Biomarkers in Contrast-Induced Acute Kidney Injury: Towards A New Perspective.

Contrast-Induced Acute Kidney Injury (CI-AKI) remains a frequent iatrogenic condition since radiological procedures using intra-vascular iodinated contrast media (CM) are being widely administered for diagnostic and therapeutic purposes. Despite the improvement of the medical healthcare system worldwide, CI-AKI is still associated with direct short-term and indirect long-term outcomes including increased morbidity and mortality, especially in patients with underlying pre-existing renal function impairment, cardiovascular disease, or diabetes that could rapidly progress into Chronic Kidney Disease. Although the RIFLE (Risk, Injury, Failure, Loss, End-Stage Kidney Disease), AKIN (Acute Kidney Injury Network), and KDIGO (Kidney Disease Improving Global Outcomes) clinical criteria and recommendation guidelines are based on traditional "gold standard" biomarkers known as serum creatinine, glomerular filtration rate, and urinary output, new reliable serum and urinary biomarkers are still needed for an effective unified diagnostic strategy for AKI. Starting from previous and recent publications on the benefits and limitations of validated biomarkers responding to kidney injury, glomerular filtration, and inflammation among others, this review unravels the role of new emerging biomarkers used alone or in combination as reliable tools for early diagnosis and prognosis of CI-AKI, taking into account patients and procedures-risk factors towards a new clinical perspective.

Efficacy of short-course treatment for prevention of congenital transmission of Chagas disease: A retrospective cohort study.

BACKGROUND: In regions with controlled vector transmission of T. cruzi, congenital transmission is the most frequent route of infection. Treatment with benznidazole (BZ) or nifurtimox (NF) for 60 days in girls and women of childbearing age showed to be effective in preventing mother to child transmission of this disease. Reports on short-course treatment (≤30 days) are scarce. METHODS: Retrospective cohort study. Offspring of women with Chagas disease who received short-course treatment (≤30 days) with BZ or NF, attended between 2003 and 2022, were evaluated. Parasitemia (microhaematocrit and/or PCR) was performed at <8 months of age, and serology (ELISA and IHA) at ≥8 months to rule out congenital infection. RESULTS: A total of 27 women receiving ≤30 days of treatment and their children were included in this study. NF was prescribed in 17/27 (63%) women, and BZ in 10/27 (37%). The mean duration of treatment was 29.2 days. None of the women experienced serious adverse events during treatment, and no laboratory abnormalities were observed. Forty infants born to these 27 treated women were included. All newborns were full term, with appropriate weight for their gestational age. No perinatal infectious diseases or complications were observed. DISCUSSION: Several studies have shown that treatment of infected girls and women of childbearing age for 60 days is an effective practice to prevent transplacental transmission of T. cruzi. Our study demonstrated that short-duration treatment (≤30 days) is effective and beneficial in preventing transplacental transmission of Chagas disease.

A systematic review and cluster analysis approach of 103 studies of high-intensity interval training on cardiorespiratory fitness.

AIMS: This study aims to systematically review the systematic reviews and meta-analyses examining the effect of high-intensity interval training (HIIT) protocols on improving cardiorespiratory fitness (CRF) and to characterize the main patterns of HIIT modalities using clustering statistical procedures to examine their potential differences on improving CRF. Finally, we aimed to develop a comprehensive guideline for reporting HIIT protocols. METHODS AND RESULTS: A systematic review was conducted on PubMed and Web of Science from their inception to 31 October 2022 for systematic reviews and meta-analysis aimed at assessing the effect of HIIT on CRF in the entire study population. The Assessment of Multiple Systematic Reviews 2 tool was used to evaluate the risk of bias of each review. Additionally, a principal component analysis testing the data adequacy for the factor solution through the Kaiser-Meyer-Olkin procedure test was conducted. Once the number of factors was identified, in order to identify data patterns according to the main characteristics of the HIIT protocols, a two-step cluster analysis was conducted. Nineteen systematic reviews and/or meta-analyses comprising 103 studies were included. Clustering of systematic reviews and meta-analyses identified three HIIT modalities ('HIIT-normal mixed', 'HIIT-long running', and 'HIIT-short cycling') underlying the interventions across the included studies. Similar effectiveness in increasing CRF among the three HIIT modalities was observed. Subgroup analyses showed no significant differences in CRF by sex, weight status, study design, and baseline physical activity level (P > 0.05), but differences were observed by age group, and exercise intensity indicator was used in the HIIT programmes (P < 0.05). CONCLUSION: All three HIIT modalities produced significant improvements of CRF, although some modalities showed greater changes for some specific age groups or intensity indicators.

In this review, including data from more than 100 individual studies, 3 patterns of high-intensity interval training (HIIT), 'HIIT-normal mixed', 'HIIT-long running', and 'HIIT-short cycling', were characterized using a cluster analysis approach. Independently of the sex, weight status, study design, and baseline physical activity level, all three proposed HIIT modalities improved cardiorespiratory fitness (CRF). However, for the age group of 20­44 years, the 'HIIT-long running' reported greater improvement in CRF than 'HIIT-short cycling'. Additionally, the heart rate as an intensity indicator reported higher CRF in 'HIIT-long running' compared with 'HIIT-normal mixed'. A HIIT reporting guideline is provided to address the lack of information on HIIT protocols and provide transparency among studies.

Skyline view of the patella does not increase fracture detection: A non-inferiority diagnostic study.

PURPOSE: Patella fractures are frequent injuries in the adult population. Initial study is made by plain radiographs and the standard set includes the skyline view of patella. Recommendation for use of this projection is variable among the experts, without data that support its performance in the diagnosis of patella fractures. The main purpose of this study was to determine the sensitivity of the antero-posterior and lateral view of the knee, without skyline view, in the diagnosis of patella fracture. METHODS: A retrospective non-inferiority diagnostic study was designed with all the knee trauma adult patients of an Emergency Department in a single center in five years. A random sample of all the consecutive patella fracture cases were taken to elaborate the case group. The control group was matched by sex and age. Two blinded orthopedic surgeons reviewed the cases and control radiographs and defined the presence of fracture, with or without skyline view, with a wash-out time of three weeks between the two evaluations. Non-inferiority was defined a priori at 90% of minimum sensitivity. RESULTS: 140 patients were evaluated (70 cases and 70 controls). Sensitivity of the set without skyline view was 92.86% (CI 95% 0.90 - 0.96) and the standard set was 97.86% (CI 95% 0.96 - 0.99), without significant differences (p = 0.1) CONCLUSION: Sensitivity of the plain radiograph set without skyline view is non-inferior to the standard set. The routine use of skyline view when suspecting patella fractures is questionable.

Traction images heavily influence lateral wall measurement in trochanteric hip fractures. A prospective study.

INTRODUCTION: hip fracture represents a global health problem, with a high morbidity and mortality rate and an increasing incidence. The treatment of trochanteric fractures is reduction and osteosynthesis, and implant selection depends mainly on the stability of the fracture and lateral wall competence. Lateral wall competence has gained relevance in recent years, which led to the modification of the AO/OTA classification. However, determination of lateral wall integrity is difficult from plain radiographs; the influence of images with traction on its measurement has not been evaluated. METHODS: prospective concordance study, emergency and post-traction radiographs of 65 patients with trochanteric fracture were evaluated by six orthopedic surgeons independently, measuring the lateral wall, classifying the fracture according to the AO/OTA 2018 classification and selecting the implant for osteosynthesis. A comparison of incompetent to intact lateral wall proportion between each image set was made. Secondary outcomes were the inter-observer correlation of lateral wall measurement and inter-observer agreement of classification and implant choice. RESULTS: the proportion of patients with an incompetent lateral wall in emergency x-ray was 37.43% (CI 95% 0.326-0.422), while the proportion in post-traction fluoroscopy was 15% (CI 95% 0.115-0.185), with a statistically significant difference (p < 0.001). 40.1% of patients with an incompetent lateral wall changed to an intact one. Inter-observer correlation for the lateral wall thickness was 0.399 (CI 95% 0.292-0.519) in emergency x-ray and 0.658 (CI 95% 0.564-0.748) in post-traction fluoroscopy, with a substantial agreement. Inter-observer agreement for the fracture classification was fair to moderate using emergency x-ray (κ 0.369 95%CI 0.330-0.408) and fair to moderate with post-traction fluoroscopy (κ 0.400, 95% CI 0.334-0.466). CONCLUSION: traction images significantly change the measurement of the lateral wall in trochanteric fractures, changing from an incompetent to a competent wall in 40% of patients. The correct classification of trochanteric fractures is crucial to make the best decision when deciding which implant to use, and the measurement of the lateral wall is determinant in the actual AO/OTA classification. Therefore, traction images appear as necessary for correct decision-making.

Virtual Clinical Simulation for Training Amongst Undergraduate Medical Students: A Pilot Randomised Trial (VIRTUE-Pilot).

BACKGROUND: Clinical virtual simulators are promising new technologies that might facilitate teaching clinical skills. OBJECTIVE: This study aimed to assess whether a virtual reality simulator might facilitate learning and improve adherence to current clinical guidelines. METHODOLOGY: A double-masked randomised trial was undertaken among fourth-year medical students at Universidad Andres Bello, Chile. Participants were randomised to a clinical virtual simulator (Body Interact®, Body Interact Inc., Austin, TX) or a small-group discussion session on the management of myocardial infarction. Main outcomes included performance in an objective structured clinical examination (OSCE) and adherence to clinical recommendations. Analyses were undertaken under the intention to treat principle by an independent statistician. RESULTS: Fifty students volunteered to participate. Most were female (30 students, 58.8%) and had a mean age of 23.0±2.7 years. Thirty-two participants (62.8%) had used virtual reality platforms before. Students allocated to the simulator showed better OSCE scores (mean difference: 2.8 points; 95% confidence interval (CI): -3.2 to +8.7 points, p=0.14) and were faster to implement diagnostic and therapeutic interventions, but not in a statistically significant way. DISCUSSION: Academic performance was slightly improved by the use the simulator, although the overall effect was smaller than expected. CONCLUSION:  This study examined the influence of a clinical virtual simulator on the academic performance and guideline adherence of undergraduate medical students, with small group discussions as a point of comparison. The findings revealed that there were no statistically significant distinctions between the two methods, potentially attributed to the selection of the comparator and the relatively brief intervention period.

Conformational Changes of Poly(Maleic Anhydride-alt-styrene) Modified with Amino Acids in an Aqueous Medium and Their Effect on Cytocompatibility and Hemolytic Response.

The conformational changes of poly(maleic anhydride-alt-styrene) (PSMA) modified with different amino acids (PSMA-Aa) were studied in an aqueous medium as a function of ionic strength and pH. The specific viscosity of PSMA-Aa decreased with increasing salt concentration due to a more compact conformation. There was a decrease in surface tension with increasing concentrations of the modified polyelectrolyte having a greater effect for the PSMA modified with l-phenylalanine at pH 7.0, demonstrating a greater surface-active character. The conformational changes were also confirmed by molecular dynamics studies, indicating that PSMA-Aa exhibits a compact structure at pH 4.0 and a more extended structure at pH 7.0. On the other hand, the conformational changes of PSMA-Aa were related to its biological response, where the higher surface-active character of the PSMA modified with l-phenylalanine correlates very well with the higher hemolytic activity observed in red blood cells, in which the surface-active capacity supports lytic potency in erythrocytes. The cytocompatibility assays indicated that there were no significant cytotoxic effects of the PSMA-Aa. Additionally, in solvent-accessible surface area studies, it was shown that the carboxylate groups of the PSMA modified with l-phenylalanine are more exposed to the solvent at pH 7.0 and high salt concentrations, which correlates with lower fluorescence intensity, reflecting a loss of mitochondrial membrane potential. It is concluded that the study of the conformational changes in PE modified with amino acids is essential for their use as biomaterials and relevant to understanding the possible effects of PE modified with amino acids in biological systems.

Modified Early Warning Score: Clinical Deterioration of Mexican Patients Hospitalized with COVID-19 and Chronic Disease.

The objective was to evaluate the Modified Early Warning Score in patients hospitalized for COVID-19 plus chronic disease. METHODS: Retrospective observational study, 430 hospitalized patients with COVID-19 and chronic disease. Instrument, Modified Early Warning Score (MEWS). Data analysis, with Cox and logistic regression, to predict survival and risk. RESULTS: Of 430 patients, 58.6% survived, and 41.4% did not. The risk was: low 53.5%, medium 23.7%, and high 22.8%. The MEWS score was similar between survivors 3.02, p 0.373 (95% CI: -0.225-0.597) and non-survivors 3.20 (95% CI: -0.224-0.597). There is a linear relationship between MEWS and mortality risk R 0.920, ANOVA 0.000, constant 4.713, and coefficient 4.406. The Cox Regression p 0.011, with a risk of deterioration of 0.325, with a positive coefficient, the higher the risk, the higher the mortality, while the invasive mechanical ventilation coefficient was negative -0.757. By providing oxygen and ventilation, mortality is lower. CONCLUSIONS: The predictive value of the modified early warning score in patients hospitalized for COVID-19 and chronic disease is not predictive with the MEWS scale. Additional assessment is required to prevent complications, especially when patients are assessed as low-risk.

Obese adolescents have higher risk for severe lower extremity fractures after falling.

INTRODUCTION: Reports vary on the impact of obesity on the incidence of lower extremity fractures after a fall. We hypothesized that obese adolescents (OA) presenting after a fall have a higher risk of any and severe lower extremity fractures compared to non-OAs. METHODS: A national database was queried for adolescents (12-17 years old) after a fall. Primary outcome included lower extremity fracture. Adolescents with a body mass index (BMI) ≥ 30 (OA) were compared to adolescents with a BMI < 30 (non-OA). RESULTS: From 20,264 falls, 2523 (12.5%) included OAs. Compared to non-OAs, the rate of any lower extremity fracture was higher for OAs (51.5% vs. 30.7%, p < 0.001). This remained true for lower extremity fractures at all locations (all p < 0.05). After adjusting for sex and age, associated risk for any lower extremity fracture (OR 2.41, CI 2.22-2.63, p < 0.001) and severe lower extremity fracture (OR 1.31, CI 1.15-1.49, p < 0.001) was higher for OAs. This remained true in subset analyses of ground level falls (GLF) and falls from height (FFH) (all p < 0.05). CONCLUSIONS: Obesity significantly impacts adolescents' risk of all types of lower extremity fractures after FFH or GLF. Hence, providers should have heightened awareness for possible lower extremity fractures in OAs. LEVEL OF EVIDENCE: IV.

Impacto en la atención médica en el Instituto de Medicina Tropical durante 4 meses de la Epidemia de Chikungunya

Introducción: La fiebre chikungunya (FCHIK) es una enfermedad emergente transmitida por mosquitos y causada por un alfavirus, el virus chikungunya (CHIKV). Aunque la mayoría de las personas se recuperan completamente en pocos días o semanas, algunos pacientes requieren hospitalización, pudiendo incluso desarrollar manifestaciones graves e incluso observarse un desenlace fatal. El objetivo del presente trabajo de investigación es describir las características de los pacientes atendidos en el Instituto de Medicina Tropical (IMT), en el marco de la actual Epidemia de Arbovirosis por Chikungunya. Materiales y Métodos: observacional, descriptivo, transversal con componente analítico, de pacientes de ambos sexos, atendidos en el IMT en sala de urgencia y en el área de hospitalización, con diagnóstico Confirmado o Sospechoso de FCHIK. Los datos fueron obtenidos de los sistemas informáticos del hospital (HIS). Resultados: Durante el periodo I (junio a octubre, 2022) fueron atendidos 19.645 pacientes (promedio de 3929 consultas mensuales) y durante el periodo II (noviembre 2022 a marzo 2023) 27.673 pacientes (promedio de 5.534,6 consultas mensuales); reflejando un incremento del 41% de consultas. El número de pacientes que requirieron hidratación y analgesia endovenosa fue incrementándose, con énfasis en los meses de enero, febrero y marzo (590, 781 y 608 casos, respectivamente). requiriendo consecuentemente el incremento de camas de hospitalización de 5 a 15 y de sillones de hidratación, de 10 a 15 sillones. Por otro lado, el número de pacientes que requirieron hospitalización se incrementó de 2 pacientes en el mes de noviembre a 54 pacientes en el mes de marzo. La letalidad fue significativamente superior en los >15 años, comparados con los ≤15 años: 12,5% (7/56) vs 2.9% (2/69), respectivamente (p<0.03. OR=4,8. (IC95%. 1 - 24.0). Conclusión: La epidemia de Chikungunya tuvo un importante impacto en la atención médica en el Instituto de Medicina Tropical, con un aumento significativo en la asistencia de pacientes febriles, traducida en alta tasa de pacientes atendidos en áreas de urgencias, y una pequeña proporción en área de internación. Este estudio subraya la importancia de una preparación adecuada y una respuesta rápida en el contexto de una epidemia para minimizar la repercusión en los servicios de atención médica hospitalaria.

Introduction: Chikungunya fever (CHIKF) is an emerging mosquito-borne disease caused by an alphavirus, chikungunya virus (CHIKV). Although most people fully recover in a few days or weeks, some patients require hospitalization and may even develop serious manifestations and even be fatal. The objective of this research work is to describe the characteristics of the patients treated at the Institute of Tropical Medicine (IMT), within the framework of the current Chikungunya Arbovirosis Epidemic. Materials and Methods: observational, descriptive, cross-sectional with an analytical component, of patients of both sexes, treated at the IMT in the emergency room and in the hospitalization area, with a confirmed or suspected diagnosis of FCHIK. Data were obtained from the hospital computer systems (HIS). Results: During period I (June to October 2022), 19,645 patients were attended (average of 3,929 monthly consultations) and during period II (November 2022 to March 2023) 27,673 patients (average of 5,534.6 monthly consultations); reflecting a 41% increase in inquiries. The number of patients who required intravenous hydration and analgesia increased, with emphasis on the months of January, February, and March (590, 781, and 608 cases, respectively). consequently requiring the increase of hospitalization beds from 5 to 15 and hydration chairs, from 10 to 15 chairs. On the other hand, the number of patients requiring hospitalization increased from 2 patients in November to 54 patients in March. Mortality was significantly higher in those >15 years, compared to those ≤15 years: 12.5% (7/56) vs 2.9% (2/69), respectively (p<0.03. OR=4.8. (IC95 %. 1 - 24.0) Conclusion: The Chikungunya epidemic had a significant impact on medical care at the Institute of Tropical Medicine, with a significant increase in the attendance of febrile patients, translated into a high rate of patients treated in emergency areas. and a small proportion in the hospitalization area. This study underscores the importance of adequate preparation and rapid response in the context of an epidemic to minimize the impact on hospital medical care services.

Population pharmacokinetics of benznidazole in neonates, infants and children using a new pediatric formulation.

BACKGROUND: There is a major need for information on pharmacokinetics (PK) of benznidazole (BNZ) in children with Chagas disease (CD). We conducted a multicentre population PK, safety and efficacy study in children, infants and neonates with CD treated with BNZ (formulated in 100 mg tablets or 12.5 mg dispersible tablets, developed by the pharmaceutical company LAFEPE, in a collaboration with DNDi). METHODS: 81 children 0-12 years old were enrolled at 5 pediatric centers in Argentina. Diagnosis of T. cruzi infection was confirmed by direct microscopic examination, or at least two positive conventional serological tests. Subject enrolment was stratified by age: newborns to 2 years (minimum of 10 newborns) and >2-12 years. BNZ 7.5 mg/kg/d was administered in two daily doses for 60 days. Five blood samples per child were obtained at random times within pre-defined time windows at Day 0 at 2-5 h post-dose; during steady state, one sample at Day 7 and at Day 30; and two samples at 12-24 h after final BNZ dose at Day 60. The primary efficacy endpoint was parasitological clearance by qualitative PCR at the end of treatment. RESULTS: Forty-one (51%) patients were under 2 years of age (including 14 newborns <1 month of age). Median age at enrolment was 22 months (mean: 43.2; interquartile range (IQR) 7-72 months). The median measured BNZ Cmax was 8.32 mg/L (IQR 5.95-11.8; range 1.79-19.38). Median observed BNZ Cmin (trough) concentration was 2 mg/L (IQR 1.25-3.77; range 0.14-7.08). Overall median simulated Css was 6.3 mg/L (IQR 4.7-8.5 mg/L). CL/F increased quickly during the first month of postnatal life and reached adult levels after approximately 10 years of age. Negative qPCR was observed at the end of treatment in all 76 patients who completed the treatment. Five patients discontinued treatment (3 due to AEs and 2 due to lack of compliance). CONCLUSION: We observed lower BNZ plasma concentrations in infants and children than those previously reported in adults treated with comparable mg/kg doses. Despite these lower concentrations, pediatric treatment was well tolerated and universally effective, with a high response rate and infrequent, mild AEs. TRIAL REGISTRATION: Registered in clinicaltrials.gov #NCT01549236.

Características clínicas y laboratoriales de la infección por el virus Chikungunya en pacientes en edad pediátrica del Instituto de Medicina Tropical

Introducción: La fiebre chikungunya (FCHIK) es una enfermedad febril transmitida por mosquitos, que en el niño tiene manifestaciones clínicas diferentes, dependiendo del grupo de edad. Objetivo: el presente trabajo tiene el propósito de identificar las características clínicas y evolutivas de la FCHIK en pacientes ≤15 años, que acudieron al Instituto de Medicina Tropical (IMT). Materiales y método: estudio observacional, descriptivo retrospectivo, basado en revisión de historias clínicas de pacientes de 0 y 15 años, que consultaron al IMT, entre noviembre/2022 y marzo/ 2023, con diagnóstico de FCHIK. Resultados: de 2050 pacientes febriles que consultaron al IMT entre noviembre/2022 y marzo/2023, 301 fueron casos de FCHIK, 10,6% (32/301) requirió hospitalización, de estos el 62,5% (20/32) era ≤1 año. La presencia de vómitos (p<0.0001.OR= 5,5 IC95% 2.2-13.2), dolor abdominal (p<0.0001.OR=40.5,5 IC95% 4.5-364.3); erupción maculo-papular-ampollar p<0.008. OR=3.5, IC95% 1.3 - 9.1), fue significativamente más frecuente en los hospitalizados. El 37.5% (12/32) fue hospitalizado en UCI y 15,6% (5/32) requirió ARM, 18.7%(6/32) presentó miocarditis; 15.6%(5/32) encefalitis, y 3.1%(1/32) encefalitis y miocarditis. No se registraron óbitos. Conclusiones: La décima parte de los pacientes con FCHIK requirieron hospitalización, de estos más de la mitad fueron <1 año. Las manifestaciones clínicas más frecuentes fueron fiebre, exantema, vómitos, irritabilidad, artralgias, lesiones ampollares. La leucopenia fue significativamente más frecuente en ≤1 año. La edad <3 meses, así como vómitos, exantema vesículo-ampollar, presencia de choque, irritabilidad, convulsiones, dolor abdominal y dificultad respiratoria se asociaron significativamente al requerimiento de hospitalización. Las complicaciones más frecuentes fueron el choque, la miocarditis y la encefalitis.

Introduction: Chikungunya fever (CHKF) is a febrile disease transmitted by mosquitoes, which presentes different clinical manifestations in children, depending on their age group. Objective: to describe the clinical and outcome characteristics of CHKF in patients ≤15 years old, who presented to the Institute of Tropical Medicine (ITM). Materials and methods: this was a retrospective, descriptive and observational study, based on the review of medical records of patients between 0 and 15 years of age, who were evaluated at the ITM, between November/2022 and March/2023, who were diagnosed with CHKF. Results: of 2050 febrile patients who consulted at the ITM between November/2022 and March/2023, 301 were cases of CHKF, 10.6% (32/301) required hospitalization, of which 62.5% (20/32) were ≤ 1 year of age. The presence of vomiting (p<0.0001, OR= 5.5, 95% CI 2.2-13.2), abdominal pain (p<0.0001, OR=40.5.5, 95% CI 4.5-364.3); maculo-papular-bullous rash (p<0.008, OR=3.5, 95% CI 1.3 - 9.1), was significantly more frequent in hospitalized patients. 37.5% (12/32) were hospitalized in the ICU and 15.6% (5/32) required ARM, 18.7% (6/32) presented myocarditis; 15.6%(5/32) encephalitis, and 3.1%(1/32) had both encephalitis and myocarditis. No deaths were registered. Conclusions: One tenth of the patients with CHKF required hospitalization, of which more than half were <1 year of age. The most frequent clinical manifestations were fever, rash, vomiting, irritability, arthralgia, and bullous lesions. Leukopenia was significantly more frequent in those ≤1 year of age. Age <3 months, as well as vomiting, vesicular-bullous rash, shock, irritability, seizures, abdominal pain, and respiratory distress were significantly associated with the need for hospitalization. The most frequent complications were shock, myocarditis and encephalitis.

Respuesta biológica en las pacientes con cáncer de mama tratadas con radioterapia intraoperatoria / Biological response in breast cancer patients using intraoperative radiotherapy

Introducción: el tratamiento conservador de la mama junto con la radioterapia es de elección en las pacientes con cáncer de mama precoz. Gracias a un mayor conocimiento de la radiobiología tumoral, la tendencia actual consiste en utilizar técnicas de irradiación parcial acelerada, entre las que destaca la radioterapia intraoperatoria (RIO). Métodos: estudio prospectivo multicéntrico dividido en 2 grupos comparativos con casos consecutivos de las pacientes a que han recibido una cirugía conservadora por cáncer de mama asociada o no a RIO. Se valora la relación de esta terapia con los valores de las proteínas involucradas en la respuesta biológica (IL6, IL8, CXCL10, IL1β y TNF- α) en muestras de suero preoperatorio y a las 24 h desde la cirugía, y de drenaje quirúrgico a las 6 y 24 h desde la cirugía. Resultados: se ha objetivado en las pacientes tratadas con RIO una disminución significativa de IL6 e IL8, así como un aumento de CXCL10 favorable para la lucha contra la progresión del tumor (p valor < 0,05). Las alteraciones del sistema inmunológico se manifiestan tanto en suero como en débito del drenaje quirúrgico a las 6 y 24 h desde la cirugía. Conclusiones: la RIO modifica la respuesta biológica en las pacientes con cáncer de mama. A pesar de que se deben desarrollar más líneas de investigación, la comprensión de los mecanismos de desarrollo del tumor, abre una nueva etapa en el desarrollo de tratamientos perioperatorios dirigidos a dianas concretas que compensen las consecuencias dañinas de la cirugía. (AU)

Introduction: Breast conserving surgery with radiotherapy is the treatment of choice in patients with early breast cancer. Due to a better understanding of tumour radiobiology, the current trend is to use accelerated partial irradiation techniques, among which intraoperative radiotherapy (RIO) stands out. Methods: Prospective multicentre study divided into two comparative groups with consecutive cases of patients who have undergone conservative surgery for breast cancer associated or not with RIO. The relation of this therapy with the values of proteins involved in the biological response (IL6, IL8, CXCL10, IL1β y TNF- α) is assessed in serum samples preoperative and 24 hours after surgery, and surgical drainage samples at 6 and 24 hours after surgery. Results: A significant decrease in IL6 and IL8, as well as an increase in CXCL10 favourable for the fight against tumour progression (p-value < 0.05) was observed in patients treated with RIO. Immune system alterations are manifested in both serum and surgical drainage debit at 6 and 24 hours after surgery. Conclusions: RIO modifies the biological response in breast cancer patients. Although more lines of research need to be developed, the understanding of the mechanisms of tumour development opens a new stage in the development of perioperative treatments directed at specific targets that compensate for the harmful consequences of surgery. (AU)

Major benznidazole metabolites in patients treated for Chagas disease: Mass spectrometry-based identification, structural analysis and detoxification pathways.

Benznidazole is the drug of choice for the treatment of Chagas disease, but its metabolism in humans is unclear. Here, we identified and characterized the major benznidazole metabolites and their biosynthetic mechanisms in humans by analyzing the ionic profiles of urine samples from patients and untreated donors through reversed-phase UHPLC-ESI-QTOF-MS and UHPLC-ESI-QqLIT-MS. A strategy for simultaneous detection and fragmentation of characteristic positive and negative ions was employed using information-dependent acquisitions (IDA). Selected precursor ions, neutral losses, and MS3 experiments complemented the study. A total of six phase-I and ten phase-II metabolites were identified and structurally characterized in urine of benznidazole-treated patients. Based on creatinine-corrected ion intensities, nitroreduction to amino-benznidazole (M1) and its subsequent N-glucuronidation to M5 were the main metabolic pathways, followed by imidazole-ring cleavage, oxidations, and cysteine conjugations. This extensive exploration of benznidazole metabolites revealed potentially toxic structures in the form of glucuronides and glutathione derivatives, which may be associated with recurrent treatment adverse events; this possibility warrants further exploration in future clinical trials. Incorporation of this knowledge of the benznidazole metabolic profile into clinical pharmacology trials could lead to improved treatments, facilitate the study of possible drug-drug interactions, and even mitigation of adverse drug reactions.

Hidatidosis pancreática en una niña de 5 años / Pancreatic echinococcosis in a 5-year-old girl

La hidatidosis pancreática representa el 0,2-0,6 % de los casos, siendo la población pediátrica la de mayor riesgo. Las lesiones suelen localizarse en cabeza del páncreas (50-58 %); la localización en cuerpo y cola del páncreas se encuentra en el 24-34 % y el 19 %, respectivamente. Dada la posibilidad de complicaciones, suele realizarse tratamiento quirúrgico. Se sugiriere indicar albendazol antes y después del acto quirúrgico por los riesgos de ruptura y diseminación de los protoescólices. Se presenta el caso de una niña de 5 años de edad con dolor abdominal progresivo y lesión quística en páncreas compatible con hidatidosis en la ultrasonografía. En la tomografía computada se observa compresión de la vía biliar. La hemoaglutinación indirecta fue negativa. Presentó elevación de la bilirrubina total, con franco predominio de bilirrubina directa, y aumento de enzimas hepáticas. Se realizó laparotomía exploradora, colecistectomía y destechamiento del quiste. Evolucionó favorablemente, continuó con albendazol durante 3 meses luego de la cirugía.

Pancreatic echinococcosis accounts for 0.2­0.6% of cases, with the pediatric population being at a higher risk. Most commonly, pancreatic lesions occur in the head of the pancreas (50­58%); and in the body and tail in 24­34% and 19% of cases, respectively. Given the potential complications, surgery is usually performed. Albendazole is recommended before and after the surgery due to the risks for rupture and dissemination of protoscolices. Here we describe the case of a 5-year-old girl with progressive abdominal pain and cystic lesion in the pancreas compatible with echinococcosis in the ultrasound. The computed tomography showed bile duct compression. Indirect hemagglutination was negative. She had elevated total bilirubin, with a clear predominance of direct bilirubin, and high liver enzymes. Exploratory laparotomy, cholecystectomy, and unroofing of the cyst were performed. The patient had a favorable course and continued with albendazole for 3 months after the surgery.

Ultrasound measurement of optic nerve sheath diameter in a healthy adult Colombian population.

BACKGROUND: Measurement of the optic nerve sheath diameter (ONSD) provides a rapid, safe, and easy method for detecting increased intracranial pressure (ICP). However, the normal mean and upper limit values may vary according to sex, age, ethnicity, and ultrasound technique. AIM: We aimed to obtain the mean ONSD in a healthy Colombian adult population and to correlate it with demographic and anthropometric measures. METHODS: In a prospective study using a 10-13 MHz linear ultrasound probe, eye transverse diameter (ETD) and ONSD in the transverse (ONSD-TP) and sagittal planes (ONSD-SP) were measured in healthy adult volunteers in Bogota, Colombia. RESULTS: A total of 100 healthy subjects were included, with a mean age of 26,7 ± 8,3 years and 62 women. The mean ETD, ONSD-TP and ONSD-SP was 23.11 mm (95% confidence interval (CI): 22.90 mm-23.32 mm), 3.96 mm (95% CI: 3.85 mm-4.07 mm) and 4.0 mm (95% CI: 3.90 mm-4.11 mm), respectively. The ONSD in both planes ranged from 2.35 mm to 5.20 mm. There was a significant correlation between ONSD-SP and ONSD-TP (p < 0.0001) but no correlation between the ocular measures and demographic or anthropometric variables (p > 0.05). The intraclass correlation between the eyes was statistically significant. CONCLUSION: Our study shows that ultrasound-measured ONSD in healthy adults in Colombia is similar to that found worldwide. An ONSD of 5.5 mm may be considered the upper limit for healthy adults in Colombia. ONSD can be measured in either plane; there is a good correlation between the two eyes; and ONSD is not modified by demographic or anthropometric characteristics.

Vision transformer assisting rheumatologists in screening for capillaroscopy changes in systemic sclerosis: an artificial intelligence model.

OBJECTIVES: The first objective of this study was to implement and assess the performance and reliability of a vision transformer (ViT)-based deep-learning model, an 'off-the-shelf' artificial intelligence solution, for identifying distinct signs of microangiopathy in nailfold capilloroscopy (NFC) images of patients with SSc. The second objective was to compare the ViT's analysis performance with that of practising rheumatologists. METHODS: NFC images of patients prospectively enrolled in our European Scleroderma Trials and Research group (EUSTAR) and Very Early Diagnosis of Systemic Sclerosis (VEDOSS) local registries were used. The primary outcome investigated was the ViT's classification performance for identifying disease-associated changes (enlarged capillaries, giant capillaries, capillary loss, microhaemorrhages) and the presence of the scleroderma pattern in these images using a cross-fold validation setting. The secondary outcome involved a comparison of the ViT's performance vs that of rheumatologists on a reliability set, consisting of a subset of 464 NFC images with majority vote-derived ground-truth labels. RESULTS: We analysed 17 126 NFC images derived from 234 EUSTAR and 55 VEDOSS patients. The ViT had good performance in identifying the various microangiopathic changes in capillaries by NFC [area under the curve (AUC) from 81.8% to 84.5%]. In the reliability set, the rheumatologists reached a higher average accuracy, as well as a better trade-off between sensitivity and specificity compared with the ViT. However, the annotators' performance was variable, and one out of four rheumatologists showed equal or lower classification measures compared with the ViT. CONCLUSIONS: The ViT is a modern, well-performing and readily available tool for assessing patterns of microangiopathy on NFC images, and it may assist rheumatologists in generating consistent and high-quality NFC reports; however, the final diagnosis of a scleroderma pattern in any individual case needs the judgement of an experienced observer.

Retrospective Analysis of Causes and Risk Factors of 30-Day Readmission After Spine Surgery for Thoracolumbar Trauma.

STUDY DESIGN: Retrospective Case Series. OBJECTIVE: This study aims to evaluate readmission rates, risk factors, and reason for unplanned 30-day readmissions after thoracolumbar spine trauma surgery. METHODS: A retrospective chart review was conducted for patients undergoing operative treatment for thoracic or lumbar trauma with open or minimally invasive surgical approach at a Level 1 urban trauma center. Patients were divided into two groups based on 30-day readmission status. Reason for readmission, reoperation rates, injury type, trauma severity, and incidence of polytrauma were compared between the two groups. RESULTS: A total of 312 patients, 69.9% male with an average age of 47 ± 19 years were included. The readmitted group included 16 patients (5.1%) of which 9 (56%) were readmitted for medical complications and 7 for surgical complications. Wound complications (31.3% of readmissions) were the most common cause of readmission, followed by non-wound related sepsis (18.9% of readmissions). A total of 6 patients (37.5%) required reoperation; 2 instrumentation failures underwent revision surgery, and 4 wound complications underwent irrigation and debridement. Patients with higher Injury Severity Scale (ISS) were more likely to be readmitted (27.8% vs 22.1%, P = .045). Concomitant lower limb surgery increased odds of readmission (OR, 4.40; 95% CI, 1.10-17.83; P = .037). CONCLUSION: Spine trauma 30-day readmission rate was 5.1%, comparable to those reported in the elective spine surgery literature. Readmitted patients were more likely to sustain concomitant operative lower limb trauma. Wound complications were the most common cause of readmission, and almost half of the patients were readmitted due to surgery-related complications.

Training Program for Orthopedic Residents in Forefoot Osteotomy Skills: Transference From a Simulator to a Cadaveric Surgical Scenario.

INTRODUCTION: An effective simulation program allows both the acquisition of surgical skills on the simulated model and the transfer of these skills to a surgical scenario. We designed a forefoot osteotomy training program and sought to determine the transferability to a cadaveric surgical scenario. METHODS: Eleven orthopedic residents and 2 foot and ankle surgeons were included. A foot simulator was used. All residents were instructed on the surgical techniques of Chevron, Akin, and triple Weil osteotomies. Eight junior residents (trainees) were enrolled in a supervised simulation program. Baseline assessment was performed on the simulator with the Objective Structured Assessment of Technical Skills (OSATS) and the Imperial College Surgical Assessment Device (ICSAD). After baseline, trainees completed a training program and had a final evaluation of proficiency on the simulator and on cadaveric specimens. Three senior residents with no simulated training (controls) and experts were assessed for comparison. RESULTS: All trainees improved from a baseline OSATS score of 11 points (9-20) to a final score of 35 points (33-35) in the simulator and 34 points (32-34) in the cadaveric specimen ( P < 0.01). Compared with baseline, the ICSAD results improved in path length (391 [205-544] to 131 [73-278] meters, P < 0.01) and number of movements (2756 [1258-3338] to 992 [478-1908], P < 0.01). The final OSATS and ICSAD scores did not differ from experts ( P = 0.1) and were significantly different from untrained residents ( P = 0.02). CONCLUSIONS: Simulated training of Chevron, Akin, and triple Weil osteotomies in orthopedic residents improved procedural proficiency, enabling successful skill transfer to a surgical scenario in cadavers. LEVEL OF EVIDENCE: II (Prospective Cohort Study).