The association of COVID-19 incidence with temperature, humidity, and UV radiation - A global multi-city analysis.

BACKGROUND AND AIM: The associations between COVID-19 transmission and meteorological factors are scientifically debated. Several studies have been conducted worldwide, with inconsistent findings. However, often these studies had methodological issues, e.g., did not exclude important confounding factors, or had limited geographic or temporal resolution. Our aim was to quantify associations between temporal variations in COVID-19 incidence and meteorological variables globally. METHODS: We analysed data from 455 cities across 20 countries from 3 February to 31 October 2020. We used a time-series analysis that assumes a quasi-Poisson distribution of the cases and incorporates distributed lag non-linear modelling for the exposure associations at the city-level while considering effects of autocorrelation, long-term trends, and day of the week. The confounding by governmental measures was accounted for by incorporating the Oxford Governmental Stringency Index. The effects of daily mean air temperature, relative and absolute humidity, and UV radiation were estimated by applying a meta-regression of local estimates with multi-level random effects for location, country, and climatic zone. RESULTS: We found that air temperature and absolute humidity influenced the spread of COVID-19 over a lag period of 15 days. Pooling the estimates globally showed that overall low temperatures (7.5 °C compared to 17.0 °C) and low absolute humidity (6.0 g/m3 compared to 11.0 g/m3) were associated with higher COVID-19 incidence (RR temp =1.33 with 95%CI: 1.08; 1.64 and RR AH =1.33 with 95%CI: 1.12; 1.57). RH revealed no significant trend and for UV some evidence of a positive association was found. These results were robust to sensitivity analysis. However, the study results also emphasise the heterogeneity of these associations in different countries. CONCLUSION: Globally, our results suggest that comparatively low temperatures and low absolute humidity were associated with increased risks of COVID-19 incidence. However, this study underlines regional heterogeneity of weather-related effects on COVID-19 transmission.

Role of meteorological factors on SARS-CoV-2 infection incidence in Italy and Spain before the vaccination campaign. A multi-city time series study.

Numerous studies have been conducted worldwide to investigate if an association exists between meteorological factors and the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection incidence. Although research studies provide conflicting results, which can be partially explained by different methods used, some clear trends emerge on the role of weather conditions and SARS-CoV-2 infection, especially for temperature and humidity. This study sheds more light on the relationship between meteorological factors and SARS-CoV-2 infection incidence in 23 Italian and 52 Spanish cities. For the purposes of this study, daily air temperature, absolute and relative humidity, wind speed, ultraviolet radiation, and rainfall are considered exposure variables. We conducted a two-stage meta-regression. In the first stage, we estimated the exposure-response association through time series regression analysis at the municipal level. In the second stage, we pooled the association parameters using a meta-analytic model. The study demonstrates an association between meteorological factors and SARS-CoV-2 infection incidence. Specifically, low levels of ambient temperatures and absolute humidity were associated with an increased relative risk. On the other hand, low and high levels of relative humidity and ultraviolet radiation were associated with a decreased relative risk. Concerning wind speed and rainfall, higher values contributed to the reduction of the risk of infection. Overall, our results contribute to a better understanding of how the meteorological factors influence the spread of the SARS-CoV-2 and should be considered in a wider context of existing robust literature that highlight the importance of measures such as social distancing, improved hygiene, face masks and vaccination campaign.

KRAS and BRAF Mutations in Stage II and III Colon Cancer: A Systematic Review and Meta-Analysis.

BACKGROUND: KRAS and BRAF mutations are well-established predictive and prognostic factors in metastatic colorectal cancer; however, their impact in the adjuvant setting has not yet been established. METHODS: We performed a meta-analysis of adjuvant phase III trials in patients with stage II and III colon cancer with available data on the impact of KRAS or BRAF mutations on both disease-free survival (DFS) and overall survival (OS). Trials were subgrouped based on whether adjustment for microsatellite instability (MSI) was performed and the subgroup effect was analyzed through a meta-regression. To increase the precision of the estimates, a joint DFS-OS (so-called "multivariate") meta-analysis was performed. All statistical tests were 2-sided. RESULTS: Nine trials were selected (QUASAR 2, PETACC-8, N0147, CALGB-89803, NSABP-C07, NSABP-C08, PETACC-3, QUASAR, MOSAIC) including a total of 10 893 patients. In the primary meta-analysis, KRAS mutation was associated with poor DFS (pooled hazard ratio [HR] = 1.36, 95% confidence interval [CI] = 1.15 to 1.61, P < .001) and OS (pooled HR = 1.27, 95% CI = 1.03 to 1.55, P = .03) and BRAF mutation was also associated with poor DFS (pooled HR = 1.33, 95% CI = 1.00 to 1.78, P = .05) and OS (pooled HR = 1.49, 95% CI = 1.31 to 1.70, P < .001). The effect of the mutations on outcome was enhanced in the MSI-adjusted subgroup for both the KRAS mutation (pooled HR for DFS = 1.43, 95% CI = 1.15 to 1.79, P = .001; and pooled HR for OS = 1.33, 95% CI = 1.03 to 1.71, P = .03) and the BRAF mutation (pooled HR for DFS = 1.59, 95% CI = 1.22 to 2.07, P = .001; and pooled HR for OS = 1.67, 95% CI = 1.37 to 2.04, P < .001). The interaction between BRAF and MSI adjustment was statistically significant for DFS (Pinteraction = .02). This interaction was even more pronounced in the DFS-OS multivariate meta-analysis. CONCLUSIONS: Both KRAS and BRAF mutations were statistically significantly associated with both DFS and OS, with the mutation effect being enhanced by MSI adjustment. Effective adjuvant treatment for microsatellite-stable BRAF or KRAS-mutated colon cancer represents an unmet clinical need, and exploring the use of recently available BRAF and KRAS inhibitors in this setting would be highly desirable.

MC1R variants and cutaneous melanoma risk according to histological type, body site, and Breslow thickness: a pooled analysis from the M-SKIP project.

Little is known on whether melanocortin 1 receptor (MC1R) associated cutaneous melanoma (CM) risk varies depending on histological subtype and body site, and whether tumour thickness at diagnosis (the most important prognostic factor for CM patients) differs between MC1R variant carriers and wild-type individuals. We studied the association between MC1R variants and CM risk by histological subtype, body site, and Breslow thickness, using the database of the M-SKIP project. We pooled individual data from 15 case-control studies conducted during 2005-2015 in Europe and the USA. Study-specific, multi-adjusted odds ratios were pooled into summary odds ratios (SOR) and 95% confidence intervals (CI) using random-effects models. Six thousand eight hundred ninety-one CM cases and 5555 controls were included. CM risk was increased among MC1R variant carriers vs. wild-type individuals. The increase in risk was comparable across histological subtypes (SOR for any variant vs. wild-type ranged between 1.57 and 1.70, always statistical significant) except acral lentiginous melanoma (ALM), for which no association emerged; and slightly greater on chronically (1.74, 95% CI 1.47-2.07) than intermittently (1.55, 95% CI 1.34-1.78) sun-exposed skin. CM risk was greater for those carrying 'R' vs. 'r' variants; correlated with the number of variants; and was more evident among individuals not showing the red hair colour phenotype. Breslow thickness was not associated with MC1R status. MC1R variants were associated with an increased risk of CM of any histological subtype (except ALM) and occurring on both chronically and intermittently sun-exposed skin.

MC1R variants in childhood and adolescent melanoma: a retrospective pooled analysis of a multicentre cohort.

BACKGROUND: Germline variants in the melanocortin 1 receptor gene (MC1R) might increase the risk of childhood and adolescent melanoma, but a clear conclusion is challenging because of the low number of studies and cases. We assessed the association of MC1R variants with childhood and adolescent melanoma in a large study comparing the prevalence of MC1R variants in child or adolescent patients with melanoma to that in adult patients with melanoma and in healthy adult controls. METHODS: In this retrospective pooled analysis, we used the M-SKIP Project, the Italian Melanoma Intergroup, and other European groups (with participants from Australia, Canada, France, Greece, Italy, the Netherlands, Serbia, Spain, Sweden, Turkey, and the USA) to assemble an international multicentre cohort. We gathered phenotypic and genetic data from children or adolescents diagnosed with sporadic single-primary cutaneous melanoma at age 20 years or younger, adult patients with sporadic single-primary cutaneous melanoma diagnosed at age 35 years or older, and healthy adult individuals as controls. We calculated odds ratios (ORs) for childhood and adolescent melanoma associated with MC1R variants by multivariable logistic regression. Subgroup analysis was done for children aged 18 or younger and 14 years or younger. FINDINGS: We analysed data from 233 young patients, 932 adult patients, and 932 healthy adult controls. Children and adolescents had higher odds of carrying MC1R r variants than did adult patients (OR 1·54, 95% CI 1·02-2·33), including when analysis was restricted to patients aged 18 years or younger (1·80, 1·06-3·07). All investigated variants, except Arg160Trp, tended, to varying degrees, to have higher frequencies in young patients than in adult patients, with significantly higher frequencies found for Val60Leu (OR 1·60, 95% CI 1·05-2·44; p=0·04) and Asp294His (2·15, 1·05-4·40; p=0·04). Compared with those of healthy controls, young patients with melanoma had significantly higher frequencies of any MC1R variants. INTERPRETATION: Our pooled analysis of MC1R genetic data of young patients with melanoma showed that MC1R r variants were more prevalent in childhood and adolescent melanoma than in adult melanoma, especially in patients aged 18 years or younger. Our findings support the role of MC1R in childhood and adolescent melanoma susceptibility, with a potential clinical relevance for developing early melanoma detection and preventive strategies. FUNDING: SPD-Pilot/Project-Award-2015; AIRC-MFAG-11831.

Can Dietary and Physical Activity Modifications Reduce Breast Density in Postmenopausal Women? The DAMA Study, a Randomized Intervention Trial in Italy.

BACKGROUND: Few randomized trials have been carried out to evaluate the effect of lifestyle modifications on mammographic breast density (MBD). The randomized 2 × 2 factorial Diet, physical Activity and MAmmography trial aimed to evaluate whether MBD can be reduced in postmenopausal women with high baseline MBD by a 24-month dietary and/or physical activity (PA) interventions. METHODS: We randomized healthy postmenopausal women, attending the Florence (Italy) mammographic screening program, ages 50 to 69 years, nonsmokers, with MBD > 50% and no recent hormone therapy, to (i) a dietary intervention focused on plant foods, with a low glycemic load, low in saturated fats and alcohol; (ii) a PA intervention combining daily moderate intensity activities and one weekly supervised session of more strenuous activity; (iii) both interventions; (iv) general recommendations. We evaluated changes in MBD based on Volpara estimates comparing baseline and follow-up digital mammograms by an intention-to-treat-analysis. RESULTS: MBD measures were available for 226 participants. An interaction emerged between treatments and thus we run analyses by arms. A decrease in volumetric percent density emerged for women in the dietary intervention (ratio 0.91; 95% CI, 0.86-0.97; P = 0.002) and in the PA intervention arm (0.93; 95% CI, 0.87-0.98; P = 0.01) in comparison with controls. No clear effect emerged in the double intervention arm. CONCLUSIONS: This intervention trial suggests that a 24-month dietary or PA intervention may reduce MBD in postmenopausal women. IMPACT: A modification of dietary habits or an increase in PA in postmenopausal women may reduce MBD. Further studies are needed to confirm these findings for planning breast cancer preventive strategies.

MC1R variants as melanoma risk factors independent of at-risk phenotypic characteristics: a pooled analysis from the M-SKIP project.

PURPOSE: Melanoma represents an important public health problem, due to its high case-fatality rate. Identification of individuals at high risk would be of major interest to improve early diagnosis and ultimately survival. The aim of this study was to evaluate whether MC1R variants predicted melanoma risk independently of at-risk phenotypic characteristics. MATERIALS AND METHODS: Data were collected within an international collaboration - the M-SKIP project. The present pooled analysis included data on 3,830 single, primary, sporadic, cutaneous melanoma cases and 2,619 controls from seven previously published case-control studies. All the studies had information on MC1R gene variants by sequencing analysis and on hair color, skin phototype, and freckles, ie, the phenotypic characteristics used to define the red hair phenotype. RESULTS: The presence of any MC1R variant was associated with melanoma risk independently of phenotypic characteristics (OR 1.60; 95% CI 1.36-1.88). Inclusion of MC1R variants in a risk prediction model increased melanoma predictive accuracy (area under the receiver-operating characteristic curve) by 0.7% over a base clinical model (P=0.002), and 24% of participants were better assessed (net reclassification index 95% CI 20%-30%). Subgroup analysis suggested a possibly stronger role of MC1R in melanoma prediction for participants without the red hair phenotype (net reclassification index: 28%) compared to paler skinned participants (15%). CONCLUSION: The authors suggest that measuring the MC1R genotype might result in a benefit for melanoma prediction. The results could be a valid starting point to guide the development of scientific protocols assessing melanoma risk prediction tools incorporating the MC1R genotype.

A multilevel model to estimate the within- and the between-center components of the exposure/disease association in the EPIC study.

In a multicenter study, the overall relationship between exposure and the risk of cancer can be broken down into a within-center component, which reflects the individual level association, and a between-center relationship, which captures the association at the aggregate level. A piecewise exponential proportional hazards model with random effects was used to evaluate the association between dietary fiber intake and colorectal cancer (CRC) risk in the EPIC study. During an average follow-up of 11.0 years, 4,517 CRC events occurred among study participants recruited in 28 centers from ten European countries. Models were adjusted by relevant confounding factors. Heterogeneity among centers was modelled with random effects. Linear regression calibration was used to account for errors in dietary questionnaire (DQ) measurements. Risk ratio estimates for a 10 g/day increment in dietary fiber were equal to 0.90 (95%CI: 0.85, 0.96) and 0.85 (0.64, 1.14), at the individual and aggregate levels, respectively, while calibrated estimates were 0.85 (0.76, 0.94), and 0.87 (0.65, 1.15), respectively. In multicenter studies, over a straightforward ecological analysis, random effects models allow information at the individual and ecologic levels to be captured, while controlling for confounding at both levels of evidence.

Power analysis to detect time trends on population-based cancer registries data: When size really matters.

Detecting statistically significant trends in incidence with cancer registries data not only depends on the size of their covered population but also on the levels of incidence rates, duration of diagnostic period and type of temporal variation. We simulated sample sizes of newly diagnosed cases based on a variety of plausible levels of cancer rates and scenarios of changing trends over a period of about 30 years. Each simulated set of cases was then analysed with joinpoint regression models. The power was derived as the relative frequency of the simulation runs where the p-value of the coefficient was less than 0.05 under the alternative model. In case of a decreasing trend with no change of direction (join), an Annual Percentage Change (APC) of 1% for an average rate of 10 per 100,000 is detectable in populations of half a million inhabitants or more with a nominal power of 80%. In a model with one joinpoint followed by an increasing trend, the minimum detectable APC increases, and an APC of about 2%, can be detected only with populations of at least 2 million. For analyses requiring a larger sample size than the actual covered population, alternative organisational strategies should be considered, such as an extension of population coverage or data pooling and merging from registries with comparable data. (i.e. when heterogeneity across merging registries is low or acceptable for the specific study question).

MC1R variants increased the risk of sporadic cutaneous melanoma in darker-pigmented Caucasians: a pooled-analysis from the M-SKIP project.

The MC1R gene is a key regulator of skin pigmentation. We aimed to evaluate the association between MC1R variants and the risk of sporadic cutaneous melanoma (CM) within the M-SKIP project, an international pooled-analysis on MC1R, skin cancer and phenotypic characteristics. Data included 5,160 cases and 12,119 controls from 17 studies. We calculated a summary odds ratio (SOR) for the association of each of the nine most studied MC1R variants and of variants combined with CM by using random-effects models. Stratified analysis by phenotypic characteristics were also performed. Melanoma risk increased with presence of any of the main MC1R variants: the SOR for each variant ranged from 1.47 (95%CI: 1.17-1.84) for V60L to 2.74 (1.53-4.89) for D84E. Carriers of any MC1R variant had a 66% higher risk of developing melanoma compared with wild-type subjects (SOR; 95%CI: 1.66; 1.41-1.96) and the risk attributable to MC1R variants was 28%. When taking into account phenotypic characteristics, we found that MC1R-associated melanoma risk increased only for darker-pigmented Caucasians: SOR (95%CI) was 3.14 (2.06-4.80) for subjects with no freckles, no red hair and skin Type III/IV. Our study documents the important role of all the main MC1R variants in sporadic CM and suggests that they have a direct effect on melanoma risk, independently on the phenotypic characteristics of carriers. This is of particular importance for assessing preventive strategies, which may be directed to darker-pigmented Caucasians with MC1R variants as well as to lightly pigmented, fair-skinned subjects.

Predictors of non-response in a UK-wide cohort study of children's accelerometer-determined physical activity using postal methods.

OBJECTIVES: To investigate the biological, social, behavioural and environmental factors associated with non-consent, and non-return of reliable accelerometer data (≥2 days lasting ≥10 h/day), in a UK-wide postal study of children's activity. DESIGN: Nationally representative prospective cohort study. SETTING: Children born across the UK, between 2000 and 2002. PARTICIPANTS: 13 681 7 to 8-year-old singleton children who were invited to wear an accelerometer on their right hip for 7 consecutive days. Consenting families were posted an Actigraph GT1M accelerometer and asked to return it by post. PRIMARY OUTCOME MEASURES: Study consent and reliable accelerometer data acquisition. RESULTS: Consent was obtained for 12 872 (94.5%) interviewed singletons, of whom 6497 (50.5%) returned reliable accelerometer data. Consent was less likely for children with a limiting illness or disability, children who did not have people smoking near them, children who had access to a garden, and those who lived in Northern Ireland. From those who consented, reliable accelerometer data were less likely to be acquired from children who: were boys; overweight/obese; of white, mixed or 'other' ethnicity; had an illness or disability limiting daily activity; whose mothers did not have a degree; who lived in rented accommodation; who exercised once a week or less; who had been breastfed; were from disadvantaged wards; had younger mothers or lone mothers; or were from households with just one, or more than three children. CONCLUSIONS: Studies need to encourage consent and reliable data return in the wide range of groups we have identified to improve response and reduce non-response bias. Additional efforts targeted at such children should increase study consent and data acquisition while also reducing non-response bias. Adjustment must be made for missing data that account for missing data as a non-random event.

Radiographic measurements of hip dysplasia at skeletal maturity--new reference intervals based on 2,038 19-year-old Norwegians.

OBJECTIVE: Normative references for radiographic measurements commonly used in the diagnosis of developmental dysplasia of the hip at skeletal maturity are incomplete. The present study therefore aimed to establish new gender-specific standards for measurements reflecting the acetabular morphology, namely Sharp's angle, the acetabular roof angle of Tönnis (AA) and the acetabular depth-width ratio (ADR), and measurements reflecting the position of the femoral head related to the acetabulum, namely the center-edge (CE) angle of Wiberg, the refined CE angle of Ogata, and the femoral head extrusion index (FHEI). The joint space width (JSW) is also reported. MATERIALS AND METHODS: The population-based 1989 Bergen Birth Cohort (n = 3,935) was invited at age 19 years to a follow-up during 2007-09, of which 2,038 (52 %) attended. A standardized antero-posterior radiograph was assessed. The normative references are presented as mean ± standard deviation (SD) and 2.5-97.5 percentiles with 95 % confidence intervals. RESULTS: A total of 2,011 (841 males, 1,170 females, mean age 18.6 (SD 0.6)) radiographs were analyzed. Sharp's angle was 38.8° ± 3.5° in males and 40.7° ± 3.5° in females, with 97.5 percentiles of 46° and 47°, respectively. The CE angle was 32.1° ± 6.1° in males and 31.0° ± 6.1° in females, with 2.5 percentiles of 21° and 20°, respectively. The FHEI was 86.0 % ± 6.3 % in males and 85.6 % ± 6.6 % in females, with 2.5 percentiles of 74° and 73°, respectively. CONCLUSIONS: Updated gender-specific reference ranges for radiographic measurements commonly used for hip dysplasia at skeletal maturity are reported, similar to or slightly wider than those described in the literature. Statistically significant gender differences have been confirmed for most of the measurements.

Melanocortin-1 receptor, skin cancer and phenotypic characteristics (M-SKIP) project: study design and methods for pooling results of genetic epidemiological studies.

BACKGROUND: For complex diseases like cancer, pooled-analysis of individual data represents a powerful tool to investigate the joint contribution of genetic, phenotypic and environmental factors to the development of a disease. Pooled-analysis of epidemiological studies has many advantages over meta-analysis, and preliminary results may be obtained faster and with lower costs than with prospective consortia. DESIGN AND METHODS: Based on our experience with the study design of the Melanocortin-1 receptor (MC1R) gene, SKin cancer and Phenotypic characteristics (M-SKIP) project, we describe the most important steps in planning and conducting a pooled-analysis of genetic epidemiological studies. We then present the statistical analysis plan that we are going to apply, giving particular attention to methods of analysis recently proposed to account for between-study heterogeneity and to explore the joint contribution of genetic, phenotypic and environmental factors in the development of a disease. Within the M-SKIP project, data on 10,959 skin cancer cases and 14,785 controls from 31 international investigators were checked for quality and recoded for standardization. We first proposed to fit the aggregated data with random-effects logistic regression models. However, for the M-SKIP project, a two-stage analysis will be preferred to overcome the problem regarding the availability of different study covariates. The joint contribution of MC1R variants and phenotypic characteristics to skin cancer development will be studied via logic regression modeling. DISCUSSION: Methodological guidelines to correctly design and conduct pooled-analyses are needed to facilitate application of such methods, thus providing a better summary of the actual findings on specific fields.

Radiological findings for hip dysplasia at skeletal maturity. Validation of digital and manual measurement techniques.

OBJECTIVE: To report on intra-observer, inter-observer, and inter-method reliability and agreement for radiological measurements used in the diagnosis of hip dysplasia at skeletal maturity, as obtained by a manual and a digital measurement technique. MATERIALS AND METHODS: Pelvic radiographs from 95 participants (56 females) in a follow-up hip study of 18- to 19-year-old patients were included. Eleven radiological measurements relevant for hip dysplasia (Sharp's, Wiberg's, and Ogata's angles; acetabular roof angle of Tönnis; articulo-trochanteric distance; acetabular depth-width ratio; femoral head extrusion index; maximum teardrop width; and the joint space width in three different locations) were validated. Three observers measured the radiographs using both a digital measurement program and manually in AgfaWeb1000. Inter-method and inter- and intra-observer agreement were analyzed using the mean differences between the readings/readers, establishing the 95% limits of agreement. We also calculated the minimum detectable change and the intra-class correlation coefficient. RESULTS: Large variations among different radiological measurements were demonstrated. However, the variation was not related to the use of either the manual or digital measurement technique. For measurements with greater absolute values (Sharp's angle, femoral head extrusion index, and acetabular depth-width ratio) the inter- and intra-observer and inter-method agreements were better as compared to measurements with lower absolute values (acetabular roof angle, teardrop and joint space width). CONCLUSION: The inter- and intra-observer variation differs notably across different radiological measurements relevant for hip dysplasia at skeletal maturity, a fact that should be taken into account in clinical practice. The agreement between the manual and digital methods is good.

Diet-related telomere shortening and chromosome stability.

Recent evidences have highlighted an influence of micronutrients in the maintenance of telomere length (TL). In order to explore whether diet-related telomere shortening had any physiological relevance and was accompanied by significant damage in the genome, in the present study, TL was assessed by terminal restriction fragment (TRF) analysis in peripheral blood lymphocytes of 56 healthy subjects for which detailed information on dietary habits was available and data were compared \with the incidence of nucleoplasmic bridges (NPBs), a marker of chromosomal instability related to telomere dysfunction visualised with the cytokinesis-blocked micronucleus assay. To increase the capability to detect even slight impairment of telomere function, the incidence of NPBs was also evaluated on cells exposed in vitro to ionising radiation. Care was taken to control for potential confounding factors that might influence TL, viz. age, hTERT genotype and smoking status. Data showed that higher consumption of vegetables was related with significantly higher mean TL (P = 0.013); in particular, the analysis of the association between micronutrients and mean TL highlighted a significant role of antioxidant intake, especially beta-carotene, on telomere maintenance (P = 0.004). However, the diet-related telomere shortening did not result in associated increased spontaneous or radiation-induced NPBs. The distribution of TRFs was also analysed and a slight prevalence of radiation-induced NPBs (P = 0.03) was observed in subjects with higher amount of very short TRFs (<2 kb). The relative incidence of very short TRFs was positively associate with ageing (P = 0.008) but unrelated to vegetables consumption and daily intake of micronutrients, suggesting that the degree of telomere erosion related with low dietary intake of antioxidants observed in this study was not so extensive to lead to chromosome instability.

The spectrum of dermatoscopic patterns in blue nevi.

BACKGROUND: Blue nevi are congenital or acquired, dermal dendritic melanocytic proliferations that can simulate melanocytic and nonmelanocytic lesions including melanoma, cutaneous metastasis of melanoma, Spitz/Reed nevi, and basal cell carcinoma. OBJECTIVE: We sought to investigate global and local dermatoscopic patterns of blue nevi compared with melanomas and basal cell carcinomas. METHODS: We retrospectively analyzed global and local features in 95 dermatoscopic images of blue nevi and in 190 melanomas and basal cell carcinomas that were selected as control lesions on the basis of similar pigmentation. Lesion pigmentation was classified as monochromatic, dichromatic, or multichromatic. RESULTS: A global pattern characterized by homogeneous pigmentation was observed in all of 95 (100%) blue nevi. Eighty of 95 (84.2%) blue nevi presented a homogeneous pattern consisting of one color (blue, black, or brown) or two colors (blue-brown, blue-gray, or blue-black). Fifteen of 95 (15.8%) blue nevi had a multichromatic (blue, gray, black, brown, and/or red) pigmentation. In all, 47 of 95 (49.5%) blue nevi were characterized by pigmentation in the absence of pigment network or any other local dermatoscopic features. And 48 of 95 (50.5%) blue nevi showed local dermatoscopic patterns including whitish scarlike depigmentation, dots/globules, vascular pattern, streaks, and networklike pattern. LIMITATIONS: The study was retrospective and involved only Caucasian people of Italian origin. CONCLUSION: The characteristic feature of blue nevi is a homogeneous pigmentation that is blue, blue-gray, blue-brown, or blue-black. We showed that a wide spectrum of local dermatoscopic features (whitish scarlike depigmentation, dots/globules, peripheral streaks or vessels) may also be present. In such cases, clinical and dermatoscopic distinction from melanoma or nonmelanocytic lesions may be difficult or impossible, and surgical excision is necessary.

Hormonal and reproductive factors in relation to melanoma in women: current review and meta-analysis.

A number of studies have focused on possible relationships between characteristics of female endocrine status and melanoma (CM) risk; however, the link between melanoma, oral contraceptive (OC) and hormonal replacement therapy (HRT) use, and reproductive factors remains controversial. A comprehensive, systematic bibliographic search of the medical literature was conducted to identify relevant studies. Random effects models were used to summarise results. Subgroup, meta-regression and sensitivity analyses have been carried out to explore sources of between-study variation and bias. We included thirty-six observational studies published in the last 30 years. Summarising a total of 5626 melanoma cases, we did not find any significant melanoma risk associated with OC and HRT use. Several reproductive factors were also investigated, summarising data on 16787 melanoma cases. We found a significantly increased melanoma risk for late age at first birth, and women with more than one child may be at a lower risk for melanoma; however, socio-economic confounders were found to play a significant role in explaining this association. This study confirmed no increased risk of CM with the use of oral contraceptives and hormone replacement therapy: exogenous female hormones do not contribute to an increased risk of CM. In contrast, significant associations of CM with parity and age at first pregnancy were observed in this meta-analysis finds and warrant further research.

Bulky DNA adducts and breast cancer risk in the prospective EPIC-Italy study.

The role of environmental carcinogen exposure in breast cancer development has long been suspected, but no specific association has been identified so far. A few molecular epidemiology studies reported that DNA adducts detected by different methods are associated with a modest increase of breast cancer risk. We aimed to evaluate the association between bulky DNA adducts, detected by the (32)P-postlabelling method in peripheral leukocytes, and the risk of developing breast cancer in the female Italian cohorts of the EPIC (European Prospective Investigation into Cancer and nutrition) study. By using a nested case-control design, breast cancer cases identified in the follow-up of over 30,000 women of EPIC-Italy study have been matched to controls by specific criteria. We measured the levels of bulky DNA adducts by the (32)P-postlabelling method in peripheral leukocytes donated at enrolment. Conditional regression analyses adjusted for selected potential confounders were used. Results on DNA adduct levels were available for 292 cases and 292 matched controls. The mean DNA adduct levels were similar in both groups (P=0.62). Multivariate regression analyses failed to show any significant association between bulky DNA adducts and breast cancer. Our results do not support any association of breast cancer risk with exposure to environmental carcinogens as measured through the levels of bulky DNA adducts in pre-diagnostic white blood cells. Larger studies by using different methods and/or biomarkers are needed to better evaluate the role of specific environmental carcinogens in breast carcinogenesis.

Newborns with sonographically dysplastic and potentially unstable hips: 6-year follow-up of an RCT.

OBJECTIVE: To examine the long-term outcome of early abduction splinting versus active sonographic surveillance in newborns with mildly dysplastic hips. PATIENTS AND METHODS: Between 1997 and 2003, 128 newborns with mildly dysplastic and potentially unstable hips on ultrasound (43° ≤ α-angle < 50°) were randomly assigned to immediate abduction treatment or sonographic surveillance. All were invited for a radiographic follow-up at 6 years. The radiographs were analyzed by a single radiologist masked to the randomization allocation, and markers of hip dysplasia (acetabular index, center-edge angle of Wiberg) and avascular necrosis were reported. RESULTS: Eighty-three participants (65%) agreed to participate in the follow-up (42 participants from the treatment group). The mean acetabular index was 14.7° (SD: 5.6°) for the treatment group and 13.9° (SD: 3.9°) for the control group (mean difference: -0.8° [95% confidence interval: -2.9° to 1.3°]). Values were within normal ranges for age for all participants except for 1 female subject from the treatment group. The mean center edge was 26.6° for those treated and 26.4° for the active surveillance group (mean difference: -0.3° [95% confidence interval: -2.5° to 2.0°]). None had markers suggestive of avascular necrosis. CONCLUSIONS: We found no difference in radiographic outcome at 6 years of age between children allocated to initial splintage for 6 weeks and those offered active sonographic surveillance. The delayed acetabular ossification or persistent dysplasia seen in a third of infants from both groups at 1 year of age had completely resolved in all but 1 of the female subjects from the treatment group.