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Background: The Rhinoplasty Health Inventory and Nasal Outcomes scale (RHINO) is a comprehensive quality of life instrument that evaluates both functional and aesthetic outcomes after rhinoplasty. Aim: to evaluate patient reported outcomes after nasal surgery using the scale. Methods: We enrolled 78 patients. Inclusion criteria were patients older than 18 years with nasal obstruction or aesthetic deformity that underwent functional and aesthetic rhinoplasty by the senior author from May 2016 to May 2017 in Perth, Australia. The patients enrolled in the study were asked to complete the scale in five different moments: before the surgery, 6 weeks, 3 months, 6 months and 1 year after the surgery. Instrument analysis was performed using Stata 14 by assessment of test-retest reliability, internal consistency reliability;construct validity and comparison of the pre- and postoperative values. Results: Patient age ranged from 18 to 80 years. The average age was 33,03 years with a standard deviation of 11,75 years. The preoperative median value was 21 with an interquartile range (18-26). The 6-week RHINO results were in median 44 (40-48), the 3-months scale median result was 44 (39-47), the 6-months median result was 42(38,5-46,5) and the 1-year result median was 46 (39-48). We found in the overall results statistically significant difference between the preoperative scale result and the first postoperative scale with a Wilcoxon test (p < 0.001). Cronbach’s ? was 0,8036. Conclusions: Overall, patients are satisfied with their outcomes. The scale proved to be a good instrument to measure this.

RESUMEN Introducción La tasa de infección después de la cirugía nasal electiva es muy baja, lo que hace que la profilaxis antibiótica de rutina sea redundante. En Colombia no disponemos de información acerca de la tasa de infección de septoplastia; por esta razón, en este artículo se busca describir la tasa de infección posquirúrgica en los pacientes llevados a septoplastia o septoplastia y turbinoplastia de la Fundación Santa Fe de Bogotá, entre los años 2016-2018. Metodología: se realizó un estudio observacional, descriptivo y retrospectivo mediante la revisión de la base de datos del servicio. Se calculó la proporción de infección para todos los individuos participan tes del estudio de manera general y estratificada por el uso de antibiótico profiláctico y posoperatorio, y se describió la frecuencia de las complicaciones. Resultados: encontramos 255 pacientes en la base de datos de la sección de otorrinolaringología, de los cuales 206 cumplieron con los criterios de inclusión. El 23,3 % de los pacientes recibió un antibiótico profiláctico y el 24,76 % recibió un antibiótico postoperatorio. La tasa de infección posoperatoria fue de 2,91 % (intervalo de confianza [IC] del 95%: 1,07-6,23). El 96,6 % de los pacientes no presentaron complicaciones. Conclusiones: nuestros hallazgos se correlacionan con la literatura global.

La pandemia de enfermedad por coronavirus 2019 (COVID-19) ha producido cambios sin precedentes en la comunidad médica. Los médicos y trabajadores de la salud que realizan o participan en exámenes o procedimientos de cabeza y cuello y de la vía aérea son susceptibles en alto riesgo de adquirir la infección por COVID 19 debido a la alta exposición a aerosoles y contaminación por gotas. En la actualidad se carece de datos de riesgo específico de infección. Sin embargo, los otorrinolaringólogos y cirujanos de cabeza y cuello, junto con los oftalmólogos y los odontólogos, son los grupos de mayor riesgo dentro de los profesionales de la salud debido a las áreas que examinan. Este documento se desarrolla con base en pautas encontradas en la literatura disponible más reciente. Es seguro que serán modificadas según la experiencia de cada país.

IntroducciónLa pandemia por el nuevo Coronavirus nos ha afectado a todos y muchos hemos tenido que cerrar o disminuir sustancialmente nuestra práctica. Sin embargo, es necesario mantener comunicación con nuestros pacientes que continúan requiriendo de nuestra atención y manejo. Es aquí donde la telemedicina en otorrinolaringología juega un rol muy importante. MétodosSe realizó una revisión narrativa de la literatura mediante una búsqueda en PUB-MED y EMBASE a conveniencia con respecto a la información disponible sobre telesalud y telemedicina en el área de la Otorrinolaringología. Además se incluyó literatura de asociaciones de otorrinolaringología a nivel mundial y lineamientos y normas del gobierno colombiano Discusión La telemedicina es una útil herramienta para la atención de pacientes en esta contingencia. Debemos seguir ciertos parámetros, elegir adecuadamente a los pacientes y actuar con honestidad y buena fe. Se realizan sugerencias del beneficio de la telesalud y telemedicina, consideraciones especiales en nuestra práctica médica, alcances de los servicios mencionados e implementación de estos en nuestros consultorios e instituciones basados en la literatura disponible, normas legales y experiencia de los autores. Conclusión En la práctica del Otorrinolaringólogo es posible implementar la telemedicina con el aval de las aseguradoras y la aceptación de los pacientes. Se debe ser extremadamente cuidadoso con el diligenciamiento de la historia clínica, con la formulación de medicamentos y seleccionar adecuadamente a los pacientes. La telemedicina en otorrinolaringología es una herramienta valiosa que nos permite continuar atendiendo a pacientes seleccionados cuidándolos a ellos y a nosotros.

BackgroundCurrent pharmacological treatments remain inadequate for a significant proportion of patients with rheumatoid arthritis (RA), and thus alternative treatment approaches are needed. Prior results from the first 12 weeks of a proof-of-concept (POC) study showed that ATHENS, a non-invasive high-frequency vagus nerve therapy, was well-tolerated with meaningful reductions in RA disease severity as measured by the American College of Rheumatology response criteria (ACR) and the Disease Activity Score using 28 joints (DAS28)[1].ObjectivesThe current analysis assessed long-term changes (52 weeks total follow-up) in disease activity as measured by ACR, DAS28, and the following MRI-assessed changes: synovitis, osteitis, bone erosion, and cartilage loss.MethodsFollowing the completion of the 12-week POC study, patients achieving a reduction in DAS28-CRP of ≥1.2 were given the option to enroll in the 9-month open-label extension (OLE) study. During the extension phase, patients were to use the wearable device for 15 minutes per day. Adjustment of conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) or biologic disease-modifying antirheumatic drugs (bDMARDs) were allowed during the OLE. Changes from baseline were assessed at 12 weeks (end of initial POC) and 52 weeks (end of the OLE). Structural damage and disease progression were evaluated by standardized MRI of the wrist and hand, with and without intravenous gadolinium-based contrast. MRIs were evaluated by two independent, central readers, blinded to clinical information and visit-order of the images, and were scored for synovitis, osteitis and bone erosion using the OMERACT-RAMRIS method. Cartilage loss was also determined using the 9-point cartilage loss scale (CARLOS).ResultsTwenty-seven of 30 patients completed the initial 12-week study, of whom 19 consented and entered the OLE. Of those 19 patients, 4 (21%) discontinued due to lack of efficacy, while the remaining 15 completed the 9-month extension. Due to the COVID-19 pandemic, 7 patients were unable to complete a 52-week MRI scan; MRI evaluations at baseline, 12 weeks, and 52 weeks were available for 8 patients.DAS28-CRP mean (standard deviation [SD]) change from baseline was -1.78 (1.01) at 12 weeks (n=19; pTable 1.Change in MRI OMERACT-RAMRIS from baseline to week 52ScoreBaseline (n=8)Week 12 (n=8)Week 52 (n=8)Change Week 12 vs BL (n=8)Change Week 52 vs BL (n=8)CARLOS, mean (SD)3.9 (5.6)3.9 (5.6)3.9 (5.6)0.0 (0.0)0.0 (0.0)Erosion, mean (SD)10.8 (10.3)10.5 (10.3)10.6 (10.3)-0.3 (0.4)-0.1 (0.8)Osteitis, mean (SD)2.8 (4.1)2.3 (3.7)1.0 (1.1)-0.5 (1.1)-1.8 (3.1)Synovitis, mean (SD)4.0 (4.2)4.1 (4.7)3.3 (4.0)0.1 (0.6)-0.7 (1.0)CARLOS = Cartilage loss score; OMERACT = Outcome Measures in Rheumatology; RAMRIS = Rheumatoid Arthritis Magnetic Resonance Imaging Scoring SystemDuring the 9-month extension study, two new adverse events were reported (cornea transplant and right hand dysesthesia) in 2 (11%) patients; neither was treatment-related and both resolved without intervention. No serious adverse events were reported.ConclusionIn patients with an initial treatment response to the Nēsos ATHENS therapy in the 12-week POC study, reductions in DAS28-CRP were sustained through 52 weeks. Although results should be interpreted cautiously given the small sample size and lack of control arm, MRI evaluation of synovitis, osteitis, bone erosion, and cartilage loss suggested no disease progression.References[1]Marsal, S., The Lancet Rheumatology, 2021. 3(4): p. e262-e269.Disclosure of InterestsCharles Peterfy Consultant of: Nesos Corp, Employee of: Spire Sciences, Héctor Corominas: None declared, Juan Jose de Agustin: None declared, Carolina Perez-Garcia: None declared, Maria Lopez Lasanta: None declared, Helena Borrell Paños: None declared, D Reina-Sanz: None declared, Raimón Sanmartí: None declared, J. Narváez: None declared, Jose Antonio Narvaez: None declared, Vivek Sharma Shareholder of: Nesos Corp., Employee of: Nesos Corp., Konstantinos Alataris Shareholder of: Nesos Corp., Employee of: Nesos Corp., Mark C. Genovese Shareholder of: Nesos Corp. and Gilead, Employee of: Gilead, Matthew Baker Shareholder of: Nesos Corp., Consultant of: Nesos Corp., Sara Marsal Consultant of: Nesos, Pfizer, Sandoz, Novartis, Gilead, Grant/research support from: Nesos, BMS, Celgene, Merck Sharp and Dohme, Pfizer, Sandoz, Novartis, Sanofi, Janssen, Union Chimique Belge Pharma

BackgroundGiven the progressive change in the management of inflammatory diseases,an observational study was conducted on the management of Early Rheumatoid Arthritis (ERA) in Catalonia.ObjectivesTo know the management of ERA in Catalonia, to assess whether the recommendations of the EULAR/ACR guidelines are followed and to study the causes of management variability,to set improvement objectives.MethodsAn observational,descriptive,and cross-sectional study was conducted,with data collection from June 15 to 30, 2021.The rheumatologists’ partners of the Catalan Society of Rheumatology were the object of study. An online survey was conducted with 304 members on the management of the ERA. Variables related to the characteristics of the respondents,the derivation and variables of the disease including clinical variables,type of treatment and outcomes used for follow-up including the impact of the SARS-CoV2 pandemic were included.The univariate study was performed using a study of proportions with Pearson’s correlation.ResultsA total of 105 members (34.5%) responded to the survey.11.6%>60 y, only 7.8% Characteristics of ERA:77.5% are derived from primary care(PC),52% have been between 6 weeks,42.1%>3 months.54.9% make a first visit within 2-4 weeks of PC referral and 14.7%> 8 weeks.100%provide previous analysis,only 47% had had RX performed.98% were previously treated(50.4%NSAIDs + CG,36.1%NSAIDs,12.3% CG).4.3% had GC doses>10 mg/day,11.3%> to 20mg/day.The treatment:DMARDs of choice in 100% is MTX,44.1% start doses of 10mg/week and 3.9%7.5 mg/week.The route of choice is oral(55.9% vs 44.1%).92.2% associate GC and 31.7% have not withdrawn them after 6 m.57.8% consider the maximum of MTX 25mg/W.87.1% use dosesPROs(HAQ 83.3%,RAPID 3 14.3%).The use of systematic ultrasound is collected in 33%, being himself who performs it in 59.9% and an expert rheumatologist in 46.1%.Finally, when asked about incidence of pandemic in the follow-up,53.3% consider that it is doing the same as before. 46.1% consider that telephone visits are not suitable for the follow-up of the ERAvs14.7% who consider that Yes.When questioning the situations in which they consider them to be appropriate,75.9% that it was adequate in the control after the beginning of the DMARDs.Regarding the treatment of ERA, 66% delayed the onset of biological DMARDs, 72.1% due to difficulty of follow-up and only 8.8% due to an increased risk of infection. When performing the univariate analysis, it is evident that having a monographic dispensary is associated with earlier onset of MTX(p< 0.001)and at doses≥15 mg/W(p = 0.05),greater nursing intervention(p< 0.001),greater use of PROs(p = 0.008)and there is a tendency to a shorter waiting time for first visits(p = 0.07).It is also associated with not considering telephone visits(p< 0.001), making them in less than 25%(p< 0.0001).Similarly,hospital level is directly proportional to initiation at higher doses of MTX(p< 0.0001),lower use of GCConclusionThe recommendations of EULAR/ACR in the treatment and follow-up of ERA are consistently followed,although the wide use of MTX orally is striking.It is evident that the variable that most influences the early onset of FAME and at higher doses,is a monographic dispensary,as well as greater presence of nursing and performance of PROs.AcknowledgementsThanks to all the members of the Catalan society of reuamtology who participated in the surveyDisclosure of InterestsNone declared

BackgroundMany patients with palindromic rheumatism (PR), mainly those with positive autoantibodies, evolve to rheumatoid arthritis (RA). Management of PR is empirical, and hydroxychloroquine (HCQ) is the most used antirheumatic drug. Abatacept (ABA) has been investigated in preclinical RA with good results. There are no randomized clinical trials in PR.ObjectivesTo present the design of a randomized clinical trial in PR (PALABA study). To describe the characteristics of the patients at study entry. The main objective is to test the hypothesis that ABA can reduce the progression of RA in seropositive (ACPA+ and/or RF+) PR patients in comparison with HCQ.MethodsPhase IV multicenter open label randomized controlled clinical trial with 42 months duration. The enrollment period was 18 months and the open randomized period 24 months. Fourteen spanish centers were included. The sample size was 70 patients (35 per arm). ABA sc 125 mg/week first year, 125 mg eow second year and HCQ oral 5mg/Kg daily were administered, both therapies in monotherapy. The main inclusion criteria were age >18 years with PR according to Guerne and Weissman modified criteria and disease evolution >3 and 1 week at baseline, with criteria of other rheumatic diseases, radiographic erosions or previous antirheumatic therapy with synthetic DMARDS were excluded. The main outcome measure is achievement of RA classification criteria (EULAR/ACR 2010) at any time during the 24-month follow-up. Secondary outcomes were the number and intensity of joint attacks, adverse events, and effects on serum ACPA and anti-carbamylated antibodies at 0,3,12,24 months of follow-up. STATISTICS: Modified Full Analysis Set and Per Protocol Population analysis.ResultsPatient one was included in June 2018. The inclusion period has been extended until April 2022 due to low recruitment rates, partly due to the COVID-19 pandemic. As of 15 Jan 2022, 51 patients have been randomized and 49 (37F/12M) have received at least one drug dose. The mean onset of symptoms was 9.9±6.3 months. In 22 patients the follow-up time was greater than 12 months. RF and ACPA (CCP2) were positive in 81.6% and 89.8% of patients respectively; 24 patients were included in the ABA arm and 25 in the HCQ arm. Seven patients withdrew from the study during follow-up due to: progression to RA (n=3), adverse events (n=2) and other reasons (n=2). The demographic, clinical and laboratory characteristics of PR patients at study entry are shown in Table 1. No significant differences in patients’ characteristics between arms were observed at enrollment except a higher prevalence of CCP2 in the HCQ arm.Table 1Baseline demographic, clinical and laboratory characteristics at study entryAge, mean (sd)49.6 (11.2)49.8 (12.0)49.4 (10.7)NSFemale, n (%)37 (75.5)19 (79.2)18 (72)NSBody mass index, mean (sd)27.(5.7)26.6 (5.5)27.4 (5.9)NSMonth of symptom duration, mean (sd)9.9 (6.3)9.8 (6.8)9.9 (5.9)NSCurrent Smokers, mean (sd)15 (30.6)6 (25)9 (36)NSNumber attacks 6 months before inclusion, mean (sd)4.65 (4.07)4.24 (2.78)5.0 (5.0)NSPIP/MCP involvement n (%)35 (71.4)16 (66.7)19 (76)NSWrist involvement, n (%)32 (65.3)17 (70.8)15 (60.0)NSInvolvement of other joints, n (%)30 (61.2)14 (58.3)16 (64.0)NSESR (mm), mean (sd)20.71 (16.8)23.13 (18.8)18.30 (14.8)NSRF positive, n (%)40 (81.6)19 (79.2)21 (84)NSACPA (CCP2) positive, n (%)44 (89.8)19 (79.2)25 (100)0.022PIP: proximal interphalangeal MCP: metacarpophalangealConclusionWe present the design of the first randomized clinical trial in PR of the efficacy of antirheumatic drugs (ABA vs HCQ) to avoid progression towards RA in patients with a high risk (recent onset PR and positive autoantibody status) of persistent arthritis. The characteristics of patients included until now are similar to those reported in recent onset PR.AcknowledgementsPALABA study investigators: Beatriz Frade-Sosa, Rosa Maria Morlà, Lola Tobalina, Maria López-Lasanta, Helena Borrell, Georgina Salvador, Andrea M Cuervo, Noemí Busquets, Eduard Graell, Carolina Pérez- García, Luciano Pocino, Delia Reina, Oscar Camacho, Hector Corominas Ana M Millan. Miquel Sala, Sonia Castell, Eduardo Kanterewicz, Josep R. Rodriguez Cros, Alejandro Escudero, Usansolo Irati, José Francisco Garcia, Francisco Javier Toro, Natividad Oreiro, Alejandro Olivé, Maria J Gómara, Cristina García-Moreno, Isabel Haro and Raimon Sanmarti.Disclosure of InterestsBeatriz Frade-Sosa: None declared, Rosa Morlà: None declared, Lola Tobalina: None declared, Carolina Perez-Garcia: None declared, Isabel Haro: None declared, Raimón Sanmartí Speakers bureau: received speaker honorariafrom Abbvie, BMS, Gebro-Pharma, Lilly, MSD, Pfizer, Sanofi and Roche, Grant/research support from: investigation grants from Abbvie, BMS, Gebro-Pharma, Lilly, MSD, Pfizer, Sanofi and Roche

BackgroundExtensive evidence has confirmed no increased risk of cancer associated to either conventional synthetic DMARDs or anti-TNF in patients with rheumatic diseases. The risk of cancer in biologic (bDMARDs) different to anti-TNF and targeted synthetic (tsDMARDs) is considerably less investigated. As new therapies are emerging, more data in real-world registries are needed to confirm safety in other treatment groups.ObjectivesTo compare the risk of cancer of tsDMARDs and other bDMARDs versus anti-TNF in patients with rheumatic diseases.MethodsData of patients enrolled in BIOBADASER 3.0 up to October 2021 with the start of any bDMARD or tsDMARD were analyzed. For each group, demographic and clinical variables were estimated. Changes to therapy and occurrence of serious adverse events collected annually. Incident cancer was defined as any cancer during the exposure classified according to Meddra dictionary leading to therapy discontinuation. Incidence rate ratios of cancer per 1000 patients-year (PYs) and 95% confidence interval were estimated. Incidence rate ratio was calculated for each group versus anti-TNF.ResultsWe identified 271 cancers in BIOBADASER 3.0, corresponding to a cancer incident rate of 7.4 (6.5-8.3) per 1000 PY of exposure. Patients exposed to anti-TNF and anti-IL17 were younger, with lower disease duration and comorbidity versus other groups. Proportionally more malignancies were identified in the anti-CTLA-4 group (3.4%) versus the anti-TNF group (2.9%). The rates of incident cancer ranged between 2.6 events/1000 PY in the anti-IL17 group and 15.3 events/1000 PY in the anti-CTLA-4 group. The rate of cancer did not differ significantly in patients exposed to JAKi [0.8 (95% CI 0.4-1.5)], anti CD20 [1.1 (95% CI 0.6-1.8)], or anti-IL6 [1.3 (95% CI 0.9-1.9)] versus anti-TNF; it was significantly lower in patients exposed to anti-Il17 [0.4 (95% CI 0.2-0.9)], and significantly higher in patients exposed to anti-CTLA-4 [2.2 (95% CI 1.4-3.2)]. The most frequent malignancy was non-melanoma skin cancer, followed by solid cancer (mainly breast cancer with 24 events and lung cancer with 14 events) and melanoma (13 events).Table 1.New Cancer Diagnosis Among Patients with anti-TNF versus other therapiesAnti-TNF (N=6356)JAKi (N=1079)Anti-CD20 (N=667)Anti-IL6 (N=1178)Anti-CTLA-4 (N=783)Anti-IL17 (N=1051)Female, n (%)3738 (58.8)868 (80.4)523 (78.4)947 (80.4)598 (76.4)492 (46.81)Mean age, (SD)54.8 (14.7)58.5 (12.4)60.9 (13.6)59.8 (15.1)64.0 (12.8)52.2 (11.6)Mean start age, (SD)49.1 (14.0)56.6 (12.3)57.9 (13.5)55.7 (15.2)59.7 (13.0)49.8 (22.2)Disease duration, median (IQR)6.2[2.2-13.0]10.4[4.7 -17.2]11.0[5.1-18.5]8.3[3.2-15.1]10.3[5.2-17.0]3.1[0.3-10.7]Charlton Index1.9 (1.3)2.4 (1.6)2.4 (1.7)2.4 (1.7)2.8 (1.9)1.8 (1.3)First line biologic, n (%)99 (53.2)2 (22.2)1 (7.1)6 (20.0)5 (18.5)2 (66.7)New cancer diagnosis, n (%)186 (2.9%)9 (0.8%)14 (2.1%)30 (2.5%)27 (3.4%)5 (0.5%)Median years of follow-up months4.2 [2.3-7.3]2.4 [1.4-3.2]1.0 [1.0-1.0]2.6 [1.3-6.6]4.4 [1.5-5.7]1.8 [1-5-2.2]Time of exposure, yrs26233.51652.71871.53196.71762.11921Cancer Incidence Rate (per 1000 PY) ancer Incide7.1 (6.1-8.2)5.4 (2.8-10.5)7.5 (4.4-12.6)9.4 (6.6-13.4)15.3 (10.5-22.3)2.6 (1.1-6.3) .6 (1.1-6.3).5.2 (4.4-6.1)6.3 (1.6-8.1)5.9 (3.3-10.6)7.5 (5-11.2)10.8 (6.9-16.9)1.6 (0.5-4.8) .6 (0.5-40.3 (0.2-0.6)0 (0-0)1.1 (0.3-4.3)0.3 (0-2.2)0.6 (0.1-4)0 (0-0) (0-0)1-4)3)9)) Rate (per1.6 (1.2-2.2)1.8 (0.6-5.6)0.5 (0.1-3.8)1.6 (0.7-3.8)4 (1.9-8.3)1 (0.3-4.2)Rate ratio (vs anti-TNF)NA0.8 (0.4-1.5)1.1 (0.6-1.8)1.3 (0.9-1.9)2.2 (1.4-3.2)0.4 (0.2-0.9)ConclusionIn this register-based study, rates of incident cancer did not differ between patients treated with anti-TNF and other bDMARDs or tsDMARDs, with the possible exception of a potential increased risk in patients treated with anti-CTLA-4.AcknowledgementsThank you to all patients, rheumatologists, and to the research personnel from the Spanish Foundation of Rheumatology who made this study possible.Disclosure of InterestsIsabel Castrejon: None declared, Juan Molina Collada: None declared, Carolina Perez-Garcia: None declared, Paloma Vela-Casasempere Speakers bureau: ROCHE, UCB, GSK, LILLY, Consultant of: PFIZER, BMS, LILLY, UCB, GSK, Abbvie, Fresenius Kabi, Grant/research support from: ROCHE, ABBVIE, PFIZER, BMS, LILLY, SANDOZ, AMGEN, Cesar Diaz-Torne: None declared, Cristina Bohórquez: None declared, J M Blanco: None declared, Fernando Sánchez-Alonso: None declared

BackgroundPatients with a history of cancer are routinely excluded from randomized controlled trials. As consequence, data on the safety of biologic disease modifying antirheumatic drugs (bDMARDS) and targeted synthetic (ts) DMARDs are limited. Although real world data from various national registries have not provided evidence of increased cancer recurrence, additional data from real-world registries may help to confirm safety of non-TNFi bDMARDs and tsDMARDs regarding cancer recurrence to guide treatment decisions.ObjectivesTo compare the risk of incident malignancy with exposure to different bDMARDs and tsDMARDs in patients with rheumatic diseases and a prior malignancy.MethodsThe study population comprised patients with a prior malignancy from the BIOBADASER 3.0 up to 2021. BIOBADASER is a large national drug safety registry of patients with rheumatic diseases starting treatment with any bDMARD or tsDMARD and followed thereafter at the time an adverse event or a change in biological therapy occurs. Incident cancer was defined as any cancer (new primaries, local recurrence or metastases) during the exposure classified according to Meddra dictionary. Incidence rate ratios of cancer per 1000 patients-year (PY) and 95% CI were estimated. Rates of incident cancer in tsDMARDs and other bDMARDs versus anti-TNF treated patients were compared.ResultsA total of 9,129 patients treated with bDMARDs and tsDMARDs are included in BIOBADASER 3.0 at the time of the study. Of them, 352 with a prior history of malignancy at time of enrollment were selected for analysis (Figure 1). Overall, there were 32 incident malignancies (17 solid cancer, 14 non-melanoma skin cancer and 1 melanoma). The overall rate of incident malignancy was 27.1 (95% CI 18.6-38.3) events/1,000 PY, ranging between none events/1000 PY in the anti-IL17 group to 51.7 events/1000 PY in the anti-CTLA-4 group (Table 1). The overall rate of incident cancer did not differ significantly in patients exposed to JAKi [0.6 (95% CI 0.1-2.5)], anti-CD20 [0.3 (95% CI 0.1-1.4)], anti-IL6 [1.2 (95% CI 0.5-3.4)] or anti-CTLA-4 [1.3 (95% CI 0.5-3.6) versus anti-TNF therapy. The rate of different types of cancer (melanoma, non-melanoma skin cancer or solid tumors) did not differ between the different treatment groups when compared to anti-TNF therapy (Table 1).Table 1.Baseline characteristics and rate of incident cancer.Anti-TNF(n = 185)JAKi(n = 61)Anti-CD20(n= 61)Anti-IL6(n= 68)Anti-CTLA-4(n= 47)Anti-IL17(n= 39)Total(n=352)Female, n (%)129 (69.7)49 (80.3)43 (70.5)54 (79.4)34 (72.3)21 (53.9)247 (70.2)Age, mean (SD)64.4 (13.1)66.7 (13.1)67.8 (10.0)70.5 (11.6)71.8 (10.4)59.5 (14.6)65.3 (13.0)Start treatment age, mean (SD)60.0 (12.9)64.8 (12.8)65.7 (9.6)67.3 (11.3)62.8 (12.7)56.9 (14.5)61.6 (12.8)Disease duration, median (IQR)6.7 (3.0-13.1)12.3 (7.4-19.6)10.8 (6.3-19.4)8.5 (4.0-16.8)8.2 (4.1-16.6)8.4 (4.7-16.1)7.0 (2.9-15.5)Time of follow-up months, mean (SD)23.1 (25.3)15.9 (13.3)11.5 (2.5)16.8 (17.6)23.7 (22.6)18.4 (15.5)17.5 (18.2)Charlson comorbidity index4.9 (2.0)5.2 (2.2)5.1 (2.0)5.5 (2.1)6.1 (2.6)6.9 (2.6)5.2 (2.1)Prior malignancyNon-lymphoproliferative (solid or melanoma), n (%)174 (94.5)58 (95.1)54 (88.5)65 (95.6)46 (97.9)36 (92.3)331 (94.0)Lymphoproliferative, n (%)9 (4.9)3 (4.9)13 (21.3)4 (5.9)4 (8.5)5 (12.8)29 (8.2)Metastatic cancer, n (%)2 (1.1)2 (3.3)2 (3.3)1 (1.5)3 (6.4)0 (0.0)7 (2.0)Incident cancerNew cancer diagnosis, n (%)182255032Time of exposure, sum (years)470,191,6163104,996,863,81178,6Rate of incident cancer (per 1,000 PY)38.3 (24.1-60.8)21.8 (5.5-87.3)12.3 (3.1-49.1)47.7 (19.8-114.5)51.7 (21.5-124.1)0 (0-0)27.1 (18.6-38.3)Rate ratio of incident cancer (vs anti-TNF)-0.6 (0.1-2.5)0.3 (0.1-1.4)1.2 (0.5-3.4)1.3 (0.5-3.6)--Figure 1.Flowchart of patients included.ConclusionThe risk of incident cancer in patients with rheumatic diseases and a prior malignancy does not differ according to the type of bDMARD and tsDMARD exposure.Disclosure of InterestsNone declared

Background:. The Standardized Cosmesis and Health Nasal Outcomes Survey (SCHNOS) questionnaire is a new instrument that was developed to evaluate both functional and cosmetic components of rhinoplasty. It is a reliable, consistent, and validated patient-reported outcome measure that is not available in Spanish. Methods:. The SCHNOS questionnaire was forward translated, back translated, and culturally adapted following international guidelines. Its psychometric validity was tested with native Spanish speakers in 2 centers in Colombia. The authors measured internal consistency, correlation, and reproducibility to determine validity of the instrument. Results:. The final Spanish version of the SCHNOS was administered to 76 native Spanish speakers. Both the SCHNOS-O (obstructive domain) and SCHNOS-C (cosmetic domain) showed a high internal consistency with Cronbach’s alpha of 0.84 and 0.94, respectively. The Spearman correlations between the items of SCHNOS-O (0.38–0.82) and SCHNOS-C (0.49–0.88) were positive and significant. Spearman’s rank correlation in the test–retest analysis for SCHNOS-O (r = 0.87) and SCHNOS-C (r = 90) was positive and statistically significant. There was statistical significance in responses obtained for SCHNOS-O (P < 0.001) but not for SCHNOS-C (P = 0.222). Conclusions:. In this study, the SCHNOS was successfully translated and culturally adapted into Spanish. The Spanish version of the SCHNOS was shown to be a reliable and valid instrument that we recommend it should be used in Spanish-speaking patients who are having functional or cosmetic rhinoplasty.

Coarse mode aerosols influence Earth's climate and biogeochemistry by interacting with long-wave radiation, promoting ice nucleation, and contributing important elements to biogeochemical cycles during deposition. Yet coarse mode aerosols have received less emphasis in the scientific literature. Here we present first efforts to globally synthesize available mass concentration, compositionand optical depth data and modeling for the coarse mode aerosols (

Objective This study aimed to determine the prevalence of nonsyndromic congenital sensorineural hearing loss at the Hospital Universitario San Ignacio, Bogotá, Colombia, and to describe the risk factors associated with this condition. Materials and Methods A prospective, observational cross-sectional study with bivariate analysis was conducted. A three-phase process using the Otoacoustic Emissions test screened all live newborns between June 2013 and June 2014. Negative cases were confirmed by Automated Auditory Brainstem Response test. Results A total of 962 newborns were screened with Otoacoustic Emissions test bilaterally: 401 males (46.36%), 464 females (53.64%). The mean weight was 2 798.10 g (95%CI: 2 766.51 - 2 839.76). The mean height was 48.60 cm (95%CI: 48.38 - 48.79). The mean age was 16.24 days (95%CI: 15.47 - 17.01). The mean maternal age was 27.37 years (95%CI: 26.76 - 27.98). There was a family history of hearing loss in 9.48% of the cases (n=90), and a family history of genetic diseases in 100 cases (10.56%). There were 14 cases of TORCH infections (1.45%), 375 admissions to the NICU (39.06%), 160 cases of neonatal jaundice (20.1%), and 79 cases of postpartum infections (8.21%). One live newborn presented with microtia. Conclusions The prevalence of congenital sensorineural hearing loss was 0.31% in both ears, and 0.11% in one ear. Currently, Colombia lacks a public universal newborn hearing screening program, and its future implementation faces great challenges. RESUMEN Objetivos Este estudio busca determinar la prevalencia de la hipoacusia neurosensorial congénita no sindrómica en el Hospital Universitario San Ignacio de Bogotá, Colombia, y describir sus factores de riesgo. Materiales y Métodos Estudio observacional, transversal y prospectivo con análisis bivariado. Todos los nacidos vivos entre junio de 2013 y junio de 2014 fueron tamizados con Emisiones Otoacusticas. Los casos negativos fueron confirmados con Potenciales Evocados Auditivos de Tronco Cerebral. Resultados Un total de 962 neonatos fueron tamizados de forma bilateral con Emisiones Otoacústicas: 401 de sexo masculino (46,36%) y 464 de sexo femenino (53,64%). El peso promedio fue de 2 798,10 g (IC95%: 2 766,51 - 2 839,76). La talla promedio fue de 48.60 cm (IC95%: 48,38 - 48,79). La edad promedio fue de 16,24 días (IC95%: 15,47 -17,01). La edad materna promedio fue de 27,37 años (IC95%: 26,76 - 27,98). Se encontró historia familiar de hipoacusia en 9.48% de los casos (n=90) e historia familiar de enfermedades genéticas en 100 casos (10,56%). Hubo 14 casos de infecciones por TORCH (1,45%), 375 admisiones a la UCI Neonatal (39,06%), 160 casos de ictericia neonatal (20,1%) y 79 casos de infecciones postnatales (8,21%). Un nacido vivo presentó microtia. Conclusiones Se encontró una prevalencia de hipoacusia neurosensorial congénita del 0,31% en ambos oídos y de 0,11% en un oído. Actualmente Colombia carece de un programa nacional de tamización de hipoacusia neonatal, y su futura implementación conlleva grandes retos.

A new series of blood-brain barrier permeable molecules designed to mimic the activity of Pleiotrophin in the CNS has been designed and synthesized. These compounds exert their action by interacting with the intracellular domain PD1 of the Protein Tyrosine-Phosphatase Receptor Z1 (PTPRZ1), and inhibiting its tyrosine phosphatase activity. The most potent compounds 10a and 12b (IC50 = 0,1 mu M) significantly increase the phosphorylation of key tyrosine residues of PTPRZ1 substrates involved in neuronal survival and differentiation, and display protective effects against amphetamine-induced toxicity. Docking and molecular dynamics experiments have been used to analyze the binding mode and to explain the observed selectivity against PTP1B. An In vivo experiment has demonstrated that 10a can cross the BBB, thus promoting the possibility of moving forward these candidates for the development of drugs for the treatment of CNS disorders, such as drug addiction and neurodegenerative diseases. (C) 2017 Elsevier Masson SAS. All rights reserved.

W. H. Schikhof (1937–2014) is considered one of the founders of p-Adic Analysis and devoted his mathematical life to expand the frontiers of this area of knowledge. At the same time, he was a loyal friend and colleague, a concerned teacher and an affectionate family man. Many of us are thankful for the privilege of having been his friends and sharing his ideas. In this article we will shortly state some biographical facts. Then we will point out and discuss different areas in which his research was crucial. At the end we present a complete list of his books and published articles.

Regional extension which initiates and promotes the rise of salt diapirs can also make diapirs fall once the supply of salt from its source is restricted. New observations on the 3D seismic data from a salt diapir in the Sorvestsnaget Basin suggest that salt moves until the end of the Eocene and is subtle to minor readjustments afterwards, revealing a more complex kinematics that previously described. Observations such as salt horns and sags and an antithetic fault linked to the western flank of the diapir suggest that salt syn-kinematics during Middle-Late Eocene included passive rising of the salt, followed by a fall. The salt horns are remnants of a taller salt diapir that, together with the indentation of the Middle-Late Eocene syn-kinematic sediment overburden above the salt, indicate diapiric fall due to restriction of salt supply by extension. Post-kinematic readjustments did not include diapiric reactivation by tectonic compression as previously thought, but minor salt rise by shortening due to gravity gliding after the tilting of the margin during Plio-Pleistocene glacial sediment loading and differential compaction of surrounding sediments. The salt diapir appears to be presently inactive and salt supply may have been restricted from its source already since Late Eocene.

The formation of mud volcanoes in the Gulf of Cadiz is closely linked to diapirism in the deep subsurface. The Mercator mud volcano (MMV) is a rare example where diapiric emplacement, in addition to being key for upward fluid migration, is also an important zone for fluid and mineral diagenesis. The most intriguing findings in the near-surface muds of the MMV are extremely high salinities of up to 5.2 M of NaCl from diapiric and evaporitic halite dissolution and the occurrence of authigenic gypsum and anhydrite crystals, both of which have not been observed to date in the Gulf of Cadiz. Employing a thermodynamic model we elucidate how the interplay of temperature pulses, strong salinity gradients, and fluid flow dynamically drive mineral dissolution and re-formation. The strong increase in salinity in the pore fluids has important implications for thermodynamic equilibria by significantly lowering the activity of water, thereby raising the gypsum–anhydrite transition zone from >1 km to about 400 m sediment depth at the MMV. This transition is further shifted to immediately below the seafloor during intervals of active mud and fluid expulsion when the MV surface temperature is heated up to at least 30 °C. As a consequence, precipitation of authigenic gypsum near the sediment surface (1–2 mbsf) has been linked to the dissolution of evaporites below the MMV. More precisely, the mechanisms generating supersaturation in the ascending gypsum-saturated MMV fluids are (1) the slow and constant cooling of these fluids along the geothermal gradient during their ascent leading to formation of ubiquitous micro-crystals and (2) the more rapid cooling after a heat pulse or transport from greater and warmer depth during an active mud volcano phase leading to the precipitation of cm-scale gypsum crystals or even fist-size concretions. The MMV fluids approaching the salt diapir from farther below have experienced a genesis similar to those of other mud volcanoes in the Gulf of Cadiz located above deep-rooted faults. These processes include clay mineral dewatering, thermogenic degradation of organic matter and deep high-temperature leaching of terrigenous sediments or continental crust.

The study carried out in this paper about some new examples of Banach spaces, consisting of certain valued fields extensions, is a typical non-archimedean feature. We determine whether these extensions are of countable type, have t-orthogonal bases, or are reflexive. As an application we construct, for a class of base fields, a norm ║ · ║ on c0, equivalent to the canonical supremum norm, without non-zero vectors that are ║ · ║-orthogonal and such that there is a multiplication on c0 making (c0, ║ · ║) into a valued field.

Some non-archimedean bounded approximation properties are introduced and studied in this paper. As an application, an affirmative answer is given, for non-spherically complete base fields, to the following problem, posed in 13, p. 95: Does there exist an absolutely convex edged set B in a non-archimedean locally convex space such that its closure is not edged?

Studying the morphology and subsurface geometry of mud volcanoes provides insights into their activity. This paper describes the internal structure of the Hakon Mosby mud volcano (HMMV) in the southwestern Barents Sea and presents a conceptual model of its evolution. The lack of a mud edifice and the profuse gas flares suggest that in the recent past the mud volcano evolution was predominantly controlled by venting of gas-rich fluids and free gas. However, the analysis of high-resolution single-channel seismic (SCS) data reveals for the first time the existence of a pseudo-mud chamber at the top of the 3 km deep central conduit. It was once created at the seabed and is now a buried expression that acts as mud chamber. The pseudo-mud chamber is situated approximately 300 m below the seafloor, directly above the 330 ka Bear Island Slide (BIS) scar reflection and below glacigenic debris flow deposits that constitute the sediment on top. The sediment profiler data indicates a younger mud deposit above the debris flows, which points to a reactivation of the mud volcano. The reactivation was most likely triggered by the contrast in density between the gas-rich mud chamber and the high-density debris flow deposits. Three stages, i.e. initiation, sealing and reactivation, and a second active period define the evolution of this young mud volcano. Both, the morphology and size of the conduit as well as in-situ temperature gradients point towards a focused and rapid fluid flow.

A non-regular inductive sequence of non-archimedean reflexive Frechet spaces is constructed. On the other hand, it is proved that every inductive sequence of reflexive Banach spaces over a spherically complete field is regular. Also, some applications are given.

The main goal of this paper is to prove that Fredholm and semi-Fredholm operators between p -adic (or non-archimedean) Banach spaces, as well as the index of those that are Fredholm, are preserved when they are perturbed by a small operator. In this way we obtain the non-archimedean counterparts of some well-known results of classical Operator Theory. For non-spherically complete fields the classical techniques are no longer valid in the p -adic context, which forces us to seek a completely different way to attack the problem. The p -adic concept of orthogonality will be one of the key tools to get our purpose.

The problem of the existence of (orthogonal) bases and basic sequences in non-archimedean locally convex spaces is studied. To this end we derive a characterization of compactoidity in terms of orthogonal sequences (Theorem 2.2).

In this paper it is proved that the index of a Fredholm operator between $p$-adic Banach spaces is preserved under compact perturbations. A case of special interest is provided when the ground field is nonspherically complete. In this case the classical techniques are no longer valid and the relation between the kernels of a Fredholm operator and that of a small compact perturbation turn out to be in general much richer than in the complex context.

For a Kothe sequence space, the classes of Λ0-nuclear spaces and spaces with the Λ0-property are introduced and studied and the relation between them is investigated. Also, we show that, for Λ0≠c0, these classes of spaces are in general different from the corresponding ones for Λ0=c0, which have been extensively studied in the non-archimedean literature (see, for example, [1]–[6]).

Convection in system with small aspect ratio is discussed when thermo-capillarity and gravity effects are present. Recent experiments in small containers show many interesting features that can be interpreted in terms of bifurcations with symmetry. In the present paper we report experimental and theoretical results in square and cylindrical vessel. Particular attention is payed to the characterization of the flow in square containers and to the possibility of rotating waves in a cylindrical container.

For finite-dimensional subspaces of ℓ∞ over a non-archimedean valued base field K we study orthocomplementation as related to the Hahn-Banach property and strictness. As a corollary we obtain that, if K is not spherically complete, a closed hyperplane in c0 having the Hahn-Banach property is orthocomplemented (Theorem 2.1, Remark 2).

By forming tensor products we construct natural examples of non-reflexive (Section 2) and nonspherically complete (Section 3) closed subspaces of the non-archimedean space l ∞ . Also, we study (Section 4) conditions under which two spherically complete Banach spaces are isomorphic; as an application we describe the spherical completion of the subspaces of l ∞ constructed in the paper.

In this paper we give a characterization of p-adic semi-Montel spaces which allows us to describe the finest polar semi-Montel topology coarser than the original topology of a locally convex space. As an application we derive that every polar semi-Montel space is a polar inductive limit of a family of nuclear spaces. We also pay attention to the connection with compactifying operators.

During measurement of the refractivity of a pulsed plasma, we have detected, with the help of a Jaminlike interferometer, the optical path variation caused by lamp windows. We attribute this variation to two causes: mechanical vibration and the slow cooling that follows the sharp heating. We conclude that neither has any influence on the measurement of plasma refractivity.

Non-Archimedean functional analysis, where alternative but equally valid number systems such as p-adic numbers are fundamental, is a fast-growing discipline widely used not just within pure mathematics, but also applied in other sciences, including physics, biology and chemistry. This book is the first to provide a comprehensive treatment of non-Archimedean locally convex spaces. The authors provide a clear exposition of the basic theory, together with complete proofs and new results from the latest research. A guide to the many illustrative examples provided, end-of-chapter notes and glossary of terms all make this book easily accessible to beginners at the graduate level, as well as specialists from a variety of disciplines.