Citations

Abstract Background Head and neck cancer represents the seventh most common cancer diagnosis globally. Maintaining sufficient nutrition is important for preventing malnutrition (undernutrition) and muscle wasting, which contribute to worse outcomes, although many patients are unable to maintain adequate oral intake throughout treatment. This guideline provides practice guidance on nutrition care for patients with head and neck cancer. Methods An interdisciplinary team developed key questions and scanned results from a systematic search of the PubMed, EMBASE, CINAHL, and Cochrane Central databases back to 2001. Recommendations were created for key questions concerning timing and duration of nutrition support (early vs delayed enteral nutrition [EN], postoperative feeding, and perioperative dietitian intervention), frequency of dietitian and speech pathology consultations, nutrition screening and assessment, macronutrient requirements, enteral access devices, adjunctive strategies (appetite stimulants and continuation of oral intake alongside EN), specialized nutrients (arginine, glutamine, ω‐3, and immunonutrition), and interdisciplinary care. Results Ninety‐two studies were included. Recommendations were made supporting early initiation of EN when oral intake is inadequate, nutrition within 24 h after surgery, weekly consultation with a dietitian during radiotherapy, malnutrition screening and assessment with validated tools, interdisciplinary models of care, dietitian involvement before and after surgery, and when to consider use of specialized nutrients. Recommendations are also provided for protein intake (1.2–1.5 g/kg/day) and energy intake (≥30 kcal/kg/day). Conclusion This guideline provides guidance for the nutrition care of patients with head and neck cancer, identifies research gaps, and calls for standardized outcome reporting to further the state of the evidence. This paper was approved by the ASPEN Board of Directors.

Abstract Objective To study maternal anxiety in pregnant women without comorbidities in the context of the COVID-19 outbreak in Brazil and to study maternal knowledge and concerns about the pandemic. Methods This is a secondary analysis from a national multicenter cross-sectional study performed in 10 cities, from June to August, 2020, in Brazil. Interviewed postpartum women, without medical or obstetrical comorbidities, were included in the present subanalysis. A structured questionnaire and the Beck Anxiety Inventory (BAI) were applied. Results Out of the 1,662 women, 763 (45.9%) met the criteria for the current analysis and 16.1% presented with moderate and 11.5% with severe maternal anxiety. Moderate or severe maternal anxiety was associated with high school education (odds ratio [OR]:1.58; 95% confidence interval [CI]:1.04–2.40). The protective factor was cohabiting with a partner (OR: 0.46; 95%CI: 0.29–0.73). There was a positive correlation between the total BAI score and receiving information about care in the pandemic (rpartial 0.15; p < 0.001); concern about vertical transmission of COVID-19 (rpartial 0.10; p = 0.01); receiving information about breastfeeding (rpartial 0.08; p = 0.03); concerns about prenatal care (rpartial 0.10; p = 0.01), and concerns about the baby contracting COVID-19 (rpartial 0.11; p = 0.004). The correlation was negative in the following aspects: self-confidence in protecting from COVID-19 (rpartial 0.08; p = 0.04), having learned (rpartial 0.09; p = 0.01) and self-confidence in breastfeeding (rpartial 0.22; p < 0.001) in the context of the pandemic. Conclusion The anxiety of pregnant women without medical or obstetrical comorbidities was associated to high school educational level and not living with a partner during the COVID-19 pandemic. Self-confidence in protecting against COVID-19 and knowledge about breastfeeding care during the pandemic reduced maternal anxiety.

AbstractThe study aimed at widening the clinical and genetic spectrum of ASXL3‐related syndrome, a neurodevelopmental disorder, caused by truncating variants in the ASXL3 gene. In this international collaborative study, we have undertaken a detailed clinical and molecular analysis of 45 previously unpublished individuals with ASXL3‐related syndrome, as well as a review of all previously published individuals. We have reviewed the rather limited functional characterization of pathogenic variants in ASXL3 and discuss current understanding of the consequences of the different ASXL3 variants. In this comprehensive analysis of ASXL3‐related syndrome, we define its natural history and clinical evolution occurring with age. We report familial ASXL3 pathogenic variants, characterize the phenotype in mildly affected individuals and discuss nonpenetrance. We also discuss the role of missense variants in ASXL3. We delineate a variable but consistent phenotype. The most characteristic features are neurodevelopmental delay with consistently limited speech, significant neuro‐behavioral issues, hypotonia, and feeding difficulties. Distinctive features include downslanting palpebral fissures, hypertelorism, tubular nose with a prominent nasal bridge, and low‐hanging columella. The presented data will inform clinical management of individuals with ASXL3‐related syndrome and improve interpretation of new ASXL3 sequence variants.

Background: The coronavirus disease 2019 (COVID-19) pandemic may have an effect on maternal anxiety and influence postpartum experience. Objective: To study the prevalence of maternal anxiety in late pregnancy in the context of the COVID-19 outbreak in Brazil and to analyze its association with maternal knowledge and concerns about the pandemic. Methods: This was a national multicenter cross-sectional study performed in 10 different public university hospitals, between 1 June and 31 August 2020, in Brazil. The inclusion criteria were: maternal age more than 18 years; gestational age more than 36 weeks at childbirth; single alive newborn without malformations; and absence of mental disorders. We applied a structured questionnaire to explore the knowledge and concerns about COVID-19. Maternal anxiety was assessed using the Beck Anxiety Inventory (BAI). Results: Of the 1662 women interviewed, the BAI score in late pregnancy indicated that 13.9% presented moderate and 9.6% severe maternal anxiety. Moderate or severe maternal anxiety was independently associated with the fear of being unaccompanied at childbirth (aOR1.12, 95% CI 1.10–1.35), and independent protective factors were confidence in knowing how to protect oneself from COVID-19 (aOR0.89, 95% CI 0.82–0.97) and how to safely breastfeed (aOR0.89, 95% CI 0.83–0.95). Conclusion: The COVID-19 pandemic has a significant impact on maternal anxiety.

Abstract Background: A polygenic hazard score (PHS), the weighted sum of 54 SNP genotypes, was previously validated for association with clinically significant prostate cancer and for improved prostate cancer screening accuracy. Here, we assess the potential impact of PHS-informed screening. Methods: United Kingdom population incidence data (Cancer Research United Kingdom) and data from the Cluster Randomized Trial of PSA Testing for Prostate Cancer were combined to estimate age-specific clinically significant prostate cancer incidence (Gleason score ≥7, stage T3–T4, PSA ≥10, or nodal/distant metastases). Using HRs estimated from the ProtecT prostate cancer trial, age-specific incidence rates were calculated for various PHS risk percentiles. Risk-equivalent age, when someone with a given PHS percentile has prostate cancer risk equivalent to an average 50-year-old man (50-year-standard risk), was derived from PHS and incidence data. Positive predictive value (PPV) of PSA testing for clinically significant prostate cancer was calculated using PHS-adjusted age groups. Results: The expected age at diagnosis of clinically significant prostate cancer differs by 19 years between the 1st and 99th PHS percentiles: men with PHS in the 1st and 99th percentiles reach the 50-year-standard risk level at ages 60 and 41, respectively. PPV of PSA was higher for men with higher PHS-adjusted age. Conclusions: PHS provides individualized estimates of risk-equivalent age for clinically significant prostate cancer. Screening initiation could be adjusted by a man's PHS. Impact: Personalized genetic risk assessments could inform prostate cancer screening decisions.

AbstractObjectivePrevious studies have reported a close relationship between malignant mesothelioma (MM) and the immune matricial microenvironment (IMM). One of the major problems in these studies is the lack of adequate adjustment for potential confounders. Therefore, the aim of this study was to identify and quantify risk factors such as IMM and various tumor characteristics and their association with the subtype of MM and survival.MethodsWe examined IMM and other tumor markers in tumor tissues from 82 patients with MM. These markers were evaluated by histochemistry, immunohistochemistry, immunofluorescence, and morphometry. Logistic regression analysis, cluster analysis, and Cox regression analysis were performed.ResultsHierarchical cluster analysis revealed two clusters of MM that were independent of clinicopathologic features. The high‐risk cluster included MM with high tumor cellularity, high type V collagen (Col V) fiber density, and low CD8+ T lymphocyte density in the IMM. Our results showed that the risk of death was increased for patients with MM with high tumor cellularity (OR = 1.63, 95% CI = 1.29‐2.89, P = .02), overexpression of Col V (OR = 2.60, 95% CI = 0.98‐6.84, P = .04), and decreased CD8 T lymphocytes (OR = 1.001, 95% CI = 0.995‐1.007, P = .008). The hazard ratio for the high‐risk cluster was 2.19 (95% CI = 0.54‐3.03, P < .01) for mortality from MM at 40 months.ConclusionMorphometric analysis of Col V, CD8+ T lymphocytes, and tumor cellularity can be used to identify patients with high risk of death from MM.

Abstract Breast, ovarian, and prostate cancers are hormone-related and may have a shared genetic basis, but this has not been investigated systematically by genome-wide association (GWA) studies. Meta-analyses combining the largest GWA meta-analysis data sets for these cancers totaling 112,349 cases and 116,421 controls of European ancestry, all together and in pairs, identified at P &lt; 10−8 seven new cross-cancer loci: three associated with susceptibility to all three cancers (rs17041869/2q13/BCL2L11; rs7937840/11q12/INCENP; rs1469713/19p13/GATAD2A), two breast and ovarian cancer risk loci (rs200182588/9q31/SMC2; rs8037137/15q26/RCCD1), and two breast and prostate cancer risk loci (rs5013329/1p34/NSUN4; rs9375701/6q23/L3MBTL3). Index variants in five additional regions previously associated with only one cancer also showed clear association with a second cancer type. Cell-type–specific expression quantitative trait locus and enhancer–gene interaction annotations suggested target genes with potential cross-cancer roles at the new loci. Pathway analysis revealed significant enrichment of death receptor signaling genes near loci with P &lt; 10−5 in the three-cancer meta-analysis. Significance: We demonstrate that combining large-scale GWA meta-analysis findings across cancer types can identify completely new risk loci common to breast, ovarian, and prostate cancers. We show that the identification of such cross-cancer risk loci has the potential to shed new light on the shared biology underlying these hormone-related cancers. Cancer Discov; 6(9); 1052–67. ©2016 AACR. This article is highlighted in the In This Issue feature, p. 932

Abstract Background: Unnecessary intervention and overtreatment of indolent disease are common challenges in clinical management of prostate cancer. Improved tools to distinguish lethal from indolent disease are critical. Methods: We performed a genome-wide survival analysis of cause-specific death in 24,023 prostate cancer patients (3,513 disease-specific deaths) from the PRACTICAL and BPC3 consortia. Top findings were assessed for replication in a Norwegian cohort (CONOR). Results: We observed no significant association between genetic variants and prostate cancer survival. Conclusions: Common genetic variants with large impact on prostate cancer survival were not observed in this study. Impact: Future studies should be designed for identification of rare variants with large effect sizes or common variants with small effect sizes. Cancer Epidemiol Biomarkers Prev; 24(11); 1796–800. ©2015 AACR.

Abstract Prostate cancer is the second most common malignancy among men worldwide. Genome-wide association studies have identified 100 risk variants for prostate cancer, which can explain approximately 33% of the familial risk of the disease. We hypothesized that a comprehensive analysis of genetic variations found within the 3′ untranslated region of genes predicted to affect miRNA binding (miRSNP) can identify additional prostate cancer risk variants. We investigated the association between 2,169 miRSNPs and prostate cancer risk in a large-scale analysis of 22,301 cases and 22,320 controls of European ancestry from 23 participating studies. Twenty-two miRSNPs were associated (P &lt; 2.3 × 10−5) with risk of prostate cancer, 10 of which were within 7 genes previously not mapped by GWAS studies. Further, using miRNA mimics and reporter gene assays, we showed that miR-3162-5p has specific affinity for the KLK3 rs1058205 miRSNP T-allele, whereas miR-370 has greater affinity for the VAMP8 rs1010 miRSNP A-allele, validating their functional role. Significance: Findings from this large association study suggest that a focus on miRSNPs, including functional evaluation, can identify candidate risk loci below currently accepted statistical levels of genome-wide significance. Studies of miRNAs and their interactions with SNPs could provide further insights into the mechanisms of prostate cancer risk. Cancer Discov; 5(4); 368–79. ©2015 AACR. See related commentary by Yousef, p. 351 This article is highlighted in the In This Issue feature, p. 333