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Background: The aim of this study was to evaluate the long-term patient satisfaction and quality of life 9 to 13 years after autologous versus alloplastic breast reconstruction and compare the data to those of an earlier study.Methods: This is a 9-year follow-up study of 92 women who underwent breast reconstruction (47 autologous and 45 alloplastic) between 2006 and 2010 and filled out the BREAST-Q questionnaire in 2010. Changes in BREAST-Q scores were analyzed by using a change score from baseline (2010) to follow-up (2019), which was presented by a mean change score with 95% confidence intervals. Linear regression analyses were performed to test which patient characteristics were related to the BREAST-Q change scores.Results: The response rate at follow-up was 60% (25 autologous and 30 alloplastic). Responders at follow-up had a lower body mass index and had less frequently undergone unilateral breast reconstruction compared to the nonresponders. Women undergoing both autologous and alloplastic breast reconstruction had significantly decreased satisfaction with breasts (-4 points), satisfaction with outcome (-8 points), and satisfaction with nipples (-20 points) over time. None of the patient characteristics, including reconstruction technique, were related to the BREAST-Q change scores.Conclusions: Satisfaction with breasts, satisfaction with outcome, and satisfaction with nipples decreased slightly over time for women undergoing alloplastic and autologous breast reconstruction. Women undergoing autologous breast reconstruction seemed to remain more satisfied with their breasts 9 to 13 years after breast reconstruction compared to women undergoing alloplastic breast reconstruction. Because of the small sample size, conclusions should be carefully drawn. However, the results were in line with the expectations based on previous literature.

There is great promise in breast cancer risk stratification to target screening and prevention. It is unclear whether adding gene panels to other risk tools improves breast cancer risk stratification and adds discriminatory benefit on a population basis.In total, 10,025 of 57,902 women aged 46 to 73 years in the Predicting Risk of Cancer at Screening study provided DNA samples. A case-control study was used to evaluate breast cancer risk assessment using polygenic risk scores (PRSs), cancer gene panel (n = 33), mammographic density (density residual [DR]), and risk factors collected using a self-completed 2-page questionnaire (Tyrer-Cuzick [TC] model version 8). In total, 525 cases and 1410 controls underwent gene panel testing and PRS calculation (18, 143, and/or 313 single-nucleotide polymorphisms [SNPs]).Actionable pathogenic variants (PGVs) in BRCA1/2 were found in 1.7% of cases and 0.55% of controls, and overall PGVs were found in 6.1% of cases and 1.3% of controls. A combined assessment of TC8-DR-SNP313 and gene panel provided the best risk stratification with 26.1% of controls and 9.7% of cases identified at1.4% 10-year risk and 9.01% of controls and 23.3% of cases at ≥8% 10-year risk. Because actionable PGVs were uncommon, discrimination was identical with/without gene panel (with/without: area under the curve = 0.67, 95% CI = 0.64-0.70). Only 7 of 17 PGVs in cases resulted in actionable risk category change. Extended case (n = 644)-control (n = 1779) series with TC8-DR-SNP143 identified 18.9% of controls and only 6.4% of stage 2+ cases at1.4% 10-year risk and 20.7% of controls and 47.9% of stage 2+ cases at ≥5% 10-year risk.Further studies and economic analysis will determine whether adding panels to PRS is a cost-effective strategy for risk stratification.

Background Breast implant–associated anaplastic large-cell lymphoma (BIA-ALCL) and its association with macrotextured breast implants may have induced plastic surgeons to change their breast augmentation and breast reconstruction practice. Objectives The aim of this study was to survey Dutch plastic surgeons about the effects of BIA-ALCL on their choice of breast implant texture and placement technique. Methods An online questionnaire was distributed to all members of the Dutch Association of Plastic Surgeons. Descriptive data were presented as frequencies and percentages. Technique alterations were analyzed by the marginal homogeneity test for paired nominal data. Results A total of 63 plastic surgeons completed the questionnaire. The majority of respondents altered their use of textured implants due to BIA-ALCL concerns for both breast augmentation and reconstruction (75.4% and 69.8%, respectively; both being statistically significant, P < .001). Microtextured and smooth/nanotextured breast implants are now most frequently used. BIA-ALCL did not influence the placement technique in breast augmentation and reconstruction (87.7% and 94.3%, respectively). Dual-plane breast implant placement is still the most favored technique for breast augmentation, and submuscular placement is still most favored for breast reconstruction. Conclusions BIA-ALCL has had a significant impact on the use of macrotextured breast implants by Dutch plastic surgeons in both aesthetic and reconstructive breast surgery. Breast implant placement technique has not been affected. Level of Evidence: 4

Item does not contain fulltext INTRODUCTION: Facial function correlates with quality of life in facial palsy. Previous studies have examined a linear relationship; based on clinical experience, we hypothesize a curved regression (i.e. quadratic or cubic) will be more fitting to show the correlation between quality of life and facial function. METHODS: We compared the fit of a linear regression model between Sunnybrook scores (facial function) and FaCE and FDI scores (quality of life) to a quadratic and cubic regression model in 125 patients cross-sectionally. RESULTS: A total of 125 patients were included, 53.6% female with a mean (standard deviation) age of 56.6 (16.7) and a median (interquartile range) duration of palsy of 6.6 (1.5; 18.3) years. The quadratic regression proved a significant improvement over a linear regression analysis in the model using the FaCE total score (linear R(2) =.346, quadratic R(2) = .378, p = .033) and the FDI physical score (linear R(2) = .245, quadratic R(2) =.276, p = .034). The cubic regression analysis was no significant improvement over a quadratic regression. DISCUSSION: The relationship between facial function and quality of life in facial palsy is not linear meaning that there is a lot of variation in QoL in cases with severe and moderate facial impairment. This is most applicable to patients suffering from post-paralysis synkinesis, proving the highly individually experienced burden of synkinesis. As the relationship is not linear it should not be included as such in future research studies.

Breast cancer (BC) patients with a germline CHEK2 c.1100delC variant have an increased risk of contralateral BC (CBC) and worse BC-specific survival (BCSS) compared to non-carriers. We aimed to assess the associations of CHEK2 c.1100delC, radiotherapy, and systemic treatment with CBC risk and BCSS. Analyses were based on 82,701 women diagnosed with invasive BC including 963 CHEK2 c.1100delC carriers; median follow-up was 9.1 years. Differential associations of treatment by CHEK2 c.1100delC status were tested by including interaction terms in a multivariable Cox regression model. A multi-state model was used for further insight into the relation between CHEK2 c.1100delC status, treatment, CBC risk and death. There was no evidence for differential associations of therapy with CBC risk by CHEK2 c.1100delC status The strongest association with reduced CBC risk was observed for the combination of chemotherapy and endocrine therapy [HR(95%CI): 0.66 (0.55–0.78)]. No association was observed with radiotherapy. Results from the multi-state model showed shorter BCSS for CHEK2 c.1100delC carriers versus non-carriers also after accounting for CBC occurrence [HR(95%CI) :1.30 (1.09–1.56)]. In conclusion, systemic therapy was associated with reduced CBC risk irrespective of CHEK2 c.1100delC status. Moreover, CHEK2 c.1100delC carriers had shorter BCSS, which appears not to be fully explained by their CBC risk. (Main MS: 3201 words)

Evidence linking coding germline variants in breast cancer (BC)-susceptibility genes other than BRCA1, BRCA2, and CHEK2 with contralateral breast cancer (CBC) risk and breast cancer-specific survival (BCSS) is scarce. The aim of this study was to assess the association of protein-truncating variants (PTVs) and rare missense variants (MSVs) in nine known (ATM, BARD1, BRCA1, BRCA2, CHEK2, PALB2, RAD51C, RAD51D, and TP53) and 25 suspected BC-susceptibility genes with CBC risk and BCSS. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated with Cox regression models. Analyses included 34,401 women of European ancestry diagnosed with BC, including 676 CBCs and 3,449 BC deaths; the median follow-up was 10.9 years. Subtype analyses were based on estrogen receptor (ER) status of the first BC. Combined PTVs and pathogenic/likely pathogenic MSVs in BRCA1, BRCA2, and TP53 and PTVs in CHEK2 and PALB2 were associated with increased CBC risk [HRs (95% CIs): 2.88 (1.70-4.87), 2.31 (1.39-3.85), 8.29 (2.53-27.21), 2.25 (1.55-3.27), and 2.67 (1.33-5.35), respectively]. The strongest evidence of association with BCSS was for PTVs and pathogenic/likely pathogenic MSVs in BRCA2 (ER-positive BC) and TP53 and PTVs in CHEK2 [HRs (95% CIs): 1.53 (1.13-2.07), 2.08 (0.95-4.57), and 1.39 (1.13-1.72), respectively, after adjusting for tumor characteristics and treatment]. HRs were essentially unchanged when censoring for CBC, suggesting that these associations are not completely explained by increased CBC risk, tumor characteristics, or treatment. There was limited evidence of associations of PTVs and/or rare MSVs with CBC risk or BCSS for the 25 suspected BC genes. The CBC findings are relevant to treatment decisions, follow-up, and screening after BC diagnosis.

Graphical abstract Sleep disorders are linked to development of type 2 diabetes and increase the risk of developing diabetes complications. Treating sleep disorders might therefore play an important role in the prevention of diabetes progression. However, the detection and treatment of sleep disorders are not part of standardised care for people with type 2 diabetes. To highlight the importance of sleep disorders in people with type 2 diabetes, we provide a review of the literature on the prevalence of sleep disorders in type 2 diabetes and the association between sleep disorders and health outcomes, such as glycaemic control, microvascular and macrovascular complications, depression, mortality and quality of life. Additionally, we examine the extent to which treating sleep disorders in people with type 2 diabetes improves these health outcomes. We performed a literature search in PubMed from inception until January 2021, using search terms for sleep disorders, type 2 diabetes, prevalence, treatment and health outcomes. Both observational and experimental studies were included in the review. We found that insomnia (39% [95% CI 34, 44]), obstructive sleep apnoea (55–86%) and restless legs syndrome (8–45%) were more prevalent in people with type 2 diabetes, compared with the general population. No studies reported prevalence rates for circadian rhythm sleep–wake disorders, central disorders of hypersomnolence or parasomnias. Additionally, several cross-sectional and prospective studies showed that sleep disorders negatively affect health outcomes in at least one diabetes domain, especially glycaemic control. For example, insomnia is associated with increased HbA1c levels (2.51 mmol/mol [95% CI 1.1, 4.4]; 0.23% [95% CI 0.1, 0.4]). Finally, randomised controlled trials that investigate the effect of treating sleep disorders in people with type 2 diabetes are scarce, based on a small number of participants and sometimes inconclusive. Conventional therapies such as weight loss, sleep education and cognitive behavioural therapy seem to be effective in improving sleep and health outcomes in people with type 2 diabetes. We conclude that sleep disorders are highly prevalent in people with type 2 diabetes, negatively affecting health outcomes. Since treatment of the sleep disorder could prevent diabetes progression, efforts should be made to diagnose and treat sleep disorders in type 2 diabetes in order to ultimately improve health and therefore quality of life. Supplementary Information The online version contains peer-reviewed but unedited supplementary material including a slideset of the figures for download, available at 10.1007/s00125-021-05541-0.

BRIP1 is a moderate susceptibility epithelial ovarian cancer (EOC) gene. Having identified the BRIP1 c.1045G>C missense variant in a number of families with EOC, we aimed to investigate the frequency of this and BRIP1.2392C>T pathogenic variant in patients with breast cancer (BC) and/or EOC. A case-control study of 3,767 cases and 2,043 controls was undertaken investigating the presence of these variants using Sanger sequencing and gene panel data. Individuals with BC and/or EOC were grouped by family history. BRIP1 c.1045G>C was associated with increased risk of BC/EOC (OR = 37.7; 95% CI 5.3-444.2; P=0.0001). The risk was highest for women with EOC (OR=140.8; 95% CI 23.5-1723.0; PT was associated with smaller risks for BC/EOC (OR=5.4; 95%CI 2.4-12.7; P=0.0003), EOC (OR=5.9; 95% CI 1.3-23.0; p=0.0550), and BC (OR=5.3; 95%CI 2.3-12.9; P=0.0009). Our study highlights the importance of BRIP1 as an EOC susceptibility gene, especially in familial EOC. The variant BRIP1 c.1045G>C, rs149364097, is of particular interest as its dominant-negative effect may confer a higher risk of EOC than that of the previously reported BRIP1 c.2392C>T nonsense variant. Dominant-negative missense variants may confer higher risks than their loss-of-function counterparts.

Polygenic risk scores (PRS) for disease risk stratification show great promise for application in general populations, but most are based on data from individuals of white European origin. We assessed two well validated PRS (SNP18, SNP143) in the Predicting-Risk-of-Cancer-At-Screening (PROCAS) study in North-West England for breast cancer prediction based on ethnicity. Overall, 9475 women without breast cancer at study entry, including 645 who subsequently developed invasive breast cancer or ductal carcinoma in situ provided DNA. All were genotyped for SNP18 and a subset of 1868 controls were genotyped for SNP143. For white Europeans both PRS discriminated well between individuals with and without cancer. For n=395 Black (n=112), Asian (n=119), mixed (n=44) or Jewish (n=120) women without cancer both PRS overestimated breast cancer risk, being most marked for women of Black and Jewish origin (p

Process intensification in a membrane reactor is an efficient and compact way to produce hydrogen. A methane-rich gas mixture that simulated the composition of pre-reformed naphtha (PRN; with a steam-to-carbon ratio of 2.7) was reformed at temperatures of 550 °C–625 °C and pressures up to 40 barg. The reactor contained commercial steam reforming catalyst and a 14.8 cm long, 2.6 μm thick Pd-1.8Au (wt. %) membrane on a porous alumina support. Methane conversions approaching 90% were obtained in the membrane reactor at a gas-hourly space velocity of 676 h−1, compared to ≤30% conversion at the same conditions in conventional reactor mode (CM) without withdrawing hydrogen through the membrane. The results were compared to steam methane reforming (SMR) in the membrane reactor at similar conditions. The nitrogen leak through the membrane increased slowly during the testing, because of both pinhole formation and some leakage through the end seals.

PURPOSE To investigate the contribution of PALB2 pathogenic gene variants (PGVs, PALB2_PGV) and the CHEK2 c.1100delC (CHEK2_1100delC) PGV to familial breast and ovarian cancer, and PALB2_PGV associated breast cancer pathology. METHODS Outcomes of germline PALB2_PGV and CHEK2_1100delC testing were recorded in 3,127 women with histologically confirmed diagnoses of invasive breast cancer, carcinoma in situ, or epithelial nonmucinous ovarian cancer, and 1,567 female controls. Breast cancer pathology was recorded in PALB2_PGV cases from extended families. RESULTS Thirty-five PALB2 and 44 CHEK2_1100delC PGVs were detected in patients (odds ratio [OR] PALB2 breast-ovarian = 5.90 [95% CI: 1.92-18.36], CHEK2 breast-ovarian = 4.46 [95% CI: 1.86-10.46], PALB2 breast = 6.16 [95% CI: 1.98-19.21], CHEK2 breast = 4.89 [95% CI: 2.01-11.34]). Grade 3 ER-positive HER2-negative, grade 3 and triple negative (TN) tumors were enriched in cases with PALB2 PGVs compared with all breast cancers known to our service (respectively: 15/43, 254/1,843, P = 0.0005; 28/37, 562/1,381, P = 0.0001; 12/43, 204/1,639, P

BackgroundWhile the likelihood of identifying constitutional breast cancer-associated BRCA1, BRCA2 and TP53 pathogenic variants (PVs) increases with earlier diagnosis age, little is known about the correlation with age at diagnosis in other predisposition genes. Here, we assessed the contribution of known breast cancer-associated genes to very early onset disease.MethodsSequencing of BRCA1, BRCA2, TP53 and CHEK2 c.1100delC was undertaken in women with breast cancer diagnosed ≤30 years. Those testing negative were screened for PVs in a minimum of eight additional breast cancer-associated genes. Rates of PVs were compared with cases ≤30 years from the Prospective study of Outcomes in Sporadic vs Hereditary breast cancer (POSH) study.ResultsTesting 379 women with breast cancer aged ≤30 years identified 75 PVs (19.7%) in BRCA1, 35 (9.2%) in BRCA2, 22 (5.8%) in TP53 and 2 (0.5%) CHEK2 c.1100delC. Extended screening of 184 PV negative women only identified eight additional actionable PVs. BRCA1/2 PVs were more common in women aged 26–30 years than in younger women (p=0.0083) although the younger age group had rates more similar to those in the POSH cohort. Out of 26 women with ductal carcinoma in situ (DCIS) alone, most were high-grade and 11/26 (42.3%) had a PV (TP53=6, BRCA2=2, BRCA1=2, PALB2=1). This PV yield is similar to the 61 (48.8%) BRCA1/2 PVs identified in 125 women with triple-negative breast cancer. The POSH cohort specifically excluded pure DCIS which may explain lower TP53 PV rates in this group (1.7%).ConclusionThe rates of BRCA1, BRCA2 and TP53 PVs are high in very early onset breast cancer, with limited benefit from testing of additional breast cancer-associated genes.

Background: Use of menopausal hormone therapy (MHT) is associated with increased risk for breast cancer. However, the relevant mechanisms and its interaction with genetic variants are not fully understood. Methods: We conducted a genome-wide interaction analysis between MHT use and genetic variants for breast cancer risk in 27,585 cases and 34,785 controls from 26 observational studies. All women were post-menopausal and of European ancestry. Multivariable logistic regression models were used to test for multiplicative interactions between genetic variants and current MHT use. We considered interaction p-values-8 as genome-wide significant, and p-values-5 as suggestive. Linkage disequilibrium (LD)-based clumping was performed to identify independent candidate variants.Results: None of the 9.7 million genetic variants tested for interactions with MHT use reached genome-wide significance. Only 213 variants, representing 18 independent loci, had p-values5. The strongest evidence was found for rs4674019 (p-value=2.27x10-7), which showed genome-wide significant interaction (p-value=3.8x10-8) with current MHT use when analysis was restricted to population-based studies only. Limiting the analyses to combined estrogen-progesterone MHT use only or to estrogen receptor (ER) positive cases did not identify any genome-wide significant evidence of interactions. Conclusions: In this large genome-wide SNP-MHT interaction study of breast cancer, we found no strong support for common genetic variants modifying the effect of MHT on breast cancer risk. These results suggest that common genetic variation has limited impact on the observed MHT–breast cancer risk association.

Background: Recreation of a spontaneous, emotional smile remains a paramount goal of smile reanimation surgery. However, optimal techniques to reliably restore spontaneity remain unknown. Dual automated machine-learning tools were used to develop an objective tool to analyze spontaneous smiling. The feasibility of this tool was tested in a sample of functional free muscle transfers. Methods: Validated humorous videos were used to elicit spontaneous smiles. Automated facial landmark recognition (Emotrics) and emotion detection software (Affdex) were used to analyze video clips of spontaneous smiling in nine normal subjects and 39 facial reanimation cases. Emotionality quotient was used to quantify the ability of spontaneous smiles to express joy. Results: The software could analyze spontaneous smiling in all subjects. Spontaneous smiles of normal subjects exhibited median 100 percent joy and 0 percent negative emotion (emotional quotient score, +100/0). Spontaneous smiles of facial palsy patients after smile reanimation, using cross-facial nerve graft, masseteric nerve, and dual innervation, yielded median emotional quotient scores of +82/0, 0/-48, and +10/-24 respectively (joy, p = 0.006; negative emotion, p = 0.034). Conclusions: Computer vision software can objectively quantify spontaneous smiling outcomes. Of the retrospective sample of cases reviewed in this study, cross-facial nerve graft-innervated gracilis functional free muscle transfer achieved a greater degree of emotionality during spontaneous smiling than masseteric or dually innervated transfer. Quantification of spontaneous smiling from standard video clips could facilitate future, blinded, multicenter trials with sufficient long-term follow-up to definitively establish the rates of spontaneity from a range of reanimation procedures.

Background: There has been huge progress over the last 30 years in identifying the familial component of breast cancer. Summary: Currently around 20% is explained by the high-risk genes BRCA1 and BRCA2, a further 2% by other high-penetrance genes, and around 5% by the moderate risk genes ATM and CHEK2. In contrast, the more than 300 low-penetrance single-nucleotide polymorphisms (SNP) now account for around 28% and they are predicted to account for most of the remaining 45% yet to be found. Even for high-risk genes which confer a 40–90% risk of breast cancer, these SNP can substantially affect the level of breast cancer risk. Indeed, the strength of family history and hormonal and reproductive factors is very important in assessing risk even for a BRCA carrier. The risks of contralateral breast cancer are also affected by SNP as well as by the presence of high or moderate risk genes. Genetic testing using gene panels is now commonplace. Key-Messages: There is a need for a more parsimonious approach to panels only testing those genes with a definite 2-fold increased risk and only testing those genes with challenging management implications, such as CDH1 and TP53, when there is strong clinical indication to do so. Testing of SNP alongside genes is likely to provide a more accurate risk assessment.

BackgroundNephroblastomatosis is a recognised precursor for the development of Wilms tumour (WT), the most common childhood renal tumour. While the majority of WT is sporadic in origin, germline intragenic mutations of predisposition genes such as WT1, REST and TRIM28 have been described in apparently isolated (non-familial) WT.Despite constitutional CNVs being a well-studied cause of developmental disorders, their role in cancer predisposition is less well defined, so that the interpretation of cancer risks associated with specific CNVs can be complex.ObjectiveTo highlight the role of a constitutional deletion CNV (delCNV) encompassing the REST tumour suppressor gene in diffuse hyperplastic perilobar nephroblastomatosis (HPLN).Methods/resultsArray comparative genomic hybridisation in an infant presenting with apparently sporadic diffuse HPLN revealed a de novo germline CNV, arr[GRCh37] 4q12(57,385,330–57,947,405)x1. The REST tumour suppressor gene is located at GRCh37 chr4:57,774,042–57,802,010.ConclusionThis delCNV encompassing REST is associated with nephroblastomatosis. Deletion studies should be included in the molecular work-up of inherited predisposition to WT/nephroblastomatosis. Detection of delCNVs involving known cancer predisposition genes can yield insights into the relationship between underlying genomic architecture and associated tumour risk.

Several studies found associations between poor sleep quality and aggression in general and (forensic) psychiatric populations. Both poor sleep and aggression have been related previously to general psychopathology, but studies rarely have addressed this possible confounding factor appropriately. The current study aimed to replicate the association between sleep quality and aggression in a forensic psychiatric sample, including adjustment for psychopathology. We used cross-sectional data from an observational study in forensic psychiatric inpatients (n = 166). Poor sleep quality was significantly associated with higher self-reported aggression, independent of general psychopathology. Poor sleep quality accounted for a substantial part of the variance in aggression. This was observed for self-reported physical aggression, verbal aggression, anger, and hostility, all showing relations with poor sleep quality that were not better accounted for by general psychopathology. Poor sleep quality was related to higher clinician-rated hostility as well, however, this association was weak and the explained variance low. These results confirm and substantiate previously found associations between sleep quality and aggression in forensic psychiatric patients. They highlight the importance of targeting sleep problems as part of the treatment of psychiatric patients with disruptive behavior and encourage further research aimed at unraveling the relation between sleep and aggression.

Objective To examine quality of life in internationally adopted children with cleft lip and/or palate (CL/P) versus non-adopted children with CL/P. Design Cross sectional study. Setting Multidisciplinary cleft team of a secondary and tertiary hospital in the Netherlands. Methods Parents of children under the age of 8 treated by the multidisciplinary cleft team of our institutions were asked to fill out a questionnaire containing demographic and clinical data and a validated parent proxy measure of cleft-specific quality of life instrument for children aged 0–8: the CleftChild-8. Adopted children were matched to non-adopted children using propensity score matching based on sex, age, type of cleft, if palatal surgery was completed and the level of education of the parent. CleftChild-8 scores were then compared between the matched samples of adopted and non-adopted children with CL/P. Main Outcome Measure(s) Differences in (sub)domain scores of the CleftChild-8. Results Most median CleftChild-8 scores of the adopted children (n = 29) were slightly lower compared to the 29 matched non-adopted children. A significant difference was seen for the domain score ‘satisfaction with (operative) treatment’ and 3 of the 13 subdomain scores: ‘post-operative results’, ‘acceptance by siblings’ and ‘acceptance by family/friends’. Conclusions By parent report, adopted children with CL/P experienced some areas of lower quality of life when compared to non-adopted children. Members of cleft teams should be aware of the problems associated with adoption and offer additional guidance and counseling to adopted children and their parents.

IMPORTANCE Study of the association of regional facial dysfunction with quality of life will lead to a better understanding of quality of life in facial palsy.OBJECTIVE To determine the association of regional facial dysfunction with facial palsy-related quality of life.DESIGN, SETTING, AND PARTICIPANTS This retrospective cohort analysis included patients with flaccid and nonflaccid (synkinetic) facial palsy treated at a tertiary care facial nerve center; the flaccid facial palsy group included 529 patients, and the nonflaccid facial palsy group included 391 patients. Data were included from all patients with facial palsy who had an eFACE score and Facial Clinimetric Evaluation (FaCE) scale total score acquired at the same time from February 1, 2014, through October 31, 2017. Linear regression analysis was performed to calculate the amount of variance in quality of life explained by the severity of facial palsy (eFACE). A relative weight analysis was performed for the contribution of each individual eFACE item in estimating quality of life.MAIN OUTCOMES AND MEASURES Facial palsy severity was measured using all 15 individual eFACE items (rated on a scale of 0 to 200, where 0 represents complete flaccidity, 100 represents a balanced aesthetic appearance, and 200 represents the worst imaginable hypertonia of a patient with synkinesis, with a transformation used for values from 101 to 200), and facial palsy-related quality of life was measured using the FaCE scale total score (range, 0 [worst] to 100 [best]).RESULTS Data of 920 individual patients (59.5% female; mean [SD] age, 48.6 [16.6] years) were available. The eFACE composite score accounted for 21.2% of the quality-of-life variance in the flaccid group and 13.9% in the nonflaccid group. With the use of all 15 individual eFACE items, these proportions increased to 29.7% and 16.8%, respectively. In both groups, oral commissure movement with smile was found to be the most important contributing item (relative weight, 0.108 [95% CI, 0.075-0.148] for the flaccid group and 0.025 [95% CI, 0.005-0.052] for the nonflaccid group). Items related to the function of periocular muscles were found to be of low importance.CONCLUSIONS AND RELEVANCE The present study suggests that the function of individual facial regions is not equally important for estimating facial palsy-related quality of life. The ability to smile is of greatest importance among patients with flaccid and nonflaccid facial palsy. The true importance of periocular function in the estimation of quality of life should be studied further in future research.

Importance: Machine learning (ML) approaches to facial landmark localization carry great clinical potential for quantitative assessment of facial function as they enable high-throughput automated quantification of relevant facial metrics from photographs. However, translation from research settings to clinical applications requires important improvements. Objective: To develop an ML algorithm for accurate facial landmarks localization in photographs of facial palsy patients, and use it as part of an automated computer-aided diagnosis system. Design, Setting, and Participants: Facial landmarks were manually localized in portrait photographs of eight expressions obtained from 200 facial palsy patients and 10 controls. A novel ML model for automated facial landmark localization was trained using this disease-specific database. Model output was compared to manual annotations and the output of a model trained using a larger database consisting only of healthy subjects. Model accuracy was evaluated by the normalized root mean square error (NRMSE) between algorithms' prediction and manual annotations. Results: Publicly available algorithms provide poor results when applied to patients compared to healthy controls (NRMSE, 8.56 +/- 2.16 vs. 7.09 +/- 2.34, p << 0.01). We found significant improvement in facial landmark localization accuracy for the clinical population when using a model trained with a relatively small number patients' photographs (1440) compared to a model trained using several thousand more images of healthy faces (NRMSE, 6.03 +/- 2.43 vs. 8.56 +/- 2.16, p << 0.01). Conclusions: Retraining a landmark detection model with a small number of clinical images significantly improved landmark detection performance in frontal view photographs of the clinical population. These results represent the first steps towards an automatic system for computer-aided assessment in facial palsy., 21 pages, 4 figures, 1 table

Genome-wide analysis identifies 32 loci associated with breast cancer susceptibility, accounting for estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 status and tumor grade. Breast cancer susceptibility variants frequently show heterogeneity in associations by tumor subtype(1-3). To identify novel loci, we performed a genome-wide association study including 133,384 breast cancer cases and 113,789 controls, plus 18,908 BRCA1 mutation carriers (9,414 with breast cancer) of European ancestry, using both standard and novel methodologies that account for underlying tumor heterogeneity by estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 status and tumor grade. We identified 32 novel susceptibility loci (P < 5.0 x 10(-8)), 15 of which showed evidence for associations with at least one tumor feature (false discovery rate < 0.05). Five loci showed associations (P < 0.05) in opposite directions between luminal and non-luminal subtypes. In silico analyses showed that these five loci contained cell-specific enhancers that differed between normal luminal and basal mammary cells. The genetic correlations between five intrinsic-like subtypes ranged from 0.35 to 0.80. The proportion of genome-wide chip heritability explained by all known susceptibility loci was 54.2% for luminal A-like disease and 37.6% for triple-negative disease. The odds ratios of polygenic risk scores, which included 330 variants, for the highest 1% of quantiles compared with middle quantiles were 5.63 and 3.02 for luminal A-like and triple-negative disease, respectively. These findings provide an improved understanding of genetic predisposition to breast cancer subtypes and will inform the development of subtype-specific polygenic risk scores.

Background: Tools to quantify layperson assessments of facial palsy are lacking. In this study, artificial intelligence was applied to develop a proxy for layperson assessments, and compare sensitivity to existing outcome measures.Methods: Artificially intelligent emotion detection software was used to develop the emotionality quotient. The emotionality quotient was defined as the percentage probability of perceived joy over the percentage probability of perceived negative emotions during smiling, as predicted by the software. The emotionality quotient was used to analyze the emotionality of voluntary smiles of normal subjects and unilateral facial palsy patients before and after smile reanimation. The emotionality quotient was compared to oral commissure excursion and layperson assessments of facial palsy patients.Results: In voluntary smiles of 10 normal subjects, 100 percent joy and no negative emotion was detected (interquartile ranges, 0/1). Median preoperative emotionality quotient of 30 facial palsy patients was 15/-60 (interquartile range, 73/62). Postoperatively, median emotionality quotient was 84/0 (interquartile range, 28/5). In 134 smile reanimation patients, no correlation was found between postoperative oral commissure excursion and emotionality quotient score. However, in 61 preoperative patients, a moderate correlation was found between layperson-assessed disfigurement and negative emotion perception (correlation coefficient, 0.516; p Conclusions: Computer vision artificial intelligence software detected less joy and more negative emotion in smiles of facial palsy patients compared with normal subjects. Following smile reanimation, significantly more joy and less negative emotion were detected. The emotionality quotient was correlated with layperson assessments. The simplicity, sensitivity, and objectivity of the emotionality quotient render it an attractive tool to serve as a potential proxy for layperson assessment, an ideal outcome measure in facial palsy.

KEY POINTS: Synkinesis can decrease quality of life in facial palsy patients. Patient-perceived severity of synkinesis may be of additional value in predicting facial palsy related-quality of life. We analyzed the additional value of the SAQ total score (perceived severity of synkinesis) in predicting FaCE total scores (quality of life) in 92 patients cross-sectionally. SAQ total score accounted for a relatively large improvement in the prediction of FaCE total scores (R2 change = 0.113, total R2 = 0.428). Patient-perceived severity synkinesis should be included in clinical management and studies of synkinesis. This article is protected by copyright. All rights reserved.

Sleep disturbances frequently co-occur with posttraumatic stress disorder (PTSD). Insomnia and nightmares are viewed as core symptoms of PTSD. Yet, relations between disturbed sleep and PTSD are far more complex: PTSD is linked to a broad range of sleep disorders and disturbed sleep markedly affects PTSD-outcome. This article provides a concise overview of the literature on prevalent comorbid sleep disorders, their reciprocal relation with PTSD and possible underlying neurophysiological mechanisms. Furthermore, diagnostic procedures, standard interventions—particularly first choice non-pharmacological therapies—and practical problems that often arise in the assessment and treatment of sleep disturbances in PTSD are described. Finally, we will present some perspectives on future multidisciplinary clinical and experimental research to develop new, more effective sleep therapies to improve both sleep and PTSD.

Whilst panel testing of an extended group of genes including BRCA1/2 is commonplace, these studies have not been subdivided by histiotype or by a priori BRCA1/2 probability. Patients with a breast cancer diagnosis undergoing extended panel testing were assessed for frequency of actionable variants in breast cancer genes other than BRCA1/2 by histiotype and Manchester score (MS) to reflect a priori BRCA1/2 likelihood. Rates were adjusted by prior testing for BRCA1/2 in an extended series. 95/1398 (6.3%) who underwent panel testing were found to be positive for actionable non-BRCA1/2 breast/ovarian cancer genes (ATM, BARD1, CDH1, CHEK2, PALB2, PTEN, RAD51C, RAD51D, TP53). As expected, PALB2, CHEK2 and ATM were predominant with 80-(5.3%). The highest rate occurred in Grade-3 ER+/HER2− breast cancers-(9.6%). Rates of non-BRCA actionable genes was fairly constant over all likelihoods of BRCA1/2 but adjusted rates were three times higher with MS &lt, 9 (BRCA1/2 = 1.5%, other = 4.7%), but was only 1.6% compared to 79.3% with MS ≥ 40. Although rates of detection of non-BRCA actionable genes are relatively constant across BRCA1/2 likelihoods this disguises an overall adjusted low frequency in high-likelihood families which have been heavily pre-tested for BRCA1/2. Any loss of detection sensitivity for BRCA1/2 actionable variants in breast cancer panels should lead to bespoke BRCA1/2 testing being conducted first.

Importance Understanding how the quality of life of adults (≥18 years) with peripheral facial palsy can be estimated using clinician measures of facial function and patient-reported variables might aid in counseling patients and in conducting research. Objectives To analyze associations between clinician-graded facial function and patient-reported quality of life in adults with peripheral facial palsy, compare associations between facial function and the physical and social functions of quality of life, and examine factors that might influence the associations. Data Sources A literature search was conducted in PubMed, Embase, CINAHL, Web of Science and PsycInfo on June 4, 2020, with no restrictions on the start date. Study Selection Twenty-three studies reporting an association between clinician-graded facial function and patient-reported quality of life in adults with peripheral facial palsy were included. Facial function instruments included the House-Brackmann, Sunnybrook Facial Grading System, and electronic clinician-graded facial function assessment. Quality-of-life instruments included the Facial Disability Index and Facial Clinimetric Evaluation Scale. Data Extraction and Synthesis Data extraction and qualitative synthesis were performed according to the Meta-analysis of Observational Studies in Epidemiology guidelines. Record screening, data extraction, and quality assessments were done by 2 researchers independently. Data were pooled using random-effects models. Main Outcomes and Measures The main outcome was the association between facial function and quality of life, quantified by Pearsonr, Spearman ρ, or regression analysis. Results In total, 23 studies (3746 participants) were included. In the 21 studies that reported on the sex of the cohorts, there were 2073 women (57.3%). Mean or median age ranged from 21 to 64 years and mean or median duration of palsy ranged from newly diagnosed to 12 years. Bell palsy (n = 1397), benign tumor (n = 980), and infection (n = 257) were the most common etiologic factors. Pooled correlation coefficients were 0.424 (95% CI, 0.375-0.471) to 0.533 (95% CI, 0.447-0.610) between facial function and Facial Clinimetric Evaluation Scale total, 0.324 (95% CI, 0.128-0.495) to 0.397 (95% CI, 0.242-0.532) between facial function and Facial Clinimetric Evaluation Scale social function, 0.423 (95% CI, 0.322-0.514) to 0.605 (95% CI, −0.124-0.910) between facial function and Facial Disability Index physical function, and 0.166 (95% CI, 0.044-0.283) to 0.208 (95% CI, 0.031-0.373) between facial function and Facial Disability Index social function. Conclusions and Relevance Associations noted in this systematic review and meta-analysis were overall low to moderate, suggesting that only a small part of quality of life is explained by facial function. Associations were higher between facial function and physical function than social function of quality of life.

To interpret the genetic profile present in a patient sample, it is necessary to know which mutations have important roles in the development of the corresponding cancer type. Named entity recognition (NER) is a core step in the text mining pipeline which facilitates mining valuable cancer information from the scientific literature. However, due to the scarcity of related datasets, previous NER attempts in this domain either suffer from low performance when deep learning based models are deployed, or they apply feature-based machine learning models or rule-based models to tackle this problem, which requires intensive efforts from domain experts, and limit the model generalization capability. In this paper, we propose EPICURE, an ensemble pre-trained model equipped with a conditional random field pattern (CRF) layer and a span prediction pattern (Span) layer to extract cancer mutations from text. We also adopt a data augmentation strategy to expand our training set from multiple datasets. Experimental results on three benchmark datasets show competitive results compared to the baseline models, validating our model's effectiveness and advances in generalization capability.

Background: The female breast comes in many different shapes and sizes. The literature remains inconclusive on the ideal breast size. This study aims to investigate and compare breast size preferences among three cohorts (patients, plastic surgeons, and laypeople) to provide a better understanding of Western European ideals. Methods: Patients, plastic surgeons, and laypeople were interviewed using a survey containing three-dimensional simulations of nine females, each depicted using five simulations with increasing breast size (1 = natural breast without breast implants, 2 = moderate, 3 = moderate plus, 4 = high, and 5 = ultra-high). Linear regression models were performed to define statistically significant associations between preferred breast size and predictor variables. Results: In total, 28 patients, 45 plastic surgeons, and 100 laypeople (50 males and 50 females) participated in this study. On average, patients (3.5 ± 0.7) preferred larger breast sizes compared to surgeons (3.0 ± 0.7) and laypeople (3.1 ± 0.8). The difference between patients and surgeons was statistically significant. Overall, males preferred larger breast sizes than women. Patients of older age and with a higher BMI preferred larger breast sizes, while higher educational level was significantly associated with smaller breast size preference. Female plastic surgeons would undergo breast augmentation, while male plastic surgeons and female lay participants seem more skeptical. Conclusions: Significant preferential differences exist between patients and surgeons. It is important for professionals to be aware of societal ideals and preferential differences to adequately consult patients and achieve more satisfactory results.

Purpose Women at increased familial breast cancer risk have been offered screening starting at an earlier age and increased frequency than national Screening Programmes for over 30 years. There are limited data on longer-term largescale implementation of this approach on cancer diagnosis. Methods Women at our institution at ≥ 17% lifetime breast cancer risk have been offered enhanced screening with annual mammography starting at age 35 or 5-years younger than youngest affected relative, with upper age limit 50 for moderate and 60 for high-risk. Breast cancer pathology, stage and receptor status were assessed as well as survival from cancer diagnosis by Kaplan–Meier analysis. Results Overall 14,311 women were seen and assessed for breast cancer risk, with 649 breast cancers occurring in 129,119 years follow up (post-prevalent annual incidence = 4.55/1000). Of 323/394 invasive breast cancers occurring whilst on enhanced screening, most were lymph-node negative (72.9%), T1 (≤ 20 mm, 73.2%) and stage-1 (61.4%), 126/394 stage2–4 (32%). 10-year breast cancer specific survival was 91.3% (95% CI 87.4–94.0) better than the 75.9% (95% CI 74.9–77.0) published for England in 2013–2017. As expected, survival was significantly better for women with screen detected cancers (p n = 75; 95% CI 84.2–97.6). Women with lobular breast cancers had worse 10-year survival at 85.9% (95% CI 66.7–94.5). Breast cancer specific survival was good for 119 BRCA1/2 carriers with 20-year survival in BRCA1:91.2% (95% CI 77.8–96.6) and 83.8% (62.6–93.5) for BRCA2. Conclusions Targeted breast screening in women aged 30–60 years at increased familial risk is associated with good long-term survival that is substantially better than expected from population data.

Purpose: Lobular breast cancer (LBC) accounts for ~ 15% of breast cancer. Here, we studied the frequency of pathogenic germline variants (PGVs) in an extended panel of genes in women affected with LBC. Methods: 302 women with LBC and 1567 without breast cancer were tested for BRCA1/2 PGVs. A subset of 134 LBC affected women who tested negative for BRCA1/2 PGVs underwent extended screening, including: ATM, CDH1, CHEK2, NBN, PALB2, PTEN, RAD50, RAD51D, and TP53.Results: 35 PGVs were identified in the group with LBC, of which 22 were in BRCA1/2. Ten actionable PGVs were identified in additional genes (ATM(4), CDH1(1), CHEK2(1), PALB2(2) and TP53(2)). Overall, PGVs in three genes conferred a significant increased risk for LBC. Odds ratios (ORs) were: BRCA1: OR = 13.17 (95%CI 2.83–66.38; P = 0.0017), BRCA2: OR = 10.33 (95%CI 4.58–23.95; P ATM: OR = 8.01 (95%CI 2.52–29.92; P = 0.0053). We did not detect an increased risk of LBC for PALB2, CDH1 or CHEK2. Conclusion: The overall PGV detection rate was 11.59%, with similar rates of BRCA1/2 (7.28%) PGVs as for other actionable PGVs (7.46%), indicating a benefit for extended panel genetic testing in LBC. We also report a previously unrecognised association of pathogenic variants in ATM with LBC.

Organic solvent nanofiltration (OSN) is gradually expanding from academic research to industrial implementation. The need for membranes with low and sharp molecular weight cutoffs that are able to operate under aggressive OSN conditions is increasing. However, the lack of comparable and uniform performance data frustrates the screening and membrane selection for processes. Here, a collaboration is presented between several academic and industrial partners analyzing the separation performance of 10 different membranes using three model process mixtures. Membrane materials range from classic polymeric and thin film composites (TFCs) to hybrid ceramic types. The model solutions were chosen to mimic cases relevant to today's industrial use: relatively low molar mass solutes (330–550 Da) in n-heptane, toluene, and anisole.

Layperson assessments are becoming increasingly important in the evaluation of surgical procedures of the face, including smile reanimation. In this study, the authors set out to answer 3 questions: (1) are esthetic scores more dependent on the assessor or the person that is being assessed, (2) how does smile reanimation change esthetic scores, (3) do sex and age of the patient and assessor explain some of the esthetic outcomes?Thirty-five assessors scored pre and postoperative photographs of 21 facial palsy patients undergoing smile reanimation. Linear mixed-effect models were used to investigate the effects of assessor and patient factors on esthetic outcome assessments, to examine changes after smile reanimation, and to determine whether sex and age explained part of the esthetic outcomes.Fifty-eight percent of variation in the esthetic scores can be explained by some assessors being more positive in their esthetic scoring compared to other assessors. Twenty-nine percent was attributed to patient baseline esthetic scores. Overall esthetic scores improved after smile reanimation. Sex and age of the patient and assessor could not explain variation in the esthetic scores.Esthetic appearance highly depends on "who is looking.'' These findings are important for preoperative counseling, and for those treating and educating patients with facial palsy.

In the present work, the potential of polyPOSS-imide membranes designed for the purification of H2 from a coke gas (utilized in the steelmaking industry) is investigated. Aiming at upscaling the membrane fabrication, tubular single-channel and multi-channel membranes were prepared, using polyhedral oligomeric silsesquioxane (POSS) nanostructures and 6FDA as reactive precursors. The gas separation performance has been investigated by means of single gas and quaternary (H2, CH4, CO2, N2) mixtures, the latter used to simulate the conditions expected at the membrane module inlet in the process of upgrading H2 from a coke oven gas. Preliminary results obtained on tubular membranes showed that the fabricated membranes can achieve high H2 permeance (>2000 GPU), displaying also suitable selectivity towards CO2, N2 and CH4. The selectivity of these upscaled tubular membrane samples meets the performance of those previously obtained for the disc-shaped lab-scale membranes. These results revealed the promising potential in the upscaling of polyPOSS-imide membranes fabricated via interfacial polymerization on ceramic porous supports for H2 upgrading.

Previous research has shown that polygenic risk scores (PRSs) can be used to stratify women according to their risk of developing primary invasive breast cancer. This study aimed to evaluate the association between a recently validated PRS of 313 germline variants (PRS313) and contralateral breast cancer (CBC) risk. We included 56,068 women of European ancestry diagnosed with first invasive breast cancer from 1990 onward with follow-up from the Breast Cancer Association Consortium. Metachronous CBC risk (N = 1,027) according to the distribution of PRS313 was quantified using Cox regression analyses. We assessed PRS313 interaction with age at first diagnosis, family history, morphology, ER status, PR status, and HER2 status, and (neo)adjuvant therapy. In studies of Asian women, with limited follow-up, CBC risk associated with PRS313 was assessed using logistic regression for 340 women with CBC compared with 12,133 women with unilateral breast cancer. Higher PRS313 was associated with increased CBC risk: hazard ratio per standard deviation (SD) = 1.25 (95%CI = 1.18-1.33) for Europeans, and an OR per SD = 1.15 (95%CI = 1.02-1.29) for Asians. The absolute lifetime risks of CBC, accounting for death as competing risk, were 12.4% for European women at the 10th percentile and 20.5% at the 90th percentile of PRS313. We found no evidence of confounding by or interaction with individual characteristics, characteristics of the primary tumor, or treatment. The C-index for the PRS313 alone was 0.563 (95%CI = 0.547-0.586). In conclusion, PRS313 is an independent factor associated with CBC risk and can be incorporated into CBC risk prediction models to help improve stratification and optimize surveillance and treatment strategies. ispartof: AMERICAN JOURNAL OF HUMAN GENETICS vol:107 issue:5 pages:837-848 ispartof: location:United States status: published

Little is known about facial function assessments of inexperienced observers in facial palsy. In this observational study learning curve was examined of two inexperienced observers assessing facial function of 100 patients using the Sunnybrook Facial Grading System. Interobserver agreement gradually improved over time, stabilizing after approximately 70 assessments. Best agreement on the voluntary movement subscore was observed, followed by synkinesis and resting symmetry subscores. Inexperienced observers can perform facial function assessments in facial palsy, but should be adequately trained first.

Background Sleep disorders are a risk factor for developing a variety of mental disorders, have a negative impact on their remission rates and increase the risk of relapse. Early identification and treatment of sleep disorders is therefore of paramount importance. Unfortunately, in mental health care sleep disorders are often poorly recognized and specific treatment frequently occurs late or not at all. This protocol-paper presents a randomized controlled trial investigating the clinical relevance of early detection and treatment of sleep disorders in mental health care. The two aims of this project are 1) to determine the prevalence of sleep disorders in different mental disorders, and 2) to investigate the contribution of early identification and adequate treatment of sleep disorders in individuals with mental disorders to their sleep, mental disorder symptoms, general functioning, and quality of life. Methods Patients newly referred to a Dutch mental health institute for psychiatric treatment will be screened for sleep disorders with the self-assessment Holland Sleep Disorders Questionnaire (HSDQ). Patients scoring above the cut-off criteria will be invited for additional diagnostic evaluation and, treatment of the respective sleep disorder. Participants will be randomly assigned to two groups: Immediate sleep diagnostics and intervention (TAU+SI-T0), or delayed start of sleep intervention (TAU+SI-T1; 6 months after inclusion). The effect of sleep treatment as add-on to treatment as usual (TAU) will be tested with regard to sleep disorder symptoms, general functioning, and quality of life (in collaboration with a psychiatric sleep centre). Discussion This trial will examine the prevalence of different sleep disorders in a broad range of mental disorders, providing information on the co-occurrence of specific sleep and mental disorders. Further, this study is the first to investigate the impact of early treatment of sleep disorders on the outcome of many mental disorders. Moreover, standard sleep interventions will be tailored to specific mental disorders, to increase their efficacy. The results of this trial may contribute considerably to the improvement of mental health care. Trial registration This clinical trial has been retrospectively registered in the Netherlands Trial Register (NL8389; https://www.trialregister.nl/trial/8389) on February 2th, 2020.

Three-dimensional stereophotogrammetry is not much used in assessing facial palsy and a comprehensive understanding of sources of variation in these measurements is lacking. The present study assessed intra- and interobserver reliability of a novel three-dimensional stereophotogrammetry measurement of facial asymmetry and examined sources of variation in these outcomes. Three photographs (rest, closed mouth smile, and maximum smile) were made of 60 participants, 30 facial palsy patients and 30 control subjects. All images were analyzed twice by 2 observers independently, to determine intra- and interobserver reliability. Variance component analysis was performed to investigate sources of variation in the outcomes. Intraobserver reliability was good with intraclass correlation coefficients ranging from 0.715 to 0.999. Interobserver reliability ranged from 0.442 to 0.929. Reliability of the smile image measurements was not clearly different from the rest images. Variation in measurement results was largely due to the status of a participant, facial palsy versus control. When splitting the sample, the facial expression was a major source of variation. Acceptable reliability of the proposed 3D facial asymmetry measurement was found, in facial palsy patients and control subjects. Interobserver reliability was marked less compared to intraobserver reliability. For follow-up data only one observer should assess 3D stereophotogrammetry measurements.

Background Parotidectomy in melanoma of the coronal scalp and face with clinically involved cervical lymph node metastasis is based on predicted cervical lymphatic drainage described by O'Brien. Methods In total, 40 parotidectomies with en bloc therapeutic neck dissection were retrospectively analyzed. Results Lymphatic spread of melanoma to the parotid lymph nodes was observed in 10 of 40 specimens (25%). Eight of the 10 parotid-positive patients developed a recurrence vs 17 of the 30 parotid-negative patients (P = 0.28). There were no differences in overall survival, melanoma-specific survival, and disease-free survival between the parotid-positive and parotid-negative patients. Conclusion Although in this series no survival differences were found, parotidectomy still merits a sustained role in therapeutic neck dissection procedures to improve regional control and to prevent facial nerve damage after surgery for a second relapse from occult metastases in the parotid.

Nephroblastomatosis is a recognised precursor for the development of Wilms tumour (WT), the most common childhood renal tumour. While the majority of WT is sporadic in origin, germline intragenic mutations of predisposition genes such asTo highlight the role of a constitutional deletion CNV (delCNV) encompassing theArray comparative genomic hybridisation in an infant presenting with apparently sporadic diffuse HPLN revealed a de novo germline CNV, arr[GRCh37] 4q12(57,385,330-57,947,405)x1. TheThis delCNV encompassing