The RNA-binding protein SRSF3 has an essential role in megakaryocyte maturation and platelet production.

RNA processing is increasingly recognized as a critical control point in the regulation of different hematopoietic lineages including megakaryocytes responsible for the production of platelets. Platelets are anucleate cytoplasts that contain a rich repertoire of RNAs encoding proteins with essential platelet functions derived from the parent megakaryocyte. It is largely unknown how RNA binding proteins contribute to the development and functions of megakaryocytes and platelets. We show that serine-arginine-rich splicing factor 3 (SRSF3) is essential for megakaryocyte maturation and generation of functional platelets. Megakaryocyte-specific deletion of Srsf3 in mice led to macrothrombocytopenia characterized by megakaryocyte maturation arrest, dramatically reduced platelet counts, and abnormally large functionally compromised platelets. SRSF3 deficient megakaryocytes failed to reprogram their transcriptome during maturation and to load platelets with RNAs required for normal platelet function. SRSF3 depletion led to nuclear accumulation of megakaryocyte mRNAs, demonstrating that SRSF3 deploys similar RNA regulatory mechanisms in megakaryocytes as in other cell types. Our study further suggests that SRSF3 plays a role in sorting cytoplasmic megakaryocyte RNAs into platelets and demonstrates how SRSF3-mediated RNA processing forms a central part of megakaryocyte gene regulation. Understanding SRSF3 functions in megakaryocytes and platelets provides key insights into normal thrombopoiesis and platelet pathologies as SRSF3 RNA targets in megakaryocytes are associated with platelet diseases.

The Year in Perioperative Echocardiography: Selected Highlights from 2023.

This article is the eighth in an annual series reviewing the research highlights of the year pertaining to the subspecialty of perioperative echocardiography for the Journal of Cardiothoracic and Vascular Anesthesia. The authors thank the editor-in-chief, Dr Kaplan, and the editorial board for the opportunity to continue this series. In most cases, these will be research articles targeted at the perioperative echocardiographic diagnosis and treatment of patients after cardiothoracic surgery; but in some cases, the articles will target the use of perioperative echocardiography in general.

The post-operative tonsillectomy (POPT) study: A multi-centre prospective paediatric cohort study.

OBJECTIVES: Tonsillectomy is the most common operation performed by otolaryngologists in the UK, despite this we have a poor understanding of the post-operative recovery. We aimed to investigate post-operative bleeding and pain following paediatric tonsillectomy using a patient diary. DESIGN: Prospective observational cohort study. SETTING: Multi-centre study involving 12 secondary and tertiary otolaryngology units across the North of England. Patients were recruited from 1st March 2020 to 30th June 2022. Multilevel ordered logistic regression model statistics were performed. PARTICIPANTS: Children (≥4 years, ≤16 years) undergoing tonsillectomy (with or without adenoidectomy) for benign pathology. MAIN OUTCOME MEASURES: Frequency and severity of post-operative bleeding. Intensity and pattern of post-operative pain. RESULTS: In total 297 children were recruited, with 91 (30.6%) diaries eligible for analysis. Post-operative bleeding occurred in 44% of children. Most frequently blood in the saliva was reported (82.9%). Increasing age significantly increased bleeding odds by 17% per year (p = .001). Bleeding frequency decreased with higher surgeon grade (p = .003) and when performing intracapsular coblation tonsillectomy (p = .02) compared with other techniques. Lower age and intracapsular coblation tonsillectomy, against other techniques, significantly reduced rates of pain post-operatively (p < .0001 and p = .0008). CONCLUSION: A high level of low-level post-operative bleeding was observed. Pain scores remained high for 5 days post-operatively then gradually reduce to normal by day 13. Intracapsular coblation tonsillectomy appears to be superior to all other techniques in terms of reducing post-operative bleeding and pain. These findings should be used to guide patients in the consent process to inform them of the expected nature of post-surgical recovery.

Highlights and Perioperative Implications from the 2022 American College of Cardiology and American Heart Association Guidelines for Diagnosis and Management of Aortic Disease.

As the understanding of aortic diseases and their complications grow, increasing importance of uniformity in diagnosis and management is crucial for optimal care of this patient population. The 2022 American College of Cardiology and American Heart Association Guidelines for Diagnosis and Management of Aortic Disease discusses these considerations in detail. The purpose of this review is to highlight essential recommendations that are of relevance to the perioperative physician who manages these patients. A few notable points include, shared decision-making with patients, creation of multidisciplinary aortic teams, lower diameter thresholds for surgery in certain situations, and increased testing for patients with heritable aortic diseases. In addition to briefly reviewing basics of aortic diseases, the authors discuss changes to guidelines that are especially relevant to perioperative care.

The Year in Cardiothoracic Transplant Anesthesia: Selected Highlights From 2021 Part II: Cardiac Transplantation.

This article spotlights the research highlights of this year that specifically pertain to the specialty of anesthesia for heart transplantation. This includes the research on recent developments in the selection and optimization of donors and recipients, including the use of donation after cardiorespiratory death and extended criteria donors, the use of mechanical circulatory support and nonmechanical circulatory support as bridges to transplantation, the effect of COVID-19 on heart transplantation candidates and recipients, and new advances in the perioperative management of these patients, including the use of echocardiography and postoperative outcomes, focusing on renal and cerebral outcomes.

Overweight, obesity and excessive weight gain in pregnancy as risk factors for adverse pregnancy outcomes: A narrative review.

The global prevalence of overweight and obesity in pregnancy is rising and this represents a significant challenge for the management of pregnancy and delivery. Women who have a pre-pregnancy body mass index greater than 25 kg m-2 are more likely than those with a body mass index in the ideal range (20-24.99 kg m-2 ) to have problems conceiving a child and are at greater risk of miscarriage and stillbirth. All pregnancy complications are more likely with overweight, obesity and excessive gestational weight gain, including those that pose a significant threat to the lives of mothers and babies. Labour complications arise more often when pregnancies are complicated by overweight and obesity. Pregnancy is a stage of life when women have greater openness to messages about their lifestyle and health. It is also a time when they come into greater contact with health professionals. Currently management of pregnancy weight gain and the impact of overweight tends to be poor, although a number of research studies have demonstrated that appropriate interventions based around dietary change can be effective in controlling weight gain and reducing the risk of pregnancy complications. The development of individualised and flexible plans for avoiding adverse outcomes of obesity in pregnancy will require investment in training of health professionals and better integration into normal antenatal care.

The RNA polymerase I transcription inhibitor CX-5461 cooperates with topoisomerase 1 inhibition by enhancing the DNA damage response in homologous recombination-proficient high-grade serous ovarian cancer.

BACKGROUND: Intrinsic and acquired drug resistance represent fundamental barriers to the cure of high-grade serous ovarian carcinoma (HGSC), the most common histological subtype accounting for the majority of ovarian cancer deaths. Defects in homologous recombination (HR) DNA repair are key determinants of sensitivity to chemotherapy and poly-ADP ribose polymerase inhibitors. Restoration of HR is a common mechanism of acquired resistance that results in patient mortality, highlighting the need to identify new therapies targeting HR-proficient disease. We have shown promise for CX-5461, a cancer therapeutic in early phase clinical trials, in treating HR-deficient HGSC. METHODS: Herein, we screen the whole protein-coding genome to identify potential targets whose depletion cooperates with CX-5461 in HR-proficient HGSC. RESULTS: We demonstrate robust proliferation inhibition in cells depleted of DNA topoisomerase 1 (TOP1). Combining the clinically used TOP1 inhibitor topotecan with CX-5461 potentiates a G2/M cell cycle checkpoint arrest in multiple HR-proficient HGSC cell lines. The combination enhances a nucleolar DNA damage response and global replication stress without increasing DNA strand breakage, significantly reducing clonogenic survival and tumour growth in vivo. CONCLUSIONS: Our findings highlight the possibility of exploiting TOP1 inhibition to be combined with CX-5461 as a non-genotoxic approach in targeting HR-proficient HGSC.

Shared roles for Scl and Lyl1 in murine platelet production and function.

The stem cell leukemia (Scl or Tal1) protein forms part of a multimeric transcription factor complex required for normal megakaryopoiesis. However, unlike other members of this complex such as Gata1, Fli1, and Runx1, mutations of Scl have not been observed as a cause of inherited thrombocytopenia. We postulated that functional redundancy with its closely related family member, lymphoblastic leukemia 1 (Lyl1) might explain this observation. To determine whether Lyl1 can substitute for Scl in megakaryopoiesis, we examined the platelet phenotype of mice lacking 1 or both factors in megakaryocytes. Conditional Scl knockout (KO) mice crossed with transgenic mice expressing Cre recombinase under the control of the mouse platelet factor 4 (Pf4) promoter generated megakaryocytes with markedly reduced but not absent Scl These Pf4Sclc-KO mice had mild thrombocytopenia and subtle defects in platelet aggregation. However, Pf4Sclc-KO mice generated on an Lyl1-null background (double knockout [DKO] mice) had severe macrothrombocytopenia, abnormal megakaryocyte morphology, defective pro-platelet formation, and markedly impaired platelet aggregation. DKO megakaryocytes, but not single-knockout megakaryocytes, had reduced expression of Gata1, Fli1, Nfe2, and many other genes that cause inherited thrombocytopenia. These gene expression changes were significantly associated with shared Scl and Lyl1 E-box binding sites that were also enriched for Gata1, Ets, and Runx1 motifs. Thus, Scl and Lyl1 share functional roles in platelet production by regulating expression of partner proteins including Gata1. We propose that this functional redundancy provides one explanation for the absence of Scl and Lyl1 mutations in inherited thrombocytopenia.

Pediatric psycho-oncology in Russia: Caregiver mental health and sleep outcomes on the oncology wards.

OBJECTIVES: Caregivers are at risk of poor sleep and elevated distress during their child's cancer treatment. Russia is currently underrepresented in the international psycho-oncology field, with no identified psychosocial standards of care, and limited or inconsistent psychological service provision, particularly for caregivers. This study aimed to determine the prevalence of Russian caregivers' psychological distress and identify factors associated with caregiver sleep duration when staying on the pediatric oncology ward. METHODS: We recruited 74 caregivers of children with cancer and 74 comparison caregivers in Rostov-on-Don, Russia. Participants completed a survey assessing clinical outcomes, sleep (St Mary's Hospital Sleep Questionnaire), and psychological distress (Depression Anxiety Stress Scales-21 [DASS-21]). RESULTS: Caregivers of children with cancer reported significantly higher scores for all DASS-21 subscales and higher depression (48.6% vs. 24.6%), anxiety (47.3% vs. 12.3%), and stress (45.9% vs. 0%) scores from "moderate" to "extremely severe." Caregivers of children with cancer reported significantly shorter sleep duration (5.82 vs. 7.49 h, t[143] = -6.22, p = 0.002), more night-time awakenings (3.20 vs. 1.25, t[135] = 6.94, p < 0.001) and worse sleep quality (46.5% vs. 9.6%; x2 [1] = 24.4, p < 0.001) than comparison caregivers. Caregivers with a higher total DASS-21 score (B = -1.32, p = 0.032) and those who were closer to diagnosis (B = -1.53, p = 0.012) reported shorter sleep duration. CONCLUSIONS: Russian caregivers of children with cancer experience high rates of psychological distress and poor sleep on the oncology ward. These findings provide an important target for future research and culturally relevant clinical interventions to improve caregivers' mental health and capacity for care.

Determinants of social functioning among adolescents and young adults with cancer: A systematic review.

OBJECTIVES: Survivors of adolescent and young adult (AYA) cancer report deficits in social functioning relative to healthy peers. Identifying factors related to their social functioning is critical to improve their long-term social outcomes. This review addressed: (1) How is social functioning defined and measured among studies of AYAs who have had cancer? (2) What factors have quantitatively/qualitatively are associated with/predictors of social functioning? and (3) What associated factors/predictors of social functioning are modifiable and amenable to intervention? METHODS: A systematic review was conducted to identify publications from 2000 to 2021, meeting these criteria: (1) mean/median age at diagnosis/treatment 13-40, (2) assessed social functioning with a validated measure and included factors associated with/predictive of social functioning and/or qualitatively assessed young people's perceptions of factors related to their social functioning and (3) was peer-reviewed/published in English. RESULTS: Thirty-seven publications were included. Definitions and measures of social functioning varied, and factors related to social functioning varied based on definition. Factors most commonly associated with decreased social functioning included treatment status (receiving or completed treatment), poor physical functioning, depression, negative body image, engaging in social comparisons, social/cultural stigma around cancer, and fatigue. Increased social functioning was most commonly associated with social support and the quality/age-appropriateness of care. CONCLUSIONS: Social functioning is multidimensional construct for AYAs diagnosed with cancer and may not be adequately assessed with measures of adjustment or quality of life. Future studies should clarify how to optimally define and measure social functioning in this population, to ensure their functioning can be protected and promoted long-term.

School and educational support programmes for paediatric oncology patients and survivors: A systematic review of evidence and recommendations for future research and practice.

OBJECTIVES: The Psychosocial Standards of Care (PSSC) in paediatric oncology prescribe the minimum standards for education support. It is unknown, however, if published education support programmes for children with cancer meet the PSSC standards for education support. Successful implementation of standards for education support is challenging but may be achieved with guidance. We aimed to (1) review education support programmes for childhood cancer patients and survivors against the PSSC standards and (2) provide practical recommendations for future research and implementation of education support programmes. METHODS: We searched PsycINFO, PubMed, CINAHL, EMBASE, and Educational Resources Information and Center databases. We reviewed the education support programmes using five evaluation criteria derived from the PSSC and summarised the structure of identified programmes. We examined the features and limitations of programmes that met all evaluation criteria. RESULTS: We identified 20 education support programmes in paediatric oncology, including peer programmes (n = 3), teacher programmes (n = 5), and school re-entry programmes (SRPs n = 12). We found that three SRPs met all evaluation criteria and that SRP components were timed according to the child's position on the cancer trajectory (e.g., diagnosis and treatment, school re-entry, and follow up throughout schooling). The supporting evidence of the programmes, however, is unclear due to the lack of adequately designed studies. CONCLUSIONS: SRPs provide a promising structure for future education support programmes. We recommend strategies for developing and evaluating education support that adheres to the PSSC and adapts to international and local contexts.

Feasibility and adherence to moderate intensity cardiovascular fitness training following stroke: a pilot randomized controlled trial.

BACKGROUND: Stroke is a leading cause of disability worldwide and the cardiovascular fitness levels of stroke survivors are diminished to an extent that impairs functioning and activities of daily living performance. While cardiovascular training seems an empirically appropriate intervention, the optimal dosage and intensity of cardiovascular training in stroke survivors remains unclear. The aim was to determine the safety and feasibility of moderate-intensity cardiovascular training following stroke, including measurement of adherence to training. METHODS: A pilot, prospective, patient- and assessor-blinded randomised controlled trial conducted in a tertiary, metropolitan hospital-based community rehabilitation centre. Eligibility criteria included ambulant (> 100 m), 6 weeks-12 months post stroke. Moderate-intensity fitness training or control (low-intensity) exercise was offered biweekly for 12 weeks. Outcome measures included adverse events, peak oxygen uptake (VO2), functional exercise capacity (6-Minute Walk Test, 10-m Walk Test) and health-related quality of life (Short Form-36) and mood (Patient Health Questionnaire, PHQ9). RESULTS: Feasibility: Seventy-one (50%) of 141 screened participants were eligible (29% did not agree to participate). Twenty participants (10 intervention, 10 control) were recruited. The median (%; IQR) supervised sessions was 19.5 (81%; 12, 20); and 20 (83%; 19, 22) in the intervention and control groups, respectively. Progression of duration and intensity was limited; mean of 10 sessions to achieve target duration (30 min). There were no adverse events. Baseline peak oxygen uptake (VO2) levels were low (15.94 ml/kg/min). Significant improvements in VO2 peak in both groups were observed (p < 0.05). Although there were no significant between-group differences, this feasibility trial was not powered to detect change. CONCLUSIONS: Moderate-intensity fitness training was safe but achievement of target duration and intensity was challenging for stroke survivors. A definitive adequately-powered randomised trial is required. Alternative fitness training protocols may need to be explored. TRIAL REGISTRATION: The trial protocol was prospectively registered on the Australian New Zealand Clinical Trials Registry ( ACTRN 12613000822785 ) on 25/07/2013.

Health service and medication use of parents of childhood cancer survivors: a controlled comparison study.

BACKGROUND: Parents of childhood cancer survivors may be vulnerable to experiencing poor health outcomes, but little is known about how these parents use healthcare. This study investigated the nature and extent of survivors' parents' healthcare and medication use relative to a comparison group. We also examined whether demographic or cancer-related factors were related to healthcare use and whether healthcare use was associated with parents' general functioning. METHODS: We conducted a cross-sectional study involving 55 parents of cancer survivors recruited through eight Australian hospitals, and 135 parents of children without a cancer diagnosis, through an online recruitment platform. Participants responded to a questionnaire assessing their health service usage, regular medications, general functioning (engagement activities including work/study) and anxiety and depression symptoms (using PROMIS short forms). We performed regression analysis to determine factors related to healthcare and medication use in parents of survivors. RESULTS: More parents of survivors reported accessing mental health services than comparison parents (56% vs. 33%, p=.003), mainly due to their use of social workers. Fewer parents of survivors reported accessing other community health services, particularly general practitioners (51% vs. 78%, p<.001). Having a child survivor who was male was associated with greater use of community health services (B= -0.67, p=.008). No other demographic or cancer-related variables were associated with health service use. Health service use was not associated with general functioning, but greater medication use was associated with higher anxiety scores (B = 1.41, p=.008). CONCLUSION: Parents of childhood cancer survivors showed different patterns of health service use relative to comparison parents, but the extent of their use was not significantly linked with demographic or cancer-related variables. Comprehensive assessment of parents' needs in clinical encounters remains vital to identify and appropriately match support needs with available services.

A review of the impact of hearing interventions on social isolation and loneliness in older people with hearing loss.

PURPOSE: Hearing loss affects many older people and is associated with social isolation and loneliness. The impact of hearing interventions however has not been established. The objective of this review is to determine the impact of hearing interventions in older people with hearing loss on social isolation and loneliness. METHODS: A literature review using PubMed, EMBASE and CINAHL databases was performed. Search terms included older people, elderly, aging, ageing, hearing aid, hearing rehabilitation, social isolation, loneliness and social interaction. English-language studies with participants aged over 60 years diagnosed with hearing loss comparing outcomes pre- and post-hearing interventions were included. RESULTS: A total of 176 articles were identified of which seven met the inclusion criteria. Five studies examined the impact of traditional hearing aids whilst two articles examined outcomes after cochlear implantation. Several outcome measures were used. Loneliness outcomes were reported in three studies and social isolation outcomes in four. All studies reported improved social isolation and loneliness scores following hearing intervention. CONCLUSIONS: Small sample sizes, a lack of high-quality evidence, heterogenicity between studies and the presence of confounding factors limits interpretation of the literature. At present, there is inadequate evidence to support the use of hearing interventions in the treatment of social isolation and loneliness in older people. Given the ageing population, the significance of this health burden cannot be underestimated, emphasising the need for further research.

RAF1 rearrangements are common in pancreatic acinar cell carcinomas.

There is now evidence that gene fusions activating the MAPK pathway are relatively common in pancreatic acinar cell carcinoma with potentially actionable BRAF or RET fusions being found in ~30%. We sought to investigate the incidence of RAF1 fusions in pancreatic malignancies with acinar cell differentiation. FISH testing for RAF1 was undertaken on 30 tumors comprising 25 'pure' acinar cell carcinomas, 2 mixed pancreatic acinar-neuroendocrine carcinomas, 1 mixed acinar cell-low grade neuroendocrine tumor and 2 pancreatoblastomas. RAF1 rearrangements were identified in 5 cases and confirmed by DNA and RNA sequencing to represent oncogenic fusions (GATM-RAF1, GOLGA4-RAF1, PDZRN3-RAF1, HERPUD1-RAF1 and TRIM33-RAF1) and to be mutually exclusive with BRAF and RET fusions, as well as KRAS mutations. Large genome-wide copy number changes were common and included 1q gain and/or 1p loss in all five RAF1 FISH-positive acinar cell carcinomas. RAF1 expression by immunohistochemistry was found in 3 of 5 (60%) of fusion-positive cases and no FISH-negative cases. Phospho-ERK1/2 expression was found in 4 of 5 RAF1-fusion-positive cases. Expression of both RAF1 and phospho-ERK1/2 was heterogeneous and often only detected at the tumor-stroma interface, thus limiting their clinical utility. We conclude that RAF1 gene rearrangements are relatively common in pancreatic acinar cell carcinomas (14.3% to 18.5% of cases) and can be effectively identified by FISH with follow up molecular testing. The combined results of several studies now indicate that BRAF, RET or RAF1 fusions occur in between one third and one-half of these tumors but are extremely rare in other pancreatic malignancies. As these fusions are potentially actionable with currently available therapies, a strong argument can be made to perform FISH or molecular testing on all pancreatic acinar cell carcinomas.

The transcription factor Erg is essential for definitive hematopoiesis and the function of adult hematopoietic stem cells.

Ets-related gene (ERG), which encodes a member of the Ets family of transcription factors, is a potent oncogene. Chromosomal rearrangements involving ERG are found in acute myeloid leukemia, acute lymphoblastic leukemia, Ewing's sarcoma and more than half of all prostate cancers; however, the normal physiological function of Erg is unknown. We did a sensitized genetic screen of the mouse for regulators of hematopoietic stem cell function and report here a germline mutation of Erg. We show that Erg is required for definitive hematopoiesis, adult hematopoietic stem cell function and the maintenance of normal peripheral blood platelet numbers.

Intrinsic apoptosis circumvents the functional decline of circulating platelets but does not cause the storage lesion.

The circulating life span of blood platelets is regulated by the prosurvival protein BCL-XL It restrains the activity of BAK and BAX, the essential prodeath mediators of intrinsic apoptosis. Disabling the platelet intrinsic apoptotic pathway in mice by deleting BAK and BAX results in a doubling of platelet life span and concomitant thrombocytosis. Apoptotic platelets expose phosphatidylserine (PS) via a mechanism that is distinct from that driven by classical agonists. Whether there is any role for apoptotic PS in platelet function in vivo, however, is unclear. Apoptosis has also been associated with the platelet storage lesion (PSL), the constellation of biochemical deteriorations that occur during blood bank storage. In this study, we investigated the role of BAK/BAX-mediated apoptosis in hemostasis and thrombosis and in the development of the PSL. We show that although intrinsic apoptosis is rapidly induced during storage at 37°C, it is not detected when platelets are kept at the standard storage temperature of 22°C. Remarkably, loss of BAK and BAX did not prevent the development of the PSL at either temperature. BAK/BAX-deficient mice exhibited increased bleeding times and unstable thrombus formation. This phenotype was not caused by impaired PS exposure, but was associated with a defect in granule release from aged platelets. Strikingly, rejuvenation of BAK/BAX-deficient platelets in vivo completely rescued the observed hemostatic defects. Thus, apoptotic culling of old platelets from the bloodstream is essential to maintain a functional, hemostatically reactive platelet population. Inhibiting intrinsic apoptosis in blood banked platelets is unlikely to yield significant benefit.

Protection from endogenous perforin: glycans and the C terminus regulate exocytic trafficking in cytotoxic lymphocytes.

Cytotoxic lymphocyte-mediated apoptosis is dependent on the delivery of perforin to secretory granules and its ability to form calcium-dependent pores in the target cell after granule exocytosis. It is unclear how cytotoxic lymphocytes synthesize and store perforin without incurring damage or death. We discovered that the extreme C terminus of perforin was essential for rapid trafficking from the endoplasmic reticulum to the Golgi compartment. Substitution of the C-terminal tryptophan residue resulted in retention of perforin in the ER followed by calcium-dependent toxic activity that eliminated host cells. We also found that N-linked glycosylation of perforin was critical for transport from the Golgi to secretory granules. Overall, an intact C terminus and N-linked glycosylation provide accurate and efficient export of perforin from the endoplasmic reticulum to the secretory granules and are critical for cytotoxic lymphocyte survival.

A call to action for expanded sleep research in pediatric oncology: A position paper on behalf of the International Psycho-Oncology Society Pediatrics Special Interest Group.

Sleep and circadian rhythms are closely related to physical and psychosocial well-being. However, sleep and circadian rhythm disruptions are often overlooked in children with cancer, as they are frequently considered temporary side effects of therapy that resolve when treatment ends. Yet, evidence from adult oncology suggests a bidirectional relationship wherein cancer and its treatment disrupt sleep and circadian rhythms, which are associated with negative health outcomes such as poor immune functioning and lower survival rates. A growing body of research demonstrates that sleep problems are prevalent among children with cancer and can persist into survivorship. However, medical and psychosocial outcomes of poor sleep and circadian rhythmicity have not been explored in this context. It is essential to increase our understanding because sleep and circadian rhythms are vital components of health and quality of life. In children without cancer, sleep and circadian disturbances respond well to intervention, suggesting that they may also be modifiable in children with cancer. We present this paper as a call to (a) incorporate sleep or circadian rhythm assessment into pediatric cancer clinical trials, (b) address gaps in understanding the bidirectional relationship between sleep or circadian rhythms and health throughout the cancer trajectory, and (c) integrate sleep and circadian science into oncologic treatment.

Total volume of cam deformity alone predicts outcome in arthroscopy for femoroacetabular impingement.

PURPOSE: Rates for arthroscopic surgery for femoroacetabular impingement (FAI) are rising and there is growing concern related to the effectiveness and costs associated with this treatment. There is a general lack of consensus as to the criteria for surgical selection of patients. The purpose of this study was to determine whether patient outcome following arthroscopic surgery for FAI could be predicted based on the size and location of deformity. The specific questions were: (1) what is the morphology of FAI in terms of size and location of deformity in a cohort of patients selected for surgery? (2) Do morphological factors predict postoperative improvement in hip scores? (3) Do morphological factors predict preoperative hip scores? (4) Are there clusters of morphological factors which explain postsurgical improvement in hip scores? MATERIALS AND METHODS: Computer tomography (CT) surgical plans of 90 hips in 79 patients who had undergone primary hip arthroscopy for FAI were retrospectively reviewed. Four parameters for the femur and acetabulum were created: total depth of deformity, maximal depth, extent and the position of maximal deformity. This data were compared with prospectively acquired preoperative and postoperative patient outcome data using generalised linear models. RESULTS: The cohort comprised 33 males and 46 females aged 37.9 (18-61). The majority (74%) had mixed morphology, 23% isolated cam, and 3% isolated pincer. Overall, the bone depth was greatest and more extensive on the femur. Increased total additional cam deformity alone predicted poorer postoperative outcome (p = 0.045). None of the morphological factors were related to preoperative scores and there was no association between the meta-variables and postoperative outcome. CONCLUSIONS: The results of this study indicate that a greater total volume of cam deformity led to poorer postoperative patient outcome scores at 1 year. This information provides the surgeon with more accurate patient-specific data for prediction of expected outcomes. LEVEL OF EVIDENCE: Level III diagnostic.