Desmoplastic melanomas are uncommon. Their behaviour differs from that of other melanoma subtypes; therefore, management guidelines for non‐desmoplastic melanomas may not be applicable. This review ...sought to examine all available evidence relating to the behaviour and management of desmoplastic melanomas, based on review of all relevant English‐language publications, and to critically assess the recommendations for their management in current published melanoma management guidelines. Compared with other melanoma subtypes, patients with ‘pure’ desmoplastic melanomas (where ≥90% of the invasive melanoma is of desmoplastic melanoma subtype) have much lower rates of sentinel node positivity and distant metastasis. Local recurrence rates are higher for desmoplastic melanomas, but resection margins wider than those recommended for non‐desmoplastic melanomas have not been shown to be of benefit. Adjuvant radiotherapy reduces the risk of local recurrence when a satisfactory histological clearance (≥8 mm) cannot be achieved. Of 29 published melanoma management guidelines identified, only 11 specified management for desmoplastic melanomas, while seven simply stated that the feature should be reported. Desmoplastic melanoma is a unique melanoma subtype with biology that differs from that of other melanoma subtypes. It requires specific management strategies but few current guidelines address these.
Aims
To investigate the effect of kisspeptin on glucose‐stimulated insulin secretion and appetite in humans.
Materials and methods
In 15 healthy men (age: 25.2 ± 1.1 years; BMI: 22.3 ± 0.5 kg m−2), ...we compared the effects of 1 nmol kg−1 h−1 kisspeptin versus vehicle administration on glucose‐stimulated insulin secretion, metabolites, gut hormones, appetite and food intake. In addition, we assessed the effect of kisspeptin on glucose‐stimulated insulin secretion in vitro in human pancreatic islets and a human β‐cell line (EndoC‐βH1 cells).
Results
Kisspeptin administration to healthy men enhanced insulin secretion following an intravenous glucose load, and modulated serum metabolites. In keeping with this, kisspeptin increased glucose‐stimulated insulin secretion from human islets and a human pancreatic cell line in vitro. In addition, kisspeptin administration did not alter gut hormones, appetite or food intake in healthy men.
Conclusions
Collectively, these data demonstrate for the first time a beneficial role for kisspeptin in insulin secretion in humans in vivo. This has important implications for our understanding of the links between reproduction and metabolism in humans, as well as for the ongoing translational development of kisspeptin‐based therapies for reproductive and potentially metabolic conditions.
We examine the relation between polycyclic aromatic hydrocarbon (PAH) emission at 8 μm and far-infrared emission from hot dust grains at 24 μm and from large dust grains at 160 and 250 μm in the ...nearby spiral galaxies NGC 2403 and M83 using data from the Spitzer Space Telescope and Herschel Space Observatory. We find that the PAH emission in NGC 2403 is better correlated with emission at 250 μm from dust heated by the diffuse interstellar radiation field (ISRF) and that the 8/250-μm surface brightness ratio is well correlated with the stellar surface brightness as measured at 3.6 μm. This implies that the PAHs in NGC 2403 are intermixed with cold large dust grains in the diffuse interstellar medium (ISM) and that the PAHs are excited by the diffuse ISRF. In M83, the PAH emission appears more strongly correlated with 160 μm emission originating from large dust grains heated by star-forming regions. However, the PAH emission in M83 is low where the 24-μm emission peaks within star-forming regions, and enhancements in the 8/160-μm surface brightness ratios appear offset relative to the dust and the star-forming regions within the spiral arms. This suggests that the PAHs observed in the 8 μm band are not excited locally within star-forming regions but either by light escaping non-axisymmetrically from star-forming regions or locally by young, non-photoionizing stars that have migrated downstream from the spiral density waves. The results from just these two galaxies show that PAHs may be excited by different stellar populations in different spiral galaxies.
Summary
Background
Allergic contact dermatitis (ACD) to cosmetics is widely reported. To ensure we are accurately diagnosing ACD, patch test series should be continually reviewed to identify relevant ...and emerging allergens and highlight those that are outdated. The current British Society for Cutaneous Allergy (BSCA) facial series recommends 26 allergens and was last modified in 2012.
Objectives
To review and update the BSCA facial series.
Methods
We retrospectively reviewed the results from 12 UK and Ireland patch test centres’ facial series from January 2016 to December 2017. We recorded the number of allergens tested in each centre and the detection rate for each allergen. Using a 0·3% positive rate as the inclusion threshold, we established which allergens in the BSCA facial series had positive patch test rates < 0·3% and > 0·3%. Allergens not in the BSCA facial series that had a positive patch test rate > 0·3% were identified.
Results
Overall, 4224 patients were patch tested to the facial series. The number of allergens included in individual centres’ facial series ranged from 24 to 66, with a total of 103 allergens tested across all centres. Twelve of the 26 allergens in the BSCA facial series had a positive patch test rate < 0·3% and 14 had a rate > 0·3%. Twenty‐five allergens not recommended in the BSCA facial series had a positive patch test rate > 0·3%.
Conclusions
This audit has highlighted the significant variation in practice that exists among patch test centres, despite a recommended facial series. The BSCA facial series has been updated and now contains 24 allergens. Fifteen allergens remain, 11 allergens have been dropped and nine new allergens have been added.
What is already known about this topic?
Facial dermatitis is one of the dominant presenting complaints of allergic contact dermatitis to cosmetics.
To ensure we are accurately diagnosing contact allergy, it is important that we patch test with relevant allergens.
Reviewing current literature and auditing patch test practice is a vital requirement to ensure we identify relevant and emerging allergens and highlight those that are outdated.
What does this study add?
Despite recommended patch test series, there is significant variation in practice among different patch test centres.
In response to this multicentre audit, the British Society for Cutaneous Allergy facial series has been updated and now contains 24 allergens: 15 allergens remain, 11 allergens have been dropped and nine new allergens have been added.
Linked Comment: Boonchai. Br J Dermatol 2021; 184:13.
Plain language summary available online
Although acute urinary tract infections are common in young women, the associated risk factors have not been defined prospectively.
We recruited sexually active young women who were starting a new ...method of contraception at a university health center or a health maintenance organization (HMO) and monitored them for six months for symptomatic urinary tract infections. Daily diaries and serial interviews were used to collect data on potential risk factors.
Among 796 women, the incidence of urinary tract infections per person-year was 0.7 in the university cohort (mean age, 23 years; n = 348) and 0.5 in the HMO cohort (mean age, 29; n = 448). In both cohorts, there were strong dose-response relations between the risk of infection and both recent use of a diaphragm with spermicide (respective relative risks for one, three, and five days of use in the past week, 1.42, 2.83, and 5.68 in the university cohort, P<0.001; and 1.29, 2.14, and 3.54 in the HMO cohort, P=0.04) and recent sexual intercourse (respective relative risks for one, three, and five days with intercourse in the past week, 1.37, 2.56, and 4.81 in the university cohort, P<0.001; and 1.24, 1.91, and 2.96 in the HMO cohort, P=0.002). The risk of acute infection was also associated with a history of recurrent infection (relative risk, 5.58 in the university group and 2.10 in the HMO group) but not with cervical-cap use, ABO-blood-group nonsecretor phenotype, or delayed postcoital voiding.
Among sexually active young women the incidence of symptomatic urinary tract infection is high, and the risk is strongly and independently associated with recent sexual intercourse, recent use of a diaphragm with spermicide, and a history of recurrent urinary tract infections.
A 1995 report of the Intergovernmental Panel on Climate Change provides a set of illustrative anthropogenic CO2 emission models leading to stabilization of atmospheric CO2 concentrations ranging from ...350 to 1,000 p.p.m. Ocean carbon-cycle models used in calculating these scenarios assume that oceanic circulation and biology remain unchanged through time. Here we examine the importance of this assumption by using a coupled atmosphere-ocean model of global warming for the period 1765 to 2065. We find a large potential modification to the ocean carbon sink in a vast region of the Southern Ocean where increased rainfall leads to surface freshening and increased stratification. The increased stratification reduces the downward flux of carbon and the loss of heat to the atmosphere, both of which decrease the oceanic uptake of anthropogenic CO2 relative to a constant-climate control scenario. Changes in the formation, transport and cycling of biological material may counteract the reduced uptake, but the response of the biological community to the climate change is difficult to predict on present understanding. Our simulation suggests that such physical and biological changes might already be occurring, and that they could substantially affect the ocean carbon sink over the next few decades.
Abstract Background Osteogenesis imperfecta (OI), the commonest inherited bone fragility disorder, affects 1 in 15,000 live births resulting in frequent fractures and reduced mobility, with ...significant impact on quality of life. Early diagnosis is important, as therapeutic advances can lead to improved clinical outcome and patient benefit. Report Whole exome sequencing in patients with OI identified, in two patients with a multi-system phenotype, compound heterozygous variants in NBAS (neuroblastoma amplified sequence). Patient 1: NBAS c.5741G > A p.(Arg1914His); c.3010C > T p.(Arg1004*) in a 10-year old boy with significant short stature, bone fragility requiring treatment with bisphosphonates, developmental delay and immunodeficiency. Patient 2: NBAS c.5741G > A p.(Arg1914His); c.2032C > T p.(Glu678*) in a 5-year old boy with similar presenting features, bone fragility, mild developmental delay, abnormal liver function tests and immunodeficiency. Discussion Homozygous missense NBAS variants cause SOPH syndrome (short stature; optic atrophy; Pelger-Huet anomaly), the same missense variant was found in our patients on one allele and a nonsense variant in the other allele. Recent literature suggests a multi-system phenotype. In this study, patient fibroblasts have shown reduced collagen expression, compared to control cells and RNAseq studies, in bone cells show that NBAS is expressed in osteoblasts and osteocytes of rodents and primates. These findings provide proof-of-concept that NBAS mutations have mechanistic effects in bone, and that NBAS variants are a novel cause of bone fragility, which is distinguishable from ‘Classical’ OI. Conclusions Here we report on variants in NBAS , as a cause of bone fragility in humans, and expand the phenotypic spectrum associated with NBAS . We explore the mechanism underlying NBAS and the striking skeletal phenotype in our patients.
Much of routine cancer care has been disrupted due to the perceived susceptibility to SARS-CoV-2 infection in cancer patients. Here, we systematically review the current evidence base pertaining to ...the prevalence, presentation and outcome of COVID-19 in cancer patients, in order to inform policy and practice going forwards. A keyword-structured systematic search was conducted on Pubmed, Cochrane, Embase and MedRxiv databases for studies reporting primary data on COVID-19 in cancer patients. Studies were critically appraised using the NIH National Heart, Lung and Blood Institute's quality assessment tool set. The pooled prevalence of cancer as a co-morbidity in patients with COVID-19 and pooled in-hospital mortality risk of COVID-19 in cancer patients were derived by random-effects meta-analyses. In total, 110 studies from 10 countries were included. The pooled prevalence of cancer as a co-morbidity in hospitalised patients with COVID-19 was 2.6% (95% confidence interval 1.8%, 3.5%, I2: 92.0%). Specifically, 1.7% (95% confidence interval 1.3%, 2.3%, I2: 57.6.%) in China and 5.6% (95% confidence interval 4.5%, 6.7%, I2: 82.3%) in Western countries. Patients most commonly presented with non-specific symptoms of fever, dyspnoea and chest tightness in addition to decreased arterial oxygen saturation, ground glass opacities on computer tomography and non-specific changes in inflammatory markers. The pooled in-hospital mortality risk among patients with COVID-19 and cancer was 14.1% (95% confidence interval 9.1%, 19.8%, I2: 52.3%). We identified impeding questions that need to be answered to provide the foundation for an iterative review of the developing evidence base, and inform policy and practice going forwards. Analyses of the available data corroborate an unfavourable outcome of hospitalised patients with COVID-19 and cancer. Our findings encourage future studies to report detailed social, demographic and clinical characteristics of cancer patients, including performance status, primary cancer type and stage, as well as a history of anti-cancer therapeutic interventions.
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