93 research outputs found

    Long-Time Behaviour and Self-Similarity in a Coagulation Equation with Input of Monomers

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    For a coagulation equation with Becker-Doring type interactions and time-independent monomer input we study the detailed long-time behaviour of nonnegative solutions and prove the convergence to a self-similar function.Comment: 30 pages, 5 Figures, now published in Markov Processes and Related Fields 12, 367-398, (2006

    Body mass index at diagnosis of a childhood brain tumor; a reflection of hypothalamic-pituitary dysfunction or lifestyle?

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    Purpose: Childhood brain tumor survivors (CBTS) are at risk of becoming overweight, which has been shown to be associated with hypothalamic-pituitary (HP) dysfunction during follow-up. Body mass index (BMI) at diagnosis is related to BMI at follow-up. It is uncertain, however, whether aberrant BMI at brain tumor diagnosis reflects early hypothalamic dysfunction or rather reflects genetic and sociodemographic characteristics. We aimed to examine whether BMI at childhood brain tumor diagnosis is associated with HP dysfunction at diagnosis or its development during follow-up. Methods: The association of BMI at diagnosis of a childhood brain tumor to HP dysfunction at diagnosis or during follow-up was examined in a Dutch cohort of 685 CBTS, excluding children with craniopharyngioma or a pituitary tumor. Individual patient data were retrospectively extracted from patient charts. Results: Of 685 CTBS, 4.7% were underweight, 14.2% were overweight, and 3.8% were obese at diagnosis. Being overweight or obese at diagnosis was not associated with anterior pituitary deficiency or diabetes insipidus at diagnosis or during follow-up. In children with suprasellar tumors, being obese at diagnosis was associated with central precocious puberty. Conclusion: Overweight or obesity at diagnosis of a childhood brain tumor seems not to be associated with pituitary deficiencies. These results suggest that genetics and lifestyle may be more important etiologic factors for higher BMI at diagnosis in these children than hypothalamic dysfunction. To improve the long-term outcome of CBTS with regards to overweight and obesity, more attention should be given to lifestyle already at the time of brain tumor treatment

    Acquired hypothalamic dysfunction in childhood: ‘what do patients need?’ – an Endo-ERN survey

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    Objective: Hypothalamic dysfunction is a rare condition and can be encountered in patients who have been diagnosed or treated for a suprasellar brain tumor. Due to its rarity, the signs and symptoms of hypothalamic dysfunction may be difficult to recognize, leading to delayed diagnosis of the suprasellar brai n tumor or to difficulties in finding the health-care expertise for hypothalamic dysfunctio n after tumor treatment. To improve the care and outcome of patients with acquired hypothalamic dysfunction, professionals are required to understand the patient’s needs. Design: A worldwide online survey was distributed from April 2022 to October 2022 to patients with childhood-onset hypothalamic dysfunction (as reported by the patient) following a brain tumor. Methods: Patients were notified about the survey through patient advocacy groups, the SIOPe craniopharyngioma working group and the Endo-ERN platform. Results: In total, 353 patients with hypothalamic dysfunction following craniopharyngioma (82.2%), low-grade glioma (3.1%) or a pituitary tumor (8.2%) or caregivers responded to the survey. Sixty-two percent had panhypopituitarism. Obesity (50.7%) and fatigue (48.2%) were considered the most important health problems. Unmet needs were reported for help with diet, exercise and psychosocial issues. Patients’ suggestions for future research include new treatments for hypothalamic obesity and alternative ways for hormone administration. Conclusions: According to the patient’s perspective, care for acquired hypothalamic dysfunction can be improved if delivered by experts with a holistic view of the patient in a multidisciplinary setting with a focus on quality of life. Future care and research on hypothalamic dysfunction must integrate the patients’ unmet needs. Significance statement: Patients with hypothalamic dysfunction may experience a variety of symptoms, which are not always adequately recognized or addressed. In previous papers, the perspective of caregivers of children with craniopharyngioma has been reported (Klages et al. 2022, Craven et al. 2022). Now we address the patients’ perspective on acquired hypothalamic dysfunction using an Endo-ERN global survey. According to the patients’ perspective, care can be improved, with needs for improvement in the domains of obesity, fatigue and lifestyle. Research may focus on ways to improve hypothalamic obesity and alternative ways for hormone administration. Ideally, care should be delivered by doctors who have a holistic view of the patient in a multidisciplinary expert team. The results of this study can be used to formulate best practices for clinical care and to design future research proposals

    Acquired hypothalamic dysfunction in childhood: "What do patients need?" - an Endo-ERN survey

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    OBJECTIVE: Hypothalamic dysfunction is a rare condition and can be encountered in patients who have been diagnosed or treated for a suprasellar brain tumor. Due to its rarity, the signs and symptoms of hypothalamic dysfunction may be difficult to recognize, leading to delayed diagnosis of the suprasellar brain tumor or to difficulties in finding the health-care expertise for hypothalamic dysfunction after tumor treatment. To improve the care and outcome of patients with acquired hypothalamic dysfunction, professionals are required to understand the patient's needs. DESIGN: A worldwide online survey was distributed from April 2022 to October 2022 to patients with childhood-onset hypothalamic dysfunction (as reported by the patient) following a brain tumor. METHODS: Patients were notified about the survey through patient advocacy groups, the SIOPe craniopharyngioma working group and the Endo-ERN platform. RESULTS: In total, 353 patients with hypothalamic dysfunction following craniopharyngioma (82.2%), low-grade glioma (3.1%) or a pituitary tumor (8.2%) or caregivers responded to the survey. Sixty-two percent had panhypopituitarism. Obesity (50.7%) and fatigue (48.2%) were considered the most important health problems. Unmet needs were reported for help with diet, exercise and psychosocial issues. Patients' suggestions for future research include new treatments for hypothalamic obesity and alternative ways for hormone administration. CONCLUSIONS: According to the patient's perspective, care for acquired hypothalamic dysfunction can be improved if delivered by experts with a holistic view of the patient in a multidisciplinary setting with a focus on quality of life. Future care and research on hypothalamic dysfunction must integrate the patients' unmet needs. SIGNIFICANCE STATEMENT: Patients with hypothalamic dysfunction may experience a variety of symptoms, which are not always adequately recognized or addressed. In previous papers, the perspective of caregivers of children with craniopharyngioma has been reported (Klages et al. 2022, Craven et al. 2022). Now we address the patients' perspective on acquired hypothalamic dysfunction using an Endo-ERN global survey. According to the patients' perspective, care can be improved, with needs for improvement in the domains of obesity, fatigue and lifestyle. Research may focus on ways to improve hypothalamic obesity and alternative ways for hormone administration. Ideally, care should be delivered by doctors who have a holistic view of the patient in a multidisciplinary expert team. The results of this study can be used to formulate best practices for clinical care and to design future research proposals

    Textbook Outcome Nationwide Analysis of a Novel Quality Measure in Pancreatic Surgery:Nationwide Analysis of a Novel Quality Measure in Pancreatic Surgery

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    Background: Textbook outcome (TO) is a multidimensional measure for quality assurance, reflecting the ‘‘ideal’’ surgical outcome. Methods: Post-hoc analysis of patients who underwent pancreatoduodenectomy (PD) or distal pancreatectomy (DP) for all indications between 2014 and 2017, queried from the nationwide prospective Dutch Pancreatic Cancer Audit. An international survey was conducted among 24 experts from 10 countries to reach consensus on the requirements for TO in pancreatic surgery. Univariable and multivariable logistic regression was performed to identify TO predictors. Between-hospital variation in TO rates was compared using observed-versus-expected rates. Results: Based on the survey (92% response rate), TO was defined by the absence of postoperative pancreatic fistula, bile leak, postpancreatectomy hemorrhage (all ISGPS grade B/C), severe complications (Clavien–Dindo III), readmission, and in-hospital mortality. Overall, 3341 patients were included (2633 (79%) PD and 708 (21%) DP) of whom 60.3% achieved TO; 58.3% for PD and 67.4% for DP. On multivariable analysis, ASA class 3 predicted a worse TO rate after PD (ASA 3 OR 0.59 [0.44–0.80]), whereas a dilated pancreatic duct (>3 mm) and pancreatic ductal ade

    Predictive value of baseline serum carbohydrate antigen 19-9 level on treatment effect of neoadjuvant chemoradiotherapy in patients with resectable and borderline resectable pancreatic cancer in two randomized trials

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    BACKGROUND: Guidelines suggest that the serum carbohydrate antigen (CA19-9) level should be used when deciding on neoadjuvant treatment in patients with resectable and borderline resectable pancreatic ductal adenocarcinoma (hereafter referred to as pancreatic cancer). In patients with resectable pancreatic cancer, neoadjuvant therapy is advised when the CA19-9 level is 'markedly elevated'. This study investigated the impact of baseline CA19-9 concentration on the treatment effect of neoadjuvant chemoradiotherapy (CRT) in patients with resectable and borderline resectable pancreatic cancers.METHODS: In this post hoc analysis, data were obtained from two RCTs that compared neoadjuvant CRT with upfront surgery in patients with resectable and borderline resectable pancreatic cancers. The effect of neoadjuvant treatment on overall survival was compared between patients with a serum CA19-9 level above or below 500 units/ml using the interaction test.RESULTS: Of 296 patients, 179 were eligible for analysis, 90 in the neoadjuvant CRT group and 89 in the upfront surgery group. Neoadjuvant CRT was associated with superior overall survival (HR 0.67, 95 per cent c.i. 0.48 to 0.94; P = 0.019). Among 127 patients (70, 9 per cent) with a low CA19-9 level, median overall survival was 23.5 months with neoadjuvant CRT and 16.3 months with upfront surgery (HR 0.63, 0.42 to 0.93). For 52 patients (29 per cent) with a high CA19-9 level, median overall survival was 15.5 months with neoadjuvant CRT and 12.9 months with upfront surgery (HR 0.82, 0.45 to 1.49). The interaction test for CA19-9 level exceeding 500 units/ml on the treatment effect of neoadjuvant CRT was not significant (P = 0.501).CONCLUSION: Baseline serum CA19-9 level defined as either high or low has prognostic value, but was not associated with the treatment effect of neoadjuvant CRT in patients with resectable and borderline resectable pancreatic cancers, in contrast with current guideline advice.</p

    Predicting overall survival and resection in patients with locally advanced pancreatic cancer treated with FOLFIRINOX:Development and internal validation of two nomograms

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    Background and Objectives Patients with locally advanced pancreatic cancer (LAPC) are increasingly treated with FOLFIRINOX, resulting in improved survival and resection of tumors that were initially unresectable. It remains unclear, however, which specific patients benefit from FOLFIRINOX. Two nomograms were developed predicting overall survival (OS) and resection at the start of FOLFIRINOX for LAPC. Methods From our multicenter, prospective LAPC registry in 14 Dutch hospitals, LAPC patients starting first-line FOLFIRINOX (April 2015-December 2017) were included. Stepwise backward selection according to the Akaike Information Criterion was used to identify independent baseline predictors for OS and resection. Two prognostic nomograms were generated. Results A total of 252 patients were included, with a median OS of 14 months. Thirty-two patients (13%) underwent resection, with a median OS of 23 months. Older age, female sex, Charlson Comorbidity Index 1, involvement of the superior mesenteric artery, celiac trunk, and superior mesenteric vein >= 270 degrees were independent factors decreasing the probability of resection (c-index: 0.79). Conclusions Two nomograms were developed to predict OS and resection in patients with LAPC before starting treatment with FOLFIRINOX. These nomograms could be beneficial in the shared decision-making process and counseling of these patients

    Identification of a novel Drosophila gene, beltless, using injectable embryonic and adult RNA interference (RNAi)

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    BACKGROUND: RNA interference (RNAi) is a process triggered by a double-stranded RNA that leads to targeted down-regulation/silencing of gene expression and can be used for functional genomics; i.e. loss-of-function studies. Here we report on the use of RNAi in the identification of a developmentally important novel Drosophila (fruit fly) gene (corresponding to a putative gene CG5652/GM06434), that we named beltless based on an embryonic loss-of-function phenotype. RESULTS: Beltless mRNA is expressed in all developmental stages except in 0–6 h embryos. In situ RT-PCR localized beltless mRNA in the ventral cord and brain of late stage embryos and in the nervous system, ovaries, and the accessory glands of adult flies. RNAi was induced by injection of short (22 bp) beltless double-stranded RNAs into embryos or into adult flies. Embryonic RNAi altered cuticular phenotypes ranging from partially-formed to missing denticle belts (thus beltless) of the abdominal segments A2–A4. Embryonic beltless RNAi was lethal. Adult RNAi resulted in the shrinkage of the ovaries by half and reduced the number of eggs laid. We also examined Df(1)RK4 flies in which deletion removes 16 genes, including beltless. In some embryos, we observed cuticular abnormalities similar to our findings with beltless RNAi. After differentiating Df(1)RK4 embryos into those with visible denticle belts and those missing denticle belts, we assayed the presence of beltless mRNA; no beltless mRNA was detectable in embryos with missing denticle belts. CONCLUSIONS: We have identified a developmentally important novel Drosophila gene, beltless, which has been characterized in loss-of-function studies using RNA interference. The putative beltless protein shares homologies with the C. elegans nose resistant to fluoxetine (NRF) NRF-6 gene, as well as with several uncharacterized C. elegans and Drosophila melanogaster genes, some with prominent acyltransferase domains. Future studies should elucidate the role and mechanism of action of beltless during Drosophila development and in adults, including in the adult nervous system
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