Background
Merkel cell carcinoma (MCC) is a rare aggressive neuroectodermal skin cancer with a high recurrence rate and a high mortality rate. Risk factors for MCC are reported to include high age, ...UV exposure, Caucasian skin type and immunosuppression. The incidence is reported to be increasing.
Objective
The purpose of this study was to describe a Swedish cohort and calculate incidence.
Methods
The study design is a retrospective cohort study of population‐based data for MCC collected by the Swedish Cancer Registry to determine the incidence of MCC in Sweden and the clinical characteristics of these tumours including demographics, TNM classification, body part distribution and overall survival after diagnosis. De‐identified data were collected from 1993 to 2012.
Results
A total of 606 cases of MCC were identified during the study period. The median age was 81 years (range 21–99) and a majority, 54.4% were women but age‐adjusted incidence is higher in men. The incidence (per 100,000) of MCC in Sweden in 1993–2012 increased from 0.09 to 0.20 for men and 0.12–0.17 for women, adjusted for age to the world standard population. For the both sexes, the increase was from 0.11 to 0.19 per 100 000, an increase of 73%. The most common site of the primary tumour was the head and neck, with 51.8% of the cases. The size of the tumour was <5 cm in 82.1% of the cases. The majority of the tumours (90.7%) had no known lymphatic spread and only a few patients had confirmed distant metastases (2.9%) when diagnosed.
Conclusions
MCC is a rare disease in Sweden, but the incidence is increasing. This study supports the finding that high age, male sex and UV exposure are risk factors for MCCs. Interventions are required to increase awareness of MCC among clinicians and the public.
The utility of plasma total tau level as a prognostic marker for cognitive decline and dementia is not well understood.
To determine (1) the association between plasma total tau level, cognitive ...decline, and risk of mild cognitive impairment (MCI) and dementia; (2) whether this association differs by the presence of elevated brain amyloid β (Aβ); and (3) whether plasma total tau level is associated with cognitive decline over a short interval of 15 months.
The present analyses included 458 participants who were enrolled in a population-based cohort study between October 2008 and June 2013. All included participants had available plasma total tau levels, Aβ positron emission tomography imaging, and a complete neuropsychological examine at the same visit, as well as at least 1 follow-up visit.
Concentration of plasma total tau.
Risk of MCI and dementia; global and domain-specific cognitive decline.
Of the 458 participants, 287 (62.7%) were men; mean (SD) age was 80.6 (5.6) years. Among cognitively normal (CN) participants oversampled for elevated brain Aβ, both the middle (hazard ratio HR, 2.43; 95% CI, 1.25-4.72) and highest (HR, 2.02; 95% CI, 1.01-4.06) tertiles of plasma total tau level, compared with the lowest, were associated with an increased risk of MCI. Among participants with MCI, higher plasma total tau levels were not significantly associated with risk of dementia (all-cause dementia or Alzheimer disease). Among all participants, higher levels of plasma total tau, examined as a continuous variable, were associated with significant (P < .05) declines in global cognition, memory, attention, and visuospatial ability over a median follow-up of 3.0 years (range, 1.1-4.9 years). In additional analyses restricting the follow-up to 15 months, plasma total tau did not predict decline among CN participants. However, among participants with MCI, higher plasma total tau levels were associated with greater decline in both visuospatial ability (regression coefficient b = -0.50 0.15, P < .001) and global cognition (b = -0.27 0.10, P = .009) at 15 months. Adjusting for elevated brain Aβ did not attenuate any association. There was no interaction between plasma total tau level and brain Aβ for prognosis with any outcome.
These results suggest that elevated plasma total tau levels are associated with cognitive decline, but the results differ based on cognitive status and the duration of follow-up. The association between plasma total tau levels and cognition is independent of elevated brain Aβ.
Alzheimer's disease (AD) is characterized by different clinical entities. Although AD phenotypes share a common molecular substrate (i.e., amyloid beta and tau accumulation), several ...clinicopathological differences exist. Brain functional networks might provide a macro-scale scaffolding to explain this heterogeneity. In this review, we summarize the evidence linking different large-scale functional network abnormalities to distinct AD phenotypes. Specifically, executive deficits in early-onset AD link with the dysfunction of networks that support sustained attention and executive functions. Posterior cortical atrophy relates to the breakdown of visual and dorsal attentional circuits, while the primary progressive aphasia variant of AD may be associated with the dysfunction of the left-lateralized language network. Additionally, network abnormalities might provide in vivo signatures for distinguishing proteinopathies that mimic AD, such as TAR DNA binding protein 43 related pathologies. These network differences vis-a-vis clinical syndromes are more evident in the earliest stage of AD. Finally, we discuss how these findings might pave the way for new tailored interventions targeting the most vulnerable brain circuit at the optimal time window to maximize clinical benefits.
•We reviewed brain connectivity in atypical variants of Alzheimer’s disease.•Network-symptom coupling is reported in AD clinical phenotypes.•Network alterations is a candidate biomarker for proteinopathies that mimic AD.•Network connectivity fingerprints may help to guide interventions in AD.
Background
Topical photodynamic therapy (PDT) is an effective treatment for superficial non‐melanoma skin cancers. Two prodrugs, 5‐aminolevulinic acid (ALA) and methyl aminolevulinate (MAL), are ...available for clinical use. There is, however, a lack of studies comparing the clinical effectiveness of these two prodrugs.
Objective
The objective of the study was to compare the clinical response between ALA‐ and MAL‐PDT when treating actinic keratosis (AK), Bowen's disease (BD), nodular basal cell carcinoma (nBCC) and superficial basal cell carcinoma (sBCC).
Methods
During the period 2002–2009, patients with AK, BD, nBCC and sBCC were treated with ALA‐ and MAL‐PDT at the Department of Dermatology at Karlskoga Hospital in Sweden using a fixed protocol. All patients were followed up approximately 6 months after treatment to evaluate the clinical results, which were analysed retrospectively.
Results
In total, 116 patients with 203 tumours were treated with PDT during the study period. ALA‐ and MAL‐PDT were used for 24 vs. 44 AK fields, 9 vs. 18 BD lesions, 19 vs. 25 nBCCs and 25 vs. 39 sBCCs. Response rates with ALA‐ and MAL‐PDT, respectively, were 63% and 75% for AK, 89% and 78% for BD, 84% and 84% for nBCC and 88% and 87% for sBCC. There were no statistically significant differences in the complete clinical response rates for ALA‐ and MAL‐PDT when used for any of the four lesion types.
Conclusion
ALA‐ and MAL‐PDT appear to be equally effective in the treatment of AK, BD, nBCC and sBCC. Nevertheless, larger, prospective, randomized and controlled studies should be carried out to confirm these results.
Summary
Background There is a need for alternative treatments for moderate to severe acne vulgaris. Preliminary experience suggests that topical methyl aminolaevulinate photodynamic therapy ...(MAL‐PDT) may have potential.
Objectives To investigate the efficacy and tolerability of MAL‐PDT for treatment of moderate inflammatory facial acne.
Patients/methods Thirty patients aged 15–28 years with moderate to severe acne were included in a blinded, prospective, randomized, placebo‐controlled multicentre study. Each side of each patient's face was randomly assigned to treatment with MAL (160 mg g−1) or placebo cream, applied for 3 h prior to illumination. A second treatment was given 2 weeks later. On each occasion, patients assessed the intensity of pain using a 10‐cm visual analogue scale. Inflammatory and noninflammatory acne lesions were counted at baseline and 4 and 10 weeks after the last PDT treatment. The investigator assessed the global severity of acne at baseline (seven patients had severe acne on at least one side of the face) and each study visit using a six‐point rating scale. Data were analysed on an intention‐to‐treat basis, including all 30 patients.
Results There was a statistically significant greater reduction in the total inflammatory lesion count with MAL‐PDT compared with placebo PDT at week 12; median reduction 54% 95% confidence interval (CI) 35–64% vs. 20% (95% CI 8–50%), P = 0·0006. MAL‐PDT was associated with more pain than placebo PDT, although intensity varied across centres and was reduced with repeated treatment. Local adverse events were consistent with this treatment modality.
Conclusions MAL‐PDT is effective in the treatment of moderate to severe inflammatory facial acne. Further studies are warranted to optimize this promising procedure.
Summary
Background Benzophenone‐3 (BZ‐3; 2‐hydroxy‐4‐methoxybenzophenone, oxybenzone) is commonly used to absorb ultraviolet (UV) radiation. BZ‐3 penetrates the skin and can be found in the urine. ...The amount varies between 0·4% and 2%. This seems to be the main metabolic pathway in rats.
Objectives To investigate the total amount of BZ‐3 excreted in the urine after repeated topical whole‐body applications of a sunscreen and to see if UV radiation has any effect on the amount excreted.
Methods Twenty‐five volunteers applied a commercially available sunscreen containing 4% BZ‐3 morning and night for 5 days. Their urine was measured during those 5 days and during a further 5 days after the last application. They were divided into groups A (unirradiated) and B. Group B received UV radiation according to skin type: UVA between 400 and 707 J cm−2, and UVB between 0·46 and 2·0 J cm−2. BZ‐3 in urine was analysed with a high‐performance liquid chromatography method.
Results The volunteers excreted 1·2–8·7% (mean 3·7%) of the total amount of BZ‐3 applied. There was no significant difference between the two groups (P < 0·99, t‐test).
Conclusions We show that a large amount of BZ‐3 is absorbed. BZ‐3 is accumulated in the body as the volunteers excreted BZ‐3 5 days after the last application.
Topical photodynamic therapy (PDT) is a widely approved therapy for actinic keratoses, Bowen's disease (squamous cell carcinoma in situ), superficial and certain thin basal cell carcinomas. ...Recurrence rates when standard treatment protocols are used are typically equivalent to existing therapies, although inferior to surgery for nodular basal cell carcinoma. PDT can be used both as lesional and field therapies and has the potential to delay/reduce the development of new lesions. A protocol using daylight to treat actinic keratoses is widely practised, with conventional PDT using a red light after typically a 3‐h period of occlusion employed for other superficial skin cancer indications as well as for actinic keratoses when daylight therapy is not feasible. PDT is a well‐tolerated therapy although discomfort associated with conventional protocol may require pain‐reduction measures. PDT using daylight is associated with no or minimal pain and preferred by patient. There is an emerging literature on enhancing conventional PDT protocols or combined PDT with another treatment to increase response rates. This guideline, published over two parts, considers all current approved and emerging indications for the use of topical PDT in dermatology, prepared by the PDT subgroup of the European Dermatology Forum guidelines committee. It presents consensual expert recommendations reflecting current published evidence.
Although stress is considered to be a negative factor for psoriasis, no convincing scientific evidence of this association exists, largely because of difficulties in measuring stress. Stress ...resilience is the ability to cope with and adapt to stressful events. Stress resilience can be measured in a standardized way and used as a marker for chronic stress.
The objective of this study is to investigate whether low stress resilience in adolescence increases the risk for onset of psoriasis and psoriatic arthritis later in life.
A cohort of Swedish men (mean age 18.3 years), enrolled in compulsory military service between 1968 and 2005, was created using data from the Swedish Military Service Conscription Register (n = 1,669,422). Stress resilience at conscription was estimated using standardized semi-structured interviews, and was divided into three categories: low, medium and high. The men were followed from conscription until new-onset psoriasis or psoriatic arthritis, death or emigration or at the latest until 31 December 2019. Cox regression models adjusted for confounders at conscription were used to obtain hazard ratios (HRs) with 95% confidence intervals (CIs) for incident psoriasis and psoriatic arthritis.
Men in the lowest stress resilience category had an increased risk of psoriasis and psoriatic arthritis (HR 1.31 (95% CI 1.26-1.36) and 1.23 (95% CI 1.15-1.32), respectively), compared with those in the highest stress resilience category. When including only hospitalized patients the HRs for psoriasis and psoriatic arthritis in the lowest stress resilience group were 1.79 (1.63-1.98) and 1.53 (1.32-1.77), respectively.
This large, prospective register study suggests that low stress resilience in adolescence is associated with an increased risk of incident psoriasis among men. The results indicate that patients with psoriasis have an inherent psychological vulnerability, and highlight the importance of addressing psychological well-being in the management of psoriasis.
In addition to approved indications in non‐melanoma skin cancer in immunocompetent patients, topical photodynamic therapy (PDT) has also been studied for its place in the treatment of, as well as its ...potential to prevent, superficial skin cancers in immune‐suppressed patients, although sustained clearance rates are lower than for immune‐competent individuals. PDT using a nanoemulsion of ALA in a daylight or conventional PDT protocol has been approved for use in field cancerization, although evidence of the potential of the treatment to prevent new SCC remained limited. High‐quality evidence supports a strong recommendation for the use of topical PDT in photorejuvenation as well as for acne, refractory warts, cutaneous leishmaniasis and in onychomycosis, although these indications currently lack approvals for use and protocols remain to be optimized, with more comparative evidence with established therapies required to establish its place in practice. Adverse events across all indications for PDT can be minimized through the use of modified and low‐irradiance regimens, with a low risk of contact allergy to photosensitizer prodrugs, and no other significant documented longer‐term risks with no current evidence of cumulative toxicity or photocarcinogenic risk. The literature on the pharmacoeconomics for using PDT is also reviewed, although accurate comparisons are difficult to establish in different healthcare settings, comparing hospital/office‐based therapies of PDT and surgery with topical ointments, requiring inclusion of number of visits, real‐world efficacy as well as considering the value to be placed on cosmetic outcome and patient preference. This guideline, published over two parts, considers all current approved and emerging indications for the use of topical photodynamic therapy in Dermatology prepared by the PDT subgroup of the European Dermatology Forum guidelines committee. It presents consensual expert recommendations reflecting current published evidence.
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