Pre-diagnostic circulating resistin concentrations and mortality among individuals with colorectal cancer: Results from the European Prospective Investigation into Cancer and Nutrition study.

Resistin is a protein involved in inflammation and angiogenesis processes and may play a role in the progression of colorectal cancer (CRC). However, it remains unclear whether resistin is associated with increased mortality after CRC diagnosis. We examined pre-diagnostic serum resistin concentrations in relation to CRC-specific and all-cause mortality among 1343 incident CRC cases from the European Prospective Investigation into Cancer and Nutrition cohort. For CRC-specific mortality as the primary outcome, hazard ratios (HRs) and 95% confidence intervals (95% CI) were estimated from competing risk analyses based on cause-specific Cox proportional hazards models and further in sensitivity analyses using Fine-Gray proportional subdistribution hazards models. For all-cause mortality as the secondary outcome, Cox proportional hazards models were used. Subgroup analyses were performed by sex, tumor subsite, tumor stage, body mass index and time to CRC diagnosis. Resistin was measured on a median of 4.8 years before CRC diagnosis. During a median follow-up of 8.2 years, 474 deaths from CRC and 147 deaths from other causes were observed. Resistin concentrations were not associated with CRC-specific mortality (HRQ4vsQ1 = 0.95, 95% CI: 0.73-1.23; Ptrend = .97; and HRper doubling of resistin concentration = 1.00; 95% CI: 0.84-1.19; P = .98) or all-cause mortality. Results from competing risk (sensitivity) analysis were similar. No associations were found in any subgroup analyses. These findings suggest no association between pre-diagnostic circulating resistin concentrations and CRC-specific or all-cause mortality among persons with CRC, and the potential insignificance of resistin in CRC progression.

Identifying modifiable risk factors to prevent aggressive colorectal cancer.

It remains unclear if pre-diagnostic factors influence the developmental pathways of colorectal cancer (CRC) that could enhance tumor aggressiveness. This study used prospective data from 205,489 cancer-free US health professionals to investigate the associations of 31 known or putative risk factors with the risk of aggressive CRC. Tumor aggressiveness was characterized by three endpoints: aggressive CRC (cancer that causes death within 5 years of diagnosis), fatal CRC, and tumor stage at diagnosis. The data augmentation method was used to assess the difference in the associations between risk factors and endpoints. We documented 3201 CRC cases, of which 899 were aggressive. The protective associations of undergoing lower endoscopy (hazard ratios [HR] 0.43, 95% confidence interval (CI) 0.37, 0.49 for aggressive versus HR 0.61, 95% CI 0.56, 0.67 for non-aggressive) and regular use of aspirin (HR 0.70, 95% CI 0.61, 0.81 versus HR 0.84, 95% CI 0.77, 0.92) were stronger for aggressive than non-aggressive CRC (pHeterogeneity <0.05). Lower intake of whole grains or cereal fiber and greater dietary inflammatory potential were associated with a higher risk of aggressive but not non-aggressive CRC. The remaining risk factors showed comparable associations with aggressive CRC and non-aggressive CRC. Aggressive cases were more likely to have KRAS-mutated tumors but less likely to have distal or MSI-high tumors (p < .007). Similar results were observed for fatal CRC and advanced tumor stages at diagnosis. These findings provide initial evidence for the role of pre-diagnostic risk factors in the pathogenesis of aggressive CRC and suggest research priorities for preventive interventions.

Prodromal dementia with Lewy bodies in REM sleep behavior disorder: A multicenter study.

INTRODUCTION: Isolated/idiopathic rapid eye movement sleep behavior disorder (iRBD) is a powerful early predictor of dementia with Lewy bodies (DLB) and Parkinson's disease (PD). This provides an opportunity to directly observe the evolution of prodromal DLB and to identify which cognitive variables are the strongest predictors of evolving dementia. METHODS: IRBD participants (n = 754) from 10 centers of the International RBD Study Group underwent annual neuropsychological assessment. Competing risk regression analysis determined optimal predictors of dementia. Linear mixed-effect models determined the annual progression of neuropsychological testing. RESULTS: Reduced attention and executive function, particularly performance on the Trail Making Test Part B, were the strongest identifiers of early DLB. In phenoconverters, the onset of cognitive decline began up to 10 years prior to phenoconversion. Changes in verbal memory best differentiated between DLB and PD subtypes. DISCUSSION: In iRBD, attention and executive dysfunction strongly predict dementia and begin declining several years prior to phenoconversion. HIGHLIGHTS: Cognitive decline in iRBD begins up to 10 years prior to phenoconversion. Attention and executive dysfunction are the strongest predictors of dementia in iRBD. Decline in episodic memory best distinguished dementia-first from parkinsonism-first phenoconversion.

Urine biomarkers enable pancreatic cancer detection up to 2 years before diagnosis.

The poor prognosis of pancreatic ductal adenocarcinoma (PDAC) is mainly attributed to late diagnosis. We assessed the predictive performance of our previously reported urine biomarker panel for earlier detection of PDAC (LYVE1, REG1B and TFF1) in prediagnostic samples, alone and in combination with plasma CA19-9. This nested case-control study included 99 PDAC cases with urine samples prospectively collected up to 5 years prior to PDAC diagnosis and 198 matched controls. The samples were obtained from the Shanghai Women's Health Study (SWHS), the Shanghai Men's Health Studies (SMHS) and the Southern Community Cohort Study (SCCS). The urine biomarkers were measured by ELISA. Plasma CA19-9 was quantified by Luminex. Multiple logistic regression and Wilcoxon rank-sum and Mann-Whitney test were used for analysis. The internal validation approach was applied and the validated AUC estimators are reported on. The algorithm of urinary protein panel, urine creatinine and age named PancRISK, displayed similar AUC as CA19-9 up to 1 year before PDAC diagnosis (AUC = 0.79); however, the combination enhanced the AUCs to 0.89, and showed good discriminative ability (AUC = 0.77) up to 2 years. The combination showed sensitivity (SN) of 72% at 90% specificity (SP), and SP of 59% at 90% SN up to 1 year and 60% SN with 80% SP and 53% SP with 80% SN up to 2 years before PDAC diagnosis. Adding the clinical information on BMI value resulted in the overall improvement in performance of the PancRISK score. When combined with CA19-9, the urinary panel reached a workable model for detecting PDAC cases up to 2 years prior to diagnosis.

Assessment of the EarlyCDT-Lung test as an early biomarker of lung cancer in ever-smokers: A retrospective nested case-control study in two prospective cohorts.

The EarlyCDT-Lung test is a blood-based autoantibody assay intended to identify high-risk individuals for low-dose computed tomography lung cancer screening. However, there is a paucity of evidence on the performance of the EarlyCDT-Lung test in ever-smokers. We conducted a nested case-control study within two prospective cohorts to evaluate the risk-discriminatory performance of the EarlyCDT-Lung test using prediagnostic blood samples from 154 future lung cancer cases and 154 matched controls. Cases were selected from those who had ever smoked and had a prediagnostic blood sample <3 years prior to diagnosis. Conditional logistic regression was used to estimate the association between EarlyCDT-Lung test results and lung cancer risk. Sensitivity and specificity of the EarlyCDT-Lung test were calculated in all subjects and subgroups based on age, smoking history, lung cancer stage, sample collection time before diagnosis and year of sample collection. The overall lung cancer odds ratios were 0.89 (95% CI: 0.34-2.30) for a moderate risk EarlyCDT-Lung test result and 1.09 (95% CI: 0.48-2.47) for a high-risk test result compared to no significant test result. The overall sensitivity was 8.4% (95% CI: 4.6-14) and overall specificity was 92% (95% CI: 87-96) when considering a high-risk result as positive. Stratified analysis indicated higher sensitivity (17%, 95% CI: 7.2-32.1) in subjects with blood drawn up to 1 year prior to diagnosis. In conclusion, our study does not support a role of the EarlyCDT-Lung test in identifying the high-risk subjects in ever-smokers for lung cancer screening in the EPIC and NSHDS cohorts.

Lipopolysaccharide-binding protein and future Parkinson's disease risk: a European prospective cohort.

INTRODUCTION: Lipopolysaccharide (LPS) is the outer membrane component of Gram-negative bacteria. LPS-binding protein (LBP) is an acute-phase reactant that mediates immune responses triggered by LPS and has been used as a blood marker for LPS. LBP has recently been indicated to be associated with Parkinson's disease (PD) in small-scale retrospective case-control studies. We aimed to investigate the association between LBP blood levels with PD risk in a nested case-control study within a large European prospective cohort. METHODS: A total of 352 incident PD cases (55% males) were identified and one control per case was selected, matched by age at recruitment, sex and study center. LBP levels in plasma collected at recruitment, which was on average 7.8 years before diagnosis of the cases, were analyzed by enzyme linked immunosorbent assay. Odds ratios (ORs) were estimated for one unit increase of the natural log of LBP levels and PD incidence by conditional logistic regression. RESULTS: Plasma LBP levels were higher in prospective PD cases compared to controls (median (interquartile range) 26.9 (18.1-41.0) vs. 24.7 (16.6-38.4) µg/ml). The OR for PD incidence per one unit increase of log LBP was elevated (1.46, 95% CI 0.98-2.19). This association was more pronounced among women (OR 2.68, 95% CI 1.40-5.13) and overweight/obese subjects (OR 1.54, 95% CI 1.09-2.18). CONCLUSION: The findings suggest that higher plasma LBP levels may be associated with an increased risk of PD and may thus pinpoint to a potential role of endotoxemia in the pathogenesis of PD, particularly in women and overweight/obese individuals.

Is the association of overweight and obesity with colorectal cancer underestimated? An umbrella review of systematic reviews and meta-analyses.

Although high body-mass index (BMI) is associated with increased risk of developing colorectal cancer (CRC), many CRC patients lose weight before diagnosis. BMI is often reported close to diagnosis, which may have led to underestimation or even reversal of direction of the BMI-CRC association. We aimed to assess if and to what extent potential bias from prediagnostic weight loss has been considered in available epidemiological evidence. We searched PubMed and Web of Science until May 2022 for systematic reviews and meta-analyses investigating the BMI-CRC association. Information on design aspects and results was extracted, including if and how the reviews handled prediagnostic weight loss as a potential source of bias. Additionally, we analyzed how individual cohort studies included in the latest systematic review handled the issue. Overall, 18 reviews were identified. None of them thoroughly considered or discussed prediagnostic weight loss as a potential source of bias. The majority (15/21) of cohorts included in the latest review did not exclude any initial years of follow-up from their main analysis. Although the majority of studies reported having conducted sensitivity analyses in which initial years of follow-up were excluded, results were reported very heterogeneously and mostly for additional exclusions of 1-2 years only. Where explicitly reported, effect estimates mostly increased with increasing length of exclusion. The impact of overweight and obesity on CRC risk may be larger than suggested by the existing epidemiological evidence.

An international multicenter survey reveals health care providers' knowledge gap in childhood central nervous system tumors.

Childhood central nervous system (CNS) tumors have longer delays in diagnosis than do other pediatric malignancies because health care providers (HCPs) lack awareness about clinical presentation of these tumors. To evaluate the knowledge gap among HCPs, we conducted a global cross-sectional survey. The survey consisted of a set of CNS tumor knowledge questions focused on symptoms, signs, and imaging indications. The survey was disseminated to HCPs via email (November 2018-March 2020). Participants had to complete a pre-test survey, attend an education seminar on CNS tumors, and complete a post-test survey. The knowledge gap was evaluated using pre-test and post-test scores. We received 889 pre-test and 392 post-test responses. Most respondents were from Asia (73.1% of pre-test responses; 87.5% of post-test responses). The median pre-test score was 40.0% (range: 13.1-92.9%). A high percentage of correct answers were given in post-test responses (median score: 77.1%, range: 14.9-98.2%). In the pre-test, 18.7% of participants accurately responded that Cushing's triad was a less common symptom, and 15.0% recognized that children aged > 10 years are at risk of late diagnosis. Surprisingly, 21.9% falsely reported that patients with malignancy experienced the longest pre-diagnostic symptom interval, and 54.5% of respondents wrongly selected medulloblastoma as the most common CNS tumor. Overall, pediatricians demonstrated a greater knowledge gap on both surveys than did other specialties.  Conclusion: Pre- and post-test surveys revealed significant knowledge gaps in childhood CNS tumors among HCPs. Thus, raising professional awareness on clinical presentations of CNS tumors through educational strategies is important to address this knowledge deficit. What is Known: • Diagnostic delay in childhood central nervous system (CNS) tumors continues to be a significant problem that negatively impacts the quality of life and treatment sequelae. • Lack of medical education on CNS tumors is a contributing factor to this problem. What is New: • Most health care providers do not realize that low-grade tumors are the most common neoplasm in children. • Health care providers fail to recognize that teenagers and adolescents are a vulnerable age group for diagnostic delays, with the longest pre-diagnostic symptom interval.

Delay in the diagnosis of paediatric brain tumours: a systematic review.

PURPOSE: A delay in obtaining a diagnosis has been associated with inferior outcomes across several cancer types, including paediatric brain tumours. However, no clear evidence exists in this population. We aimed to quantify the reported pre-diagnostic symptom interval (PSI) as the time from onset of first symptoms to diagnosis in the literature, in addition to evaluating the relationship between delay and outcomes, including survival. METHODS: A systematic review of the literature was performed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. MEDLINE, Wiley Online Library, Web of Science and EMBASE databases were searched. We considered all sources published between 1st January 2010 and 5th November 2022. Children and adolescents aged under 21 years, with new symptomatic primary brain tumour diagnoses, were included. RESULTS: Of 3123 studies identified, 11 were included for analysis. Owing to study heterogeneity, a quantitative meta-analysis was not feasible; however, a narrative synthesis was performed. The median reported PSI varied widely, ranging between 28 and 760.8 days. We failed to identify a significant association between prolonged PSI and inferior overall survival. Few factors were consistently associated with prolonged PSI, amongst them only tumour grade and patient age. CONCLUSION: Delayed diagnosis of paediatric brain tumours was not associated with inferior survival within this review. This 'waiting time' paradox appears to result from several confounding factors including tumour biology, patient population and key systematic factors that were inconsistently reported. Diagnostic interval clearly presents a complex variable, reflected further by disparity in the reporting of delay within the literature. Ultimately diagnostic interval is unlikely to provide a meaningful representation for all tumour types and should not detract from sharp clinical acumen and prompt diagnosis.

Pre-diagnostic cognitive and functional impairment in multiple sporadic neurodegenerative diseases.

INTRODUCTION: The pathophysiological processes of neurodegenerative diseases begin years before diagnosis. However, pre-diagnostic changes in cognition and physical function are poorly understood, especially in sporadic neurodegenerative disease. METHODS: UK Biobank data were extracted. Cognitive and functional measures in individuals who subsequently developed Alzheimer's disease (AD), Parkinson disease, frontotemporal dementia, progressive supranuclear palsy, dementia with Lewy bodies, or multiple system atrophy were compared against individuals without neurodegenerative diagnoses. The same measures were regressed against time to diagnosis, after adjusting for the effects of age. RESULTS: There was evidence for pre-diagnostic cognitive impairment and decline with time, particularly in AD. Pre-diagnostic functional impairment and decline were observed in multiple diseases. DISCUSSION: The scale and longitudinal follow-up of UK Biobank participants provides evidence for cognitive and functional decline years before symptoms become obvious in multiple neurodegenerative diseases. Identifying pre-diagnostic functional and cognitive changes could improve selection for preventive and early disease-modifying treatment trials.

Circulating C-reactive protein increases lung cancer risk: Results from a prospective cohort of UK Biobank.

Chronic inflammation has been associated with the development of lung cancer. In this study, we examined the association between C-reactive protein (CRP) and lung cancer in a prospective cohort study and used Mendelian randomization (MR) to clarify the causality. We included 420 977 participants from the UK Biobank (UKB) in the analyses; 1892 thereof were diagnosed with lung cancer during the follow-up. Hazards ratios (HRs) of CRP concentrations were estimated by Cox proportional hazard models and two approaches of MR analysis were performed. Besides, we added CRP concentrations to epidemiological model of lung cancer to evaluate its prediagnostic role through time-dependent receiver operating characteristic curve analysis. Elevated CRP levels were associated with a 22% increased lung cancer risk per 1 SD increase (HR = 1.22, 95% confidence interval [CI] = 1.18-1.26). Positive associations were observed in small cell lung cancer (HR = 1.21, 95% CI = 1.10-1.33), lung adenocarcinoma (HR = 1.17, 95% CI = 1.11-1.23) and lung squamous cell carcinoma (HR = 1.22, 95% CI = 1.14-1.31). No genetical association of circulating CRP levels and lung cancer risk was observed in MR analysis. When added to a risk model of lung cancer, CRP improved the performance of model as long as 8 years among current smokers (basic model: C-statistic = 0.78 [95% CI = 0.75-0.80]; CRP model: C-statistic = 0.79 [95% CI = 0.76-0.81]; Pnonadjusted  = .003, Padjusted  = .014). Our results did not support the causal association of circulating CRP with lung cancer risk. However, circulating CRP could be a prediagnostic marker of lung cancer as long as 8 years in advance for current smokers.

Healthy Cotwins Share Gut Microbiome Signatures With Their Inflammatory Bowel Disease Twins and Unrelated Patients.

BACKGROUND & AIMS: It is currently unclear whether reported changes in the gut microbiome are cause or consequence of inflammatory bowel disease (IBD). Therefore, we studied the gut microbiome of IBD-discordant and -concordant twin pairs, which offers the unique opportunity to assess individuals at increased risk of developing IBD, namely healthy cotwins from IBD-discordant twin pairs. METHODS: Fecal samples were obtained from 99 twins (belonging to 51 twin pairs), 495 healthy age-, sex-, and body mass index-matched controls, and 99 unrelated patients with IBD. Whole-genome metagenomic shotgun sequencing was performed. Taxonomic and functional (pathways) composition was compared among healthy cotwins, IBD-twins, unrelated patients with IBD, and healthy controls with multivariable (ie, adjusted for potential confounding) generalized linear models. RESULTS: No significant differences were observed in the relative abundance of species and pathways between healthy cotwins and their IBD-twins (false discovery rate <0.10). Compared with healthy controls, 13, 19, and 18 species, and 78, 105, and 153 pathways were found to be differentially abundant in healthy cotwins, IBD-twins, and unrelated patients with IBD, respectively (false discovery rate <0.10). Of these, 8 (42.1%) of 19 and 1 (5.6%) of 18 species, and 37 (35.2%) of 105 and 30 (19.6%) of 153 pathways overlapped between healthy cotwins and IBD-twins, and healthy cotwins and unrelated patients with IBD, respectively. Many of the shared species and pathways have previously been associated with IBD. The shared pathways include potentially inflammation-related pathways, for example, an increase in propionate degradation and L-arginine degradation pathways. CONCLUSIONS: The gut microbiome of healthy cotwins from IBD-discordant twin pairs displays IBD-like signatures. These IBD-like microbiome signatures might precede the onset of IBD. However, longitudinal follow-up studies are needed to infer a causal relationship.

Socioeconomic position and prediagnostic health care contacts in children with cancer in Denmark: a nationwide register study.

BACKGROUND: While underlying mechanisms and pathways of social inequalities in cancer survival have been extensively examined in adults, this is less so for children with cancer. Hypothesized mechanisms include prediagnostic utilization of and navigation through the health care system, which may differ by socioeconomic resources of the families. In this nationwide register-based study we investigated the association between measures of family socioeconomic position in relation to prediagnostic health care contacts and stage of disease at diagnosis in children with cancer in Denmark. METHODS: We identified all children diagnosed with a cancer at ages 0-15 years in 1998-2016 (N = 3043) from the Danish Childhood Cancer Registry. We obtained comprehensive information on measures of socioeconomic position, parental health and prediagnostic contacts to both general practitioners and hospitals 24 months prior to diagnosis from various national registries. We fitted multivariable conditional logistic regression models for the association of family socioeconomic and health-related variables with firstly, frequent health care contacts and secondly, advanced stage. RESULTS: We found higher odds ratios (OR) of frequent both overall and emergency health care contacts in the last 3 months before diagnosis in children from households with short parental education and mixed affiliation to work market, when compared to children with high family socioeconomic position. Further, children of parents with depression or of non-Western origin, respectively, had higher OR for frequent overall and emergency contacts. We found no association between socioeconomic position, parental health and stage of disease. CONCLUSION: Families with socioeconomic disadvantage, non-Western origin or depression more frequently utilize prediagnostic health care services, both generally and in the acute setting, indicating that some disadvantaged families may struggle to navigate the health care system when their child is sick. Reassuringly, this was not reflected in disparities in stage at diagnosis. In order to improve the diagnostic process and potentially reduce health care contacts, attention and support should be given to families with a high number of health care contacts over a short period of time.

Accelerating diagnosis of Parkinson's disease through risk prediction.

BACKGROUND: Characterization of prediagnostic Parkinson's Disease (PD) and early prediction of subsequent development are critical for preventive interventions, risk stratification and understanding of disease pathology. This study aims to characterize the role of the prediagnostic period in PD and, using selected features from this period as novel interception points, construct a prediction model to accelerate the diagnosis in a real-world setting. METHODS: We constructed two sets of machine learning models: a retrospective approach highlighting exposures up to 5 years prior to PD diagnosis, and an alternative model that prospectively predicted future PD diagnosis from all individuals at their first diagnosis of a gait or tremor disorder, these being features that appeared to represent the initiation of a differential diagnostic window. RESULTS: We found many novel features captured by the retrospective models; however, the high accuracy was primarily driven from surrogate diagnoses for PD, such as gait and tremor disorders, suggesting the presence of a distinctive differential diagnostic period when the clinician already suspected PD. The model utilizing a gait/tremor diagnosis as the interception point, achieved a validation AUC of 0.874 with potential time compression to a future PD diagnosis of more than 300 days. Comparisons of predictive diagnoses between the prospective and prediagnostic cohorts suggest the presence of distinctive trajectories of PD progression based on comorbidity profiles. CONCLUSIONS: Overall, our machine learning approach allows for both guiding clinical decisions such as the initiation of neuroprotective interventions and importantly, the possibility of earlier diagnosis for clinical trials for disease modifying therapies.

Inflammatory serum markers and risk and severity of prostate cancer: The PROCA-life study.

Whether chronic inflammation mirrored by high levels of systemic inflammatory markers such as high sensitive-CRP (hs-CRP) and white blood cell count (WBC) are associated with prostate cancer development remains unclear. In the Prostate Cancer Study throughout Life (PROCA-life), a prospective population-based cohort study, 7,356 men were included. Prediagnostic WBC and hs-CRP were assessed from blood collected at study entry; 2,210 participants also had a second CRP measure during follow-up. During a mean 11.8 years follow-up, 509 men developed prostate cancer (mean age at diagnosis 71.7 years). Multivariable Cox proportional hazard regression models were used to study whether individual biomarkers (WBC, hs-CRP), a combined score based on analyte tertiles (score range 2-6), or change in CRP were associated with risk and severity of prostate cancer. We observed a positive dose-response relationship between hs-CRP and prostate cancer risk with a Hazard Ratio (HR) per mg/l of 1.3, 95% CI 1.00-1.07. Men with an increase in hs-CRP between two measurements (Δhs-CRP) of ≥1.00 mg/l had a 36% increased risk of prostate cancer (HR 1.36, 95% CI 1.02-1.82), compared to men with no change or decrease in hs-CRP. Men with a systemic inflammatory score of 5 or 6 had a 68% higher risk of being diagnosed with metastatic disease (HR 1.68, 95% CI, 1.04-2.73) compared to men with lower scores. Our study supports that hs-CRP including repeated measurements alone or in combination with WBC may be a useful inflammation-related biomarker for prostate cancer risk and prognosis.

Early Detection of Pancreatic Cancer: Opportunities and Challenges.

Most patients with pancreatic ductal adenocarcinoma (PDAC) present with symptomatic, surgically unresectable disease. Although the goal of early detection of PDAC is laudable and likely to result in significant improvement in overall survival, the relatively low prevalence of PDAC renders general population screening infeasible. The challenges of early detection include identification of at-risk individuals in the general population who would benefit from longitudinal surveillance programs and appropriate biomarker and imaging-based modalities used for PDAC surveillance in such cohorts. In recent years, various subgroups at higher-than-average risk for PDAC have been identified, including those with familial risk due to germline mutations, a history of pancreatitis, patients with mucinous pancreatic cysts, and elderly patients with new-onset diabetes. The last 2 categories are discussed at length in terms of the opportunities and challenges they present for PDAC early detection. We also discuss current and emerging imaging modalities that are critical to identifying early, potentially curable PDAC in high-risk cohorts on surveillance.

Central adiposity at diagnosis may reduce prostate cancer-specific mortality in African-Caribbean men with prostate cancer: 10-year follow-up of participants in a case-control study.

PURPOSE: General and central adiposity are associated with the risk of developing prostate cancer (PCa), but the role of these exposures on PCa survival among men of African ancestry are less studied. This study aimed to investigate the association of anthropometry at diagnosis with all-cause and PCa-specific mortality and evaluate whether androgen deprivation therapy (ADT) modulated this risk. METHODS: Associations between body mass index (BMI), waist circumference (WC), and waist-to-hip ratio (WHR) at diagnosis and mortality were examined in 242 men with newly diagnosed PCa enrolled between 2005 and 2007 and re-evaluated 10.9 years later. Multi-variable Cox proportional hazard models were used to examine associations of body size variables (using standard WHO cut-points and as continuous variables) with mortality, adjusted for sociodemographic characteristics, Gleason score, smoking, diabetes, primary treatment, and ADT therapy. RESULTS: A total of 139 deaths (all-cause mortality 6.98/100 person-years) occurred (PCa-specific deaths, 56; other causes, 66; causes unknown, 17). In multi-variable analysis BMI, WC and WHR categories at diagnosis were not associated with all-cause mortality even after adjusting for ADT. While WHR (but not BMI or WC) when included as a continuous variable predicted lower PCa-specific mortality (multi-variable adjusted WHR per 0.1 difference: HR, 0.50; 95%CI 0.28, 0.93), the effect disappeared with ADT covariance and excluding deaths within the first 2 years. CONCLUSION: Our study suggests that central adiposity as measured by WHR may improve long-term survival among men of African ancestry. Metabolic studies to understand the mechanism for this association are needed.

Application of a Simple Parkinson's Disease Risk Score in a Longitudinal Population-Based Cohort.

BACKGROUND: Identifying individuals at risk of developing Parkinson's disease (PD) is critical to define target populations for future neuroprotective trials. OBJECTIVE: The objective of this study was to apply the PREDICT-PD algorithm of risk indicators for PD in a prospective community-based study (the Bruneck study), representative of the general elderly population. METHODS: PREDICT-PD risk scores were calculated based on risk factor assessments obtained at baseline (2005, n = 574 participants). Cases of incident PD were identified at 5-year and 10-year follow-ups. Participants with PD or secondary parkinsonism at baseline were excluded (n = 35). We analyzed the association of log-transformed risk scores with the presence of well-established markers as surrogates for PD risk at baseline and with incident PD at follow-up. RESULTS: A total of 20 participants with incident PD were identified during follow-up (11 after 5 years and 9 after 10 years). Baseline PREDICT-PD risk scores were associated with incident PD with odds ratios of 2.09 (95% confidence interval, 1.35-3.25; P = 0.001) after 5 years and of 1.95 (1.36-2.79; P < 0.001) after 10 years of follow-up per doubling of risk scores. In addition, higher PREDICT-PD scores were significantly correlated with established PD risk markers (olfactory dysfunction, signs of rapid eye movement sleep behavior disorder and motor deficits) and significantly associated with higher probability for prodromal PD according to the Movement Disorder Society research criteria at baseline. CONCLUSIONS: The PREDICT-PD score was associated with an increased risk for incident PD in our sample and may represent a useful first screening step in future algorithms aiming to identify cases of prodromal PD. © 2020 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

Prediagnostic symptoms and signs of adult glioma: the patients' view.

BACKGROUND: Little is known about the symptoms glioma patients experience in the year before diagnosis, either or not resulting in health care usage. This study aimed to determine the incidence of symptoms glioma patients experienced in the year prior to diagnosis, and subsequent visits to a general practitioner (GP). METHODS: Glioma patients were asked to complete a 30-item study-specific questionnaire focusing on symptoms they experienced in the 12 months before diagnosis. For each indicated symptom, patients were asked whether they consulted the GP for this issue. RESULTS: Fifty-nine patients completed the questionnaires, 54 (93%) with input of a proxy. The median time since diagnosis was 4 months (range 1-12). The median number of symptoms experienced in the year before diagnosis was similar between gliomas with favourable and poor prognosis, i.e. 6 (range 0-24), as were the five most frequently mentioned problems: fatigue (n = 34, 58%), mental tiredness (n = 30, 51%), sleeping disorder (n = 24, 41%), headache (n = 23, 39%) and stress (n = 20, 34%). Twenty-six (44%) patients visited the GP with at least one issue. Patients who did consult their GP reported significantly more often muscle weakness (11 vs 3, p = 0.003) than patients who did not, which remained significant after correction for multiple testing, which was not the case for paralysis in hand/leg (10 vs 4), focussing (11 vs 6) or a change in awareness (9 vs 4). CONCLUSIONS: Glioma patients experience a range of non-specific problems in the year prior to diagnosis, but only patients who consult the GP report more often neurological problems.

Time to diagnosis and clinical characteristics in pediatric brain tumor patients.

PURPOSE: We aimed to identify factors that affect the time to diagnosis in pediatric brain tumors and investigate the effect of time to diagnosis on clinical outcome. METHODS: A retrospective study of children with brain tumors aged less than 18 years diagnosed at the University of Tsukuba Hospital over a period of 7 years was conducted. RESULTS: Eighty-five consecutive patients, with a mean age of 9.1 years, were included in the study. The median interval from symptom onset to diagnosis was 45 days (range 0-1673); median interval from symptom onset to first presentation was 31.0 days; and median interval from first presentation to diagnosis was 13.5 days. Germinoma had the longest interval from symptom onset to first presentation, and from first presentation to diagnosis. Patients presenting with endocrine disorder had a significantly longer interval from symptom onset to first presentation (p = 0.019); those with visual disturbance (p = 0.016) or endocrine disorder (p = 0.030) had significantly longer intervals from first presentation to diagnosis. CONCLUSION: Pediatric brain tumor patients with germinoma and presenting symptoms of endocrine disorder or visual disturbance have a longer time to diagnosis. Although improved prognosis is not clearly related to a shorter time to diagnosis, we believe that early diagnosis can lead to improved treatment and better quality of life. A detailed medical history and neuroimaging studies at the earliest time possible are important for early diagnosis.