used for unconventionally fractionated schemes, and V75Gy₃?<?75% may be a useful guideline.     

Sex differences in pain-related symptoms and self-initiated school nurse visits among pre-adolescents

We examined sex differences in self-initiated school nurse visits and pain-associated symptoms in 57 pre-adolescents (36 girls), aged 9-11, with a brief, pain-focused version of the Children's Somatization Inventory (CSI). Using sequential multiple regression, pain symptom scores, sex, and their interaction were analyzed in relation to nurse visits prospectively collected for 1 year. Neither sex, nor pain scores alone, predicted total nurse visits. For girls only, higher pain symptom scores predicted increased total visits and increased visits for complaints with documented physical findings. For both sexes, higher pain symptom scores predicted more visits for complaints without documented physical findings. A complex relationship between sex, pain-related symptoms, and self-initiated nurse visits was found in this pre-adolescent sample. Our findings suggest pain-focused symptom measures may be useful in studies of early predictors of adult pain-related healthcare utilization.     

Increased Act1/IL-17R expression in Hirschsprung’s disease

Purpose

Hirschsprung’s disease-associated enterocolitis (HAEC) is the most common cause of morbidity and mortality in Hirschsprung’s disease (HSCR). Altered intestinal epithelial barrier function is implicated in the pathogenesis of HAEC. IL-17 is a proinflammatory cytokine that plays a crucial role in host defense against microbial organisms in the development of inflammatory diseases. Act1 is an essential adaptor molecule required for the IL-17-mediated inflammatory responses via interaction with IL-17 receptor (IL-17R). We designed this study to investigate the hypothesis that Act1/Il-17R expression is upregulated in HSCR.

Methods

We investigated Act1 and IL17R expression in ganglionic andaganglionic bowel of HD patients (n = 10) and controls (n = 10). qPCR, Western blotting and confocal immunofluorescence were performed.

Main results

qPCR and Western blot analysis revealed that Act1 and IL17R are strongly expressed in the aganglionic and ganglionic colon of patients with HSCR. Act1 and IL17R expression was significantly increased in HSCR specimens compared to controls (p < 0.05). Confocal microscopy revealed a markedly increased expression of Act1 and IL17R in the colonic epithelium of patients with HSCR compared to controls.

Conclusion

To our knowledge, we report, for the first time, the expression of Act1 in the human colon. The increased expression of Act1 and Il-17 in the aganglionic and ganglionic bowel in HSCR may result in IL-17-mediated increased inflammatory response leading to the development of HAEC

     

Reporting of neuropsychological dysfunction remains discrepant between individuals with traumatic brain injury and their close others up to five years post-injury

Purpose: The degree to which individuals with traumatic brain injury (TBI) and their close others share a common understanding and experience of post-injury neuropsychological changes is currently unclear. The aim of this preliminary study was to longitudinally examine levels of agreement between self and close other reports of neuropsychological dysfunction following TBI and explore factors associated with these agreement levels. Method: Sixty-three people with TBI and their nominated close others independently completed the Structured Outcome Questionnaire at 1- and 5-years post-injury, reporting whether the person with TBI was experiencing any negative cognitive, behavioural or emotional changes compared to pre-injury. Results: Agreement levels between pair members ranged from chance to approximately 75% across neuropsychological domains and did not significantly change over 1- and 5-year time points. In the case of pair disagreement, close others were generally more likely to report difficulties. Pair disagreement was significantly associated with close other anxiety. Conclusions: Agreement between self and close others remains limited up to 5-years post-injury which questions the practice of using these reports interchangeably in research and clinical practice. Preliminary findings suggest some association between pair disagreement and close other psychological function; however, further research is warranted.

• Implications for Rehabilitation

• Reporting of neuropsychological dysfunction between individuals with TBI and their close others is not sufficiently reliable to warrant interchangeable use within research or clinical practice.

• Including both individuals with TBI and their close others in clinical assessments will facilitate a more holistic understanding of the client’s difficulties and their relationships with those close to them.

• Preliminary findings indicate that disagreement between individuals with TBI and their close others may be associated with close other anxiety. Clinicians should be aware of the potential for disagreement to impact on the psychological health of close others.

     

The antivascular action of physiotherapy ultrasound on a murine tumor: role of a microbubble contrast agent

This study investigated whether a microbubble-containing ultrasound contrast agent had a role in the antivascular action of physiotherapy ultrasound on tumor neovasculature. Ultrasound images (B-mode and contrast-enhanced power Doppler [0.02 mL Definity]) were made of 22 murine melanomas (K1735²²). The tumor was insonated (I_SATA = 1.7 W cm^–2, 1 MHz, continuous output) for 3 min and the power Doppler observations of the pre- and postinsonation tumor vascularities were analyzed. Significant reductions (p = 0.005 for analyses of color-weighted fractional area) in vascularity occurred when a contrast-enhanced power Doppler study occurred before insonation. Vascularity was unchanged in tumors without a pretherapy Doppler study. Histologic studies revealed tissue structural changes that correlated with the ultrasound findings. The underlying etiology of the interaction between the physiotherapy ultrasound beam, the microbubble-containing contrast agent and the tumor neovasculature is unknown. It was concluded that contrast agents play an important role in the antivascular effects induced by physiotherapy ultrasound. (E-mail: sehgalc@uphs.upenn.edu)     

Integration of nurse practitioners into a family health network

A randomized controlled study called Anticipatory and Preventative Team Care (APTCare) explored a new role for nurse practitioners (NPs) within a multidisciplinary team. The aim of the study was to evaluate whether integrating NPs and a pharmacist was an effective approach for the management of patients living with multiple chronic illnesses. Over an 18-month period, three part-time NPs and a pharmacist became part of a rural Family Health Network (FHN). They established relationships with study patients and collaborated to provide optimum care. Each NP had 40 patients, all of whom received care in the home. Study results showed that an initial home visit was invaluable for establishing a care plan, developing a relationship with the patient and assessing the home environment. Ongoing monitoring at home, however, was found to be an inefficient use of the NP role. By the end of the study, all clinicians agreed that the NP role had been successfully integrated into the multidisciplinary team.