Molnupiravir for Oral Treatment of Covid-19 in Nonhospitalized Patients.

BACKGROUND: New treatments are needed to reduce the risk of progression of coronavirus disease 2019 (Covid-19). Molnupiravir is an oral, small-molecule antiviral prodrug that is active against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: We conducted a phase 3, double-blind, randomized, placebo-controlled trial to evaluate the efficacy and safety of treatment with molnupiravir started within 5 days after the onset of signs or symptoms in nonhospitalized, unvaccinated adults with mild-to-moderate, laboratory-confirmed Covid-19 and at least one risk factor for severe Covid-19 illness. Participants in the trial were randomly assigned to receive 800 mg of molnupiravir or placebo twice daily for 5 days. The primary efficacy end point was the incidence hospitalization or death at day 29; the incidence of adverse events was the primary safety end point. A planned interim analysis was performed when 50% of 1550 participants (target enrollment) had been followed through day 29. RESULTS: A total of 1433 participants underwent randomization; 716 were assigned to receive molnupiravir and 717 to receive placebo. With the exception of an imbalance in sex, baseline characteristics were similar in the two groups. The superiority of molnupiravir was demonstrated at the interim analysis; the risk of hospitalization for any cause or death through day 29 was lower with molnupiravir (28 of 385 participants [7.3%]) than with placebo (53 of 377 [14.1%]) (difference, -6.8 percentage points; 95% confidence interval [CI], -11.3 to -2.4; P = 0.001). In the analysis of all participants who had undergone randomization, the percentage of participants who were hospitalized or died through day 29 was lower in the molnupiravir group than in the placebo group (6.8% [48 of 709] vs. 9.7% [68 of 699]; difference, -3.0 percentage points; 95% CI, -5.9 to -0.1). Results of subgroup analyses were largely consistent with these overall results; in some subgroups, such as patients with evidence of previous SARS-CoV-2 infection, those with low baseline viral load, and those with diabetes, the point estimate for the difference favored placebo. One death was reported in the molnupiravir group and 9 were reported in the placebo group through day 29. Adverse events were reported in 216 of 710 participants (30.4%) in the molnupiravir group and 231 of 701 (33.0%) in the placebo group. CONCLUSIONS: Early treatment with molnupiravir reduced the risk of hospitalization or death in at-risk, unvaccinated adults with Covid-19. (Funded by Merck Sharp and Dohme; MOVe-OUT ClinicalTrials.gov number, NCT04575597.).

Natalizumab-immunogenicity evaluation in patients with infusion related events or disease exacerbations.

Introduction: Natalizumab is a biologic drug for relapsing-remitting multiple sclerosis that may induce the generation of anti-drug antibodies in some patients. Anti-natalizumab antibodies (ANA) increase the risk of adverse events and reduce efficacy, being useful biomarkers for monitoring treatment response. Methods: Retrospective observational study including MS patients treated with natalizumab that experienced infusion-related events (IRE) or disease exacerbations (DE). ANA were tested by Elisa including a screening and a confirmation assay. Patients were further classified as transient (one positive result) or persistent (two or more positive results) ANA. Results: A total of 1251 MS patients were included and 153 (12.3%) had ANA with at least one single point determination, which were more frequent among patients with IRE compared to those with DE (21,6% vs.10.8%) during the first six infusions. Two or more determinations ANA were performed in 184 patients, being 31.5% permanently positive and 7.1% transiently positive. Interestingly, 26.1% of patients that experienced DE had persistent ANA, while 2.6% were transient. In contrast, 43% of patients with IRE had persistent ANA, and 9.3% had transient antibodies. Patients with persistent antibodies had more frequently high levels at the first sampling compared to patients with transient ANA. Conclusion: Real-world evidence shows that the presence of ANA is behind an important percentage of patients treated with natalizumab that experience IRE, as well as DE but in a lower degree. These findings support the need to systematically evaluate ANA towards a personalized management of these patients to avoid undesired complications.

Effect of agave fructans on xanthan rheology: Impact on sodium caseinate emulsion properties.

The influence of agave fructans (AF) (1-10%) and xanthan (from 0.03% to 0.25%) in combination with sodium caseinate (SC) at 1% on the rheological and physicochemical properties of aqueous phases and emulsions was evaluated. Steady-state flow behavior, particle size distribution, and stability studies were used to characterize the systems. The aqueous systems displayed the shear-thinning behavior characteristic of xanthan solutions; however, this behavior was modified by the presence of SC and AF due to interactions between AF-SC and AF-xanthan based on predominant hydrogen bonding because of the hydroxyl groups on AF. In emulsions, an increase in viscosity due to the effect of the AF concentration reflects a probable association of fructan aggregates on the surface of SC particles that reinforce the interfacial layer of SC, while xanthan contributes to an increase in the viscosity of the continuous phase, which effectively prevents coalescence and floc formation even at higher concentrations, despite the possible existence of a depletion flocculation effect attenuated by the interaction between AF-SC and AF-xanthan. PRACTICAL APPLICATION: These results can be of use, in an important way, in the design of stable functional emulsions in which there is an application for agave fructans recognized as dietary fiber, also considering their peculiar way of interacting with xanthan favoring its stabilizing functionality.

Soluble Receptor Isoform of IFN-Beta (sIFNAR2) in Multiple Sclerosis Patients and Their Association With the Clinical Response to IFN-Beta Treatment.

Purpose: Interferon beta receptor 2 subunit (IFNAR2) can be produced as a transmembrane protein, but also as a soluble form (sIFNAR2) generated by alternative splicing or proteolytic cleavage, which has both agonist and antagonist activities for IFN-ß. However, its role regarding the clinical response to IFN-ß for relapsing-remitting multiple sclerosis (RRMS) is unknown. We aim to evaluate the in vitro short-term effects and after 6 and 12 months of IFN-ß therapy on sIFNAR2 production and their association with the clinical response in MS patients. Methods: Ninety-four RRMS patients were included and evaluated at baseline, 6 and 12 months from treatment onset. A subset of 41 patients were classified as responders and non-responders to IFN-ß therapy. sIFNAR2 serum levels were measured by ELISA. mRNA expression for IFNAR1, IFNAR2 splice variants, MxA and proteases were assessed by RT-PCR. The short-term effect was evaluated in PBMC from RRMS patients after IFN-ß stimulation in vitro. Results: Protein and mRNA levels of sIFNAR2 increased after IFN-ß treatment. According to the clinical response, only non-responders increased sIFNAR2 significantly at both protein and mRNA levels. sIFNAR2 gene expression correlated with the transmembrane isoform expression and was 2.3-fold higher. While MxA gene expression increased significantly after treatment, IFNAR1 and IFNAR2 only slightly increased. After short-term IFN-ß in vitro induction of PBMC, 6/7 patients increased the sIFNAR2 expression. Conclusions: IFN-ß administration induces the production of sIFNAR2 in RRMS and higher levels might be associated to the reduction of therapeutic response. Thus, levels of sIFNAR2 could be monitored to optimize an effective response to IFN-ß therapy.

Adipose-derived mesenchymal stem cells (AdMSC) for the treatment of secondary-progressive multiple sclerosis: A triple blinded, placebo controlled, randomized phase I/II safety and feasibility study.

BACKGROUND: Currently available treatments for secondary progressive multiple sclerosis(SPMS) have limited efficacy and/or safety concerns. Adipose-mesenchymal derived stem cells(AdMSCs) represent a promising option and can be readily obtained using minimally invasive procedures. PATIENTS AND METHODS: In this triple-blind, placebo-controlled study, cell samples were obtained from consenting patients by lipectomy and subsequently expanded. Patients were randomized to a single infusion of placebo, low-dose(1x106cells/kg) or high-dose(4x106cells/kg) autologous AdMSC product and followed for 12 months. Safety was monitored recording adverse events, laboratory parameters, vital signs and spirometry. Expanded disability status score (EDSS), magnetic-resonance-imaging, and other measures of possible treatment effects were also recorded. RESULTS: Thirty-four patients underwent lipectomy for AdMSCs collection, were randomized and thirty were infused (11 placebo, 10 low-dose and 9 high-dose); 4 randomized patients were not infused because of karyotype abnormalities in the cell product. Only one serious adverse event was observed in the treatment arms (urinary infection, considered not related to study treatment). No other safety parameters showed changes. Measures of treatment effect showed an inconclusive trend of efficacy. CONCLUSION: Infusion of autologous AdMSCs is safe and feasible in patients with SPMS. Larger studies and probably treatment at earlier phases would be needed to investigate the potential therapeutic benefit of this technique.

Locally advanced cervix cancer: a study of 156 cases from a single institution / Cáncer de cérvix localmente avanzado: un estudio de 156 casos en un único hospital

Objective: The objective of our study was to identify prognostic factors, management strategies, and outcomes for locally advanced cervical cancer in our hospital. Material and methods: We performed a retrospective study of 156 patients with locally advanced cervical cancer (FIGO IB2-IVA). All patients underwent staging of the para-aortic lymph nodes by computed tomography. A total of 93 patients with para-aortic lymph nodes with no signs of malignancy in the imaging tests underwent pretherapy surgical staging up to the level of the left renal vein. All patients were treated with chemoradiation. Results: The study included a total of 156 patients. The average age was 54.04 years (range 28-97 years). Squamous cell carcinoma was the most frequent histological type (82.1%). Most patients had FIGO stage IIB disease (43.6%). Histopathology revealed metastatic disease in the para-aortic lymph nodes in 19.3% of patients. The status of the para-aortic lymph nodes was the only factor that was independently associated with an increased risk of mortality (OR 33 [95% CI, 8-135.89], p<0.0001). Conclusions: Patients with an advanced tumor stage at the time of diagnosis and those with pathological para-aortic lymph nodes are at greater risk of developing distant metastases and of more frequent disease-related mortality. In this group of high-risk patients, a more marked therapeutic effort must be made in order to improve survival

Objetivo: El objetivo del estudio fue identificar los factores pronósticos, las estrategias de manejo y los resultados de los cánceres cervicales localmente avanzados tratados en nuestro hospital. Material y métodos: Estudio retrospectivo de 156 pacientes con cánceres cervicales localmente avanzados (FIGO IB2-IVA). A todas las pacientes se les realizó estadiaje de los ganglios linfáticos paraaórticos mediante Tomografía Axial Computarizada. 93 pacientes con ganglios linfáticos paraaórticos sin signos de malignidad en las pruebas de imagen fueron sometidas a estadiaje quirúrgico preterapéutico hasta el nivel de la vena renal izquierda. Todas las pacientes fueron tratadas con quimio-radioterapia. Resultados: El estudio incluyo un total de 156 pacientes. La edad media fue de 54,04 años (rango 28-97 años). El carcinoma de células escamosas fue el tipo histológico más frecuente (82,1%). La mayoría de las paciente tenían un estadio FIGO IIB (43,6%). El estudio anatomopatológico reveló enfermedad metastásica en ganglios paraórticos en un 19,3% de la pacientes. El estado de los ganglios para-aórticos fue el único factor que se asoció de manera independiente con el incremento del riesgo de mortalidad [OR 33 (IC 95% 8-135,89; p<0,0001]. Conclusiones: Las pacientes con un estadio tumoral avanzado en el momento del diagnóstico y aquellas con ganglios paraórticos patológicos tienen mayor riesgo de desarrollar metástasis a distancia y mayores tasas de mortalidad causadas por la enfermedad. En este grupo de pacientes de alto riesgo se debe realizar un esfuerzo terapéutico superior con el fin de mejorar la supervivencia de esta enfermedad

Representación social de la consulta estomatológica en jóvenes de un área de salud de Santiago de Cuba / Social representation of the stomatological services in young people from a health area in Santiago de Cuba

Se efectuó un estudio descriptivo de 80 jóvenes en las edades de 19 a 25 años, pertenecientes al Consultorio Médico de la Familia No. 11 del área de salud del Policlínico Docente "Ramón López Peña" de Santiago de Cuba, desde febrero hasta mayo del 2015, para lo cual se empleó una metodología mixta, con una estrategia de triangulación de datos en un sentido cuanticualitativo, a fin de determinar las representaciones sociales de estos jóvenes sobre la consulta estomatológica, luego de aplicar un cuestionario y una entrevista elaborados a tal efecto. Los principales resultados indicaron que la representación social de la consulta estomatológica en dicho grupo poblacional, estaba conformada por un núcleo figurativo que comprendió el reconocimiento de la importancia y necesidad del mencionado servicio, mayormente influenciado por los familiares de los encuestados, así como la existencia de estados emocionales como la tensión y el miedo. El campo representacional estuvo asociado a las molestias ocasionadas por los procedimientos estomatológicos, a la presencia de caries dental como motivo principal de visita a la consulta y a la demanda de asistencia en el Cuerpo de Guardia de Estomatología.

A descriptive study of 80 young people from 19 to 25 years, belonging to the doctor´s office Number 11 from "Ramón López Peña" Teaching Polyclinic health area in Santiago de Cuba was carried out from February to May, 2015, for which a mixed methodology was used, with a triangulation strategy of data in a quantitative-qualitative sense, in order to determine the social representations of these young people on the stomatological services, after applying a questionnaire and an interview elaborated for this aim. The main results indicated that the social representation of the stomatological services in this population group, was conformed by a figurative nucleus including the recognition of the importance and necessity of the aforementioned service, mostly influenced by the relatives of those interviewed, as well as the existence of emotional states as the tension and fear. The representative field was associated with the discomfort caused by the stomatological procedures, to the presence of tooth decay as main reason for visiting the department and to the demand of care in the Stomatology emergency room.

Finalización electiva versus manejo expectante en el control de la gestación prolongada: estudio prospectivo de 200 gestantes / Elective termination versus expectant management in prolonged pregnancy: a prospective study of 200 pregnant women

Objetivo. Comparar la finalización electiva de la gestación prolongada versus el manejo expectante, en gestaciones de bajo riesgo obstétrico. Material y método. Ensayo clínico controlado y aleatorizado entre actuaciones activas y expectantes, sobre una muestra de 200 mujeres con gestación prolongada de bajo riesgo obstétrico entre febrero de 2003 y junio de 2005 en el Hospital Universitario Materno-Infantil de Canarias. Resultados. El grupo estudio está formado por 200 pacientes - 102 del grupo activa y 98 del grupo expectante -. No se encontraron diferencias epidemiológicas entre ambos grupos. El parto no fue inducido en un porcentaje de gestantes significativamente superior en el grupo activa frente al grupo expectante (51% vs 35,7%, p=0,02; OR 0,53 [CI 95% 0,3-0,94]), es decir, el número de inducciones es significativamente superior en el grupo de manejo expectante. Una tasa significativamente menor de gestantes del grupo activa presentó líquido amniótico meconial durante la dilatación (15,7% vs 28,6% p=0,02; OR 0,47 [IC 95% 0,23-0,93]). No existen diferencias significativas con relación al tipo de parto, no obstante el porcentaje de intervención cesárea fue marcadamente inferior en el grupo activa frente al grupo expectante ([12,7% vs 18,4%, p=0,3; OR 0,65 [IC 95% 0.3-1.41]). Los resultados perinatales no muestran diferencias significativas entre ambos grupos. Conclusiones. La finalización electiva en el semana 42, en gestaciones de bajo riesgo obstétrico con condiciones cervicales desfavorables, parece reducir la tasa de cesáreas sin comprometer los resultados perinatales (AU)

Objective. To compare elective termination versus expectant management in low-risk prolonged pregnancy. Material and method. We performed a controlled randomized clinical trial comparing the results of active and expectant approaches in the management of low-risk prolonged pregnancy in a sample of 200 women between February 2003 and June 2005 at the Maternity Ward of the Canary Islands University Hospital. Results. The study group consisted of 200 patients. There were 102 in the active management group and 98 in the expectant management group. No between-group epidemiologic differences were found. Labor was not induced in a significantly higher proportion of patients in the active than in the expectant group [51% vs 35.7%, p=0.02; OR 0.53 (95% CI 0.3-0.94)] i.e. the induction rate was significantly higher in the expectant group. The proportion of patients with meconium-stained amniotic fluid during labor was significantly lower in the active management group [15.7% vs 28.6% p=0.02; OR 0.47 (95% CI 0.23-0.93)]. No significant differences were found in the type of delivery, although the proportion of cesarean sections was noticeably lower in the active management than in the expectant management group [(12.7% vs 18.4%, p=0.3; OR 0.65 (95% CI 0.3-1.41)]. No significant differences were found in perinatal outcomes between the two groups. Conclusions. Elective termination of low-risk pregnancies with unfavorable cervical findings at week 42 seems to reduce the rate of cesarean section without impairing perinatal outcome (AU)

Tumor mülleriano mixto maligno: la experiencia de un único centro con 43 casos de 1990-2006 / Mixed malignant Mullerian tumours: the experience of a single centre with 43 cases from 1990-2006

Objetivo: Se realiza un estudio descriptivo de las pacientes con diagnóstico de tumor mülleriano mixto maligno (TMMM) en términos de epidemiología, diagnóstico, tratamiento, seguimiento, recurrencias y supervivencia. Material y método: Se revisaron los archivos anatomo-patológicos y las historias médicas de las pacientes tratadas durante el período 1.990-2.006. Las supervivencias se analizan mediante las curvas de Kaplan-Meier. Se emplea un análisis de regresión logística en el estudio uni y multivariable.Resultados43 pacientes son incluidas en esta revisión. El tratamiento inicial fue quirúrgico en el 79% de los casos. El 34,9% de las pacientes se diagnosticaron en estadio I; 16,3% en estadio II; 34,9% en estadio III y 9,3% en estadio IV. Se alcanzó una respuesta completa en el 60,4%. La enfermedad persistió en el 39,6%. La supervivencia libre de enfermedad a los 2, 5 y 10 años fue del 50%, con una mediana de 15 meses (IC 95% 6-32). La tasa de recurrencia fue del 42,3% con un tiempo medio de 8,4 meses. La supervivencia total a los 2, 5 y 10 años fue del 26% con una mediana de 7 meses (IC 95% 1-44). En el análisis univariante el tamaño tumoral, la invasión linfovascular, el estadio y la radioterapia pélvica adyuvante son factores pronósticos. En el análisis multivariante la invasión linfovascular, el estadio y la radioterapia son factores pronósticos independientes. Conclusión: Los TMMM son tumores de comportamiento clínico extremadamente agresivo con un pronóstico pobre. Los factores pronósticos que afectan la supervivencia son el estadio, la invasión linfovascular y la radioterapia pélvica (AU)

Objective: Malignant mixed Müllerian tumours (MMMT) patients were retrospectively evaluated in terms of epidemiology, diagnosis, treatment, follow-up, recurrent disease and survival. Methods: Medical and histopathology records were reviewed during the 17-year period 1990-2006. Survival rates were analysed by means of the Kaplan-Meier technique. The Cox proportional hazards regression model was used in uni- and multivariate analysis. Results: A total of 43 patients were included in this study. First-line treatment was surgery in 79% of cases. Stage I, II, III and IV were identified in 34.9%, 16.3%, 34.9% and 9.3%, respectively. A complete response was achieved in 60.4% of patients. The disease was progressive in 39.6%. Event–free survival at 2, 5 and 10 years was 50% for all, with a median time of 15 months (95% CI,6-32). There was a 42.3% recurrence-rate with a mean time to recurrence of 8.4 months. The 2, 5 and 10-years overall survival was 26% with a median time of 7 months (95% CI, 1-44). In the univariate analysis tumour size, lymphovascular infiltration, stage and pelvic radiotherapy are prognostic factors. In the multivariate analysis lymphovascular infiltration, stage and radiotherapy were found to have an independent influence on overall survival. Conclusions: MMMT are tumours of aggressive clinical behaviour with a poor prognosis. Stage, lymphovascular infiltration and adjuvant radiotherapy are the dominant prognostic factors (AU)