Development and External Validation of a Model to Predict Overall Survival in Patients With Resected Gallbladder Cancer.

OBJECTIVE: The aim of this study was to develop and validate a clinical prediction model to predict overall survival in patients with nonmetastatic, resected gallbladder cancer (GBC). BACKGROUND: Although several tools are available, no optimal method has been identified to assess survival in patients with resected GBC. METHODS: Data from a Dutch, nation-wide cohort of patients with resected GBC was used to develop a prediction model for overall survival. The model was internally validated and a cohort of Australian GBC patients who underwent resection was used for external validation. The performance of the American Joint Committee on Cancer (AJCC) staging system and the present model were compared. RESULTS: In total, 446 patients were included; 380 patients in the development cohort and 66 patients in the validation cohort. In the development cohort median survival was 22 months (median follow-up 75 months). Age, T/N classification, resection margin, differentiation grade, and vascular invasion were independent predictors of survival. The externally validated C-index was 0.75 (95%CI: 0.69-0.80), implying good discriminatory capacity. The discriminative ability of the present model after internal validation was superior to the ability of the AJCC staging system (Harrell C-index 0.71, [95%CI: 0.69-0.72) vs. 0.59 (95% CI: 0.57-0.60)]. CONCLUSION: The proposed model for the prediction of overall survival in patients with resected GBC demonstrates good discriminatory capacity, reasonable calibration and outperforms the authoritative AJCC staging system. This model can be a useful tool for physicians and patients to obtain information about survival after resection and is available from https:// gallbladderresearch.shinyapps.io/Predict_GBC_survival/.

WHO 2022 classification of penile and scrotal cancers: updates and evolution.

Squamous cell carcinoma (SCC) is the most common malignant tumour of the penis. The 2022 WHO classification reinforces the 2016 classification and subclassifies precursor lesions and tumours into human papillomavirus (HPV)-associated and HPV-independent types. HPV-associated penile intraepithelial neoplasia (PeIN) is a precursor lesion of invasive HPV- associated SCC, whereas differentiated PeIN is a precursor lesion of HPV-independent SCC. Block-type positivity of p16 immunohistochemistry is the most practical daily utilised method to separate HPVassociated from HPVindependent penile SCC. If this is not feasible, the term SCC, not otherwise specified (NOS) is appropriate. Certain histologies that were previously classified as "subtypes" are now grouped, and coalesced as "patterns", under the rubric of usual type SCC and verrucous carcinoma (e.g. usual-type SCC includes pseudohyperplastic and acantholytic/pseudoglandular carcinoma, and carcinoma cuniculatum is included as a pattern of verrucous carcinoma). If there is an additional component of the usual type of invasive SCC (formerly termed hybrid histology), the tumour would be a mixed carcinoma (e.g. carcinoma cuniculatum or verrucous carcinoma with usual invasive SCC); in such cases, reporting of the relative percentages in mixed tumours may be useful. The consistent use of uniform nomenclature and reporting of percentages will inform the refinement of future reporting classification schemes and guidelines/recommendations. The classification of scrotal tumours is provided for the first time in the fifth edition of the WHO Blue book, and it follows the schema of penile cancer classification for both precursor lesions and the common SCC of the scrotum. Basal cell carcinoma of the scrotum may have a variable clinical course and finds a separate mention.

Moderators of the Effectiveness of UPcomplish on Office Workers' Sedentary Behaviour, Quality of Life, and Psychosocial Determinants: A Stepped Wedge Design.

BACKGROUND: In the earlier developed and evaluated 12-week UPcomplish intervention, the aim was to reduce sedentary behaviour (SB) among office workers and increase their quality of life (QoL). In the current study, we explored moderators of effectiveness. METHOD: We applied a stepped wedge design with five intervention groups starting with time lags of seven weeks (n = 142, 96 females). Participants wore the VitaBit to continuously measure SB and received surveys about QoL and psychosocial determinants at the beginning, middle, and end of the intervention. We regressed baseline participant characteristics and behaviours onto intra-individual improvements (centred around calendar week means) in determinants, SB, performance objectives, and QoL. RESULTS: Those scoring high in baseline intention, task performance, stress, vitality, and emotional well-being improved less in these variables. Baseline stress (ß = - 0.05 [SE = 0.01; 95% CI = - 0.08, - 0.02; pcorrected = .02]) and emotional well-being (ß = 0.02 [SE = 0.01; 95% CI = 0.01, 0.03; pcorrected = .02]) were associated with improvement in contextual performance. Baseline attitude (ß = - 12.92 [SE = 3.93; 95% CI = - 20.80, - 5.04; pcorrected = .02]) and perceived behavioural control (PBC; ß = - 9.27 [SE = 3.04; 95% CI = - 15.37, - 3.16; pcorrected = .03]) were negatively associated with improvements in emotional well-being. Post hoc analyses with a sub-group scoring lower in determinants revealed that improvement in PBC was positively associated with SB registration. CONCLUSION: Participants scoring low in baseline determinants might profit from UPcomplish via an increase in PBC. In combination with changes within organizations (e.g. the implementation of standing desks), UPcomplish might potentially reduce SB. TRIAL REGISTRATION: NL7503 - registered 1 February 2019.

Nutritional changes during the COVID-19 pandemic: a rapid scoping review on the impact of psychological factors.

COVID-19 and the resulting measures to curb the spread of the virus have significantly changed our lives, including our nutritional choices. In this rapid scoping review an overview is provided of what psychological factors may be associated with peoples' eating behaviour during COVID-19 restrictions. Relevant literature was identified using PubMed, PsycInfo, CINAHL and MEDLINE databases from 2019 onwards. For included studies, information on study characteristics, eating behaviours, and psychological factors were extracted. 118 articles were included, representing 30 countries. Findings indicated that most people consumed more and unhealthy food in times of COVID-19 restrictions, while some consumed less but often for the wrong reasons. Several psychological factors, related to (1) affective reactions, (2) anxiety, fear and worriers, (3) stress and (4) subjective and mental wellbeing were found to be associated with this increase in food consumption. These outcomes may help to be better inform future interventions, and with that, to be better prepared in case of future lockdown scenarios.

Just-in-Time, but Still Planned: Lessons Learned From Speeding up the Development and Implementation of an Intervention to Promote COVID-19 Vaccination in University Students.

The process of developing a behavior change intervention can cover a long time period. However, in times of need, this development process has to be more efficient and without losing the scientific rigor. In this article, we describe the just-in-time, planned development of an online intervention in the field of higher education, promoting COVID-19 vaccination among university students, just before they were eligible for being vaccinated. We demonstrate how intervention development can happen fast but with sufficient empirical and theoretical support. In the developmental process, Intervention Mapping (IM) helped with decision-making in every step. We learned that the whole process is primarily depending on the trust of those in charge in the quality of the program developers. Moreover, it is about applying theory, not about theory-testing. As there was no COVID-19-related evidence available, evidence from related fields helped as did theoretical knowledge about change processes, next to having easy access to the target population and important stakeholders for informed qualitative and quantitative research. This project was executed under unavoidable time pressure. IM helped us with systematically developing an intervention, just-in-time to positively affect vaccine acceptance among university students.

Defining the rate of nutritional and metabolic derangements after pancreatic resection.

BACKGROUND AND AIMS: Pancreatic resection is associated with pancreatic exocrine insufficiency (PEI) leading to nutritional consequences. The Pancreatic Nutrition Clinic was established to diagnose and manage PEI through standardised nutritional assessment. In this prospective observational study, we aimed to define the rate of PEI, diabetes mellitus and nutritional abnormalities in patients who underwent pancreatic resection. METHODS: All Pancreatic Nutrition Clinic patients were included for analysis. Clinical data were prospectively obtained at initial assessment. Biochemical data included micronutrient levels, faecal elastase-1 and haemoglobin A1c. Bone mineral density and nutritional assessment were undertaken. RESULTS: Ninety-eight patients were included. Fifty-nine per cent (58/98) had undergone a pancreatoduodenectomy. Ninety-three patients had a faecal elastase-1 result, 65% (60/93) of which had a faecal elastase-1 less than 200 µg/g of faeces. Seventy-five patients (76%) of the total population required PERT, and thirty-nine (40%) were classified as malnourished using the patient-generated subjective global assessment tool. Seventy-two per cent (70/97) had a biochemical deficiency of one or more micronutrients. Thirty-eight people (39%) had diabetes mellitus. Of the seventy-eight patients with a bone mineral density scan available for analysis, 29% (23/78) had osteoporosis and 49% (38/78) osteopenia. CONCLUSIONS: Pancreatic exocrine insufficiency, micronutrient deficiency, bone disease, diabetes mellitus and malnutrition are highly prevalent in patients who have undergone pancreatic resection.

The Effects of UPcomplish on Office Workers' Sedentary Behaviour, Quality of Life and Psychosocial Determinants: A Stepped-Wedge Design.

BACKGROUND: Sedentary behaviour (SB) affects cardiometabolic health and quality of life (QoL). We examine the effects of UPcomplish, a 12-week data-driven intervention, on SB, QoL and psychosocial determinants among office workers. METHODS: Participants were recruited via judgement sampling. Five groups starting with time-lags of 7 weeks (n = 142, 96 females) received 14 feedback messages (FBMs) which were tailored to SB patterns, goals and hurdles. Participants received questionnaires at the beginning, middle and end of the intervention and wore an accelerometer measuring SB, operationalized as proportions (compositional data approach, CoDA) and summed squared sitting bouts (SSSB). We used linear mixed-effects models with random intercepts for weeks (between-subjects) and individuals (within-subjects). RESULTS: UPcomplish did not reduce SB. Within-subjects compared to baseline, FBM #3 (ßCoDA = 0.24, p < .001, 95% CI [0.15, 0.33]; ßSSSB = 20.83, p < .001, 95% CI [13.90, 27.28]) and #4 (ßCoDA = 0.20, p < .001, 95% CI [0.11, 0.29]; ßSSSB = 24.80, p < .001, 95% CI [15.84, 33.76]) increased SB. QoL was unaffected. Perceived susceptibility was lower after FBMs #6 to #8 (ßbetween = - 0.66, p = .04, 95% CI [- 1.03, - 0.30]; ßwithin = - 0.75, p = .02, 95% CI [- 1.18, - 0.32]). Within-subjects, intentions to sit less were higher after FBMs #1 to #5 (1.14, p = .02, 95% CI [0.61, 1.66]). Improvements in determinants and in SB were not associated, nor were improvements in SB and in QoL. CONCLUSIONS: Compared to VitaBit only, UPcomplish was not beneficial. Environmental restructuring might be superior, but detailed analyses of moderators of effectiveness are needed.

Vaginal bacterial load in the second trimester is associated with early preterm birth recurrence: a nested case-control study.

OBJECTIVE: To assess the association between vaginal microbiome (VMB) composition and recurrent early spontaneous preterm birth (sPTB)/preterm prelabour rupture of membranes (PPROM). DESIGN: Nested case-control study. SETTING: UK tertiary referral hospital. SAMPLE: High-risk women with previous sPTB/PPROM <34+0 weeks' gestation who had a recurrence (n = 22) or delivered at ≥37+0 weeks without PPROM (n = 87). METHODS: Vaginal swabs collected between 15 and 22 weeks' gestation were analysed by 16S rRNA gene sequencing and 16S quantitative PCR. MAIN OUTCOME MEASURE: Recurrent early sPTB/PPROM. RESULTS: Of the 109 high-risk women, 28 had anaerobic vaginal dysbiosis, with the remainder dominated by lactobacilli (Lactobacillus iners 36/109, Lactobacillus crispatus 23/109, or other 22/109). VMB type and diversity were not associated with recurrence. Women with a recurrence, compared to those without, had a higher median vaginal bacterial load (8.64 versus 7.89 log10 cells/mcl, adjusted odds ratio [aOR] 1.90, 95% CI 1.01-3.56, P = 0.047) and estimated Lactobacillus concentration (8.59 versus 7.48 log10 cells/mcl, aOR 2.35, (95% CI 1.20-4.61, P = 0.013). A higher recurrence risk was associated with higher median bacterial loads for each VMB type after stratification, although statistical significance was reached only for L. iners domination (aOR 3.44, 95% CI 1.06-11.15, P = 0.040). Women with anaerobic dysbiosis or L. iners domination had a higher median vaginal bacterial load than women with a VMB dominated by L. crispatus or other lactobacilli (8.54, 7.96, 7.63, and 7.53 log10 cells/mcl, respectively). CONCLUSIONS: Vaginal bacterial load is associated with early sPTB/PPROM recurrence. Domination by lactobacilli other than L. iners may protect women from developing high bacterial loads. Future PTB studies should quantify vaginal bacteria and yeasts. TWEETABLE ABSTRACT: Increased vaginal bacterial load in the second trimester may be associated with recurrent early spontaneous preterm birth.

Social Ecological Barriers for Healthy Eating of Obese Children and Their Caregivers in Low-income Families in South Korea.

In this qualitative study, the focus is on healthy eating in children from low-income families who visit a Community Child Care center (CCC) in South Korea. Barriers for healthy eating were identified using focus group interviews with low-income overweight and obese children and their caregivers and applying a social ecological model as well as the framework analysis for qualitative data. The need for theory- and evidence-based health promotion interventions is indicated, at the level of the family, but also at the level of collaboration among all stakeholders, as well as multi-level policy changes.

First-in-human phase I clinical trial of the NY-ESO-1 protein cancer vaccine with NOD2 and TLR9 stimulants in patients with NY-ESO-1-expressing refractory solid tumors.

Cholesteryl pullulan (CHP) is a novel antigen delivery system. CHP and New York esophageal squamous cell carcinoma 1 (NY-ESO-1) antigen complexes (CHP-NY-ESO-1) present multiple epitope peptides to the MHC class I and II pathways. Adjuvants are essential for cancer vaccines. MIS416 is a non-toxic microparticle that activates immunity via the nucleotide-binding oligomerization domain 2 (NOD2) and TLR9 pathways. However, no reports have explored MIS416 as a cancer vaccine adjuvant. We conducted a first-in-human clinical trial of CHP-NY-ESO-1 with MIS416 in patients with NY-ESO-1-expressing refractory solid tumors. CHP-NY-ESO-1/MIS416 (µg/µg) was administered at 100/200, 200/200, 200/400 or 200/600 (cohorts 1, 2, 3 and 4, respectively) every 2 weeks for a total of 6 doses (treatment phase) followed by one vaccination every 4 weeks until disease progression or unacceptable toxicity (maintenance phase). The primary endpoints were safety and tolerability, and the secondary endpoint was the immune response. In total, 26 patients were enrolled. Seven patients (38%) continued vaccination in the maintenance phase. Grade 3 drug-related adverse events (AEs) were observed in six patients (23%): anorexia and hypertension were observed in one and five patients, respectively. No grade 4-5 drug-related AEs were observed. Eight patients (31%) had stable disease (SD). Neither augmentation of the NY-ESO-1-specific IFN-γ-secreting CD8+ T cell response nor an increase in the level of anti-NY-ESO-1 IgG1 was observed as the dose of MIS416 was increased. In a preclinical study, adding anti-PD-1 monoclonal antibody to CHP-NY-ESO-1 and MIS416 induced significant tumor suppression. This combination therapy is a promising next step.

Salivary cortisol, cortisone and serum cortisol concentrations are related to age and body mass index in healthy children and young people.

BACKGROUND: Saliva is an ideal medium in which to measure cortisol in children. However, there are very few data reporting salivary cortisol or cortisone concentrations in healthy children since the introduction of liquid chromatography-mass spectrometry (LC-MS/MS) to routine laboratory practice. DESIGN: Early morning serum cortisol, salivary cortisol and cortisone were measured on fasting samples, and salivary hormones were measured in samples collected every 2 hours during waking hours, and 30 minutes after waking the following morning. PARTICIPANTS: 43 healthy paediatric volunteers (19 female), median age 11.5 years, range 6.2-18.7, participated. RESULTS: Early morning serum cortisol (265 nmol/L, 156-516) correlated strongly with salivary cortisol (4.7 nmol/L, 1.1-14.6) and cortisone (28.8 nmol/L, 11.7-56.6), P < .0001 for both. Serum cortisol, salivary cortisol and salivary cortisone correlated directly with age (P < .0001, P = .002 and P = .015, respectively), and salivary cortisone/cortisol ratio correlated indirectly with age (P = .007). Between 08.00 and 21.00, area under the curve for salivary cortisol (mean ± 1 SD) was 41.8 ± 19.1 and for cortisone 213.0 ± 61.2. Salivary cortisol was undetectable in 25/130 (19%) of samples collected after 13.00, while cortisone was always detectable. DISCUSSION: Salivary cortisol and cortisone concentrations are strongly related to serum cortisol concentrations; however, cortisone may be a preferable measure as cortisol is often undetectable. Age may be an important factor in the interpretation of early morning cortisol measurements made in serum and saliva.

Learning to coexist with wildfire.

The impacts of escalating wildfire in many regions - the lives and homes lost, the expense of suppression and the damage to ecosystem services - necessitate a more sustainable coexistence with wildfire. Climate change and continued development on fire-prone landscapes will only compound current problems. Emerging strategies for managing ecosystems and mitigating risks to human communities provide some hope, although greater recognition of their inherent variation and links is crucial. Without a more integrated framework, fire will never operate as a natural ecosystem process, and the impact on society will continue to grow. A more coordinated approach to risk management and land-use planning in these coupled systems is needed.

Associating sporadic, foodborne illness caused by Shiga toxin-producing Escherichia coli with specific foods: a systematic review and meta-analysis of case-control studies.

Shiga toxin-producing Escherichia coli (STEC) infections are a significant public health issue, with foodborne transmission causing >1 million illnesses worldwide each year. We conducted a systematic review and meta-analysis (PROSPERO registry # CRD42017074239), to determine the relative association of different food types with sporadic illnesses caused by STEC. Searches were conducted from 01 August to 30 September 2017, using bibliographic and grey literature databases, websites and expert consultation. We identified 22 case-control studies of sporadic STEC infection in humans, from 10 countries within four World Health Organization subregions, from 1985 to 2012. We extracted data from 21 studies, for 237 individual measures in 11 food categories and across three status types (raw or undercooked, not raw and unknown). Beef was the most significant food item associated with STEC illness in the Americas and Europe, but in the Western Pacific region, chicken was most significant. These findings were not significantly moderated by the raw or cooked status of the food item, nor the publication year of the study. Data from the African, South-East Asian and Eastern Mediterranean subregions were lacking and it is unclear whether our results are relevant to these regions.

Hepatic late adverse effects after antineoplastic treatment for childhood cancer.

BACKGROUND: Survival rates have greatly improved as a result of more effective treatments for childhood cancer. Unfortunately, the improved prognosis has been accompanied by the occurrence of late, treatment-related complications. Liver complications are common during and soon after treatment for childhood cancer. However, among long-term childhood cancer survivors, the risk of hepatic late adverse effects is largely unknown. To make informed decisions about future cancer treatment and follow-up policies, it is important to know the risk of, and associated risk factors for, hepatic late adverse effects. This review is an update of a previously published Cochrane review. OBJECTIVES: To evaluate all the existing evidence on the association between antineoplastic treatment (that is, chemotherapy, radiotherapy involving the liver, surgery involving the liver and BMT) for childhood cancer and hepatic late adverse effects. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2018, Issue 1), MEDLINE (1966 to January 2018) and Embase (1980 to January 2018). In addition, we searched reference lists of relevant articles and scanned the conference proceedings of the International Society of Paediatric Oncology (SIOP) (from 2005 to 2017) and American Society of Pediatric Hematology/Oncology (ASPHO) (from 2013 to 2018) electronically. SELECTION CRITERIA: All studies, except case reports, case series, and studies including fewer than 10 patients that examined the association between antineoplastic treatment for childhood cancer (aged 18 years or less at diagnosis) and hepatic late adverse effects (one year or more after the end of treatment). DATA COLLECTION AND ANALYSIS: Two review authors independently performed the study selection and 'risk of bias' assessment. The 'risk of bias' assessment was based on earlier checklists for observational studies. For the original version of the review, two review authors independently performed data extraction. For the update of the review, the data extraction was performed by one reviewer and checked by another reviewer. MAIN RESULTS: Thirteen new studies were identified for the update of this review. In total, we included 33 cohort studies including 7876 participants investigating hepatic late adverse effects after antineoplastic treatment (especially chemotherapy and radiotherapy) for different types of childhood cancer, both haematological and solid malignancies. All studies had methodological limitations. The prevalence of hepatic late adverse effects, all defined in a biochemical way, varied widely, between 0% and 84.2%. Selecting studies where the outcome of hepatic late adverse effects was well-defined as alanine aminotransferase (ALT) above the upper limit of normal, indicating cellular liver injury, resulted in eight studies. In this subgroup, the prevalence of hepatic late adverse effects ranged from 5.8% to 52.8%, with median follow-up durations varying from three to 23 years since cancer diagnosis in studies that reported the median follow-up duration. A more stringent selection process using the outcome definition of ALT as above twice the upper limit of normal, resulted in five studies, with a prevalence ranging from 0.9% to 44.8%. One study investigated biliary tract injury, defined as gamma-glutamyltransferase (γGT) above the upper limit of normal and above twice the upper limit of normal and reported a prevalence of 5.3% and 0.9%, respectively. Three studies investigated disturbance in biliary function, defined as bilirubin above the upper limit of normal and reported prevalences ranging from 0% to 8.7%. Two studies showed that treatment with radiotherapy involving the liver (especially after a high percentage of the liver irradiated), higher BMI, and longer follow-up time or older age at evaluation increased the risk of cellular liver injury in multivariable analyses. In addition, there was some suggestion that busulfan, thioguanine, hepatic surgery, chronic viral hepatitis C, metabolic syndrome, use of statins, non-Hispanic white ethnicity, and higher alcohol intake (> 14 units per week) increase the risk of cellular liver injury in multivariable analyses. Chronic viral hepatitis was shown to increase the risk of cellular liver injury in six univariable analyses as well. Moreover, one study showed that treatment with radiotherapy involving the liver, higher BMI, higher alcohol intake (> 14 units per week), longer follow-up time, and older age at cancer diagnosis increased the risk of biliary tract injury in a multivariable analysis. AUTHORS' CONCLUSIONS: The prevalence of hepatic late adverse effects among studies with an adequate outcome definition varied considerably from 1% to 53%. Evidence suggests that radiotherapy involving the liver, higher BMI, chronic viral hepatitis and longer follow-up time or older age at follow-up increase the risk of hepatic late adverse effects. In addition, there may be a suggestion that busulfan, thioguanine, hepatic surgery, higher alcohol intake (>14 units per week), metabolic syndrome, use of statins, non-Hispanic white ethnicity, and older age at cancer diagnosis increase the risk of hepatic late adverse effects. High-quality studies are needed to evaluate the effects of different therapy doses, time trends, and associated risk factors after antineoplastic treatment for childhood cancer.

Population-Based Long-Term Cardiac-Specific Mortality Among 34 489 Five-Year Survivors of Childhood Cancer in Great Britain.

BACKGROUND: Increased risks of cardiac morbidity and mortality among childhood cancer survivors have been described previously. However, little is known about the very long-term risks of cardiac mortality and whether the risk has decreased among those more recently diagnosed. We investigated the risk of long-term cardiac mortality among survivors within the recently extended British Childhood Cancer Survivor Study. METHODS: The British Childhood Cancer Survivor Study is a population-based cohort of 34 489 five-year survivors of childhood cancer diagnosed from 1940 to 2006 and followed up until February 28, 2014, and is the largest cohort to date to assess late cardiac mortality. Standardized mortality ratios and absolute excess risks were used to quantify cardiac mortality excess risk. Multivariable Poisson regression models were used to evaluate the simultaneous effect of risk factors. Likelihood ratio tests were used to test for heterogeneity and trends. RESULTS: Overall, 181 cardiac deaths were observed, which was 3.4 times that expected. Survivors were 2.5 times and 5.9 times more at risk of ischemic heart disease and cardiomyopathy/heart failure death, respectively, than expected. Among those >60 years of age, subsequent primary neoplasms, cardiac disease, and other circulatory conditions accounted for 31%, 22%, and 15% of all excess deaths, respectively, providing clear focus for preventive interventions. The risk of both overall cardiac and cardiomyopathy/heart failure mortality was greatest among those diagnosed from 1980 to 1989. Specifically, for cardiomyopathy/heart failure deaths, survivors diagnosed from 1980 to 1989 had 28.9 times the excess number of deaths observed for survivors diagnosed either before 1970 or from 1990 on. CONCLUSIONS: Excess cardiac mortality among 5-year survivors of childhood cancer remains increased beyond 50 years of age and has clear messages in terms of prevention strategies. However, the fact that the risk was greatest in those diagnosed from 1980 to 1989 suggests that initiatives to reduce cardiotoxicity among those treated more recently may be having a measurable impact.

Shared motherhood IVF: high delivery rates in a large study of treatments for lesbian couples using partner-donated eggs.

Shared motherhood IVF treatment is becoming increasingly accepted among assisted reproductive techique practitioners and patients in Europe, although data on its overall efficiency remain scarce. This 6-year retrospective study from a single, private, UK HFEA-regulated centre included consecutive lesbian couples (n = 121) undergoing shared motherhood IVF treatment (141 cycles). Recipients were more parous and had undergone more previous intrauterine insemination and IVF treatments than donor partners, who had slightly higher ovarian reserve markers than recipients. Indications in most cycles (60%) were non-medical. Most (79%) egg-providers were stimulated with gonadotrophin releasing hormone antagonist protocol, and no moderate or severe cases of ovarian hyperstimulation syndrome (OHSS) arose. A total of 172 fresh and vitrified-warmed embryo transfers were carried out: 70% at the blastocyst-stage and 58% involved a single embryo. Cumulative live birth rate per receiver was 60% (72/120), and twin delivery rate was 14% (10/72). Perinatal outcome parameters were better for singleton than twin pregnancies, although the latter also achieved generally favourable outcomes. No significant difference in cumulative outcomes were found between synchronized and non-synchronized cycles. Shared motherhood IVF combines ovarian stimulation with single blastocyst transfer to provide a safe and effective treatment modality offering reassuring obstetrical and perinatal outcomes.

Medullary Thyroid Carcinoma: Survival Analysis and Evaluation of Mutation-Specific Immunohistochemistry in Detection of Sporadic Disease.

INTRODUCTION: Medullary thyroid cancer (MTC) is a rare tumour of neuroendocrine origin with a more aggressive profile than differentiated thyroid cancer. Familial cases of MTC are associated with RET mutations whilst RAS mutations appear to be a frequent finding in RET negative tumours. The aims of this study were to analyse survival outcomes in MTC and to evaluate the role of RAS immunohistochemistry in the identification of sporadic disease. MATERIALS AND METHODS: A retrospective cohort study of consecutive patients with MTC was undertaken. The primary outcome measures were overall survival and disease-free survival. Survival analysis was performed on the basis of sporadic and familial disease. Patients had routine RET testing using the capillary (Sanger) sequencing method. Histopathological MTC slides from 100 patients were tested for HRASQ61R, a common somatic RAS mutation in MTC, with mutation-specific immunohistochemistry (IHC). RESULTS: A total of 195 patients had surgical treatment of MTC in the period 1980 to 2016. There were 83 males and 112 females with a mean age of 53.0 years. A total of 39 (20%) patients had familial disease. Sporadic cases had a higher median pre-op calcitonin (969.5 vs. 257.5 pg/ml), greater mean primary tumour size (23.5 vs. 12.5 mm) and more distant metastases (12.8 vs. 10.3%). Multivariate analysis showed age (p = 0.005), Multiple Endocrine Neoplasia Type 2 (MEN2) status (p = 0.021) and distant metastasis (p = 0.002) to be significant independent predictors of survival. Significant independent predictors for disease-free survival were age (p = 0.015), MEN2 (p = 0.002), pre-op calcitonin (p = 0.033) and venous invasion (p = 0.001). The overall 5-year survival was 100% for familial MTC and 78% for sporadic MTC. The 10-year disease-free survival was 94% for familial MTC and 61% for sporadic cases. A total of 100 cases of MTC underwent mutation-specific IHC for HRASQ61R. Of these, 18 had confirmed MEN2. IHC had 100% specificity in excluding MEN2. Twelve (12%) of 100 patients stained positive for HRASQ61R mutation. CONCLUSION: In the era of genetic testing, RET status significantly influences disease-specific survival in MTC. Mutation-specific IHC for HRASQ61R may have a role in the identification of patients presenting with sporadic disease.

Validation of the VitaBit Sit-Stand Tracker: Detecting Sitting, Standing, and Activity Patterns.

Sedentary behavior (SB) has detrimental consequences and cannot be compensated for through moderate-to-vigorous physical activity (PA). In order to understand and mitigate SB, tools for measuring and monitoring SB are essential. While current direct-to-customer wearables focus on PA, the VitaBit validated in this study was developed to focus on SB. It was tested in a laboratory and in a free-living condition, comparing it to direct observation and to a current best-practice device, the ActiGraph, on a minute-by-minute basis. In the laboratory, the VitaBit yielded specificity and negative predictive rates (NPR) of above 91.2% for sitting and standing, while sensitivity and precision ranged from 74.6% to 85.7%. For walking, all performance values exceeded 97.3%. In the free-living condition, the device revealed performance of over 72.6% for sitting with the ActiGraph as criterion. While sensitivity and precision for standing and walking ranged from 48.2% to 68.7%, specificity and NPR exceeded 83.9%. According to the laboratory findings, high performance for sitting, standing, and walking makes the VitaBit eligible for SB monitoring. As the results are not transferrable to daily life activities, a direct observation study in a free-living setting is recommended.

Risk stratification of childhood cancer survivors necessary for evidence-based clinical long-term follow-up.

BACKGROUND: Reorganisation of clinical follow-up care in England was proposed by the National Cancer Survivorship Initiative (NCSI), based on cancer type and treatment, ranging from Level 1 (supported self-management) to Level 3 (consultant-led care). The objective of this study was to provide an investigation of the risks of serious adverse health-outcomes associated with NCSI Levels of clinical care using a large population-based cohort of childhood cancer survivors. METHODS: The British Childhood Cancer Survivor Study (BCCSS) was used to investigate risks of specific causes of death, subsequent primary neoplasms (SPNs) and non-fatal non-neoplastic outcomes by NCSI Level. RESULTS: Cumulative (excess) risks of specified adverse outcomes by 45 years from diagnosis among non-leukaemic survivors assigned to NCSI Levels 1, 2 and 3 were for: SPNs-5% (two-fold expected), 14% (four-fold expected) and 21% (eight-fold expected); non-neoplastic death-2% (two-fold expected), 4% (three-fold expected) and 8% (seven-fold expected); non-fatal non-neoplastic condition-14%, 27% and 40%, respectively. Consequently overall cumulative risks of any adverse health outcome were 21%, 45% and 69%, respectively. CONCLUSIONS: Despite its simplicity the risk stratification tool provides clear and strong discrimination between survivors assigned to different NCSI Levels in terms of long-term cumulative and excess risks of serious adverse outcomes.

Colorectal cancer resection in the Australian nonagenarian patient.

AIM: The nonagenarian population is a rapidly growing segment of the Australian population. Surgical resection continues to offer the best chance of long-term survival in colorectal cancer. The primary aims of the present study were to evaluate the 30-day mortality and survival of Australian patients ≥ 90 years of age undergoing surgical resection for colorectal cancer in our health service. The secondary aims were to examine the clinicopathological characteristics of the patients and their tumours. METHOD: All patients ≥ 90 years of age undergoing surgical resection for colorectal cancer from 1998 to 2012 were identified in a centralized multihospital database. Key clinicopathological data, 30-day mortality and long-term overall survival were recorded for each patient. RESULTS: There were 121 patients identified of median age 91 years, 74% of whom were female. The median tumour size was 40 mm, and 51% of operations were carried out as an emergency. The TNM stage was Stage I/II in 57%, Stage III in 40% and Stage IV in 3%. The 30-day mortality was 6.6% (eight of 121) and the 1-, 3- and 5-year overall survival rates were 82.6%, 50.2% and 32.3%, respectively. CONCLUSION: Surgical resection in the nonagenarian patient has an acceptable mortality and offers good overall survival.