Pharmacological reprogramming of zebrafish lateral line supporting cells to a migratory progenitor state.

In the zebrafish lateral line, non-sensory supporting cells readily re-enter the cell cycle to generate new hair cells and supporting cells during homeostatic maintenance and following damage to hair cells. This contrasts with supporting cells from mammalian vestibular and auditory sensory epithelia which rarely re-enter the cell cycle, and hence loss of hair cells results in permanent sensory deficit. Lateral line supporting cells are derived from multipotent progenitor cells that migrate down the trunk midline as a primordium and are deposited to differentiate into a neuromast. We have found that we can revert zebrafish support cells back to a migratory progenitor state by pharmacologically altering the signaling environment to mimic that of the migratory primordium, with active Wnt signaling and repressed FGF signaling. The reverted supporting cells migrate anteriorly and posteriorly along the horizontal myoseptum and will re-epithelialize to form an increased number of neuromasts along the midline when the pharmacological agents are removed. These data demonstrate that supporting cells can be readily reprogrammed to a migratory multipotent progenitor state that can form new sensory neuromasts, which has important implications for our understanding of how the lateral line system matures and expands in fish and also suggest avenues for returning mammalian supporting cells back to a proliferative state.

Model of structural equations on the perception of aspects of school life and substance consumption as predictors of problem behavior in adolescents.

Introduction: Problematic behavior and drug use are behaviors of social concern, especially in adolescence. There are school factors that can contribute to their development or prevent them. The objective was to establish explanatory models of the relationship between various school variables with the consumption of alcohol, tobacco and cannabis; determining its direct and/or indirect relationship with problematic behaviors. Materials and methods: The study was cross-sectional with a sample of 346 students (Main Age=14.81; 54% women) from secondary education. Structural Equation Model (SEM) were carried to analyze the relationship between the dimensions of the Scale of perception of aspects of school life and alcohol, tobacco and cannabis consume with the presence of Problematic Behavior. Results: Problem behavior was predicted by alcohol, tobacco and cannabis consume, and binge drinking. Different aspects of school life differentially predicted problem behavior and drug use. Sense of challenge was observed as having a reciprocal predictive relationship with problem behavior. Perception of oneself at school predicts both alcohol and tobacco use; while the value given to school predicts binge drinking. Discussion: These findings suggests that, when addressing problem behavior and drug use that affect minors in school and have repercussions on class dynamics and academic outcomes, we should not focus exclusively on these problem areas, but rather take a more integrated approach that includes modifying different school-related aspects that act as risk factors for these types of problems.

Lung ultrasound and procalcitonin, improving antibiotic management and avoiding radiation exposure in pediatric critical patients with bacterial pneumonia: a randomized clinical trial.

BACKGROUND: Pneumonia is a major public health problem with an impact on morbidity and mortality. Its management still represents a challenge. The aim was to determine whether a new diagnostic algorithm combining lung ultrasound (LUS) and procalcitonin (PCT) improved pneumonia management regarding antibiotic use, radiation exposure, and associated costs, in critically ill pediatric patients with suspected bacterial pneumonia (BP). METHODS: Randomized, blinded, comparative effectiveness clinical trial. Children < 18y with suspected BP admitted to the PICU from September 2017 to December 2019, were included. PCT was determined at admission. Patients were randomized into the experimental group (EG) and control group (CG) if LUS or chest X-ray (CXR) were done as the first image test, respectively. Patients were classified: 1.LUS/CXR not suggestive of BP and PCT < 1 ng/mL, no antibiotics were recommended; 2.LUS/CXR suggestive of BP, regardless of the PCT value, antibiotics were recommended; 3.LUS/CXR not suggestive of BP and PCT > 1 ng/mL, antibiotics were recommended. RESULTS: 194 children were enrolled, 113 (58.2%) females, median age of 134 (IQR 39-554) days. 96 randomized into EG and 98 into CG. 1. In 75/194 patients the image test was not suggestive of BP with PCT < 1 ng/ml; 29/52 in the EG and 11/23 in the CG did not receive antibiotics. 2. In 101 patients, the image was suggestive of BP; 34/34 in the EG and 57/67 in the CG received antibiotics. Statistically significant differences between groups were observed when PCT resulted < 1 ng/ml (p = 0.01). 3. In 18 patients the image test was not suggestive of BP but PCT resulted > 1 ng/ml, all of them received antibiotics. A total of 0.035 mSv radiation/patient was eluded. A reduction of 77% CXR/patient was observed. LUS did not significantly increase costs. CONCLUSIONS: Combination of LUS and PCT showed no risk of mistreating BP, avoided radiation and did not increase costs. The algorithm could be a reliable tool for improving pneumonia management. CLINICAL TRIAL REGISTRATION: NCT04217980.

Nucleolar stress caused by arginine-rich peptides triggers a ribosomopathy and accelerates aging in mice.

Nucleolar stress (NS) has been associated with age-related diseases such as cancer or neurodegeneration. To investigate how NS triggers toxicity, we used (PR)n arginine-rich peptides present in some neurodegenerative diseases as inducers of this perturbation. We here reveal that whereas (PR)n expression leads to a decrease in translation, this occurs concomitant with an accumulation of free ribosomal (r) proteins. Conversely, (PR)n-resistant cells have lower rates of r-protein synthesis, and targeting ribosome biogenesis by mTOR inhibition or MYC depletion alleviates (PR)n toxicity in vitro. In mice, systemic expression of (PR)97 drives widespread NS and accelerated aging, which is alleviated by rapamycin. Notably, the generalized accumulation of orphan r-proteins is a common outcome of chemical or genetic perturbations that induce NS. Together, our study presents a general model to explain how NS induces cellular toxicity and provides in vivo evidence supporting a role for NS as a driver of aging in mammals.

Efficacy of the use of perfluorocarbon as a temporary tamponade agent in severe ocular trauma and/or complex retinopexy: a scoping review.

BACKGROUND: Perfluorocarbon (PFC)possesses unique chemical properties that favor the pigment epithelium's adhesion and allows the drainage of subretinal fluid through retinal holes present in retinal detachment cases. However, PFC as a temporary tamponade agent has been limited due to its high potential for toxicity. MAIN BODY: We conducted a scoping review regarding the use of PFC in vitreoretinal surgery as a temporary tamponade in subjects with severe ocular trauma or severe retinal detachment who received a therapeutic intervention (vitrectomy via posterior approach with the use of PFC as a temporary tamponade), compared to vitrectomy without the use of PFC as a temporary tamponade. Outcomes of interest were retinal reattachment, visual acuity (VA), postoperative complications and retinal toxicity. The search was performed in Medline, Medline In-Process & Other Non-Indexed Citations, Medline Daily Update, Embase databases. Reference lists from relevant review articles were also included. Two hundred thirty-eight studies were found, with no duplicate entries. In the first selection, 230 articles were eliminated; in the second selection, 6 additional articles were discarded. In total, 8 articles were obtained in this review. Two selected articles corresponded to animal studies and 6 to studies in humans. Regarding study design, 5 were case series, and 1 was a cohort study. CONCLUSION: PFC as a short-term tamponade had high rates of reapplication, improved VA, and the most frequent adverse effects were reversible after PFC withdrawal. Nonetheless, the quality of the studies was poor. Studies with more rigorous methodologies are needed to determine visual and structural outcomes and potential risks of PFC use as a temporary tamponade in vitreoretinal surgery.

Dynamic Micropatterning Reveals Substrate-Dependent Differences in the Geometric Control of Cell Polarization and Migration.

Cells are highly dynamic and adopt variable shapes and sizes. These variations are biologically important but challenging to investigate in a spatiotemporally controlled manner. Micropatterning, confining cells on microfabricated substrates with defined geometries and molecular compositions, is a powerful tool for controlling cell shape and interactions. However, conventional binary micropatterns are static and fail to address dynamic changes in cell polarity, spreading, and migration. Here, a method for dynamic micropatterning is reported, where the non-adhesive surface surrounding adhesive micropatterns is rapidly converted to support specific cell-matrix interactions while allowing simultaneous imaging of the cells. The technique is based on ultraviolet photopatterning of biotinylated polyethylene glycol-grafted poly-L-lysine, and it is simple, inexpensive, and compatible with a wide range of streptavidin-conjugated ligands. Experiments using biotinylation-based dynamic micropatterns reveal that distinct extracellular matrix ligands and bivalent integrin-clustering antibodies support different degrees of front-rear polarity in human glioblastoma cells, which correlates to altered directionality and persistence upon release and migration on fibronectin. Unexpectedly, however, neither an asymmetric cell shape nor centrosome orientation can fully predict the future direction of migration. Taken together, biotinylation-based dynamic micropatterns allow easily accessible and highly customizable control over cell morphology and motility.

Predictores del estado de salud funcional posingreso en cuidados intensivos en pacientes sépticos / Predictors of Post-Admission Functional Health Status in Intensive Care in Septic Patients

Introducción: Los pacientes críticos pediátricos son susceptibles de presentar alteraciones del flujo sanguíneo cerebral que impliquen un deterioro de su estado de salud funcional. Objetivo: Identificar factores predictores de mayor riesgo de mala evolución funcional en pacientes pediátricos críticos con sepsis. Métodos: Se realizó un estudio de cohortes retrospectivo con menores de 18 años de edad con sepsis, ingresados en la unidad de cuidados intensivos pediátricos. Se recogieron variables epidemiológicas, clínicas y del estado de salud funcional previas al ingreso, al alta y a los 6 meses. El estado de salud funcional se evaluó mediante la escala de categorías de estado global y cerebral pediátrico. Se evaluó el cambio del estado funcional entre el ingreso y a los 6 meses del alta. Se realizó un análisis univariante para comparar grupos considerando el mal pronóstico y el cambio del estado funcional y su relación con las variables. Resultados: Se incluyeron 46 pacientes. A los 6 meses del alta, cuatro (8,7 por ciento) presentaron mal pronóstico funcional y ocho (17,4 por ciento) empeoramiento funcional respecto al ingreso. No se encontraron asociaciones entre las variables predictoras y la morbilidad, aunque se observó cierta tendencia en algunas como mayor soporte inotrópico (VIS > 20: 12,5 por ciento vs. 50 por ciento, p= 0,075), extracorpóreo y de reemplazo renal (25 por ciento vs. 2,6 por ciento, p= 0,074) y estancia hospitalaria más prolongada (50 por ciento vs. 15,8 por ciento , p= 0,055). Conclusiones: El soporte en la unidad de cuidados intensivos pediátricos no fue un predictor de morbilidad funcional en la muestra(AU)

Introduction: Critically ill pediatric patients are susceptible to cerebral blood flow alterations that imply a deterioration of their functional health status. Objective: To identify predictors of a higher risk of poor functional outcome in critically ill pediatric patients with sepsis. Methods: A retrospective cohort study was conducted with children under 18 years of age with sepsis, who were admitted to the pediatric intensive care unit. Epidemiological, clinical, and functional health status variables were collected prior to admission, discharge, and after 6 months. Functional health status was assessed using the Pediatric Global State and Brain Status Category Scale. The change in performance status between admission and 6 months after discharge was assessed. A univariate analysis was performed to compare groups considering poor prognosis and change in functional status and their relationship with the variables. Results: A total of 46 patients were included. At 6 months after discharge, four (8.7 percent) had a poor functional prognosis and eight (17.4 percent) had functional worsening at admission. No associations were found between the predictor variables and morbidity, although some trends were observed in some variables, such as greater inotropic support (SIV > 20: 12.5 percent vs. 50 percent, p = 0.075), extracorporeal and renal replacement (25 percent vs. 2.6 , percent p = 0.074), and longer hospital stay (50 percent vs. 15.8 percent , p = 0.055). Conclusions: Support in the pediatric intensive care unit was not a predictor of functional morbidity in the sample(AU)

Risk factors and outcome of Chimeric Antigen Receptor T-Cell patients admitted to Pediatric Intensive Care Unit: CART-PICU study.

Introduction: Chimeric antigen receptor (CAR)T-cell CD19 therapy is an effective treatment for relapsed/refractory B-cell acute lymphoblastic leukemia. It can be associated with life-threatening toxicities which often require PICU admission. Purpose: to describe clinical characteristics, treatment and outcome of these patients. Methods: Prospective observational cohort study conducted in a tertiary pediatric hospital from 2016-2021. Children who received CAR-T admitted to PICU were included. We collected epidemiological, clinical characteristics, cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), treatment, length of stay and mortality. Results: CAR T-cells (4-1BB constructs) were infused in 59 patients. Twenty-four (40.7%) required PICU admission, length of stay was 4 days (IQR 3-6). Median age was 8.3 years (range 4-24). Patients admitted to PICU presented higher disease burden before infusion: 24% blasts in bone marrow (IQR 5-72) vs. 0 (0-6.9), p<0.001. No patients with <5% blasts were admitted to PICU. Main reasons for admissions were CRS (n=20, 83.3%) and ICANS (n=3, 12.5%). Fourteen patients (58.3%) required inotropic support, 14(58.3%) respiratory. Sixteen patients (66.6%) received tocilizumab, 10(41.6%) steroids, 6(25.0%) anakinra, and 5(20.8%) siltuximab. Ten patients (41.6%) presented neurotoxicity, six of them severe (ICANS 3-4). Two patients died at PICU (8.3%) because of refractory CRS-hemophagocytic lymphohistyocitosis (carHLH) syndrome. There were no significant differences in relapse rate after CAR-T in patients requiring PICU, it was more frequently CD19 negative (p=0.344). Discussion: PICU admission after CAR-T therapy was mainly due to CRS. Supportive treatment allowed effective management and high survival. Some patients presenting with carHLH, can suffer a fulminant course.

Integration of Phenotype Term Prioritization and Gene Expression Analysis Reveals a Novel Variant in the PERP Gene Associated with Autosomal Recessive Erythrokeratoderma.

Hereditary palmoplantar keratodermas (PPKs) are a clinically and genetically heterogeneous group of disorders characterized by excessive epidermal thickening of palms and soles. Several genes have been associated with PPK including PERP, a gene encoding a crucial component of desmosomes that has been associated with dominant and recessive keratoderma. We report a patient with recessive erythrokeratoderma (EK) in which whole exome sequencing (WES) prioritized by human phenotype ontology (HPO) terms revealed the presence of the novel variant c.153C > A in the N-terminal region the PERP gene. This variant is predicted to have a nonsense effect, p.(Cys51Ter), resulting in a premature stop codon. We demonstrated a marked reduction in gene expression in cultured skin fibroblasts obtained from the patient. Despite the PERP gene is expressed at low levels in fibroblasts, our finding supports a loss-of-function (LoF) mechanism for the identified variant, as previously suggested in recessive EK. Our study underscores the importance of integrating HPO analysis when using WES for molecular genetic diagnosis in a clinical setting, as it facilitates continuous updates regarding gene-clinical feature associations.

Quantification of a qualitative sepsis code: laying the foundations for the automation revolution.

To quantify a qualitative screening tool for the early recognition of sepsis in children with fever either visiting the emergency department or already admitted to hospital. Prospective observational study including febrile patients under 18 years of age. Sepsis diagnosis was the main outcome. A multivariable analysis was performed with 4 clinical variables (heart rate, respiratory rate, disability, and poor skin perfusion). The cut-off points, odds ratio, and coefficients of these variables were identified. The quantified tool was then obtained from the coefficients. The area under the curve (AUC) was obtained and internal validation was performed using k-fold cross-validation. Two hundred sixty-six patients were included. The multivariable regression confirmed the independent association of the 4 variables with the outcome. The quantified screening tool yielded an excellent AUC, 0.825 (95%CI 0.772-0.878, p < 0.001), for sepsis prediction.  Conclusion: We successfully quantified a sepsis screening tool, and the resulting model has an excellent discriminatory power. What is Known: • Screening tests have to be based only on clinical variables that needs minimum technological support. • The current Sepsis Code is a qualitative screening tool. What is New: • The current screening tool was quantified using four clinical variables, weighted according to the deviation from normality and differentiated according to the age of the patient. • The resulting model has an excellent discriminatory power in identifying septic patients among febrile pediatric patients.

Analysis of immune-mediated reactions in patients with non-small cell lung cancer treated with nivolumab and its association with effectiveness.

OBJECTIVE: To study immune-related adverse events (irAEs) in non-small cell lung cancer (NSCLC) patients treated with nivolumab, as well as to assess whether these reactions could be predictors of further effectiveness of therapy. METHODS: Retrospective, observational and longitudinal study. All NSCLC patients who received nivolumab between February 2015-May 2020 were included. In terms of safety, irAEs and their severity were registered and to evaluate the effectiveness, overall survival (OS) and progression free survival (PFS) were calculated. RESULTS: 75 patients were included. 32 patients (43%) were reported irAES. Mainly the irAEs affected the skin (36%). Followed by pneumonitis (20%), gastrointestinal reactions (12%), endocrine (12%) and hepatitis (12%). Regarding severity, 92% were moderate. The median PFS was 9.49 months on the group with irAEs versus 1.99 months on the group without irAEs group (p < 0.0001). The median OS was 17.44 months versus 7.67 months respectively (p = 0.0001). According to the incidence of irAEs developed ( = > 2 vs. 1 vs. 0), the median PFS was 20.53 versus 5.35 versus 1.99 months respectively (p < 0.0001). The median OS was 23.41 versus 15.80 versus 7.67 months, respectively (p = 0.0002). CONCLUSION: In a significant number of patients irAEs occur, generally of grade 1-2 severity, affecting mainly the skin, lungs and gastrointestinal system. We confirm that the development of irAEs in patients with NSCLC treated with nivolumab is a strong predictor of treatment effectiveness in both PFS and OS, with statistically significant results. On those patients who experience two or more immunorelated adverse events the greatest benefit has been observed.

Endoftalmitis endógena por Klebsiella pneumoniae: reporte de 2 casos y revisión de literatura referente a K. pneumoniae hipermucoviscosa e hipermucovirulenta / Endogenous Klebsiella pneumoniae endophthalmitis: report of 2 cases and literature review regarding hypermucoviscous and hypermucovirulent K. pneumoniae

Objetivo: Reportar dos casos de endoftalmitis endógena por Klebsiella pneumoniae hipermucoviscosa y revisar las características clínicas de esta entidad que ha aumentado su prevalencia en países occidentales. Observaciones: Dos pacientes fueron diagnosticados con endoftalmitis endógena por K. pneumoniae con confirmación microbiológica de un origen abdominal, uno de ellos por un absceso hepático y el otro por un absceso renal. Ambos pacientes fueron sometidos a vitrectomía precoz, y a antibióticos intravítreos/intravenosos, no obstante uno requirió evisceración y el otro presentó una agudeza visual de percepción de luz. Conclusiones e importancia: K. pneumoniae es la primera causa de endoftalmitis endógena en Asia oriental, pero es poco frecuente en los países occidentales. Sin embargo su prevalencia en esta última población parece estar aumentando en asociación con las variantes hipermucoviscosas e hipervirulentas de este microorganismo. La detección temprana y el tratamiento temprano de esta enfermedad son fundamentales para preservar la anatomía del ojo.

Objective: To report two cases of hypermucoviscous Klebsiella pneumoniae endogenous endophthalmitis and to review the clinical characteristics of this aggressive disease whose prevalence appears to be increasing in western countries. Observations: Two patients were diagnosed with K. pneumoniae endogenous endophthalmitis with microbiological confirmation of an abdominal source, one from a hepatic abscess and the other with a renal abscess. Both patients underwent early vitrectomy, and intravitreal/intravenous antibiotics, nonetheless one required evisceration and the other presented a postoperative visual acuity of light perception. Conclusions and importance: K. pneumoniae is the first cause of endogenous endophthalmitis in eastern Asia, but it is rare in western countries. Nevertheless, its prevalence in the latter population appears to be increasing in association with the hypermucoviscous and hypervirulent variants of this microorganism. The early detection and early management of this disease are pivotal to preserve the anatomy of the eye.

Semaphorin3B promotes an anti-inflammatory and pro-resolving phenotype in macrophages from rheumatoid arthritis patients in a MerTK-dependent manner.

Previous works from our group show that Semaphorin3B (Sema3B) is reduced in RA and plays a protective role in a mouse arthritis model. In turn, MerTK plays a protective function in murine arthritis models, is expressed by synovial tissue macrophages and is linked to remission in patients with RA. In this study, we examined the role of Sema3B in the phenotypic characteristics of RA macrophages and the implication of MerTK. Peripheral blood monocytes from RA patients were differentiated into IFN-γ (RA MØIFN-γ) or M-CSF (RA MØM-CSF) macrophages and stimulated with LPS, Sema3B or their combination. Alternatively, RA fibroblast like synoviocytes (FLS) were stimulated with RA MØIFN-γ and RA MØM-CSF supernatants. Gene expression was determined by qPCR and protein expression and activation by flow cytometry, ELISA and western blot. Sema3B down-regulated the expression of pro-inflammatory mediators, in both RA MØIFN-γ and RA MØM-CSF. We observed a similar reduction in RA FLS stimulated with the supernatant of Sema3B-treated RA MØIFN-γ and RA MØM-CSF. Sema3B also modulated cell surface markers in macrophages towards an anti-inflammatory phenotype. Besides, MerTK expression and activation was up-regulated by Sema3B, just as GAS6 expression, Resolvin D1 secretion and the phagocytic activity of macrophages. Importantly, the inhibition of MerTK and neuropilins 1 and 2 abrogated the anti-inflammatory effect of Sema3B. Our data demonstrate that Sema3B modulates the macrophage characteristics in RA, inducing a skewing towards an anti-inflammatory/pro-resolving phenotype in a MerTK-dependant manner. Therefore, here we identify a new mechanism supporting the protective role of Sema3B in RA pathogenesis.

Moving in the right direction: tobacco packaging and labeling in the Americas.

Objectives: To assess the adoption of tobacco packaging and labeling policies based on the World Health Organization (WHO) Framework Convention on Tobacco Control (FCTC)'s Article 11 guidelines, in the WHO Region of the Americas (AMRO). Methods: We reviewed tobacco control laws in AMRO from the Campaign for Tobacco-Free Kids' Tobacco Control Laws database. We analyzed four sub-policy areas for smoked and smokeless tobacco products: 1) health warning labels (HWLs), 2) constituents and emissions (C&Es), 3) misleading tobacco packaging and labeling, and 4) standardized "plain" packaging. Results: Of 35 countries in AMRO, 31 have tobacco packaging and labeling laws. Twenty-six countries require pictorial HWLs, 24 require warnings printed on at least 50% of the front and back of the packs, and 24 rotate a single or multiple (from 2 to 16) warnings within a specified period (from 5 up to 24 months). Only 21 countries require descriptive messages on toxic C&Es information. Twenty-seven countries ban brand descriptors with references to implied harm reduction (e.g., "light"), 24 ban figures, colors, and other signs, but only 13 prohibit emission yields printed on the packs. Only Canada and Uruguay have adopted standardized tobacco packaging while Uruguay also requires a single presentation (one brand variant) per brand family. Conclusion: Many countries in AMRO have made good progress in adopting multiple, rotating, large pictorial HWLs and banning misleading brand descriptors. However, there needs to be greater attention on other tobacco packaging and labeling provisions with a focus on implementing standardized tobacco packaging.

Progress in adopting bans on tobacco advertising, promotion, and sponsorship in the Americas: lessons from Uruguay and Argentina.

Objective: To assess progress in and barriers to implementing bans on tobacco advertising, promotion and sponsorship (TAPS) in Uruguay, which has a complete ban, and Argentina, with a partial ban. Methods: Legislation on TAPS bans in Uruguay and Argentina was reviewed and relevant published literature, news stories, civil society reports and tobacco industry reports retrieved to analyze progress in implementing TAPS bans. Results: In Uruguay, the complete TAPS ban, which includes standardized tobacco packaging, maintains high compliance and severely limits exposure of TAPS, despite a few problems with corporate social responsibility, social media, and transnational advertising. In Argentina, the partial TAPS ban has more problems with compliance and exposure to TAPS. The most important barriers to implementing TAPS bans in both countries are the tobacco companies. In Uruguay, tobacco companies do not comply in a few areas but the complete ban greatly minimizes this. In Argentina, however, tobacco companies can more easily exploit gaps in the partial TAPS ban, such as advertising at the points of sale, promoting contests, and using influencers on social media. Conclusions: The partial TAPS ban in Argentina illustrates the problems with enforcement and the tobacco industry's ability to exploit loopholes and continue to market their products, especially to young people. A complete TAPS ban, including standardized tobacco packaging, as in Uruguay, is easier to implement and enforce and is effective in reducing exposure to tobacco advertising. Nevertheless, governments should prioritize implementing TAPS bans on social media, which remains a difficult sphere to monitor and allows tobacco companies to continue recruiting and targeting young people.

Foamy Cell Histiocytosis Is a Diagnostic Pitfall: A Case Report of Xanthomatosis Secondary to Sitosterolemia Mimicking Progressive Nodular Histiocytosis.

ABSTRACT: We report a noteworthy case of a 10-year-old girl who presented with papular and nodular lesions on the skin that were clinically and histologically mistaken for progressive nodular histiocytosis. During the clinical management of the patient, the high lipid levels raised the suspicion of lipid metabolism disease and helped us to make the correct diagnosis of sitosterolemia. In sitosterolemia, proper management such as restriction of plant sterol intake and administration of cholesterol absorption inhibitor can improve prognosis.

Inter- and intra-observer variability in the selection of therapy for infantile hemangiomas among pediatric dermatologists in Spain.

BACKGROUND: Guidelines and expert recommendations on infantile hemangiomas (IH) are aimed at increasing homogeneity in clinical decisions based on the risk of sequelae. OBJECTIVE: The objective was to analyze the inter- and intra-observer agreement among pediatric dermatologists in the choice of treatment for IH. METHODS: We performed a cross-sectional inter-rater and intra-rater agreement study within the Spanish infantile hemangioma registry. Twenty-seven pediatric dermatologists were invited to participate in a survey with 50 clinical vignettes randomly selected within the registry. Each vignette contained a picture of an infantile hemangioma with a clinical description. Raters chose therapy among observation, topical timolol, or oral propranolol. The same survey reordered was completed 1 month later to assess intra-rater agreement. Vignettes were stratified into hemangioma risk categories following the Spanish consensus on IH. The agreement was measured using kappa statistics appropriate for the type of data (Gwet's AC1 coefficient and Gwet's paired t test). RESULTS: Twenty-four dermatologists completed the survey. Vignettes represented 7.8% of the Spanish hemangioma registry. The inter-rater agreement on the treatment decision was fair (AC1  = 0.39, 95% confidence interval [CI]: 0.30-0.47). When stratified by risk category, good agreement was reached for high-risk hemangiomas (AC1  = 0.77, 95% CI: 0.51-1.00), whereas for intermediate- and low-risk categories, the agreement was only fair (AC1 0.31, 95% CI: 0.16-0.46 and AC1  = 0.38, 95% CI: 0.27-0.48, respectively). Propranolol was the main option for high-risk hemangiomas (86.4%), timolol for intermediate-risk (36.8%), and observation for low-risk ones (55.9%). The intra-rater agreement was good. The inter-rater agreement between pediatric dermatologists on the treatment of IH is only fair. Variability was most significant with intermediate- and low-risk hemangiomas.

Perfil antibiótico de estreptococos del grupo viridans aislados de cavidad oral en individuos con uso prolongado de antibióticos / Antibiotic profile of viridans streptococci group isolated of oral cavity from patients with prolonged use of antibiotics

RESUMEN Los estreptococos del grupo viridans (EGV) son un grupo heterogéneo de bacterias saprófitas anaerobias facultativas que forman parte de la flora normal de cavidad oral. El incremento de la resistencia antibiótica de este grupo de bacterias cobra importancia en pacientes hospitalizados con terapia antibiótica prolongada, en los cuales estos microorganismos pueden ser sustituidos por bacterias multirresistentes. Objetivos: Determinar el porcentaje de cepas de EGV aisladas de cavidad oral resistentes a los antibióticos utilizados en el tratamiento de diversas patologías infecciosas hospitalarias. Material y Métodos: Estudio observacional descriptivo en el que se incluyeron 60 pacientes hospitalizados con historia de terapia antibiótica por más de 3 semanas. Las muestras se procesaron siguiendo protocolos estandarizados de recolección, aislamiento e identificación para EGV de cavidad oral y un protocolo de pruebas de sensibilidad antibiótica. Los resultados se muestran en tablas y gráficas de frecuencia. Resultados: La principal indicación para terapia antibiótica intrahospitalaria fue infección orofacial: 28,33%. La penicilina fue el antibiótico más utilizado ya sea en terapia única, combinada o múltiple en todos los pacientes. Se aislaron en total 108 cepas de EGV, con un promedio de 1,8 cepas por paciente. La especie predominantemente identificada fue S. mutans. El 96,3% de las cepas de EGV fue sensible a todos los antibióticos incluidos en el panel. Conclusiones: El uso de distintas combinaciones y modalidades de terapia antibiótica no tiene efecto en la susceptibilidad de EGV aislados de cavidad oral en pacientes hospitalizados, independiente de la duración del tratamiento.

ABSTRACT Viridans group streptococci (VGS) are a heterogeneous group of saprophytic facultative anaerobic bacteria that are part of the normal flora of the oral cavity. The increased resistance to multiple antibiotics in this group of bacteria becomes important in prolonged antibiotic therapies inpatient where these common microorganisms are replaced by multi-resistant bacteria. Objectives: To determine the percentage of VGS strains isolated from oral cavity resistant to antibiotics used in hospital infectious diseases. Material and methods: This is a descriptive cross-sectional study that included 60 hospitalized patients with a history of antibiotic therapy for more than 3 weeks. The samples were processed following standardized protocols for collection, isolation and identification of oral cavity VGS and a protocol of antibiotic susceptibility testing. The results are shown in tables and graphics of absolute and relative frequencies. Results: The main indication for antibiotic therapy was orofacial infection with a 28.33%. Penicillin was the antibiotic further used either in single, combined or multiple therapies in all patients. A total of 108 samples (1.8 per patient swabs) were collected. The predominantly identified specie was Streptococcus mutans. The 96.3% of all VGS strains were sensitive to all antibiotics included in the panel. Conclusion: Using different combinations and types of antibiotic therapy inpatient has no effect on the susceptibility of VGS isolated from oral cavity separate from treatment.