Role of PATJ in stroke prognosis by modulating endothelial to mesenchymal transition through the Hippo/Notch/PI3K axis.

Through GWAS studies we identified PATJ associated with functional outcome after ischemic stroke (IS). The aim of this study was to determine PATJ role in brain endothelial cells (ECs) in the context of stroke outcome. PATJ expression analyses in patient's blood revealed that: (i) the risk allele of rs76221407 induces higher expression of PATJ, (ii) PATJ is downregulated 24 h after IS, and (iii) its expression is significantly lower in those patients with functional independence, measured at 3 months with the modified Rankin scale ((mRS) ≤2), compared to those patients with marked disability (mRS = 4-5). In mice brains, PATJ was also downregulated in the injured hemisphere at 48 h after ischemia. Oxygen-glucose deprivation and hypoxia-dependent of Hypoxia Inducible Factor-1α also caused PATJ depletion in ECs. To study the effects of PATJ downregulation, we generated PATJ-knockdown human microvascular ECs. Their transcriptomic profile evidenced a complex cell reprogramming involving Notch, TGF-ß, PI3K/Akt, and Hippo signaling that translates in morphological and functional changes compatible with endothelial to mesenchymal transition (EndMT). PATJ depletion caused loss of cell-cell adhesion, upregulation of metalloproteases, actin cytoskeleton remodeling, cytoplasmic accumulation of the signal transducer C-terminal transmembrane Mucin 1 (MUC1-C) and downregulation of Notch and Hippo signaling. The EndMT phenotype of PATJ-depleted cells was associated with the nuclear recruitment of MUC1-C, YAP/TAZ, ß-catenin, and ZEB1. Our results suggest that PATJ downregulation 24 h after IS promotes EndMT, an initial step prior to secondary activation of a pro-angiogenic program. This effect is associated with functional independence suggesting that activation of EndMT shortly after stroke onset is beneficial for stroke recovery.

Trap and ambush therapy using sequential primary and tumor escape-selective oncolytic viruses.

In multiple models of oncolytic virotherapy, it is common to see an early anti-tumor response followed by recurrence. We have previously shown that frontline treatment with oncolytic VSV-IFN-ß induces APOBEC proteins, promoting the selection of specific mutations that allow tumor escape. Of these mutations in B16 melanoma escape (ESC) cells, a C-T point mutation in the cold shock domain-containing E1 (CSDE1) gene was present at the highest frequency, which could be used to ambush ESC cells by vaccination with the mutant CSDE1 expressed within the virus. Here, we show that the evolution of viral ESC tumor cells harboring the escape-promoting CSDE1C-T mutation can also be exploited by a virological ambush. By sequential delivery of two oncolytic VSVs in vivo, tumors which would otherwise escape VSV-IFN-ß oncolytic virotherapy could be cured. This also facilitated the priming of anti-tumor T cell responses, which could be further exploited using immune checkpoint blockade with the CD200 activation receptor ligand (CD200AR-L) peptide. Our findings here are significant in that they offer the possibility to develop oncolytic viruses as highly specific, escape-targeting viro-immunotherapeutic agents to be used in conjunction with recurrence of tumors following multiple different types of frontline cancer therapies.

The spike protein of SARS-CoV-2 induces heme oxygenase-1: Pathophysiologic implications.

BACKGROUND: Acute kidney injury (AKI) is both a consequence and determinant of outcomes in COVID-19. The kidney is one of the major organs infected by the causative virus, SARS-CoV-2. Viral entry into cells requires the viral spike protein, and both the virus and its spike protein appear in the urine of COVID-19 patients with AKI. We examined the effects of transfecting the viral spike protein of SARS-CoV-2 in kidney cell lines. METHODS: HEK293, HEK293-ACE2+ (stably overexpressing ACE2), and Vero E6 cells having endogenous ACE2 were transfected with SARS-CoV-2 spike or control plasmid. Assessment of gene and protein expression, and syncytia formation was performed, and the effects of quercetin on syncytia formation examined. FINDINGS: Spike transfection in HEK293-ACE2+ cells caused syncytia formation, cellular sloughing, and focal denudation of the cell monolayer; transfection in Vero E6 cells also caused syncytia formation. Spike expression upregulated potentially nephrotoxic genes (TNF-α, MCP-1, and ICAM1). Spike upregulated the cytoprotective gene HO-1 and relevant signaling pathways (p-Akt, p-STAT3, and p-p38). Quercetin, an HO-1 inducer, reduced syncytia formation and spike protein expression. INTERPRETATION: The major conclusions of the study are: 1) Spike protein expression in kidney cells provides a relevant model for the study of maladaptive and adaptive responses germane to AKI in COVID-19; 2) such spike protein expression upregulates HO-1; and 3) quercetin, an HO-1 inducer, may provide a clinically relevant/feasible protective strategy in AKI occurring in the setting of COVID-19. FUNDING: R01-DK119167 (KAN), R01-AI100911 (JPG), P30-DK079337; R01-DK059600 (AA).

Oncolytic measles virus therapy enhances tumor antigen-specific T-cell responses in patients with multiple myeloma.

Oncolytic virus therapy leads to immunogenic death of virus-infected tumor cells and this has been shown in preclinical models to enhance the cytotoxic T-lymphocyte response against tumor-associated antigens (TAAs), leading to killing of uninfected tumor cells. To investigate whether oncolytic virotherapy can increase immune responses to tumor antigens in human subjects, we studied T-cell responses against a panel of known myeloma TAAs using PBMC samples obtained from ten myeloma patients before and after systemic administration of an oncolytic measles virus encoding sodium iodide symporter (MV-NIS). Despite their prior exposures to multiple immunosuppressive antimyeloma treatment regimens, T-cell responses to some of the TAAs were detectable even before measles virotherapy. Measurable baseline T-cell responses against MAGE-C1 and hTERT were present. Furthermore, MV-NIS treatment significantly (P < 0.05) increased T-cell responses against MAGE-C1 and MAGE-A3. Interestingly, one patient who achieved complete remission after MV-NIS therapy had strong baseline T-cell responses both to measles virus proteins and to eight of the ten tested TAAs. Our data demonstrate that oncolytic virotherapy can function as an antigen agnostic vaccine, increasing cytotoxic T-lymphocyte responses against TAAs in patients with multiple myeloma, providing a basis for continued exploration of this modality in combination with immune checkpoint blockade.

CD45 y leucemia linfoide aguda pediátrica / CD45 and childhood acute lymphoblastic leukemia

Introducción: El CD45 se expresa en las células hematopoyéticas, su determinación es indispensable para la clasificación inmunofenotípica de la leucemia linfoide aguda (LLA). Objetivo: Evaluar la expresión del antígeno CD45 en los blastos de pacientes pediátricos con LLA y su relación con las características biológicas, morfológicas y clínicas al inicio de la enfermedad, la respuesta al tratamiento y la supervivencia global (SG) de los enfermos. Métodos: Se estudiaron 160 pacientes con LLA entre diciembre del 2012 y diciembre del 2017, tratados con el protocolo ALL-IC BFM-SG 2009. El inmunofenotipaje celular de la médula ósea se realizó por citometría de flujo. Resultados: El fenotipo B CD45+ predominó en los menores de seis años de edad y en los mayores de diez, el fenotipo T CD45+. Se encontró diferencia significativa entre la ausencia de adenopatías mediastínicas, el fenotipo leucémico y la ausencia de CD45 (p=0.004); entre la respuesta a la prednisona en sangre periférica al día ocho, el fenotipo leucémico y la ausencia de CD45 (p=0.001). Se encontraron diferencias significativas entre la respuesta a la prednisona en sangre periférica el día ocho y la respuesta en médula ósea el día 33, según fenotipo leucémico (p=0.009) y la presencia en los blastos del antígeno CD45 (p=0.02). Se encontró diferencia significativa entre la SG de los enfermos, según fenotipo leucémico y la ausencia del antígeno CD45 (p=0.017). Conclusión: La expresión o ausencia del antígeno de CD45 en los blastos tiene relación con la respuesta al tratamiento y la SG de pacientes pediátricos con LLA(AU)

Introduction: CD45 is expressed in hematopoietic cells, its determination is essential for the immunophenotypic classification of acute lymphoid leukemia (ALL). Objective: To evaluate the expression of the CD45 antigen in the blasts of pediatric patients with ALL and its relationship with the biological, morphological and clinical characteristics at the onset of the disease, the response to treatment and the overall survival (OS) of the patients. Methods: 160 patients with ALL were studied between December 2012 and December 2017, treated with the ALL-IC BFM-SG 2009 protocol. Bone marrow cellular immunophenotyping was performed by flow cytometry. Results: Patients with the CD45 + B phenotype predominated in those under six years of age, while those with a CD45 + T phenotype in those older than ten. A significant difference was found between the absence of mediastinal lymph nodes, the leukemic phenotype and the absence of CD45 (p = 0.004). A significant difference was found between the response to prednisone in peripheral blood at day eight, the leukemic phenotype and the absence of CD45, p = 0.001. Significant differences were found between the response to prednisone in peripheral blood on day eight and the response in bone marrow on day 33, according to leukemic phenotype and the presence in blasts of the CD45 antigen (p = 0.009 and p = 0.02, respectively). A significant difference was found between the OS of patients, according to leukemic phenotype and the absence of the CD45 antigen, p = 0.017. Conclusion: The expression or absence of the CD45 antigen in blasts is related to the response to treatment and OS of pediatric patients with ALL(AU)

The Maritime Declaration of Health (MDH) as a tool to detect maritime traffic-related health risks: analysis of MDH forms submitted to Spanish ports, October 2014 to March 2015.

The international maritime traffic of people and goods has often contributed to the spread of pathogens affecting public health. The Maritime Declaration of Health (MDH), according to the International Health Regulations (IHR) (2005), is a document containing data related to the state of health on board a ship during passage and on arrival at port. It is a useful tool for early detection of public health risks. The main objective of our study was to evaluate compliance with the model provided in the IHR, focusing on the format and degree of completion of MDH forms received at Spanish ports. We reviewed the content of 802 MDH forms submitted to nine Spanish ports between October 2014 and March 2015. Study results show that 22% of MDH forms presented did not comply with the recommended model and 39% were incomplete. The proportion of cargo ships with correct and complete MDH forms was lower than passenger ships; thus, the nine health questions were answered less frequently by cargo ships than passenger ships (63% vs 90%, p value < 0.001). The appropriate demand and usage of MDH forms by competent authorities should improve the quality of the document as a tool and improve risk assessment.

Expresión del antígeno CD45 en la Leucemia Linfoide Aguda Pediátrica / Evaluation of CD45 antigen expression in acute lymphoblastic leukemia

Introducción: la leucemia linfoide aguda (LLA) es la neoplasia más frecuente en la infancia. La determinación del antígeno CD45 discrimina entre los blastos y las células reactivas en la médula ósea (MO). Objetivo: evaluar la expresión del antígeno CD45 sobre los blastos de pacientes con LLA, según los distintos subtipos inmunológicos, su posible relación con las características biológicas y clínicas de presentación de la enfermedad y la respuesta al tratamiento antileucémico. Métodos: se estudiaron 150 pacientes con LLA procedentes de varios servicios oncohematológicos del país, entre enero del 2008 y mayo del 2015. El inmunofenotipaje celular de la MO se realizó por citometría de flujo. Resultados: el antígeno CD45 mostró una gran heterogeneidad de expresión sobre los linfoblastos. Del total de enfermos estudiados, 19,3 por ciento no expresaron sobre los blastos el antígeno CD45, 36,7 por ciento presentaron una expresión moderada y 44 por ciento mostraron una alta densidad de expresión. Se encontró diferencia significativa al comparar el fenotipo leucémico con la expresión del antígeno CD45 sobre los blastos (p = 0,000). Ningún enfermo presentó adenopatías mediastinales, con diferencias significativas (p = 0,000), según el fenotipo y la expresión de CD45. Los pacientes con LLA-T cuyos blastos no expresaron CD45 tuvieron una mala respuesta al tratamiento anti-leucémico los días 8 y 15 en sangre periférica y MO, respectivamente. Conclusión: la expresión de CD45 sobre los blastos, pudiera ser considerada como un factor pronóstico adicional para la estratificación en diferentes grupos de riesgos, de la LLA en el niño(AU)

Introduction: Acute lymphoblastic leukemia (ALL) is the most frequent neoplasia in infancy. Determination of CD45 antigen discriminates between blasts and reactive cells in the bone marrow (MO). Objective: To evaluate the expression of the CD45 antigen on the blasts of patients with ALL, according to the different immunological subtypes, their possible relation with the biological and clinical characteristics of the disease and the response to antileukemic treatment. Methods : 150 patients with ALL were studied from various onco-hematological services of the country, between January 2008 and May 2015. The cellular immunophenotyping of the MO was performed by flow cytometry. Results : The CD45 antigen showed a great heterogeneity of expression on the lymphoblasts. Of the total number of patients studied, 19.3 percent did not express the CD45 antigen on the blasts, 36.7 percent presented moderate expression and 44 percent showed a high expression density of it.A significant difference was found when comparing the leukemic phenotype with the expression of the CD45 antigen on the blasts (p = 0.000). No patient had mediastinal lymphadenopathy, with significant differences (p = 0.000), according to the phenotype and CD45 expression. Patients with T-ALL whose blasts did not express CD45 had a poor response to anti-leukemic treatment on days 8 and 15 in peripheral blood and MO, respectively. Conclusion: CD45 expression on blasts could be considered as an additional prognostic factor for stratification in different risk groups of ALL in children(AU)

Respuesta al tratamiento con interferón beta en pacientes con esclerosis múltiple. Validación del Rio Score / Response to treatment with interferon beta in patients with multiple sclerosis. Validation of the Rio Score

Introducción. Se han propuesto diferentes criterios de respuesta al tratamiento con interferón beta, y el Rio Score es uno de los más utilizados. El objetivo de este estudio fue validar la utilidad del Rio Score en una cohorte independiente. Pacientes y métodos. Estudio multicéntrico, prospectivo y longitudinal de pacientes con esclerosis múltiple remitente recurrente tratados con interferón beta. Los pacientes fueron clasificados basándose en la presencia de brotes, lesiones activas (nuevas en T2 o lesiones que captaban gadolinio) en la resonancia magnética, incremento confirmado de la discapacidad o combinaciones de estas variables (brotes, incremento en la Expanded Disability Status Scale y lesiones activas) tras un año de tratamiento. Se utilizó un análisis de regresión con el fi n de identificar las variables de predicción de respuesta después de un seguimiento de tres años. Resultados. Se incluyó a 249 pacientes con esclerosis múltiple remitente recurrente. El modelo logístico confirmó que la presencia de dos (odds ratio = 6,6; IC 95% = 2,7-16,1; p < 0,0001) o tres (odds ratio = 8,5; IC 95% = 1,6-46; p < 0,01) variables positivas durante el primer año de tratamiento confería un riesgo significativo de actividad (brotes o progresión) en los siguientes dos años. Conclusiones. Se confirma, en una cohorte independiente, la utilidad del Rio Score para identificar a pacientes con un mayor riesgo de desarrollar actividad clínica o progresión de la discapacidad durante el tratamiento con interferón beta (AU)

Introduction. Different criteria have been proposed for the response to treatment with interferon beta, and the Rio Score is one of the most widely used. The aim of this study was to validate the usefulness of the Rio Score in an independent cohort. Patients and methods. A multi-centre, prospective, longitudinal study was conducted on patients with relapsing-remitting multiple sclerosis treated with interferon beta. The patients were classified according to the presence of attacks, active lesions (new in T2 or gadolinium enhancing lesions) in magnetic resonance imaging, a confirmed increase in disability or combinations of these variables (attacks, increase on the Expanded Disability Status Scale and active lesions) after one year’s treatment. Regression analysis was used in order to identify the response-predicting variables after a three-year follow-up. Results. The sample consisted of 249 patients with relapsing-remitting multiple sclerosis. The logistic model confirmed that the presence of two (odds ratio = 6.6; CI 95% = 2.7-16.1; p < 0.0001) or three (odds ratio = 8.5; CI 95% = 1.6-46; p < 0.01) positive variables during the first year of treatment were indicative of a significant risk of activity (attacks or progression) in the next two years. Conclusions. The usefulness of the Rio Score is confirmed, in an independent cohort, as a means of identifying patients with a higher risk of developing clinical activity or progression of disability during treatment with interferon beta (AU)

Definitive Management of Oligometastatic Melanoma in a Murine Model Using Combined Ablative Radiation Therapy and Viral Immunotherapy.

PURPOSE: The oligometastatic state is an intermediate state between a malignancy that can be completely eradicated with conventional modalities and one in which a palliative approach is undertaken. Clinically, high rates of local tumor control are possible with stereotactic ablative radiation therapy (SABR), using precisely targeted, high-dose, low-fraction radiation therapy. However, in oligometastatic melanoma, virtually all patients develop progression systemically at sites not initially treated with ablative radiation therapy that cannot be managed with conventional chemotherapy and immunotherapy. We have demonstrated in mice that intravenous administration of vesicular stomatitis virus (VSV) expressing defined tumor-associated antigens (TAAs) generates systemic immune responses capable of clearing established tumors. Therefore, in the present preclinical study, we tested whether the combination of systemic VSV-mediated antigen delivery and SABR would be effective against oligometastatic disease. METHODS AND MATERIALS: We generated a model of oligometastatic melanoma in C57BL/6 immunocompetent mice and then used a combination of SABR and systemically administered VSV-TAA viral immunotherapy to treat both local and systemic disease. RESULTS: Our data showed that SABR generates excellent control or cure of local, clinically detectable, and accessible tumor through direct cell ablation. Also, the immunotherapeutic activity of systemically administered VSV-TAA generated T-cell responses that cleared subclinical metastatic tumors. We also showed that SABR induced weak T-cell-mediated tumor responses, which, particularly if boosted by VSV-TAA, might contribute to control of local and systemic disease. In addition, VSV-TAA therapy alone had significant effects on control of both local and metastatic tumors. CONCLUSIONS: We have shown in the present preliminary murine study using a single tumor model that this approach represents an effective, complementary combination therapy model that addresses the need for both systemic and local control in oligometastatic melanoma.

Diagnosis of bacteraemia and growth times.

OBJECTIVE: The objective of this study was to predict the diagnosis of bacteraemia as a function of the time at which the automated BacT/Alert system continuously detects microorganism growth. METHODS: A retrospective study of a database of 1334 patients with a positive blood culture between January 2011 and June 2013 was conducted. Together with the final blood culture results and the patient's history, growth was then analysed to assess whether it represented true bacteraemia or bacterial contamination. The earliest detection times of bacterial growth in each batch of blood cultures were analysed in a blinded fashion after classification. RESULTS: In total, 590 batches of blood cultures corresponded to true bacteraemia and 744 to bacterial contamination. In the bacteraemia group, the median growth time was 12.72 h (interquartile range (IQR) 10.08-17.58 h). In the contaminated blood culture group, the median growth time was 20.6h (IQR 17.04-32.16 h) (p<0.001). Analysis of the receiver operating characteristics (ROC) curve (area under the curve 0.80, 95% confidence interval 0.771-0.826) showed that 90% of the contaminants grew after 14.7h (sensitivity 90.5%, specificity 63.4%, positive predictive value (PPV) 65.9%, negative predictive value (NPV) 90.7%). Forty-five percent of the bacteraemia organisms grew in under 12h (sensitivity 45.3%, specificity 95%, PPV 87.8%, NPV 68.7%). Microorganisms such as Candida sp and Bacteroides sp presented median growth times significantly longer than those of the other microorganisms. The administration of antibiotics in the week prior to bacteraemia was found to delay the growth time of microorganisms (p<0.001). CONCLUSIONS: Knowing the time to detection of microorganism growth can help to distinguish between true bacteraemia and bacterial contamination, thus allowing more timely clinical decisions to be made, before definitive microorganism identification.

Eficacia del implante de células mononucleares autólogas en el tratamiento de la periodontitis crónica / Effectiveness of autologous mononuclear cells implant in patients with chronic periodontitis

Introducción: los buenos resultados en la regeneración de tejidos mediante la implantación de células mononucleares en distintas especialidades médicas en el mundo y en Cuba, ha motivado a considerar el periodonto como candidato para esta terapia.Objetivo: determinar la eficacia del implante de células mononucleares autólogas en el tratamiento de la periodontitis crónica a 48 meses de evolución. Material y Métodos: se realizó un ensayo clínico fase III, aleatorizado y controlado en pacientes con periodontitis crónica durante los años 2008 a 2014. De ese grupo de pacientes se evaluaron 30 que tenían 48 ó más meses de recibir tratamiento en la consulta de Periodoncia del Hospital Enrique Cabrera en el período comprendido de febrero a mayo de 2015; 15 habían recibido tratamiento con células mononucleares (grupo estudio) y 15 terapia convencional (grupo control). La movilización a la sangre periférica de las células mononucleares se realizó mediante la aplicación del factor estimulador de colonias de granulocitos (FEC-G). Resultados: se aprecia una disminución del promedio de todas las variables clínicas, que es marcada en cada uno de los períodos evolutivos con respecto al estado inicial de los pacientes a los 6, 12, 36 y 48 meses posteriores al tratamiento en el grupo de estudio, mientras que en el control las manifestaciones de la enfermedad fueron reapareciendo paulatinamente a medida que avanzaba el tiempo post-tratamiento. Estos resultados fueron significativos. Conclusiones: la terapia celular regenerativa con células mononucleares autólogas es eficaz para el tratamiento de pacientes con periodontitis y su efecto es prolongado(AU)

Introduction: over the last years, in Cuba and other countries, encouraging results have been obtained in different medical specialties in the field of tissue regeneration by implanting stem cells; it has motivated us to consider periodontal tissue as a target for this therapy. Objective: To determine the efficacy of the implant of mononuclear autologous cells for the treatment of 48 months evolution chronic periodontitis. Material and Methods: 30 patients attending the Periodontology Clinic of the "Enrique Cabrera" hospital for over48 months during years 2008 to 2014 where included in the study, divided into two groups 15 patients each: group A were treated with autologous mononuclear cells and group B, who underwent classic therapy. The peripheral blood autologous mononuclear cells (MNC-SP) were mobilized with granulocyte colony- stimulating factor (G-CSF). Results: group A patients showed a significant average decrease in all clinical variables, more remarkable in every of the evolution periods as compared to the initial stage of every patient at 6, 12, 24 and 48 months after starting the treatment. In Group B patients, signs of the disease gradually reappeared as the post-treatment period proceeded.Conclusions: regenerative cell therapy with MNC-SP is effective and long lasting in patients with periodontitis(AU)

Morbilidad y mortalidad de la hemoglobinopatía sc en el Instituto de Hematología e Inmunología: Experiencia de 36 años / Morbility and mortality of hemoglobinopathy sc at the Institute of Hematology and Immunology: Experience of 36 years

Introducción: la hemoglobinopatía SC es la segunda variante de la drepanocitosis más frecuente en Cuba; sin embargo, existen pocos trabajos dirigidos a su estudio. Objetivo: realizar una caracterización de la historia natural de lahemoglobinopatía HSC, Métodos: se realizó un estudio observacional, descriptivo, retrospectivo y longitudinal en 148 pacientes con hemoglobinopatía HSC seguidos al menos 2 años en el Instituto de Hematología e Inmunología (1973-2009). Se definieron los eventos hematológicos según las normas cubanas de la drepanocitosis y los exámenes complementarios se realizaron en condiciones basales del paciente. Se utilizó la prueba de Chi Cuadrado para determinar asociación entre variables. Los parámetros de laboratorio se compararon mediante la prueba t Student. Para la estimación de la sobrevida global (SG) se empleó el método de Kaplan Meier. Resultados: predominó el sexo femenino (56,1 por ciento). La crisis vasoclusiva dolorosa (91,2 por ciento) y el síndrome torácico agudo (35,1 por ciento) fueron las manifestaciones clínicas más frecuentes. El 10,8 por ciento presentó afecciones oftalmológicas (hemovítreo, retinopatía, desprendimiento de retina y catarata). La esplenomegalia predominó en los pacientes menores de 40 años y la hepatomegalia se encontró en todas las edades. Hubo 36 mujeres con embarazos sin mortalidad materna ni perinatal y 26 abortos (65,4 por ciento fueron espontáneos). La anemia fue ligera pero más acentuada en el sexo femenino. Las funciones hepática y renal, mostraron deterioro con la edad. La supervivencia global a los 50 años fue del 79 por ciento. La causa de muerte más frecuente fue la insuficiencia renal crónica. Conclusiones: el aumento de la calidad y expectativa de vida de la HSC en Cuba es el resultado de la atención médica multidisciplinaria y el fácil acceso a los servicios de urgencia

Introduction: hemoglobinophatySC (HSC) is the second most common variant of sickle cell disease in Cuba and the world; nevertheless, there are few studies aimed in this field. Objective: to make the characterization of the natural history of HSC. Methods: an observational, descriptive, retrospective and longitudinal study was performed in 148 patients with HSC followed for at least two years at the Institute of Hematology and Immunology in the period 1973-2009. Hematological events according to Cuban procedures in sickle cell disease were determined and complementary studies were performed. Results: there was a predominance of females (56.1 percent). Vasocclusive painful crises (91.2 percent) and acute chest syndrome (35.1 percent) were the most frequent clinical events. Ophthalmology affections were present in 10,8 percent (hemovitreous, retinopathy, retinal detachment and cataract). Splenomegaly was predominant in patients under 40 years and hepatomegaly was found in all ages. There were 36 women with pregnancies without maternal or perinatal mortality. From 26 abortions (65.4 percent were spontaneous). Anemia was mild but more pronounced in females. Liver and kidney functions showed deterioration with age. Overall survival at 50 years was 79 percent. The main cause of death was chronic renal failure. Conclusions: increasing the quality of life and life expectancy of HSC in Cuba is the result of multidisciplinary comprehensive care and easy access to emergency services