Circadian rhythm bifurcation induces flexible phase resetting by reducing circadian amplitude.

Shift-work and jet-lag-related disorders are caused by the limited flexibility of the suprachiasmatic nucleus (SCN), a master circadian clock in the hypothalamus, to adjust to new light-dark (LD) cycles. Recent findings confirmed here establish that behavioral jet lag after simulated time-zone travel is virtually eliminated following bifurcated circadian entrainment under a novel and atypical 24-h light:dark:light:dark (LDLD) cycle. To investigate the mechanisms of this fast resetting, we examined the oscillatory stability of the SCN and peripheral tissues in LDLD-bifurcated mice employing the dissection procedure as a perturbing resetting stimulus. SCN, lung, liver, and adrenal tissue were extracted at times throughout the day from female and male PER2::Luciferase knock-in mice entrained to either LDLD or a normal LD cycle. Except for adrenals, the phase of the cultured explants was more strongly set by dissection under LDLD than under normal LD. Acute bioluminescence levels of SCN explants indicate that the rhythm amplitude of PER2 is reduced and phase is altered in LDLD. Real-time quantitative PCR suggests that amplitude and rhythmicity of canonical clock genes in the lung, liver, and kidney are also significantly reduced in LDLD in vivo. Furthermore, spatiotemporal patterns of PER2 peak time in cultured SCN were altered in LDLD. These results suggest that altered gene expression patterns in the SCN caused by bifurcation likely result in fast resetting of behavior and cultured explants, consistent with previously reported mathematical models. Thus, non-invasive, simple light manipulations can make circadian rhythms more adaptable to abrupt shifts in the environmental LD cycle.

Predicting the prognosis of undifferentiated pleomorphic soft tissue sarcoma: a 20-year experience of 266 cases.

BACKGROUND: Undifferentiated pleomorphic sarcoma (UPS) is a rare malignant tumour of mesenchymal origin, which was conceived following re-classification of malignant fibrous histiocytoma (MFH). The objective of this study is to determine prognostic factors for the outcome of UPS, following multi-modal treatment. METHODS: Data of UPS tumours from 1996 to 2016 were collected, totalling 266 unique UPS patients. Median follow-up was 7.8 years. All tumours were retrospectively analysed for prognostic factors of the disease, including local recurrence (LR) and metastatic disease (MD) at diagnosis, tumour size, grade, location and depth, patient age, adjuvant therapy and surgical margin. Overall survival (OS), post-treatment LR and metastatic-free survival were assessed as outcomes. RESULTS: The 5- and 10-year OS rates for all ages were 60% and 48%, respectively, with a median survival time of 10.1 years. Multivariate analysis revealed that the adverse prognostic factors associated with decreased OS were older age (P < 0.001; hazard ratio 1.03) and MD at diagnosis (P = 0.001; 2.89), with upper extremity tumours being favourable (P = 0.043; 2.30). Poor prognosis for post-operative LR was associated with older age (P = 0.046; 1.03) and positive surgical margins (P = 0.028; 2.68). Increased post-treatment MD was seen in patients with large tumours (5-9 cm (P < 0.001; 4.42), ≥10 cm (P < 0.001; 6.80)) and MD at diagnosis (P < 0.001; 3.99), adjuvant therapy was favourable, shown to reduce MD (P < 0.001; 0.34). CONCLUSIONS: UPS is a high-grade soft tissue sarcoma, for which surgery striving for negative margins, with radiotherapy, is the treatment of choice. Older age, lower extremity location, MD at presentation, large size and positive surgical margins, were unfavourable.

Metastatic bone disease of the pelvis and extremities: rationalizing orthopaedic treatment.

BACKGROUND: Choosing the appropriate treatment for patients presenting with impending or pathological fractures is difficult and understanding the prognosis based on certain characteristics can help inform the decision to treat and construct to use in a palliative setting. We retrospectively analysed patients presenting with metastatic bone disease in the extremities and pelvis. METHODS: Patients presenting with metastatic bone disease to the extremities or pelvis who underwent orthopaedic treatment from 1996 to 2012 were identified. Survival rates were calculated using life table analysis. Univariate and multivariate analysis was achieved with Cox proportional hazards regression. RESULTS: There were a total of 462 patients. An overall 1-, 2- and 5-year survival rate of 45%, 29% and 13% was identified, respectively. In the multivariate analysis, preoperative haemoglobin was found to be an independent predictor of better survival while lung histotype, age, pathological fracture and previous combined therapy were negative predictors of survival. Patients undergoing prosthetic replacement had a significantly longer period of hospitalization in comparison to those undergoing internal fixation. CONCLUSION: This study has contributed to our understanding of the survival rate and survival prognostication for patients presenting for orthopaedic treatment of metastatic bone disease.

'Beware the lump in the foot!': predictors of recurrence and survival in bone and soft-tissue sarcomas of the foot and ankle.

BACKGROUND: Although benign lumps around the foot and ankle are common, sarcomas in this area are frequently missed, and the consequences can be disastrous. Patients are often referred to tumour centres after suboptimal prior surgical excision. The predictors of local recurrence, metastasis and survival in this cohort have yet to be elucidated. METHODS: We performed a retrospective review of 61 consecutive patients that were surgically treated for a bone (BS) or soft-tissue sarcoma (STS) of the foot and ankle between 1996 and 2012 at a specialist tumour centre. Factors such as tumour versus non-tumour centre surgery and BS versus STS were examined. Univariate and multivariate analyses were performed to determine which factors predicted local recurrence, metastasis and survival. RESULTS: The overall 5-year survival rates were 74% in the STS group and 90% in the BS group. Furthermore, 33 (54%) patients had STS. Non-tumour centre surgery was performed in 23 (38%) patients. Overall local recurrence rate was 6.6%. Intra-lesional margins predicted a local recurrence, whereas non-tumour centre surgery was a predictor for developing a metastasis post-treatment. Tumour size, STS, radical margins (i.e. entire anatomical compartment removed with tumour) and metastasis, either at the time of referral or post-treatment, were associated with higher mortality. CONCLUSION: STSs of the foot and ankle appear to have a worse prognosis than BSs. Early referral to a specialist tumour centre before surgical intervention is recommended.

Predicting blood loss and transfusion requirement in patients undergoing surgery for musculoskeletal tumors.

BACKGROUND: Few studies have systematically identified factors associated with blood loss in musculoskeletal tumor surgery. We aimed to identify risk factors for requiring large-volume transfusion in musculoskeletal tumor surgery and created an interactive model to predict red blood cell transfusion requirements based on patient characteristics. These data will facilitate planning in hospital blood banks and aid identification of specific groups for future interventions targeted at reducing blood utilization. Only one similar study has been published and there are minimal data surrounding interventions designed to minimize blood loss in musculoskeletal tumor surgery. STUDY DESIGN AND METHODS: We retrospectively analyzed a database containing 1322 consecutive surgeries, performed at a quaternary referral center in Melbourne, Australia. Using logistic regression analysis and a negative truncated binomial logistic regression model, we developed prediction models for transfusion requirement. RESULTS: The following factors were associated with large-volume transfusion: malignant tumors, bone tumors, sacral and pelvic tumors, high American Society of Anesthesiologists (ASA) score, and tumor size of more than 5 cm. High ASA score was also strongly associated with 30-day mortality. CONCLUSIONS: Preoperative planning in high-risk patients is critical to ensure adequate blood product supply, minimize wastage, and optimize the patient's general health before surgery. These patients would be ideal targets for future randomized studies aimed at reducing blood utilization.

Respiratory syncytial virus prophylaxis: a survey of pediatric solid organ transplant centers.

RSV can cause respiratory illness after SOT, yet preventive recommendations are lacking for this population. To ascertain current preventive practices against RSV disease in pediatric SOT candidates and recipients, a survey was developed. The survey was mailed to 108 SOT programs in the United States (liver, 42; heart, 28; lung, 11; intestinal, 25; and heart-lung, 2). Results were tabulated and analyzed using standard methods. Sixty-two percent (67/108) of surveys were completed. Forty-nine percent (33/67) of programs reported using RSV prophylaxis; palivizumab was used at 97% (32/33) of centers with 26 giving palivizumab to candidates and 27 to recipients. Prophylaxis was provided to infants aged 0-12 months by 27/29 (93%) of responding centers; 23/29 of centers extended its use to infants aged 0-24 months. Three centers gave prophylaxis to children between ages two and four yr and two centers for those over four yr. RSV prophylactic strategies, and in particular the use of palivizumab, are employed by almost 50% of responding pediatric SOT centers. Strategies varied at centers based on age and organ type. Data on RSV hospitalization and outcome are needed to refine approaches to RSV immunoprophylaxis in these high-risk patients.

Diagnostic virology practices for respiratory syncytial virus and influenza virus among children in the hospital setting: a national survey.

A survey was sent to the emergency room and laboratory directors of 400 randomly selected US hospitals to assess the diagnostic testing practices for respiratory syncytial virus and influenza virus in children. The results demonstrate that the majority of hospitals routinely perform viral testing for both viruses and use virology testing practices appropriate for the reasons reported for testing.

Parental opinions about facial plastic surgery for individuals with down syndrome.

Facial plastic surgery is an intervention that some have proposed to improve the physical functioning, appearance, and social acceptance of individuals with Down syndrome. Our purpose in this study was to examine the opinions of parents of children with Down syndrome about this practice. Two hundred and fifty parents responded with usable surveys and were generally familiar with the practice, yet the majority of respondents did not support the surgery. The literature on this topic is reviewed, and related issues are discussed.

The extent, nature, and precipitating factors of nurse assault among three groups of registered nurses in a regional medical center.

INTRODUCTION: This study investigated nurse perceptions of the incidence and nature of verbal and physical assault or abuse by patients and their family members or visitors. METHODS: A survey was given to ED, ICU, and general floor nurses in a 770-bed acute care north Florida medical center. RESULTS: The response rate was 68.8% (86 out of 125). Large percentages of nurses reported being victims of verbal assault or abuse and physical assault by patients and family members or visitors; 88% reported being verbally assaulted and 74% reported being physically assaulted while at work in the past year. ED nurses reported the highest rates of these incidences, with 100% reporting verbal assault and 82.1% reporting physical assault within the past year. Assaults were most commonly perpetrated by patients with cognitive dysfunction (79.1%), patients with substance abuse (60.5%), and persons who were angry because of the patient's condition (55.8%). Surprising information: the most common causes of assault by family members and visitors were anger related to enforcement of hospital policies (58.1%), anger related to the patient's condition/situation (57%), anger related to long wait times (47.7%), and anger related to the health care system in general (46.5%). DISCUSSION: Nurses were confused about what legally constitutes "assault" and "abuse"; nurse rights versus patient rights; and policies and procedures for reporting assault or abuse incidences. Our results indicate that nurses are experiencing abusive and assaultive behavior from family members and visitors just as often as they are from patients, and ED nurses are at higher risk. Nurses perceive a lack of institutional support and an institutional emphasis on patient rights and satisfaction and do not feel safe in the workplace.