Project description:ImportanceThe incidence of skin cancer is increasing and evaluation of the utility of total body skin examination (TBSE) in detecting incidental skin cancers is warranted.ObjectivesTo evaluate the proportion and rate of incidental skin cancer detection in urgent skin cancer clinics and investigate the rate of incidental skin cancer detection in 2 groups based on the degree of clinical suspicion of the index lesion for malignancy.Design, setting, and participantsA multicenter retrospective cohort study with a case note review of consecutive secondary care consultations was conducted using data from 2 urgent suspected skin cancer screening clinics in UK National Health Service trusts. The study was performed from January 1, 2015, to March 31, 2016, and data analysis was performed from October 14, 2018, to February 1, 2019. Patients included those presenting with a skin lesion suspicious of malignancy who were referred to the urgent suspected skin cancer clinic (N = 5944) over 15 months. Patients who accepted and received a TBSE were subsequently included in the analysis.Main outcomes and measuresThe proportion and rate of incidental skin cancer detection through TBSE and whether a clinically suspicious (malignant) index lesion was associated with a higher chance of having a malignant incidental lesion.ResultsOf the 5944 patients referred to the clinic, 4726 individuals (79.5%) were evaluated. In the cohort included in the analyses, the median age was 57 years (interquartile range, 39-73 years); 2567 patients (54.3%) were women. A total of 1117 skin cancers were identified; of these, 242 lesions (21.7%) were detected incidentally through TBSE, including 197 of 570 (34.6%) basal cell carcinomas, 16 of 250 (6.4%) squamous cell carcinomas, and 25 of 215 (11.6%) melanomas. The detection rate of incidental malignant lesions was 5.1 lesions per 100 patients examined (5.1%; 95% CI, 4.5%-5.8%). There was a higher detection rate of histologically confirmed incidental malignant lesions in individuals with clinically suspicious index lesions requiring biopsy (10.9%; 95% CI, 9.5%-12.5%) compared with those presenting with clinically benign index lesions (2.0%; 95% CI, 1.6%-2.5%) (P < .001).Conclusions and relevanceThe findings of this study support the use of TBSE for urgent skin cancer referrals, highlighting the potential harms of solitary lesion assessment in a subgroup. Individuals presenting with a clinically suspicious index lesion requiring biopsy are most likely to benefit from TBSE and should be counseled regarding the benefit.
Project description:BackgroundOlder adults with bacterial skin infections may present with atypical symptoms, making diagnosis difficult. There is limited authoritative guidance on how older adults in the community present with bacterial skin infections. To date there have been no systematic reviews assessing the diagnostic value of symptoms and signs in identifying bacterial skin infections in older adults in the community.MethodsWe searched Medline and Medline in process, Embase and Web of Science, from inception to September 2017. We included cohort and cross-sectional studies assessing the diagnostic accuracy of symptoms and signs in predicting bacterial skin infections in adults in primary care aged over 65?years. The QUADAS-2 tool was used to assess study quality.ResultsWe identified two observational studies of low-moderate quality, with a total of 7991 participants, providing data to calculate the diagnostic accuracy of 5 unique symptoms in predicting bacterial skin infections. The presence of wounds [LR+: 7.93 (CI 4.81-13.1)], pressure sores [LR+: 4.85 (CI 2.18-10.8)] and skin ulcers [LR+: 6.26 (CI 5.49-7.13)] help to diagnose bacterial skin infections. The presence of urinary incontinence does not help to predict bacterial skin infections (LR?+?'s of 0.99 and 1.04; LR-'s of 0.96 and 1.04).ConclusionsCurrently, there is insufficient evidence to inform the diagnosis of bacterial skin infections in older adults in the community; clinicians should therefore rely upon their clinical judgement and experience. Evidence from high quality primary care studies in older adults, including studies assessing symptoms traditionally associated with bacterial skin infections (e.g. erythema and warmth), is urgently needed to guide practice.
Project description:There is strong evidence for a role of environmental risk factors involved in susceptibility to develop multiple keratinocyte cancers (mKCs), but whether genes are also involved in mKCs susceptibility has not been thoroughly investigated. We investigated whether single nucleotide polymorphisms (SNPs) are associated with susceptibility for mKCs. A genome-wide association study (GWAS) of 1,666 cases with mKCs and 1,950 cases with single KC (sKCs; controls) from Harvard cohorts (the Nurses' Health Study [NHS], NHS II, and the Health Professionals Follow-Up Study) and the Framingham Heart Study was carried-out using over 8 million SNPs (stage-1). We sought to replicate the most significant statistical associations (p-value? 5.5x10-6) in an independent cohort of 574 mKCs and 872 sKCs from the Rotterdam Study. In the discovery stage, 40 SNPs with suggestive associations (p-value ?5.5x10-6) were identified, with eight independent SNPs tagging all 40 SNPs. The most significant SNP was located at chromosome 9 (rs7468390; p-value = 3.92x10-7). In stage-2, none of these SNPs replicated and only two of them were associated with mKCs in the same direction in the combined meta-analysis. We tested the associations for 19 previously reported basal cell carcinoma-related SNPs (candidate gene association analysis), and found that rs1805007 (MC1R locus) was significantly associated with risk of mKCs (p-value = 2.80x10-4). Although the suggestive SNPs with susceptibility for mKCs were not replicated, we found that previously identified BCC variants may also be associated with mKC, which the most significant association (rs1805007) located at the MC1R gene.
Project description:Visual inspection with Acetic Acid (VIA) and Visual Inspection with Lugol’s Iodine (VILI) are increasingly recommended in various cervical cancer screening protocols in low-resource settings. Although VIA is more widely used, VILI has been advocated as an easier and more specific screening test. VILI has not been well-validated as a stand-alone screening test, compared to VIA or validated for use in HIV-infected women. We carried out a randomized clinical trial to compare the diagnostic accuracy of VIA and VILI among HIV-infected women. Women attending the Family AIDS Care and Education Services (FACES) clinic in western Kenya were enrolled and randomized to undergo either VIA or VILI with colposcopy. Lesions suspicious for cervical intraepithelial neoplasia 2 or greater (CIN2+) were biopsied. Between October 2011 and June 2012, 654 were randomized to undergo VIA or VILI. The test positivity rates were 26.2% for VIA and 30.6% for VILI (p = 0.22). The rate of detection of CIN2+ was 7.7% in the VIA arm and 11.5% in the VILI arm (p = 0.10). There was no significant difference in the diagnostic performance of VIA and VILI for the detection of CIN2+. Sensitivity and specificity were 84.0% and 78.6%, respectively, for VIA and 84.2% and 76.4% for VILI. The positive and negative predictive values were 24.7% and 98.3% for VIA, and 31.7% and 97.4% for VILI. Among women with CD4+ count < 350, VILI had a significantly decreased specificity (66.2%) compared to VIA in the same group (83.9%, p = 0.02) and compared to VILI performed among women with CD4+ count ? 350 (79.7%, p = 0.02). VIA and VILI had similar diagnostic accuracy and rates of CIN2+ detection among HIV-infected women.
Project description:Deciphering absolute configuration of a single molecule by direct visual inspection is the next step in compound identification, with far-reaching implications for medicinal chemistry, pharmacology, and natural product synthesis. We demonstrate the feasibility of this approach utilizing low temperature atomic force microscopy (AFM) with a CO-functionalized tip to determine the absolute configuration and orientation of a single, adsorbed [123]tetramantane molecule, the smallest chiral diamondoid. We differentiate between single enantiomers on Cu(111) by direct visual inspection, and furthermore identify molecular dimers and molecular clusters. The experimental results are confirmed by a computational study that allowed quantification of the corresponding intermolecular interactions. The unique toolset of absolute configuration determination combined with AFM tip manipulation opens a route for studying molecular nucleation, including chirality-driven assembly or reaction mechanisms.
Project description:In the present study, we evaluated the effect of deleting Twist1 on keratinocyte proliferation and on skin tumor development using the two-stage chemical carcinogenesis model. BK5.Cre?×?Twist1(flox/flox) mice, which have a keratinocyte-specific Twist1 knockout (Twist1 KO), developed significantly reduced numbers of papilloma (70% reduction) and squamous cell carcinoma (75% reduction) as well as delayed tumor latency compared to wild-type (WT) mice. Interestingly, knockdown of Twist1 in primary keratinocytes impeded cell cycle progression at the G1/S transition that coincided with reduced levels of the cell cycle proteins c-Myc, Cyclin E1, and E2F1 and increased levels of p53 and p21. Furthermore, ChIP analyses revealed that Twist1 bound to the promoter regions of Cyclin E1, E2F1, and c-Myc at the canonical E-box binding motif suggesting a direct transcriptional regulation. Further analyses of Twist1 KO mice revealed a significant reduction in the number of label-retaining cells as well as the number of ?6-integrin(+) /CD34(+) cells in the hair follicles of untreated mice compared to WT mice. These mice also exhibited significantly reduced epidermal proliferation in response to TPA treatment that again correlated with reduced levels of cell cycle regulators and increased levels of p53 and p21. Finally, Twist1 deficiency in keratinocytes led to an upregulation of p53 via its stabilization and nuclear localization, which is responsible for the increased expression of p21 in these cells. Collectively, these findings indicate that Twist1 has a novel role in epithelial carcinogenesis by regulating proliferation of keratinocytes, including keratinocyte stem cells during tumor promotion.
Project description:A variety of well-characterized cutaneous paraneoplastic syndromes (PNS) are diagnosed during internal malignancies; however, the spectrum of keratinocyte skin neoplasms (KSC) related to PNS is still obscure. The aim of the present review is to compile and evaluate the literature data on PNS associated with a keratinocyte skin neoplasm (KSC). Employing Pubmed, MEDLINE was searched for KSC-associated PNS reports. Forty relevant entries were assembled, reporting a total of 41 PNS cases associated with a KSC (34 male). No review paper compiling this topic was found. Six distinct PNS entities were identified, and malignancy associated hypercalcemia (MAH; 78%), anemia (10%) and Bazex syndrome (5%) were the most frequently reported among them. 85% of the PNS were reported in association with SCC, 10% with BCC, and the rest with adnexal tumors. The median age of the patients at the time of PNS diagnosis was 58 years (range: five-83 years). In most cases the PNS was diagnosed either concurrently or after the KSC diagnosis. KSC predisposing conditions, as scars (22%) or hidradenitis suppurativa (20%), were reported in >70% of the PNS cases. Most PNS resolved after KSC treatment. In conclusion, PNS of a rather limited spectrum of entities are reported in association with KSC. They also seem to be rare, possibly reflecting a limited capacity of KSC to provoke overt PNS.
Project description:Behavior analysts commonly use visual inspection to analyze single-case graphs, but studies on its reliability have produced mixed results. To examine this issue, we compared the Type I error rate and power of visual inspection with a novel approach-machine learning. Five expert visual raters analyzed 1,024 simulated AB graphs, which differed on number of points per phase, autocorrelation, trend, variability, and effect size. The ratings were compared to those obtained by the conservative dual-criteria method and two models derived from machine learning. On average, visual raters agreed with each other on only 75% of graphs. In contrast, both models derived from machine learning showed the best balance between Type I error rate and power while producing more consistent results across different graph characteristics. The results suggest that machine learning may support researchers and practitioners in making fewer errors when analyzing single-case graphs, but replications remain necessary.