Epiteliopatía en limpiaparabrisas en pacientes con blefaroespasmo o espasmo hemifacial / Lid wiper epitheliopathy in patients with blepharospasm and/or hemifacial spasm

Objetivo Evaluar la presencia de epiteliopatía en limpiaparabrisas en pacientes con blefaroespasmo o espasmo hemifacial antes del tratamiento habitual con toxina botulínica y 4 semanas después. Métodos Estudio prospectivo compuesto por 31 ojos de 20 pacientes con diagnóstico neurológico de espasmo hemifacial (9 ojos de 9 pacientes) y blefaroespasmo esencial (22 ojos de 11 pacientes). Se evaluaron antes y 4 semanas después de la infiltración con toxina botulínica diversos parámetros de superficie ocular con el cuestionario OSDI, test de Schirmer, tiempo de rotura lagrimal y tinciones de fluoresceína y verde de lisamina valoradas con el test de Oxford y el grado de afectación del limpiaparabrisas palpebral. Resultados El 100% de los pacientes presentaron afectación del limpiaparabrisas palpebral antes (30% grado leve y 70% moderado) y después del tratamiento con toxina (100% grado leve). El 75% de los pacientes presentaron un OSDI normal-leve antes del tratamiento; después del tratamiento fue del 80%. El tiempo de rotura lagrimal fue de 7,2±0,2 s antes y de 7,5±0,7 s después del tratamiento. El test de Schirmer fue de 11,4±5,5 y 12,5±5,5mm antes y después del tratamiento. El test de Oxford resultó patológico inicialmente en el 69,3% de los pacientes; tras 4 semanas solo fue patológico en el 54%. Conclusión La epiteliopatía en limpiaparabrisas está presente en el 100% de los pacientes con blefaroespasmo o espasmo hemifacial. El principal mecanismo fisiopatológico que la desencadena en estos pacientes es el aumento en el coeficiente de fricción, ya que el volumen y la estabilidad lagrimal son normales (AU)

Objective To evaluate the presence of wiper epitheliopathy in patients with blepharospasm and/or hemifacial spasm before and 4 weeks after routine treatment with botulinum toxin. Methods Prospective study comprising 31 eyes of 20 patients with neurological diagnosis of hemifacial spasm (9 eyes of 9 patients) and essential blepharospasm (22 eyes of 11 patients). Various ocular surface parameters were assessed before and 4 weeks after infiltration with botulinum toxin using the OSDI questionnaire, Schirmer's test, tear break-up time, fluorescein and lissamine green staining assessed with the Oxford test and the degree of involvement of the palpebral wiper. Results 100% of the patients had palpebral wiper involvement before (30% mild and 70% moderate) and after toxin treatment (100% mild). 75% of patients had mild-normal OSDI before treatment, after treatment it was 80%. The tear break-up time was 7.2±0.2 sg before and 7.5±0.7 sg after treatment. Schirmer's test was 11.4±5.5 and 12.5±5.5mm before and after treatment. The Oxford test was initially pathological in 69.3% of patients, after 4 weeks it was pathological in only 54%. Conclusion Wiper epitheliopathy is present in 100% of patients with blepharospasm and/or hemifacial spasm. The main pathophysiological mechanism that triggers it in these patients is the increase in the coefficient of friction, as tear volume and stability are norma (AU)

Lid wiper epitheliopathy in patients with blepharospasm and/or hemifacial spasm.

OBJECTIVE: To evaluate the presence of wiper epitheliopathy in patients with blepharospasm and/or hemifacial spasm before and 4 weeks after routine treatment with botulinum toxin. METHODS: Prospective study comprising 31 eyes of 20 patients with neurological diagnosis of hemifacial spasm (9 eyes of 9 patients) and essential blepharospasm (22 eyes of 11 patients). Various ocular surface parameters were assessed before and 4 weeks after infiltration with botulinum toxin using the OSDI questionnaire, Schirmer's test, tear break-up time (BUT), fluorescein and lissamine green staining assessed with the Oxford test and the degree of involvement of the palpebral wiper. RESULTS: 100% of the patients had palpebral wiper involvement before (30% mild and 70% moderate) and after toxin treatment (100% mild). 75% of patients had mild-normal OSDI before treatment, after treatment it was 80%. The BUT was 7.2 ±â€¯0.2 sg before and 7.5 ±â€¯0.7 sg after treatment. Schirmer's test was 11.4 ±â€¯5.5 and 12.5 ±â€¯5.5 mm before and after treatment. The Oxford test was initially pathological in 69.3% of patients, after 4 weeks it was pathological in only 54%. CONCLUSION: Wiper epitheliopathy is present in 100% of patients with blepharospasm and/or hemifacial spasm. The main pathophysiological mechanism that triggers it in these patients is the increase in the coefficient of friction, as tear volume and stability are normal.

Primary conjunctival amyloidosis and allergic conjunctivitis. / Amiloidosis conjuntival primaria y conjuntivitis alérgica.

Primary conjunctival amyloidosis is a rare disease of unknown origin, secondary to the deposit of amyloid material within the conjunctiva itself, producing a tumour. In the case presented, the concurrence of allergic conjunctivitis and chronic eye scratching could be triggers of the excessive production of immunoglobulins. The deposit of insoluble immunoglobulin light chains located within the conjunctiva itself causes this conjunctival mass.

High resolution anterior segment optical coherence tomography for differential diagnosis between corneo-conjunctival intraepithelial neoplasia and pterygium. / Tomografía de coherencia óptica de segmento anterior de alta resolución como método de diagnóstico diferencial entre neoplasia intraepitelial córneo-conjuntival y pterygium.

OBJECTIVE: To assess if anterior segment optical coherence tomography (AS-OCT) is a noninvasive diagnostic method suitable to differentiate benign corneo-conjunctival lesions (pterygium) from premalignant lesions (corneo-conjunctival intraepithelial neoplasia, CIN). MATERIAL AND METHODS: An observational, analytical and cross-sectional study was conducted in 22 eyes with conjunctival lesions clinically suspicious for pterygium and CIN during two years. Morphological differences between both lesions were studied with AS-OCT; epithelial thicknesses (EE) and extension length on corneal surface (GIC) were compared between both groups. A surgical excision of the lesion was performed for histopathological diagnosis. RESULTS: Mean age of patients with pterygium (n=18) was 52.67±15 y.o and 74±12 y.o in subjects with CIN (n=4) (p<0.021). In pterygia, AS-OCT showed typical features (normal, thinning or slightly thickened EE; 77.4±26µm), in addition to an increase in wedge-shaped subepithelial tissue. Patients with CIN had a mean thickened EE (262.5±124µm) and strongly hyperreflective, with abrupt transition between normal and pathological epithelium. Analysis of EE between subjects with pterygium and CIN revealed statistically significant differences (p<0.002). ROC curve revealed a 100% sensitivity and specificity of OCT-SA in differentiation between CIN and pterygium, using 141µm as cutoff point of EE. CONCLUSION: AS-OCT is a useful tool for the differentiation between pterygium and CIN able to provide typical morphological characteristics. An EE greater than 141µm in AS-OCT suggests a sensitivity and specificity of 100% for the diagnosis of CIN.

Morphology of the Meibomian gland evaluated using meibography in patients with hypohidrotic ectodermal dysplasia. / Morfología de las glándulas de Meibomio valorada por meibografía en pacientes con displasia ectodérmica hipohidrótica.

INTRODUCTION: Hypohidrotic ectodermal dysplasia (HED) is a rare disease that results from the abnormal development of the ectodermal germ layer in early embryogenesis. In these patients, hypoplasia of Meibomian glands is one of the most frequent ophthalmological manifestations. The main aim of this study is to evaluate the usefulness of meibography for the morphology of Meibomian glands in a group of patients with HED, and to compare it with a control group. METHODS: A total of 14 eyes of 7 patients diagnosed with HED were included, and 32 eyes of 16 patients were included as a control group. The meibographic study was carried out using CA-800 Corneal Analyser (Topcon®). Grading of images was assessed by a meibomian gland atrophy score: grade 0, no alterations; grade 1, ≤25% gland atrophy; grade 2, 25% to 50% gland atrophy; grade 3, 51% to 75% gland atrophy; and grade 4 >75% gland atrophy. Both groups were compared using the Mann-Whitney U non-parametric test. RESULTS: All patients with HED showed some degree of gland atrophy, with 57% showing severe atrophy (>75% of gland atrophy), 35.8% with a grade 3, and 7.2% grade 2. The mean grade of glandular atrophy in HED was 3 (1-4). In the control group, 62.5% had no involvement (grade 0), with 28.1% showing grade 1 and 9.4% grade 2 gland atrophy. The mean glandular atrophy grade within the control group was 0 (0-2). There were statistically significant differences between both groups. CONCLUSIONS: Meibography is a simple diagnostic tool that allows to differentiate between patients without disease and those with HED.

Brentuximab vedotin and ESHAP is highly effective as second-line therapy for Hodgkin lymphoma patients (long-term results of a trial by the Spanish GELTAMO Group).

BACKGROUND: In this work, we assessed the efficacy and safety of brentuximab vedotin (BV) plus ESHAP (BRESHAP) as second-line therapy for Relapsed/Refractory Hodgkin lymphoma (RRHL) to improve the results before autologous stem-cell transplantation (ASCT). PATIENTS AND METHODS: This was a multicenter, open-label, phase I-II trial of patients with RRHL after first-line chemotherapy. Treatment had three 21-day cycles of etoposide, solumedrol, high-dose AraC, and cisplatin. BV was administered at three dose levels (0.9, 1.2, and 1.8 mg/kg) intravenous on day ‒1 to 3 + 3 cohorts of patients. Final BV dose was 1.8 mg/kg. Responding patients proceeded to ASCT, followed by three BV courses (1.8 mg/kg, every 21 days). Main end points for evaluation were maximum tolerable dose and overall and complete response (CR) before ASCT. RESULTS: A total of 66 patients were recruited (median age 36 years; range 18-66): 40 were primary refractory, 16 early relapse and 10 late relapse. There were 39 severe adverse events were reported in 22 patients, most frequently fever (n = 25, 35% neutropenic), including 3 deaths. Grade 3-4 hematological toxicity presented in 28 cases: neutropenia (n = 21), thrombocytopenia (n = 14), and anemia (n = 7). Grade ≥3-4 extrahematological adverse events (≥5%) were non-neutropenic fever (n = 13) and hypomagnesaemia (n = 3). Sixty-four patients underwent stem-cell mobilization; all collected >2×10e6/kg CD34+ cells (median 5.75; range 2.12-33.4). Overall response before transplant was 91% (CI 84% to 98%), including 70% (CRs 95% CI 59% to 81%). 60 patients were transplanted with no failure engraftments. Post-transplant response was CR in 49 patients (82% CI 73% to 91%) and partial responses in six (10% CI 5% to 15%). After a mean follow-up of 27 months, the 30-month time to treatment to failure was 74% (95% CI 68% to 80%), progression-free survival 71% (95% CI 65% to 77%), and overall survival 91% (CI 84% to 98%). CONCLUSION: BRESHAP looks a safe and effective pre-transplant induction regimen, does not jeopardize transplant and allows long-term remissions and survival.

Primary lymphocytic lymphoma of lacrimal gland. / Linfoma linfocítico primario de glándula lagrimal.

CASE REPORT: We report a case of primary small-cell lymphocytic lacrimal gland lymphoma in a male diagnosed with primary antiphospholipid syndrome. These rare lymphomas are usually presented in the clinic as disseminations secondary to chronic lymphocytic leukaemia, and the primary site is rare in the orbit. DISCUSSION: Non-Hodgkin lymphomas are a heterogeneous group of tumours. Although treatment in the IE stage is usually radiotherapy, due to its association with antiphospholipid syndrome, systemic treatment with rituximab was administered.

Toxicity and efficacy of busulfan and fludarabine myeloablative conditioning for HLA-identical sibling allogeneic hematopoietic cell transplantation in AML and MDS.

The safety and efficacy of a 4-day myeloablative conditioning (MAC) regimen consisting of Bu 3.2 mg/kg and fludarabine 40 mg/m(2)/day for HLA-identical sibling allogeneic hematopoietic cell transplantation (HCT) in myeloid malignancies was investigated in 133 patients (median age, 47 years; range 19-74 years) with de novo AML (60%), secondary AML (20%) or myelodysplastic syndrome (20%). All patients engrafted. Hepatic veno-occlusive disease occurred in five patients (4%), and severe toxicities, mostly mucositis, occurred in twenty-three (17%) patients. The non-relapse mortality (NRM) at 100 days was 1.5%. The incidences of acute GVHD grade 2-4 and grade 3-4 were 32 and 13%, respectively. At a median follow-up of 38 months, the cumulative incidence of chronic GVHD was 67%. The relapse incidence was 30% (27 and 31%, respectively, in patients with early- and late-stage disease), and the overall NRM was 15%. The actuarial 4-year disease-free survival (DFS) and overall survival (OS) were 54 and 62%, respectively. Patients aged <50 years had better outcomes compared with older patients (DFS 64 vs 42%, P=0.006; OS 73 vs 47%, P<0.001, respectively).

How can we improve problem solving in undergraduate biology? Applying lessons from 30 years of physics education research.

If students are to successfully grapple with authentic, complex biological problems as scientists and citizens, they need practice solving such problems during their undergraduate years. Physics education researchers have investigated student problem solving for the past three decades. Although physics and biology problems differ in structure and content, the instructional purposes align closely: explaining patterns and processes in the natural world and making predictions about physical and biological systems. In this paper, we discuss how research-supported approaches developed by physics education researchers can be adopted by biologists to enhance student problem-solving skills. First, we compare the problems that biology students are typically asked to solve with authentic, complex problems. We then describe the development of research-validated physics curricula emphasizing process skills in problem solving. We show that solving authentic, complex biology problems requires many of the same skills that practicing physicists and biologists use in representing problems, seeking relationships, making predictions, and verifying or checking solutions. We assert that acquiring these skills can help biology students become competent problem solvers. Finally, we propose how biology scholars can apply lessons from physics education in their classrooms and inspire new studies in biology education research.

The submarine volcano eruption at the island of El Hierro: physical-chemical perturbation and biological response.

On October 10 2011 an underwater eruption gave rise to a novel shallow submarine volcano south of the island of El Hierro, Canary Islands, Spain. During the eruption large quantities of mantle-derived gases, solutes and heat were released into the surrounding waters. In order to monitor the impact of the eruption on the marine ecosystem, periodic multidisciplinary cruises were carried out. Here, we present an initial report of the extreme physical-chemical perturbations caused by this event, comprising thermal changes, water acidification, deoxygenation and metal-enrichment, which resulted in significant alterations to the activity and composition of local plankton communities. Our findings highlight the potential role of this eruptive process as a natural ecosystem-scale experiment for the study of extreme effects of global change stressors on marine environments.

Effect of addition of rituximab to salvage chemotherapy on outcome of patients with diffuse large B-cell lymphoma relapsing after an autologous stem-cell transplantation.

BACKGROUND: We have investigated if rituximab-based salvage regimens improve response rates and survival of patients with diffuse large B-cell lymphoma (DLBCL) relapsing after an autologous stem-cell transplantation (ASCT). PATIENTS AND METHODS: We have retrospectively analyzed 82 patients with DLBCL who received salvage therapy for relapse or progression after ASCT. Patients were divided into two groups, according to whether rituximab-based salvage regimens were given (n = 42, 'R-' group) or not (n = 40, 'R+' group) after ASCT. RESULTS: Patients in the R+ group had better complete remission (CR) (55% versus 21.4%, P = 0.006) and overall response (OR) (75% versus 40.4%, P = 0.001) rates, and better 3-year event-free survival (EFS) (37% versus 9%, P = 0.002) and overall survival (OS) (50% versus 20%, P = 0.005) than patients in the R- group. Patients retreated with rituximab had better CR (42.9% versus 21.4%, P = 0.032) and OR (66.7% versus 40.4%, P = 0.019) rates, and better OS (36.2% versus 20% at 3 years, P = 0.05) and EFS (36.2% versus 9% at 3 years, P = 0.05) than patients who received chemotherapy alone at relapse after ASCT. CONCLUSIONS: The addition of rituximab to salvage chemotherapy improves response rates and EFS in patients with relapsed DLBCL after ASCT. These patients may benefit from rituximab retreatment, although larger prospective studies are needed to confirm these results.

Estudio epidemiológico observacional para evaluar el manejo de los trastornos gastrointestinales en el paciente con tratamiento antiagregante / An observational epidemiological studyto evaluate the management of gastrointestinal disorders in patients on antiplatelet therapy

Introducción. Las alteraciones gastrointestinales a modo de dispepsia, náuseas, diarreas, estreñimiento, úlcerapéptica o hemorragia gastrointestinal son efectos indeseables asociados frecuentemente a los fármacos antiagregantesplaquetarios. Objetivo. Identificar la estrategia terapéutica que se asocia a una mayor reducción de los problemas gastrointestinalesasociados a antiagregantes plaquetarios. Pacientes y métodos. De modo consecutivo, se incluyeron pacientesambulatorios tratados crónicamente con fármacos antiagregantes plaquetarios, que presentaban trastornos gastrointestinalesatribuidos por el investigador al tratamiento antiagregante. Se registraron las estrategias utilizadas para el manejode los trastornos gastrointestinales y se estudió el grado de satisfacción de los pacientes mediante escalas analógicasvisuales de tolerabilidad, calidad de vida y facilidad para el cumplimiento de la medicación, tanto con el tratamiento farmacológicoinicial como con el tratamiento farmacológico instaurado para manejar los trastornos gastrointestinales. Resultados.Se reclutaron 609 pacientes (55,3% hombres). Los pacientes inicialmente tratados tanto con triflusal en solucióncomo con triflusal en cápsulas toleraban mejor la medicación que los inicialmente tratados con ácido acetilsalicílico (p <0,0001). El cambio de tratamiento antiagregante o de dosis fue la estrategia más utilizada (65% de los casos). En 385 pacientes(63,2%) se realizó un cambio de tratamiento farmacológico. El cambio del tratamiento antiagregante inicial portriflusal solución mejoró la tolerabilidad del tratamiento y la calidad de vida, al tiempo que redujo la dificultad para elcumplimiento de la medicación. Conclusión. El triflusal en solución es una buena alternativa en pacientes que presententrastornos gastrointestinales asociados a tratamiento antiagregante crónicoAU)

Introduction. Gastrointestinal disorders like dyspepsia, nausea, diarrhoea, constipation, peptic ulcers or gastrointestinalhaemorrhages are undesirable side-effects that are often associated to antiplatelet therapy. Aim. To identifythe therapeutic strategy that leads to the greatest reduction in the number of gastrointestinal problems associated withantiplatelet drugs. Patients and methods. Our sample consisted of consecutive outpatients undergoing chronic antiplatelettherapy who presented gastrointestinal disorders that the researcher attributed to the antiplatelet therapy. Thestrategies used this to manage the gastrointestinal disorders were recorded and the degree of patients’ satisfaction wasstudied by means of visual analogical scales for measuring tolerability, quality of life and ease of treatment compliance,for both the initial pharmacological treatment and pharmacological treatment that was established to manage thegastrointestinal disorders. Results. The sample was made up of 609 patients (55.3% males). Patients who were initiallytreated with triflusal solution and with triflusal capsules tolerated medication better than those who were initially treatedwith acetylsalicylic acid (p < 0.0001). Changing the antiplatelet therapy or the doses was the most widely used strategy(65% of cases). Pharmacological treatment was changed in 385 patients (63.2%). Changing the initial antiplatelettherapy for triflusal solution improved treatment tolerability and quality of life, while also lessening the difficultiesinvolved in achieving medication compliance. Conclusions. Triflusal solution is a good alternative in patients whopresent gastrointestinal disorders associated to chronic antiplatelet therapy(AU)

Hematopoietic SCT for peripheral T-cell lymphoma.

Results of conventional chemotherapy for high-risk peripheral T-cell lymphoma (PTCL) are poor compared with those for their aggressive B-cell counterparts. We aim to review the current data on the use of hematopoietic SCT in these patients in both frontline and salvage settings. With respect to autologous SCT (ASCT), conclusions from retrospective studies are that ASCT in the salvage setting is as useful in PTCL as in aggressive B-cell lymphomas and also that consolidation in first complete response of high-risk patients has very good results when compared with conventional chemotherapy (with long-term PFS higher than 50%). From first frontline prospective clinical trials, it appears that ASCT is feasible and has a low TRM (<5%); consolidation in first complete response is associated with a very good outcome; around 25% of patients do not undergo ASCT due mainly to disease progression; new approaches aimed at increasing the number of chemosensitive patients should be found. Furthermore, 25-30% of patients deemed complete responders post transplant still relapse afterward. For all these mainly chemoresistant patients, there is preliminary evidence that allogeneic SCT (Allo-SCT) may produce a plateau in survival curves (with long-term PFS around 50%), which indicates a graft-versus-PTCL effect. For this reason, Allo-SCT procedures are the object of ongoing clinical trials.

The results of consolidation with autologous stem-cell transplantation in patients with peripheral T-cell lymphoma (PTCL) in first complete remission: the Spanish Lymphoma and Autologous Transplantation Group experience.

BACKGROUND: Peripheral T-cell lymphoma (PTCL) is a heterogeneous group of aggressive lymphomas associated with poor prognosis with standard chemotherapy. Consolidation with autologous stem-cell transplantation (ASCT) may improve survival. We present 74 patients transplanted in first complete response (CR) from the Spanish Lymphoma and Autologous Transplantation Group cooperative group. PATIENTS AND METHODS: Median age was 46 years. Eighty-eight percent presented advanced (III-IV) Ann Arbor stage; 53% had B symptoms; 52% had high lactate dehydrogenase; 65% had two or three risk factors of the adjusted-International Prognostic Index; 58% presented a high Tumor score and in 14% more than two adverse factors of the Prognostic Index for peripheral T-cell lymphoma (PIT) were observed. RESULTS: With a median follow-up of 67 months from diagnosis, the 5-year overall survival (OS) was 68% and progression-free survival (PFS) reached 63%. The multivariate analysis showed that the only factor associated with a shorter OS and PFS was the presence of more than two risk factors from the PIT risk system. CONCLUSIONS: In a retrospective study with a prolonged follow-up, consolidation with ASCT in CR patients who had presented unfavorable prognostic factors at diagnosis substantially increased the OS and PFS when compared with conventional chemotherapy. The PIT risk system identified 14% of patients without benefit from ASCT consolidation. Thus, other innovative therapies are still necessary in certain cases.

Prognostic factors affecting long-term outcome after stem cell transplantation in Hodgkin's lymphoma autografted after a first relapse.

PURPOSE: To analyse outcome and prognostic factors for overall survival (OS) and time to treatment failure (TTF) in 357 patients with Hodgkin's lymphoma (HL) undergoing an autologous stem cell transplantation (ASCT) after a first relapse and reported to the The Grupo Espanol de Linfomas/Trasplante Autologo de Medula Osea (GEL/TAMO) Cooperative Group. METHODS: Two hundred and twenty males and 137 females with a median age of 29 years were autografted in second remission (n=181), first sensitive relapse (n=148) and first resistant relapse (n=28). RESULTS: Five-year actuarial TTF and OS were of 49% +/- 3% and 57% +/- 3%. Advanced stage at diagnosis, complementary radiotherapy before ASCT, a short first complete response (CR) and detectable disease at ASCT adversely influenced TTF. Year of transplant < or =1995, bulky disease at diagnosis, a short first CR, detectable disease at ASCT and > or =1 extranodal areas involved at ASCT were adverse factors for OS. CONCLUSIONS: ASCT constitutes a therapeutic option for HL patients after a first relapse. Promising results are observed in patients with low tumour burden at diagnosis, autografted after a long CR and without detectable disease at ASCT. Innovative approaches should be pursued for patients with risk factors at relapse.