Carcinoma basocelular de la piel cabelluda tratado con HeberFERON. Seguimiento clínico, ecográfico e histopatológico

Fundamento: El carcinoma basocelular es infrecuente en la piel cabelluda. Es un tumor de invasión local y crecimiento lento, puede ser agresivo, destruir tejidos vecinos, causar ulceración e invadir en profundidad cartílago y hueso. Objetivo: Evaluar los resultados de la aplicación del HeberFERON y el seguimiento con ecografía cutánea en pacientes con carcinoma basocelular en la piel cabelluda. Metodología: Se realizó un estudio observacional, descriptivo y longitudinal en una serie de casos con diagnóstico de carcinoma basocelular de la piel cabelluda en el Policlínico Centro de la ciudad Sancti Spíritus, durante el período de 10 de julio del 2018 a 29 de julio del 2022. Se incluyeron 6 casos. Las variables estudiadas fueron la respuesta al tratamiento mediante la clínica, la ecografía cutánea e histopatología y presencia de eventos adversos. Resultados: Predominó el sexo masculino, subtipo histológico sólido, subtipo clínico nódulo ulcerativo, tamaño del tumor mayor de 30 mm y tiempo de evolución de más de 12 meses; la respuesta al tratamiento en la mayoría de los casos fue parcial. Los eventos adversos fueron dolor y ardor en el sitio de inyección, fiebre, edema y eritema perilesional. Conclusiones: El HeberFERON resultó de utilidad en los pacientes con carcinoma basocelular del cuero cabelludo ya que redujo el tumor en unos casos y en otros lo eliminó. La ecografía permitió la evaluación en tiempo real de la neoplasia; los eventos adversos más frecuentes fueron la fiebre y el dolor en el sitio de inyección, a pesar de ello ningún paciente abandonó el tratamiento.

Background: Basal cell carcinoma is uncommon in the scalp. It is a slow-growing locally invasive tumor, it can be aggressive in destroying neighboring tissues, cause ulceration and invade deep into the cartilage and bone. Objective: To evaluate the results of HeberFERON application and follow-up with cutaneous echographical in patients with scalp basal cell carcinoma. Methodology: An observational, descriptive and longitudinal study was conducted in a series of cases diagnosed with scalp basal cell carcinoma at the Center Polyclinic in Sancti Spíritus city during the period from July 10, 2018 to July 29, 2022. Six clinical cases were included. The studied variables were the answer to the treatment by clinical, cutaneous echographical and histopathology and the presence of adverse events. Results: Male sex predominated, solid histologic subtype, clinical subtype ulcerative nodule, tumor size greater than 30 mm and evolution time of over 12 months; the treatment response in most cases was partial; adverse events were pain and burning at the injection site, fever, edema and perilesional erythema. Conclusion: It was observed that in patients with scalp basal cell carcinoma, the HeberFERON treatment reduced in some cases and eliminated the tumor in others. Echography allowed real-time evaluation of the neoplasm, fever and pain at the injection site were the most frequent adverse events. In spite of this, none of the patients abandoned the therapy.

HeberFERON en el tratamiento del carcinoma basoescamoso / HeberFERON in Treating Basosquamous Carcinoma

Introducción: El carcinoma basoescamoso es un subtipo agresivo de carcinoma basocelular compuesto por células basaloides y áreas de células escamosas con una zona de transición intermedia, con tendencia a la recurrencia y metástasis. Objetivo: Describir el caso clínico de una paciente con un carcinoma basoescamoso en región temporal cerca del canto externo del ojo izquierdo. Presentación de caso: Se presentó el caso de una paciente con un carcinoma basoescamoso en región temporal cerca del canto externo del ojo izquierdo de 30 mm de diámetro. Se aplicó HeberFERON con respuesta completa al eliminar el tumor. Conclusiones: El HeberFERON es una opción no quirúrgica de tratamiento que puede ser usada en el carcinoma basoescamoso de localización facial que por su tamaño puede provocar mutilaciones o deformidades en esta zona(AU)

Introduction: Basal squamous cell carcinoma is an aggressive subtype of basal cell carcinoma composed of basaloid cells and areas of squamous cells with an intermediate transition zone, with a tendency to recur and metastasize. Objective: To describe the clinical case of a patient with a basal squamous cell carcinoma in the temporal region near the external canthus of the left eye. Case report: This paper reports a case of a female patient with a basal squamous cell carcinoma in the temporal region near the external canthus of her left eye with 30 mm diameter. HeberFERON was used with complete response when eliminating the tumor. Conclusions: HeberFERON is a non-surgical treatment option that can be used in facial basal squamous cell carcinoma that, due to its size, can cause mutilations or deformities in this area(AU)

HeberFERON en el tratamiento de pacientes con carcinoma basocelular en zona de alto riesgo / HeberFERON in the Treatment of Patients with Basal Cell Carcinoma on a High-Risk Zone

Introducción: El carcinoma basocelular es un tumor de invasión local de crecimiento; se origina en las células epidérmicas de los folículos pilosos o las células basales de la epidermis, cuando se localizan en zona de alto riesgo en la cara tienen un mayor índice de recurrencia tumoral y de invasión a estructuras adyacentes y subyacentes. Objetivo: Evaluar los resultados de la aplicación del HeberFERON en pacientes con carcinoma basocelular en zona de alto riesgo. Métodos: Se realizó un estudio observacional, descriptivo y prospectivo en pacientes con diagnóstico clínico, dermatoscópico e histopatológico de carcinoma basocelular en zona de alto riesgo, tratados con HeberFERON en la consulta del Policlínico Centro de Sancti Spíritus desde el 12 de enero de 2016 hasta el 25 de marzo de 2022. La muestra quedó conformada por 62 pacientes Las principales variables estudiadas fueron la respuesta al tratamiento y los eventos adversos. Resultados: Predominó el sexo masculino, el área urbana, fototipocutáneo III y la edad mayor de 40 años. La localización más frecuente fue la nasal; el subtipo clínico el nódulo ulcerativo; el histológico, el sólido; el tumor primitivo y menor de 2 cm; la respuesta al tratamiento fue completa en la mayoría de los pacientes. Los eventos adversos más comunes fueron dolor y ardor en el sitio de inyección, edema y eritema perilesional, fiebre y cefalea. Conclusiones: La mayoría de los pacientes tratados con HeberFERON tuvieron una respuesta completa, los eventos adversos fueron los descritos en la literatura por el uso de interferones, sin cambio en la actitud farmacológica(AU)

Introduction: Basal cell carcinoma is a growing and locally invasive tumor; it originates in the epidermal cells of hair follicles or the basal cells of the epidermis. When located in a high-risk facial zone, they present a higher rate of tumor recurrence and invasion to adjacent and underlying structures. Objective: To evaluate the results of HeberFERON application in patients with basal cell carcinoma on a high-risk zone. Methods: An observational, descriptive and prospective study was conducted in patients with a clinical, dermatoscopic and histopathological diagnosis of basal cell carcinoma on a high-risk zone, treated with HeberFERON in the consultation of Policlínico Centro of Sancti Spíritus, from January 12, 2016 to March 25, 2022. The sample was made up of 62 patients. The main variables studied were response to treatment and adverse events. Results: There was a predominance of the male sex, the urban area, skin phototype III and age over 40 years. The most frequent localization was nasal; the clinical subtype, ulcerative nodule; the histological subtype, solid. The response to treatment was complete in most patients. The most common adverse events were pain and burning at the injection site, perilesional erythema and edema, fever and headache. Conclusions: Most patients treated with HeberFERON had a complete response; the adverse events were those described in the literature due to the use of interferons, with no change in pharmacological behavior(AU)

HeberFERON en el tratamiento de pacientes con carcinoma basocelular de la oreja / HeberFERON in the treatment of patients with basal cell carcinoma of the ear

Fundamento: El carcinoma basocelular de la región auricular es considerado uno de los más agresivos y con peor pronóstico, suele ser destructivo y mutilante por lo que el tratamiento conservador, como es el uso de los interferones, es importante en la práctica médica habitual. Objetivo: Evaluar los resultados de la aplicación del HeberFERON en una serie de pacientes con carcinoma basocelular en la región auricular. Metodología: Se realizó un estudio observacional, descriptivo y longitudinal en una serie de casos con diagnóstico clínico, dermatoscópico e histopatológico de carcinoma basocelular de la oreja que recibieron tratamiento con HeberFERON en el Policlínico Centro de la ciudad Sancti Spíritus, durante el período del 20 de febrero de 2017 a 20 de diciembre de 2022. En total se incluyeron 29 pacientes. Se realizó una evaluación inicial, durante y 16 semanas después del tratamiento; se les inyectó 10.5 UI de HeberFERON 3 veces por semana perilesional e intradérmico hasta completar 9 dosis. Las variables fueron la respuesta al tratamiento y presencia o no de eventos adversos. Resultados: Predominó el sexo masculino, la localización en la concha de la oreja, subtipo clínico nódulo ulcerativo y el histológico sólido, con respuesta completa en la mayoría de los pacientes. Como eventos adversos más comunes se presentaron dolor en el sitio de inyección, fiebre, edema y eritema perilesional. Conclusiones: La respuesta al tratamiento fue favorable en la mayoría de los pacientes y los eventos adversos que se observaron fueron los descritos en la literatura sin cambio en la actitud farmacológica.

Background: Basal cell carcinoma of the auricular region is one of the most aggressive cancers and with the worst prognosis, is usually destructive and mutilating, therefore conservative treatment, such as the use of interferons, is important in routine medical practice. Objective: To evaluate the results of HeberFERON application in a series of patients with basal cell carcinoma in the auricular region. Methodology: An observational, descriptive and longitudinal study was conducted on a series of cases with clinical, dermoscopic and histopathologic diagnosis of basal cell carcinoma of the ear treated with HeberFERON at the Center Polyclinic in Sancti Spíritus city, during the period from February 20, 2017 through December 20, 2022. A total of 29 patients were included in the study. An evaluation was conducted at the start of treatment, during treatment, and 16 weeks after treatment; the patients were treated with 10.5 IU of HeberFERON by perilesional and intradermal injections three times a week until completing nine doses. The variables were the response to the treatment and the presence or absence of any adverse events. Results: The male sex predominated, location in the ear turbinate, clinical subtype ulcerative nodule and solid histologic subtype, with a complete response in the majority of patients. The most common adverse events were injection site pain, fever, edema, and perilesional erythema. Conclusions: The response to treatment was favorable in most patients, and the adverse events observed were those described in the literature, with no change in pharmacologic attitude.

Tratamiento con HeberFERON( en el carcinoma basal palpebral

El carcinoma basal palpebral representa un 90 % de los tumores malignos oculares con una alta morbilidad. Su incidencia tiene un comportamiento diferente en las distintas partes del mundo y, por lo general, aumenta con la edad. El diagnóstico positivo se realiza por la evaluación histológica de la muestra mediante biopsia escisional. El tratamiento ideal es el quirúrgico, aunque existen otras opciones de tratamiento. El no quirúrgico tiene como objetivo la eliminación del tumor, así como evitar las complicaciones o las secuelas funcionales y estéticas por la cirugía. Se reconocen numerosas opciones dentro de la modalidad terapéutica no quirúrgica; imiquimod, 5-fluorouracilo, inhibidores de la vía de Hedgehog y los interferones. Diversos estudios han demostrado la utilidad de los interferones en monoterapia o como terapia combinada, en pacientes no susceptibles de actuaciones quirúrgicas. Por esta razón, se decidió revisar la literatura científica actual sobre la eficacia y seguridad del HeberFERON® en el tratamiento del carcinoma basal palpebral. Se realizó una búsqueda actualizada teniendo en cuenta los descriptores correspondientes a las palabras clave relacionadas con la temática a investigar, en las bases de datos bibliográficas Medline (buscador PubMed), SciELO, Ebsco, Clinical Key y en Google Académico. Se recuperaron 35 artículos que su contenido respondía al tema de estudio.

Palpebral basal carcinoma represents 90% of ocular malignant tumors with high morbidity. Its incidence has a different behavior in different parts of the world and generally increases with age. Positive diagnosis is made by histological evaluation of the specimen by excisional biopsy. The ideal treatment is surgical, although other treatment options are available. Non-surgical treatment is aimed at eliminating the tumor, as well as avoiding the complications or functional and esthetic sequelae of surgery. Numerous options are recognized within the non-surgical therapeutic modality; imiquimod, 5-fluorouracil, Hedgehog pathway inhibitors and interferons. Several studies have demonstrated the usefulness of interferons in monotherapy or as combination therapy in patients not amenable to surgery. For this reason, it was decided to review the current scientific literature on the efficacy and safety of HeberFERON® in the treatment of palpebral basal cell carcinoma. An updated search was carried out taking into account the descriptors corresponding to the key words related to the subject under investigation, in the bibliographic databases Medline (PubMed search engine), SciELO, Ebsco, Clinical Key and Google Scholar. Thirty-five articles were retrieved whose content corresponded to the subject of the study.

Type 1–type 2 interferon imbalance in dry eye disease

Purpose: Dry eye disease (DED) is characterized by altered ocular surface proinflammatory and antiinflammatory factors. Interferons (IFNs) are a class of pleiotropic cytokines well known for their antimicrobial, inflammatory, and immunomodulatory roles. Hence, this study investigates the ocular surface expression of different types of IFNs in patients with DED. Methods: The cross?sectional, observational study included patients with DED and normal subjects. Conjunctival impression cytology (CIC) samples were obtained from the study subjects (controls, n = 7; DED, n = 8). The mRNA expression levels of type 1 IFN (IFN?, IFN?), type 2 IFN (IFN?), and type 3 IFN (IFN?1, IFN?2, IFN?3) were measured by quantitative PCR (polymerase chain reaction) in CIC samples. IFN? and IFN? expression under hyperosmotic stress was also studied in human corneal epithelial cells (HCECs) in vitro. Results: The mRNA expression levels of IFN? and IFN? were significantly lower and that of IFN? was significantly higher in DED patients compared to healthy controls. The mRNA levels of IFN?, IFN?, and IFN? were significantly lower compared to IFN? in DED patients. An inverse association between tonicity?responsive enhancer?binding protein (TonEBP; hyperosmotic stress maker) and IFN? or IFN? expression and a positive association between TonEBP and IFN? expression was observed in CIC samples. The expression of IFN? was lower than IFN? in HCECs undergoing hyperosmotic stress compared to HCECs without the stress. Conclusion: The presence of an imbalance between type 1 and type 2 IFNs in DED patients suggests newer pathogenic processes in DED, plausible ocular surface infection susceptibility in DED patients, and potential therapeutic targets in the management of DED

Modulation of type I interferon signaling by natural products in the treatment of immune-related diseases / 中国天然药物

Type I interferon (IFN) is considered as a bridge between innate and adaptive immunity. Proper activation or inhibition of type I IFN signaling is essential for host defense against pathogen invasion, tumor cell proliferation, and overactive immune responses. Due to intricate and diverse chemical structures, natural products and their derivatives have become an invaluable source inspiring innovative drug discovery. In addition, some natural products have been applied in clinical practice for infection, cancer, and autoimmunity over thousands of years and their promising curative effects and safety have been well-accepted. However, whether these natural products are primarily targeting type I IFN signaling and specific molecular targets involved are not fully elucidated. In the current review, we thoroughly summarize recent advances in the pharmacology researches of natural products for their type I IFN activity, including both agonism/activation and antagonism/inhibition, and their potential application as therapies. Furthermore, the source and chemical nature of natural products with type I IFN activity are highlighted and their specific molecular targets in the type I IFN pathway and mode of action are classified. In conclusion, natural products possessing type I IFN activity represent promising therapeutic strategies and have a bright prospect in the treatment of infection, cancer, and autoimmune diseases.

Clinical effects of pegylated interferon alfa-2b combined with nucleotide analogues therapy on HBV associated liver cancer / 国际外科学杂志

Objective:To evaluate the effects of pegylated interferon (Peg-IFN) alfa-2b combined with nucleotide analogues (NAs) on the recurrence of hepatitis B-related liver cancer after resection, and to explore the changes of HBsAg and HBV DNA in patients with chronic hepatitis B liver cancer during postoperative treatment.Methods:The prospective study was conducted. Clinical data of 43 patients with hepatitis B-related liver cancer who underwent radical resection treated in 900th Hospital of People′s Liberation Army were prospectively analyzed from January 2020 to December 2021. Among 43 patients, there were 39 males and 4 females, the age was 30-76 years. According to different treatment methods they were divided into two groups, the patients treated by Peg-IFN alfa-2b combined with NAs were devided into the IFN group( n=10), and those treated by NAs alone into the NAs group( n=33). Two-pair semi-quantitative were collected every 3 months after operation. The recurrence-free survival rate, recurrence time after 2 years in the two groups, the clearance rate and the negative rate of HBsAg and HBV DNA in the two groups. Peg-IFN alfa-2b was evaluated in improving the prognosis of hepatitis B-related liver cancer. The measurement data of normal distribution were expressed by mean±standard deviation ( ± s), and t-test was used for comparison between the two groups. Chi-square test was used for comparison between the two groups of count data. Repeated analysis of measurement variance was used for analysis HBsAg and HBV DNA changes of the interferon group overall survival time and recurrence-free surrival time of patients was estimated using Kaplan-Meier method and the difference between groups was assessed using Log-rank test. Results:HBsAg and HBV DNA: The HBsAg clearance rate at 24 weeks and that at 48 weeks in the IFN group were 24.6% and 59.0% respectively. The HBsAg negative rate at 48 weeks was 16.7%. The HBV DNA clearance rate at 24 weeks and that at 48 weeks were 33.9% and 53.8% respectively. The HBV DNA negative rate was 0 at 48 weeks. The levels of HBsAg and HBV DNA in the IFN group decreased gradually with time. There were statistically differences between the levels of HBsAg and HBV DNA at 0 weeks, 24 weeks and 48 weeks( P<0.05). The 2-year overall survival rates of IFN group and NAs group were 100% and 90.9% respectively. The 2-year recurrence-free survival rates were 90.0% and 63.6% respectively. There were no significant statistical differences in the overall survival rate and recurrence-free survival rate between the groups ( P>0.05). The postoperative recurrence time of the IFN group and the NAs group were (15.00±7.07) months and (5.78±3.39) months respectively. The difference between the two groups was statistically significant ( t=3.160, P<0.01). Conclusion:Long-term antiviral therapy of Peg-IFN alfa-2b combined with NAs can prolong the recurrence time of liver cancer, reduce the levels of HBsAg and HBV DNA in serum, and potentially improve the survival rate of the patients compared with therapy of NAs alone.

Interferon-related gene array in predicting the efficacy of interferon therapy in chronic hepatitis B / 生物医学工程学杂志

This study aims to clarify host factors of IFN treatment in the treatment of chronic hepatitis B (CHB) patients by screening the differentially expressed genes of IFN pathway CHB patients with different response to interferon (IFN) therapy. Three cases were randomly selected in IFN-responding CHB patients (Rs), non-responding CHB patients (NRs) and healthy participants, respectively. The human type I IFN response RT 2 profiler PCR array was used to detect the expression levels of IFN-related genes in peripheral blood monocytes (PBMCs) from healthy participants and CHB patients before and after Peg-IFN-α 2a treatment. The results showed that more differentially expressed genes appeared in Rs group than NRs group after IFN treatment. Comparing with healthy participants, IFNG, IL7R, IRF1, and IRF8 were downregulated in both Rs and NRs group before IFN treatment; CXCL10, IFIT1, and IFITM1 were upregulated in the Rs; IL13RA1 and IFI35 were upregulated in the NRs, while IFRD2, IL11RA, IL4R, IRF3, IRF4, PYHIN1, and ADAR were downregulated. The expression of IL15, IFI35 and IFI44 was downregulated by 4.09 ( t = 10.58, P < 0.001), 5.59 ( t = 3.37, P = 0.028) and 10.83 ( t = 2.8, P = 0.049) fold in the Rs group compared with the NRs group, respectively. In conclusion, IFN-response-related gene array is able to evaluate IFN treatment response by detecting IFN-related genes levels in PBMC. High expression of CXCL10, IFIT1 and IFITM1 before treatment may suggest satisfied IFN efficacy, while high expression of IL13RA1, IL15, IFI35 and IFI44 molecules and low expression of IFRD2, IL11RA, IL4R, IRF3, IRF4, PYHIN1 and ADAR molecules may be associated with poor IFN efficacy.

Tratamiento del carcinoma basocelular de la nariz con una combinación de interferones Alpha-2b y Gamma / Treatment of basal cell carcinoma of the nose with a combination of Interferon alpha-2b and gamma

Introducción: El carcinoma basocelular es una neoplasia maligna derivada de las células epidérmicas de los folículos pilosos o células no queratinizadas puede ser desfigurante y originar deformidades o pérdida de la función del órgano afectado, es más frecuente en zonas sobresalientes como la nariz. Objetivo: Describir los resultados de la aplicación de la combinación sinérgica de interferones alpha-2b y gamma en una serie de casos con carcinoma basocelular nasal. Material y métodos: Se realizó un estudio de serie de casos clínicos, se incluyeron 28 pacientes con diagnóstico clínico, dermatoscópico e histopatológico de carcinoma basocelular de la nariz que acudieron a consulta de dermatología del Policlínico Centro de Sancti Spíritus en el período de 17 de enero de 2016 a 28 de diciembre de 2021. Se realizó una evaluación inicial y otra final a las 16 semanas después del comienzo del tratamiento. Se administró 10,5 UI de HeberFERON, 3 veces por semana perilesional e intradérmica hasta completar 9 dosis. Las variables principales fueron la respuesta al tratamiento y presencia o no de evento adversos. Resultados: Predominó el sexo masculino, fototipocutáneo II, localización en el dorso y ala nasal, subtipo clínico nódulo ulcerativo y el histológico sólido. En la mayoría de los pacientes desapreció el tumor al culminar el esquema terapéutico. Como eventos adversos más comunes se presentaron dolor en el sitio de inyección, fiebre, edema y eritema perilesional. Conclusiones: La respuesta al tratamiento fue completa en la mayoría de los pacientes y los eventos adversos los descritos en la literatura sin cambios en la actitud farmacológica(AU)

Introduction: Basal cell carcinoma is a malignant neoplasm derived from epidermal cells of hair follicles or non-keratinized cells with a high potential for local destruction, which can be disfiguring and may invade the surrounding tissue, resulting in deformities or loss of function of the affected organ, being more frequent in protruding areas such as the nose. Objective: To describe the results of the application of the synergistic combination of interferon alpha-2b and gamma in a series of cases with nasal basal cell carcinoma. Material and Methods: An observational, descriptive and longitudinal study was carried out in a series of 28 clinical cases with basal cell carcinoma of the nose who attended the dermatology clinic of Policlínico Centro in Sancti Spiritus in the period from january 2016 to december 2021. Cases with a clinical, dermoscopic and histopathological diagnoses were included. An initial and a final evaluation at the end of the 16 weeks of treatment were carried out; also, 10,5 IU of HeberFERON was administered 3 times per week perilesional and intradermally until completing 9 doses. The main variables were response to treatment and presence or absence of adverse events. Results: Male sex, skin phototype II, location on the dorsum and nasal ala, clinical subtype ulcerative nodule, and solid histological subtype predominated. In most of the patients, the tumor disappeared at the end of the therapeutic regime. The most common adverse events were pain at the injection site, fever, edema and perilesional erythema. Conclusions: There was a complete response to treatment in most patients and the adverse events were those described in the literature with no change in the pharmacological attitude(AU)

Uso profiláctico de nasalferon contra la COVID-19 en trabajadores de la salud. Estudio de vigilancia temprana / Prophylactic use of nasalferon against COVID-19 in healthcare workers. Early surveillance stud

RESUMEN Introducción: En Cuba se empezó la aplicación nasal de IFN alfa 2b recombinante humano (Nasalferon) en personal de riesgo para prevenir la infección por el SARS-CoV-2. Objetivo: caracterizar la seguridad de los expuestos al uso del Nasalferon en el Centro de Investigaciones Médico Quirúrgicas y explorar el efecto del uso profiláctico del fármaco contra cuadros respiratorios agudos causados preferentemente por el SARS-CoV-2. Material y Métodos: Estudio epidemiológico monocéntrico, prospectivo, abierto, de vigilancia temprana en trabajadores sanitarios, a los que se le administró nasalferon. Se realizó la vigilancia mediante el método de Vigilancia del Monitoreo de Eventos Adversos Ligados a la Prescripción. La variable principal fue la presencia de eventos adversos. Secundariamente se exploró el efecto del fármaco en la prevención de infección por el virus. Para el análisis de la variable principal se estimó la proporción de sujetos con cada uno de los eventos adversos que se presentaron. Se estimaron, además, la distribución de frecuencia del tipo de evento, intensidad, gravedad y la causalidad o imputabilidad. Resultados: Se incluyeron 86 sujetos, de ellos, 50 experimentaron 15 tipos de eventos adversos. No se reportaron eventos severos ni graves. Los catalogados como moderados fueron: cefalea, leucopenia, decaimiento e hipertensión arterial. Durante el tiempo que duró el tratamiento y hasta un mes después de este, ninguno de los sujetos incluidos presentó COVID-19 ni otros cuadros respiratorios agudos virales. Conclusiones: El Nasalferon resultó ser un fármaco seguro y tolerable y los sujetos incluidos no presentaron cuadros respiratorios agudos relacionados o no con la COVID-19.

ABSTRACT Introduction: In Cuba, the nasal application of recombinant human IFN-alpha- 2b (nasalferon) began in personnel at risk in order to prevent SARS-CoV-2 infection. Objective: To characterize the safety in those subjects exposed to the use of Nasalferon at the Surgical Medical Research Center and to explore the effect of the prophylactic use of the drug against acute respiratory symptoms mainly caused by SARS-CoV-2. Material and Methods: Monocentric, prospective, open, and early surveillance epidemiological study conducted in healthcare workers who were administered Nasalferon. Surveillance was performed using the Prescription-Related Adverse Event Monitoring Surveillance method. The main variable was the presence of adverse events. Secondarily, the effect of the drug in preventing virus infection was explored. For the analysis of the main variable, the proportion of subjects who experienced each of the adverse events was estimated. In addition, the frequency distribution of the type of event, intensity, severity, and causality or imputability were estimated. Results: A total of 86 subjects were included; 50 of them experienced 15 types of adverse events. No severe or serious events were reported. Headache, leukopenia, decay, and arterial hypertension were classified as moderate ones. During the whole duration of the treatment and until a month after it, none of the subjects included in the study presented COVID-19 or other viral acute respiratory symptoms. Conclusions: Nasalferon proved to be a safe and tolerable drug and the included subjects did not present acute respiratory symptoms related or unrelated to COVID-19.

Research advances in interferon-stimulated genes in treatment of hepatitis B virus infection / 临床肝胆病杂志

Hepatitis B virus (HBV) infection is closely associated with the adverse events such as liver cirrhosis, liver cancer, and liver failure and remains a serious threat to human health. Pegylated interferon is an indispensable drug for the treatment of chronic hepatitis B (CHB), and interferon-stimulated genes are associated with a variety of viruses, but few studies have mentioned their association with hepatitis B and their predictive effect after the treatment of hepatitis B with interferon. This article introduces the predictive factors for interferon treatment of CHB and summarizes the association of interferon-stimulated genes with hepatitis B and their predictive effect, so as to provide a reference for clinical work and basic research.

HeberFERON en el carcinoma basocelular periocular. Serie de casos / HeberFERON in periocular basal cell carcinoma. Case series

RESUMEN Fundamento: El carcinoma basocelular periocular es una lesión tumoral que surge de las células basales de la epidermis y los folículos pilosos, con un alto potencial de destrucción local, pueden ser desfigurantes e invaden el tejido que los rodea dando lugar a deformidades o pérdida de la función del órgano afectado. En orden de aparición es más común en el párpado inferior, el canto medial, el párpado superior y el canto temporal. Objetivo: Describir los resultados de la aplicación del HeberFERON en una serie de casos con carcinoma basocelular periocular que acudieron a consulta de dermatología del Policlínico Centro, de enero de 2017 a diciembre del 2020. Metodología: Se realizó un estudio de serie de casos clínicos con carcinoma basocelular periocular que acudieron a la consulta de dermatología del Policlínico Centro. Se incluyeron 17 casos con diagnóstico clínico, dermatoscópico e histopatológico. Se realizó una evaluación inicial, durante y 16 semanas después del tratamiento; se administró 10.5 UI de HeberFERON 3 veces por semana perilesional e intradérmica hasta completar 9 dosis. Las variables principales fueron la respuesta al tratamiento y la presencia o no de eventos adversos. Resultados: Predominó el sexo masculino, el fototipocutáneo II, la localización en párpado inferior, el subtipo clínico nódulo ulcerativo y el histológico sólido, se logró respuesta completa en la mayoría de los pacientes. Como eventos adversos se presentaron dolor en el sitio de inyección, fiebre, mal estar general, edema y eritema perilesional. Conclusiones: La respuesta al tratamiento fue favorable en la mayoría de los pacientes tratados con HeberFERON.

ABSTRACT Background: Periocular basal cell carcinoma is a tumor lesion arising from the epidermis and hair follicles basal cells, with a high potential local destruction, can be disfiguring and invade the surrounding tissue leading to deformities or loss of function of the affected organ. In order of appearance it is most common in the lower eyelid, medial edge, upper eyelid and temporal edge. Objective: To describe the results of the application of HeberFERON in a case series with periocular basal cell carcinoma who attended dermatology appointment at the Policlínico Centro, from January 2017 to December 2020. Methodology: A series study of clinical cases with periocular basal cell carcinoma who attended the dermatology appointment at the Policlínico Centro was conducted. 17 cases with clinical, dermatoscopic and histopathological diagnosis were included. A baseline evaluation was conducted, during and 16 weeks after treatment; 10.5 IU of HeberFERON was administered 3 times a week perilesional and intradermally until completing 9 doses. The main variables were the treatment response and the presence or absence of adverse events. Results: Male sex, phototypocutaneous II, lower eyelid location, clinical subtype ulcerative nodule and solid histological subtype predominated, complete response was achieved in most patients. Adverse events were pain at the injection site, fever, general malaise, edema and perilesional erythema. Conclusions: Treatment response was favorable in most patients treated with HeberFERON.

Seguridad del HeberFERON( en pacientes con carcinoma basal palpebral / Safety of HeberFERON in patients with basal cell eyelid carcinoma

Objetivo: Evaluar la seguridad del HeberFERON( en el tratamiento del carcinoma basal palpebral. Métodos: Se realizó un estudio descriptivo en pacientes con carcinoma basal palpebral, a quienes se les aplicó HeberFERON( perilesional, de enero del año 2013 a enero de 2018. La muestra quedó constituida por 20 pacientes que cumplieron los criterios de inclusión. La dosis protocolizada fue de 3,5 x 106 UI, perilesional, dos veces a la semana por 5 semanas consecutivas. Las variables del estudio fueron: edad, sexo, color de la piel, localización del tumor, así como tipo y grado de evento adverso. Para todas las variables del estudio fueron calculadas las frecuencias absolutas y relativas. Resultados: La población estudiada con carcinoma basal palpebral mostró mayor frecuencia entre los 60 y 79 años de edad (80 por ciento) y las lesiones se presentaron fundamentalmente en el párpado inferior (60 (). El eritema palpebral y el dolor en el sitio de la inyección constituyeron los eventos adversos oculares más frecuentes (95,0 y 70,0 por ciento respectivamente) y se presentaron en el 95 por ciento de los pacientes investigados. Los eventos adversos sistémicos (fiebre, artralgia y la cefalea) prevalecieron en el 100 por ciento de los casos, en quienes el grado de severidad fue leve. Conclusiones: El HeberFERON( en el tratamiento del carcinoma basal palpebral es una buena alternativa no quirúrgica; es seguro y bien tolerado(AU)

Objective: Evaluate the safety of HeberFERON in the treatment of basal cell eyelid carcinoma. Methods: A descriptive study was conducted of patients with basal cell eyelid carcinoma undergoing perilesional HeberFERON therapy from January 2013 to January 2018. The sample was composed of 20 patients meeting the inclusion criteria. The protocol dose was 3.5 x 106 UI perilesional twice a week for five consecutive weeks. The variables analyzed were age, sex, skin color and tumor location, as well as adverse event type and degree. Absolute and relative frequencies were estimated for all the study variables. Results: The prevailing age group in the study basal cell eyelid carcinoma population was 60-79 years (80 percent). The most common lesion site was the lower eyelid (60 percent). Eyelid erythema and injection site pain were the most frequent ocular adverse events (95.0 percent and 70.0 percent, respectively), presenting in 95 percent of the study subjects. Systemic adverse events (fever, arthralgia and headache) prevailed in 100 percent of the cases studied, among whom the degree of severity was mild. Conclusions: HeberFERON is a good non-surgical alternative for basal cell eyelid carcinoma. It is safe and well tolerated(AU)

Respuesta clínica del tratamiento con HerberFERON( en pacientes con carcinoma basal palpebral / Clinical response to treatment with HerberFERON® in patients with basal palpebral carcinoma

Objetivo: Determinar la respuesta clínica en pacientes con carcinoma basal palpebral tratados con HeberFERON. Métodos: Se realizó un estudio descriptivo en pacientes con carcinoma basal palpebral, a quienes se les aplicó HeberFERON( perilesional en el Instituto Cubano de Oftalmología "Ramón Pando Ferer", de enero del año 2013 a enero de 2015. La muestra quedó constituida por 10 pacientes que cumplieron con los criterios de inclusión. Las variables del estudio fueron: edad, sexo, color de la piel, forma clínica, diámetro tumoral, subtipo histológico del tumor, así como la respuesta clínica después del tratamiento de los casos estudiados. Para todas las variables del estudio fueron calculadas las frecuencias absolutas y relativas. Resultados: Predominaron el género masculino y los sujetos de piel blanca. En los pacientes estudiados se presentaron la forma clínica nódulo ulcerativo, el subtipo histológico tumoral poco diferenciado y la respuesta clínica objetiva. Conclusiones: En la mayoría de los pacientes se logró una buena respuesta clínica al tratamiento con HeberFERON(, por lo que este tratamiento se convierte una nueva alternativa no quirúrgica(AU)

Objective: To determine the clinical response in patients with basal palpebral carcinoma treated with HeberFERON(. Methods: A descriptive study was carried out in patients with eyelid cell basal carcinoma tried with HeberFERON in the Cuban Institute of Ophthalmology "Ramón Pando Ferrer" from January 2013 to January 2015. The sample consisted of 10 patients who fulfilled the inclusion criteria. The study variables were: age, sex, skin color, clinical form, tumor diameter, histological subtype of the tumor, as well as the clinical response after treatment of the cases studied. In all the variables, absolute and relative frequencies were calculated. Results: Male gender and white-skinned subjects predominated. The clinical form ulcerative nodule, poorly differentiated histological tumor subtype, and objective clinical response were present in the patients studied. Conclusions: In most of the patients a good clinical answer was achieved to the treatment with HeberFERON, which becomes a new non surgical alternative(AU)

Importancia de los interferones tipo I en la respuesta inmune antiviral contra el Virus del Papiloma Humano / Importance of type I interferons in the antiviral immune response against the Human Papillomavirus

Resumen Los interferones (IFNs) son citoquinas fundamentales en la modulación de la inmunidad innata y adaptativa del hospedero, el papel de los IFNs tipo I en el control de la infección por el Virus del Papiloma Humano (VPH) es crucial para una eficiente respuesta antiviral del huésped. Esta revisión profundiza sobre las funciones de los IFNs tipo I en la infección causada por el VPH y los mecanismos de evasión de este virus para inactivar los IFNs tipo I, todos estos mecanismos necesarios para el desarrollo y progresión de lesiones malignas en los tejidos infectados por el VPH.

Abstract The interferons (IFNs) are very important cytokines in the interface between innate and adaptive immunity of the host, the role type I IFNs in the control of HPV is pivotal for an efficient immune response, so a wide knowledge about this topic will contribute understanding HPV pathogenicity mechanism. This review focuses on the HPV evasion mechanisms for the type I IFNs which are necessary for a malignant lesion development, otherwise develops knowledge about the type I IFNs functions on the HPV infection.

Ocular surface findings in impression cytology after interferon a2b or mitomycin C in rabbits / Achados em citologia de impressão da superfície ocular após uso de interferon alfa-2b ou mitomicina C: estudo em coelho

ABSTRACT Objective: To describe ocular surface findings in impression cytology obtained from healthy rabbit conjunctiva treated with interferon alpha-2b eyedrop, and compare them to findings after use of mitomycin C 0.02%. Methods: An experimental study using a rabbit model was performed between September 2013 and October 2014 at the Faculdade de Medicina de Marília, Universidade Federal de São Paulo, Clínica de Olhos Moacir Cunha. Thirty New Zealand white rabbits were divided into 6 groups and received interferon alpha-2b or mitomycin C 0.02%. Impression cytology (IC) was performed prior to topical applications and at15, 30 and 60 days of use. The following variables were analyzed in impression cytology: goblet cells, cellularity, cell-to-cell adhesion, nucleus/cytoplasm ratio, nuclear chromatin, inflammatory cells keratinization, and cytomegaly. Results: The major findings in impression cytology after us of interferon alpha-2b included loss of goblet cells (50.8%), reduced cell-to-cell adhesion (26.2%), abnormal nucleus/cytoplasm ratio (20%) and reduced cellularity (15.4%). After use of mitomycin C 0.02%, the most common changes included loss of goblet cells (46.2%), abnormal nucleus/cytoplasm ratio (25.6%), less cell-to-cell adhesion (23.1%), and reduced cellularity (20.5%). There were no significant differences in any variable when comparing impression cytology after interferon alpha-2b and after mitomycin C 0.02%. Goblet cell loss was more pronounced at days 30 and 60, as compared to impression cytology at day 15 for both drugs. Conclusion: The loss of goblet cells, reduced cell-to-cell adhesion and cellularity, along with abnormal nucleus/cytoplasm ratio were the most common findings in impression cytology after use of interferon alpha-2b. These findings are similar to those described for use of mitomycin C 0.02%. ..

RESUMO Objetivo: Descrever os achados em citologia de impressão de conjuntiva sadia de coelho submetida ao uso de colírio de interferon alfa-2b e compará-los ao que foi encontrado após uso da mitomicina C 0,02%. Métodos: Estudo experimental realizado em modelo animal no período entre setembro de 2013 e outubro de 2014 nas dependências da Faculdade de Medicina de Marília, da Universidade Federal de São Paulo e da Clínica de Olhos Moacir Cunha. Trinta coelhos albinos da raça Nova Zelândia foram divididos em seis grupos e receberam interferon alfa-2b ou mitomicina C. A citologia de impressão foi realizada antes do início dos colírios e após 15, 30, 60 dias de seu uso. As seguintes variáveis foram analisadas na citologia de impressão: células caliciformes, celularidade, adesão intercelular, razão núcleo/citoplasma, cromatina, células inflamatórias, queratinização e citomegalia. Resultados: Os principais achados na citologia de impressão após o uso do interferon alfa-2b foram a redução de células caliciformes (50,8%), a diminuição da adesão intercelular (26,2%), a alteração da razão N/C (20%) e a redução da celularidade (15,4%). Após o uso da mitomicina C 0,02%, foram mais frequentes a redução das células caliciformes (46,2%), a alteração da razão N/C (25,6%), a adesão intercelular (23,1%) e a redução da celularidade (20,5%). Não houve diferença estatisticamente significante para nenhuma das variáveis estudas quando se compararam as citologias de impressão após interferon alfa-2b com as citologias de impressão após mitomicina C 0,02%. Independentemente da substância utilizada, as citologias colhidas 30 e 60 dias após início das drogas apresentaram maior redução de células caliciformes quando comparadas com as citologias de impressão colhidas após 15 dias. Conclusão: A redução das células caliciformes, a diminuição da adesão intercelular, a alteração da razão N/C e a diminuição da celularidade foram as alterações mais frequentes na citologia de impressão colhida após o uso de interferon alfa-2b. Os achados em citologias de impressão após o uso de interferon alfa-2b são semelhantes àqueles encontrados após o uso da mitomicina C 0,02%.

A clinical study of clinical cure after the addition of interferon therapy in chronic hepatitis B patients with low-level HBsAg previously treated with nucleos(t)ide analogues / 临床肝胆病杂志

ObjectiveTo investigate the population with an advantage of clinical cure previously treated with nucleos(t)ide analogues (NAs), and to provide more methods for clinicians in pursuing the clinical cure of hepatitis B. MethodsA total of 42 chronic hepatitis B patients with low-level HBsAg who received NAs treatment in Hebi Third People’s Hospital from October 2017 to October 2019 were enrolled as subjects and divided into combination treatment group (group A) and NA monotherapy group (group B). The 22 subjects in group A were treated with NAs combined with PEG-IFN antiviral therapy for 48 weeks, and some patients withdrew from PEG-IFN after 24 weeks and continued to receive NA monotherapy, while the 20 subjects in group B received NA antiviral therapy alone. Both groups were observed till week 48, and the five makers for hepatitis B were measured to evaluate clinical outcome. The t-test was used for comparison of continuous data between two groups, and the Fisher’s exact test was used for comparison of categorical data between two groups; a multivariate logistic regression analysis was used to perform a multivariate analysis. ResultsCompared with group B at the 48-week treatment endpoint, group A had significantly higher HBsAg clearance rate (45.5% vs 0, P＜0.01) and HBsAg seroconversion rate (31.8% vs 0, P＜0.01). The population with HBsAg ＜1000 IU/ml, ＜500 IU/ml, ＜100 IU/ml, and ＜10 IU/ml had an HBsAg clearance rate of 52.6%, 61.5%, 66.7%, and 100%, respectively, and the population with an HBsAg level of 500-1000 IU/ml, 100-500 IU/ml, 10-100 IU/ml, and ＜10 IU/ml had an HBsAg clearance rate of 33.3%, 50%, 40%, and 100%, respectively. The 4 patients with baseline HBsAg ＜10 IU/ml (accounting for 18.2% in group A) achieved clinical cure at week 12 of combined treatment, and after observation to week 48, 2 patients had an anti-HBs level of ＞100 IU/ml and 2 had an anti-HBs level of ＞1000 IU/ml. The multivariate logistic regression analysis of HBsAg clearance showed that age at the initiation of combined treatment affected HBsAg clearance (odds ratio ［OR］=0.877, 95% confidence interval ［CI］: 0.781-0.985, P=0.026), and most of the patients with HBsAg clearance had an age of 36-49 (44.20±4.49) years; baseline HBsAg level also had an impact on HBsAg clearance (OR=0.996, 95% CI: 0.992-1.000, P=0.050). ConclusionThe addition of interferon therapy in chronic hepatitis B patients with low-level HBsAg previously treated with NAs can significantly improve the clinical cure rate. The younger the age and the lower the HBsAg level, the shorter the duration of combined treatment. Age and baseline HBsAg level are more important than the duration and type of NA medication.

Effect of entecavir antiviral therapy alone or combined with interferon on the risk of hepatocellular carcinoma in patients with chronic hepatitis B / 临床肝胆病杂志

ObjectiveTo investigate the effect of entecavir (ETV) alone or combined with interferon (IFN) on the risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB). MethodsA retrospective analysis was performed for 409 patients with CHB who were admitted to Beijing Ditan Hospital from January 2008 to December 2014, and according to their antiviral therapy, they were divided into ETV+IFN group with 169 patients (IFN treatment for ≥6 months) and ETV group with 240 patients (ETV treatment for ≥12 months). The patients were followed up to June 2019, and the development of HCC was the outcome event. The Mann-Whitney U test was used for comparison of continuous variables between two groups, and the chi-square test was used for comparison of categorical variables between two groups. The propensity score matching (PSM) method was used to eliminate baseline differences between groups, the Kaplan-Meier method and the log-rank test were used to compare the incidence rate of HCC between groups, and the Cox proportional-hazards regression model analysis was used to investigate the risk factors for the development of HCC. ResultsThe median follow-up time in this study was 5.4 years (IQR: 4.9-7.9). There was no significant difference in the cumulative incidence rate of HCC between the two groups before and after PSM (before PSM: 1.2% vs 2.8%, χ2=1.423, P=0.233; after PSM: 1.7% vs 4.1%, χ2=1.676, P=0.195), and the subgroup analysis also showed no significant difference in the cumulative incidence rate of HCC between the two groups in the non-high risk population (1.3% vs 1.5%, χ2=0.335, P=0.563). The Cox proportional-hazards regression model showed that age was an independent risk factor for HCC (hazard ratio=1.107, 95% confidence interval: 1.005-1.219, P=0.038). ConclusionFor CHB patients without a high risk of cancer, compared with ETV monotherapy, ETV combined with IFN for at least 6 months does not significantly reduce the risk of HCC.

Hepatite C e as novas estratégias de tratamento: revisão deliteratura / Hepatitis C and the new treatment strategies: literature review

As hepatites virais são uma das maiores causas de transplantes hepáticos no mundo, com destaque para hepatite C (HCV), com mais de 240 milhões de pessoas infectadas. A história da HCV é marcada pela evolução silenciosa da doença, afetando negativamente o diagnóstico, sendo que os primeiros sintomas manifestam-se apenas na fase aguda e avançada da doença, comprometendo a eficácia do tratamento. Estudos apontam que cerca de 350 mil pessoas perdem a vida anualmente em decorrência da doença. O tratamento dos casos de HCV era feito pela combinação dos medicamentos interferon e ribavirina, no entanto, essa combinação tem como um grande problema a limitação de seu uso em alguns pacientes e, principalmente, seus intensos efeitos colaterais. Esse estudo se dedicou a apresentar os novos tratamentos, através de revisão de literatura, com coleta de dados em Pubmed, SciElo, entre outros bancos de dados, servindo como um informativo às pessoas doentes e seus familiares. A revisão apontou que uma avaliação da gravidade da doença hepática deve ser feita com a finalidade de fornecer subsídios ao processo de decisão sobre o regime de tratamento mais adequado. Essas novas terapias foram introduzidas e demonstraram melhores resultados, perfil de segurança e eficácia.

Viral hepatitis is one of the biggest causes of liver transplants in the world, with hepatitis C (HCV), with more than 240 million people infected all over the world. The history of HCV is marked by the silent evolution of the disease, negatively affecting the diagnosis, and the first symptoms manifest only in the acute and advanced stage of thedisease, compromising the effectiveness of the treatment. Studies indicate that about 350,000 people die each year from the disease.The treatment of HCV cases was made by the combination of interferon and ribavirin, however, this combination has a major problem limiting its use in some patients and especially its intense side effects. This study was dedicated to presenting the new treatments, through literature review, with data collection in Pubmed, SciELO, among other databases, serving as an informative to sick people and their families. The review pointed out that an assessment of the severity of liver disease should be done in order to provide input to the decision process o n the most appropriate treatment regimen. These new therapies were introduced and demonstrated better results, safety profile and efficacy