Endoscopic Ventricular Lavage in Pediatric Pyogenic Cerebral Ventriculitis Associated with Shunt: Outcomes and Technical Notes.

OBJECTIVE: Pyogenic cerebral ventriculitis (PCV) is a rare infectious entity characterized by a potent inflammatory reaction of the ventricular ependyma, which in most cases leads to death. We aim to present the technical note and protocol, based on our center's 10-year experience of the use of endoscopic ventricular lavage (EVL) in pediatric patients with PCV and ventricular peritoneal shunt. METHODS: For this study, all pediatric patients (<16 years) with VP shunts and PCV who were treated with EVL between January 2012 and January 2022 were included. RESULTS: Thirty-four pediatric patients with ventriculitis were analyzed. The median age was 6 years, with 61.7% being male. Most consultations occurred on Day 2 of symptoms. Fever (38.2%) and altered consciousness (26.5%) were the most common initial symptoms. Early ventriculitis was observed in 67.7% of patients. Pathogen identification in the initial cerebrospinal fluid sample was 70.6%, while samples from ventricular peritoneal shunt yielded 23.53% and catheter culture 79.4%. Gram-positive bacteria, mainly S.epidermidis (44.1%), was the most commonly isolated agent. EVL was performed in 73.5% on the second or third day. Reinfection occurred in 23.5%, and 26.5% of patients died. Concordance analysis showed 85.3% agreement between LP and catheter tip samples. Functionality improved, with 55.88% achieving a Lansky score of 90. Early ventriculitis was associated with better Lansky scores. CONCLUSION: EVL can be a useful tool in the management of PCV in cases with VP shunts. Our study suggests a higher chance of isolating an infection-causing germ in the catheter tip culture specimen compared to the cerebrospinal fluid culture. However, future studies with a larger number of patients, or multicentric studies are required for further analysis.

Parada cardiorrespiratoria intrahospitalaria: incidencia, factores pronósticos y resultados / In-hospital cardiac arrest: incidence, prognostic factors and results

Introducción y objetivos: La parada cardiorrespiratoria (PCR) intrahospitalaria es una entidad clínica con elevada morbimortalidad que presentan hasta el 2% de los pacientes ingresados. La PCR supone un importante problema de salud pública a nivel económico, social y sanitario, susceptible de revisión y mejora. El objetivo de este estudio es determinar su incidencia, la recuperación de la circulación espontánea (RCE) y la supervivencia en el Hospital de la Princesa, así como las características clínicas y demográficas de los pacientes que la sufren. Material y métodos: Estudio observacional, retrospectivo, descriptivo, de tipo registro de casos, durante un periodo de 12 meses, de pacientes por los que se avisó por PCR al equipo de intervención rápida (EIR) compuesto por el servicio de Anestesiología y Reanimación. Resultados: Un total de 44 pacientes fueron incluidos en el estudio, de los cuales 22 (50%) eran mujeres. La edad media fue de 75,70 años (±15,78 años). La incidencia obtenida fue de 2,88 PCR por cada 100.000 ingresos hospitalarios; 22 (50%) pacientes consiguieron la RCE y 11 (25%) obtuvieron la supervivencia al alta hospitalaria. La comorbilidad más prevalente en los pacientes con PCR fue la hipertensión arterial (63,64%). No fueron presenciadas el 66,7% de las PCR y solo el 15,9% presentaron un ritmo desfibrilable. Conclusiones: Los resultados obtenidos son similares a los presentados en otros grandes estudios. Por esta razón, recomendamos implementar EIR y dedicar tiempo a la formación del personal hospitalario en torno a la PCR.(AU)

Background and aims: In-hospital cardiac arrest (CA) is a clinical entity with high morbidity and mortality that occurs in up to 2% of hospitalized patients. It is a public health problem with important economic, social, and medical repercussions, and as such its incidence needs to be reviewed and improved. The aim of this study was to determine the incidence of in-hospital CA, return of spontaneous circulation (ROSC), and survival rates at Hospital de la Princesa, and to define the clinical and demographic characteristics of patients with in-hospital CA. Material and methods: Retrospective observational chart review of patients presenting in-hospital CA and treated by anaesthesiologists from the hospital's rapid intervention team. Data were collected over 1 year. Results: Forty-four patients were included in the study, of which 22 (50%) were women. Mean age was 75.70 years (±15.78 years), and incidence of in-hospital CA was 2.88 per 100,000 hospital admissions. Twenty-two patients (50%) achieved ROSC and 11 patients (25%) survived until discharge home. The most prevalent comorbidity was arterial hypertension (63.64%); 66.7% of cases were not witnessed, and only 15.9% presented a shockable rhythm. Conclusions: These results are similar to those reported in other larger studies. We recommend introducing immediate intervention teams and devoting time to training hospital staff in in-hospital CA.(AU)

Standardization of Strategies to Perform a Parafascicular Tubular Approach for the Resection of Brain Tumors in Eloquent Areas.

OBJECTIVE: The aim of this work is to define a methodological strategy for the minimally invasive tubular retractor (MITR) parafascicular transulcal approach (PTA) for the management of brain tumors sited in eloquent areas. METHODS: An observational prospective study was designed to evaluate the benefits of PTA associated with MITRs, tractography and intraoperative cortical stimulation. They study was conducted from June 2018 to June 2021. Information regarding white matter tracts was processed, preventing a potential damage during the approach and/or resection. All patients older than 18 years who had a single brain tumor lesion were included in the study. Patients with a preoperative Karnofsky Performance Scale (KPS) score greater than 70% and a Glasgow Coma Scale (GCS) score > 14 points were included. RESULTS: 72 patients were included in the study, the mean age was 49.6, the most affected gender was male, 12.5% presented aphasia, 11.1% presented paraphasia, 41.6% had motor deficit, 9.7% had an affection in the optic pathway, the most frequently affected region was the frontal lobe (26.3%), the most frequent lesions were high-grade gliomas (34.7%) and the measurement of the incisions was on average 5.58 cm. Of the patients, 94.4% underwent a total macroscopic resection and 90.2% did not present new postoperative neurological deficits. In all cases, a PTA was used. CONCLUSION: Tubular minimally invasive approaches (MIAs) allow one to perform maximal safe resection of brain tumors in eloquent areas, through small surgical corridors. Future comparative studies between traditional and minimally invasive techniques are required to further investigate the potential of these surgical nuances.

Análisis de la adherencia farmacológica utilizando la receta electrónica en una farmacia comunitaria: estudio ‘REACT’ / Analysis of medication adherence using electronic prescriptions in a community pharmacy: ‘REACT’ study

Antecedentes: la falta de adherencia de los pacientes a sus tratamientos tiene un gran impacto tanto clínico como económico. Aunque existen diferentes métodos para medir la adherencia, los estudios retrospectivos son cada vez más utilizados por ser objetivos y menos sensibles a la percepción del paciente, interfiriendo menos en su vida. El sistema de receta electrónica proporciona a la farmacia comunitaria una herramienta útil para llevar a cabo esta investigación.Objetivos: utilizar el sistema de receta electrónica para medir la adherencia de los pacientes a su medicación crónica, analizando diferentes grupos terapéuticos y la salud mental de los pacientes.Métodos: se desarrolló un estudio observacional, ambispectivo y longitudinal. La adherencia se evaluó mediante la Proportion of Days Covered (PDC) por paciente y por tratamiento y con el test de Morisky Green Levine. A través del sistema de receta electrónica se obtuvieron datos sobre los medicamentos dispensados a los pacientes durante los últimos 12 meses. Los datos sobre la salud mental de los pacientes se recogieron mediante el cuestionario PHQ-2.Resultados: se reclutaron un total de 300 pacientes, pero sólo 290 se incluyeron en el análisis. El 25,5 % (IC: 20,6-30,9) se clasificó como polimedicado. El PDC por paciente tuvo una mediana de 0,90 (AI: 0,73-1). Según el cuestionario de Morisky Green Levine, el 57,9 % de los pacientes (IC: 52,0-63,6) eran adherentes a sus tratamientos. La concordancia entre el test de Morisky Green Levine y el PDC fue de kappa=0,086.Conclusiones: la receta electrónica resultó ser una herramienta útil para conocer la adherencia de la población a sus tratamientos crónicos medida con el PDC. (AU)

Gravedad de los pacientes ingresados por EPOC agudizada en el ensayo clínico SLICE / Severity of patients admitted for acute COPDin the SLICE clinical trial

Introducción: Hay poca información actualizada sobre las características clínicas y la gravedad de los pacientes con EPOC que ingresan por una agudización. Nuestro objetivo fue caracterizar a los pacientes que ingresan por agudización de EPOC según la limitación al flujo aéreo: obstrucción leve (Volumen Espiratorio Forzado en el primer segundo [VEF1] ≥ 80%); moderada (VEF1 50 - 79%); grave (VEF1 30 - 49%); o muy grave (VEF1 <3 0%).Métodos: Realizamos un análisis post-hoc del ensayo clínico multicéntrico SLICE (Significance of Pulmonary Embolism in COPD Exacerbations), que reclutó pacientes consecutivos con agudización de EPOC que requirieron ingreso en 18 hospitales españoles en el periodo comprendido entre septiembre de 2014 y julio de 2020.Resultados: Incluimos 737 pacientes, con una edad media (DE) de 70,2 ± 9,9 años, y un predominio de hombres (73,5%). La espirometría clasificó a los pacientes con obstrucción leve, moderada, grave o muy grave en el 8%, 31,5%, 45% y el 15,5%, respectivamente. Al comparar a los pacientes de acuerdo al grado de obstrucción, observamos que los pacientes con mayor obstrucción al flujo aéreo eran más jóvenes (leve: 71,7 ± 8,8, moderada: 72,4 ± 10, grave: 70,2 ± 9,8, muy grave: 66,6 ± 9,2; p < 0,001), presentaban más insuficiencia respiratoria crónica (37,3% vs. 30,2% vs. 44,9% vs. 64,3%; p < 0,001), presentaban más cianosis (5,8% vs. 5,9% vs. 8,5% vs. 15,3%; p < 0,001), presentaron mayor porcentaje de agudizaciones y estaban más taquicárdicos a su llegada al centro hospitalario (92 ± 16 latidos por minuto [lpm] vs. 94 ± 18 vs. 96 ± 18 lpm vs. 99 ± 18 lpm; p < 0,001). Además, la gasometría arterial al ingreso mostraba un pH menor y una pCO2 mayor cuanto más grave era la obstrucción al flujo aéreo (p < 0,001). Conclusión: La gravedad de la obstrucción al flujo aéreo se asocia con la forma de presentación y el resultado de la gasometría arterial del paciente con agudización de EPOC que requiere ingreso hospitalario. (AU)

Introduction: There is little up-to-date information on the clinical characteristics and severity of COPD patients admitted for an exacerbation. Our objective was to characterize patients admitted due to COPD exacerbation according to airflow limitation: mild obstruction (Forced Expiratory Volume in 1 second [FEV1] ≥ 80%); moderate (FEV1 50 - 79%); severe (FEV1 30 - 49%); or very severe (FEV1 <3 0%).Methods: We performed a post-hoc analysis of the multicenter clinical trial SLICE (Significance of Pulmonary Embolism in COPD Exacerbations), which recruited consecutive patients with COPD exacerbation who required admission to 18 Spanish hospitals in the period between September 2014 and July 2020.Results: We included 737 patients, with a mean (SD) age of 70.2 ± 9.9 years, and a predominance of men (73.5%). Spirometry classified patients with mild, moderate, severe, or very severe obstruction in 8%, 31.5%, 45%, and 15.5%, respectively. When comparing the patients according to the degree of obstruction, we observed that the patients with greater airflow obstruction were younger (mild: 71.7 ± 8.8, moderate: 72.4 ± 10, severe: 70.2 ± 9.8, very severe: 66.6 ± 9.2; p < 0.001), had more chronic respiratory failure (37.3% vs. 30.2% vs. 44.9% vs. 64.3%; p < 0.001), had more cyanosis (5.8% vs. 5.9% vs. 8.5% vs. 15.3%; p < 0.001), had a higher percentage of exacerbations and were more tachycardic on arrival at the center hospital (92 ± 16 beats per minute [bpm] vs. 94 ± 18 vs. 96 ± 18 bpm vs. 99 ± 18 bpm; p < 0.001). In addition, arterial blood gases on admission showed a lower pH and a higher pCO2 the more severe the airflow obstruction was (p < 0.001).Conclusion: The severity of the airflow obstruction is associated with the form of presentation and the result of the arterial blood gases of the patient with COPD exacerbation who requires hospital admission. (AU)

Mass Spectrometry Identification of Biomarkers in Extracellular Vesicles From Plasmodium vivax Liver Hypnozoite Infections.

Latent liver stages termed hypnozoites cause relapsing Plasmodium vivax malaria infection and represent a major obstacle in the goal of malaria elimination. Hypnozoites are clinically undetectable, and presently, there are no biomarkers of this persistent parasite reservoir in the human liver. Here, we have identified parasite and human proteins associated with extracellular vesicles (EVs) secreted from in vivo infections exclusively containing hypnozoites. We used P. vivax-infected human liver-chimeric (huHEP) FRG KO mice treated with the schizonticidal experimental drug MMV048 as hypnozoite infection model. Immunofluorescence-based quantification of P. vivax liver forms showed that MMV048 removed schizonts from chimeric mice livers. Proteomic analysis of EVs derived from FRG huHEP mice showed that human EV cargo from infected FRG huHEP mice contain inflammation markers associated with active schizont replication and identified 66 P. vivax proteins. To identify hypnozoite-specific proteins associated with EVs, we mined the proteome data from MMV048-treated mice and performed an analysis involving intragroup and intergroup comparisons across all experimental conditions followed by a peptide compatibility analysis with predicted spectra to warrant robust identification. Only one protein fulfilled this stringent top-down selection, a putative filamin domain-containing protein. This study sets the stage to unveil biological features of human liver infections and identify biomarkers of hypnozoite infection associated with EVs.

Advancing Key Gaps in the Knowledge of Plasmodium vivax Cryptic Infections Using Humanized Mouse Models and Organs-on-Chips.

Plasmodium vivax is the most widely distributed human malaria parasite representing 36.3% of disease burden in the South-East Asia region and the most predominant species in the region of the Americas. Recent estimates indicate that 3.3 billion of people are under risk of infection with circa 7 million clinical cases reported each year. This burden is certainly underestimated as the vast majority of chronic infections are asymptomatic. For centuries, it has been widely accepted that the only source of cryptic parasites is the liver dormant stages known as hypnozoites. However, recent evidence indicates that niches outside the liver, in particular in the spleen and the bone marrow, can represent a major source of cryptic chronic erythrocytic infections. The origin of such chronic infections is highly controversial as many key knowledge gaps remain unanswered. Yet, as parasites in these niches seem to be sheltered from immune response and antimalarial drugs, research on this area should be reinforced if elimination of malaria is to be achieved. Due to ethical and technical considerations, working with the liver, bone marrow and spleen from natural infections is very difficult. Recent advances in the development of humanized mouse models and organs-on-a-chip models, offer novel technological frontiers to study human diseases, vaccine validation and drug discovery. Here, we review current data of these frontier technologies in malaria, highlighting major challenges ahead to study P. vivax cryptic niches, which perpetuate transmission and burden.

Preoperative nutritional status assessed using the CONUT tool and its relationship with the appearance of major postoperative complications.

INTRODUCTION: Malnutrition is a risk factor for the appearance of major postoperative complications; therefore, early identification and perioperative optimization of surgical patients may improve postoperative outcomes. The objective of our study was to determine the prevalence of moderate or high under nutrition alerts in patients undergoing major non-cardiac surgery, and their relationship with the appearance of major postoperative complications. Nutritional status was calculated using the CONUT tool. MATERIAL AND METHODS: A retrospective observational study in 190 patients who underwent major non-cardiac surgery over two consecutive years. Preoperative nutritional status was calculated using CONUT, and the patients' medical records were reviewed to determine their epidemiological characteristics and major complications. RESULTS: The under nutrition alert was moderate in 17% of patients, and high in 10%. A high under nutrition alert was an independent risk factor for treatment with vasoactive drugs (OR 3.58; 95% CI 1.18-10.89; p = 0.025), respiratory support (OR 7.63; 95% CI 1.25-46.43; p = 0.027), renal support (OR 23.29; 95% CI 2.0-271.08; p = 0.012), prolonged hospital stay (Coef 20.16; 95% CI 2.10-38.22; p = 0.029) and higher in-hospital mortality (OR 7.15; 95% CI 1.31-39.02; p = 0.023). CONCLUSIONS: In total, 10% of patients who underwent major non-cardiac surgery presented serious preoperative deterioration in their nutritional status. A high under nutrition alert was an independent risk factor for the appearance of major postoperative complications.

Anatomic variations of the floor of the third ventricle: Surgical implications for endoscopic third ventriculostomy.

Background: Endoscopic third ventriculostomy (ETV) is currently used as a treatment for different types of hydrocephalus. However, the anatomical endoscopic variants of the third ventricle floor (3VF), as well as their surgical implications, have been underrated. The anatomic variations of the 3VF can influence the technique and the success rate of the ETV. The purpose of this article is to describe the anatomical variations of 3VF, assess their incidence, and discuss the implications for ETV. Methods: Intraoperative videos of 216 patients who underwent ETV between January 2012 and February 2020 at Hospital Infantil Universitario de San José, Bogotá, Colombia were reviewed. One hundred and eighty patients who met the criteria to demonstrate the type of 3VF were selected. Results: 3VF types were classified as follows: (1) Thinned, (2) thickened, (3) partially erased, (4) globular or herniated, and (5) narrowed. Conclusion: Knowledge of anatomical variations of the 3VF is paramount for ETV and it influences the success rate of the procedure.

Estado nutricional preoperatorio valorado mediante la herramienta CONUT y su relación con la aparición de complicaciones mayores postoperatorias / Preoperative nutritional status assessed using the CONUT tool and its relationship with the appearance of major postoperative complications

Introducción: La desnutrición es un factor de riesgo para la aparición de complicaciones mayores postoperatorias, por lo que una identificación precoz de los pacientes, acompañada de una optimización perioperatoria, puede relacionarse con una mejoría de los resultados. El objetivo de nuestro estudio fue conocer la prevalencia de alerta nutricional moderada o alta, calculada por el sistema CONUT, en los pacientes intervenidos de cirugía mayor no cardiaca y su relación con la aparición de complicaciones mayores postoperatorias. Material y métodos: Estudio retrospectivo observacional que incluyó 190 pacientes intervenidos de cirugía mayor no cardiaca en el periodo de dos años consecutivos, con alerta nutricional CONUT calculada previa a la intervención. Se revisaron las historias clínicas para conocer las características epidemiológicas de los pacientes así como las complicaciones mayores asociadas. Resultados: La prevalencia de alerta nutricional moderada fue del 17% y alta del 10%. Tener una alerta nutricional alta fue factor de riesgo independiente de necesidad de tratamiento con drogas vasoactivas (OR 3,58; IC 95% 1,18-10,89; p=0,025), terapia de soporte respiratorio (OR 7,63; IC 95% 1,25-46,43; p=0,027), soporte renal (OR 23,29; IC 95% 2,0-271,08; p=0,012), aumento de estancia hospitalaria (coef. 20,16; IC 95% 2,10-38,22; p=0,029) y mayor mortalidad durante el ingreso (OR 7,15; IC 95% 1,31-39,02; p=0,023). Conclusiones: El 10% de los pacientes que se intervinieron de cirugía mayor no cardiaca presentaron un deterioro preoperatorio grave del estado nutricional. Una alerta nutricional alta fue factor de riesgo independiente para la aparición de complicaciones mayores postoperatorias.(AU)

Introduction: Malnutrition is a risk factor for the appearance of major postoperative complications; therefore, early identification and perioperative optimization of surgical patients may improve postoperative outcomes. The objective of our study was to determine the prevalence of moderate or high under nutrition alerts in patients undergoing major non-cardiac surgery, and their relationship with the appearance of major postoperative complications. Nutritional status was calculated using the CONUT tool. Material and methods: A retrospective observational study in 190 patients who underwent major non-cardiac surgery over two consecutive years. Preoperative nutritional status was calculated using CONUT, and the patients’ medical records were reviewed to determine their epidemiological characteristics and major complications.ResultsThe under nutrition alert was moderate in 17% of patients, and high in 10%. A high under nutrition alert was an independent risk factor for treatment with vasoactive drugs (OR 3.58; 95% CI 1.18-10.89; p=.025), respiratory support (OR 7.63; 95% CI 1.25-46.43; p=.027), renal support (OR 23.29; 95% CI 2.0-271.08; p=.012), prolonged hospital stay (coef. 20.16; 95% CI 2.10-38.22; p=.029) and higher in-hospital mortality (OR 7.15; 95% CI 1.31-39.02; p=.023). Conclusions: In total, 10% of patients who underwent major non-cardiac surgery presented serious preoperative deterioration in their nutritional status. A high under nutrition alert was an independent risk factor for the appearance of major postoperative complications.(AU)

Prevalencia de obesidad y riesgo cardiovascular en trabajadores del área de hidrocarburos / Prevalence of obesity and cardiovascular risk in workers in the hydrocarbon area

Resumen Introducción: La enfermedad cardiovascular (infarto de miocardio, muerte cardíaca y accidente cerebrovascular fatal o no fatal) es la principal causa de muerte prematura y de discapacidad en el mundo. Es responsable de más de 17 millones de muertes anuales y afecta principalmente a la población que se ubica en los países de ingresos bajos y medios. Se estima que el 80% de la carga mundial se produce en estos países. Objetivo: Establecer la prevalencia de obesidad y riesgo cardiovascular mediante los criterios de Framingham en una población de trabajadores de la industria de producción de hidrocarburos. Método: Se desarrolló un estudio observacional descriptivo, epidemiológico, en el que se tuvo en cuenta la población de los trabajadores de la empresa Montajes JM, Cerritos CPE6, Proyecto 176, en el departamento del Meta (Puerto Gaitán). Se representaron las variables en promedio, intervalos de confianza y desviación estándar, procediendo a desarrollar un análisis por sexo para cada uno de los factores de riesgo. Resultados: En la población del programa de riesgo cardiovascular se encontró un promedio de edad de 38.11 años y un índice de masa corporal de 26.00 m2/kg. El 7.58% presentó hipertensión arterial, el 1.08% diabetes mellitus y el 24.91% tabaquismo. El riesgo cardiovascular calculado con la escala de Framingham fue del 4.48%. El índice de masa corporal, la edad y la presión arterial sistólica no son estadísticamente significativos para la valoración del riesgo con la escala Framingham. Conclusiones: La prevalencia de obesidad fue del 64.9%, en tanto que el 75% de las personas que trabajan en hidrocarburos tenían riesgo leve de enfermedad cardiovascular.

Abstract Introduction: Cardiovascular disease is one of the main causes of premature death and disability worldwide (myocardial infarction, cardiac death and fatal or non-fatal stroke) is responsible for more than 17 million annual deaths, in patients of low- and middle-income countries, it is estimated that 80% of the global burden occurs in these countries. Objective: To establish the prevalence of obesity and cardiovascular risk, evaluated using the Framingham criteria in a population of workers in the hydrocarbon production industry. Method: An observational, descriptive, epidemiological study was carried out of a population of workers of the company Montajes JM, Cerritos CPE6 Project 176, in Puerto Gaitan in the department of Meta, Colombia. The variables in average, standard deviation and confidence intervals were described, with a comparative analysis of risk factors by sex. Results: In the population of the cardiovascular risk program, an average age of 38.11 years old and a body mass index of 26.00 m2/kg were found. 7.58% presented high blood pressure, 1.08% diabetes mellitus and 24.91% were found to smoke. The cardiovascular risk calculated with the Framingham scale was found to be 4.48%. Body mass index, age and systolic blood pressure were not statistically significant for the risk assessment using the Framingham scales. Conclusions: The prevalence of obesity in the group of workers in the hydrocarbon drilling industry was 64.9% and 75% had a slight risk of cardiovascular disease.

Morphological and Transcriptional Changes in Human Bone Marrow During Natural Plasmodium vivax Malaria Infections.

BACKGROUND: The presence of Plasmodium vivax malaria parasites in the human bone marrow (BM) is still controversial. However, recent data from a clinical case and experimental infections in splenectomized nonhuman primates unequivocally demonstrated the presence of parasites in this tissue. METHODS: In the current study, we analyzed BM aspirates of 7 patients during the acute attack and 42 days after drug treatment. RNA extracted from CD71+ cell suspensions was used for sequencing and transcriptomic analysis. RESULTS: We demonstrated the presence of parasites in all patients during acute infections. To provide further insights, we purified CD71+ BM cells and demonstrated dyserythropoiesis and inefficient erythropoiesis in all patients. In addition, RNA sequencing from 3 patients showed that genes related to erythroid maturation were down-regulated during acute infections, whereas immune response genes were up-regulated. CONCLUSIONS: This study thus shows that during P. vivax infections, parasites are always present in the BM and that such infections induced dyserythropoiesis and ineffective erythropoiesis. Moreover, infections induce transcriptional changes associated with such altered erythropoietic response, thus highlighting the importance of this hidden niche during natural infections.

Cryptic erythrocytic infections in Plasmodium vivax, another challenge to its elimination.

Human malaria caused by Plasmodium vivax infection (vivax malaria) is a major global health issue. It is the most geographically widespread form of the disease, accounting for 7 million annual clinical cases, the majority of cases in America and Asia and an estimation of over 2.5 billion people living under risk of infection. The general perception towards vivax malaria has shifted recently, following a series of reports, from being viewed as a benign infection to the recognition of its potential for more severe manifestations including fatal cases. However, the underlying pathogenic mechanisms of vivax malaria remain largely unresolved. Asymptomatic carriers of malaria parasites are a major challenge for malaria elimination. In the case of P. vivax, it has been widely accepted that the only source of cryptic parasites is hypnozoite dormant stages. Here, we will review new evidence indicating that cryptic erythrocytic niches outside the liver, in particular in the spleen and bone marrow, can represent a major source of asymptomatic infections. The origin of such parasites is being controversial and many key gaps in the knowledge of such infections remain unanswered. Yet, as parasites in these niches seem to be sheltered from immune response and antimalarial drugs, research on this area should be reinforced if elimination of malaria is to be achieved. Last, we will glimpse into the role of reticulocyte-derived exosomes, extracellular vesicles of endocytic origin, as intercellular communicators likely involved in the formation of such cryptic erythrocytic infections.

Pitting of malaria parasites in microfluidic devices mimicking spleen interendothelial slits.

The spleen is a hematopoietic organ that participates in cellular and humoral immunity. It also serves as a quality control mechanism for removing senescent and/or poorly deformable red blood cells (RBCs) from circulation. Pitting is a specialized process by which the spleen extracts particles, including malaria parasites, from within circulating RBCs during their passage through the interendothelial slits (IES) in the splenic cords. To study this physiological function in vitro, we have developed two microfluidic devices modeling the IES, according to the hypothesis that at a certain range of mechanical stress on the RBC, regulated through both slit size and blood flow, would force it undergo the pitting process without affecting the cell integrity. To prove its functionality in replicating pitting of malaria parasites, we have performed a characterization of P. falciparum-infected RBCs (P.f.-RBCs) after their passage through the devices, determining hemolysis and the proportion of once-infected RBCs (O-iRBCs), defined by the presence of a parasite antigen and absence of DAPI staining of parasite DNA using a flow cytometry-based approach. The passage of P.f.-RBCs through the devices at the physiological flow rate did not affect cell integrity and resulted in an increase of the frequency of O-iRBCs. Both microfluidic device models were capable to replicate the pitting of P.f.-RBCs ex vivo by means of mechanical constraints without cellular involvement, shedding new insights on the role of the spleen in the pathophysiology of malaria.

Septic shock from disseminated tuberculosis with splenic tuberculous abscess.

Splenic tuberculosis is a little-known and difficult to diagnose entity due to its low presentation of symptoms. It corresponds to one of the forms of extrapulmonary presentation of the disease, which in turn have a greater association with immunocompromised states such as diabetes mellitus. We present the case of a patient with diabetes mellitus who was admitted in the context of septic shock secondary to a probable splenic abscess, requiring surgical intervention. A total splenectomy was performed, managing to isolate Mycobacterium tuberculosis from the surgical specimen.

La tuberculosis esplénica es poco conocida y de difícil diagnóstico por su escasa presentación de síntomas. Corresponde a una de las formas de presentación extrapulmonar de la enfermedad, las cuales tienen mayor asociación con estados de inmunocompromiso, como la diabetes mellitus. Presentamos el caso de un paciente con diabetes mellitus que ingresó con choque séptico secundario a un probable absceso esplénico, requiriendo intervención quirúrgica en la que se llevó a cabo esplenectomía total y estudio histopatológico, con identificación de Mycobacterium tuberculosis en la pieza quirúrgica.

Preoperative nutritional status assessed using the CONUT tool and its relationship with the appearance of major postoperative complications. / Estado nutricional preoperatorio valorado mediante la herramienta CONUT y su relación con la aparición de complicaciones mayores postoperatorias.

INTRODUCTION: Malnutrition is a risk factor for the appearance of major postoperative complications; therefore, early identification and perioperative optimization of surgical patients may improve postoperative outcomes. The objective of our study was to determine the prevalence of moderate or high under nutrition alerts in patients undergoing major non-cardiac surgery, and their relationship with the appearance of major postoperative complications. Nutritional status was calculated using the CONUT tool. MATERIAL AND METHODS: A retrospective observational study in 190 patients who underwent major non-cardiac surgery over two consecutive years. Preoperative nutritional status was calculated using CONUT, and the patients' medical records were reviewed to determine their epidemiological characteristics and major complications. RESULTS: The under nutrition alert was moderate in 17% of patients, and high in 10%. A high under nutrition alert was an independent risk factor for treatment with vasoactive drugs (OR 3.58; 95% CI 1.18-10.89; p=.025), respiratory support (OR 7.63; 95% CI 1.25-46.43; p=.027), renal support (OR 23.29; 95% CI 2.0-271.08; p=.012), prolonged hospital stay (coef. 20.16; 95% CI 2.10-38.22; p=.029) and higher in-hospital mortality (OR 7.15; 95% CI 1.31-39.02; p=.023). CONCLUSIONS: In total, 10% of patients who underwent major non-cardiac surgery presented serious preoperative deterioration in their nutritional status. A high under nutrition alert was an independent risk factor for the appearance of major postoperative complications.

Plasmodium vivax epidemiology in Ethiopia 2000-2020: A systematic review and meta-analysis.

BACKGROUND: Ethiopia is one of the scarce African countries where Plasmodium vivax and P. falciparum co-exist. There has been no attempt to derive a robust prevalence estimate of P. vivax in the country although a clear understanding of the epidemiology of this parasite is essential for informed decisions. This systematic review and meta-analysis, therefore, is aimed to synthesize the available evidences on the distribution of P. vivax infection by different locations/regions, study years, eco-epidemiological zones, and study settings in Ethiopia. METHODS: This study was conducted in accordance with Preferred Reposting Items for Systematic Reviews and Meta Analyses (PRISMA) guidelines. Studies conducted and published over the last two decades (2000 to 2020) that reported an estimate of P. vivax prevalence in Ethiopia were included. The Cochrane Q (χ2) and the I2 tests were used to assess heterogeneity, and the funnel plot and Egger's test were used to examine publication bias. A p-value of the χ2 test <0.05 and an I2 value >75% were considered presence of considerable heterogeneity. Random effect models were used to obtain pooled estimate of P. vivax infection prevalence. This study is registered with PROSPERO (International Prospective Register of Systematic Reviews): ID CRD42020201761. RESULTS: We screened 4,932 records and included 79 studies that enrolled 1,676,659 confirmed malaria cases, from which 548,214 (32.69%) were P. vivax infections and 1,116,581 (66.59%) were due to P. falciparum. The rest were due to mixed infections. The pooled estimate of P. vivax prevalence rate was 8.93% (95% CI: 7.98-9.88%) with significant heterogeneity (I2 = 100%, p<0.0001). Regional differences showed significant effects (p<0.0001, and I2 = 99.4%) on the pooled prevalence of P. vivax, while study years (before and after the scaling up of interventional activities) did not show significant differences (p = 0.9, I2 = 0%). Eco-epidemiological zones considered in the analysis did show a significant statistical effect (p<0.001, I2 = 78.5%) on the overall pooled estimate prevalence. Also, the study setting showed significant differences (p = 0.001, and I2 = 90.3%) on the overall prevalence, where significant reduction of P. vivax prevalence (4.67%, 95%CI: 1.41-7.93%, p<0.0001) was observed in studies conducted at the community level. The studies included in the review demonstrated lack of publication bias qualitatively (symmetrical funnel plot) and quantitatively [Egger's test (coefficient) = -2.97, 95% CI: -15.06-9.13, p = 0.62]. CONCLUSION: The estimated prevalence of P. vivax malaria in Ethiopia was 8.93% with P. vivax prevailing in the central west region of Ethiopia, but steadily extending to the western part of the country. Its distribution across the nation varies according to geographical location, study setting and study years.

Evaluation of splenic accumulation and colocalization of immature reticulocytes and Plasmodium vivax in asymptomatic malaria: A prospective human splenectomy study.

BACKGROUND: A very large biomass of intact asexual-stage malaria parasites accumulates in the spleen of asymptomatic human individuals infected with Plasmodium vivax. The mechanisms underlying this intense tropism are not clear. We hypothesised that immature reticulocytes, in which P. vivax develops, may display high densities in the spleen, thereby providing a niche for parasite survival. METHODS AND FINDINGS: We examined spleen tissue in 22 mostly untreated individuals naturally exposed to P. vivax and Plasmodium falciparum undergoing splenectomy for any clinical indication in malaria-endemic Papua, Indonesia (2015 to 2017). Infection, parasite and immature reticulocyte density, and splenic distribution were analysed by optical microscopy, flow cytometry, and molecular assays. Nine non-endemic control spleens from individuals undergoing spleno-pancreatectomy in France (2017 to 2020) were also examined for reticulocyte densities. There were no exclusion criteria or sample size considerations in both patient cohorts for this demanding approach. In Indonesia, 95.5% (21/22) of splenectomy patients had asymptomatic splenic Plasmodium infection (7 P. vivax, 13 P. falciparum, and 1 mixed infection). Significant splenic accumulation of immature CD71 intermediate- and high-expressing reticulocytes was seen, with concentrations 11 times greater than in peripheral blood. Accordingly, in France, reticulocyte concentrations in the splenic effluent were higher than in peripheral blood. Greater rigidity of reticulocytes in splenic than in peripheral blood, and their higher densities in splenic cords both suggest a mechanical retention process. Asexual-stage P. vivax-infected erythrocytes of all developmental stages accumulated in the spleen, with non-phagocytosed parasite densities 3,590 times (IQR: 2,600 to 4,130) higher than in circulating blood, and median total splenic parasite loads 81 (IQR: 14 to 205) times greater, accounting for 98.7% (IQR: 95.1% to 98.9%) of the estimated total-body P. vivax biomass. More reticulocytes were in contact with sinus lumen endothelial cells in P. vivax- than in P. falciparum-infected spleens. Histological analyses revealed 96% of P. vivax rings/trophozoites and 46% of schizonts colocalised with 92% of immature reticulocytes in the cords and sinus lumens of the red pulp. Larger splenic cohort studies and similar investigations in untreated symptomatic malaria are warranted. CONCLUSIONS: Immature CD71+ reticulocytes and splenic P. vivax-infected erythrocytes of all asexual stages accumulate in the same splenic compartments, suggesting the existence of a cryptic endosplenic lifecycle in chronic P. vivax infection. Findings provide insight into P. vivax-specific adaptions that have evolved to maximise survival and replication in the spleen.