Serum microRNA profiles as prognostic/predictive markers in the multimodality therapy of locally advanced adenocarcinomas of the gastroesophageal junction

Neoadjuvant multimodality treatment is frequently applied to improve the poor prognosis of locally advanced adenocarcinomas of the gastroesophageal junction. This study aimed to asses if serum microRNA profiles are useable as response indicators in this therapeutic setting. Fifty patients with locally advanced adenocarcinomas of the gastroesophageal junction were included in the study. All patients received neoadjuvant therapy and subsequently underwent surgical resection. Histomorphologic regression was defined as major histopathological response when resected specimens contained less than 10% vital residual tumor cells. Circulating RNA was isolated from pretherapeutic/post‐neoadjuvant blood serum samples. RNA from nine patients was applied to PCR microarray analyses Based on these findings possible predictive miRNA markers were validated by quantitative RT‐PCR analyses. Depending on the histomorphologic regression, a differential serum microRNA profile was identified by microarray analyses. Based on the divergent miRNA pattern, miR‐21, miR‐192, miR‐222, miR‐302c, miR‐381 and miR‐549 were selected for further validation. During neoadjuvant therapy, there was a significant increase of miR 222 and miR‐549. Although on an expanded patient cohort, the six microRNAs could not be validated as markers for therapy response, there was a significant correlation between a high miR‐192 and miR‐222 expression with a high T‐category as well as miR‐302c and miR‐222 expression significantly correlated with overall survival. Comprehensive miRNA profiling showed a differential microRNA expression pattern depending on the histomorphologic regression in the multimodality therapy of locally advanced adenocarcinomas of the gastroesophageal junction. Moreover, using single RT‐PCR analyses a prognostic impact of miR‐222 and miR‐302c was detected.     

Perceived self‐efficacy gained from,and health effects of,a rehabilitation program after hip joint replacement

Objective

To examine whether a routine multidisciplinary inpatient rehabilitation program can increase patient self‐efficacy, and to investigate the effects of high self‐efficacy at admission, and increases in self‐efficacy, on health changes in patients who undergo such rehabilitation after hip joint replacement.

Methods

Participants in this longitudinal study were 1,065 patients who underwent inpatient rehabilitation after hip joint replacement. Questionnaires were administered at admission, discharge, and 6‐month followup. The main outcome variables were disability, pain, depressive symptomatology, and self‐efficacy to cope with disability and pain.

Results

Significant improvements from admission to discharge from the inpatient rehabilitation program in disability, pain, depressive symptoms, and self‐efficacy were found. In addition, higher levels of self‐efficacy at admission and larger increases in self‐efficacy over the course of the program predicted larger health changes (i.e., greater decreases in disability, pain, and depressive symptoms). Results were generally similar for health changes from discharge to 6‐month followup.

Conclusion

A routine multidisciplinary inpatient rehabilitation program after hip joint replacement can result in enhanced self‐efficacy.

     

Influence of compensated radioiodine therapy on thyroid volume and incidence of hypothyroidism in Graves' disease

Abstract. Objectives . To investigate the long-term effect of radioactive iodine (¹³¹I) on thyroid function and size in patients with Graves' disease. Setting . Out-patient clinic in Herlev Hospital. Subjects . One hundred and seventeen consecutive patients (104 women) with Graves' disease selected for ¹³¹I treatment and followed for a minimum of 12 months (range 1–10 years, median 5 years). Interventions . ¹³¹I dose was calculated based on thyroid volume and 24-h ¹³¹I uptake. Main outcome measures . Standard thyroid function variables and ultrasonically determined thyroid volume before treatment as well as 0.75, 1.5, 3, 6 and 12 months after treatment, and then once a year were investigated. Results . Seventy-eight patients were cured by one ¹³¹I dose and 30 by two doses, while the remaining nine patients received additional doses (range one to five doses, median one dose). Within one year, 25% developed hypothyroidism, and hereafter, hypothyroidism developed at a constant rate of 3% per year independent of antithyroid pretreatment. The cumulative 10-year risk of hypothyroidism was 60%. Initial median thyroid volume was 33 mL (range 9–106 mL). At 12 months after the last ¹³¹I dose, median thyroid volume was reduced to 14 mL (range 6–36 mL) (P < 0.00001). The median reduction being 58% (range 0–80%,), hereafter no further reduction occurred. A significant reduction in thyroid volume was also noted in patients needing subsequent ¹³¹I doses and in those developing hypothyroidism within the first year. Conclusions . ¹³¹I normalizes thyroid volume in patients with Graves' disease. Hypothyroidism seems an inevitable end result of this treatment. The present study suggests that it will be impossible to modify ¹³¹I therapy in a way to achieve both early control of hyperthyroidism and a low incidence of hypothyroidism.     

Phonological development of toddlers with unilateral cleft lip and palate who were treated with and without infant orthopedics: a randomized clinical trial.

OBJECTIVE: To investigate the phonological development of toddlers from 2 to 3 years of age with complete unilateral cleft lip and palate (UCLP) treated during the first year of life with and without infant orthopedics (IO). DESIGN: In a randomized clinical trial (Dutchcleft), two groups of children were followed up: one treated with IO (IO group) and another that did not receive IO (non-IO group). Phonological skills were analyzed at 2, 2.5, and 3 years of age using a system for assessing phonological development of Dutch children (Fonologische Analyse van het Nederlands: FAN). The analysis included number of acquired consonants, order of phonological development, use of phonological processes, and occurrence of nasal escape. PATIENTS: Criteria for inclusion were complete UCLP, no soft tissue bands, no other malformations, parents fluent in Dutch, birth weight of a minimum of 2500 g, and gestation time of a minimum of 38 weeks. INTERVENTIONS: IO treatment based on a modified Zurich approach was started within 2 weeks after birth and used until soft palate closure at 12 months of age. Children in the non-IO group visited the clinic for an extra check-up at 6 weeks as well as before and after lip repair and soft palate closure. All other interventions were the same across groups. RESULTS: Phonological development of most 2.5-year-old IO children was normal or delayed. Most children in the non-IO group followed an abnormal developmental pattern. At age 3, the children in the IO group had acquired more initial consonants. There were no group differences in the use of phonological processes or the occurrence of nasal escape. CONCLUSIONS: Children treated with IO during their first year of life followed a more normal path of phonological development between 2 and 3 years of age.     

Intermittent versus continuous neuroleptic treatment in a rat model

The treatment schedule for neuroleptic therapy is of relevance when evaluating the development of side-effects. Seventy-five rats were treated discontinuously or continuously with the predominantly dopamine D₂ receptor blocker haloperidol or the combined dopamine D₁/D₂ receptor blocker zuclopenthixol for 15 weeks. During and after treatment, a broad spectrum of behavioural parameters including vacuous chewing movements and tongue protrusions were observed. Discontinuous neuroteptic treatment as opposed to continuous neuroleptic treatment produced a significant long-lasting increase in oral activity. The changes were most pronounced in haloperidol-treated rats. The differences observed may have methodological implications for animal models of neuroleptic-induced movement disorders. Our finding are consistent with the hypothesis that pharmacological sensitization to the dyskinetic side-effects of neuroleptics develops when the drug effect is allowed to wear off between repeated administration.