Ivermectin for COVID-19 in adults in the community (PRINCIPLE): An open, randomised, controlled, adaptive platform trial of short- and longer-term outcomes.

BACKGROUND: The evidence for whether ivermectin impacts recovery, hospital admissions, and longer-term outcomes in COVID-19 is contested. The WHO recommends its use only in the context of clinical trials. METHODS: In this multicentre, open-label, multi-arm, adaptive platform randomised controlled trial, we included participants aged ≥18 years in the community, with a positive SARS-CoV-2 test, and symptoms lasting ≤14 days. Participants were randomised to usual care, usual care plus ivermectin tablets (target 300-400 µg/kg per dose, once daily for 3 days), or usual care plus other interventions. Co-primary endpoints were time to first self-reported recovery, and COVID-19 related hospitalisation/death within 28 days, analysed using Bayesian models. Recovery at 6 months was the primary, longer term outcome. TRIAL REGISTRATION: ISRCTN86534580. FINDINGS: The primary analysis included 8811 SARS-CoV-2 positive participants (median symptom duration 5 days), randomised to ivermectin (n = 2157), usual care (n = 3256), and other treatments (n = 3398) from June 23, 2021 to July 1, 2022. Time to self-reported recovery was shorter in the ivermectin group compared with usual care (hazard ratio 1·15 [95% Bayesian credible interval, 1·07 to 1·23], median decrease 2.06 days [1·00 to 3·06]), probability of meaningful effect (pre-specified hazard ratio ≥1.2) 0·192). COVID-19-related hospitalisations/deaths (odds ratio 1·02 [0·63 to 1·62]; estimated percentage difference 0% [-1% to 0·6%]), serious adverse events (three and five respectively), and the proportion feeling fully recovered were similar in both groups at 6 months (74·3% and 71·2% respectively (RR = 1·05, [1·02 to 1·08]) and also at 3 and 12 months. INTERPRETATION: Ivermectin for COVID-19 is unlikely to provide clinically meaningful improvement in recovery, hospital admissions, or longer-term outcomes. Further trials of ivermectin for SARS-Cov-2 infection in vaccinated community populations appear unwarranted. FUNDING: UKRI/National Institute of Health Research (MC_PC_19079).

Recommendations for reporting equivalent black carbon (eBC) mass concentrations based on long-term pan-European in-situ observations.

A reliable determination of equivalent black carbon (eBC) mass concentrations derived from filter absorption photometers (FAPs) measurements depends on the appropriate quantification of the mass absorption cross-section (MAC) for converting the absorption coefficient (babs) to eBC. This study investigates the spatial-temporal variability of the MAC obtained from simultaneous elemental carbon (EC) and babs measurements performed at 22 sites. We compared different methodologies for retrieving eBC integrating different options for calculating MAC including: locally derived, median value calculated from 22 sites, and site-specific rolling MAC. The eBC concentrations that underwent correction using these methods were identified as LeBC (local MAC), MeBC (median MAC), and ReBC (Rolling MAC) respectively. Pronounced differences (up to more than 50 %) were observed between eBC as directly provided by FAPs (NeBC; Nominal instrumental MAC) and ReBC due to the differences observed between the experimental and nominal MAC values. The median MAC was 7.8 ± 3.4 m2 g-1 from 12 aethalometers at 880 nm, and 10.6 ± 4.7 m2 g-1 from 10 MAAPs at 637 nm. The experimental MAC showed significant site and seasonal dependencies, with heterogeneous patterns between summer and winter in different regions. In addition, long-term trend analysis revealed statistically significant (s.s.) decreasing trends in EC. Interestingly, we showed that the corresponding corrected eBC trends are not independent of the way eBC is calculated due to the variability of MAC. NeBC and EC decreasing trends were consistent at sites with no significant trend in experimental MAC. Conversely, where MAC showed s.s. trend, the NeBC and EC trends were not consistent while ReBC concentration followed the same pattern as EC. These results underscore the importance of accounting for MAC variations when deriving eBC measurements from FAPs and emphasize the necessity of incorporating EC observations to constrain the uncertainty associated with eBC.

Assessing key behavioural theories of drought risk adaptation: Evidence from rural Kenya.

The Horn of Africa Drylands are increasingly experiencing severe droughts, which impose a threat on traditional livelihood strategies. Understanding adaptation behavior in rural communities is key to helping reduce the impact of these droughts. We investigate adaptation behavior by assessing four established economic and social psychological theories on decision making under risk: expected utility theory (EUT), rank dependent utility theory (RDU), protection motivation theory (PMT), and theory of planned behavior (PMT). To measure adaptation behavior and the theory constructs, we conducted a household survey in Kenya (N = 502). Regression analysis shows that the economic theories (EUT and RDU) have the best fit for our data. Risk and time preferences are found to play an important role in adaptation decisions. An analysis of differences in decision making for distinct types of adaptation measures shows that risk averse (agro-)pastoralists are more likely to implement adaptation measures that are adjustments to their current livelihood practices, and less willing to invest in adaptation measures that require a shift to other livelihood activities. Moreover, we find significant effects for elements of the social psychological theories (PMT and TPB). A person's belief in their own ability to implement an adaptation measure (perceived self-efficacy) and adaptation by family and friends are important factors in explaining adaptation decisions. Finally, we find that the type of adaptation measures that people implement is influenced by, among others, gender, education level, access to financial resources, and access to government support or aid. Our analysis gives insights into the drivers of individual adaptation decisions, which can enhance policies promoting adaptation of dryland communities.

The variability of mass concentrations and source apportionment analysis of equivalent black carbon across urban Europe.

This study analyzed the variability of equivalent black carbon (eBC) mass concentrations and their sources in urban Europe to provide insights into the use of eBC as an advanced air quality (AQ) parameter for AQ standards. This study compiled eBC mass concentration datasets covering the period between 2006 and 2022 from 50 measurement stations, including 23 urban background (UB), 18 traffic (TR), 7 suburban (SUB), and 2 regional background (RB) sites. The results highlighted the need for the harmonization of eBC measurements to allow for direct comparisons between eBC mass concentrations measured across urban Europe. The eBC mass concentrations exhibited a decreasing trend as follows: TR > UB > SUB > RB. Furthermore, a clear decreasing trend in eBC concentrations was observed in the UB sites moving from Southern to Northern Europe. The eBC mass concentrations exhibited significant spatiotemporal heterogeneity, including marked differences in eBC mass concentration and variable contributions of pollution sources to bulk eBC between different cities. Seasonal patterns in eBC concentrations were also evident, with higher winter concentrations observed in a large proportion of cities, especially at UB and SUB sites. The contribution of eBC from fossil fuel combustion, mostly traffic (eBCT) was higher than that of residential and commercial sources (eBCRC) in all European sites studied. Nevertheless, eBCRC still had a substantial contribution to total eBC mass concentrations at a majority of the sites. eBC trend analysis revealed decreasing trends for eBCT over the last decade, while eBCRC remained relatively constant or even increased slightly in some cities.

COVID-19 had no impact on emergency urological admissions at an Australian tertiary hospital.

BACKGROUNDS: The COVID-19 pandemic is an unprecedented threat to health and healthcare systems. There is no published data on the impact on urological presentations in Australia. METHODS: A retrospective analysis of all admissions under the urology service at Liverpool Hospital, Australia from February 1st to April 30th for 2020 and the previous 5 years. RESULTS: There was a total of 397 admissions in 2020 and 438 in 2019. The mean age, proportion of male, and mean length of stay were similar. In 2020, there were 229 emergency admissions. Over the same period during the previous 5 years, there were between 195 and 218 emergency admissions. In 2019, there were 220 planned admissions and 168 in 2020. Between 2019 and 2020, there was no significant difference in the proportion of patients with admission longer than 10 days (P = 0.602), requiring intensive care unit admission (P = 0.708) or inpatient operative management (P = 0.171). Among the emergency admissions, the mean Charlson Comorbidity Index was significantly lower in 2020 compared to 2019 (P = 0.009). CONCLUSIONS: Despite the pervasive fear of the COVID-19 pandemic and multiple, substantial alterations to hospital systems, structures and elective operating restrictions, no significant difference in numbers or acuity of emergency admissions were observed. Due to limitations in elective operating, there was an expected reduction in planned admissions. Our findings are in contrast to multiple recent studies and may be the result of our patient demographic where health-seeking behaviours appear to have not been significantly influenced by the pandemic.

Real-Time Dynamics of the Formation of Hydrated Electrons upon Irradiation of Water Clusters with Extreme Ultraviolet Light.

Free electrons in a polar liquid can form a bound state via interaction with the molecular environment. This so-called hydrated electron state in water is of fundamental importance, e.g., in cellular biology or radiation chemistry. Hydrated electrons are highly reactive radicals that can either directly interact with DNA or enzymes, or form highly excited hydrogen (H^{*}) after being captured by protons. Here, we investigate the formation of the hydrated electron in real-time employing extreme ultraviolet femtosecond pulses from a free electron laser, in this way observing the initial steps of the hydration process. Using time-resolved photoelectron spectroscopy we find formation timescales in the low picosecond range and resolve the prominent dynamics of forming excited hydrogen states.

Polymorphisms in ACE and ACTN3 Genes and Blood Pressure Response to Acute Exercise in Elite Male Athletes from Serbia.

Physiological adaptations to various types of prolonged and intensive physical activity, as seen in elite athletes from different sports, include changes in blood pressure (BP) response to acute exercise. Also, functional polymorphisms of the angiotensin I converting enzyme (ACE) and alfa-actinin-3 (ACTN3) genes are shown to be associated with BP parameters changes, both in athletes and sedentary population. In this study, an Alu insertion (I)/deletion (D) polymorphism in ACE gene, as well as nonsense mutation in the gene encoding ACTN3 have been scored in 107 elite Serbian athletes classified according to their sporting discipline to power/sprint (short distance runners/swimmers), endurance (rowers, footballers, middle-distance swimmers) or mixed sports (water polo, handball, volleyball players). Presence of nonfunctional allele in ACTN3 is associated with significantly increased maximal systolic BP (SBPmax, p = 0.04). Athletes with Alu insertion in ACE had significantly (p = 0.006) larger decline of systolic BP after 3 minutes of recovery (SBPR3), calculated as the percentage of maximal SBP response during exercise stress testing. Concomitant presence of non-functional variant in ACTN3 gene decreased this beneficiary effect of ACE mutation on SBPR3. Long term enrollment in power/sprint sports significantly increased resting diastolic BP (DBPrest: 74 mmHg) and SBPmax (197 mmHg) and improved SBPR3 (74.8%) compared to enrolment in endurance (72 mmHg; 178 mmHg; 81.1%) and mixed sports (69 mmHg; 185 mmHg; 80.0%). Lack of the effect of genotype by sport interaction on BP parameters suggests that the long-term effects of different disciplines on BP are not mediated by these two genes.

Fracturas periprotésicas de fémur sobre prótesis de cadera y rodilla. Análisis de una serie de 34 casos y revisión de las series españolas en los últimos 20 años / Peri-prosthetic femoral fractures of hip or knee arthroplasty. Analysis of 34 cases and a review of Spanish series in the last 20 years

Objetivo. Evaluar las fracturas periprotésicas de fémur analizando las características de los pacientes, el tipo de tratamiento y los resultados, y compararlas con las series españolas publicadas en los últimos 20 años. Material y método. Evaluación retrospectiva de las fracturas periprotésicas de fémur atendidas en nuestro centro entre 2010 y 2014. Revisión de las historias clínicas y encuesta telefónica sobre la situación actual. Resultados. Hemos analizado 34 fracturas periprotésicas de fémur, 20 sobre prótesis de cadera y 14 sobre prótesis de rodilla. La edad media fue 79,9 años. El 91% tenían comorbilidad previa y hasta un 36% tenían al menos 3 enfermedades sistémicas previas. La estancia hospitalaria media fue 8,7 días, mayor en los casos tratados quirúrgicamente. Hasta el 60,6% de los pacientes presentaron complicaciones y la tasa de mortalidad ha sido del 18%. El 61,5% de los pacientes no recuperaron el estado funcional previo a la fractura, con mayor dolor en los pacientes con artroplastia de cadera. Discusión. Las fracturas periprotésicas de fémur son cada vez más frecuentes, porque cada vez se realizan más artroplastias y en pacientes más mayores. El tratamiento es complejo, porque a la propia dificultad de la fractura se añade la presencia de un implante previo, la baja calidad ósea y la comorbilidad. Conclusiones. Las fracturas periprotésicas de fémur suponen una merma en la calidad de vida de los pacientes. Requieren un tratamiento individualizado. La tasa de complicaciones y de mortalidad es muy elevada (AU)

Purpose.To evaluate peri-prosthetic femoral fractures by analysing type of patient, treatment and outcomes, and to compare them with Spanish series published in the last 20 years. Material and methods.A retrospective review of the medical records of patients with peri-prosthetic femoral fractures treated in our hospital from 2010 to 2014, and telephone survey on the current status. Results. A total of 34 peri-prosthetic femoral fractures were analysed, 20 in hip arthroplasty and 14 in knee arthroplasty. The mean age of the patients was 79.9 years, and 91% had previous comorbidity, with up to 36% having at least 3 prior systemic diseases. Mean hospital stay was 8.7 days, and was higher in surgically-treated than in conservative-treated patients. The majority (60.6%) of patients had complications, and mortality was 18%. Functional status was not regained in 61.5% of patients, and pain was higher in hip than in knee arthroplasty. Discussion. Peri-prosthetic femoral fractures are increasing in frequency. This is due to the increasing number of arthroplasties performed and also to the increasing age of these patients. Treatment of these fractures is complex because of the presence of an arthroplasty component, low bone quality, and comorbidity of the patients. Conclusion. Peri-prosthetic femoral fractures impair quality of life. They need individualised treatment, and have frequent complications and mortality (AU)

Peri-prosthetic femoral fractures of hip or knee arthroplasty. Analysis of 34 cases and a review of Spanish series in the last 20 years. / Fracturas periprotésicas de fémur sobre prótesis de cadera y rodilla. Análisis de una serie de 34 casos y revisión de las series españolas en los últimos 20 años.

PURPOSE: To evaluate peri-prosthetic femoral fractures by analysing type of patient, treatment and outcomes, and to compare them with Spanish series published in the last 20 years. MATERIAL AND METHODS: A retrospective review of the medical records of patients with peri-prosthetic femoral fractures treated in our hospital from 2010 to 2014, and telephone survey on the current status. RESULTS: A total of 34 peri-prosthetic femoral fractures were analysed, 20 in hip arthroplasty and 14 in knee arthroplasty. The mean age of the patients was 79.9 years, and 91% had previous comorbidity, with up to 36% having at least 3 prior systemic diseases. Mean hospital stay was 8.7 days, and was higher in surgically-treated than in conservative-treated patients. The majority (60.6%) of patients had complications, and mortality was 18%. Functional status was not regained in 61.5% of patients, and pain was higher in hip than in knee arthroplasty. DISCUSSION: Peri-prosthetic femoral fractures are increasing in frequency. This is due to the increasing number of arthroplasties performed and also to the increasing age of these patients. Treatment of these fractures is complex because of the presence of an arthroplasty component, low bone quality, and comorbidity of the patients. CONCLUSION: Peri-prosthetic femoral fractures impair quality of life. They need individualised treatment, and have frequent complications and mortality.

Increased peri-ductal collagen micro-organization may contribute to raised mammographic density.

BACKGROUND: High mammographic density is a therapeutically modifiable risk factor for breast cancer. Although mammographic density is correlated with the relative abundance of collagen-rich fibroglandular tissue, the causative mechanisms, associated structural remodelling and mechanical consequences remain poorly defined. In this study we have developed a new collaborative bedside-to-bench workflow to determine the relationship between mammographic density, collagen abundance and alignment, tissue stiffness and the expression of extracellular matrix organising proteins. METHODS: Mammographic density was assessed in 22 post-menopausal women (aged 54-66 y). A radiologist and a pathologist identified and excised regions of elevated non-cancerous X-ray density prior to laboratory characterization. Collagen abundance was determined by both Masson's trichrome and Picrosirius red staining (which enhances collagen birefringence when viewed under polarised light). The structural specificity of these collagen visualisation methods was determined by comparing the relative birefringence and ultrastructure (visualised by atomic force microscopy) of unaligned collagen I fibrils in reconstituted gels with the highly aligned collagen fibrils in rat tail tendon. Localised collagen fibril organisation and stiffness was also evaluated in tissue sections by atomic force microscopy/spectroscopy and the abundance of key extracellular proteins was assessed using mass spectrometry. RESULTS: Mammographic density was positively correlated with the abundance of aligned periductal fibrils rather than with the abundance of amorphous collagen. Compared with matched tissue resected from the breasts of low mammographic density patients, the highly birefringent tissue in mammographically dense breasts was both significantly stiffer and characterised by large (>80 µm long) fibrillar collagen bundles. Subsequent proteomic analyses not only confirmed the absence of collagen fibrosis in high mammographic density tissue, but additionally identified the up-regulation of periostin and collagen XVI (regulators of collagen fibril structure and architecture) as potential mediators of localised mechanical stiffness. CONCLUSIONS: These preliminary data suggest that remodelling, and hence stiffening, of the existing stromal collagen microarchitecture promotes high mammographic density within the breast. In turn, this aberrant mechanical environment may trigger neoplasia-associated mechanotransduction pathways within the epithelial cell population.

Enclosing the commons: reasons for the adoption and adaptation of enclosures in the arid and semi-arid rangelands of Chepareria, Kenya.

The adoption and adaptation of enclosures in the arid and semi-arid rangelands of sub-Saharan Africa is driven and sustained by a combination of factors. However, reviews indicate that these factors cannot be generalized, as they tend to be case specific. A study was therefore conducted to explore the history and reasons for enclosure establishment in Chepareria, a formerly degraded communal rangeland in north-western Kenya. While Vi-Agroforestry Organization accounting for 52.5 % was the main source of knowledge on enclosure establishment; it has now emerged that rangeland enclosures among the Pokot pastoral community existed prior to land management interventions by Vi- Agroforestry. Results indicated that there are three categories of enclosures which were established for boundary demarcation, provide grazing reserves, enable proper land management, facilitate crop cultivation in a pastoral setup and to curb land degradation. The role of self-trigger [accounting for most of the spontaneous enclosures (73.5 %)] indicates the continued establishment and expansion of areas under enclosure management as private land ownership accounting for 51.7 % of enclosure tenure continues to gain momentum in Chepareria. While rangeland enclosures in Chepareria were mainly established for boundary demarcation, to alleviate pasture scarcity and enable proper management of formerly degraded areas; they have facilitated land restoration and rehabilitation by increasing flexibility in land, fodder and livestock management amongst agro-pastoralists in Chepareria over the last three decades. To ensure that rehabilitated areas do not revert to their previously degraded state; technical interventions are needed to allow for a more intensive use of rangeland resources within enclosed areas.

Global occurrence of anti-infectives in contaminated surface waters: Impact of income inequality between countries.

The presence anti-infectives in environmental waters is of interest because of their potential role in the dissemination of anti-infective resistance in bacteria and other harmful effects on non-target species such as algae and shellfish. Since no information on global trends regarding the contamination caused by these bioactive substances is yet available, we decided to investigate the impact of income inequality between countries on the occurrence of anti-infectives in surface waters. In order to perform such study, we gathered concentration values reported in the peer-reviewed literature between 1998 and 2014 and built a database. To fill the gap of knowledge on occurrence of anti-infectives in African countries, we also collected 61 surface water samples from Ghana, Kenya, Mozambique and South Africa, and measured concentrations of 19 anti-infectives. A mixed one-way analysis of covariance (ANCOVA) model, followed by Turkey-Kramer post hoc tests was used to identify potential differences in anti-infective occurrence between countries grouped by income level (high, upper-middle and lower-middle and low income) according to the classification by the World Bank. Comparison of occurrence of anti-infectives according to income level revealed that concentrations of these substances in contaminated surface waters were significantly higher in low and lower-middle income countries (p=0.0001) but not in upper-middle income countries (p=0.0515) compared to high-income countries. We explained these results as the consequence of the absence of or limited sewage treatment performed in lower income countries. Furthermore, comparison of concentrations of low cost anti-infectives (sulfonamides and trimethoprim) and the more expensive macrolides between income groups suggest that the cost of these substances may have an impact on their environmental occurrence in lower income countries. Since wastewaters are the most important source of contamination of anti-infectives and other contaminants of emerging concern in the environment, it is expected that deleterious effects to the aquatic biota caused by these substances will be more pronounced in countries with inadequate wastewater and collection infrastructure. With the information currently available, we could not evaluate either the role of the receiving environment or the importance of regulatory frameworks on the occurrence of anti-infectives in surface waters. Future studies should focus on these two factors in order to better evaluate risks to aquatic ecosystems in LM&LICs. We propose that CECs such as anti-infectives could be used as a new class of environmental degradation indicators that could be helpful to assess the state of development of wastewater collection and treatment infrastructure around the world.

A novel androgen signalling pathway uses dihydrotestosterone, but not testosterone, to activate the EGF receptor signalling cascade in prostate stromal cells.

BACKGROUND AND PURPOSE: Human prostate growth and function are tightly controlled by androgens that are generally thought to exert their effects by regulating gene transcription. However, a rapid, non-genomic steroid action, often involving an elevation of intracellular calcium ([Ca(2+) ]i ), has also been described in a number of cell types. In this study we investigate whether androgens acutely regulate [Ca(2+) ]i in stromal cells derived from the human prostate. EXPERIMENTAL APPROACH: Human-cultured prostatic stromal cells (HCPSCs) were loaded with the calcium-sensitive fluorophore, fura-2-acetoxymethyl ester (FURA-2AM) (10 µM). Changes in [Ca(2+) ]i in response to the androgens, dihydrotestosterone (DHT) and testosterone, as well as EGF were measured by fluorescence microscopy. KEY RESULTS: DHT, but not testosterone (0.03-300 nM), elicited concentration-dependent elevations of [Ca(2+) ]i within 1 min of addition. These responses were blocked by the androgen receptor antagonist, flutamide (10 µM); the sarcoplasmic reticulum ATPase pump inhibitor, thapsigargin (1 µM); the inositol trisphosphate receptor inhibitor, 2-aminoethyldiphenyl borate (50 µM) and the PLC inhibitor, U-73122 (1 µM). Responses were also blocked by the L-type calcium channel blocker, nifedipine (1 µM), and by removal of extracellular calcium. A similar transient elevation of [Ca(2+) ]i was elicited by EGF (100 ng·mL(-1) ). The EGF receptor inhibitor, AG 1478 (30 nM), and the MMP inhibitor, marimastat (100 nM), blocked the DHT-induced elevation of [Ca(2+) ]i . CONCLUSIONS AND IMPLICATIONS: These studies show that DHT elicits an androgen receptor-dependent acute elevation of [Ca(2+) ]i in HCPSC, most likely by activating EGF receptor signalling.

Effect of the shutdown of a large coal-fired power plant on ambient mercury species.

In the spring of 2008, a 260MWe coal-fired power plant (CFPP) located in Rochester, New York was closed over a 4month period. Using a 2-years data record, the impacts of the shutdown of the CFPP on nearby ambient concentrations of three Hg species were quantified. The arithmetic average ambient concentrations of gaseous elemental mercury (GEM), gaseous oxidized mercury (GOM), and particulate mercury (PBM) during December 2007-November 2009 were 1.6ngm(-3), 5.1pgm(-3), and 8.9pgm(-3), respectively. The median concentrations of GEM, GOM, and PBM significantly decreased by 12%, 73%, and 50% after the CFPP closed (Mann-Whitney test, p<0.001). Positive Matrix Factorization (EPA PMF v4.1) identified six factors including O3-rich, traffic, gas phase oxidation, wood combustion, nucleation, and CFPP. When the CFPP was closed, median concentrations of GEM, GOM, and PBM apportioned to the CFPP factor significantly decreased by 25%, 74%, and 67%, respectively, compared to those measured when the CFPP was still in operation (Mann-Whitney test, p<0.001). Conditional probability function (CPF) analysis showed the greatest reduction in all three Hg species was associated with northwesterly winds pointing toward the CFPP. These changes were clearly attributable to the closure of the CFPP.

Factores de riesgo para el desarrollo de metástasis cutáneas locorregionales como forma única de recaída en los pacientes con melanoma / Risk Factors for the Development of Locoregional Cutaneous Metastases as the Sole Form of Recurrence in Patients With Melanoma

Introducción: Las metástasis cutáneas locorregionales (en tránsito y satelitosis) constituyen un evento poco estudiado en la progresión del melanoma, con diferencias patogénicas y pronósticas respecto a otras formas de recaída locorregional. Conocer las variables predictivas de este evento sería de gran utilidad en su prevención, diagnóstico precoz y tratamiento. El objetivo de este trabajo fue evaluar los posibles factores de riesgo asociados a la aparición de metástasis cutáneas locorregionales como primera forma de recaída en la progresión metastásica del melanoma. Material y métodos: Entre 2000 y 2010, los datos de 1.327 pacientes diagnosticados de melanoma en estadios I y II fueron recogidos de forma prospectiva en nuestras consultas. Durante el seguimiento, un total de 112 (8,4%) pacientes sufrió progresión metastásica de su enfermedad. De ellos, 36 pacientes presentaron metástasis cutáneas locorregionales no concurrentes con otras formas de recurrencia. Las características clínicas e histológicas de este subgrupo fueron evaluadas. Resultados: En el análisis univariante, los factores predictivos significativos fueron la edad del paciente, el espesor del tumor primario, la localización, la ulceración, el índice mitósico y el tipo histológico. Después del análisis multivariante, se mantuvieron como factores de riesgo independientes el espesor (razón de riesgo [RR] 5,6 e IC 95%: 2,7-11,5), la localización del tumor primario en miembros inferiores (RR 3,4 e IC 95%: 1,0-11,5), en cabeza/cuello (RR 4,8 e IC 95%: 1,7-13,5) y en zonas acrales (RR 6,7 e IC 95%: 2,2-20,8). Conclusión: Los pacientes con melanomas de más de 2mm de Breslow, localizados en miembros inferiores, cabeza/cuello y zonas acrales tienen un mayor riesgo de padecer metástasis cutáneas locorregionales. Estos datos podrían ser útiles en el diseño de futuras guías para el seguimiento y manejo del melanoma (AU)

Background: While locoregional cutaneous metastases (in transit and satellite) in melanoma have received little attention from researchers to date, they have pathogenic and prognostic features that distinguish them from other forms of locoregional recurrence. Identifying predictors of these metastases would be of great value for their prevention, early diagnosis, and treatment. The aim of this study was to identify the risk factors associated with locoregional cutaneous metastases as the first form of recurrence in the metastatic progression of melanoma. Material and methods: Between 2000 and 2010, we prospectively collected the data of 1327 patients diagnosed with stage I and II melanoma. During follow up, 112 patients (8.4%) developed metastases. Of these, 36 had exclusively locoregional cutaneous metastases. The clinical and histological characteristics of this subgroup were evaluated. Results: In the univariate analysis, significant predictors were patient age, primary tumor thickness, site, ulceration, mitotic index, and histological type. After multivariate analysis, the independent risk factors were tumor thickness (risk ratio [RR] 5.6; 95% CI: 2.7-11.5) and the location of the primary tumor on the lower limbs (RR 3.4; 95% CI: 1.0-11.5), on the head or neck (RR 4.8; 95% IC: 1.7-13.5), or in acral sites (RR 6.7; 95% IC: 2.2-20.8). Conclusion: Patients who have melanomas with a Breslow thickness of more than 2 mm located on the lower limbs, head, neck, or acral sites have a higher risk of developing locoregional cutaneous metastases. These findings could be useful in the design of future guidelines for the monitoring and management of melanoma (AU)

Risk factors for the development of locoregional cutaneous metastases as the sole form of recurrence in patients with melanoma.

BACKGROUND: While locoregional cutaneous metastases (in transit and satellite) in melanoma have received little attention from researchers to date, they have pathogenic and prognostic features that distinguish them from other forms of locoregional recurrence. Identifying predictors of these metastases would be of great value for their prevention, early diagnosis, and treatment. The aim of this study was to identify the risk factors associated with locoregional cutaneous metastases as the first form of recurrence in the metastatic progression of melanoma. MATERIAL AND METHODS: Between 2000 and 2010, we prospectively collected the data of 1327 patients diagnosed with stage I and II melanoma. During follow up, 112 patients (8.4%) developed metastases. Of these, 36 had exclusively locoregional cutaneous metastases. The clinical and histological characteristics of this subgroup were evaluated. RESULTS: In the univariate analysis, significant predictors were patient age, primary tumor thickness, site, ulceration, mitotic index, and histological type. After multivariate analysis, the independent risk factors were tumor thickness (risk ratio [RR] 5.6; 95% CI: 2.7-11.5) and the location of the primary tumor on the lower limbs (RR 3.4; 95% CI: 1.0-11.5), on the head or neck (RR 4.8; 95% IC: 1.7-13.5), or in acral sites (RR 6.7; 95% IC: 2.2-20.8). CONCLUSION: Patients who have melanomas with a Breslow thickness of more than 2mm located on the lower limbs, head, neck, or acral sites have a higher risk of developing locoregional cutaneous metastases. These findings could be useful in the design of future guidelines for the monitoring and management of melanoma.

Mitotic rate and subcutaneous involvement are prognostic factors for survival after recurrence in patients with only locoregional skin metastasis as the first site of recurrence from cutaneous melanoma.

BACKGROUND: Few reports on literature give detailed figures on prognostic factors of locoregional skin recurrence in cutaneous melanoma. OBJECTIVE: The aim of this study was to evaluate clinical and histological prognostic factors following development of locoregional cutaneous metastasis as the only progression site from melanoma. METHODS: Data from 1327 stage I and II melanoma patients who visited Instituto Valenciano de Oncología and Consorcio Hospital General Universitario de Valencia from 2000 to 2010 were documented in a prospective manner. During follow up, 112 (8.4%) of them developed recurrent disease. A retrospective analysis revealed a subset of 36 patients with locoregional cutaneous metastases as a first event. RESULTS: Significant prognostic factors in the univariate analysis were Breslow thickness, tumor mitotic rate and the presence subcutaneous involvement of the skin metastasis. After multivariate analysis the independent predictive factors for survival after recurrence were tumor mitotic rate (hazard ratio [HR]: 8.6; 95% CI: 1.0-77.2) and subcutaneous involvement of the skin metastasis (HR: 4.3; 95% CI: 1.0-18.5). CONCLUSION: The survival after recurrence of melanoma patients that has relapsed with only locoregional cutaneous metastasis depends on the mitotic rate of the primary tumor and the subcutaneous involvement of the metastasis.

Estudio multicéntrico de casos y controles sobre factores de riesgo de desarrollar un melanoma cutáneo en la Comunidad Valenciana / Multicenter Case-Control Study of Risk Factors for Cutaneous Melanoma in Valencia, Spain

Introducción: En la población general es importante identificar aquellos subgrupos con un riesgo elevado de padecer un melanoma cutáneo, por la posibilidad de aplicar medidas preventivas y de detección temprana de la enfermedad. La mayoría de los estudios realizados que evalúan estos factores de riesgo tienen una aplicabilidad limitada en nuestro medio, debido a que las poblaciones estudiadas están sometidas a distintos factores ambientales y los rasgos pigmentarios son diferentes. Objetivos: Identificar qué características fenotípicas individuales y relacionadas con la exposición solar son factores de riesgo para desarrollar un melanoma cutáneo en la población de la Comunidad Valenciana. Métodos: Realizamos un estudio multiinstitucional observacional de casos y controles. Fueron incluidos 242 casos de melanoma incidentes tratados en 5 hospitales, y 173 controles recogidos entre los acompañantes de los pacientes entre enero de 2007 y junio de 2008. La información fue recogida mediante un cuestionario estandarizado y validado. Fue calculada la odds ratio (OR) para cada variable y ajustada mediante regresión logística múltiple. Resultados: Los fototipos I-II, el color de pelo rubio o pelirrojo, el color de ojos claro, la presencia de abundantes nevos melanocíticos y los antecedentes personales de queratosis actínicas o de cáncer cutáneo no melanoma fueron los factores de riesgo estadísticamente significativos. Tras el estudio multivariado solo el color de pelo rubio o pelirrojo (OR=1,9), la presencia de múltiples nevos melanocíticos (OR=3,1), los fototipos I-II (OR=2,1) y los antecedentes personales de queratosis actínicas (OR=3,5) o de cáncer cutáneo no melanoma (OR=8,1) se mantuvieron en el modelo como las variables predictivas independientes relacionadas con el desarrollo de melanoma. Conclusiones: Nuestro estudio apoya la importancia de una serie de factores que indican predisposición genética (color de pelo y fototipo) y ambientales relacionados con la exposición solar. Los pacientes con múltiples nevos melanocíticos adquiridos, y también aquellos con marcadores de daño solar crónico (queratosis actínicas y cáncer cutáneo no melanoma), presentaron un significativo aumento del riesgo (AU)

Introduction: It is important to identify subgroups within the general population that have an elevated risk of developing cutaneous melanoma because preventive and early-detection measures are useful in this setting. The findings of most studies that have evaluated risk factors for cutaneous melanoma are of limited application in Spain because the populations studied have different pigmentary traits and are subject to different environmental factors. Objective: To identify the phenotypic characteristics and amount of exposure to sunlight that constitute risk factors for cutaneous melanoma in the population of the Autonomous Community of Valencia, Spain. Methods: We performed a multicenter observational case-control study. In total, the study included 242 patients with melanoma undergoing treatment in 5 hospitals and 173 controls enrolled from among the companions of the patients between January 2007 and June 2008.The information was collected by means of a standardized, validated questionnaire. The odds ratio (OR) was calculated for each variable and adjusted using a multiple logistic regressionmodel. Results: The risk factors found to be statistically significant were skin phototypes I and II, blondor red hair, light eye color, abundant melanocytic nevi, and a personal history of actinic keratosisor nonmelanoma skin cancer. After the multivariate analysis, only blond or red hair (OR = 1.9), multiple melanocytic nevi (OR = 3.1), skin phototypes I and II (OR = 2.1), and a personal history of actinic keratosis (OR = 3.5) or nonmelanoma skin cancer (OR = 8.1) maintained significance in the model as independent predictive variables for melanoma. Conclusions: Our study supports the importance of certain factors that indicate genetic predisposition(hair color and skin phototype) and environmental factors associated with exposure to sunlight. Patients with multiple acquired melanocytic nevi and patients with markers of chronic skin sun damage (actinic keratosis and nonmelanoma cancer) presented a significant increase in risk (AU)