Analysis of the Differential Efficacy of the Reduced Version Over the Extended Version of an Affective-Sexual Education Program for Adults with Intellectual Disabilities.

Recently, with the increase in demand, multiple intervention proposals aimed at improving the sexual health of people with intellectual disabilities have emerged. Among them is the SALUDIVERSEX program, which takes a positive approach to sexuality. It has an extended version, consisting of 16 sessions and whose efficacy has already been proven, and a reduced version of 10 sessions. Thus, the present study aimed to test the differential efficacy of the two versions. A total of 208 participants (103 women and 105 men) aged between 19 and 67 years (M = 37.23, SD = 10.66) completed a battery of instruments before and after the intervention. Statistical analyses showed that users who participated in the reduced version of the program presented a significantly higher rate of improvement in their sexual behaviors compared to those who participated in the extended version (Sexual response: ß10 = - 0.46 ± 0.19, p = .034; Sex practices: ß10 = - 0.52 ± 0.23, p = .037; Use condoms: ß10 = - 1.56 ± 0.59, p = .017), as well as a significantly higher decrease in the risk of suffering sexual abuse (ß10 = 3.95 ± 0.64, p < .001). However, no statistically significant differences in sexuality knowledge were obtained with respect to the improvement between the two versions (ß10 = - 0.09 ± 1.21, p = .94). Meanwhile, the professionals who applied the program found that those who participated in the reduced version, although they presented a significantly greater increase in their knowledge about privacy (ß10 = - 0.48 ± 0.08, p < .001), did not improve their concerns about their inappropriate sexual behaviors as much as the users of the extended version (ß10 = - 1.35 ± 0.21, p < .001). Thus, although both versions were effective, the reduced version seems to do so to a greater extent and in a shorter time, which makes it the more recommendable option.

People with intellectual disabilities' sexuality from three different perspectives: Parents, professionals, and themselves.

BACKGROUND: A positive conception of sexuality among people with intellectual disabilities is crucial and relies on several social and interpersonal contexts. The goal of this study is to analyse the interaction and impact of three different contextual groups: individuals with intellectual disabilities, their parents, and professionals working with them. METHODS: Survey data were collected from 330 people with intellectual disabilities attending occupational centres in eastern Spain, 330 parents, and 100 professionals. RESULTS: Correlation and variance analyses of dyad-level data show significant differences among the three groups in all variables. Professionals perceived people with intellectual disabilities to have higher knowledge of socio-sexual norms than people with intellectual disabilities actually appear to be, but they are also more concerned about aspects related to this area of people with intellectual disabilities. Compared to people with intellectual disabilities and professionals, parents perceived people with intellectual disabilities to have lower sexual knowledge. CONCLUSIONS: Our study demonstrates inconsistent perceived knowledge of people with intellectual disabilities' socio-sexual norms and sexual knowledge among the three groups, leading to disparate levels of concern regarding people with intellectual disabilities sexuality. Thus, the need to collect information from different perspectives for more accurate reporting and the critical need for sex education programs that involve the target population, but also parents and professionals who frequently interact with people with intellectual disabilities are highlighted.

SALUDIVERSEX: A quality of life and sexual health intervention for adults with mild intellectual disabilities.

Individuals with intellectual disabilities need an affective and sexual education adapted to their characteristics. There are few interventions that meet these objectives and offer empirical evidence of their efficacy. To respond to the limitations of existing interventions, an evidence-based affective-sexual educational intervention for adults with a mild degree of intellectual disability is proposed: SALUDIVERSEX. Participants will be randomly assigned to an intervention group that will receive the SALUDIVERSEX program or to a waiting list group. The intervention will be implemented by educators of occupational centers after a thorough training phase. Our main hypothesis is that the SALUDIVERSEX program will improve the sexual health and quality of life, through the joint action built into three components: the acquisition of basic information, the development of skills and strategies and the achievement of healthy attitudes towards the experience and expression of sexuality. The results of this approach could have important implications for optimizing the quality of life and self-determination of individuals with Intellectual disability by contributing to the development of healthy sexuality.

Sexual life of Spanish women during the lockdown by COVID-19: Differences according to sexual orientation?

The COVID-19 pandemic may have exacerbated the sexual health differences that already existed among women based on their sexual orientation. Therefore, a total of 971 Spanish women aged 18-60 years (84 % heterosexual and 16 % with a minority sexual orientation) answered an ad hoc online questionnaire about sexual behavior during April 2020. Compared to heterosexual women, sexual minority women showed a greater increase in sexual frequency, masturbated more, had more sex with a housemate, and engaged in more online sexual activities during lockdown. The emotional impact of the pandemic, having privacy, and age showed a relationship with the quality of sexual life, but not sexual orientation. Based on these results, women's sexual lives are not as closely related to their sexual orientation as they are to other variables. Therefore, it seems more necessary to address issues affecting women in general during lockdown than to focus on their specific sexual orientation.

Genetic and phenotypic characterisation of HIV-associated aggressive B-cell non-Hodgkin lymphomas, which do not occur specifically in this population: diagnostic and prognostic implications.

The frequency of aggressive subtypes of B-cell non-Hodgkin lymphoma (B-NHL), such as high-grade B-cell lymphomas (HGBL) with MYC and BCL2 and/or BCL6 rearrangement (HGBL-DH/TH) or Burkitt-like lymphoma (BL) with 11q aberration, is not well known in the HIV setting. We aimed to characterise HIV-associated aggressive B-NHL according to the 2017 WHO criteria, and to identify genotypic and phenotypic features with prognostic impact. Seventy-five HIV-associated aggressive B-NHL were studied by immunohistochemistry (CD10, BCL2, BCL6, MUM1, MYC, and CD30), EBV-encoded RNAs (EBERs), and fluorescence in situ hybridisation (FISH) to evaluate the status of the MYC, BCL2, and BCL6 genes and chromosome 11q. The 2017 WHO classification criteria and the Hans algorithm, for the cell-of-origin classification of diffuse large B-cell lymphomas (DLBCL), were applied. In DLBCL cases, the frequencies of MYC and BCL6 rearrangements (14.9 and 27.7%, respectively) were similar to those described in HIV-negative patients, but BCL2 rearrangements were infrequent (4.3%). MYC expression was identified in 23.4% of DLBCL cases, and coexpression of MYC and BCL2 in 13.0%, which was associated with a worse prognosis. As for BL cases, the expression of MUM1 (30.4%) conferred a worse prognosis. Finally, the prevalence of HGBL-DH/TH and BL-like with 11q aberration are reported in the HIV setting. The phenotypic and genotypic characteristics of HIV-associated aggressive B-NHL are similar to those of the general population, except for the low frequency of BCL2 rearrangements in DLBCL. MYC and BCL2 coexpression in DLBCL, and MUM-1 expression in BL, have a negative prognostic impact on HIV-infected individuals.

Development and psychometric properties of an instrument for the Assessment of Sexual Behaviour and Knowledge of people with Intellectual Disability.

BACKGROUND: This paper presents psychometric properties of an instrument for the Assessment of Sexual Behaviour and Knowledge of people with Intellectual Disability (ASBKID), other-reported by professionals who are in daily contact with them. METHODS AND PROCEDURES: Assessments of 236 individuals with intellectual disability were obtained from 100 professionals. RESULTS: Confirmatory factor analysis revealed a four-factor structure: concern about the user's inappropriate or uninhibited sexual behaviour; perception of the user's knowledge about privacy and social norms; perception of the user's knowledge about sexuality; and concerns about the user's sexuality. A multi-group CFA was also conducted in men and women, confirming the adequacy of this four-factor structure by gender. The reliability of the factors ranged from 0.74 to 0.92. CONCLUSIONS: The psychometric results obtained support the use of the ASBKID as a valid and reliable measure for the assessment of sexual behaviour and knowledge in both men and women with intellectual disability.

Development and psychometric properties of a self-report instrument for the assessment of sexual behaviour and concerns of people with mild intellectual disabilities (SEBECOMID-S).

BACKGROUND: This paper presents a description of the development and psychometric properties of a self-report instrument for the assessment of sexual behaviour and concerns of people with mild intellectual disabilities (SEBECOMID-S). METHODS AND PROCEDURES: The study included 281 people with mild intellectual disabilities. The psychometric properties were examined through exploratory factorial analysis, descriptive statistics, and reliability indices. RESULTS: The exploratory factor analyses offered a structure with three factors: concern about the appropriateness of their sexual behaviour, sexual practices performed, and safe sex practices. The model presents an excellent fit (χ2 /df = 1.10, RMSEA = 0.019, CFI = 0.997, TLI = 0.995, and SRMR = 0.065). General test reliability was good (α = 0.77, Ω = 0.76). CONCLUSIONS: SEBECOMID-S is a valid and reliable tool to obtain objective information about the sexual behaviour and concerns of people with mild intellectual disabilities. The use of this instrument will make it possible to adjust their training to their real experiences, making it more effective.

Estimating sexual knowledge of people with mild intellectual disability through a valid and reliable assessment scale: The ISK-ID.

BACKGROUND: Despite the relevance of assessing sexual knowledge in people with Intellectual Disability, there is a lack of appropriate assessment tools to measure this domain. The current study tests the psychometric properties of the new 'Inventory of Sexual Knowledge of people with Intellectual Disability' (ISK-ID). METHOD: 345 individuals with mild intellectual disability completed the ISK-ID before and after the implementation of a sexual education program. Psychometric properties of the ISK-ID were analysed according to Multidimensional Item Response Theory (MIRT). RESULTS: Its underlying factorial structure, along with parameters derived from the MIRT (item discrimination, difficulty, and participant's ability), support the use of the ISK-ID as a measure of sexual knowledge. Moreover, the ISK-ID was able to detect changes in the level of sexual knowledge resulting from educational interventions (i.e., responsiveness). CONCLUSIONS: The ISK-ID is an appropriate assessment tool to measure sexual knowledge in men and women with mild intellectual disability.

A phase 3 trial of azacitidine versus a semi-intensive fludarabine and cytarabine schedule in older patients with untreated acute myeloid leukemia.

BACKGROUND: Options to treat elderly patients (≥65 years old) newly diagnosed with acute myeloid leukemia (AML) include intensive and attenuated chemotherapy, hypomethylating agents with or without venetoclax, and supportive care. This multicenter, randomized, open-label, phase 3 trial was designed to assess the efficacy and safety of a fludarabine, cytarabine, and filgrastim (FLUGA) regimen in comparison with azacitidine (AZA). METHODS: Patients (n = 283) were randomized 1:1 to FLUGA (n = 141) or AZA (n = 142). Response was evaluated after cycles 1, 3, 6, and 9. Measurable residual disease (MRD) was assessed after cycle 9. When MRD was ≥0.01%, patients continued with the treatment until relapse or progressive disease. Patients with MRD < 0.01% suspended treatment to enter the follow-up phase. RESULTS: The complete remission (CR) rate after 3 cycles was significantly better in the FLUGA arm (18% vs 9%; P = .04), but the CR/CR with incomplete recovery rate at 9 months was similar (33% vs 29%; P = .41). There were no significant differences between arms in early mortality at 30 or 60 days. Hematologic toxicities were more frequent with FLUGA, especially during induction. The 1-year overall survival (OS) rate and the median OS were superior with AZA versus FLUGA: 47% versus 27% and 9.8 months (95% confidence interval [CI], 5.6-14 months) versus 4.1 months (95% CI, 2.7-5.5 months; P = .005), respectively. The median event-free survival was 4.9 months (95% CI, 2.8-7 months) with AZA and 3 months (95% CI, 2.5-3.5 months) with FLUGA (P = .001). CONCLUSIONS: FLUGA achieved more remissions after 3 cycles, but the 1-year OS rate was superior with AZA. However, long-term outcomes were disappointing in both arms (3-year OS rate, 10% vs 5%). This study supports the use of an AZA backbone for future combinations in elderly patients with AML.

Factors Associated with Condom Use in Anal Intercourse Among Spanish Men Who Have Sex with Men: Proposal for an Explanatory Model.

Men who have sex with men (MSM) account for more than half of the new HIV diagnoses in Spain. This study aims to carry out a descriptive analysis of the sexual practices and frequency of condom use of MSM and identify the variables that explain inconsistent condom use during anal intercourse. The sample consists of 405 men between 18 and 60 years of age (M = 28.94; SD = 9.35). The results indicate that the percentage of consistent condom use is 72.9% for anal intercourse. Lack of risk perception, high self-esteem, and greater sensation-seeking are risk factors for risky sexual behavior. In contrast, high levels of sexual assertiveness and self-efficacy are protective factors. The proposed model explains between 33.8 and 49.2% of the variance. These findings highlight the importance of designing and implementing condom promotion programs for MSM who engage in anal intercourse with specific sections that consider the acquisition of assertive skills and reduce the risks associated with a perceived invulnerability to HIV.

RESUMEN: Los hombres que tienen sexo con hombres (HSH) constituyen más de la mitad de los nuevos diagnósticos por VIH en España. El objetivo de este estudio es realizar un análisis descriptivo de las prácticas sexuales y la frecuencia de uso del preservativo en HSH e identificar las variables explicativas del uso inconsistente del preservativo en el coito anal. La muestra está formada por 405 hombres con edades comprendidas entre 18 y 60 años (M = 28.94; DT = 9.35). Los resultados indican que el porcentaje de uso sistemático del preservativo es del 72.9% en el coito anal. La ausencia de percepción de riesgo, un elevado nivel de autoestima y una mayor búsqueda de sensaciones sexuales constituyen factores de riesgo para la conducta sexual de riesgo. Por el contrario, altos niveles de asertividad sexual y de autoeficacia son factores de protección. El modelo propuesto explica entre el 33.8% y el 49.2% de la varianza. Estos hallazgos determinan la importancia de diseñar e implementar programas de promoción del uso del preservativo para HSH que practican coito anal con secciones específicas que consideren la adquisición de habilidades asertivas y reduzcan los riesgos asociados a la sensación de invulnerabilidad frente al VIH.

Immunological Synapse Formation Induces Mitochondrial Clustering and Mitophagy in Dendritic Cells.

The immunological synapse (IS) is a superstructure formed during T cell activation at the zone of contact between T cells and dendritic cells (DCs). The IS includes specific molecular components in the T cell and DCs sides that may result in different functionality. Most of the studies on the IS have focused on the T cell side of this structure and, in contrast, the information available on the IS of DCs is sparse. Autophagy is a cellular process involved in the clearance of damaged proteins and organelles via lysosomal degradation. Mitophagy is the selective autophagy of damaged mitochondria. In this study, it is shown that IS formation induces clustering of mitochondria in the IS of DCs and partial depolarization of these organelles. At the IS of the DCs also accumulate autophagy and mitophagy markers, even when the kinase complex mTORC1, an inhibitor of the autophagy, is active. Together the results presented indicate that IS formation induces local clustering of mitochondria and mitophagy, which could be a homeostatic mechanism to control the quality of mitochondria in this region. The data underline the complexity of the regulatory mechanisms operating in the IS of DCs.

Cardiac dysfunction and remodeling regulated by anti-angiogenic environment in patients with preeclampsia: the ANGIOCOR prospective cohort study protocol.

BACKGROUND: Cardiovascular diseases (CVD) are cause of increased morbidity and mortality in spite of advances for diagnosis and treatment. Changes during pregnancy affect importantly the maternal CV system. Pregnant women that develop preeclampsia (PE) have higher risk (up to 4 times) of clinical CVD in the short- and long-term. Predominance of an anti-angiogenic environment during pregnancy is known as main cause of PE, but its relationship with CV complications is still under research. We hypothesize that angiogenic factors are associated to maternal cardiac dysfunction/remodeling and that these may be detected by new cardiac biomarkers and maternal echocardiography. METHODS: Prospective cohort study of pregnant women with high-risk of PE in first trimester screening, established diagnosis of PE during gestation, and healthy pregnant women (total intended sample size n = 440). Placental biochemical and biophysical cardiovascular markers will be assessed in the first and third trimesters of pregnancy, along with maternal echocardiographic parameters. Fetal cardiac function at third trimester of pregnancy will be also evaluated and correlated with maternal variables. Maternal cardiac function assessment will be determined 12 months after delivery, and correlation with CV and PE risk variables obtained during pregnancy will be evaluated. DISCUSSION: The study will contribute to characterize the relationship between anti-angiogenic environment and maternal CV dysfunction/remodeling, during and after pregnancy, as well as its impact on future CVD risk in patients with PE. The ultimate goal is to improve CV health of women with high-risk or previous PE, and thus, reduce the burden of the disease. TRIAL REGISTRATION: NCT04162236.

New prognosis score including absolute lymphocyte/monocyte ratio, red blood cell distribution width and beta-2 microglobulin in patients with diffuse large B-cell lymphoma treated with R-CHOP: Spanish Lymphoma Group Experience (GELTAMO).

The International Prognostic Index (IPI) is the most widely used score for non-Hodgkin lymphoma but lacks the ability to identify a high-risk population in diffuse large B-cell lymphoma (DLBCL). Low absolute lymphocyte count and high monocytes have proved to be unfavourable factors. Red-cell distribution width (RDW) has been associated with inflammation and beta-2 microglobulin (B2M) with tumour load. The retrospective study included 992 patients with DLBCL treated with R-CHOP. In the multivariate analysis, age, Eastern Cooperative Oncology Group performance status (ECOG-PS), stage, bulky mass, B2M, RDW, and lymphocyte/monocyte ratio (LMR) were independently related to progression-free survival (PFS). A new prognosis score was generated with these variables including age categorized into three groups (0, 1, 2 points); ECOG ≥ 3-4 with two; stage III/IV, bulky mass, high B2M, LMR < 2·25 and RDW > 0·96 with one each; for a maximum of 9. This score could improve the discrimination of a very high-risk subgroup with five-year PFS and overall survival (OS) of 19% and 24% versus 45% and 59% of R (revised)-IPI respectively. This score also showed greater predictive ability than IPI. A new score is presented including complete blood cell count variables and B2M, which are readily available in real-life practice without additional tests. Compared to R-IPI, it shows a more precise high-risk assessment and risk discrimination for both PFS and OS.

Beyond Chemoattraction: Multifunctionality of Chemokine Receptors in Leukocytes.

The word chemokine is a combination of the words chemotactic and cytokine, in other words cytokines that promote chemotaxis. Hence, the term chemokine receptor refers largely to the ability to regulate chemoattraction. However, these receptors can modulate additional leukocyte functions, as exemplified by the case of CCR7 which, apart from chemotaxis, regulates survival, migratory speed, endocytosis, differentiation and cytoarchitecture. We present evidence highlighting that multifunctionality is a common feature of chemokine receptors. Based on the activities that they regulate, we suggest that chemokine receptors can be classified into inflammatory (which control both inflammatory and homeostatic functions) and homeostatic families. The information accrued also suggests that the non-chemotactic functions controlled by chemokine receptors may contribute to optimizing leukocyte functioning under normal physiological conditions and during inflammation.

Evaluation of the MD Anderson tumor score for diffuse large B-cell lymphoma in the rituximab era.

OBJECTIVES: Diffuse large B-cell lymphoma (DLBCL) is an aggressive heterogeneous lymphoma with standard treatment. However, 30%-40% of patients still fail, so we should know which patients are candidates for alternative therapies. IPI is the main prognostic score but, in the rituximab era, it cannot identify a very high-risk (HR) subset. The MD Anderson Cancer Center reported a score in the prerituximab era exclusively considering tumor-related variables: Tumor Score (TS). We aim to validate TS in the rituximab era and to analyze its current potential role. METHODS: From GELTAMO DLBCL registry, we selected those patients homogeneously treated with R-CHOP (n = 1327). RESULTS: Five-years PFS and OS were 62% and 74%. All variables retained an independent prognostic role in the revised TS (R-TS), identifying four different risk groups, with 5-years PFS of 86%, 71%, 50%, and very HR (28%). With a further categorization of three variables of the original TS (Ann Arbor Stage, LDH and B2M), we generated a new index that allowed an improvement in HR assessment. CONCLUSIONS: (a) All variables of the original TS retain an independent prognostic role, and R-TS remains predictive in the rituximab era; (b) R-TS and additional categorization of LDH, B2M, and AA stage (enhanced TS) increased the ability to identify HR subsets.

Plasma Epstein-Barr Virus Load as an Early Biomarker and Prognostic Factor of Human Immunodeficiency Virus-related Lymphomas.

BACKGROUND: Epstein-Barr virus (EBV) has been implicated in lymphomagenesis and can be found infecting tumor cells and in plasma at lymphoma diagnosis, especially in human immunodeficiency virus (HIV)-infected patients. Our aim was to evaluate the usefulness of plasma EBV load as biomarker and prognostic factor in HIV-positive patients with lymphomas. METHODS: EBV loads were measured by polymerase chain reaction in plasma samples of 81 HIV-positive patients' lymphomas at different moments: within 1 year before lymphoma diagnosis, at diagnosis, and at complete response (CR). Control samples included HIV-negative patients with lymphomas and HIV-positive patients without neoplasia or opportunistic infections. RESULTS: HIV-positive patients with lymphomas had more frequently-detectable EBV load at lymphoma diagnosis (53%) than either HIV-negative patients with the same lymphoma type (16%; P < .001) or HIV-positive individuals without neoplasia or opportunistic infection (1.2%; P < .001). HIV-positive lymphoma patients with detectable EBV load in plasma at lymphoma diagnosis had statistically significant decrease of EBV load at CR. High EBV load (>5000 copies/mL) at lymphoma diagnosis was an independent negative prognostic factor for overall survival and progression-free survival in HIV-positive patients with lymphomas. Detectable plasma EBV loads identified HIV-positive subjects that would eventually develop lymphoma (area under the curve, 82%; 95% CI: 0.67-0.96). CONCLUSIONS: Plasma EBV load can be used as a biomarker and as a prognostic factor in HIV-positive patients with lymphomas. The presence of the EBV load in the plasma of an HIV-positive patient can be an early predictor of lymphoma development.

Incidence and outcome after first molecular versus overt recurrence in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia included in the ALL Ph08 trial from the Spanish PETHEMA Group.

BACKGROUND: Disease recurrence occurs in 20% to 40% of adults with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) who are treated with chemotherapy and tyrosine kinase inhibitors (TKIs). In the current study, the authors report the incidence, treatment, and outcome after first disease recurrence in young and older adults treated in the ALL Ph08 trial (ClinicalTrials.gov identifier NCT01491763). METHODS: Patients aged 18 to 55 years with de novo Ph+ ALL were treated with imatinib concurrently with standard-dose induction and consolidation therapy followed by allogeneic hematopoietic stem cell transplantation (allo-HSCT) when possible. In patients with first disease recurrence, the authors analyzed the type of recurrence, timing, location, presence of kinase domain mutations, type of treatment, and outcomes. RESULTS: Of the 125 patients, 28 patients (22%) developed disease recurrence before (4 patients) or after (24 patients) HSCT, with the recurrences being molecular in 11 patients (39%) and overt in 17 patients (61%). T315I was the most common mutation noted at the time of disease recurrence. Change in TKI was the most frequent treatment for patients with molecular disease recurrence whereas rescue chemotherapy and TKI change followed by second allo-HSCT when possible were performed for the most part in patients with overt disease recurrence. A total of 20 patients (71%) achieved response. The median disease-free survival (DFS) and overall survival (OS) were 8.5 months and 15.3 months, respectively. A trend for better DFS and OS was observed in patients with molecular recurrence compared with those with overt recurrence (median of 16.9 months vs 6.3 months [P = .05] and 28.7 months vs 11.5 months [P = .05] for DFS and OS, respectively). CONCLUSIONS: Disease recurrence was frequent in young and older adults with Ph+ ALL who were treated with imatinib and chemotherapy with HSCT. Although the majority of patients responded to rescue therapy, their outcomes were poor, especially with regard to overt disease recurrence.

Response duration and survival shorten after each relapse in patients with follicular lymphoma treated in the rituximab era.

Follicular lymphoma (FL) is an indolent disease characterized by long survival but frequent relapses. Before the introduction of rituximab, the clinical course of these patients showed a shorter response duration (RD) after each relapse. In this study, we analysed if this pattern of shortened responses remains in patients treated in the rituximab era. We selected 348 patients newly diagnosed with FL in two institutions between 2001 and 2014 that received chemoimmunotherapy. After a median follow-up of 6·3 years, 10-year progression-free and overall survivals were 53% and 72%, respectively. All patients received first-line, 111 second-line and 41 third-line treatments, with a 5-year RD of 62%, 39% and 24%, respectively (P < 0·0001). Variables predicting longer RD after first-line treatment were normal ß2microglobulin, complete remission achievement and maintenance with rituximab. Patients with longer RD after first-line showed significantly longer RD after second-line therapy. Autologous stem-cell transplantation after second-line therapy did not significantly impact RD. Median survival after first, second and third therapies was not reached, 7·6 and 4·8 years, respectively, whereas relative survival with respect to a sex- and age-matched Spanish population, the decrease in the life expectancy at 10 years was 17%, 45% and 79%, respectively. Thus, RD still shortens after each relapse in patients with FL treated in first line with rituximab combinations.

Efficacy and Safety of Sarilumab for the Treatment of Posterior Segment Noninfectious Uveitis (SARIL-NIU):: The Phase 2 SATURN Study.

PURPOSE: To assess efficacy and safety of sarilumab, a human anti-interleukin-6 receptor antibody, for treatment of posterior segment noninfectious uveitis (NIU). DESIGN: Randomized, double-masked, placebo-controlled, phase 2 study. PARTICIPANTS: Fifty-eight patients (eyes) with noninfectious intermediate, posterior, or panuveitis. METHODS: Eyes received treatment every 2 weeks for 16 weeks with subcutaneous sarilumab 200 mg or placebo. MAIN OUTCOME MEASURES: The primary end point was the proportion of patients with ≥2-step reduction in vitreous haze (VH) on the Miami scale or with a reduction of systemic corticosteroids (prednisolone or equivalent) to a dose of <10 mg/day at week 16. Primary end point was based on VH evaluation by a central reading center. Investigator evaluation of VH was a prespecified, planned secondary analysis. RESULTS: At week 16, proportion of patients taking sarilumab or placebo with ≥2-step reduction in VH or corticosteroid dose <10 mg/day was 46.1% vs. 30.0% (P = 0.2354) based on central reading center assessment of VH and 64.0% vs. 35.0% (P = 0.0372) based on investigator assessment of VH, respectively. In the subgroup of eyes with VH grade ≥2 at baseline, the mean VH reduction from baseline to week 16 was significantly greater with sarilumab vs. placebo regardless of assessment by the central reading center (-2.1 [n = 11] vs. -1.7 [n = 3], respectively; P = 0.0255) or investigator (-2.5 [n = 19] vs. -1.2 [n = 11], respectively; P = 0.0170). The mean best-corrected visual acuity gain from baseline to week 16 was greater with sarilumab vs. placebo in the overall population (8.9 vs. 3.6 letters, respectively; P = 0.0333) and in the subgroup of eyes with central subfield thickness (CST) ≥300 µm at baseline (12.2 [n = 13] vs. 2.1 [n = 7] letters, respectively; P = 0.0517). Corresponding changes in CST were -46.8 vs. +2.6 µm (P = 0.0683) in the overall population and -112.5 [n = 13] vs. -1.8 [n = 6] µm (P = 0.1317) in the subgroup of eyes with CST ≥300 µm at baseline, respectively. The most common ocular adverse events were worsening of uveitis (0 [placebo] and 3 [sarilumab] patients) and retinal infiltrates (1 [placebo] and 2 [sarilumab] patients). CONCLUSIONS: Subcutaneous sarilumab may provide clinical benefits in the management of NIU of the posterior segment, especially in eyes with uveitic macular edema.