Objective To evaluate the global prevalence of erectile dysfunction (ED); as well as its association with physiological and pathological ageing by examining the relationship between ED and cardiovascular disease (CVD), benign prostatic hyperplasia (BPH), and dementia. We also aimed to characterise discrepancies caused by the use of different ED screening tools. Methods The Excerpta Medica dataBASE (EMBASE) and Medical Literature Analysis and Retrieval System Online (MEDLINE) were searched to find population‐based studies investigating the prevalence of ED and the association between ED and CVD, BPH, and dementia in the general population. Results The global prevalence of ED was 3–76.5%. ED was associated with increasing age. Use of the International Index of Erectile Function (IIEF) and Massachusetts Male Aging Study (MMAS)‐derived questionnaire identified a high prevalence of ED in young men. ED was positively associated with CVD. Men with ED have an increased risk of all‐cause mortality odds ratio (OR) 1.26 (95% confidence interval [CI] 1.01–1.57), as well as CVD mortality OR 1.43 (95% CI 1.00–2.05). Men with ED are 1.33–6.24‐times more likely to have BPH then men without ED, and 1.68‐times more likely to develop dementia than men without ED. Conclusion ED screening tools in population‐based studies are a major source of discrepancy. Non‐validated questionnaires may be less sensitive than the IIEF and MMAS‐derived questionnaire. ED constitutes a large burden on society given its high prevalence and impact on quality of life, and is also a risk factor for CVD, dementia, and all‐cause mortality.

Immune and inflammatory cascades may play multiple roles in ovarian cancer. We aimed to identify relationships between expression of immune and inflammatory mediators and patient outcomes. We interrogated differential gene expression of 44 markers and marker combinations (n = 1,978) in 1,656 ovarian carcinoma patient tumors, alongside matched 5-year overall survival (OS) data in silico. Using machine learning methods, we investigated whether genomic expression of these 44 mediators can discriminate between malignant and non-malignant tissues in 839 ovarian cancer and 115 nonmalignant ovary samples. We furthermore assessed inflammation markers in 289 ovarian cancer patients' sera in the Swedish Apolipoprotein MOrtality-related RISk (AMORIS) cohort. Expression of the 44 mediators could discriminate between malignant and non-malignant tissues with at least 96% accuracy. Higher expression of classical Th1, Th2, Th17, anti-parasitic/infection and M1 macrophage mediator signatures were associated with better OS. Contrastingly, inflammatory and angiogenic mediators, CXCL-12, C-reactive protein (CRP) and platelet-derived growth factor subunit A (PDGFA) were negatively associated with OS. Of the serum inflammatory markers in the AMORIS cohort, women with ovarian cancer who had elevated levels of haptoglobin (≥1.4 g/L) had a higher risk of dying from ovarian cancer compared to those with haptoglobin levels <1.4 g/L (HR = 2.09, 95% CI:1.38-3.16). Our findings indicate that elevated "classical" immune mediators, associated with response to pathogen antigen challenge, may confer immunological advantage in ovarian cancer, while inflammatory markers appear to have negative prognostic value. These highlight associations between immune protection, inflammation and clinical outcomes, and offer opportunities for patient stratification based on secretome markers.

Background Nested case-control studies examining the association between serum markers of chronic inflammation, focused on three specific biomarkers (CRP, IL-8 and TNF-α), and risk of pancreatic cancer have reported no associations. In this study, we evaluated associations between standard pre-diagnostic serum markers of chronic inflammation (CRP, albumin, haptoglobin and leukocytes) and pancreatic cancer risk in the Swedish Apolipoprotein-related MORtality RISk (AMORIS) prospective cohort study. Methods We selected all participants (≥20 years old) with baseline measurements of CRP, albumin, haptoglobin and leukocytes between 1985 and 1996 ( n = 61,597). Participants were excluded if they had a history of chronic pancreatitis and all individuals were free from pancreatic cancer at baseline. Cox proportional multivariable hazards regression analysis was carried out for medical cut-offs of CRP, albumin, haptoglobin and leukocytes. Results We observed an increased risk of pancreatic cancer for those individuals with higher levels of serum haptoglobin (≥1.4 g/L), CRP (≥10 mg/L) and leukocytes (≥10 × 10 9 cells/L) compared to those with haptoglobin levels < 1.4 g/L, CRP levels < 10 mg/L and Leukocyte levels < 10 × 10 9 cells/L [haptoglobin HR: 2.23 (95% CI 1.72–2.88), CRP HR: 1.32 (95% CI 1.00–1.74), leukocytes HR: 2.20 (95% CI 1.52–3.18)]. No associations were noted for serum albumin. Conclusions We found an increased risk of pancreatic cancer associated with pre-diagnostic serum levels of haptoglobin, CRP and leukocytes. Our finding suggests a possible role of chronic inflammation in the aetiology of pancreatic cancer and highlight the need to further investigate this association.

Background: The nature of humoral immunity in carcinogenesis remains poorly understood. In this systematic review and metaanalysis, we aimed to evaluate the association of serum immunoglobulin classes with solid cancer and test our hypothesis that the immune escape of tumors is accompanied by dysregulated systemic immunoglobulin class-switching.Methods: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we systematically searched the Cochrane Library, Embase, and MEDLINE/PubMed databases for observational studies investigating the association between serum immunoglobulins (IgA, IgG, and IgM) and histologically confirmed diagnosis of solid cancer in adults. We selected case-control studies, including more than 20 cases, and those explicitly stating that no form of anticancer treatment was administered prior to immunoglobulin measurement. No eligible cohort studies were identified. The primary summary measure was the standardized mean differ-ence (SMD) with 95% confidence intervals (CI) calculated using a random effects model.Results: Pooling 11 eligible studies comparing serum IgA levels in 1,351 patients and 560 control subjects revealed a statistically significant SMD (1.50; 95% CI, 0.96-2.04). Nonsignificant SMDs were observed for the 14 selected studies investigating serum IgG [SMD, À0.02 (95% CI, À0.22 to 0.18)] and for the 10 studies reporting serum IgM [SMD, 0.11 (95% CI, À0.10 to 0.32)]. Substantial heterogeneity between studies was observed despite sensitivity analysis by immunoglobulin measurement method, control matching, type of cancer, stage of disease, and sequential study exclusion.Conclusions: Serum immunoglobulin levels in patients diagnosed with solid cancer might be skewed toward class-switching to IgA, possibly reflecting Th2-polarized immunity.Impact: Further combinatorial analyses of serum immunoglobulin isotypes alongside other immune parameters in databases and observational studies are warranted.