Mohs micrographic surgery in immunosuppressed vs immunocompetent patients: Results of a prospective nationwide cohort study (REGESMOHS, Spanish registry of Mohs surgery).

BACKGROUND: Immunosuppressed (IS) patients, particularly solid organ transplant recipients and those on immunosuppressive therapy, face a higher incidence and recurrence of nonmelanoma skin cancers (NMSC), including basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). Mohs micrographic surgery (MMS) is the preferred treatment for high-risk NMSC due to its high cure rate and margin examination capabilities. However, IS patients may experience more complications, such as surgical site infections, and a greater risk of recurrence, making their outcomes a subject of interest. OBJECTIVES: This study aimed to compare IS and immunocompetent (IC) patients undergoing MMS for NMSC in terms of baseline characteristics, intra- and post-surgical complications, and postoperative recurrence rates. METHODS: The study utilized data from the REGESMOHS registry, a 7-year prospective cohort study in Spain. It included 5226 patients, categorizing them into IC (5069) and IS (157) groups. IS patients included solid organ transplant recipients, those on immunosuppressive treatments, individuals with haematological tumours and HIV-positive patients. Patient data, tumour characteristics, surgical details and outcomes were collected and analysed. RESULTS: IS patients demonstrated a higher proportion of SCC, multiple synchronous tumours and tumours invading deeper structures. Complex closures, unfinished MMS and more surgical sections were observed in the IS group. Although intra-operative morbidity was higher among IS patients, this difference became non-significant when adjusted for other variables such as year of surgery, antiplatelet/anticoagulant treatment or type of closure. Importantly, IS patients had a substantially higher recurrence rate (IRR 2.79) compared to IC patients. CONCLUSIONS: This study suggests that IS patients may be at a higher risk of development of AE such as bleeding or tumour necrosis and are at a higher risk of tumour recurrence. Close follow-up and consideration of the specific characteristics of NMSC in IS patients are crucial. Further research with extended follow-up is needed to better understand the long-term outcomes for this patient group.

Real-world effectiveness and safety of bimekizumab for hidradenitis suppurativa: An ambispective observational study.

In this original research, we present the results in terms of effectiveness and safety of bimekizumab for hidradenitis suppurativa in real clinical practice. Results indicated significant improvement in all activity scores and patient-reported outcomes at week 16, including a notable decrease in mean IHS4 from 27.1 to 15.6 (p < 0.001), HS-PGA from 5.1 to 3.2 (p < 0.001), VAS pain from 8.3 to 4.7 (p < 0.001) and DLQI from 21.6 to 12.6 (p < 0.001). Bimekizumab, administered every 2 or 4 weeks, was well-tolerated with no discontinuations and no new safety concerns identified. These findings corroborate the drug's effectiveness and favourable safety profile observed in phase 3 clinical trials, supporting its use in real-world clinical practice for treating HS.

Development and validation of a model to predict complex Mohs micrographic surgery in clinical practice: REGESMOSH scale.

INTRODUCTION: There is still a need to develop a simple algorithm to identify patients likely to need complex Mohs micrographic surgery (MMS) and optimize MMS schedule. The main objectives of this study are to identify factors associated with a complex MMS and develop a predictor model of the number of stages needed in surgery and the need for a complex closure. MATERIALS AND METHODS: A nationwide prospective cohort study (REGESMOHS, the Spanish Mohs surgery registry) was conducted including all patients with a histological diagnosis of basal cell carcinoma (BCC). Factors related to three or more stages and a complex closure (that needing a flap and/or a graft) were explored and predictive models were constructed and validated to construct the REGESMOSH scale. RESULTS: A total of 5226 patients that underwent MMS were included in the REGESMOHS registry, with 4402 (84%) having a histological diagnosis of BCC. A total of 3689 (88.9%) surgeries only needed one or two stages and 460 (11.1%) required three or more stages. A model to predict the need for three or more stages included tumour dimension, immunosuppression, recurrence, location in risk areas, histological aggressiveness and previous surgery. Regarding the closure type, 1616 (38.8%) surgeries were closed using a non-complex closure technique and 2552 (61.2%) needed a complex closure. A model to predict the need for a complex closure included histological aggressiveness, evolution time, patient age, maximum tumour dimension and location. CONCLUSION: We present a model to predict MMS needing ≥3 stages and a complex closure based on epidemiological and clinical data validated in a large population (with real practice variability) including different centres that could be easily implemented in clinical practice. This model could be used to optimize surgery schedule and properly inform patients about the surgery duration.

Longitudinal study of the flash glucose monitoring system in type 1 diabetics: An mHealth ally in times of COVID-19.

AIMS AND OBJECTIVES: The aim of this study was to assess the effect of the FreeStyle Libre device implantation in adult type 1 diabetics in a Health Area of Castilla La Mancha (Spain) during the COVID-19 pandemic. BACKGROUND: FreeStyle Libre is a so-called mHealth device that supports health care. During COVID-1 confinement, diabetic patients could have improved their glycaemic monitoring thanks to these devices, although health care in these patients may have been limited due to confinement. METHODS: A 12-month longitudinal study in which a total of 206 type I diabetics participated, belonging to a single health area. Sociodemographic and analytical data and the Self Care Inventory Revised questionnaire (SCI-R) were collected. STROBE checklist was followed. RESULTS: The analysis showed differences related to the use of the sensor. After the study period, patients obtained better levels of basal glucose, glycosylated haemoglobin, creatinine, cholesterol, triglycerides and LDL. In addition, a significant increase in the total score of the SCI-R questionnaire was observed after the use of the monitor (MD -7.77; 95% CI -10.43, -8.29). The same occurred with different SCI-R items such as diet (MD -2.995; 95% CI -3.24, -2.57), glucose determination (MD -3.21; 95% CI -3.52, -2.91), medication administration (MD -2.58; 95% CI -2.53, -1.96) and hypoglycaemic episodes (MD -1.07; 95% CI -1.21, -0.93). In the analysis by groups, worse values of glycosylated haemoglobin and adherence to treatment (p < .05) were observed in overweight/obese subjects versus those with normal weight after one year of study. CONCLUSION: The use of flash monitoring is related to better adherence to most of the recommended habits in diabetes. Nevertheless, there seems to be no relationship with an improvement in physical exercise and preventive aspects of diabetes. A good nursing intervention to support physical exercise and the use of mHealth devices could improve the control of diabetic patients. RELEVANCE TO CLINICAL PRACTICE: The use of this mHealth device has shown positive results and reduced complications. Despite less contact with healthcare facilities due to the pandemic, type 1 diabetic patients have improved their blood results and adherence after using the device for one year. Nursing staff should focus on promoting physical activity and routine disease care in type 1 diabetics.

Psychosocial factors related to physical activity in frail and prefrail elderly people.

BACKGROUND: Increased physical activity (PA) is a very important factor in a healthy aging lifestyle. Psychosocial factors have also a main role in the initiation and maintenance of this behavior, but nowadays its implications for frailty elderly people are unknown, therefore, the aim of this study was to identify the psychosociological variables of behavior change that influence the practice of (PA) in frail and prefrail elderly. METHODS: A total of 103 frail and pre-frail elderly people (72 females) participated in this cross-sectional study, on the framework of the EXERNET-Elder3.0 project. Age ranged from 68-94 years (mean = 80.4 ± 5.9 years). Individualized face-to-face interviews according to the constructs of the Transtheoretical Model of Change (TTM) [(decisional balance (DB) and self-efficacy (SE)], social support (SS) (family and friends) and outcome expectations (OE) were administered to all participants. RESULTS: Significant differences were found in DB, perceived benefits (PBn), SE, family-related SS and OE as a function of stages of change (SoC) (p < 0.005), but no significant were found in perceived barriers (PBrr) (p = 0.259) and friends-related SS (p = 0.068). According to the Scheffé post-hoc test, those in advanced SoC (Action-Maintenance), scored higher than those in lower SoC (Precontemplation-Contemplation and Preparation). CONCLUSION: The scores obtained from the study variables differed according to the SoC, supporting the external validity for the use of the TTM in frailty elderly. Further research is needed to determine the impact of PBrr and friends-related SS on this people, as well as to identify the validity of this model in the long-term in this population.

Mohs micrographic surgery in dermatofibrosarcoma protuberans: Rate and risk factors for recurrence in a prospective cohort study from the Spanish Registry of Mohs Surgery (REGESMOHS) and review of the literature.

Characterization of patients, surgery procedures and the risk factors for dermatofibrosarcoma protuberans (DFSP) recurrences is poorly defined. In this study, we aimed to describe the demographics, tumor characteristics and interventions of DFSP treated with Mohs micrographic surgery (MSS) to determine the rate and risk factors for recurrence. Data were collected from REGESMOHS, a nationwide prospective cohort study of patients treated with MMS in Spain. From July 2013 to February 2020, 163 patients with DFSP who underwent MMS were included. DFSP was mostly located on trunk and extremities. Recurrent tumors had deeper tumor invasion and required higher number of MMS stages. Paraffin MMS was the most frequently used technique. Overall recurrence rate was 0.97 cases/100 person-years (95% IC = 0.36-2.57). No differences were found in epidemiological, tumor, surgery characteristics or surgical technique (frozen or paraffin MMS [p = 0.6641]) in terms of recurrence. Median follow-up time was 28.6 months with 414 patient-years of follow-up. In conclusion, we found an overall low recurrence rate of DFSP treated with MMS. None of the studied risk factors, including MMS techniques, was associated with higher risk for recurrence.

Long-term follow-up of patients with nodular lymphocyte predominant Hodgkin lymphoma: A report from the Spanish Lymphoma Oncology Group.

Nodular lymphocytic predominance Hodgkin lymphoma (NLPHL) is a very uncommon subtype of Hodgkin lymphoma (HL), representing approximately 5% of all HL cases, with an incidence of 0.3/100,000 cases per year and with unique characteristics which distinguish it from classic Hodgkin lymphoma. Given its low frequency, there is a lack of prospective randomized studies to inform practice, the accumulated experience of academic groups being the main source of relevant information for the management of these patients. Eighty-five patients recruited by the Spanish Lymphoma Group (GOTEL) from 12 different hospitals were retrospectively analyzed to describe their sociodemographic and clinical characteristics. The median follow-up was 16 years, with a 10-year overall survive of 92.9% and 81.2% at 20 years. Five patients developed a second malignancy. No transformation to a more aggressive lymphoma was detected. A total of 31% tumor relapses was found: 77% in a single location; most of them at a supra-diaphragmatic level. Patients received different first-line treatments, and progression was observed in 3/4 (75%) of the patients who did not receive any type of treatment, 6/23 (26%) who received both chemotherapy (CH) and radiotherapy (RT), 12/43 (27%) who received RT and 7/15 (47%) that received only CH treatment. The mean time to relapse was 3 years and 47% presented relapses beyond 5 years (higher probability in stage IV p < 0.001). This is one of the longest follow-up series of NLPHL published, confirming its excellent prognosis, and that treatments may be adapted to reduce toxicity. Causes of death in these patients are varied, and the minority due to a primary malignancy relapses.

Risk Factors and Rate of Recurrence after Mohs Surgery in Basal Cell and Squamous Cell Carcinomas: A Nationwide Prospective Cohort (REGESMOHS, Spanish Registry of Mohs Surgery).

Randomized studies to assess the efficacy of Mohs micrographic surgery in basal cell and squamous cell carcinomas are limited by methodological and ethical issues and a lack of long follow-up periods. This study presents the "real-life" results of a nationwide 7-years cohort on basal cell carcinoma and squamous cell carcinoma treated with Mohs micrographic surgery. A prospective cohort was conducted in 22 Spanish centres (from July 2013 to February 2020) and a multivariate analysis, including characteristics of patients, tumours, surgeries and follow-up, was performed. A total of 4,402 patients followed up for 12,111 patient-years for basal cell carcinoma, and 371 patients with 915 patient-years of follow-up for squamous cell carcinoma were recruited. Risk factors for recurrence included age, non-primary tumours and more stages or unfinished surgeries for both tumours, and immunosuppression for squamous cell carcinoma. Incidence rates of recurrence were 1.3 per 100 person-years for basal cell carcinoma (95% confidence interval 1.1-1.5) and 4.5 for squamous cell carcinoma (95% confidence interval 3.3-6.1), being constant over time (0-5 years). In conclusion, follow-up strategies should be equally intense for at least the first 5 years, with special attention paid to squamous cell carcinoma (especially in immunosuppressed patients), elderly patients, non-primary tumours, and those procedures requiring more stages, or unfinished surgeries.

Nursing students' experience and training in healthcare aid during the COVID-19 pandemic in Spain.

BACKGROUND: During the COVID-19 pandemic health crisis, in some countries such as Spain, nursing students have offered to provide health assistance, but the role they have played, their degree of preparedness to face the situation, and what must be improved in their training to be ready for these situations is unknown. OBJECTIVE: Describe the experience and perceptions of students of the Nursing university degree during their participation as health support in the COVID-19 health crisis in Spain. DESIGN: We conducted a cross-sectional survey study. METHOD: 503 students enrolled in the 4th course of the Nursing degree in Spain during the months of March and April 2020. An online questionnaire was developed, based on a pilot study and distributed through the Nursing Association, students' unions and students' associations. Variables were used to describe their participation, degree of preparedness and training needs to determine how to improve training through descriptive statistics, as well as nonparametric tests to analyse the relationship between training and degree of preparedness nursing students. Results are reported according to the STROBE Statement. RESULTS: 73.2% (368) of students offered to participate in healthcare aid, of which 225 were actively involved. 27.8% carried out nursing tasks without supervision, and 47.7% assisted COVID-19 patients as any other nurse. Only 3.4% felt very prepared to work in the field of intensive care, finding that those students who perceived a higher degree of preparedness had received previous training in personal protective equipment and mechanical ventilation (p < 0.005). The highest scores for training activities that may improve their preparedness were simulations to improve levels of anxiety and stress when managing critical patients, simulation in ventilatory support and mandatory practices in services where ventilators are used. CONCLUSIONS: Although three out of four students were willing to provide health assistance, they recognise that they were not specially prepared in the field of intensive care and demand training with simulation to improve anxiety and stress levels in the management of critical patients and simulation in ventilatory support. RELEVANCE TO CLINICAL PRACTICE: Students have been vital resources for our health system and society when they have been needed. It is now up to us, both teachers and health authorities, to share their efforts by implementing the necessary improvements in training and safety measures not only because these affects the health and safety of the patient, but because they will be essential parts in future pandemics.

Microbiota characterization of sheep milk and its association with somatic cell count using 16s rRNA gene sequencing.

This work aimed to use 16S ribosomal RNA sequencing with the Illumina MiSeq platform to describe the milk microbiota from 50 healthy Assaf ewes. The global observed microbial community for clinically healthy milk samples analysed was complex and showed a vast diversity. The core microbiota of the sheep milk includes five genera: Staphylococcus, Lactobacillus, Corynebacterium, Streptococcus and Escherichia/Shigella. Although there are some differences, some of these genera are common with the microbiota core pattern of milk from other species, especially with dairy cows. The microbial composition of the studied samples, based on the definition of amplicon sequence variants, was analysed through a correlation network. A preliminary analysis by grouping the milk samples based on their somatic cell count (SCC), which is considered an indicator of subclinical mastitis (SM), showed certain differences for the core of the samples identified as SM. The differences in the microbiota diversity pattern among samples might also suggest that subclinical mastitis would be associated with the significant increase in some genera that are inhabitants of the mammary gland and a remarkable concomitant reduction in the microbial diversity. Additionally, we have also presented here a preliminary analysis to assess the impact of the sheep milk microbiome on SCC, as an indicator of subclinical mastitis. The results here reported provide a first characterization of the sheep milk microbiota and settle the basis for future studies in this field.

Adaptation and validation of the Euthanasia Attitude Scale into Spanish.

BACKGROUND: Considering the extensive debate that is currently taking place in Spain regarding euthanasia, it is important to examine the attitude of professionals who perform most of their duties at the bedside of these patients and their families. OBJECTIVES: The aim of the present study was to present an adaptation and validation of the Euthanasia Attitude Scale and to evaluate its psychometric properties among a sample of nursing students in Spain. RESEARCH DESIGN: A cross-sectional study design was conducted. PARTICIPANTS AND RESEARCH CONTEXT: Non-probabilistic sampling was used to recruit 396 Spanish nursing students. METHODS: A self-report questionnaire, including socio-demographic data and the Euthanasia Attitude Scale, were used for data collection. The psychometric properties of the Euthanasia Attitude Scale were assessed, including reliability and validity. Fit indices of the overall model were computed. ETHICAL CONSIDERATIONS: This study was approved by the Hospital Ethical Committee. Students were informed of the aims and procedures and provided written informed consent prior to data collection. RESULTS: The factorial solution comprised four domains and the scale demonstrated adequate internal consistency (Cronbach's alpha = .878). For the exploratory factor analysis, the Kaiser-Meyer-Olkin index of sampling adequacy was .905 and the Bartlett's Test of Sphericity was 2972.79 (p < .001). The initial factorial solution revealed four factors with eigenvalues of 6.78 for the first factor, 1.90 for the second one, 1.29 for the third, and 1.10 for the fourth factor. Moreover, there was a significant relationship between religiosity and the domains of the Euthanasia Attitude Scale. DISCUSSION: This study obtained a Cronbach's alpha coefficient of .88 which is in consonance with the findings reported by other studies whereby none of the items were removed and the initial structure based on four domains was conserved, with a factorial solution that explains 52.79% of the total variance. The displacement of some items of the domain may be explained by certain religious and/or cultural components as, in accordance with other studies, people with firm religious beliefs are more inclined to refuse euthanasia. CONCLUSION: According to the findings of this study, the Euthanasia Attitude Scale is a reliable and valid instrument to measure the attitudes toward euthanasia in a sample of Spanish nursing students. This Spanish adaptation will be valuable in future studies examining the attitude and implication of nurses, understanding that nurses are key figures in the euthanasia debate.

Protein tyrosine phosphatase PTPN22 regulates IL-1ß dependent Th17 responses by modulating dectin-1 signaling in mice.

A single nucleotide polymorphism within the PTPN22 gene is a strong genetic risk factor predisposing to the development of multiple autoimmune diseases. PTPN22 regulates Syk and Src family kinases downstream of immuno-receptors. Fungal ß-glucan receptor dectin-1 signals via Syk, and dectin-1 stimulation induces arthritis in mouse models. We investigated whether PTPN22 regulates dectin-1 dependent immune responses. Bone marrow derived dendritic cells (BMDCs) generated from C57BL/6 wild type (WT) and Ptpn22-/- mutant mice, were pulsed with OVA323-339 and the dectin-1 agonist curdlan and co-cultured in vitro with OT-II T-cells or adoptively transferred into OT-II mice, and T-cell responses were determined by immunoassay. Dectin-1 activated Ptpn22-/- BMDCs enhanced T-cell secretion of IL-17 in vitro and in vivo in an IL-1ß dependent manner. Immunoblotting revealed that compared to WT, dectin-1 activated Ptpn22-/- BMDCs displayed enhanced Syk and Erk phosphorylation. Dectin-1 activation of BMDCs expressing Ptpn22R619W (the mouse orthologue of human PTPN22R620W ) also resulted in increased IL-1ß secretion and T-cell dependent IL-17 responses, indicating that in the context of dectin-1 Ptpn22R619W operates as a loss-of-function variant. These findings highlight PTPN22 as a novel regulator of dectin-1 signals, providing a link between genetically conferred perturbations of innate receptor signaling and the risk of autoimmune disease.

Protein tyrosine phosphatase PTPN22 regulates LFA-1 dependent Th1 responses.

A missense C1858T single nucleotide polymorphism within PTPN22 is a strong genetic risk factor for the development of multiple autoimmune diseases. PTPN22 encodes a protein tyrosine phosphatase that negatively regulates immuno-receptor proximal Src and Syk family kinases. Notably, PTPN22 negatively regulates kinases downstream of T-cell receptor (TCR) and LFA-1, thereby setting thresholds for T-cell activation. Alterations to the quality of TCR and LFA-1 engagement at the immune synapse and the regulation of downstream signals can have profound effects on the type of effector T-cell response induced. Here we describe how IFNγ+ Th1 responses are potentiated in Ptpn22-/- T-cells and in T-cells from mice expressing Ptpn22R619W (the mouse orthologue of the human genetic variant) as they age, or following repeated immune challenge, and explore the mechanisms contributing to the expansion of Th1 cells. Specifically, we uncover two LFA-1-ICAM dependent mechanisms; one T-cell intrinsic, and one T-cell extrinsic. Firstly, we found that in vitro anti-CD3/LFA-1 induced Th1 responses were enhanced in Ptpn22-/- T-cells compared to WT, whereas anti-CD3/anti-CD28 induced IFNy responses were similar. These data were associated with an enhanced ability of Ptpn22-/- T-cells to engage ICAM-1 at the immune synapse when incubated on planar lipid bilayers, and to form conjugates with dendritic cells. Secondly, we observed a T-cell extrinsic mechanism whereby repeated stimulation of WT OT-II T-cells with LPS and OVA323-339 pulsed Ptpn22-/- bone marrow derived dendritic cells (BMDCs) was sufficient to enhance Th1 cell development compared to WT BMDCs. Furthermore, this response could be reversed by LFA-1 blockade. Our data point to two related but distinct mechanisms by which PTPN22 regulates LFA-1 dependent signals to enhance Th1 development, highlighting how perturbations to PTPN22 function over time to regulate the balance of the immune response.

Does Jacobson's relaxation technique reduce consumption of psychotropic and analgesic drugs in cancer patients? A multicenter pre-post intervention study.

BACKGROUND: Cancer patients often suffer from emotional distress as a result of the oncological process. The purpose of our study was to determine whether practice of Jacobson's relaxation technique reduced consumption of psychotropic and analgesic drugs in a sample of cancer patients. METHODS: This was a multicenter pre-post intervention design. Participants were 272 patients aged over 18 years attending 10 Spanish public hospitals with oncological pathologies and anxiety symptoms. The intervention consisted of a protocol of abbreviated progressive muscle relaxation training developed by Bernstein and Borkovec. This was followed up by telephone calls over a 1-month period. The intervention was performed between November 2014 and October 2015. Sociodemographic variables related to the oncological process, mental health variables, and intervention characteristics were measured. RESULTS: A reduction in the consumption of psychotropic and analgesic drugs was observed throughout the follow-up period. Improvement was observed throughout the 4-week follow-up for all the parameters assessed: anxiety, relaxation, concentration, and mastery of the relaxation technique. CONCLUSIONS: The practice of abbreviated Jacobson's relaxation technique can help to decrease the consumption of psychotropic and analgesic drugs. Patients experienced positive changes in all the evaluated parameters, at least during the 1-month follow-up. To confirm these findings, additional long-term studies are needed that include control groups. TRIAL REGISTRATION: ISRCTN 81335752 , DOI 10.1186/ISRCTN81335752 17. Date of registration: 22/11/2016 (retrospectively registered).

High-resolution analysis of selection sweeps identified between fine-wool Merino and coarse-wool Churra sheep breeds.

BACKGROUND: With the aim of identifying selection signals in three Merino sheep lines that are highly specialized for fine wool production (Australian Industry Merino, Australian Merino and Australian Poll Merino) and considering that these lines have been subjected to selection not only for wool traits but also for growth and carcass traits and parasite resistance, we contrasted the OvineSNP50 BeadChip (50 K-chip) pooled genotypes of these Merino lines with the genotypes of a coarse-wool breed, phylogenetically related breed, Spanish Churra dairy sheep. Genome re-sequencing datasets of the two breeds were analyzed to further explore the genetic variation of the regions initially identified as putative selection signals. RESULTS: Based on the 50 K-chip genotypes, we used the overlapping selection signals (SS) identified by four selection sweep mapping analyses (that detect genetic differentiation, reduced heterozygosity and patterns of haplotype diversity) to define 18 convergence candidate regions (CCR), five associated with positive selection in Australian Merino and the remainder indicating positive selection in Churra. Subsequent analysis of whole-genome sequences from 15 Churra and 13 Merino samples identified 142,400 genetic variants (139,745 bi-allelic SNPs and 2655 indels) within the 18 defined CCR. Annotation of 1291 variants that were significantly associated with breed identity between Churra and Merino samples identified 257 intragenic variants that caused 296 functional annotation variants, 275 of which were located across 31 coding genes. Among these, four synonymous and four missense variants (NPR2_His847Arg, NCAPG_Ser585Phe, LCORL_Asp1214Glu and LCORL_Ile1441Leu) were included. CONCLUSIONS: Here, we report the mapping and genetic variation of 18 selection signatures that were identified between Australian Merino and Spanish Churra sheep breeds, which were validated by an additional contrast between Spanish Merino and Churra genotypes. Analysis of whole-genome sequencing datasets allowed us to identify divergent variants that may be viewed as candidates involved in the phenotypic differences for wool, growth and meat production/quality traits between the breeds analyzed. The four missense variants located in the NPR2, NCAPG and LCORL genes may be related to selection sweep regions previously identified and various QTL reported in sheep in relation to growth traits and carcass composition.

A phase II study to evaluate lenalidomide in combination with metronomic-dose cyclophosphamide in patients with heavily pretreated classical Hodgkin lymphoma.

BACKGROUND: Relapsed or refractory (R/R) classical Hodgkin lymphoma (cHL) after autologous stem cell transplantation (ASCT) remains a challenge. For these patients treatments with different mechanisms of action rather than classical chemotherapy are needed. PATIENTS AND METHODS: Patients with R/R cHL after ASCT were recruited in a phase II trial (EUDRA CT: 2009-016588-12). Lenalidomide was administered at 20 mg/day for 21 days and cyclophosphamide at 50 mg/day for 28 days (cycles every 28 days). Dose escalation for lenalidomide was permitted. In 2009 we considered that this treatment would be promising if response rate were over 60% and a Simon two-stage binomial design was used to calculate the sample size. A total of 46 patients were planned but the trial would be stopped if less than seven responses after four cycles were obtained in the first 16 patients. RESULTS: The trial was closed early because only five responses were observed after four cycles in the first 16 patients included. Median age was 34 years (18-77). The median number of previous lines was five (2-6). At inclusion, 10 patients were primary refractory and 11 refractory to the last therapy. A total of 110 cycles were administered, with grade≥3 toxicity in 43 cycles (39%). One non-neutropenic patient developed septic shock resulting in death. An ORR of 38% (1 CR and 5 PR) was observed and a total of 10 patients (62%) achieved clinical benefit. Median progression free survival and overall survival were seven and 19 months, respectively. With a median follow-up of 19 months (3-38+), three-year progression-free and overall survival were 6% and 31%, respectively. CONCLUSION: The optimistic assumptions of this trial led to an early closure. However, the promising clinical benefit observed with the oral combination of lenalidomide and metronomic cyclophosphamide may justify its use for outpatient palliative treatment.

Episcleral infantile hemangioma successfully treated with topical timolol.

Episcleral hemangiomas are usually associated with neonatal hemangiomatosis. Recently, propranolol has been described for the treatment of this entity. We present for the first time a patient with an episcleral hemangioma without neonatal hemangiomatosis successfully treated with topical timolol.

Prevalence of neck and low back pain in community-dwelling adults in Spain: an updated population-based national study (2009/10-2011/12).

PURPOSE: To estimate time trends in the prevalence of neck (NP) and low back pain (LBP) from 2009 to 2012; and to determine the socio-demographic features, self-rated health status, co-morbidity, lifestyle-related habits, and health care service associated with NP and LBP in Spanish adults. OUTCOME MEASURES: The European Health Interview Survey for Spain (2009) and the Spanish National Health Survey (2011). METHODS: A total of 43,072 subjects were included. We analyzed data collected from the European Health Interview Survey for Spain conducted in 2009 (n = 22,188), and the Spanish National Health Survey in 2011 (n = 20,884). We considered the presence of isolated NP, LBP and both (NP&LBP). We analyzed socio-demographic features; self-perceived health status; lifestyle habits; comorbid diseases, and professional treatment using logistic regression models. RESULTS: The prevalence of isolated NP, LBP and NP&LBP increased from 2008/9 to 2011/12 (7.86 vs. 8.56 %; 5.18 vs.5.44 %; 10.61 vs.11.12 %, respectively). Being female, increased the probability of isolated NP and NP&LBP, but decreased the probability of LBP. The prevalence of all pain localizations increased with older age, lower education level, poor self-rated health, smoker, comorbidities, psychological distress (anxiety or depression), hospital and physiotherapist visits and consumed drugs for pain, in 2008/9 as compared to 2011/12. Moreover, LBP, and NP&LBP were associated with obesity, whereas NP&LBP was associated with being married. CONCLUSIONS: The prevalence of LBP, NP and NP&LBP had increased in the last 3 years in Spain.