Histological features of melanoma associated with CDKN2A genotype

Background: Inherited susceptibility genes have been associated with histopathologic characteristics of tumors. Objective: We sought to identify associations between histology of melanomas and CDKN2A genotype. Methods: This was a case-control study design comparing 28 histopathologic tumor features among individuals with sporadic melanomas (N = 81) and cases from melanoma families with (N = 123) and without (N = 120) CDKN2A germline mutations. Results: Compared with CDKN2A− cases, mutation carriers tended to have histologic features of superficial spreading melanoma subtype including higher pigmentation (Ptrend = .02) and increased pagetoid scatter (Ptrend = .07) after adjusting for age at diagnosis, sex, and American Joint Committee on Cancer thickness category. Similar associations were observed when comparing mutation carriers with a combined group of CDKN2A− (wild type) and sporadic melanomas. The presence of spindle cell morphology in the vertical growth phase was also an important predictor of genotype. Of the 15 cases with this phenotype, none were observed to harbor a CDKN2A mutation. Limitations: Our study examined rare mutations and may have been underpowered to detect small, but biologically significant associations between histology and genotype. Conclusion: Familial melanomas with CDKN2A mutations preferentially express a histologic phenotype of dense pigmentation, high pagetoid scatter, and a non-spindle cell morphology in the vertical growth phase

Canonical Wnt signals combined with suppressed TGFβ/BMP pathways promote renewal of the native human colonic epithelium

Background: A defining characteristic of the human intestinal epithelium is that it is the most rapidly renewing tissue in the body. However, the processes underlying tissue renewal and the mechanisms that govern their coordination have proved difficult to study in the human gut. Objective: To investigate the regulation of stem cell-driven tissue renewal by canonical Wnt and TGFβ/bone morphogenetic protein (BMP) pathways in the native human colonic epithelium. Design: Intact human colonic crypts were isolated from mucosal tissue samples and placed into 3D culture conditions optimised for steady-state tissue renewal. High affinity mRNA in situ hybridisation and immunohistochemistry were complemented by functional genomic and bioimaging techniques. The effects of signalling pathway modulators on the status of intestinal stem cell biology, crypt cell proliferation, migration, differentiation and shedding were determined. Results: Native human colonic crypts exhibited distinct activation profiles for canonical Wnt, TGFβ and BMP pathways. A population of intestinal LGR5/OLFM4-positive stem/progenitor cells were interspersed between goblet-like cells within the crypt-base. Exogenous and crypt cell-autonomous canonical Wnt signals supported homeostatic intestinal stem/progenitor cell proliferation and were antagonised by TGFβ or BMP pathway activation. Reduced Wnt stimulation impeded crypt cell proliferation, but crypt cell migration and shedding from the crypt surface were unaffected and resulted in diminished crypts. Conclusions: Steady-state tissue renewal in the native human colonic epithelium is dependent on canonical Wnt signals combined with suppressed TGFβ/BMP pathways. Stem/progenitor cell proliferation is uncoupled from crypt cell migration and shedding, and is required to constantly replenish the crypt cell population

Association of germline variants in telomere maintenance genes (POT1, TERF2IP, ACD, and TERT) with spitzoid morphology in familial melanoma: A multi-center case series

Spitzoid morphology in familial melanoma has been associated with germline variants in POT1, a telomere maintenance gene (TMG), suggesting a link between telomere biology and spitzoid differentiation. The aim is to assess if familial melanoma cases associated with germline variants in TMG (POT1, ACD, TERF2IP, and TERT ) commonly exhibit spitzoid morphology.Medicin

Fasting and surgery timing (FaST) audit

Background & aimsInternational guidance advocates the avoidance of prolonged preoperative fasting due to its negative impact on perioperative hydration. This study aimed to assess the adherence to these guidelines for fasting in patients undergoing elective and emergency surgery in the East Midlands region of the UK.MethodsThis prospective audit was performed over a two-month period at five National Health Service (NHS) Trusts across the East Midlands region of the UK. Demographic data, admission and operative details, and length of preoperative fasting were collected on adult patients listed for emergency and elective surgery.ResultsOf the 343 surgical patients included within the study, 50% (n = 172) were male, 78% (n = 266) had elective surgery and 22% (n = 77) underwent emergency surgery. Overall median fasting times (Q1, Q3) were 16.1 (13.0, 19.4) hours for food and 5.8 (3.5, 10.7) hours for clear fluids. Prolonged fasting >12 h was documented in 73% (n = 250) for food, and 21% (n = 71) for clear fluids. Median fasting times from clear fluids and food were longer in the those undergoing emergency surgery when compared with those undergoing elective surgery: 13.0 (6.4, 22.6) vs. 4.9 (3.3, 7.8) hours, and 22.0 (14.0, 37.4) vs. 15.6 (12.9, 17.8) hours respectively, p < 0.0001.ConclusionsDespite international consensus on the duration of preoperative fasting, patients continue to fast from clear fluids and food for prolonged lengths of time. Patients admitted for emergency surgery were more likely to fast for longer than those having elective surgery

Warm, Humid, and High Sun Exposure Climates Are Associated with Poorly Controlled Eczema: PEER (Pediatric Eczema Elective Registry) Cohort, 2004–2012

Anecdotal reports of children experiencing eczema flares during winter and summer months along with global variation in eczema prevalence has fueled speculation that climate may modulate disease activity. The aim of this study was to determine whether long-term weather patterns affect the severity and persistence of eczema symptoms in children. We performed a prospective cohort study of US children (N=5,595) enrolled in PEER (Pediatric Eczema Elective Registry) between 2004 and 2012 to evaluate the effect of climate (daily temperature, daily sun exposure, daily humidity) on the severity of eczema symptoms. Odds ratios (ORs) were calculated for the patient-evaluated outcome of disease control. Multivariate logistic regression modeling adjusting for gender, race, income, and topical medication use demonstrated that higher temperature (OR=0.90, 95% confidence interval (CI): 0.87–0.93, P<0.001) and increased sun exposure (OR=0.93, 95% CI: 0.89–0.98, P=0.009) were associated with poorly controlled eczema. Higher humidity (OR=0.90, 95% CI: 0.812–0.997, P=0.04) was also associated with poorly controlled disease, but the statistical significance of this association was lost in our multivariate analysis (P=0.44)

Future growth of physicians and non-physician providers within the U.S. Dermatology workforce

Trends in the training, supply, availability, career decisions, and retirement of US dermatology physicians are not well delineated. The current study evaluates whether growth in the dermatology workforce will keep pace with population expansion in the United States. A dermatologist supply model was projected to 2030 drawing on data from the American Academy of Dermatology, American Medical Association, Bureau of Labor Statistics, American Association of Medical Colleges, and other associations. The clinically active dermatologist workforce in 2015 was 36 per capita (1,000,000); entry following postgraduate training was age 30 with career separation at age 65 on average. Added to the provider model are physician assistants and nurse practitioners in dermatology practices. A linear regression micro simulation model based on age cohorts produced a per capita supply of dermatology providers of 61 (±3) per 1,000,000 by 2030, up from 47 in 2016. The dermatology workforce is growing faster than population expansion. Workforce estimates could be affected by changing trends in retirement and training of dermatology providers. Investments in training of nurse practitioners and physician assistants, in addition to training more doctors, may be an effective strategy for increasing access to care in populations with low dermatologist density

Future growth of physicians and non-physician providers within the U.S. Dermatology workforce

Trends in the training, supply, availability, career decisions, and retirement of US dermatology physicians are not well delineated. The current study evaluates whether growth in the dermatology workforce will keep pace with population expansion in the United States. A dermatologist supply model was projected to 2030 drawing on data from the American Academy of Dermatology, American Medical Association, Bureau of Labor Statistics, American Association of Medical Colleges, and other associations. The clinically active dermatologist workforce in 2015 was 36 per capita (1,000,000); entry following postgraduate training was age 30 with career separation at age 65 on average. Added to the provider model are physician assistants and nurse practitioners in dermatology practices. A linear regression micro simulation model based on age cohorts produced a per capita supply of dermatology providers of 61 (±3) per 1,000,000 by 2030, up from 47 in 2016. The dermatology workforce is growing faster than population expansion. Workforce estimates could be affected by changing trends in retirement and training of dermatology providers. Investments in training of nurse practitioners and physician assistants, in addition to training more doctors, may be an effective strategy for increasing access to care in populations with low dermatologist density