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BackgroundThe Receptor Binding Domain (RBD) of the SARS-CoV-2 spike protein is the target for many COVID-19 vaccines. Here we report results for phase 1 clinical trial of two COVID-19 vaccine candidates based on recombinant dimeric RBD (d-RBD).MethodsWe performed a randomized, double-blind, phase I clinical trial in the National Centre of Toxicology in Havana. Sixty Cuban volunteers aged 19-59 years were randomized into three groups (20 subjects each): 1) FINLAY-FR-1 (50 mcg d-RBD plus outer membrane vesicles from N. meningitidis); 2) FINLAY-FR-1A-50 mcg d-RBD (three doses); 3) FINLAY-FR-1A-25 mcg d-RDB (three doses). The FINLAY-FR-1 group was randomly divided to receive a third dose of the same vaccine candidate (homologous schedule) or of FINLAY-FR-1A-50 (heterologous schedule). The primary outcomes were safety and reactogenicity. The secondary outcome was vaccine immunogenicity. Humoral response at baseline and following each vaccination was evaluated using live-virus neutralization test, anti-RBD IgG ELISA and in-vitro neutralization test of RBD:hACE2 interaction.ResultsMost adverse events were of mild intensity (63.5%), solicited (58.8%), and local (61.8%); 69.4% with causal association with vaccination. Serious adverse events were not found. The FINLAY-FR-1 group reported more adverse events than the other two groups. After the third dose, anti-RBD seroconversion was 100%, 94.4% and 90% for the FINLAY-FR-1, FINLAY-FR-1A-50 and FINLAY-FR-1A-25 respectively. The in-vitro inhibition of RBD:hACE2 interaction increased after the second dose in all formulations. The geometric mean neutralizing titres after the third dose rose significantly in the group vaccinated with FINLAY-FR-1 with respect to the other formulations and the COVID-19 Convalescent Serum Panel. No differences were found between FINLAY-FR-1 homologous or heterologous schedules.ConclusionsVaccine candidates were safe and immunogenic, and induced live-virus neutralizing antibodies against SARS-CoV-2. The highest values were obtained when outer membrane vesicles were used as adjuvant.Trial registryhttps://rpcec.sld.cu/en/trials/RPCEC00000338-En

Introduction Total pancreatectomy (TP) is an uncommon operation, with indications that have not been clearly defined and non-standardized postoperative results. We present a national multicentric study on TP and a comparison with the existing literature. Methods A prospective observational study using data from the national registry of patients after pancreaticoduodenectomy and TP performed for any indication during the study period: January 1–December 31, 2015. Results 1016 patients were included from 73 hospitals, 112 of whom had undergone TP. The percentage of TP from the total number of cases was 11%. The mean age was 63.5 years, and 57.2% were males. The most frequently suspected radiological diagnosis was pancreatic cancer (58/112 cases). The most common TP technique was “mesentery artery first” (43/112 cases). Venous resections were performed in 23 patients (20.5%). The percentage of postoperative complications within 90 days was 50%, but major complications (>IIIA) were only 20.7%. The overall 90-day mortality was 8% (9 patients). The average stay was 20.7 days. The 3 most frequent definitive histological diagnoses were: adenocarcinoma of the pancreas, intraductal papillary mucinous neoplasm and chronic pancreatitis. The R0 rate was 67.8%. Conclusions This study shows that the morbidity and mortality results of TP in Spain are similar or superior to previous publications. More precise TP studies are necessary, focused on specific complications such as endocrine insufficiency.

Resumen Introduccion La pancreatectomia total (PT) es una intervencion infrecuente, con unas indicaciones no claramente definidas y unos resultados postoperatorios no estandarizados. Presentamos un estudio multicentrico nacional sobre PT y una comparacion con la literatura existente. Metodos Estudio prospectivo observacional realizado mediante el registro nacional de pacientes operados de duodenopancreatectomia cefalica y PT realizadas por cualquier indicacion durante el periodo comprendido entre el 1 enero y el 31 diciembre del 2015. Resultados Se incluyo a 1.016 pacientes, pertenecientes a 73 centros; de ellos, 112 correspondian a PT. El porcentaje de PT/numero total de casos es del 11%. La edad media fue 63,5 anos y eran varones un 57,2%. El diagnostico radiologico de sospecha mas frecuente fue cancer de pancreas (58/112 casos). La tecnica de la PT mas habitual fue «arteria mesenterica primero» (43/112 casos). Se efectuaron resecciones venosas en 23 pacientes (20,5%). El porcentaje de complicaciones postoperatorias a 90 dias fue 50%, pero las complicaciones mayores (> IIIA) solo el 20,7%. La mortalidad global a 90 dias fue del 8% (9 pacientes). La estancia media fue 20,7 dias. Los 3 diagnosticos histologicos definitivos mas frecuentes fueron: adenocarcinoma de pancreas, neoplasia mucinosa papilar intraductal y pancreatitis cronica. La tasa de R0 fue del 67,8%. Conclusiones Este estudio demuestra que los resultados de morbimortalidad de la PT en Espana son similares o superiores a los publicados previamente. Es necesario un estudio mas especifico sobre PT centrado en complicaciones especificas, como la insuficiencia endocrina.

Background Multimodal rehabilitation allows optimization of functional recovery in surgery patients by reducing the post-operative stress and hospital stay duration, without increasing the morbidity and mortality. It is reportedly successful in other surgical disciplines, and guidelines for its application to gynecological surgery are available; however, most evidence for these guidelines is derived from observational and/or retrospective studies. Therefore, this study aimed to investigate the applicability of an enhanced recovery after surgery (ERAS) protocol in laparoscopic gynecological surgery and its influence on the postoperative stay, morbidity, mortality and readmission, through a prospective approach. Methods This prospective cohort study was performed on 90 patients who underwent laparoscopic hysterectomy for benign causes from October 2017 to October 2019. Patients in whom the ERAS (ERAS group, n = 30) and traditional (control group, n = 60) protocols were implemented were compared. All patients were followed for six months. Results The groups were homogeneous and did not differ significantly with respect to the demographic characteristics (age, ASA score, body mass index), surgical indications, and surgery types. Adherence to the ERAS protocol was over 99%. The postoperative hospital-stay durations were 1.73 days (r = 1–3) and 2.97 days (r = 2–6) in the ERAS and control groups (p = 0.000). No significant intergroup differences were observed in the rates of complications and readmissions. Conclusions The ERAS protocol is applicable in laparoscopic gynecological surgery and can be implemented with good adherence. This can allow optimization of patient recovery by reducing the hospital stay duration, without increasing the rates of morbidity, mortality, or readmission.

Background: As a first step towards a vaccine protecting COVID-19 convalescents from reinfection, we evaluated FINLAY-FR-1A vaccine in a clinical trial. Methods: Thirty COVID-19 convalescents aged 22-57 years were studied: convalescents of mild COVID-19, asymptomatic convalescents, both with PCR-positive at the moment of diagnosis; and individuals with subclinical infection detected by viral-specific IgG. They received a single intramuscular injection of the FINLAY-FR-1A vaccine (50 µg of the recombinant dimeric receptor binding domain). The primary outcomes were safety and reactogenicity, assessed over 28 days after vaccination. The secondary outcome was vaccine immunogenicity. Humoral response at baseline and following vaccination was evaluated by ELISA and live-virus neutralization test. The effector T cellular response was also assessed. Cuban Public Registry of Clinical Trials, WHO-ICTRP: https://rpcec.sld.cu/en/trials/RPCEC00000349-En. Findings: No serious adverse events were reported. Minor adverse events were found, the most common, local pain: 3 (10%) and redness: 2 (6·7%). The vaccine elicited a >21 fold increase in IgG anti-RBD antibodies 28 days after vaccination. The median of inhibitory antibody titres (94·0%) was three times greater than that of the COVID-19 convalescent panel. Virus neutralization titres higher than 1:160 were found in 24 (80%) participants. There was also an increase in RBD-specific T cells producing IFN-I³ and TNF-α. Interpretation: A single dose of the FINLAY-FR-1A vaccine against SARS-CoV-2 was an efficient booster of pre-existing natural immunity, with excellent safety profile. Funding: Partial funding for this study was received from the Project-2020-20, Fondo de Ciencia e Innovacion (FONCI), Ministry of Science, Technology and the Environment, Cuba.   RESUMEN. Antecedentes: Como un primer paso hacia una vacuna que proteja a los convalecientes de COVID-19 de la reinfeccion, evaluamos la vacuna FINLAY-FR-1A en un ensayo clinico. Metodos: Se estudiaron treinta convalecientes de COVID-19 de 22 a 57 anos: convalecientes de COVID-19 leve y convalecientes asintomaticos, ambos con prueba PCR positiva al momento del diagnostico; e individuos con infeccion subclinica detectada por IgG especifica viral. Los participantes recibieron una dosis unica por via intramuscular de la vacuna FINLAY-FR-1A (50 µg del dominio de union al receptor recombinante dimerico del SARS CoV-2). Las variables de medida primarias fueron la seguridad y la reactogenicidad, evaluadas durante 28 dias despues de la vacunacion. La variable secundaria, la inmunogenicidad. La respuesta humoral, al inicio del estudio y despues de la vacunacion, se evaluo por ELISA y mediante la prueba de neutralizacion del virus vivo. Tambien se evaluo la respuesta de celulas T efectoras. Registro Publico Cubano de Ensayos Clinicos, WHO-ICTRP: https://rpcec.sld.cu/en/trials/RPCEC00000349-En. Resultados: No se reportaron eventos adversos graves. Se encontraron eventos adversos leves, los mas comunes, dolor local: 3 (10%) y enrojecimiento: 2 (6·7%). La vacuna estimulo un incremento >21 veces de los anticuerpos IgG anti-RBD 28 dias despues de la vacunacion. La mediana de los titulos de anticuerpos inhibidores (94·0%) fue aproximadamente tres veces mayor que la del panel de convalecientes de COVID-19. Se encontraron titulos de neutralizacion viral superiores a 1:160 en 24 (80%) de los participantes. Tambien hubo un aumento en las celulas T especificas de RBD que producen IFN-I³ y TNF-α. Interpretacion: Una sola dosis de la vacuna FINLAY-FR-1A contra el SARS-CoV-2 reforzo eficazmente la inmunidad natural preexistente, con un excelente perfil de seguridad. Financiamiento: Se recibio un financiamiento parcial del Proyecto-2020-20, Fondo de Ciencia e Innovacion (FONCI), Ministerio de Ciencia, Tecnologia y Medio Ambiente, Cuba.

Background Müllerian adenosarcoma is a rare malignancy. These tumors occur mainly in the uterus, but also in extrauterine locations, usually related to endometriosis. Because of their rarity, there is limited data on optimal management strategies. Case presentation We present a 44-year-old woman with a history of endometriosis who consults for chronic pelvic pain. In the imaging tests, a heterogeneous mass is observed that impresses endometriosis, encompassing the uterus and left appendage. Surgery is performed by finding an extrauterine adenosarcoma that affected the uterus, ovary and bladder wall. Conclusion This is a rare case but should be considered in a patient with atypical clinical characteristics or preoperative pathology, so we show the diagnostic and therapeutic strategies carried out for the resolution of the case.

This review is aimed to focus on NSCLC as an emerging and promising model for active immunotherapy and the challenges for its inclusion in the current clinical scenario. Cancer vaccines for NSCLC have been focused as a therapeutic option based on the identification of a tumor hallmark and the active immunization with the related molecules that triggers cellular and/or humoral responses that consequently destroy or delay the rate of malignant progression. This therapeutic intervention in an established disease state has been aimed to impact into prolonging patient´s survival with ethically accepted quality of life. Understanding of relationship between structure and function in cancer vaccines is essential to interpret their opportunities to impact into prolonging survival and increasing quality of life in cancer patients. It is widely accepted that the failure of the cancer vaccines in the NSCLC scenario is related with its introduction in the advanced disease stages and poor performance status of the patients due to the combination of the tumor induced immunosuppression with the immune senescence. Despite first, second and emerging third line of onco-specific treatments the life expectancy for NSCLC patients diagnosed at advanced stages is surrounding the 12 months of median survival and in facts the today real circumstances are extremely demanding for the success inclusion of cancer vaccines as therapeutic choice in the clinical scenario. The kinetics of the active immunizations encompasses a sequential cascade of clinical endpoints: starting by the activation of the immune system, followed by the antitumor response and finalizing with the consequential impact on patients’ overall survival. Today this cascade of clinical endpoints is the backbone for active immunization assessment and moreover the concept of cancer vaccines, applied in the NSCLC setting, is just evolving as a complex therapeutic strategy, in which the opportunities for cancer vaccines start from the selection of the target cancer hallmark, followed by the vaccine formulation and its platforms for immune potentiating, also cover the successful insertion in the standard of care, the chronic administration beyond progression disease, the personalization based on predictors of response and the potential combination with other targeted therapies.