Improved Tool for Predicting Skin Irritation on Reconstructed Human Epidermis Models Based on Electrochemical Impedance Spectroscopy.

The rabbit skin irritation test has been the standard for evaluating the irritation potential of chemicals; however, alternative methods that do not use animal testing are actively encouraged. Reconstructed human epidermis (RhE) models mimic the biochemical and physiological properties of the human epidermis and can be used as an alternative method. On RhE methods, the metabolic activity of RhE models is used to predict skin irritation, with a reduction in metabolic activity indicating a reduced number of viable cells and linking cell death to skin irritation processes. However, new challenges have emerged as the use of RhE models increases, including the need for non-invasive and marker-free methodologies to assess cellular states. Electrochemical impedance spectroscopy (EIS) is one such methodology that can meet these requirements. In this study, our results showed that EIS can differentiate between irritant and non-irritant chemicals, with a significant increase in the capacitance values observed in the irritant samples. A ROC curve analysis showed that the prediction method based on EIS met OECD TG 439 requirements at all time points and had 95% within-laboratory reproducibility. Comparison with the MTT viability assay showed that prediction using EIS achieved higher sensitivity, specificity, and accuracy. These results suggest that EIS could potentially replace animal testing in the evaluation of irritation potential and could be a valuable addition to in vitro testing strategies.

A Simple, Safe, and Effective Method for Preparing Autologous Bio-Based Fibrin Glue for Ophthalmic Use.

This study proposes a method to prepare autologous bio-based fibrin glue (FG) for use in ophthalmic surgery. FGs containing three fibrinogen concentrations and a thrombin concentrate were prepared using human blood from five donors (FG1: physiological fibrinogen concentration; FG2 and FG3: concentrated fibrinogen). The adhesion strength was tested, and the clinical safety and efficacy were studied in rabbit eyes in conjunctival surgery. A commercial FG was used as a control. From each donor, 2 mL of FG was prepared, containing 1 mL of 3.49 ± 0.78 (FG1), 17.74 ± 4.66 (FG2), or 47.46 ± 9.36 mg/mL (FG3) of fibrinogen and 1 mL of 2248.12 ± 604.20 UI/mL of thrombin. The average adhesion strength increased with the fibrinogen concentration, from 1.49 ± 0.39 kPa (FG1) to 3.14 ± 1.09 kPa (FG3). FG1 showed poor results when used for autograft adhesion. In contrast, the conjunctival autografts were successfully grafted using FG2 and FG3, revealing equivalent adhesion properties compared with commercial FG, but with less inflammation. In conclusion, FGs could be prepared on demand within minutes from small volumes of human blood, using a method that results in FGs which exhibit good adhesion capacity and are also safe and effective in a preclinical study.

Polymerizable Skin Hydrogel for Full Thickness Wound Healing.

The skin is the largest organ in the human body, comprising the main barrier against the environment. When the skin loses its integrity, it is critical to replace it to prevent water loss and the proliferation of opportunistic infections. For more than 40 years, tissue-engineered skin grafts have been based on the in vitro culture of keratinocytes over different scaffolds, requiring between 3 to 4 weeks of tissue culture before being used clinically. In this study, we describe the development of a polymerizable skin hydrogel consisting of keratinocytes and fibroblast entrapped within a fibrin scaffold. We histologically characterized the construct and evaluated its use on an in vivo wound healing model of skin damage. Our results indicate that the proposed methodology can be used to effectively regenerate skin wounds, avoiding the secondary in vitro culture steps and thus, shortening the time needed until transplantation in comparison with other bilayer skin models. This is achievable due to the instant polymerization of the keratinocytes and fibroblast combination that allows a direct application on the wound. We suggest that the polymerizable skin hydrogel is an inexpensive, easy and rapid treatment that could be transferred into clinical practice in order to improve the treatment of skin wounds.

In-house performance assessment of 3D QobuR-Reconstructed Human Cornea-Like Epithelium (RhCE) for the evaluation of eye hazard.

To replace the Draize eye irritation test (OECD Test Guideline 404), several test methods based on reconstructed cornea-like epithelium (RhCE) have been developed and adopted in the OECD TG 492. The objective of this study was to stablish the experimental procedures and evaluate the performance assessment of QobuR-RhCE, an in-house RhCE model to be used for the evaluation of eye hazard. We define the essential structural, functional and procedural elements of the test method components to help assuring that the proposed test method is based on the same concepts as the validated reference methods. Performance assessment was evaluated in accordance with the revised performance standards for the assessment of proposed similar or modified in vitro reconstructed human cornea-like epithelium and the minimum list of reference chemicals was evaluated. As result, the proposed method scored 93.3% sensibility, 60% specificity, 76.7% accuracy and 96.7% within-laboratory reproducibility (WLR), providing a similar performance in comparison to the validated reference methods. Additionally, we describe a secondary endpoint based on Transepithelial Electrical Resistance (TEER) that could be of use to better discriminate between irritants and non-irritants. Taken together the results indicate that the QobuR-RhCE test method is an accurate screening tool that can be used as a standalone alternative to evaluate ocular irritation.

Impedance-based non-invasive assay for ocular damage prediction on in vitro 3D reconstructed human corneal epithelium.

Reconstructed human cornea-like epithelium (RhCE) holds unprecedented promise for toxicological analyses and the replacement of animal use. However, current standards to evaluate potential ocular irritancy present a major downfall, the need to invasively alter tissue samples to evaluate cell viability. In this study, the applicability of impedance analysis was validated by monitoring the change in cell capacitance during tissue maturation and before and after chemical application using coupled electrodes. Our results indicate that cell maturation on RhCE models can be evaluated during model production using capacitance sensing offering a faster and simpler quality control criteria for RhCE model usability. Additionally, cell capacitance resulted to be more sensitive in detecting slight cell damages than methods based on cell metabolism, and when integrated into OECD-approved testing strategies, capacitance sensing performed as good as currently accepted methodologies displaying 66% sensitivity, 100% specificity and 83% accuracy when evaluated at 300 Hz. In summary, a quantitative analysis to predict in vivo ocular irritation based on changes in RhCE capacitance by impedance spectroscopy is suggested. This methodology represents a non-invasive and non-destructive alternative that would enable the monitoring of reversible effects or repeated dose toxicity.

Efficacy and safety of itacitinib versus placebo in combination with corticosteroids for initial treatment of acute graft-versus-host disease (GRAVITAS-301): a randomised, multicentre, double-blind, phase 3 trial.

BACKGROUND: Acute graft-versus-host disease (GVHD) is a common and life-threatening complication of allogeneic haematopoietic stem cell transplantation (HSCT); there is an urgent unmet need for effective therapies. We aimed to evaluate the Janus kinase 1 inhibitor itacitinib versus placebo, both in combination with corticosteroids, for initial treatment of acute GVHD. METHODS: GRAVITAS-301 was an international, double-blind, adaptive (group sequential design) phase 3 study conducted at 129 hospitals and community practices in 19 countries. Eligible patients were aged 18 years or older, had previously received allogeneic HSCT for a haematological malignancy, developed grades II-IV acute GVHD, and received up to 2 days of systemic corticosteroids. Patients were stratified by clinical standard-risk or high-risk acute GVHD and randomly assigned (1:1), via a centralised interactive voice response system, to receive either oral itacitinib (200 mg) or placebo once daily, both in addition to corticosteroids. The primary endpoint was overall response rate (ORR) at day 28 (defined as the proportion of patients with complete response, very good partial response, or partial response 28 days after the start of treatment). For sample size determination, an absolute improvement in ORR at day 28 over standard therapy of 16% was considered clinically meaningful. Efficacy analyses were performed in the intention-to-treat population; safety analyses included patients who received at least one dose of study drug. GRAVITAS-301 is registered with ClinicalTrials.gov (NCT03139604) and is complete. FINDINGS: Between July 19, 2017, and Oct 3, 2019, 439 patients were randomly assigned to receive either itacitinib plus corticosteroids (n=219; itacitinib group) or placebo plus corticosteroids (n=220; placebo group). 173 (39%) patients were female and 390 (89%) were White. At baseline, 107 (24%) of 439 patients (itacitinib 51 [23%] of 219; placebo 56 [25%] of 220) had clinical high-risk acute GVHD. The ORR at day 28 was 74% (95% CI 67·6-79·7; 162 of 219; complete response 53% [116 of 219]) for itacitinib and 66% (59·7-72·6; 146 of 220; complete response, 40% [89 of 220]) for placebo (odds ratio for ORR 1·45, 95% CI 0·96-2·20; two-sided p=0·078). Grade 3 or worse adverse events occurred in 185 (86%) of 215 itacitinib recipients and 178 (82%) of 216 placebo recipients, and most commonly included thrombocytopenia or platelet count decreased (78 [36%] vs 68 [31%]), neutropenia or neutrophil count decreased (49 [23%] vs 45 [21%]), anaemia (42 [20%] vs 26 [12%]), and hyperglycaemia (26 [12%] vs 28 [13%]). Treatment-related deaths occurred in three of 215 patients (1%) in the itacitinib group and four of 216 (2%) in the placebo group. INTERPRETATION: The observed improvement in ORR at day 28 with the addition of itacitinib versus placebo to corticosteroids did not reach the prespecified significance level. Further studies might provide additional insight into the utility of selective JAK1 inhibition for the treatment of acute GVHD. FUNDING: Incyte.

Caracterización de pacientes operados por cáncer pulmonar en el Hospital Universitario "Manuel Ascunce Domenech" / Characterization of Patients Operated on for Pulmonary Cancer at Manuel Ascunce Domenech Pulmonary Cancer

Introducción: La cirugía es el tratamiento de elección que ofrece la curación a un grupo de pacientes afectados de cáncer pulmonar, aun así, la supervivencia global para todos los estadios a 5 años se mantiene baja. Objetivo: Caracterizar los pacientes operados de cáncer pulmonar en el período comprendido desde el 1ro de marzo del 2015 hasta el 1ro de agosto del 2020. Métodos: Se realizó un estudio, observacional, retrospectivo de corte transversal, para describir el comportamiento de la morbimortalidad quirúrgica de los pacientes portadores de cáncer pulmonar en el Hospital Provincial Universitario "Manuel Ascunce Domenech" de la ciudad de Camagüey, desde marzo del 2015 y agosto del 2020. El universo de estudio se conformó por 211 pacientes operados con diagnóstico de cáncer pulmonar. Resultados: La edad que predominó fue entre 61 a 70 años y el sexo masculino. El adenocarcinoma y el carcinoma epidermoide fueron los diagnósticos histológicos más frecuentes. La lobectomía superior derecha fue la resección que con más frecuencia se realizó, así como algún tipo de linfadenectomía mediastinal fue realizada en más de la mitad de los casos. Las complicaciones más frecuentes fueron las relacionadas con la fuga de aire. El índice de fallecidos fue bajo encontrándose las complicaciones cardiovasculares y el tromboembolismo pulmonar, las causas de mayor frecuencia. Conclusiones: La cirugía en el cáncer pulmonar es el tratamiento de elección en etapas tempranas con una baja morbilidad y mortalidad en pacientes que reúnan las condiciones de operabilidad(AU)

Introduction: Surgery is the treatment of choice that offers cure to a group of patients affected by pulmonary cancer; yet five-year overall survival for all stages remains low. Objective: To characterize the patients operated on for pulmonary cancer in the period from March 1, 2015 to August 1, 2020. Methods: An observational, retrospective and cross-sectional study was carried out to describe the behavior of surgical morbidity and mortality since March 2015 and August 2020 in patients with pulmonary cancer at Manuel Ascunce Domenech University Provincial Hospital in Camagüey City. The study universe was made up of 211 patients operated on with a diagnosis of pulmonary cancer. Results: There was a predominance of the age 61-70 years and the male sex. Adenocarcinoma and squamous cell carcinoma were the most frequent histological diagnoses. Right upper lobectomy was the most frequently performed resection, as well as some type of mediastinal lymphadenectomy, performed in more than half of the cases. The most frequent complications were those related to air leakage. The death rate was low, with cardiovascular complications and pulmonary thromboembolism being the most frequent causes. Conclusions: Surgery is the treatment of choice for pulmonary cancer in early stages, with low morbidity and mortality in patients who meet operability conditions(AU)

Mini Cleanroom for the Manufacture of Advanced Therapy Medicinal Products (ATMP): Bioengineered Corneal Epithelium.

Among several requirements for the manufacture of Advanced Therapy Medicinal Products (ATMP) are: following the guidelines of a pharmaceutical quality system, complying with Good Manufacturing Practice (GMP) and access to a cleanroom fulfilling strict environmental conditions (Class A work area and Class B environment). This makes ATMP expensive. Moreover, the production of many of these therapeutic products may also be unprofitable, as in most cases their use is limited to a few patients and to a single batch per manufacturing unit. To reduce costs, ATMP may be produced in a scaled-down system isolated from the external environment (isolator), allowing for placement of this facility in a Class D environment, which is much more permissive and less costly. In this work, we confirm that it is possible to manufacture bioengineered corneal epithelium inside an isolator while fulfilling all the safety assurance standards at an affordable cost for patients. This small-scale ultra-clean working environment complies with GMP guidelines and could be a solution for the high costs associated with conventional cleanroom ATMP production.

Fibrin-Plasma Rich in Growth Factors Membrane for the Treatment of a Rabbit Alkali-Burn Lesion.

The purpose of this work is to describe the use of Fibrin-Plasma Rich in Growth Factors (PRGF) membranes for the treatment of a rabbit alkali-burn lesion. For this purpose, an alkali-burn lesion was induced in 15 rabbits. A week later, clinical events were evaluated and rabbits were divided into five treatment groups: rabbits treated with medical treatment, with a fibrin-PRGF membrane cultured with autologous or heterologous rabbit Limbal Epithelial Progenitor Cells (LEPCs), with a fibrin-PRGF membrane in a Simple Limbal Epithelial Transplantation and with a fibrin-PRGF membrane without cultured LEPCs. After 40 days of follow-up, corneas were subjected to histochemical examination and immunostaining against corneal or conjunctival markers. Seven days after alkali-burn lesion, it was observed that rabbits showed opaque cornea, new blood vessels across the limbus penetrating the cornea and epithelial defects. At the end of the follow-up period, an improvement of the clinical parameters analyzed was observed in transplanted rabbits. However, only rabbits transplanted with cultured LEPCs were positive for corneal markers. Otherwise, rabbits in the other three groups showed positive staining against conjunctival markers. In conclusion, fibrin-PRGF membrane improved the chemically induced lesions. Nonetheless, only fibrin-PRGF membranes cultured with rabbit LEPCs were able to restore the corneal surface.

Proposed global prognostic score for systemic mastocytosis: a retrospective prognostic modelling study.

BACKGROUND: Several risk stratification models have been proposed in recent years for systemic mastocytosis but have not been directly compared. Here we designed and validated a risk stratification model for progression-free survival (PFS) and overall survival (OS) in systemic mastocytosis on the basis of all currently available prognostic factors, and compared its predictive capacity for patient outcome with that of other risk scores. METHODS: We did a retrospective prognostic modelling study based on patients diagnosed with systemic mastocytosis between March 1, 1983, and Oct 11, 2019. In a discovery cohort of 422 patients from centres of the Spanish Network on Mastocytosis (REMA), we evaluated previously identified, independent prognostic features for prognostic effect on PFS and OS by multivariable analysis, and designed a global prognostic score for mastocytosis (GPSM) aimed at predicting PFS (GPSM-PFS) and OS (GPSM-OS) by including only those variables that showed independent prognostic value (p<0·05). The GPSM scores were validated in an independent cohort of 853 patients from centres in Europe and the USA, and compared with pre-existing risk models in the total patient series (n=1275), with use of Harrells' concordance index (C-index) as a readout of the ability of each model to risk-stratify patients according to survival outcomes. FINDINGS: Our GPSM-PFS and GPSM-OS models were based on unique combinations of independent prognostic factors for PFS (platelet count ≤100 × 109 cells per L, serum ß2-microglobulin ≥2·5 µg/mL, and serum baseline tryptase ≥125 µg/L) and OS (haemoglobin ≤110 g/L, serum alkaline phosphatase ≥140 IU/L, and at least one mutation in SRSF2, ASXL1, RUNX1, or DNMT3A). The models showed clear discrimination between low-risk and high-risk patients in terms of worse PFS and OS prognoses in the discovery and validation cohorts, and further discrimination of intermediate-risk patients. The GPSM-PFS score was an accurate predictor of PFS in systemic mastocytosis (C-index 0·90 [95% CI 0·87-0·93], vs values ranging from 0·85 to 0·88 for pre-existing models), particularly in non-advanced systemic mastocytosis (C-index 0·85 [0·76-0·92], within the range for pre-existing models of 0·80 to 0·93). Additionally, the GPSM-OS score was able to accurately predict OS in the entire cohort (C-index 0·92 [0·89-0·94], vs 0·67 to 0·90 for pre-existing models), and showed some capacity to predict OS in advanced systemic mastocytosis (C-index 0·72 [0·66-0·78], vs 0·64 to 0·73 for pre-existing models). INTERPRETATION: All evaluated risk classifications predicted survival outcomes in systemic mastocytosis. The REMA-PFS and GPSM-PFS models for PFS, and the International Prognostic Scoring System for advanced systemic mastocytosis and GPSM-OS model for OS emerged as the most accurate models, indicating that robust prognostication might be prospectively achieved on the basis of biomarkers that are accessible in diagnostic laboratories worldwide. FUNDING: Carlos III Health Institute, European Regional Development Fund, Spanish Association of Mastocytosis and Related Diseases, Rare Diseases Strategy of the Spanish National Health System, Junta of Castile and León, Charles and Ann Johnson Foundation, Stanford Cancer Institute Innovation Fund, Austrian Science Fund.

Reduced graphene oxide membranes in ocular regenerative medicine.

Biological membranes are currently used in Ophthalmology in order to treat different ocular disorders. These membranes have different properties such as cellular biocompatibility and promoting wound healing. Moreover, intrinsic antimicrobial properties could also be desirable because it would allow their use reducing the risk of infections. Graphene and its derivatives are promising biomaterials that already proved their bactericidal effect. However, their clinical use is limited due to the controversial results regarding their toxicity. In this work, we have developed and characterized a reduced graphene oxide membrane (rGOM) for its use in ocular Regenerative Medicine, and studied its in vitro and in vivo biocompatibility and genotoxicity with different types of human ocular cells. We proved that rGOM allowed the growth of different ocular cells without inducing in vitro or in vivo cytotoxicity or genotoxicity in the short-term. These results indicate that rGOM may be a promising candidate in Regenerative Medicine for the treatment of different ocular pathologies.

Development of an in-house reconstructed human epidermis model as an alternative method in skin corrosion assessment.

Defining the corrosive properties of chemical products generally involves the use of animal models for human health safety assessment. However, a few alternatives to animal experimentation are currently internationally accepted in order to reduce animal suffering. One of these alternatives makes use of in vitro reconstructed human epidermis (RhE) models and predicts corrosive potential based on the evaluation of cell viability after topical exposure. These models rely on its similarity to human skin, both functional and histological, and are currently worldwide marketed by a few private companies. In this manuscript, we describe the fundamentals of the production of a Do It Yourself (DIY) RhE model, and the operating procedures for the assessment of skin corrosion based on the guidelines proposed for the development of new alternative methods for skin corrosion. Our results indicate that the DIY-RhE model resembles the anatomy of the normal human epidermis as seen by immunohistochemical analysis. Moreover, barrier properties of DIY-RhE were assessed by the measure of Transepithelial Electrical Resistance. Applicability of DIY-RhE for the assessment of skin corrosion was evaluated by measuring cell viability after topical exposure of twelve reference chemicals for 3 and 60 min. Predictive performance resulted in 100% sensitivity, 100% specificity and 100% accuracy matching current requirements for new RhE models proposed for the discrimination of corrosives and non-corrosives.

From exotic to invasive in record time: The extreme impact of Rugulopteryx okamurae (Dictyotales, Ochrophyta) in the strait of Gibraltar.

In 2015, the exotic seaweed Rugulopteryx okamurae was detected for the first time on the south side of the Strait of Gibraltar, in Ceuta (northern Africa). This highly sensitive area is ideal for monitoring local environmental impacts arising from global warming, as well as the intrusion of alien species. Within one year, R. okamurae became an invasive species with an overflowing competitive capacity and growth. In 2015, more than 5000 tons of upstream biomass was extracted from beaches in Ceuta, and it has since spread irrepressibly on rocky illuminated bottoms of the subtidal zone to a maximum observed depth of 40 m. The highest coverage (80-90%) of R. okamurae in Ceuta was observed between 10 and 20 m depth in illuminated habitats, where it was having a severe impact on local benthic communities which were displaced. Between 5 and 30 m depth, coverage of R. okamurae exceeded 70% over a wide variety of substrate types. A submarine sentinel sessile bioindicators permanent quadrats (SBPQ) station installed in 2013 on poorly lit, vertical, and shady substrate in the El Estrecho Natural Park, on the north side of the Strait of Gibraltar (Tarifa), detected the presence of R. okamurae in July 2016 and recorded the subsequent increase in coverage. These findings reveal the useful role of this type of monitoring SBPQ sentinel station for the detection of impacts and exotic species in marine protected areas, and for the monitoring of global warming based on indicator species. We conclude that the catastrophic bloom of R. okamurae exhibited an initial geographical expansion (2015-2017) to the northern coastal area of the Strait of Gibraltar (Tarifa-Gibraltar) and subsequent extension in the south of the Iberian Peninsula, towards the Atlantic coast (2018) and the Mediterranean coast (2019). This bloom could have been associated with the temperature peak in July 2015 and was thus possibly linked to global warming.

[Sex-related differences in patients with ST-segment elevation myocardial infarction]. / Diferencias relacionadas al sexo en pacientes con infarto agudo de Miocardio ST Elevado.

Objective: To determine the epidemiological characteristics, location of the infarction, type and times of reperfusion, as well as in-hospital adverse events, distributed by sex in patients with ST-segment elevation myocardial infarction (STEMI) in Peru. Methods: It is a sub-analysis of the PEruvian Registry of ST-segment Elevation Myocardial Infarction (PERSTEMI), which was an observational, prospective and multicenter study about patients over 18 years-old, who were hospitalized for ST-segment elevation myocardial infarction. Epidemiological and clinical characteristics, management and in-hospital adverse events were compared according to sex. Results: 396 patients were studied, 20.9% were female, with a predominance of octogenarian population over men. High blood pressure was the most frequent risk factor in women (74.7 Vs. 50%, p = 0.001); as well as atypical clinical manifestations such as dyspnea (40.9 Vs. 27.1%, p = 0.012) and syncope (10.8 vs. 3.8%, p = 0.017). On the other hand, the inferior wall myocardial infarction was more frequent in women (51.8 vs. 38.98%). There were no significant differences regarding the reperfusion therapy used (Fibrinolysis, primary PCI, PCI in general); as well as in times of ischemia (6 vs. 5.6 hours, p = 0.456), reperfusion times and hospital stay between both sexes. However, the female sex presented higher in-hospital mortality (21.6 vs. 7%, p = 0.001), mechanical complications (8.4 vs. 1.9%, p = 0.008), cardiogenic shock (15.6 vs. 9.5%, p= 0.087) and heart failure (33.7 vs. 24.9%, p = 0.072). Conclusions: STEMI in females presents at significantly older age compared to males and is associated with higher in-hospital mortality and mechanical complications.

Leiomiosarcoma de la vena cava superior con extensión a las cavidades cardíacas derechas / Leiomyosarcoma of the superior vena cava with extension to the right heart cavities

RESUMEN Fundamento: el leiomiosarcoma de la vena cava superior es una enfermedad rara y más cuando se extiende a las cavidades cardíacas. Objetivo: presentar una paciente con leiomiosarcoma de la vena cava superior que se extendió de forma intraluminal a las cavidades derechas del corazón lo que provocó obstrucción de las mismas y choque cardiogénico. Caso clínico: paciente de 45 años de edad, blanca, femenina sin antecedentes mórbidos de salud, la cual presentó enrojecimiento del rostro y agotamiento de las extremidades al peinarse. Se le realiza tomografía axial computarizada donde se identificó una lesión sugestiva de trombosis, se decide su traslado hacia un centro especializado, se llega a la conclusión de que la paciente era portadora de una lesión tumoral no trombótica, la cual resultó ser benigna en una biopsia realizada por lo cual se decide seguimiento. La paciente reingresa en estado de shock cardiogénico por progresión de la enfermedad y se decide su tratamiento quirúrgico de emergencia, durante la cirugía fallece. Conclusiones: el leiomiosarcoma de la vena cava superior es una enfermedad rara, existen pocos reportes en la literatura sobre este padecimiento. Se presentó un caso en el cual el tumor se extendía de forma intraluminal a las cavidades cardíacas derechas (aurícula y ventrículo).

ABTRACT Background: the leiomyosarcoma of the superior cava vein is a rare illness and more when it extends to the cardiac cavities. Objective: to present to the medical community a female patient with leiomyosarcoma of the superior cava vein that extended intraluminal form to the right cavities of the heart causing obstruction and cardiogenic shock. Clinical case: a 45-year-old white female patient with no morbid health history, who presented redness of the face and exhaustion of the extremities when combing. A computerized axial tomography was performed where a lesion suggestive of thrombosis was identified. It was decided to transfer her to a specialized center, in which it is concluded that the patient was a carrier of a non-thrombotic tumor lesion, which turned out to be benign in a biopsy done for which follow-up is decided. The patient reenters in a state of cardiogenic shock due to progression of the disease, which is why her emergency surgical treatment is decided and die during surgery. Conclusions: the leiomyosarcoma of the superior vena cava is a rare illness, with few reports in the literature. A case in which the tumor extended intraluminally to the right cardiac cavities (atrium and ventricle) is presented.

Leiomiosarcoma de la vena cava superior con extensión a las cavidades cardíacas derechas / Leiomyosarcoma of the superior vena cava with extension to the right heart cavities

Fundamento: el leiomiosarcoma de la vena cava superior es una enfermedad rara y más cuando se extiende a las cavidades cardíacas. Objetivo: presentar una paciente con leiomiosarcoma de la vena cava superior que se extendió de forma intraluminal a las cavidades derechas del corazón lo que provocó obstrucción de las mismas y choque cardiogénico.Caso clínico: paciente de 45 años de edad, blanca, femenina sin antecedentes mórbidos de salud, la cual presentó enrojecimiento del rostro y agotamiento de las extremidades al peinarse. Se le realiza tomografía axial computarizada donde se identificó una lesión sugestiva de trombosis, se decide su traslado hacia un centro especializado, se llega a la conclusión de que la paciente era portadora de una lesión tumoral no trombótica, la cual resultó ser benigna en una biopsia realizada por lo cual se decide seguimiento. La paciente reingresa en estado de shock cardiogénico por progresión de la enfermedad y se decide su tratamiento quirúrgico de emergencia, durante la cirugía fallece. Conclusiones: el leiomiosarcoma de la vena cava superior es una enfermedad rara, existen pocos reportes en la literatura sobre este padecimiento. Se presentó un caso en el cual el tumor se extendía de forma intraluminal a las cavidades cardíacas derechas (aurícula y ventrículo)(AU)

Background: the leiomyosarcoma of the superior cava vein is a rare illness and more when it extends to the cardiac cavities. Objective: to present to the medical community a female patient with leiomyosarcoma of the superior cava vein that extended intraluminal form to the right cavities of the heart causing obstruction and cardiogenic shock. Clinical case: a 45-year-old white female patient with no morbid health history, who presented redness of the face and exhaustion of the extremities when combing. A computerized axial tomography was performed where a lesion suggestive of thrombosis was identified. It was decided to transfer her to a specialized center, in which it is concluded that the patient was a carrier of a non-thrombotic tumor lesion, which turned out to be benign in a biopsy done for which follow-up is decided. The patient reenters in a state of cardiogenic shock due to progression of the disease, which is why her emergency surgical treatment is decided and die during surgery.Conclusions: the leiomyosarcoma of the superior vena cava is a rare illness, with few reports in the literature. A case in which the tumor extended intraluminally to the right cardiac cavities (atrium and ventricle) is presented(AU)

Resultados del tratamiento con pleurostomía en pacientes con neumotórax espontáneo / Outcomes of Pleurostomy Treatment in Patients with Spontaneous Pneumothorax

RESUMEN Introducción: La presencia de aire dentro de la cavidad pleural es definida como neumotórax. El tratamiento quirúrgico inicial es la pleurostomía, que puede acarrear complicaciones, relacionadas con varios factores, entre los cuales se encuentra el diámetro de la sonda intratorácica utilizada. Objetivo: Evaluar los resultados del tratamiento con pleurostomía en pacientes con neumotórax espontáneo en el Hospital Universitario Manuel Ascunce Domenech. Método: Se realizó un estudio descriptivo longitudinal retrospectivo desde septiembre de 2012 hasta septiembre de 2017. Se estudiaron 63 pacientes afectos de neumotórax espontáneos que recibieron pleurostomía como tratamiento inicial. Resultados: Los neumotórax espontáneos primarios representaron 56 por ciento de los casos. Del total de pacientes, 82 por ciento eran fumadores. En todos los pacientes el síntoma predominante fue el dolor. Las complicaciones fueron más frecuentes con el uso de sondas pleurales de menor diámetro (86 por ciento). Conclusiones: El neumotórax espontáneo primario fue el de mayor frecuencia. Las causas predominantes en el neumotórax secundario fueron las bulas de enfisema y la enfermedad pulmonar obstructiva crónica. En la totalidad de los casos, estuvo presente algunos de los síntomas del síndrome pleural con predominancia absoluta del dolor. El mayor número de complicaciones se presentó en pacientes fumadores(AU)

ABSTRACT Introduction: The presence of air within the pleural cavity is defined as pneumothorax. The initial surgical treatment is pleurostomy, which can lead to complications associated with several factors, among which is the diameter of the intrathoracic probe that is used. Objective: To evaluate the outcomes of the treatment with pleurostomy in patients with spontaneous pneumothorax at Manuel Ascunce Domenech University Hospital. Method: A retrospective, longitudinal, descriptive study was conducted from September 2012 to September 2017. We studied 63 patients affected by spontaneous pneumothorax who received pleurostomy as initial treatment. Results: Primary spontaneous pneumothorax accounted for 56 percent of the cases. From the total amount of patients, 82 percent were smokers. In all patients, the predominant symptom was pain. Complications were more frequent with the use of pleural probes of smaller diameter (86 percent). The primary spontaneous pneumothorax was the most frequent. The predominant causes of secondary pneumothorax were bullous emphysema and chronic obstructive pulmonary disease. In all the cases, some of the symptoms of pleural syndrome with absolute predominance of pain were present. The greatest number of complications occurred in smoking patients. Conclusions: Pleurostomy, with the use of the drainage catheter, is the initial treatment for all patients with spontaneous pneumothorax in our hospital, regardless of the diameter of the probe to be used according to the type of pneumothorax (primary or secondary)(AU)

Análisis de los resultados de la evaluación multidisciplinaria de pacientes con cáncer pulmonar / Outcome Analysis of the Multidisciplinary Evaluation of Patients with Lung Cancer

RESUMEN Introducción: El cáncer de pulmón representa una gran carga de enfermedad a nivel global. La centralización de la atención de los pacientes para el diagnóstico y tratamiento añade un salto de calidad en la atención sanitaria. Objetivo: Evaluar los resultados de la consulta multidisciplinaria de cáncer pulmonar en la provincia de Camagüey. Métodos: Se realizó un estudio observacional analítico retrospectivo desde noviembre de 2015 hasta febrero de 2017. El universo quedó conformado por 182 pacientes evaluados en la consulta multidisciplinaria con cáncer pulmonar. La muestra, la cual fue de tipo probabilística, la constituyeron los 182 pacientes diagnosticados de cáncer pulmonar, coincidiendo con el universo. Se trabajó con una población objetiva conformada por todos los pacientes adultos que acudieron a la consulta antes mencionada y que fueron diagnosticados de cáncer pulmonar en la sistemática diagnóstica. Resultados: Prevaleció el sexo masculino y el grupo de edad entre 60 y 69 años. Todos los pacientes tenían relación con el hábito de fumar, y al menos, una radiografía de tórax al momento de la primera evaluación. El síntoma fundamental fue la tos. Más de la mitad de los pacientes acudieron antes de 60 días de comienzo de los síntomas, y recibieron el diagnóstico e iniciaron el tratamiento antes del mes. El adenocarcinoma fue el tipo histológico más frecuente, como la localización tumoral periférica, el estado funcional se deterioró en relación con la etapa clínica y el tratamiento quirúrgico fue el más indicado. Conclusiones: La atención multidisciplinaria en pacientes con cáncer pulmonar se ha convertido en el estándar de cuidado. La centralización de la atención, así como la aplicación de una vía clínica optimiza el uso de la tecnología disponible adecuada a cada caso en particular(AU)

ABSTRACT Introduction: Lung cancer represents a great burden of disease worldwide. Patient care centralization for diagnosis and treatment adds a leap in the quality of health care. Objective: To evaluate the results of the multidisciplinary consultation of lung cancer in the province of Camagüey. Methods: A retrospective, analytical, observational study was conducted from November 2015 to February 2017. The study population consisted of 182 patients with lung cancer who were evaluated in the multidisciplinary consultation. The sample, which was probabilistic, was made up of 182 patients diagnosed with lung cancer, coinciding with the population. We worked with an objective population made up of all the adult patients who attended the aforementioned consultation and who were diagnosed with lung cancer in the diagnostic systematics. Results: There was a predominance of the male sex and the age group between 60 and 69 years old. All the patients were associated with the smoking habit, and had at least one chest radiograph at the time of the first evaluation. The main symptom was coughing. More than half of the patients came before 60 days after the onset of symptoms, were diagnosed and started treatment before the month. The adenocarcinoma was the most frequent histological type, as the peripheral tumor location. The functional state was deteriorated in relation to the clinical stage and the surgical treatment was the most indicated. Conclusions: Multidisciplinary care in patients with lung cancer has become the standard of care. The centralization of care, as well as the application of a clinical approach, optimizes the use of available technology appropriate to each particular case(AU)

QobuR - A new in vitro human corneal epithelial model for preclinical drug screening.

A new in vitro human corneal epithelial model (QobuR) obtained from normal limbal tissue has been developed to study ocular irritancy of different ophthalmic compounded drugs. Phenotypical characterization and trans-epithelial electrical resistance (TEER) of QobuR revealed essential similarities compared with a native human cornea, displaying functional markers and TEER values near 1500 Ωcm2 at day 7th of cellular differentiation. Using this model, ocular irritancy and barrier integrity alterations were evaluated using MTT reaction and variations in TEER. We found that some of the Non-Irritant products evaluated still damage the corneal epithelial integrity and current protocols for ocular irritancy should therefore include a barrier integrity evaluation. Moreover, in order to comprehensively evaluate corneal permeability of the active ingredients, we propose the use of QobuR as an all-in-one alternative method for evaluating ocular irritancy, barrier disruptions and permeability rates of topically applied ocular drugs to improve current in vitro drug testing procedures.

El cáncer del pulmón: algunas consideraciones epidemiológicas, del diagnóstico y el tratamiento / Lung cancer: some epidemiologic, diagnoses and treatment considerations

Fundamento: el cáncer es una de las causas principales de muerte alrededor del mundo. En el año 2012 hubo 14 millones de casos nuevos, así como 8,2 millones de muertes relacionadas. Dentro de todas las localizaciones del cáncer, es el pulmón el de mayor incidencia y mortalidad para el hombre y en el caso de la mujer ocupa el segundo lugar. Objetivos: realizar una actualización en aspectos epidemiológicos, del diagnóstico, así como del tratamiento del cáncer pulmonar a nivel global, regional y local.Métodos: se realizó una búsqueda en las bases de datos Pub Med, SciELO, Medline, Cochrane, Lilacs, mediante EndNote y Clinical Key, en un período desde el primero de septiembre al 15 de diciembre de 2017. Se emplearon las palabras claves: lung cancer, epidemiology, diagnostic, treatment, screening. Se realizó una revisión bibliográfica de un total 302 artículos de ellos se utilizaron 40 citas la mayoría de ellas de los últimos tres y cinco años. Se consideraron para la revisión, artículos originales, revisiones a texto completo, así como artículos de opinión. Desarrollo: se abordaron aspectos del cáncer pulmonar relacionados con estadísticas globales, regionales y locales, así como de los indicadores de impacto, aspectos relacionados con el diagnóstico precoz a través del tamizaje y elementos novedosos de ensayos clínicos relacionados con la aplicación de la vacuna CIMAvax-EGF. Conclusiones: con el elevado aporte del cáncer de pulmón a la morbilidad y mortalidad general en Cuba y en particular en la provincia de Camagüey, así como el consecuente impacto negativo en la duración y calidad de vida de la población, se considera pertinente y necesario el diseño de un programa integral asistencial organizacional para atender a pacientes con esta terrible y letal enfermedad(AU)

Background: cancer is one of the leading causes of death around the world. In 2012, there were 14 million of new cases, as well as 8.2 million related deaths. Within all cancer locations, the lung is the one with the highest incidence and mortality for men and in the case of women, it occupies the second place. Objectives: to carry out an update on epidemiological aspects of diagnosis, as well as the treatment of lung cancer at a global, regional and local level. Methods: a search on Pub Med, SciELO, Medline, Cochrane, Lilacs databases using EndNote and Clinical Key was carried out, from September 1 to December 15, 2017. The following keywords were used: lung cancer, epidemiology, diagnostic, treatment, screening. A bibliographic review of a total of 302 articles was made, of them 40 citations were used, most of them from the last three and five years. Original articles, full-text reviews, as well as opinion articles were considered for the review. Development: aspects of lung cancer, related to global, regional and local statistics, as well as impact indicators, aspects related to early diagnosis through screening and novel elements of clinical trials related to the application of the vaccine CIMAvax-EGF were addressed. Conclusions: with the high contribution of lung cancer to morbidity and general mortality in Cuba and in particular in Camagüey province, as well the negative consequent impact on the duration and quality of life of the population, it is considered necessary to design a comprehensive organizational assistance program to care for patients with this terrible and lethal disease(AU)