Description of BCG and Tuberculosis Disease in a Cohort of 79 Patients with Chronic Granulomatous Disease.

PURPOSE: Chronic granulomatous disease (CGD) is an inherited immunodeficiency caused by pathogenic variants of genes encoding the enzyme complex NADPH oxidase. In countries where tuberculosis (TB) is endemic and the Bacillus Calmette-Guérin (BCG) vaccine is routinely administered, mycobacteria are major disease-causing pathogens in CGD. However, information on the clinical evolution and treatment of mycobacterial diseases in patients with CGD is limited. The present study describes the adverse reactions to BCG and TB in Mexican patients with CGD. METHODS: Patients with CGD who were evaluated at the Immunodeficiency Laboratory of the National Institute of Pediatrics between 2013 and 2024 were included. Medical records were reviewed to determine the clinical course and treatment of adverse reactions to BCG and TB disease. RESULTS: A total of 79 patients with CGD were included in this study. Adverse reactions to BCG were reported in 55 (72%) of 76 patients who received the vaccine. Tuberculosis was diagnosed in 19 (24%) patients. Relapse was documented in three (10%) of 31 patients with BGC-osis and six (32%) of 19 patients with TB, despite antituberculosis treatment. There was no difference in the frequency of BCG and TB disease between patients with pathogenic variants of the X-linked CYBB gene versus recessive variants. CONCLUSIONS: This report highlights the importance of considering TB in endemic areas and BCG complications in children with CGD to enable appropriate diagnostic and therapeutic approaches to improve prognosis and reduce the risk of relapse.

PTEN loss shapes macrophage dynamics in high grade serous ovarian carcinoma.

High-grade serous ovarian carcinoma (HGSC) remains a disease of poor prognosis that is unresponsive to current immune checkpoint inhibitors. Although PI3K pathway alterations, such as PTEN loss, are common in HGSC, attempts to target this pathway have been unsuccessful. We hypothesized that aberrant PI3K pathway activation may alter the HGSC immune microenvironment and present a targeting opportunity. Single-cell RNA sequencing identified populations of resident macrophages specific to Pten-null omental tumors in murine models, which were confirmed by flow cytometry. These macrophages derived from peritoneal fluid macrophages and had a unique gene expression program, marked by high expression of the enzyme heme oxygenase-1 (HMOX1). Targeting resident peritoneal macrophages prevented the appearance of HMOX1hi macrophages and reduced tumor growth. Furthermore, direct inhibition of HMOX1 extended survival in vivo. RNA sequencing identified IL33 in Pten-null tumor cells as a likely candidate driver leading to the appearance of HMOX1hi macrophages. Human HGSC tumors also contained HMOX1hi macrophages with a corresponding gene expression program. Moreover, the presence of these macrophages correlated with activated tumoral PI3K/mTOR signaling and poor overall survival in HGSC patients. In contrast, tumors with low numbers of HMOX1hi macrophages were marked by increased adaptive immune response gene expression. These data suggest targeting HMOX1hi macrophages as a potential therapeutic strategy for treating poor prognosis HGSC.

Controversy in the initial nodal staging of rectal cancer (MRI or PET/CT?).

OBJECTIVE: To compare the usefulness of MRI and PET/CT in nodal staging (N) of patients with locally advanced rectal cancer (LARC). MATERIAL AND METHODS: Retrospective study of patients with LARC, who completed their initial staging with PET/CT, between January-20 and March-23. Regional nodes were assessed, and N was determined using both techniques according to TNM criteria. Concordance between MRI and PET/CT was analyzed. The accuracy of both techniques was calculated for those patients who underwent direct surgery. Non-regional pelvic lymph nodes were evaluated by both modalities. RESULTS: Among the 73 patients, 48 were ultimately diagnosed with a locally advanced stage. Of these, 39 underwent neoadjuvant treatment (chemoradiotherapy) followed by surgery, and 9 direct surgery. In 25, the PET/CT extension study revealed distant disease, leading to systemic treatment. Weak concordance was observed between MRI and PET/CT in determining N (k=0.286; p<0.005). Out of 73 patients, 31(42%) exhibited concordance, and 42(58%) showed discordance. In 83% of the discordant cases, MRI overstaged compared to PET/CT, with 17 cases indicating nodal involvement (N+) by MRI and N0 by PET/CT. Diagnostic accuracy was 78% for both techniques. Sensitivity, specificity, positive predictive value, and negative predictive value were 80%, 75%, 80%, and 75% for MRI, and 60%, 100%, 100%, and 67%, for PET/CT. PET/CT identified pelvic metastatic adenopathies in 8 patients that were not visible/doubtful by MRI. CONCLUSIONS: In the initial nodal staging of rectal cancer MRI overstages relative to PET/CT. Both modalities are complementary, PET/CT offers higher specificity and MRI higher sensitivity.

Social and mental health characteristics of adolescents living with HIV in Mexico: Implications for adherence to antiretroviral treatment.

Mexico is the third Latin American country with the most children and adolescents living with human immunodeficiency virus (ALHIV). There is a lack of information on the characteristics of this population. We aimed to describe the social and mental health characteristics of Mexican ALHIV. A census was conducted of all adolescent patients with HIV at a pediatric hospital (n = 47; mean age 14.39, S.D. = 3.65) and their caregivers. We collected data on socio-demographic characteristics, family, intelligence, mental health, adverse life events, substance use, treatment, knowledge of Antiretroviral Treatment (ART) and HIV, and biomarkers. Most cases were transmitted vertically and self-reported ART adherence was above 90%. Some obstacles to adherence were medicine discomfort, believing that they did not need it, and forgetfulness. The vulnerabilities were intellectual disability, adverse life events, possible mental health problems, and little knowledge of their illness and treatment. These findings suggest the importance of interventions to improve the perception and knowledge of HIV and ART to increase ART adherence.

Pertinencia de enfermería, según las competencias percibidas por los graduados de la Universidad de Guayaquil

Fundamento: la pertinencia en salud se relaciona con la coherencia existente en un proyecto de intervención según las necesidades de sus beneficiarios; en ello es muy importante que el profesional posea facultades para combinar sus capacidades en el logro de un propósito determinado. Objetivo: determinar indicadores de empleabilidad según las competencias en graduados de la carrera de Enfermería de la Universidad de Guayaquil . Métodos: estudio descriptivo/explicativo con una muestra representativa de 136 graduados de los últimos cinco años, a los que se les aplica un instrumento validado por juicio de expertos (0,89: alfa de Cronbach). Se midieron 17 indicadores de empleabilidad interna y seis de empleabilidad externa. Resultados: los graduados de enfermería perciben la empleabilidad como atributos y competencias del ser, con habilidades de resolución de problemas, ser reflexivos, pensamiento crítico, conductas éticas y liderazgo efectivo. En relación con la empleabilidad externa los egresados se consideraron con competencias de atributos que los hacen competitivos en el entorno laboral de enfermería. Conclusiones: los graduados de la carrera de enfermería de la universidad de Guayaquil poseen los atributos y competencias de una empleabilidad interna y externa de acuerdo con los objetivos y perfiles del profesional de enfermería.

Foundation: the relevance in health is related to the existing coherence in an intervention project according to the needs of its beneficiaries; In this it is very important that the professional has the faculties to combine his capacities in the achievement of a certain purpose. Objective: to determine employability indicators according to the competencies in graduates of the Guayaquil University nursing career. Methods: descriptive/explanatory study with a representative sample of 136 graduates of the last five years, to whom an instrument validated by expert judgment (0.89: Cronbach's alpha) was applied. 17 indicators of internal employability and six of external employability were measured. Results Nursing graduates perceive employability as attributes and competencies of being, with problem-solving skills, being reflective, critical thinking, ethical behaviors, and effective leadership. In relation to external employability, graduates were considered to have attribute competencies that make them competitive in the nursing work environment. Conclusions: Nursing graduates from the Guayaquil University have the attributes and competencies of internal and external employability in accordance with the expectations of the objectives and the nursing professional's profiles.

First report on mycetoma in Turkana County-North-western Kenya.

Mycetoma is one of the six Neglected Tropical Diseases that are prevalent in Turkana County (northwest Kenya). The aim of the study was to estimate the prevalence of mycetoma in the county, as well as to describe the main causative agents involved in the disease using methods affordable locally. Based on the data collected by the team of cooperative medicine Cirugia en Turkana (Surgery in Turkana), a specific study for mycetoma was started during the 16th humanitarian medicine campaign in February 2019. Patients with suspected mycetoma were studied at the Lodwar County Referral Hospital (LCRH). After informing the patient and getting their consent, the lesions were examined and sampled (mainly by biopsy) and clinical data were recorded. Samples were washed in sterile saline solution and cut in fragments. Some of these were inoculated on Sabouraud Dextrose Agar, Malt Extract Agar, and diluted Nutrient Agar plates. One fragment of each sample was used for DNA extraction. The DNA and the rest of the fragments of samples were kept at -20°C. All cultures were incubated at room temperature at the LCRH laboratory. The DNA obtained from clinical samples was submitted to PCR amplification of the ITS-5.8S and the V4-V5 16S rRNA gene region, for the detection and identification of fungi and bacteria respectively. From February 2019 till February 2022, 60 patients were studied. Most of them were men (43, 74,1%) between 13 and 78 y.o. (mean age 37). Half of the patients were herdsmen but, among women 40% (6) were housewives and 26.7% (4) charcoal burners. Lesions were mainly located at the feet (87.9%) and most of the patients (54; 93.1%) reported discharge of grains in the exudate, being 27 (46.6%) yellow or pale colored and 19 (32.8%) of them dark grains. Culture of clinical samples yielded 35 fungal and bacterial putative causative agents. Culture and molecular methods allowed the identification of a total of 21 causative agents of mycetoma (39.6% of cases studied). Most of them (17) corresponded to fungi causing eumycetoma (80.9%) being the most prevalent the genus Madurella (7; 41.2%), with two species involved (M. mycetomatis and M. fahalii), followed by Aspergillus (2; 11.8%). Other minority genera detected were Cladosporium, Fusarium, Acremonium, Penicillium, and Trichophyton (5.9% each of them). Actinobacteria were detected in 19.1% of samples, but only Streptomyces somaliensis was identified as a known agent of mycetoma, the rest being actinobacteria not previously described as causative agents of the disease, such as Cellulosimicrobium cellulans detected in two of the patients. Although Kenya is geographically located in the mycetoma belt, to our knowledge this is the first report on mycetoma in this country from 1973, and the first one for Turkana County.

Percepción sobre riesgos laborales en Enfermería durante la pandemia COVID-19 / Occupational hazard perceptions in nursing during the COVID-19 pandemic

Fundamento: La pandemia de COVID-19 ha incrementado los riesgos laborales en los profesionales de Enfermería, por ello es necesario conocer las percepciones del personal de salud como valor cualitativo a tener en cuenta en la gestión efectiva de su proceso laboral. Objetivo: Describir la percepción del profesional de Enfermería frente a los riesgos laborales durante la pandemia COVID-19, desde un enfoque fenomenológico. Metodología: Investigación cualitativa (descriptiva-explicativa) de tipo fenomenológico, estudiando las percepciones de 13 profesionales de Enfermería sobre los riesgos laborales de tipo físico, biológico, fisiológico y ergonómico, acontecidos en el Hospital del IESS "Dr. Efrén Jurado", en Guayaquil, Ecuador. Resultados: Se observó que los profesionales emplean estrategias de afrontamiento frente a los riesgos laborales, asimismo fomentan una conducta de autocuidado, siguen protocolos de bioseguridad, fortalecen la comunicación efectiva en el equipo de trabajo, brindan apoyo emocional al paciente, proyectan una actitud positiva y empática y mantienen su fortaleza en Dios; los profesionales constantemente experimentan miedo al contagio, tristeza, frustración e impotencia en su jornada laboral. Conclusiones: Los hallazgos se aproximan al modelo de creencias de salud, describiendo componentes que interactúan para originar una conducta o actitud de prevención de riesgo entre enfermeros, una percepción individual donde intervienen las creencias y los factores modificables como aspectos emocionales relacionados con los sentimientos.

Background: The COVID-19 pandemic has increased occupational hazards in nursing professionals, therefore, it is necessary to know the perceptions of health staff as a qualitative value to be taken into account in the effective management of their work process. Objective: To describe the perception of the Nursing professional in relation to occupational risks during the COVID-19 pandemic, from a phenomenological point of view. Methodology: Qualitative research (descriptive-explanatory) of the phenomenological type, studying the perceptions of 13 nursing professionals about physical occupational hazards, biological, physiological and ergonomic, occurred at the IESS Hospital "Dr. Efrén Jurado", in Guayaquil, Ecuador. Results: It was observed that the professionals use strategies for coping against occupational hazards, they also encourage self-care behaviors, follow biosafety protocols enhance effective communication in the work team, provide emotional support to the patient, project an attitude of positivity and compassion, and remain strong in God; professionals constantly experience fear of infection, sadness, frustration and powerlessness in their daily work. Conclusions: Findings approach the health belief model, describing components that interact to create a risk prevention behavior or attitude among nurses, an individual perception that involves beliefs and modifiable factors such as emotional aspects related to feelings.

Cytogenetic Assessment and Risk Stratification in Myelofibrosis with Optical Genome Mapping.

Cytogenetic assessment in myelofibrosis is essential for risk stratification and patient management. However, an informative karyotype is unavailable in a significant proportion of patients. Optical genome mapping (OGM) is a promising technique that allows for a high-resolution assessment of chromosomal aberrations (structural variants, copy number variants, and loss of heterozygosity) in a single workflow. In this study, peripheral blood samples from a series of 21 myelofibrosis patients were analyzed via OGM. We assessed the clinical impact of the application of OGM for disease risk stratification using the DIPSS-plus, GIPSS, and MIPSS70+v2 prognostic scores compared with the standard-of-care approach. OGM, in combination with NGS, allowed for risk classification in all cases, compared to only 52% when conventional techniques were used. Cases with unsuccessful karyotypes (n = 10) using conventional techniques were fully characterized using OGM. In total, 19 additional cryptic aberrations were identified in 9 out of 21 patients (43%). No alterations were found via OGM in 4/21 patients with previously normal karyotypes. OGM upgraded the risk category for three patients with available karyotypes. This is the first study using OGM in myelofibrosis. Our data support that OGM is a valuable tool that can greatly contribute to improve disease risk stratification in myelofibrosis patients.

Serum Vitamins A and E at Mid-Pregnancy and Their Relationships with Both Maternal and Cord Blood Antioxidant Status and Perinatal Conditions: The NELA Cohort.

INTRODUCTION: Most of the pregnant women do not achieve the recommended dietary intake of vitamins A and E. These vitamins may counteract oxidative stress involved in some adverse perinatal outcomes. We aimed to assess the associations between maternal vitamin A and E at mid-pregnancy with both maternal and fetal outcomes and to identify possible early biomarkers during pregnancy to predict and prevent oxidative stress in the offspring. METHODS: Data on dietary and serum levels of vitamins A and E were collected from 544 pregnant women from the Nutrition in Early Life and Asthma (NELA) study, a prospective mother-child cohort set up in Spain. RESULTS: There were large discrepancies between low dietary vitamin E intake (78% of the mothers) and low serum vitamin E levels (3%) at 24 weeks of gestation. Maternal serum vitamins A and E at mid-pregnancy were associated with higher antioxidant status not only in the mother at this time point (lower hydroperoxides and higher total antioxidant activity [TAA]) but also with the newborn at birth (higher TAA). Gestational diabetes mellitus (GDM) was negatively associated with maternal serum vitamin A (OR: 0.95 CI: 0.91-0.99, p = 0.009) at mid-pregnancy. Nevertheless, we could not detect any association between GDM and oxidative stress parameters. CONCLUSIONS: In conclusion, maternal vitamin A and E serum levels may be used as an early potential biomarker of antioxidant status of the neonate at birth. Control of these vitamins during pregnancy could help avoid morbid conditions in the newborn caused by oxidative stress in GDM pregnancies.

COVID-19 en trabajadores activos durante la cuarentena. Realidad de un sector urbano de Caracas, Venezuela / COVID-19 in active workers during quarantine. Reality of an urban sector of Caracas, Venezuela

La pandemia por COVID-19 resultó un problema para la salud pública mundial, que impactó particularmente al sector de trabajadores que debían trabajar y estar expuestos durante el periodo de cuarentena. Objetivo, analizar la incidencia de COVID-19 y sus características en trabajadores(as) activos(as) durante 34 semanas. Investigación descriptiva y transversal. Población constituida por todos los trabajadores(as) activos de sectores priorizados, con diagnóstico confirmado de COVID-19. De los 1.186 casos confirmados, 658 casos (55%) correspondió a trabajadores activos, una incidencia de 1,7 casos x 1000 (mayor a la esperada), con predominio en trabajadores(as) del sector salud (267casos), choferes del transporte y trabajadores de funerarias (253 casos). El 68,7% menor de 40 años y predominio del sexo masculino (61,2%). En el personal de salud, el 30% correspondió a personal de enfermería y 22% en médicos. La tasa de mortalidad en la población de trabajadores activos fue de 0,07 x cada 1000, con un índice de mortalidad de 0,05 y un índice de recuperación del 95,5%, comportamiento similar al de la población general. Sin embargo, la tasa de letalidad (trabajadores activos positivos fallecidos) fue del 4,4% (29 casos), donde el 75% (22/29) fueron enfermeras y médicos, lo que confirmó al sector salud y trabajadores(as) de servicios, como población trabajadora altamente expuesta y vulnerable, lo que justificó priorizar las medidas de prevención en estos trabajadores, al iniciar el sistema de vigilancia epidemiológica, la vacunación y la dotación con uso adecuado de la protección personal(AU)

The COVID-19 Pandemic was a problem for global public health, which particularly impacted the sector of workers who had to work and were exposed during the quarantine period. The objective was to analyze the incidence of COVID- 19 and its characteristics in active workers during 34 weeks. Descriptive and cross-sectional research. Population made up of all active workers in prioritized sectors, with a confirmed diagnosis of COVID-19. Of the 1,186 confirmed cases, 658 cases (55%) corresponded to active workers, an incidence of 1.7 cases per 1,000 (higher than expected), with a predominance of workers in the health sector (267 cases), transport drivers and funeral home workers (253 cases). 68.7% under 40 years of age and predominance of the male sex (61.2%). In health personnel, 30% corresponded to nursing personnel and 22% to doctors. The mortality rate in the population of active workers was 0.07 x every 1000, with a mortality rate of 0.05 and a recovery rate of 95.5%, behavior similar to that of the general population. However, the fatality rate (deceased positive active workers) was 4.4% (29 cases), where 75% (22/29) were nurses and doctors, which confirmed the health sector and service workers, as a highly exposed and vulnerable working population, which justified prioritizing prevention measures in these workers, by initiating the epidemiological surveillance system, vaccination and provision with adequate use of personal protection(AU)

Outcomes of Corneal Transplant in Childhood Glaucoma.

PRCIS: Childhood glaucoma produces alterations in the postnatal development and function of various ocular structures, including the cornea. Childhood glaucoma patients present lower corneal transplant survival rates. Our series shows outcomes of corneal transplant in childhood glaucoma with survival rates of 29% at 2 years. OBJECTIVE: To investigate the surgical outcome of different types of keratoplasty in eyes with childhood glaucoma. PATIENTS AND METHODS: A retrospective review was made of the medical records from 17 eyes of 15 patients who were diagnosed with childhood glaucoma and received a corneal transplantation between January 2010 and July 2020. Patient demographics, intraocular pressure, previous ocular surgery, comorbidities, corneal transplant surgery, and follow-up outcome were collected. The primary efficacy endpoint was graft survival (in months) until failure, the latter being considered as irreversible loss of corneal transparency. Secondary efficacy points were the need for an increase in topical hypotensive therapy and the need for additional surgery. RESULTS: Seventeen eyes of 15 patients were included, 11 eyes (10 patients) with primary congenital glaucoma and 6 with other types of childhood glaucoma. Corneal transplantation was performed at the mean age of 23.76 ± 14.86 years. At the time of the transplantation, the number of topical medications was 1.35 ± 1.27, intraocular pressure was 15.00 ± 8.34 mm Hg, and patients had received up to 7 glaucoma surgeries. Descemet stripping automated endothelial keratoplasty was performed in 13 eyes (76%) and penetrating keratoplasty in 4 (24%). After surgery, 7 (41%) eyes required increased topical treatment and 2 (12%) glaucoma surgery. Twelve eyes (71%) developed graft failure at 24 months, the mean time of survival being 13.88 ± 8.25 months. CONCLUSIONS: Management of corneal decompensation in childhood glaucoma poses a challenge. In this series of childhood glaucoma with corneal transplantations, the survival rate was 29% at 24 months.

Effect of Hypercholesterolemia, Systemic Arterial Hypertension and Diabetes Mellitus on Peripapillary and Macular Vessel Density on Superficial Vascular Plexus in Glaucoma.

BACKGROUND/AIMS: Vascular factors are involved in the development of glaucoma, including diseases such as hypercholesterolemia (HC), systemic arterial hypertension (SAH), and diabetes mellitus (DM). The aim of this study was to determine the effect of glaucoma disease on peripapillary vessel density (sPVD) and macular vessel density (sMVD) on the superficial vascular plexus, controlling differences on comorbidities such as SAH, DM and HC between glaucoma patients and normal subjects. METHODS: In this prospective, unicenter, observational cross-sectional study, sPVD and sMVD were measured in 155 glaucoma patients and 162 normal subjects. Differences between normal subjects and glaucoma patients' groups were analyzed. A linear regression model with 95% confidence and 80% statistical power was performed. RESULTS: Parameters with greater effect on sPVD were glaucoma diagnosis, gender, pseudophakia and DM. Glaucoma patients had a sPVD 1.2% lower than healthy subjects (Beta slope 1.228; 95%CI 0.798-1.659, p < 0.0001). Women presented 1.19% more sPVD than men (Beta slope 1.190; 95%CI 0.750-1.631, p < 0.0001), and phakic patients presented 1.7% more sPVD than men (Beta slope 1.795; 95%CI 1.311-2.280, p < 0.0001). Furthermore, DM patients had 0.9% lower sPVD than non-diabetic patients (Beta slope 0.925; 95%CI 0.293-1.558, p = 0.004). SAH and HC did not affect most of the sPVD parameters. Patients with SAH and HC showed 1.5% lower sMVD in the outer circle than subjects without those comorbidities (Beta slope 1.513; 95%CI 0.216-2.858, p = 0.021 and 1.549; 95%CI 0.240-2.858, p = 0.022 respectively. CONCLUSIONS: Glaucoma diagnosis, previous cataract surgery, age and gender seem to have greater influence than the presence of SAH, DM and HC on sPVD and sMVD, particularly sPVD.

Machine Learning Improves Risk Stratification in Myelofibrosis: An Analysis of the Spanish Registry of Myelofibrosis.

Myelofibrosis (MF) is a myeloproliferative neoplasm (MPN) with heterogeneous clinical course. Allogeneic hematopoietic cell transplantation remains the only curative therapy, but its morbidity and mortality require careful candidate selection. Therefore, accurate disease risk prognostication is critical for treatment decision-making. We obtained registry data from patients diagnosed with MF in 60 Spanish institutions (N = 1386). These were randomly divided into a training set (80%) and a test set (20%). A machine learning (ML) technique (random forest) was used to model overall survival (OS) and leukemia-free survival (LFS) in the training set, and the results were validated in the test set. We derived the AIPSS-MF (Artificial Intelligence Prognostic Scoring System for Myelofibrosis) model, which was based on 8 clinical variables at diagnosis and achieved high accuracy in predicting OS (training set c-index, 0.750; test set c-index, 0.744) and LFS (training set c-index, 0.697; test set c-index, 0.703). No improvement was obtained with the inclusion of MPN driver mutations in the model. We were unable to adequately assess the potential benefit of including adverse cytogenetics or high-risk mutations due to the lack of these data in many patients. AIPSS-MF was superior to the IPSS regardless of MF subtype and age range and outperformed the MYSEC-PM in patients with secondary MF. In conclusion, we have developed a prediction model based exclusively on clinical variables that provides individualized prognostic estimates in patients with primary and secondary MF. The use of AIPSS-MF in combination with predictive models that incorporate genetic information may improve disease risk stratification.

Efficacy and safety of the PreserFlo implant with mitomycin C in childhood glaucoma after previous failed glaucoma surgeries.

PURPOSE: This study aims to evaluate the efficacy and safety of the PreserFlo MicroShunt (Santen, Osaka, Japan) in lowering intraocular pressure (IOP) in childhood glaucoma patients with previous failed glaucoma surgeries. METHODS: This is a prospective case review of consecutive PreserFlo procedures performed in childhood glaucoma patients after failed surgeries. Age, sex, diagnosis, and previous glaucoma surgeries, as well as visual acuity, IOP, and treatment in the preoperative visit and all follow-up visits were collected. Outcome measures included IOP reduction from baseline, mean IOP change from baseline at month 6, medication use at 6 months, complications, adverse events, and need for further procedures. RESULTS: Fourteen patients were included, 8 (57%) males and 6 (43%) females; the mean age was 27.5 ± 13.5 years. Nine patients (64%) had at least two trabeculectomies, and 6 patients (43%) had at least one trabeculectomy and a glaucoma drainage implant. The mean IOP change from baseline was 11.3 ± 4.9 mmHg at 12 months. At 12 months, 12 patients (86%) presented ≥ 20% IOP lowering from baseline, and 11 patients (79%) presented ≥ 30%. The mean medication count decreased from 3.9 ± 0.7 (baseline) to 0.7 ± 1.3 (12 months). No intraoperative complications were reported. No adverse events were noted. No secondary filtration surgery was required, although bleb needling was required in one case, 1 month after the surgery. CONCLUSIONS: PreserFlo with MMC can be used successfully to treat uncontrolled IOP in childhood glaucoma cases with previous failed surgeries. Larger studies with longer follow-up are needed to further explore the role of the device in resistant childhood glaucoma cases.

Glaucoma medical treatment as a predictor of XEN45 subconjunctival gel implant hypotensive efficacy.

PURPOSE: The aim of this study was to determine the preoperative characteristics influencing hypotensive efficacy of the XEN45 gel stent in patients with open-angle glaucoma at one-year follow-up. MATERIALS AND METHODS: This was a retrospective multicentre study. All patients who underwent XEN45 gel stent implantation between January 2017 and January 2021 were included. The main study outcome was the assessment of one-year postoperative intraocular pressure (IOP) and glaucoma medication differences according to the number and type of preoperative topical treatments or glaucoma surgery, glaucoma stage and time since diagnosis. Follow-up period was 1-year post-surgery in all cases. IOP reduction and surgery success (not requiring reoperation or pressure failures [IOP > 18 mmHg and < 20% reduction in IOP]), safety and cost savings in topical glaucoma therapy after surgery were secondarily assessed. Linear regression analysis to determine the preoperative parameters influence on 1-year postoperative results was performed. RESULTS: XEN45 gel stent was implanted in 85 patients. One-year postoperative mean IOP dropped from 20.6 ± 4.1 to 13.7 ± 2.8 mmHg (p < 0.0001). Likewise, mean number of topical treatments decreased from 2.05 ± 0.9 to 0.36 ± 0.65 (p < 0.001). Both were mainly influenced by the number of preoperative glaucoma treatments, such that for each one-glaucoma medication increase, postoperative intraocular pressure increased by 1.18 mmHg (95% CI 0.56-1.79, p < 0.0001) and number of glaucoma medications increased by 0.3 (95% CI 0.16-0.43, p < 0.001). Overall success rates (with and without supplemental glaucoma medication use) were 97.6% (95% CI 94.5-100%), 87.1% (95% CI 80.2-87.1%) and 61.2% (95% CI 51.6-72.5%) at 3, 6 months and 1 year after surgery. No sight-threatening adverse events were reported. Mean annual cost savings on medical treatment since surgery reached EUR 251.19 ± 169. 93 euros. CONCLUSIONS: One year after surgery, XEN45 gel implant significantly reduced IOP and number of topical medications with an adequate safety profile being both mainly influenced by the number of preoperative glaucoma treatments.

Diagnóstico nutricional y neurológico según antigüedad, nivel neurológico y tipo de lesión en paciente raquimedular

Introducción: La lesión medular (LM) es un problema médico contemporáneo caracterizado por datos insuficientes sobre prevalencia y debilidad de modelización en metodología. Objetivo: Establecer las interrelaciones del estado nutricional y la condición neurológica-funcional con signos clínicos: tiempo y tipo de lesión, nivel de lesión y severidad del trauma raquimedular dorso lumbar. Material y Métodos: Estudio descriptivo transversal de 102 pacientes con trauma raquimedular al ingreso, 85 hombres y 17 mujeres (febrero 2016 - enero de 2020, CIREN) La Habana, Cuba. Se realizó evaluación nutricional, neurológica (nivel, grado y severidad de lesión) mediante escalas ASIA, Independencia SCIM-III e índice de Barthel. Se obtienen medias, desviación estándar, error estándar y análisis de varianza para distribuciones normales. Se utilizó SPSS versión 26. Resultados: La edad promedio fue 29,7 ± 8,1 años. La antigüedad del trauma fue 3,1 ± 1,4 años. La lesión raquimedular ocurrió en 50,6 % del segmento T7- L3 en pacientes con lesión completa. Hubo deficiencia energética crónica (4,9 %), según Índice de Masa Corporal; el 50,6 % fueron ≥ 22 kg/m2, según criterio de riesgo de Nash. El 73,5 % clasificaban en escala A de ASIA. La correlación entre Catz y Barthel demostró asociación significativa (p< 0,01). La disminución de masa muscular, área muscular del brazo, reflectividad y sensibilidad es significativa según antigüedad, tipo, nivel y severidad de lesiones (p< 0,05). Se discute debilidad metodológica de estimaciones para masa muscular esquelética. Conclusiones: Se caracterizan antigüedad de lesión, tono muscular y nivel neurológico de lesión medular como condicionantes interactivos del diagnóstico.

Introduction: Spinal cord injury (SCI) is a contemporary medical problem characterized by insufficient data on prevalence and weak modelling methodology. Objective: To establish nutritional status and neurological-functional condition interrelationships with clinical signs: time and type of injury, level of injury and severity of dorsal lumbar spinal cord injury. Material and Methods: A cross-sectional descriptive study of 102 patients with spinal cord trauma on admission (85 men and 17 women) was conducted from February 2016 to January 2020, in CIREN, Havana, Cuba. Nutritional and neurological assessment (level, degree and severity of injury) was performed using ASIA scales, SCIM-III Independence, and Barthel index. Means, standard deviation, standard error and analysis of variance for normal distributions were obtained. SPSS version 26 was used. Results: The mean age was 29.7 ± 8.1 years. The age of trauma was 3.1 ± 1.4 years. Spinal cord injury occurred in 50.6 % of the T7- L3 segment in patients with complete injury. There was chronic energy deficiency (4.9 %), according to Body Mass Index; 50.6 % were ≥22 kg/m2, according to Nash risk criteria. In addition, 73.5 % were classified on the ASIA A scale. The correlation between Catz and Barthel showed a significant association (p< 0.01). The decrease in muscle mass, arm muscle area, reflectivity and sensitivity were significant according to age, type, level and severity of injury (p< 0.05). Methodological weakness of estimates for skeletal muscle mass is discussed. Conclusions: Time of injury, muscle tone and neurological level of spinal cord injury are characterized as interactive determinants of the diagnosis.

Predictors of thrombosis and bleeding in 1613 myelofibrosis patients from the Spanish Registry of Myelofibrosis.

Available data have proved insufficient to develop consensus recommendations on the prevention of thrombosis and bleeding in myelofibrosis (MF). We evaluated the incidence and risk factors of vascular complications in 1613 patients from the Spanish Myelofibrosis Registry. Over a total of 6981 patient-years at risk, 6.4% of the study population had at least one thrombotic event after MF diagnosis, amounting to an incidence rate of 1.65 per 100 patient-years. Prior history of thrombosis, the JAK2 mutation, and the intermediate-2/high-risk International Prognostic Scoring System (IPSS) categories conferred an increased thrombotic risk after adjustment for the risk-modifying effect of anti-thrombotic and cytoreductive treatments. History of thrombosis and the JAK2 mutation allowed us to pinpoint a group of patients at higher risk of early thrombosis. No decreased incidence of thrombosis was observed while patients were on anti-thrombotic or cytoreductive treatment. An increased risk of venous thrombosis was found during treatment with immunomodulatory agents. A total of 5.3% of patients had at least one episode of major bleeding, resulting in an incidence rate of 1.5 events per 100 patient-years. Patients in the intermediate-2/high-risk IPSS categories treated with anti-coagulants had an almost sevenfold increased risk of major bleeding. These findings should prove useful for guiding decision-making in clinical practice.

New Prognostic Factors in Operated Extracapsular Hip Fractures: Infection and GammaTScore.

There is no universal postoperative classification of extracapsular hip fractures (ECFs). We wondered if infection (according to infection after fracture fixation criteria (IAFF)), immediate partial weight bearing (PWB) and/or the new GammaTScore tool could predict early cut-out. We also examined the correlation between GammaTScore and time to consolidation and studied long-term survival. This was a retrospective cohort study of low-energy complete ECFs operated with Gamma3T nailing in 2014 and fully monitoring, in patients aged over 65. Ten not distally locked cases, one late cut-out, one cut-through, one osteonecrosis and one pseudarthrosis were discarded. Patients were classified into early cut-out (7/204; 3.55%) and no early cut-out (197/204; 96.45%). There was a lower percentage of A2 fractures according to the AO Foundation/Orthopaedic Trauma Association classification (AO/OTA, 1997) in early cut-out. IAFF and only the GammaTScore reduction parameter were different for early cut-out, in opposition to immediate PWB, tip-to-apex distance (TAD) or the Baumgaertner-Fogagnolo classification. GammaTScore inversely correlated with consolidation (p < 0.01). Long-term survival time was not statistically significantly lower in the early cut-out group. Small sample of cases may limit our results. Apart from an important role of IAFF, GammaTScore would be useful for predicting consolidation, avoiding complications and reducing costs. Further studies are needed for reliability.

Complexing the Oncolytic Adenoviruses Ad∆∆ and Ad-3∆-A20T with Cationic Nanoparticles Enhances Viral Infection and Spread in Prostate and Pancreatic Cancer Models.

Oncolytic adenoviruses (OAd) can be employed to efficiently eliminate cancer cells through multiple mechanisms of action including cell lysis and immune activation. Our OAds, AdΔΔ and Ad-3∆-A20T, selectively infect, replicate in, and kill adenocarcinoma cells with the added benefit of re-sensitising drug-resistant cells in preclinical models. Further modifications are required to enable systemic delivery in patients due to the rapid hepatic elimination and neutralisation by blood factors and antibodies. Here, we show data that support the use of coating OAds with gold nanoparticles (AuNPs) as a possible new method of virus modification to help augment tumour uptake. The pre-incubation of cationic AuNPs with AdΔΔ, Ad-3∆-A20T and wild type adenovirus (Ad5wt) was performed prior to infection of prostate/pancreatic cancer cell lines (22Rv, PC3, Panc04.03, PT45) and a pancreatic stellate cell line (PS1). Levels of viral infection, replication and cell viability were quantified 24-72 h post-infection in the presence and absence of AuNPs. Viral spread was assessed in organotypic cultures. The presence of AuNPs significantly increased the uptake of Ad∆∆, Ad-3∆-A20T and Ad5wt in all the cell lines tested (ranging from 1.5-fold to 40-fold), compared to virus alone, with the greatest uptake observed in PS1, a usually adenovirus-resistant cell line. Pre-coating the AdΔΔ and Ad-3∆-A20T with AuNPs also increased viral replication, leading to enhanced cell killing, with maximal effect in the most virus-insensitive cells (from 1.4-fold to 5-fold). To conclude, the electrostatic association of virus with cationic agents provides a new avenue to increase the dose in tumour lesions and potentially protect the virus from detrimental blood factor binding. Such an approach warrants further investigation for clinical translation.

A Viral Suppressor of RNA Silencing May Be Targeting a Plant Defence Pathway Involving Fibrillarin.

To establish productive infections, viruses must be able both to subdue the host metabolism for their own benefit and to counteract host defences. This frequently results in the establishment of viral-host protein-protein interactions that may have either proviral or antiviral functions. The study of such interactions is essential for understanding the virus-host interplay. Plant viruses with RNA genomes are typically translated, replicated, and encapsidated in the cytoplasm of infected cells. Despite this, a significant array of their encoded proteins has been reported to enter the nucleus, often showing high accumulation at subnuclear structures such as the nucleolus and/or Cajal bodies. However, the biological significance of such a distribution pattern is frequently unknown. Here, we explored whether the nucleolar/Cajal body localization of protein p37 of Pelargonium line pattern virus (PLPV, genus Pelarspovirus, family Tombusviridae), might be related to potential interactions with the nucleolar/Cajal body marker proteins, fibrillarin and coilin. The results revealed that p37, which has a dual role as coat protein and as suppressor of RNA silencing, a major antiviral system in plants, is able to associate with these cellular factors. Analysis of (wildtype and/or mutant) PLPV accumulation in plants with up- or downregulated levels of fibrillarin or coilin have suggested that the former might be involved in an as yet unknown antiviral pathway, which may be targeted by p37. The results suggest that the growing number of functions uncovered for fibrillarin can be wider and may prompt future investigations to unveil the plant antiviral responses in which this key nucleolar component may take part.