Obtaining assent for research involving children in Malaysia: a position statement from the Academy of Medicine of Malaysia College of Paediatrics.

The Academy of Medicine of Malaysia College of Paediatrics acknowledges the role of children in research and this position statement explores the ethical considerations in obtaining assent from minors in the Malaysian context. It highlights the importance in respecting children's agency and navigating cultural complexities. The College proposes flexibility in the minimum age for assent of at least nine years old, while emphasising the need for a tailored assent procedure. Addressing language and cultural diversities and expanding local empirical research on a formal assent process are some building blocks in developing a standardised nationwide process in obtaining assent from children.

Latent class analysis of structured histopathology in prognosticating surgical outcomes of chronic rhinosinusitis with nasal polyps in Singapore.

BACKGROUND: Structured histopathology profiling is recommended when reporting chronic rhinosinusitis with nasal polyp (CRSwNP) tissue. The objective of this study is to identify features in structured histopathology that predict outcome after functional endoscopic sinus surgery (FESS) in a cohort of CRSwNP patients from Singapore. METHODS: Latent class analysis was performed on structured histopathology reports of 126 CRSwNP patients who had undergone FESS. Outcome measures were polyp recurrence, need for systemic corticosteroids, revision surgery or biologics, and disease control at 2 years post-FESS. RESULTS: Three classes were identified. Class 1 was characterised by mild, predominantly lymphoplasmacytic inflammation. Class 2 comprised of 100 eosinophils/HPF, hyperplastic seromucinous glands, mucosal ulceration and mucin containing eosinophil aggregates and Charcot-Leyden crystals. Classes 2 and 3 were significantly associated with uncontrolled disease at 2 years post-FESS. Class 3 was additionally associated with the need for systemic corticosteroids. CONCLUSIONS: Eosinophil count, degree of inflammation, predominant inflammatory type, hyperplastic seromucinous glands, mucosal ulceration and mucin containing eosinophil aggregates and Charcot-Leyden crystals predicted need for systemic corticosteroids and uncontrolled disease at 2 years post-FESS. The presence of >100 eosinophils/HPF should be reported, as this subset of tissue eosinophilia was associated with less favourable outcomes after FESS.

Strength, durability, and microstructure of self-compacting geopolymer concrete produced with copper slag aggregates.

Lack of vibrations on fresh concrete negatively influences the compaction and thus the quality of concrete. This is particularly concerning with geopolymer concrete (GPC) containing sodium silicate (Na2SiO3), which is viscous in nature. In this study, self-compacting geopolymer concrete (SCGC) containing fly ash (FA) and ultrafine slag (UFS) with copper slag aggregates (CSA) was proposed and investigated. CSA were used as a substitute to sand (by weight) in SCGC at different percentages up to 60%. In the fresh state, slump, T500 slump flow, V-funnel, L-box, U-box, and sieve aggregation ratio tests were performed to investigate flowability, passing ability, and viscosity. At the hardened state, the compressive strength, water absorption, chloride ion resistance and sorptivity tests were examined. The flowability of SCGC improved when CSA were added, and the highest slump of 735 mm was achieved for the mix with 60% CSA. Substitution of up to 20% of CSA enhanced the properties of SCGC at all ages. Mix having 20% CSA (20CSA-SCGC) was superior to other mixes, exhibiting the highest compressive strength (47 MPa) at 365 days while possessing the lowest water absorption, sorptivity, and the highest chloride ion resistance. Scanning electron microscopy (SEM) and energy-dispersive spectroscopy (EDS) analyses also confirmed the improved microstructure of Mix 20CSA-SCGC. Meanwhile, X-ray diffraction (XRD) analysis confirmed the presence of quartz and calcium silicate hydrate (CSH) products, which were the main contributors to properties enhancement.

COVID-19 vaccination for children in Malaysia - A position statement by the College of Paediatrics, Academy of Medicine of Malaysia.

The availability of COVID-19 vaccines and mass vaccination programmes in adults have significantly reduced the case attack rates and disease burden. COVID-19 vaccination successfully decreases the population at risk of infection, allowing for the safer re-opening of economies and reducing the pandemic's crippling impact on healthcare systems. However, the rapidly mutating severe acute respiratory syndrome-coronavirus-2 poses challenges in diminishing vaccine-induced immunity and vaccinating a significant proportion of adults to achieve herd immunity. These challenges necessitated adolescent vaccination. With the recent emergence of the highly transmissible Omicron variant and the increasing COVID-19 hospitalisation rates of children below 12 years old, many countries opted to also vaccinate younger children. Phase II/III clinical trials and real-world experience demonstrate that COVID-19 vaccinations are effective and safe for younger children and adolescents. Before Malaysia introduced its national COVID-19 vaccination programme for children 5-11 years old (which ran between March and June 2022), an expert advisory statement was issued by the College of Paediatrics, Academy of Medicine of Malaysia, to highlight the benefits and importance of vaccinating children. The advisory statement included clarifications about vaccine-related side effects such as post-vaccination myocarditis and allergic reactions to encourage informed decision making by healthcare providers and parents. This paper, which was prepared based on the critical appraisal of the current evidence, evaluation of the international experiences and the positive impact of COVID-19 vaccination in children, collectively sums up the rationale to support and ensure the success of the nationwide vaccination programme for children. Hence, the College recommends COVID-19 vaccination for children in Malaysia.

Stabilization of the Hinge Region of Human E-selectin Enhances Binding Affinity to Ligands Under Force.

INTRODUCTION: E-selectin is a member of the selectin family of cell adhesion molecules expressed on the plasma membrane of inflamed endothelium and facilitates initial leukocyte tethering and subsequent cell rolling during the early stages of the inflammatory response via binding to glycoproteins expressing sialyl LewisX and sialyl LewisA (sLeX/A). Existing crystal structures of the extracellular lectin/EGF-like domain of E-selectin complexed with sLeX have revealed that E-selectin can exist in two conformation states, a low affinity (bent) conformation, and a high affinity (extended) conformation. The differentiating characteristic of the two conformations is the interdomain angle between the lectin and the EGF-like domain. METHODS: Using molecular dynamics (MD) simulations we observed that in the absence of tensile force E-selectin undergoes spontaneous switching between the two conformational states at equilibrium. A single amino acid substitution at residue 2 (serine to tyrosine) on the lectin domain favors the extended conformation. RESULTS: Steered molecular dynamics (SMD) simulations of E-selectin and PSGL-1 in conjunction with experimental cell adhesion assays show a longer binding lifetime of E-selectin (S2Y) to PSGL-1 compared to wildtype protein. CONCLUSIONS: The findings in this study advance our understanding into how the structural makeup of E-selectin allosterically influences its adhesive dynamics.

Supercharged eGFP-TRAIL Decorated NETs to Ensnare and Kill Disseminated Tumor Cells.

BACKGROUND: NETosis is an innate immune response elicited by activated neutrophils to fight microbial infections. Activated neutrophils release DNA fibers decorated with anti-microbial proteins called neutrophil extracellular traps (NETs) into the extracellular space to trap and kill surrounding microbes. METHODS: Here, we show that tumor-derived IL-8 released by cancer cells also activates the release of NETs. Until now, there have been no existing technologies that leverage NETs as an anti-tumor drug delivery vehicle. In this study, we demonstrate the re-engineering of neutrophils to express an apoptosis-inducing chimeric protein, supercharged eGFP-TRAIL, on NETs that can ensnare and kill tumor cells while retaining their anti-microbial capabilities. RESULTS: We observed significant TRAIL-induced apoptosis in tumor cells captured by TRAIL-decorated NETs. CONCLUSIONS: This work demonstrates NETs as a promising technology to deliver protein in response to local cytokine signals.

A simplified method for the efficient purification and refolding of recombinant human TRAIL.

Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) belongs to the TNF cytokine superfamily that specifically induces apoptosis in a broad spectrum of human cancer cell lines but not in most healthy cells. The antitumor potential of recombinant human TRAIL (rhTRAIL) has attracted great attention among biologists and oncologists. However, attempts to express rhTRAIL in Escherichia coli often results in limited yield of bioactive protein due to the formation of inclusion bodies (IBs), which are dense insoluble particulate protein aggregates inside cells. We describe herein a highly simplified method to produce pure bioactive rhTRAIL using E. coli. The method is straightforward and requires only basic laboratory equipment, with highly efficient purification and high yield of renaturation, and may also be applied to produce other proteins that form IBs in E. coli.

Crouzon syndrome: Genetic and intervention review.

Crouzon syndrome exhibits considerable phenotypic heterogeneity, in the aetiology of which genetics play an important role. FGFR2 mediates extracellular signals into cells and the mutations in the FGFR2 gene cause this syndrome occurrence. Activated FGFs/FGFR2 signaling disrupts the balance of differentiation, cell proliferation, and apoptosis via its downstream signal pathways. However, very little is known about the cellular and molecular factors leading to severity of this phenotype. Revealing the molecular pathology of craniosynostosis will be a great value for genetic counselling, diagnosis, prognosis and early intervention programs. This mini-review summarizes the fundamental and recent scientific literature on genetic disorder of Crouzon syndrome and presents a graduated strategy for the genetic approach, diagnosis and the management of this complex craniofacial defect.

Comparison of symptom clusters associated with fatigue in older and younger survivors of colorectal cancer.

PURPOSE: Cancer-related fatigue (CRF) is one of the most frequently reported symptoms in cancer survivors. To be able to optimally treat CRF, knowledge of symptoms that interact with CRF is helpful. During aging, changes occur in body composition with progressive deterioration in physiological functions and metabolic processes causing a decline of adaptive capacity. Therefore, symptoms caused by cancer and its treatment might coexist in different symptom clusters in older cancer survivors, compared to younger survivors. The purpose of this analysis was to identify and compare symptom clusters that include CRF between older and younger survivors of colorectal cancer (CRC). METHODS: Data were drawn from a cross-sectional study from the Netherlands Cancer Registry. In total, 1698 stage I and II CRC survivors diagnosed from 2000 to 2009 completed questionnaires on fatigue and psychological distress. Survivors were categorized in two groups based on age (≤65 versus >65 years) Symptom clusters were assessed using principal component analysis. A sensitivity analysis was performed on the results with categorical principal component analysis. RESULTS: In both age groups, three components including two symptom clusters were identified: an emotional symptom cluster containing anxiety, fatigue, and depression; a pain symptom cluster containing pain and insomnia; and a third component containing dyspnea only. CONCLUSIONS: Symptom clusters in survivors of CRC appear to be independent of age. In treating CRC survivors for fatigue, regardless of age, it is advisable to assess depression and anxiety and, if necessary, refer for further diagnosis and treatment.

Comparison of human and mouse E-selectin binding to Sialyl-Lewis(x).

BACKGROUND: During inflammation, leukocytes are captured by the selectin family of adhesion receptors lining blood vessels to facilitate exit from the bloodstream. E-selectin is upregulated on stimulated endothelial cells and binds to several ligands on the surface of leukocytes. Selectin:ligand interactions are mediated in part by the interaction between the lectin domain and Sialyl-Lewis x (sLe(x)), a tetrasaccharide common to selectin ligands. There is a high degree of homology between selectins of various species: about 72 and 60 % in the lectin and EGF domains, respectively. In this study, molecular dynamics, docking, and steered molecular dynamics simulations were used to compare the binding and dissociation mechanisms of sLe(x) with mouse and human E-selectin. First, a mouse E-selectin homology model was generated using the human E-selectin crystal structure as a template. RESULTS: Mouse E-selectin was found to have a greater interdomain angle, which has been previously shown to correlate with stronger binding among selectins. sLe(x) was docked onto human and mouse E-selectin, and the mouse complex was found to have a higher free energy of binding and a lower dissociation constant, suggesting stronger binding. The mouse complex had higher flexibility in a few key residues. Finally, steered molecular dynamics was used to dissociate the complexes at force loading rates of 2000-5000 pm/ps(2). The mouse complex took longer to dissociate at every force loading rate and the difference was statistically significant at 3000 pm/ps(2). When sLe(x)-coated microspheres were perfused through microtubes coated with human or mouse E-selectin, the particles rolled more slowly on mouse E-selectin. CONCLUSIONS: Both molecular dynamics simulations and microsphere adhesion experiments show that mouse E-selectin protein binds more strongly to sialyl Lewis x ligand than human E-selectin. This difference was explained by a greater interdomain angle for mouse E-selectin, and greater flexibility in key residues. Future work could introduce similar amino acid substitutions into the human E-selectin sequence to further modulate adhesion behavior.

Identification of germline alterations in breast cancer predisposition genes among Malaysian breast cancer patients using panel testing.

Although an association between protein-truncating variants and breast cancer risk has been established for 11 genes, only alterations in BRCA1, BRCA2, TP53 and PALB2 have been reported in Asian populations. Given that the age of onset of breast cancer is lower in Asians, it is estimated that inherited predisposition to breast cancer may be more significant. To determine the potential utility of panel testing, we investigated the prevalence of germline alterations in 11 established and 4 likely breast cancer genes in a cross-sectional hospital-based cohort of 108 moderate to high-risk breast cancer patients using targeted next generation sequencing. Twenty patients (19%) were identified to carry deleterious mutations, of whom 13 (12%) were in the BRCA1 or BRCA2, 6 (6%) were in five other known breast cancer predisposition genes and 1 patient had a mutation in both BRCA2 and BARD1. Our study shows that BRCA1 and BRCA2 account for the majority of genetic predisposition to breast cancer in our cohort of Asian women. Although mutations in other known breast cancer genes are found, the functional significance and breast cancer risk have not yet been determined, thus limiting the clinical utility of panel testing in Asian populations.

Compound heterozygous mutations in TTC7A cause familial multiple intestinal atresias and severe combined immunodeficiency.

Familial multiple intestinal atresias is an autosomal recessive disease with or without combined immunodeficiency. In the last year, several reports have described mutations in the gene TTC7A as causal to the disease in different populations. However, exact correlation between different genotypes and various phenotypes are not clear. In this study, we report identification of novel compound heterozygous mutations in TTC7A gene in a Malay girl with familial multiple intestinal atresias and severe combined immunodeficiency (MIA-SCID) by whole exome sequencing. We found two mutations in TTC7A: one that destroyed a putative splicing acceptor at the junction of intron 17/exon 18 and one that introduced a stop codon that would truncate the last two amino acids of the encoded protein. Reviewing the recent reports on TTC7A mutations reveals correlation between the position and nature of the mutations with patient survival and clinical manifestations. Examination of public databases also suggests carrier status for healthy individuals, making a case for population screening on this gene, especially in populations with suspected frequent founder mutations.

Endothelial retention and phenotype on carbonized cardiovascular implant surfaces.

Heart valve disease is an increasing clinical burden for which there is no effective treatment outside of prosthetic replacement. Over the last 20 years, clinicians have increasingly preferred the use of biological prosthetics to mechanical valves despite their superior durability because of the lifelong anticoagulation therapy that is required. Mechanical valve surface engineering has largely focused on being as non-thrombogenic as possible, but despite decades of iteration has had insufficient impact on the anticoagulation burden. In this study, we systematically evaluate the potential for endothelialization of the pyrolytic carbon surface used in mechanical valves. We compared adsorbed adhesion ligand type (collagen I, fibronectin, laminin, and purified adhesion domain fragments GFOGER and FN7-10) and concentration on endothelial adhesion rates and adhesion strength on Medtronic-Hall prosthetic valve surfaces. Regardless of ligand type or concentration, endothelial adhesion strengthening was insufficient for their intended ultra-high shear stress environment. We then hypothesized that microfabricated trenches would reduce shear stress to tolerable levels while maintaining endothelial access to the flow stream, thereby promoting a confluent and anticoagulant endothelial monolayer. Computational fluid dynamics simulations predicted an empirical relationship of channel width, depth, and spacing that would maintain interior surface shear stress within tolerable levels. Endothelial cells seeded to confluence in these channels retained a confluent monolayer when exposed to 600 dyn/cm(2) shear stress for 48 h regardless of applied adhesive ligand. Furthermore, sheared EC expressed a mature anti-coagulant profile, including endothelial nitric oxide synthase (eNOS), VE-cadherin, and significantly downregulated plasminogen activator inhibitor-1 (PAI-1). As a final test, channeled pyrolytic carbon surfaces with confluent EC reduced human platelet adhesion 1000-fold over pyrolytic carbon alone. These results advance a promising biohybrid approach to enable active moderation of local coagulative response in mechanical heart valves, which could significantly extend the utility of this important treatment for heart valve disease.

Stem cell enrichment with selectin receptors: mimicking the pH environment of trauma.

The isolation of hematopoietic stem and progenitor cells (HSPCs) is critical for transplantation therapy and HSPC research, however current isolation techniques can be prohibitively expensive, time-consuming, and produce variable results. Selectin-coated microtubes have shown promise in rapidly isolating HSPCs from human bone marrow, but further purification of HSPCs remains a challenge. Herein, a biomimetic device for HSPC isolation is presented to mimic the acidic vascular microenvironment during trauma, which can enhance the binding frequency between L-selectin and its counter-receptor PSGL-1 and HSPCs. Under acidic pH conditions, L-selectin coated microtubes enhanced CD34+ HSPC adhesion, as evidenced by decreased cell rolling velocity and increased rolling flux. Dynamic light scattering was utilized as a novel sensor to confirm an L-selectin conformational change under acidic conditions, as previously predicted by molecular dynamics. These results suggest that mimicking the acidic conditions of trauma can induce a conformational extension of L-selectin, which can be utilized for flow-based, clinical isolation of HSPCs.

Sinonasal blue naevus: case report and clinicopathological review.

OBJECTIVE: To highlight the important clinical and histological features of sinonasal blue naevi. METHODS: A case of blue naevus of the nasal cavity is described (including endoscopic and histological pictures) and the existing literature is reviewed. RESULTS: There have been five reported cases (including the presented case). Clinically, sinonasal blue naevi are heavily pigmented lesions that are small and asymptomatic. Histopathologically, blue naevi exhibit heavily pigmented dendritic melanocytes that are never abnormal in form. CONCLUSION: Blue naevus should be a differential diagnosis for pigmented lesions within the sinonasal cavity, despite its rarity. It may be initially suspected by its small size and asymptomatic nature. However, histological examination is required for definitive diagnosis, looking for the key microscopic features described above.

The impact of comorbidity on Health-Related Quality of Life among cancer survivors: analyses of data from the PROFILES registry.

PURPOSE: The aim of this study was to assess the difference in explained variance of Health-Related Quality of Life (HRQoL) between comorbidity, sociodemographic characteristics and cancer characteristics. This association was assessed among thyroid cancer, colorectal cancer, and (non-)Hodgkin's lymphoma patients. METHODS: Data from three large population-based surveys on survivors of thyroid cancer, colorectal cancer, and (non-)Hodgkin's lymphoma were used. Cancer-specific HRQoL was assessed with the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30) of which physical function, emotional function, fatigue, and pain were included in the analyses. Comorbidity was assessed using the Self-reported Comorbidity Questionnaire. The association between comorbidity and HRQoL was assessed with multivariate linear regression models. Semi-partial R (2) was reported to assess the amount of variance in HRQoL explained by comorbidity in comparison with sociodemographic and cancer characteristics. RESULTS: In total, 3,792 cancer survivors were included in this analysis. The variance in HRQoL subscales explained by comorbidity was higher compared with sociodemographic and cancer characteristics for physical function (11-17 vs. 2-4 and 1-2 %, respectively) and emotional function (7-17 vs. 1-3 and 1-3 %, respectively), regardless of cancer type. In addition, comorbidity explained 7-20 and 11-13 % of the variance in pain and fatigue, respectively, compared to 0-4 % for both sociodemographic and cancer characteristics. Osteoarthritis and back pain were strongly associated with physical function and pain, while depression was strongly associated with emotional function. Depression and back pain were strongly associated with fatigue. CONCLUSIONS: This study showed that comorbidity explained more variance in physical and emotional function, pain, and fatigue in comparison with sociodemographic and cancer characteristics in cancer survivors, regardless of cancer type. Our findings emphasize the importance of adjusting for the presence of comorbid diseases when assessing HRQoL in cancer survivors. IMPLICATION FOR CANCER SURVIVORS: Cancer survivors suffering from comorbid diseases experience lower levels of health-related quality of life. Clinicians should become more aware of the impact of comorbidity on HRQoL and provide necessary psychological support to assist self-management of comorbid diseases.

Effect of extracellular pH on selectin adhesion: theory and experiment.

Selectins mediate circulatory leukocyte trafficking to sites of inflammation and trauma, and the extracellular microenvironments at these sites often become acidic. In this study, we investigated the influence of slightly acidic pH on the binding dynamics of selectins (P-, L-, and E-selectin) to P-selectin glycoprotein ligand-1 (PSGL-1) via computational modeling (molecular dynamics) and experimental rolling assays under shear in vitro. The P-selectin/PSGL-1 binding is strengthened at acidic pH, as evidenced by the formation of a new hydrogen bond (seen computationally) and the observed decrease in the rolling velocities of model cells. In the case of L-selectin/PSGL-1 binding dynamics, the binding strength and frequency increase at acidic pH, as indicated by the greater cell-rolling flux of neutrophils and slower rolling velocities of L-selectin-coated microspheres, respectively. The cell flux is most likely due to an increased population of L-selectin in the high-affinity conformation as pH decreases, whereas the velocities are due to increased L-selectin/PSGL-1 contacts. In contrast to P- and L-selectin, the E-selectin/PSGL-1 binding does not exhibit significant changes at acidic pH levels, as shown both experimentally and computationally.

Quality of life of older rectal cancer patients is not impaired by a permanent stoma.

BACKGROUND: The current study was undertaken to investigate the impact of a stoma on the HRQL with a special focus on age. MATERIALS AND METHODS: Using the Eindhoven Cancer Registry, rectal cancer patients diagnosed between 1998 and 2007 in 4 hospitals were identified. All patients underwent TME surgery. Survivors were approached to complete the SF-36 and EORTC QLQ-C38 questionnaires. HRQL scores of the four groups, stratified by stoma status (stoma/no stoma) and age at operation (<70 and ≥ 70), were compared. The SF-36 and the QLQ-CR38 sexuality subscale scores of the survivors were compared with an age- and sex-matched Dutch norm population. RESULTS: Median follow-up of 143 patients was 3.4 years. Elderly had significantly worse physical function (p = 0.0003) compared to younger patients. Elderly (p = 0.005) and patients without a stoma (p = 0.009) had worse sexual functioning compared to younger patients and patients with a stoma. Older males showed more sexual dysfunction (p = 0.01) when compared to younger males. In comparison with the normative population, elderly with a stoma had worse physical function (p < 0.01), but slightly better mental health (p < 0.05). Elderly without a stoma had better emotional role function (p < 0.01), and younger patients had worse sexual functioning and enjoyment (both p < 0.0001). CONCLUSIONS: Older patients with a stoma have comparable HRQL to older patients without a stoma or the normative population, indicating the feasibility of a permanent stoma for elderly patients with a low situated rectal carcinoma. The negative impact of treatment on sexual functioning as found in the current study calls for further attention to alleviate this problem in sexually active patients.

Tropical distal renal tubular acidosis: clinical and epidemiological studies in 78 patients.

BACKGROUND: Distal renal tubular acidosis (dRTA) caused by mutations of the SLC4A1 gene encoding the erythroid and kidney isoforms of anion exchanger 1 (AE1 or band 3) has a high prevalence in some tropical countries, particularly Thailand, Malaysia, the Philippines and Papua New Guinea (PNG). Here the disease is almost invariably recessive and can result from either homozygous or compound heterozygous SLC4A1 mutations. METHODS: We have collected and reviewed our own and published data on tropical dRTA to provide a comprehensive series of clinical and epidemiological studies in 78 patients. RESULTS: Eight responsible SLC4A1 mutations have been described so far, four of them affecting multiple unrelated families. With the exception of the mutation causing South-East Asian ovalocytosis (SAO), none of these mutations has been reported outside the tropics, where dRTA caused by SLC4A1 mutations is much rarer and almost always dominant, resulting from mutations that are quite different from those found in the tropics. SLC4A1 mutations, including those causing dRTA, may cause morphological red cell changes, often with excess haemolysis. In dRTA, these red cell changes are usually clinically recessive and not present in heterozygotes. The high tropical prevalence of dRTA caused by SLC4A1 mutations is currently unexplained. CONCLUSION: A hypothesis suggesting that changes in red cell metabolism caused by these mutations might protect against malaria is put forward to explain the phenomenon, and a possible mechanism for this effect is proposed.

Higher prevalence of sexual dysfunction in colon and rectal cancer survivors compared with the normative population: a population-based study.

BACKGROUND: To compare colorectal cancer survivors with a normative population regarding erectile dysfunction, ejaculation problems, dyspareunia, dry vagina, sexual functioning (SF) and enjoyment (SE). In addition, the sociodemographic, clinical and psychological correlates of (dys)function in survivors are examined. PATIENTS AND METHODS: The European Organisation for Research and Treatment of Cancer (EORTC) QLQ-CR38 sexuality subscales were completed by survivors (n=1371; response rate 82%), of which 1359 received surgical treatment and were included in the analysis. The normative population consisted of 400 participants (response rate 78%). RESULTS: Erectile problems were more often present in rectal cancer (54%) than colon cancer survivors (25%) and the normative population (27%; p<.0001). They also had more ejaculation problems (68%) than colon cancer survivors (47%; p<.001). Dry vagina was common in colon (28%) and rectal cancer survivors (35%), while the normative population scored lower (5%; p=.003). In addition, colon (9%) and rectal cancer survivors (30%) experienced more pain during intercourse than the normative population (0%; p=.001). SE for men was similar across groups, while women with colorectal cancer reported lower scores than the normative population. Higher age, being a woman, not having a partner, a low educational level, rectal cancer, depressive symptoms and fatigue were associated with lower SF. Lower SE was associated with higher age and being a woman, depressive symptoms and cardiovascular disease. CONCLUSION: SF was deteriorated in both sexes after cancer, which affected women's SE negatively. Attention towards sexual (dys)function in colorectal cancer survivors is needed.