Pharmacogenetic biomarkers for secukinumab response in psoriasis patients in real-life clinical practice.

BACKGROUND: Prediction of the response to a biological treatment in psoriasis patients would allow efficient treatment allocation. OBJECTIVE: To identify polymorphisms associated with secukinumab response in psoriasis patients in a daily practice setting. METHODS: We studied 180 SNPs in patients with moderate-to-severe plaque psoriasis recruited from 15 Spanish hospitals. Treatment effectiveness was evaluated by absolute PASI ≤3 and ≤1 at 6 and 12 months. Individuals were genotyped using a custom Taqman array. Multiple logistic regression models were generated. Sensitivity, specificity and area under the curve (AUC) were analysed. RESULTS: A total of 173 patients were studied at 6 months, (67% achieved absolute PASI ≤ 3 and 65% PASI ≤ 1) and 162 at 12 months (75% achieved absolute PASI ≤ 3 and 64% PASI ≤ 1). Multivariable analysis showed the association of different sets of SNPs with the response to secukinumab. The model of absolute PASI≤3 at 6 months showed best values of sensitivity and specificity. Four SNPs were associated with the capability of achieving absolute PASI ≤ 3 at 6 months. rs1801274 (FCGR2A), rs2431697 (miR-146a) and rs10484554 (HLCw6) were identified as risk factors for failure to achieve absolute PASI≤3, while rs1051738 (PDE4A) was protective. AUC including these genotypes, weight of patients and history of biological therapy was 0.88 (95% CI 0.83-0.94), with a sensitivity of 48.6% and specificity of 95.7% to discriminate between both phenotypes. CONCLUSION: We have identified a series of polymorphisms associated with the response to secukinumab capable of predicting the potential response/non-response to this drug in patients with plaque psoriasis.

Moderate to Severe Psoriasis in Pediatric and Young Patients: The BIOBADADERM Registry Experience. / Psoriasis moderada-grave en pacientes pediátricos y jóvenes: experiencia en el registro BIOBADADERM.

Childhood-onset psoriasis generally follows an indolent course but patients with moderate or severe disease may require systemic treatment. The aim of this study was to determine the relative proportion of children and young people aged up to 21 years with moderate to severe psoriasis in the BIOBADADERM registry and to analyze the characteristics of these patients, treatments used, and adverse events. Of the 3946 patients in the registry, 24 were aged 21 years or younger. They had mean age of 16.1 years on starting treatment. When the registry was started, they had a Psoriasis Area and Severity Index of 9.4 and 67% were being treated with a conventional systemic drug. Treatment was discontinued in 14 patients (58%) due to adverse events or a loss or lack of effectiveness. In conclusion, the BIOBADADERM registry shows that young people account for a small proportion of psoriasis patients receiving systemic treatment, and they are more likely to be treated using conventional systemic drugs.

Psoriasis moderada-grave en pacientes pediátricos y jóvenes: experiencia en el registro BIOBADADERM / Moderate to Severe Psoriasis in Pediatric and Young Patients: The BIOBADADERM Registry Experience

El comienzo de la psoriasis en la edad pediátrica, aunque generalmente leve, puede requerir tratamiento sistémico en las formas moderadas o graves de la enfermedad. El objetivo de este trabajo es analizar la frecuencia relativa, las características de los pacientes, el tratamiento empleado y los eventos adversos (EA) observados a partir del registro BIOBADADERM en niños y jóvenes con psoriasis moderada-grave. Del total de 3.946 pacientes del registro, se incluyen 24 pacientes menores de 21 años, con una edad media al inicio del tratamiento en BIOBADADERM de 16,1 años y un PASI medio de 9,4. El 67% de los pacientes estaba en tratamiento sistémico clásico al inicio del registro. Catorce pacientes (58%) suspendieron el tratamiento por pérdida o falta de eficacia o por EA. En conclusión, los datos del registro BIOBADADERM muestran que los menores representan un grupo muy pequeño dentro de los pacientes con psoriasis que reciben tratamiento sistémico y son manejados más frecuentemente con tratamientos clásicos (AU)

Childhood-onset psoriasis generally follows an indolent course but patients with moderate or severe disease may require systemic treatment. The aim of this study was to determine the relative proportion of children and young people aged up to 21 years with moderate to severe psoriasis in the BIOBADADERM registry and to analyze the characteristics of these patients, treatments used, and adverse events. Of the 3946 patients in the registry, 24 were aged 21 years or younger. They had mean age of 16.1 years on starting treatment. When the registry was started, they had a Psoriasis Area and Severity Index of 9.4 and 67% were being treated with a conventional systemic drug. Treatment was discontinued in 14 patients (58%) due to adverse events or a loss or lack of effectiveness. In conclusion, the BIOBADADERM registry shows that young people account for a small proportion of psoriasis patients receiving systemic treatment, and they are more likely to be treated using conventional systemic drugs (AU)

[Translated article] Moderate to Severe Psoriasis in Pediatric and Young Patients: The BIOBADADERM Registry Experience / Psoriasis moderada-grave en pacientes pediátricos y jóvenes: experiencia en el registro BIOBADADERM

Childhood-onset psoriasis generally follows an indolent course but patients with moderate or severe disease may require systemic treatment. The aim of this study was to determine the relative proportion of children and young people aged up to 21 years with moderate to severe psoriasis in the BIOBADADERM registry and to analyze the characteristics of these patients, treatments used, and adverse events. Of the 3946 patients in the registry, 24 were aged 21 years or younger. They had mean age of 16.1 years on starting treatment. When the registry was started, they had a Psoriasis Area and Severity Index of 9.4 and 67% were being treated with a conventional systemic drug. Treatment was discontinued in 14 patients (58%) due to adverse events or a loss or lack of effectiveness. In conclusion, the BIOBADADERM registry shows that young people account for a small proportion of psoriasis patients receiving systemic treatment, and they are more likely to be treated using conventional systemic drugs (AU)

El comienzo de la psoriasis en la edad pediátrica, aunque generalmente leve, puede requerir tratamiento sistémico en las formas moderadas o graves de la enfermedad. El objetivo de este trabajo es analizar la frecuencia relativa, las características de los pacientes, el tratamiento empleado y los eventos adversos (EA) observados a partir del registro BIOBADADERM en niños y jóvenes con psoriasis moderada-grave. Del total de 3.946 pacientes del registro, se incluyen 24 pacientes menores de 21 años, con una edad media al inicio del tratamiento en BIOBADADERM de 16,1 años y un PASI medio de 9,4. El 67% de los pacientes estaba en tratamiento sistémico clásico al inicio del registro. Catorce pacientes (58%) suspendieron el tratamiento por pérdida o falta de eficacia o por EA. En conclusión, los datos del registro BIOBADADERM muestran que los menores representan un grupo muy pequeño dentro de los pacientes con psoriasis que reciben tratamiento sistémico y son manejados más frecuentemente con tratamientos clásicos (AU)

Characterization and Outcomes in Patients Treated With Apremilast in Routine Clinical Practice in Spain: Results From the APPRECIATE Study. / Caracterización y resultados de pacientes tratados con apremilast en la práctica clínica habitual española: resultados del estudio APPRECIATE.

BACKGROUND AND OBJECTIVES: It is necessary to expand the knowledge in the use of apremilast in clinical practice. The APPRECIATE study (NCT02740218) aims to describe the characteristics of patients with psoriasis treated with apremilast, to evaluate their perspectives and those of dermatologists, as well as the outcomes obtained in clinical practice in Spain. METHODS: Observational, retrospective, cross-sectional, multicenter study of patients with chronic plaque psoriasis who could be contacted 6 (±1) months after apremilast initiation. The data were obtained from medical records and questionnaires from patients and physicians. RESULTS: A total of 80 patients were evaluated; at apremilast onset, they showed mean (standard deviation, SD) Psoriasis Area and Severity Index (PASI) = 8.3 (5.3), mean (SD) Dermatology Life Quality Index (DLQI) = 8.9 (6.6). At six months, 58.8% (n=47) of patients continued apremilast treatment (discontinuations due to lack of efficacy [16.3%], safety/tolerability [20.0%]). In patients continuing treatment, PASI75 was achieved by 36.7% of patients; mean (95% CI) DLQI score was 2.2 (0.7-3.6) and mean (SD) Patient Benefit Index score was 2.8 (0.8). Compliance with physicians' expectations was correlated with benefits reported by patients (r=0.636). Adverse events were reported by 56.3% of patients (the most common were diarrhoea and nausea). CONCLUSIONS: Patients receiving apremilast for 6 months in Spanish clinical practice, reported substantial improvements in their quality of life (mean DLQI reduced by more than 6 points) and disease severity (PASI75 achieved by over one-third of patients), despite less skin involvement than patients who enrolled in clinical trials.

Cambios en las tendencias de la prescripción y causas de la interrupción en los tratamientos biológicos indicados en la psoriasis durante los primeros 10 años. Datos obtenidos del registro español Biobadaderm / Changing Trends in Drug Prescription and Causes of Treatment Discontinuation of First Biologic Over Ten Years in Psoriasis in the Spanish Biobadaderm Registry

ANTECEDENTES Y OBJETIVOS: Las guías sobre el tratamiento de la psoriasis habitualmente no incluyen las recomendaciones acerca de cuál debe ser la primera línea de tratamiento sistémico o biológico. Los objetivos de este estudio fueron describir las tendencias en la prescripción del primer fármaco biológico y comparar la retirada de los fármacos y las tasas de efectos adversos a lo largo de los 10 años de seguimiento. MATERIAL Y MÉTODOS: Se utilizó el registro Biobadaderm para determinar cuál fue el primer fármaco biológico indicado en pacientes con psoriasis naïve para biológicos, así como cuál es la tasa de efectos adversos y los motivos de suspensión de los fármacos. Los resultados obtenidos se compararon en tres periodos distintos de tiempo (2008-2010, 2011-2014, 2015-2018). RESULTADOS: Los fármacos anti-TNF fueron los biológicos prescritos con mayor frecuencia entre los años 2008 y 2010. Ustekinumab se convirtió en el tratamiento biológico más indicado a partir de 2014. El motivo principal de suspensión de los tratamientos fueron los efectos adversos, la falta de eficacia y la remisión de la enfermedad. La probabilidad de suspender los fármacos por uno de estos motivos fue cada vez menor si se compara con el periodo de tiempo previo. CONCLUSIONES: El presente estudio identifica cuáles fueron las tendencias en la prescripción del primer fármaco biológico en la práctica clínica habitual entre los años 2008 y 2018. Sugiere que los dermatólogos estamos cada vez más seguros en cuanto al perfil de seguridad y somos cada vez más exigentes en cuanto a la eficacia de los fármacos

BACKGROUND AND OBJECTIVES: Current psoriasis guidelines do not usually include recommendations about first line classical or biologic treatment. The objectives of this study were: to describe shifts in the prescription of the first biological treatment, and to compare treatment withdrawal and rates of adverse events over ten years. MATERIAL AND METHODS: Biobadaderm registry was analyzed to describe: first biological prescription in bio-naïve patients, adverse events rate and reasons for drug withdrawal comparing three periods of time (2008-2010, 2011-2014, 2015-2018). RESULTS: Anti-TNF drugs were the most prescribed biological drug from 2008 to 2010. Ustekinumab has become the most prescribed first biologic since 2014. The main reasons for drug discontinuation were adverse events, lack of efficacy and remission. In each period any treatment was less likely to be discontinued due to any of these three reasons comparing to the previous period. CONCLUSIONS: The present study identifies trends in prescription of the first biological antipsoriatic drug in clinical practice from 2008 to 2018. It suggests that we have become more comfortable with the safety profile and more exigent with the efficacy of the drugs

Changing Trends in Drug Prescription and Causes of Treatment Discontinuation of First Biologic Over Ten Years in Psoriasis in the Spanish Biobadaderm Registry. / Cambios en las tendencias de la prescripción y causas de la interrupción en los tratamientos biológicos indicados en la psoriasis durante los primeros 10 años. Datos obtenidos del registro español Biobadaderm.

BACKGROUND AND OBJECTIVES: Current psoriasis guidelines do not usually include recommendations about first line classical or biologic treatment. The objectives of this study were: to describe shifts in the prescription of the first biological treatment, and to compare treatment withdrawal and rates of adverse events over ten years. MATERIAL AND METHODS: Biobadaderm registry was analyzed to describe: first biological prescription in bio-naïve patients, adverse events rate and reasons for drug withdrawal comparing three periods of time (2008-2010, 2011-2014, 2015-2018). RESULTS: Anti-TNF drugs were the most prescribed biological drug from 2008 to 2010. Ustekinumab has become the most prescribed first biologic since 2014. The main reasons for drug discontinuation were adverse events, lack of efficacy and remission. In each period any treatment was less likely to be discontinued due to any of these three reasons comparing to the previous period. CONCLUSIONS: The present study identifies trends in prescription of the first biological antipsoriatic drug in clinical practice from 2008 to 2018. It suggests that we have become more comfortable with the safety profile and more exigent with the efficacy of the drugs.

Real-world effectiveness and safety of apremilast in psoriasis at 52 weeks: a retrospective, observational, multicentre study by the Spanish Psoriasis Group.

BACKGROUND: Little has been published on the real-world effectiveness and safety of apremilast in psoriasis. OBJECTIVES: To evaluate the effectiveness, safety and drug survival of apremilast at 52 weeks in patients with moderate to severe plaque psoriasis or palmoplantar psoriasis in routine clinical practice. METHODS: Retrospective, multicentre study of adult patients with moderate to severe plaque psoriasis or palmoplantar psoriasis treated with apremilast from March 2016 to March 2018. RESULTS: We studied 292 patients with plaque psoriasis and 85 patients with palmoplantar psoriasis. The mean (SD) Psoriasis Area and Severity Index (PASI) score was 10.7 (7.0) at baseline and 3.0 (4.2) at 52 weeks. After 12 months of treatment, 73.6% of patients had a PASI score of 3 or less. In terms of relative improvement by week 52, 49.7% of patients achieved PASI-75 (≥75% reduction in PASI score) and 26.5% achieved PASI-90. The mean physician global assessment score for palmoplantar psoriasis fell from 4.2 (5.2) at baseline to 1.3 (1.3) at week 52. Overall drug survival after 1 year of treatment with apremilast was 54.9 %. The main reasons for treatment discontinuation were loss of efficacy (23.9%) and adverse events (15.9%). Almost half of the patients in our series (47%) experienced at least one adverse event. The most common events were gastrointestinal problems. CONCLUSIONS: Apremilast may be a suitable alternative for the treatment of moderate to severe psoriasis and palmoplantar psoriasis. Although the drug has a good safety profile, adverse gastrointestinal effects are common.

Resección transoral endoscópica de tiroides lingual / Endoscopic transoral resection of lingual thyroid

La presencia de tejido tiroideo ectópico en la base de la lengua es muy infrecuente, y la mayoría de los pacientes tienen hipotiroidismo. La indicación de tratamiento depende de la presencia o no de síntomas; la cirugía es la primera elección. Diversas técnicas quirúrgicas han sido descriptas, pero para nosotros el abordaje transoral con endoscopios constituye la mejor opción, por la buena exposición y la mínima morbilidad que produce. Se describe el caso clínico de una mujer que consultó por odinofagia, con diagnóstico de tiroides lingual y que fue tratada con éxito mediante un abordaje transoral con asistencia de endoscopios. (AU)

The presence of ectopic thyroid tissue at the base of the tongue is very rare, and most patients have hypothyroidism. The indication of treatment depends on the presence or not of symptoms, surgery being the first choice. Various surgical techniques have been described, being for us the transoral approach with endoscopes the best option, due to the good exposure, and minimum morbidity that it produces. The clinical case of a woman who consulted for odynophagia, with a diagnosis of lingual thyroid and who was successfully treated by a transoral approach with endoscopic assistance is described. (AU)

Osteopenia and Osteoporosis in Patients with Bronchiectasis: Association with Respiratory Parameters, Body Composition, Muscle Strength and Bone Remodeling Biomarkers.

The prevalence of osteopenia/osteoporosis has not been sufficiently studied in people with bronchiectasis not due to cystic fibrosis (BC), nor has its relationship with other variables (clinical, body composition and bone turnover and inflammation markers) been sufficiently studied. Our aim was to determine the prevalence of osteopenia and osteoporosis and related factors in patients with BC. We did a cross-sectional study in people with BC in a clinically stable state. Spirometric parameters, annual exacerbations and analysis with bone turnover markers (BTM) and inflammation markers were evaluated. Densitometry (DXA) was performed for body composition, bone mineral density (BMD) and handgrip strength. 123 patients were studied (65% women, mean age 49.6 ± 18.8, Body Mass Index (BMI) 24.8 ± 4.7 kg/m2). 62.8% and 62.5% of men and women, respectively, had normal bone mineral density, 30.2% and 22.2% osteopenia and 7% and 15% osteoporosis. 52 patients (56.2%) had low fat-free mass: 68.9% women and 28.6% men. Patients with decreased bone mass had significantly lower muscle strength, maximum expiratory volume in the first second (FEV1%), vitamin D, higher levels of C-terminal telopeptide of type 1 collagen (CTX) and total osteocalcin and underarboxylated osteocalcin (ucOC). We observed significant and negative correlations between BMD and the number of serious exacerbations per year CTX and undercarboxylated osteocalcin. We observed significant positive correlations between BMD, fat free mass index (FFMI) and handgrip dynamometry. The study suggest that the prevalence of osteoporosis was high in relation to the demographic characteristics. Respiratory parameters, body composition, muscle strength and bone remodeling markers were associated with a lower bone mineral density.

Estudio de la rigidez arterial en pacientes con un evento coronario agudo y enfermedad pulmonar obstructiva crónica confirmada por espirometría / Study of arterial stiffness in patients with an acute coronary event and chronic obstructive pulmonary disease confirmed by spirometry

Antecedentes y objetivos: La enfermedad pulmonar obstructiva crónica (EPOC) empeora el pronóstico de los pacientes con un evento coronario agudo (ECA) tratado con intervención coronaria percutánea. Objetivo: evaluar el efecto de la EPOC sobre la rigidez arterial en pacientes con un ECA. Métodos: Pacientes con un ECA tratado con intervención coronaria percutánea. Al mes se realizó una espirometría posbroncodilatación y se determinó la rigidez arterial y marcadores de daño miocárdico (troponina T y ProBNP). Resultados: Se incluyeron 68 pacientes, de los cuales un 33% tenían EPOC (59% no diagnosticados). Los pacientes con EPOC presentaron valores más altos de rigidez arterial tras ajustar por edad y cifras tensionales. Los niveles de troponina T y ProBNP fueron más altos en los pacientes con EPOC. Conclusiones: La rigidez arterial es mayor en los pacientes con un ECA si tienen EPOC concomitante. Estos hallazgos pueden ayudar a explicar el peor pronóstico de los pacientes con ambas patologías

Background and objectives: Chronic obstructive pulmonary disease (COPD) worsens the prognosis for patients with an acute coronary event (ACE) treated with percutaneous coronary intervention. Objective To assess the effect of COPD on arterial stiffness in patients with an ACE. Methods: The study included patients with an ACE treated with percutaneous coronary intervention. At 1 month, postbronchodilation spirometry was performed, and arterial stiffness and markers of myocardial damage (troponin T and ProBNP) were measured. Results: We included 68 patients, 33% of whom had COPD (59% undiagnosed). The patients with COPD presented higher arterial stiffness values after adjusting for age and blood pressure readings. The troponin T and ProBNP levels were higher in the patients with COPD. Conclusions: Arterial stiffness is greater in patients with an ACE if they have concomitant COPD. These findings can help explain the poorer prognosis of patients with both conditions

Study of arterial stiffness in patients with an acute coronary event and chronic obstructive pulmonary disease confirmed by spirometry. / Estudio de la rigidez arterial en pacientes con un evento coronario agudo y enfermedad pulmonar obstructiva crónica confirmada por espirometría.

BACKGROUND AND OBJECTIVES: Chronic obstructive pulmonary disease (COPD) worsens the prognosis for patients with an acute coronary event (ACE) treated with percutaneous coronary intervention. Objective To assess the effect of COPD on arterial stiffness in patients with an ACE. METHODS: The study included patients with an ACE treated with percutaneous coronary intervention. At 1 month, postbronchodilation spirometry was performed, and arterial stiffness and markers of myocardial damage (troponin T and ProBNP) were measured. RESULTS: We included 68 patients, 33% of whom had COPD (59% undiagnosed). The patients with COPD presented higher arterial stiffness values after adjusting for age and blood pressure readings. The troponin T and ProBNP levels were higher in the patients with COPD. CONCLUSIONS: Arterial stiffness is greater in patients with an ACE if they have concomitant COPD. These findings can help explain the poorer prognosis of patients with both conditions.

Solid-liquid-liquid wettability and its prediction with surface free energy models.

Understanding wettability in solid-liquid-liquid (SLL or immersed) systems is important for numerous applications. However, predicting SLL wetting behavior on smooth surfaces has received little attention. The objective of this work was to explore alternatives to predict SLL wettability. To this end, we first present a review of solid surface free energy (σS) data obtained from solid-liquid-air (SLA) contact angle (θLa) data and a summary of available SLL contact angle data for selected materials. Next, the existing surface free energy models for SLA systems are discussed in terms of their applicability to predict wettability of SLL systems. Finally, the SLL wettability of toluene drops on glass, mica, stainless steel and PTFE immersed in equilibrated Toluene-water-isopropyl alcohol (IPA) solutions was determined via contact angle (θO) measurements through the oil phase using the inverted sessile drop method over a wide range of interfacial tensions (γo-aq). The results were plotted as γo-aq·cosθO vs. γo-aq, showing a smooth wetting transition from water-wetting to oil-wetting with decreasing γo-aq for glass and stainless steel. Mica remained water-wetting, while PTFE oil-wetting. The Geometric (GM) and Harmonic (HM) mean approaches, and the Equation-of-State (EQS), originally developed for SLA systems, were extended to SLL systems. The extended GM and HM approaches could fit the SLL behavior after fitting the dispersive and polar contributions of the solid surface free energy (σSd, σSp), which required additional SLA θLa measurements using PTFE as the reference surface. However, attempts at predicting θO for systems with high γo-aq resulted in significant deviations, a problem linked to the high σSd values required to fit the wettability of low γo-aq systems (toluene-water-IPA). The extended EQS (e-EQS) method produced reasonable predictions of γo-aq·cosθO for all the available experimental and literature data. The e-EQS method required fitting one of the interfacial energy terms (γS-L). For low surface energy materials, such as PTFE, the γS-o value should be fitted. For high surface energy materials, the γS-aq should be fitted instead. The fitted values of γS-o for PTFE and γS-aq for glass were consistent with the values obtained from Young's equation applied to SLA data.

Cumulative exposure to biological therapy and risk of cancer in patients with psoriasis: a meta-analysis of Psonet studies from Israel, Italy, Spain, the U.K. and Republic of Ireland.

BACKGROUND: Cancer risk following long-term exposure to systemic immunomodulatory therapies in patients with psoriasis is possible. OBJECTIVES: To assess a dose-response relationship between cumulative length of exposure to biological therapy and risk of cancer. METHODS: Four national studies (a healthcare database from Israel, and prospective cohorts form Italy, Spain and the U.K. and Republic of Ireland) collaborating through Psonet (European Registry of Psoriasis) participated in these nested case-control studies, including nearly 60 000 person-years of observation. 'Cases' were patients who developed an incident cancer. Patients with previous cancers and benign or in situ tumours were excluded. Four cancer-free controls were matched to each case on year of birth, sex, geographic area and registration year. Follow-up for controls was censored at the date of cancer diagnosis for the matched case. Conditional logistic regression was performed by each registry. Results were pooled using random-effects meta-analysis. RESULTS: A total of 728 cases and 2671 controls were identified. After matching, differences between cases and controls were present for the Charlson Comorbidity Index in all three registries, and in the prevalence of previous exposure to psoralen-ultraviolet A and smoking (the British Association of Dermatologists Biologic Interventions Register only). The risk of first cancers was not significantly associated with cumulative exposure to biologics (adjusted odds ratio per year of exposure 1·02, 95% confidence interval 0·92-1·13). Results were similar if squamous and basal cell carcinomas were included in the outcome. CONCLUSIONS: Cumulative length of exposure to biological therapies in patients with psoriasis in real-world clinical practice does not appear to be linked to a higher risk of cancer after several years of use.

Is mitotic rate still useful in the management of patients with thin melanoma?

BACKGROUND: T1 melanoma substaging was recently modified by the American Joint Committee on Cancer (AJCC). Although sentinel lymph node (SLN) positivity is the most important prognostic factor in melanoma, there is a lack of consensus on whether SLN biopsy should be performed in patients with thin melanoma (≤1 mm). OBJECTIVE: The main aim of this study was to investigate predictors of SLN positivity in patients with thin melanoma, with a special emphasis on mitotic rate. A secondary aim was to evaluate survival in this group of patients. MATERIALS AND METHODS: Retrospective multicenter observational study with analysis of age, sex, tumour location, thickness, mitotic rate, regression and microscopic satellites. Predictive factors were identified using a classification and regression tree (CART) approach. Melanoma-specific survival according to SLN status was estimated using Kaplan-Meier curves. RESULTS: We analysed 203 patients with a melanoma ≤1 mm. Using the new AJCC staging criteria, the CART algorithm identified a 7.5% likelihood of SLN positivity in T1a patients. In the case of T1b melanoma, there was a 14.3% likelihood of SLN positivity in patients with a mitotic rate >1 mitosis/mm2 and a 3.2% likelihood in those with ≤1 mitoses/mm2 . None of the patients with T1b disease who had ≤1 mitoses/mm2 and regression had SLN positivity. In T1b patients, 5-year melanoma-specific survival was 98.7% in the SLN-negative group and 75% in the SLN-positive group (P = 0.05). When stratified by mitotic rate, survival was 100% for patients with a mitotic rate of ≤1 mitoses/mm2 and 91.4% for those with >1 mitosis/mm2 (P = 0.022). There were no deaths in the T1a subgroup. CONCLUSIONS: Sentinel lymph node metastasis was less common in patients with T1b melanoma who had a mitotic rate of ≤1 mitoses/mm2 . Performance of SLN biopsy should be carefully considered in this subgroup of patients, particularly considering the good prognosis.

Reproductive biology of Ferocactus recurvus (Mill.) Borg subsp. recurvus (Cactaceae) in the Tehuacán-Cuicatlán Valley, Mexico.

Mexico has one of the highest diversities of barrel cacti species worldwide; however, all are threatened and require conservation policies. Information on their reproductive biology is crucial, but few studies are available. Ferocactus recurvus subsp. recurvus is a barrel cactus endemic to the Tehuacán-Cuicatlán Valley. Our research aimed to characterise its floral and pollination biology. We hypothesised bee pollination, as suggested by its floral morphology and behaviour, and self-incompatibility, like most barrel cacti studied. Three study sites were selected in the semiarid Zapotitlán Valley, Mexico. We examined 190 flowers from 180 plants to determine: morphometry and behaviour of flowers, flower visitors and probable pollinators, and breeding system. Flowers showed diurnal anthesis, lasting 2-5 days, the stigma being receptive on day 2 or 3 after the start of anthesis. Flowers produced scarce/no nectar and main visitors were bees (Apidae), followed by flies (Muscidae), ants (Formicidae), thrips (Thripidae) and hummingbirds (Throchilidae); however, only native bees and occasionally wasps contacted the stigma and anthers. Pollination experiments revealed that this species is self-incompatible and xenogamous. In natural conditions, fruit set was 60% and cross-pollination fruit set was 100%. Percentage seed germination resulting from cross-pollination was higher than in the control treatment. Our results provide ecological information for conservation programmes to ensure a high probability of breeding and seed production in natural populations of F. recurvus.

Valoración pronóstica de mortalidad y hospitalizaciones en pacientes ambulatorios con EPOC avanzada. Utilidad del índice CODEX / Prognostic assessment of mortality and hospitalizations of outpatients with advanced chronic obstructive pulmonary disease. Usefulness of the CODEX index

Objetivos: Validar el índice CODEX en pacientes ambulatorios con EPOC avanzada. Pacientes y métodos: Se estudió a todos los pacientes con EPOC controlados en una unidad de pacientes crónicos respiratorios. Se calcularon los índices BODEX y CODEX y su relación con mortalidad, hospitalizaciones o ambas, y se realizó un análisis por número de eventos (mortalidad o reingresos), mediante el análisis de riesgos proporcionales de Cox. Resultados: Se incluyó a 80 pacientes (90% varones) con una edad media de 73,4 años. El seguimiento medio fue de 656 días con un rango intercuartílico (25-75%) de 417-642 días. Un total de 17 pacientes fallecieron (21%) y 57 (71,3%) requirieron hospitalización por EPOC. El índice CODEX se relacionó significativamente con la mortalidad (p<0,008; HR: 1,56; IC 95%: 1,1-2,15), el ingreso hospitalario (p<0,01; HR: 1,35; IC 95%: 1,13-1,62) y la variable combinada (p<0,03; HR: 1,27; IC 95%: 1,1-1,5). El BODEX no se asoció con la mortalidad (p=0,17), pero sí con los ingresos (p<0,001; HR: 1,4; IC 95%: 1,15-1,73) y la variable combinada (p<0,03; HR: 1,2; IC 95%: 1,02-1,34). Durante el seguimiento se produjeron 187 eventos. Tanto el índice CODEX (p<0,001; HR:1,17; IC 95%:1,1-1,27) como el BODEX (p<0,02; HR: 1,12; IC 95%: 1,02-1,23) se relacionaron con el número de eventos, aunque tras ajustar por la interacción entre ambos índices solo el CODEX conservó la significación estadística para la variable combinada por pacientes (p<0,03) y en el análisis por número de eventos (p<0,001). Conclusiones: Tanto el CODEX como el BODEX son útiles en la predicción de ingresos hospitalarios, aunque la capacidad pronóstica del CODEX es superior al BODEX tanto en mortalidad como en ingresos hospitalarios

Objectives: To validate the CODEX index in outpatients with advanced chronic obstructive pulmonary disease (COPD). Patients and methods: We studied all patients with COPD treated in a chronic respiratory disease unit. We calculated the BODEX and CODEX indices and their relationship with mortality, hospitalisations or both and performed an analysis by number of events (mortality and/or readmissions), using the Cox proportional hazards analysis. Results: We included 80 patients (90% men) with a mean age of 73.4 years. The mean follow-up was 656 days, with an interquartile range (25-75%) of 417-642 days. Seventeen patients died (21%) and 57 (71.3%) required hospitalisation for COPD. The CODEX index was significantly related to mortality (P<.008; HR: 1.56; 95% CI: 1.1-2.15), hospitalisations (P<.01; HR: 1.35; 95% CI: 1.13-1.62) and the combined variable (P<.03; HR: 1.27; 95% CI: 1.1-1.5). The BODEX index was not associated with mortality (P=.17) but was associated with hospitalisation (P<.001; HR: 1.4; 95% CI: 1.15-1.73) and the combined variable (P<.03; HR: 1.2; 95% CI: 1.02-1.34). There were 187 events during follow-up. Both the CODEX (P<.001; HR: 1.17; 95% CI: 1.1-1.27) and BODEX (P<.02; HR: 1.12; 95% CI: 1.02-1.23) indices were related to the number of events. However, after adjusting for the interaction between the 2 indices, only the CODEX index maintained statistical significance for the combined variable for patients (P<.03) and in the analysis by number of events (P<.001). Conclusions: Both the CODEX and BODEX indices are useful for predicting hospitalisations, although the prognostic ability of the CODEX index is greater than that of the BODEX index, both for mortality and hospitalisations

Limits to the host range of the highly polyphagous tephritid fruit fly Anastrepha ludens in its natural habitat.

Anastepha ludens (Diptera: Tephritidae) is a highly polyphagous fruit fly that is able to develop in a wide range of hosts. Understanding the limits of this pest's host range could provide valuable information for pest management and plant breeding for pest resistance. Previous studies have shown that guavas (Psidium guajava (Myrtaceae) L.), are not attacked under natural conditions by A. ludens. To understand this phenomenon, guavas were exposed to natural infestation by A. ludens and to other fruit fly species that infest guavas in nature (Anastrepha striata Schiner, Anastepha fraterculus (Wiedemann), Anastepha obliqua (Macquart)). Once the susceptible phenological stage of guavas was determined, fruit infestation levels were compared between A. ludens and A. striata. Choice and non-choice tests were performed under field-cage conditions. Under field conditions, guavas were susceptible to A. striata and A. fraterculus attack all the way from when fruit was undeveloped to when fruit began to ripen. No infestation by A. ludens was recorded under natural conditions. Similar results were obtained when forced exposures were performed, indicating that unripe guavas were preferred by A. striata over ripe fruit, and that infestation rates were higher at early fruit maturity stages. Under forced oviposition conditions, A. ludens larvae were unable to develop in unripe guavas but did so in fully ripe fruit. However, A. ludens fitness parameters were dramatically affected, exhibiting reduced survival and reduced pupal weight compared to conspecifics that developed in a natural host, grapefruit. We confirm that P. guajava should not be treated as a natural host of this pestiferous species, and suggest that both behavioral aspects and the fact that larvae are unable to adequately develop in this fruit, indeed represent clear limits to A. ludens's broad host range.