Nanoparticle-Based Secretory Granules Induce a Specific and Long-Lasting Immune Response through Prolonged Antigen Release.

Developing prolonged antigen delivery systems that mimic long-term exposure to pathogens appears as a promising but still poorly explored approach to reach durable immunities. In this study, we have used a simple technology by which His-tagged proteins can be assembled, assisted by divalent cations, as supramolecular complexes with progressive complexity, namely protein-only nanoparticles and microparticles. Microparticles produced out of nanoparticles are biomimetics of secretory granules from the mammalian hormonal system. Upon subcutaneous administration, they slowly disintegrate, acting as an endocrine-like secretory system and rendering the building block nanoparticles progressively bioavailable. The performance of such materials, previously validated for drug delivery in oncology, has been tested here regarding the potential for time-prolonged antigen release. This has been completed by taking, as a building block, a nanostructured version of p30, a main structural immunogen from the African swine fever virus (ASFV). By challenging the system in both mice and pigs, we have observed unusually potent pro-inflammatory activity in porcine macrophages, and long-lasting humoral and cellular responses in vivo, which might overcome the need for an adjuvant. The robustness of both innate and adaptive responses tag, for the first time, these dynamic depot materials as a novel and valuable instrument with transversal applicability in immune stimulation and vaccinology.

Vaccine-carditis study: Spanish multicenter registry of inflammatory heart disease after COVID-19 vaccination.

INTRODUCTION AND OBJECTIVES: Vaccines against SARS-CoV-2 have been a major scientific and medical achievement in the control of the COVID-19 pandemic. However, very infrequent cases of inflammatory heart disease have been described as adverse events, leading to uncertainty in the scientific community and in the general population. METHODS: The Vaccine-Carditis Registry has included all cases of myocarditis and pericarditis diagnosed within 30 days after COVID-19 vaccination since August 1, 2021 in 29 centers throughout the Spanish territory. The definitions of myocarditis (probable or confirmed) and pericarditis followed the consensus of the Centers for Disease Control and the Clinical Practice Guidelines of the European Society of Cardiology. A comprehensive analysis of clinical characteristics and 3-month evolution is presented. RESULTS: From August 1, 2021, to March 10, 2022, 139 cases of myocarditis or pericarditis were recorded (81.3% male, median age 28 years). Most cases were detected in the 1st week after administration of an mRNA vaccine, the majority after the second dose. The most common presentation was mixed inflammatory disease (myocarditis and pericarditis). 11% had left ventricular systolic dysfunction, 4% had right ventricular systolic dysfunction, and 21% had pericardial effusion. In cardiac magnetic resonance studies, left ventricular inferolateral involvement was the most frequent pattern (58%). More than 90% of cases had a benign clinical course. After a 3-month follow-up, the incidence of adverse events was 12.78% (1.44% mortality). CONCLUSIONS: In our setting, inflammatory heart disease after vaccination against SARS-CoV-2 predominantly affects young men in the 1st week after the second dose of RNA-m vaccine and presents a favorable clinical course in most cases.

CAG and GGN repeat polymorphisms in the androgen receptor gene of a Chilean pediatric cohort with idiopathic inguinal cryptorchidism.

BACKGROUND: Cryptorchidism is one of the most common congenital disorders in boys and it is associated with a higher risk of sub-fertility and testicular cancer. Testicular descent occurs during embryo-fetal development in two phases, transabdominal and inguino-scrotal. In the latter process, androgens play a leading role. The androgen receptor has in its N-terminal domain, two aminoacidic repeats encoded by polymorphic nucleotide repetitions: (CAG)nCAA and GGN. The number of repetitions of these trinucleotides has been associated with different transactivation capacities and sensitivities of the androgen receptor response. OBJECTIVE: To determine whether pediatric Chilean individuals with idiopathic inguinal cryptorchidism have a different number of CAG and/or GGN repeats polymorphisms compared with controls. MATERIALS AND METHODS: A total of 109 cases with idiopathic inguinal cryptorchidism (26 bilateral and 83 unilateral) were studied by polymerase chain reaction amplification from DNA extracted from peripheral blood, followed by fragment size analysis by capillary electrophoresis, which were compared with 140 controls. RESULTS: The CAG26 repeats allele was increased in the total cases (8.3% vs. 1.4%; p = 0.012; odds ratio = 6.21, 95% confidence interval 1.31-29.4), and in bilateral cases compared to controls (11.5% vs. 1.4%; p = 0.028; odds ratio = 9 CI 95% 1.43-56.8). Similarly, CAG > 22 alleles were increased in the total cases (62.4% vs. 49.3%, p = 0.041), and more significantly in bilateral cases (73.1% vs. 49.3%; p = 0.032; odds ratio = 2.79, 95% confidence interval 1.1-7.1). In addition, CAG < 18 alleles were not observed among cases, but were present in 5.7% of controls (p = 0.01). Regarding the GGN repeats, no differences were observed between cases and controls either when analyzing separately unilateral and bilateral cryptorchidism. The joint analysis of the distribution of CAG and GGN alleles showed that the CAG26 allele was present with GGN23, hence the combination CAG26/GGN23 alleles was equally increased in bilateral cases compared with controls (11.5% vs. 1.4%). In contrast, CAG < 18 was preferably observed in the combination CAG < 18/GGN≠23 and was absent in the total cases (4.3% vs. 0%; p = 0.037). DISCUSSION: These results suggest that greater lengths of CAG alleles may contribute to a diminished androgen receptor function. The CAG26 allele alone or in combination with GGN23 was associated with a higher risk of bilateral cryptorchidism. On the other hand, CAG < 18 and the CAG < 18/GGN≠23 allele combination may reduce the probability of cryptorchidism.

Differential presentation of hypersensitivity reactions to carboplatin and oxaliplatin: Phenotypes, endotypes, and management with desensitization.

BACKGROUND: Drug hypersensitivity reactions (DHRs) to platinum-based drugs are heterogenous and restrict their access, and drug desensitization (DD) has provided a ground-breaking procedure for their re-introduction, although the response is heterogeneous. We aimed to identify the phenotypes, endotypes, and biomarkers of reactions to carboplatin and oxaliplatin and their response to DD. METHODS: Seventy-nine patients presenting with DHRs to oxaliplatin (N = 46) and carboplatin (N = 33) were evaluated at the Allergy Departments of two tertiary care hospitals in Spain. Patient symptoms, skin testing, biomarkers, and outcomes of 267 DDs were retrospectively analyzed. RESULTS: Oxaliplatin-reactive patients presented with type I (74%), cytokine release reaction (CRR) (11%), and mixed (Mx) (15%) phenotypes. In contrast, carboplatin reactive patients presented with predominantly type I (85%) and Mx (15%) but no CRRs. Out of 267 DDs, breakthrough reactions (BTRs) to oxaliplatin occurred twice as frequently as carboplatin (32% vs. 15%; p < .05). Phenotype switching from type I to another phenotype was observed in 46% of oxaliplatin DDs compared to 21% of carboplatin DDs. Tryptase was elevated in type I and Mx reactions, and IL-6 in CRR and Mx, indicating different mechanisms and endotypes. CONCLUSION: Carboplatin and oxaliplatin induced three different types of reactions with defined phenotypes and endotypes amendable to DD. Although most of the initial reactions for both were type I, oxaliplatin presented with unique CRR reactions. During DD, carboplatin reactive patients presented mostly type I BTR, while oxaliplatin-reactive patients frequently switched from type I to CRR, providing a critical difference and the need for personalized DD protocols.

Asociación entre condición física y fase angular en el adulto mayor: Un estudio piloto

El diagnóstico por bioimpedancia (BIA) y el ángulo de fase (AnF), como indicador, permiten monitorear el estado físico, de salud y nutricional en adultos mayores. El objetivo de este estudio fue establecer la relación entre la condición física y valores de fase angular por bioimpedancia en un grupo de adultos mayores sedentarios. Participaron voluntariamente 24 adultos mayores sedentarios (21 mujeres y 3 hombres). A cada participante se les midió bioimpedancia, fuerza de presión manual y test de 6 minutos del Senior Fitness Test (SFT). Posteriormente se analizaron los resultados, correlacionando el ángulo de fase (AnF) y condición física cardiorrespiratoria según sexo y el AnF con la fuerza de presión manual. El 71% presentó una media de AnF por debajo de la referencia (4,5º ± 0,4), específicamente, el 67% de los hombres y el 62% de las mujeres. La correlación entre AnF y capacidad física cardiorrespiratoria arrojó un valor de R2= 0,50; p<0,0001. La asociación entre AnF y fuerza de presión manual fue de R2=0,35; p=0,0023. Se encontró una relación significativa entre una prueba de condición física cardiorrespiratoria y AnF y entre la fuerza de presión manual y AnF. Es de importancia clínica incluir parámetros objetivos de valoración celular en adultos mayores como el AnF.

The diagnosis by bioimpedance (BIA) and the phase angle (PhA) are indicators, that allow monitoring of the physical health and nutritional status of older adults. The objective of this study was to establish the relationship between physical fitness and phase angle values by bioimpedance in a group of sedentary older adults. 24 elderly sedentary volunteers participated (21 women and 3 men). Each participant underwent bioimpedance, manual dynamometry, and the 6-minute Senior Fitness Test (SFT). Subsequently, the results were analyzed, making a correlation between PhA and cardiorespiratory physical condition, another between PhA and cardiorespiratory physical condition according to sex and finally an association between PhA and handgrip strength. R71% presented a PhA mean below the reference (4.5º ± 0.4), specifically 67% of men and 62% of women. The correlation between PhA and cardiorespiratory fitness showed a value of R2= 0.50; p<0.0001. The association between PhA and handgrip strength was R2=0.35; p=0.0023. A significant relationship was found between a cardiorespiratory fitness test and PhA and between handgrip strength and PhA. It is of clinical importance to include objective cellular assessment parameters in older adults such as PhA.

O diagnóstico por bioimpedância (BIA) e ângulo de fase (AnF), como indicador, permitem monitorar o estado físico, de saúde e nutricional de idosos. O objetivo deste estudo foi estabelecer a relação entre a condição física e os valores da fase angular por bioimpedância em um grupo de idosos sedentários. Participaram voluntariamente 24 idosos sedentários (21 mulheres e 3 homens). Cada participante foi medido bioimpedância, força de pressão manual e teste de 6 minutos do Senior Fitness Test (SFT). Posteriormente, os resultados foram analisados, correlacionando o ângulo de fase (AnF) e a condição física cardiorrespiratória de acordo com o sexo e o AnF com a força de pressão manual. 71% apresentaram média do LAn abaixo da referência (4,5º ± 0,4), sendo 67% dos homens e 62% das mulheres. A correlação entre o LAn e a aptidão cardiorrespiratória deu um valor de R2= 0,50; p<0,0001. A associação entre LAn e força de pressão manual foi R2=0,35; p=0,0023. Encontrou-se relação significativa entre teste de aptidão cardiorrespiratória e NF e entre força de pressão manual e NF. É de importância clínica incluir parâmetros objetivos de avaliação celular em adultos mais velhos, como AnF.

Características de pacientes con SARS-CoV-2 en estado crítico en un centro COVID-19 de referencia en Uruguay

Introducción: la pandemia de COVID-19 produjo una alta mortalidad en el mundo. Sin embargo, las presentaciones más críticas de la enfermedad han sido poco caracterizadas en nuestra región. Objetivo: estudiar la presentación clínica, evolución y mortalidad en pacientes ingresados en la unidad de medicina intensiva de un centro COVID-19 de referencia. Pacientes y método: estudio clínico, prospectivo, observacional de SARS-CoV-2 durante las primeras etapas de la pandemia en Uruguay. Se definió mortalidad en unidad de cuidados intensivos (UCI) como desenlace primario. Resultados: en 274 pacientes, la edad mediana fue de 65 años (IQR 54-73), el sexo masculino representó el 57% y el índice de Charlson tuvo una mediana de 3 (IQR 2-5). La mortalidad en UCI fue 59,9%. Las principales causas de muerte fueron: hipoxemia refractaria, disfunción orgánica múltiple y shock refractario. La edad (Odds Ratio (OR) = 1,06; IC de 95% 1,03 - 1,09), ocupación de camas (OR = 1,04, IC 95%: 1,02 - 1,07), sexo masculino (OR = 2,14, IC 95%: 0,93 - 5,06), ventilación mecánica invasiva (OR = 51,7, IC 95%: 16,5 - 208,6), coinfección al ingreso (OR = 2,34, IC 95%: 0,88 - 6,77) y enfermedad renal crónica previa (OR = 13,1, IC 95%: 2,29 - 129,2) fueron predictores independientes de mortalidad. La primera ola de la pandemia se produjo por la circulación de las variantes P.6 y P.1 del coronavirus, en una población con muy bajo porcentaje de vacunación (8%). Conclusiones: estos resultados en pacientes críticos aportan una descripción detallada del impacto de la pandemia por SARS-CoV-2 en un centro de referencia y constituyen una base para enfrentar futuros eventos epidémicos.

Introduction: COVID-19 has caused high mortality worldwide. However, the most critical presentations of the disease have been poorly characterized in our region. Objective: to study the clinical presentation, progression, and mortality in patients admitted to the Intensive Care Unit (ICU) of a COVID-19 Reference Center. Patients and methods: clinical, prospective, observational study of SARS-CoV-2 during the early stages of the pandemic in Uruguay. ICU mortality was defined as the primary outcome. Results: in 274 patients, the median age was 65 years (IQR 54-73), male gender accounted for 57%, and the Charlson Index was 3 (IQR 2-5). ICU mortality was 59.9%. The main causes of death were refractory hypoxemia, multiple organ dysfunction, and refractory shock. Age (Odds Ratio (OR) = 1.06; 95% CI 1.03 - 1.09), bed occupancy (OR= 1.04, 95% CI: 1.02 -1.07), male gender (OR= 2.14, 95% CI 0.93 - 5.06), invasive mechanical ventilation (OR= 51.7, 95% CI 16.5 - 208.6), coinfection at admission (OR= 2.34, 95% CI 0.88 - 6.77), and pre-existing chronic kidney disease (OR= 13.1, 95% CI 2.29 - 129.2) were independent predictors of mortality. The first wave of the pandemic was driven by the circulation of the P.6 and P.1 variants of the coronavirus in a population with a very low vaccination percentage (8%). Conclusions: these results in critical patients provide a detailed description of the impact of the SARS-CoV-2 pandemic in a reference center and serve as a foundation for addressing future epidemic events.

Introdução: a COVID-19 causou alta morbimortalidade em todo o mundo, embora as formas graves da doença tenham sido pouco caracterizadas nos países da América Latina. Objetivos: analisar o quadro clínico, a evolução e a mortalidade em pacientes com COVID-19 atendidos em uma unidade de terapia intensiva (UTI) em um Centro de Referência. Métodos: Estudo clínico, prospectivo e observacional de pacientes com SARS-CoV-2 durante a primeira onda da pandemia no Uruguai. A mortalidade na UTI foi o resultado primário. Resultados: oram estudados 274 pacientes, com uma mediada de idade de 65 anos (IQR 54-73), sendo a maioria do sexo masculino (57%). O índice de Charlson foi de 3 (IQR 2-5). A mortalidade geral na UTI foi de 59,9%. As principais causas de morte foram hipoxemia refratária, disfunção orgânica múltipla e choque refratário. A idade (Odds Ratio (OR) = 1,06; IC 95% 1,03-1,09), ocupação de leitos (OR = 1,04; IC 95%: 1,02-1,07), sexo masculino (OR = 2,14; IC 95%: 0,93-5,06), ventilação mecânica invasiva (OR = 51,7; IC 95%: 16,5-208,6), coinfecção na admissão (OR = 2,34; IC 95%: 0,88-6,77) e doença renal crônica pré-existente (OR = 13,1; IC 95%: 2,29-129,2) foram preditores independentes de mortalidade. A primeira onda da pandemia foi impulsionada pela circulação das variantes P.6 e P.1 do SARS-CoV-2 em uma população com uma taxa de vacinação muito baixa (8%). Conclusões: esses resultados em pacientes críticos fornecem uma descrição detalhada do impacto da pandemia SARS-CoV-2 em um Centro de Referência e constituem uma base para o enfrentamento de futuros eventos epidêmicos.

Clinical Characteristics and Prognostic Impact of Short Physical Performance Battery in Hospitalized Patients with Acute Heart Failure-Results of the PROFUND-IC Registry.

BACKGROUND: Most patients diagnosed with heart failure (HF) are older adults with multiple comorbidities. Multipathological patients constitute a population with common characteristics: greater clinical complexity and vulnerability, frailty, mortality, functional deterioration, polypharmacy, and poorer health-related quality of life with more dependency. OBJECTIVES: To evaluate the clinical characteristics of hospitalized patients with acute heart failure and to determine the prognosis of patients with acute heart failure according to the Short Physical Performance Battery (SPPB) scale. METHODS: Observational, prospective, and multicenter cohort study conducted from September 2020 to May 2022 in patients with acute heart failure as the main diagnosis and NT-ProBNP > 300 pg. The cohort included patients admitted to internal medicine departments in 18 hospitals in Spain. Epidemiological variables, comorbidities, cardiovascular risk factors, cardiovascular history, analytical parameters, and treatment during admission and discharge of the patients were collected. Level of frailty was assessed by the SPPB scale, and dependence, through the Barthel index. A descriptive analysis of all the variables was carried out, expressed as frequencies and percentages. A bivariate analysis of the SPPB was performed based on the score obtained (SPPB ≤ 5 and SPPB > 5). For the overall analysis of mortality, HF mortality, and readmission of patients at 30 days, 6 months, and 1 year, Kaplan-Meier survival curves were used, in which the survival experience among patients with an SPPB > 5 and SPPB ≤ 5 was compared. RESULTS: A total of 482 patients were divided into two groups according to the SPPB with a cut-off point of an SPPB < 5. In the sample, 349 patients (77.7%) had an SPPB ≤ 5 and 100 patients (22.30%) had an SPPB > 5. Females (61%) predominated in the group with an SPPB ≤ 5 and males (61%) in those with an SPPB > 5. The mean age was higher in patients with an SPPB ≤ 5 (85.63 years). Anemia was more frequent in patients with an SPPB ≤ 5 (39.5%) than in patients with an SPPB ≥ 5 (29%). This was also seen with osteoarthritis (32.7%, p = 0.000), diabetes (49.6%, p = 0.001), and dyslipidemia (69.6%, p = 0.011). Patients with an SPPB score > 5 had a Barthel index < 60 in only 4% (n = 4) of cases; the remainder of the patients (96%, n = 96) had a Barthel index > 60. Patients with an SPPB > 5 showed a higher probability of survival at 30 days (p = 0.029), 6 months (p = 0.031), and 1 year (p = 0.007) with (OR = 7.07; 95%CI (1.60-29.80); OR: 3.9; 95%CI (1.30-11.60); OR: 6.01; 95%CI (1.90-18.30)), respectively. No statistically significant differences were obtained in the probability of readmission at 30 days, 6 months, and 1 year (p > 0.05). CONCLUSIONS: Patients admitted with acute heart failure showed a high frequency of frailty as assessed by the SPPB. Patients with an SPPB ≤ 5 had greater comorbidities and greater functional limitations than patients with an SPPB > 5. Patients with heart failure and a Barthel index > 60 frequently presented an SPPB < 5. In daily clinical practice, priority should be given to performing the SPPB in patients with a Barthel index > 60 to assess frailty. Patients with an SPPB ≤ 5 had a higher risk of mortality at 30 days, 6 months, and 1 year than patients with an SPPB ≤ 5. The SPPB is a valid tool for identifying frailty in acute heart failure patients and predicting 30-day, 6-month, and 1-year mortality.

Caracterización de las cirugías laparoscópicas en el Servicio de Ginecología del Hospital Materno-Infantil Ángel Arturo Aballí / Characterization of Laparoscopic Surgeries in the Gynecology Service at Hospital Materno-Infantil Ángel Arturo Aballí

Introducción: La cirugía laparoscópica ginecológica permite intervenir a la paciente sin tener que abrir el abdomen, pues consiste en realizar pequeñas incisiones. Actualmente se emplea en enfermedades como el cáncer o en la extracción de quistes y miomas, por lo que se puede aplicar en casi cualquier intervención de cirugía ginecológica. Objetivo: Caracterizar los procedimientos laparoscópicos del Servicio de Ginecología en el Hospital Materno-Infantil Ángel Arturo Aballí en el período comprendido entre enero del 2018 y diciembre del 2021. Métodos: Se realizó un estudio observacional, descriptivo, retrospectivo de corte longitudinal con el fin de describir la actividad asistencial laparoscópica. La muestra fue de 180 pacientes, según el criterio de selección no probabilístico de los investigadores. Resultados: La edad promedio fue 41,6 años. Según los antecedentes, predominó el tamaño del útero con 91,1 por ciento (n = 164). Dentro de las indicaciones quirúrgicas, se encontró la paridad satisfecha en un 34,4 por ciento, seguido del tumor de ovario (18,9 por ciento), las neoplasias intraepiteliales cervicales (13,4 por ciento) y el fibroma uterino sintomático. En cuanto a la cirugía mayor, se encontró la histerectomía abdominal laparoscópica en un 49,0 por ciento (n = 78), seguido de la salpingectomía con un 38,9 por ciento, resultados con significación desde el punto de vista estadístico (p = 0,004). En cuanto a la cirugía menor, el 11,6 por ciento de la muestra recibió la ablación de los focos endometriales. Las complicaciones fueron escasas. Conclusiones: Los procederes laparoscópicos del Servicio de Ginecología del Hospital Materno-Infantil Ángel Arturo Aballí se consideraron adecuados de acuerdo a los indicadores quirúrgicos(AU)

Introduction: Laparoscopic gynecological surgery allows for the patient to undergo surgery without having to open their abdomen, since it consists in making small incisions. It is currently used in diseases such as cancer or in the removal of cysts and myomas; therefore, it can be applied in almost any gynecological surgery. Objective: To characterize the laparoscopic procedures of the gynecology service at Hospital Materno-Infantil Ángel Arturo Aballí, in the period from January 2018 to December 2021. Methods: An observational, descriptive, retrospective and longitudinal study was carried out in order to describe the laparoscopic assistance activity. The sample consisted of 180 patients, according to the researchers' nonprobabilistic selection criteria. Results: The mean age was 41.6 years. Concerning antecedents, uterine size predominated, with 91.1 percent (n = 164). Among surgical indications, satisfied parity was found in 34.4 percent , followed by ovarian tumor (18.9 percent ), cervical intraepithelial neoplasms (13.4 percent ) and symptomatic uterine fibroid. With respect to major surgery, laparoscopic abdominal hysterectomy was found in 49.0 percent (n = 78), followed by salpingectomy, with 38.9 percent ; such results are statistically significant (p = 0.004). Regarding minor surgery, 11.6 percent of the sample received ablation of endometrial focuses. Complications were rare. Conclusions: The laparoscopic procedures of the gynecology service at Hospital Materno-Infantil Ángel Arturo Aballí are considered adequate according to the surgical indicators(AU)

Immune responses following neonatal vaccination with conserved F4 fragment of VtaA proteins from virulent Glaesserella parasuis adjuvanted with CAF®01 or CDA.

Glaesserella parasuis is a Gram-negative bacterium that colonizes the upper airways of swine, capable of causing a systemic infection called Glässer's disease. This disease is more frequent in young post-weaning piglets. Current treatments against G. parasuis infection are based on the use of antimicrobials or inactivated vaccines, which promote limited cross-protection against different serovars. For this reason, there is an interest in developing novel subunit vaccines with the capacity to confer effective protection against different virulent strains. Herein, we characterize the immunogenicity and the potential benefits of neonatal immunization with two different vaccine formulations based on the F4 polypeptide, a conserved immunogenic protein fragment from the virulence-associated trimeric autotransporters of virulent G. parasuis strains. With this purpose, we immunized two groups of piglets with F4 combined with cationic adjuvant CAF®01 or cyclic dinucleotide CDA. Piglets immunized with a commercial bacterin and non-immunized animals served as control groups. The vaccinated piglets received two doses of vaccine, at 14 days old and 21 days later. The immune response induced against the F4 polypeptide varied depending on the adjuvant used. Piglets vaccinated with the F4+CDA vaccine developed specific anti-F4 IgGs, biased towards the induction of IgG1 responses, whereas no anti-F4 IgGs were de novo induced after immunization with the CAF®01 vaccine. Piglets immunized with both formulations displayed balanced memory T-cell responses, evidenced upon in vitro re-stimulation of peripheral blood mononuclear cells with F4. Interestingly, pigs immunized with F4+CAF®01 controlled more efficiently a natural nasal colonization by a virulent serovar 4 G. parasuis that spontaneously occurred during the experimental procedure. According to the results, the immunogenicity and the protection afforded by F4 depend on the adjuvant used. F4 may represent a candidate to consider for a Glässer's disease vaccine and could contribute to a better understanding of the mechanisms involved in protection against virulent G. parasuis colonization.

Siltuximab Monotherapy in Tafro Syndrome: A Case Report and Review of the Literature.

TAFRO syndrome is characterized by the presence of thrombocytopenia, anasarca, fever, reticular myelofibrosis, organomegaly, and is frequently associated with kidney damage in the form of membranoproliferative glomerulonephritis (MPGN) or thrombotic microangiopathy (TMA). Treatment is based on corticosteroids. A 59-year-old man who suffered from heart disease, pancytopenia and hepatosplenomegaly of unknown etiology developed nephrotic syndrome and progressive renal insufficiency, with a kidney biopsy suggestive of MPGN with a "full-house" immunofluorescence pattern. Positron emission tomography (PET) revealed multiple lymphadenopathies which histologically were compatible with multicentric Castleman's disease. The patient was diagnosed with TAFRO syndrome and treatment with siltuximab was started, with evident improvement at 3 months. TAFRO syndrome is a rare entity which may present with severe kidney involvement and histological findings of MPGN or TMA, with or without immune complex deposits. Our case suggests that a corticosteroid-free regimen with siltuximab could be an attractive therapeutic option.

Fenotipos inesperados en el síndrome de Alport: la necesidad del estudio genético / Unexpected phenotypes in Alport syndrome: the need for genetic testing

El diagnóstico del síndrome de Alport supone un reto en la edadpediátrica, debido a la ausencia de fenotipos clínicos esperados de la enfermedad, su clásica caracterización de entidad rara y la práctica muy restringida de biopsias renales con análisis rutinario de la muestra por microscopía electrónica durante la infancia. Se presentan las características clínicas y genéticas de 6 pacientes pediátricos (4 mujeres) diagnosticados de síndromede Alport en dos centros hospitalarios entre 2018 y 2021. Todos los pacientes presentaron un debut clínico claramente diferente y ninguno presentó complicaciones auditivas nioftalmológicas. La mitad carecía de antecedentes familiares de enfermedad renal crónica. Ninguna biopsia renal realizada confirmó el diagnóstico. Todos los pacientes fueron confirmadosgenéticamente y fueron el caso índice del estudio familiar. Esta serie ilustra la presencia de fenotipos clínicos inesperados en el síndrome de Alport y refleja la necesidad de incorporar el estudio genético para su diagnóstico.

The diagnosis of Alport syndrome is a challenge in the pediatric age, due to the absence of expected clinical phenotypes of the disease, its classic characterization of a rare disease and the very restricted practice of renal biopsies with routine analysis of the sample by electron microscopy during infancy. The clinical and genetic characteristics of 6 pediatric patients (4 women) diagnosed with Alport syndrome in two hospital centers between 2018 and 2021 are reported. All patients presented a clearly different clinical debut and none presented auditory or ophthalmological complications. Half had no family history of chronic kidney disease. No kidney biopsy performed confirmed the diagnosis. All patients were genetically confirmed and were the index case in the family study. This series illustrates the presence of unexpected clinical phenotypes in Alport syndrome and reflects the need for the incorporation of the genetic study for its diagnosis.

[Unexpected phenotypes in Alport syndrome: the need for genetic testing]. / Fenotipos inesperados en el síndrome de Alport: la necesidad del estudio genético.

The diagnosis of Alport syndrome is a challenge in the pediatric age, due to the absence of expected clinical phenotypes of the disease, its classic characterization of a rare disease and the very restricted practice of renal biopsies with routine analysis of the sample by electron microscopy during infancy. The clinical and genetic characteristics of 6 pediatric patients (4 women) diagnosed with Alport syndrome in two hospital centers between 2018 and 2021 are reported. All patients presented a clearly different clinical debut and none presented auditory or ophthalmological complications. Half had no family history of chronic kidney disease. No kidney biopsy performed confirmed the diagnosis. All patients were genetically confirmed and were the index case in the family study. This series illustrates the presence of unexpected clinical phenotypes in Alport syndrome and reflects the need for the incorporation of the genetic study for its diagnosis.

El diagnóstico del síndrome de Alport supone un reto en la edad pediátrica, debido a la ausencia de fenotipos clínicos esperados de la enfermedad, su clásica caracterización de entidad rara y la práctica muy restringida de biopsias renales con análisis rutinario de la muestra por microscopía electrónica durante la infancia. Se presentan las características clínicas y genéticas de 6 pacientes pediátricos (4 mujeres) diagnosticados de síndrome de Alport en dos centros hospitalarios entre 2018 y 2021. Todos los pacientes presentaron un debut clínico claramente diferente y ninguno presentó complicaciones auditivas ni oftalmológicas. La mitad carecía de antecedentes familiares de enfermedad renal crónica. Ninguna biopsia renal realizada confirmó el diagnóstico. Todos los pacientes fueron confirmados genéticamente y fueron el caso índice del estudio familiar. Esta serie ilustra la presencia de fenotipos clínicos inesperados en el síndrome de Alport y refleja la necesidad de incorporar el estudio genético para su diagnóstico.

Risk factors for posttraumatic empyema in diaphragmatic injuries.

BACKGROUND: Penetrating diaphragmatic injuries are associated with a high incidence of posttraumatic empyema. We analyzed the contribution of trauma severity, specific organ injury, contamination severity, and surgical management to the risk of posttraumatic empyema in patients who underwent surgical repair of diaphragmatic injuries at a level 1 trauma center. METHODS: This is a retrospective review of the patients who survived more than 48 h. Univariate OR calculations were performed to identify potential risk factors. Multiple logistic regression was used to calculate adjusted ORs and identify independent risk factors. RESULTS: We included 192 patients treated from 2011 to 2020. There were 169 (88.0) males. The mean interquartile range, (IQR) of age, was 27 (22-35) years. Gunshot injuries occurred in 155 subjects (80.7%). Mean (IQR) NISS and ATI were 29 (18-44) and 17 (10-27), respectively. Thoracic AIS was > 3 in 38 patients (19.8%). Hollow viscus was injured in 105 cases (54.7%): stomach in 65 (33.9%), colon in 52 (27.1%), small bowel in 42 (21.9%), and duodenum in 10 (5.2%). Visible contamination was found in 76 patients (39.6%). Potential thoracic contamination was managed with a chest tube in 128 cases (66.7%), with transdiaphragmatic pleural lavage in 42 (21.9%), and with video-assisted thoracoscopy surgery or thoracotomy in 22 (11.5%). Empyema occurred in 11 patients (5.7%). Multiple logistic regression identified thoracic AIS > 3 (OR 6.4, 95% CI 1.77-23. 43), and visible contamination (OR 5.13, 95% IC 1.26-20.90) as independent risk factors. The individual organ injured, or the method used to manage the thoracic contamination did not affect the risk of posttraumatic empyema. CONCLUSION: The severity of the thoracic injury and the presence of visible abdominal contamination were identified as independent risk factors for empyema after penetrating diaphragmatic trauma.

Comparative evaluation of two collagen-based biomaterials with different compositions used for bone graft: An experimental animal study.

A large number of materials with different compositions and shapes have been proposed and studied for the purpose of bone tissue regeneration. Collagen-based materials have shown promising results for this application, with improved physicochemical properties. The aim of the present in vivo animal study was to evaluate and compare two commercially available collagen-based biomaterials for bone regeneration, with these being implanted in circumferential bone defects created in the calvarium of rabbits. Twenty rabbits received bilateral parietal osteotomies, performed with the aid of a 6.5 mm diameter trephine. Two groups were created: the BC group, where the defect was filled with a scaffold composed of 90% bovine bone particles and 10% porcine collagen, and the EG group, where the defect was filled with a scaffold composed of 75% hydroxyapatite particles of bovine origin and 25% bovine collagen. Ten animals were sacrificed at 30 days and another 10 at 45 days after implantation, and the samples were processed and histologically analyzed. In the evaluations of the samples at 30 days, no important differences were found in the results. However, in the samples at 45 days after surgery, the EG group showed better results than the BC group samples, mainly in terms of the amount of bone matrix formation (P < 0.0001) and the volume in area measured in each sample, where the EG group had a value 65% higher than that in the BC group samples. Based on the results obtained, we conclude that the amount of collagen and the particle characteristics present in the composition of the scaffolds can directly influence the amount of neoformation and/or bone regeneration.

Outcomes of transitional care programs on adolescent chronic inflammatory systemic diseases: systematic review and meta-analyses.

BACKGROUND: Patients with juvenile chronic inflammatory systemic diseases (jCID) are vulnerable to many circumstances when transitioning to adult-centered healthcare; this increases the burden of disease and worsen their quality of life. METHODS: MEDLINE, Embase, Web of Science and Scopus were searched from inception to March 16th, 2021. We included observational, randomized controlled trials and quasi-experimental studies that evaluated a transitional care program for adolescents and young adults with jCIDs. We extracted information regarding health-related quality of life, disease activity, drop-out rates, clinical attendance rates, hospital admission rates, disease-related knowledge, surgeries performed, drug toxicity and satisfaction rates. RESULTS: Fifteen studies met our inclusion criteria. The implementation of transition programs showed a reduction on hospital admission rates for those with transition program (OR 0.28; 95% CI 0.13 to 0.61; I 2 = 0%; p = 0.97), rates of surgeries performed (OR 0.26; 95% CI 0.12 to 0.59; I 2 = 0%; p = 0.50) and drop-out rates from the adult clinic (OR 0.23; 95% CI 0.12 to 0.46; I 2 = 0%; p = 0.88). No differences were found in other outcomes. CONCLUSION: The available body of evidence supports the implementation of transition programs as it could be a determining factor to prevent hospital admission rates, surgeries needed and adult clinic attendance rates.

Polymorphisms in ACE, ACE2, AGTR1 genes and severity of COVID-19 disease.

BACKGROUND: Infection by the SARS-Cov-2 virus produces in humans a disease of highly variable and unpredictable severity. The presence of frequent genetic single nucleotide polymorphisms (SNPs) in the population might lead to a greater susceptibility to infection or an exaggerated inflammatory response. SARS-CoV-2 requires the presence of the ACE2 protein to enter in the cell and ACE2 is a regulator of the renin-angiotensin system. Accordingly, we studied the associations between 8 SNPs from AGTR1, ACE2 and ACE genes and the severity of the disease produced by the SARS-Cov-2 virus. METHODS: 318 (aged 59.6±17.3 years, males 62.6%) COVID-19 patients were grouped based on the severity of symptoms: Outpatients (n = 104, 32.7%), hospitalized on the wards (n = 73, 23.0%), Intensive Care Unit (ICU) (n = 84, 26.4%) and deceased (n = 57, 17.9%). Comorbidity data (diabetes, hypertension, obesity, lung disease and cancer) were collected for adjustment. Genotype distribution of 8 selected SNPs among the severity groups was analyzed. RESULTS: Four SNPs in ACE2 were associated with the severity of disease. While rs2074192 andrs1978124showed a protector effectassuming an overdominant model of inheritance (G/A vs. GG-AA, OR = 0.32, 95%CI = 0.12-0.82; p = 0.016 and A/G vs. AA-GG, OR = 0.37, 95%CI: 0.14-0.96; p = 0.038, respectively); the SNPs rs2106809 and rs2285666were associated with an increased risk of being hospitalized and a severity course of the disease with recessive models of inheritance (C/C vs. T/C-T/T, OR = 11.41, 95% CI: 1.12-115.91; p = 0.012) and (A/A vs. GG-G/A, OR = 12.61, 95% CI: 1.26-125.87; p = 0.0081). As expected, an older age (OR = 1.47), male gender (OR = 1.98) and comorbidities (OR = 2.52) increased the risk of being admitted to ICU or death vs more benign outpatient course. Multivariable analysis demonstrated the role of the certain genotypes (ACE2) with the severity of COVID-19 (OR: 0.31, OR 0.37 for rs2074192 and rs1978124, and OR = 2.67, OR = 2.70 for rs2106809 and rs2285666, respectively). Hardy-Weinberg equilibrium in hospitalized group for I/D SNP in ACE was not showed (p<0.05), which might be due to the association with the disease. No association between COVID-19 disease and the different AGTR1 SNPs was evidenced on multivariable, nevertheless the A/A genotype for rs5183 showed an higher hospitalization risk in patients with comorbidities. CONCLUSIONS: Different genetic variants in ACE2 were associated with a severe clinical course and death groups of patients with COVID-19. ACE2 common SNPs in the population might modulate severity of COVID-19 infection independently of other known markers like gender, age and comorbidities.