Dorsal root ganglion inflammation by oxaliplatin toxicity: DPEP1 as possible target for peripheral neuropathy prevention.

BACKGROUND: Peripheral neuropathy (PN) constitutes a dose-limiting side effect of oxaliplatin chemotherapy that often compromises the efficacy of antineoplastic treatments. Sensory neurons damage in dorsal root ganglia (DRG) are the cellular substrate of PN complex molecular origin. Dehydropeptidase-1 (DPEP1) inhibitors have shown to avoid platin-induced nephrotoxicity without compromising its anticancer efficiency. The objective of this study was to describe DPEP1 expression in rat DRG in health and in early stages of oxaliplatin toxicity. To this end, we produced and characterized anti-DPEP1 polyclonal antibodies and used them to define the expression, and cellular and subcellular localization of DPEP1 by immunohistochemical confocal microscopy studies in healthy controls and short term (six days) oxaliplatin treated rats. RESULTS: DPEP1 is expressed mostly in neurons and in glia, and to a lesser extent in endothelial cells. Rats undergoing oxaliplatin treatment developed allodynia. TNF-𝛼 expression in DRG revealed a pattern of focal and at different intensity levels of neural cell inflammatory damage, accompanied by slight variations in DPEP1 expression in endothelial cells and in nuclei of neurons. CONCLUSIONS: DPEP1 is expressed in neurons, glia and endothelial cells of DRG. Oxaliplatin caused allodynia in rats and increased TNF-α expression in DRG neurons. The expression of DPEP1 in neurons and other cells of DRG suggest this protein as a novel strategic molecular target in the prevention of oxaliplatin-induced acute neurotoxicity.

Untargeted metabolomics analysis of serum and urine unveils the protective effect of cilastatin on altered metabolic pathways during cisplatin-induced acute kidney injury.

Acute kidney injury (AKI) is one of the most serious complications of cisplatin anticancer therapies. Cilastatin is a highly promising nephroprotective agent to eventually enter clinical use, but its biochemical mechanism is still not fully understood. We have employed an untargeted metabolomics approach based on capillary electrophoresis mass spectrometry (CE-MS) analysis of serum and urine from an in vivo rat model, to explore the metabolic pathways involved in cisplatin-induced AKI and cilastatin nephroprotection. A total of 155 and 76 identified metabolites were found to be significantly altered during cisplatin treatment in urine and serum, respectively. Most of these altered metabolites were either partially or totally recovered by cilastatin and cisplatin co-treatment. The main metabolic pathways disturbed by cisplatin during AKI involved diverse amino acids metabolism and biosynthesis, tricarboxylic acids (TCA) cycle, nicotinate and nicotinamide metabolism, among others. Cilastatin was proved to protect diverse cisplatin-altered pathways involving metabolites related to immunomodulation, inflammation, oxidative stress and amino acid metabolism in proximal tubules. However, cisplatin-altered mitochondrial metabolism (especially, the energy-producing TCA cycle) remained largely unprotected by cilastatin, suggesting an unresolved mitochondrial direct damage. Multivariate analysis allowed effective discrimination of cisplatin-induced AKI and cilastatin renoprotection based on metabolic features. A number of potential serum and urine biomarkers could also be foreseen for cisplatin-induced AKI detection and cilastatin nephroprotection.

Significance of Pathologic Response in Patients With Early and Locally Advanced Breast Cancer Treated With Neoadjuvant Chemotherapy in a Middle-Income Country. A Real-World Historical Cohort.

PURPOSE: Breast cancer (BC) is the most frequent neoplasm in women in Colombia and is associated with a higher mortality rate than in other countries and regions. Neoadjuvant chemotherapy (NACT) has become a standard treatment in locally advanced BC and provides an opportunity to improve clinical outcomes in BC. This study aims to describe characteristics, treatment patterns, and outcomes after NACT in a cohort of Colombian patients with BC. METHODS: We performed a retrospective cohort study. We included adult patients with BC treated with NACT. Clinical charts were retrospectively reviewed. Descriptive statistics and time to event for overall survival analyses were performed. Recursive partitioning was performed for survival curves to assess the complex relationship between survival times and other variables. RESULTS: Three hundred and fourteen patients were included for analysis. The pathologic complete response after neoadjuvant chemotherapy (ypCR) rate was 34.4%, with a higher ypCR in triple-negative BC (TNBC; 46.9%) and human epidermal growth factor receptor 2-positive BC (72.7%). Those who did not achieve ypCR had a higher percentage of death and relapse. The median follow-up was 4.9 years, with an 88.2% 5-year overall survival (OS). CONCLUSION: A total of 62.6% of the total patients identified were not treated with NACT, indicating a low utilization. Our global ypCR rate was higher when compared with similar studies in Colombia, likely because of differences in the NACT treatment regimens. ypCR was only associated with OS in the TNBC subgroup, emphasizing the importance of pursuing ypCR in these patients. We consider the use of NACT a valuable opportunity to implement innovative treatment approaches that improve outcomes in Colombian patients with BC.

Germline mutations of breast cancer susceptibility genes through expanded genetic analysis in unselected Colombian patients.

BACKGROUND: In Colombia and worldwide, breast cancer (BC) is the most frequently diagnosed neoplasia and the leading cause of death from cancer among women. Studies predominantly involve hereditary and familial cases, demonstrating a gap in the literature regarding the identification of germline mutations in unselected patients from Latin-America. Identification of pathogenic/likely pathogenic (P/LP) variants is important for shaping national genetic analysis policies, genetic counseling, and early detection strategies. The present study included 400 women with unselected breast cancer (BC), in whom we analyzed ten genes, using Whole Exome Sequencing (WES), know to confer risk for BC, with the aim of determining the genomic profile of previously unreported P/LP variants in the affected population. Additionally, Multiplex Ligation-dependent Probe Amplification (MLPA) was performed to identify Large Genomic Rearrangements (LGRs) in the BRCA1/2 genes. To ascertain the functional impact of a recurrent intronic variant (ATM c.5496 + 2_5496 + 5delTAAG), a minigene assay was conducted. RESULTS: We ascertained the frequency of P/LP germline variants in BRCA2 (2.5%), ATM (1.25%), BRCA1 (0.75%), PALB2 (0.50%), CHEK2 (0.50%), BARD1 (0.25%), and RAD51D (0.25%) genes in the population of study. P/LP variants account for 6% of the total population analyzed. No LGRs were detected in our study. We identified 1.75% of recurrent variants in BRCA2 and ATM genes. One of them corresponds to the ATM c.5496 + 2_5496 + 5delTAAG. Functional validation of this variant demonstrated a splicing alteration probably modifying the Pincer domain and subsequent protein structure. CONCLUSION: This study described for the first time the genomic profile of ten risk genes in Colombian women with unselected BC. Our findings underscore the significance of population-based research, advocating the consideration of molecular testing in all women with cancer.

Tubular biomarkers and histology in lupus nephritis.

INTRODUCTION: The relevance of tubulo-interstitial involvement for kidney prognosis has recently been emphasized, but validated biomarkers for predicting histology are still lacking. The aim of our study was to evaluate different serum and urinary markers of tubular damage in patients with lupus nephritis (LN) and to correlate them with kidney histopathology. METHODS: A single-center retrospective study was conducted from January 2016 to December 2021. Serum and urine samples were collected on the same day of kidney biopsy and correlated with histologic data from a cohort of 15 LN patients. We analyzed the following urinary markers, adjusted for urine creatinine: beta 2-microglobulin, alpha 1-microglobulin, NGAL, uKIM-1, MCP-1, uDKK-3, and uUMOD. The serum markers sKIM-1 and sUMOD were also analyzed. RESULTS: A positive and strong correlation was observed between the degree of interstitial fibrosis (rho = 0.785, p = .001) and tubular atrophy (rho = 0.781, p = .001) and the levels of uDKK3. uUMOD also showed an inverse and moderate correlation with interstitial fibrosis (rho = -0.562, p = .037) and tubular atrophy (rho = -0.694, p = .006). Patients with >10% cortical interstitial inflammation had higher levels of uKIM-1 [4.9 (3.9, 5.5) vs. 0.8 (0.6, 1.5) mcg/mg, p = .001], MCP-1 [3.8 (2. 3, 4.2) vs. 0.7 (0.3, 1.2) mcg/mg, p = .001], sKIM-1 [9.2 (5.9, 32.7) vs. 1.4 (0, 3.5) pg/mL, p = .001], and lower sUMOD [8.7 (0, 39.7) vs. 46.1 (35.7, 53) ng/mL, p = .028]. CONCLUSION: The use of specific urinary and serum biomarkers of tubular dysfunction or injury may help to predict certain histologic parameters in LN patients.

Using Iron L-Edge and Nitrogen K-Edge X-ray Absorption Spectroscopy to Improve the Understanding of the Electronic Structure of Iron Carbene Complexes.

Iron-centered N-heterocyclic carbene compounds have attracted much attention in recent years due to their long-lived excited states with charge transfer (CT) character. Understanding the orbital interactions between the metal and ligand orbitals is of great importance for the rational tuning of the transition metal compound properties, e.g., for future photovoltaic and photocatalytic applications. Here, we investigate a series of iron-centered N-heterocyclic carbene complexes with +2, + 3, and +4 oxidation states of the central iron ion using iron L-edge and nitrogen K-edge X-ray absorption spectroscopy (XAS). The experimental Fe L-edge XAS data were simulated and interpreted through restricted-active space (RAS) and multiplet calculations. The experimental N K-edge XAS is simulated and compared with time-dependent density functional theory (TDDFT) calculations. Through the combination of the complementary Fe L-edge and N K-edge XAS, direct probing of the complex interplay of the metal and ligand character orbitals was possible. The σ-donating and π-accepting capabilities of different ligands are compared, evaluated, and discussed. The results show how X-ray spectroscopy, together with advanced modeling, can be a powerful tool for understanding the complex interplay of metal and ligand.

Tubular biomarkers in proteinuric kidney disease: histology correlation and kidney prognosis of tubular biomarkers.

Background: Proteinuria is not only a biomarker of chronic kidney disease (CKD) but also a driver of CKD progression. The aim of this study was to evaluate serum and urinary tubular biomarkers in patients with biopsied proteinuric kidney disease and to correlate them with histology and kidney outcomes. Methods: A single-center retrospective study was conducted on a cohort of 156 patients from January 2016 to December 2021. The following urinary and serum biomarkers were analyzed on the day of kidney biopsy: beta 2 microglobulin (ß2-mcg), alpha 1 microglobulin (α1-mcg), neutrophil gelatinase-associated lipocalin (NGAL), urinary kidney injury molecule-1 (uKIM-1), monocyte chemoattractant protein-1 (MCP-1), urinary Dickkopf-3 (uDKK3), uromodulin (urinary uUMOD), serum kidney injury molecule-1 (sKIM-1) and serum uromodulin (sUMOD). A composite outcome of kidney progression or death was recorded during a median follow-up period of 26 months. Results: Multivariate regression analysis identified sUMOD (ß-0.357, P < .001) and uDKK3 (ß 0.483, P < .001) as independent predictors of interstitial fibrosis, adjusted for age, estimated glomerular filtration rate (eGFR) and log proteinuria. Elevated levels of MCP-1 [odds ratio 15.61, 95% confidence interval (CI) 3.52-69.20] were associated with a higher risk of cortical interstitial inflammation >10% adjusted for eGFR, log proteinuria and microhematuria. Upper tertiles of uDKK3 were associated with greater eGFR decline during follow-up. Although not a predictor of the composite outcome, doubling of uDKK3 was a predictor of kidney events (hazard ratio 2.26, 95% CI 1.04-4.94) after adjustment for interstitial fibrosis, eGFR and proteinuria. Conclusions: Tubular markers may have prognostic value in proteinuric kidney disease, correlating with specific histologic parameters and identifying cases at higher risk of CKD progression.

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.

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.

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.

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.

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

Pancreatic echinococcosis accounts for 0.2-0.6% of cases, with the pediatric population being at a higher risk. Most commonly, pancreatic lesions occur in the head of the pancreas (50-58%); and in the body and tail in 24-34% 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 abdominalpain 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.

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.

Información, narrativas y vivencias de los equipos de salud del Hospital Vilardebó ante la nueva Ley de Salud Mental No 19529 / Information, narratives and experiences of the health teams of the Hospital Vilardebó before the new Law of Mental Health N.o 19.529

La nueva Ley de Salud Mental N.o 19.529 promueve el cierre paulatino de los establecimientos asilares y monovalentes en todo el país. Dentro del sector público se encuentra el Hospital Vilardebó. En esta investigación se exploraron los significados que los equipos de salud de dicho hospital construyen sobre la implementación de la Ley N.o 19.529. Para esto se diseñó un estudio descriptivo. A partir de un muestreo teórico estratificado, la población quedó conformada por 69 personas con formación en medicina general, psiquiatría, psicología, trabajo social y enfermería. A través de un cuestionario autoadministrado, se indagó la información sobre la nueva ley, el reconocimiento de cambios institucionales, la modificación de las prácticas laborales, y los afectos movilizados. De los resultados se destaca un manejo heterogéneo de la información sobre la nueva normativa. Se advierte, asimismo, un proceso de transición institucional donde se observan narrativas contradictorias sobre los cambios en curso.

The new Mental Health Law N 19.529 promotes gradual closure of asylums and monovalent institutions throughout the country. Hospital Vilardebó is the public health psychiatric hospital. This research explores the meanings that health teams assign to this law's implemen tation by means of a descriptive study. Based on a theoretical stratified sample, 69 workers with training in general medicine, psychiatry, psychology, social work and nursing answered a self-administered questionnaire regarding the new law, institutional and work practice changes, and affects involved. The results highlight a heterogeneous handling of information on new regulations. Likewise, an institutional transitional process is noted, with contradictory narratives regarding ongoing changes.

The value of active follow up of a newly acquired hepatitis B infection - lessons for current approaches.

Abstract: The standard practice of blood borne virus (BBV) follow-up in New South Wales is a passive approach of general-practitioner-led testing. The value of this approach is unknown. We undertook an active contact tracing method with the aims of investigating a potential hepatitis B source, along with accurately measuring the participation rate, to consider the value of this and other follow-up methods for future BBV investigations. Investigation of a newly-acquired hepatitis B infection was undertaken at a dental practice identified as a possible exposure site. To screen for hepatitis B infection among potential source or co-exposed clients, we actively followed up with staff and clients of the practice to request they undertake hepatitis B serology. Eligible staff and clients received up to four phone calls and were provided with a pathology request form by the public health unit (PHU). Access to free serology was offered to people who did not have access to Medicare. Reminder calls were made if serology results were not received by the PHU. As the ordering doctor, the public health physician was responsible for providing results and referring for follow-up care. Of 160 clients, 63 (39%) undertook hepatitis B serology. Of these 63, none were found to have hepatitis B infection. It was estimated the active investigation involved an extra 430 hours of PHU staff time at a cost in Australian dollars of $30,000. Active follow-up allows an accurate participation rate to be documented. Despite intense active follow-up, only 39% of clients undertook testing, bringing into question the yield of the usual approach in which active follow-up of potential mass BBV exposures is not undertaken. While active follow-up is resource intensive, it should be considered where the risks and consequences from the BBV infection are high.

Estudio aleatorizado, doble ciego, placebo controlado de doxiciclina en pacientes con dengue. Modulación de citoquinas y respuesta clínica

Resumen Introducción: Los niveles de citoquinas podrían ser determinantes en la severidad de la Fiebre Dengue. La supresión de su actividad con inmunomoduladores modificaría su evolución. Objetivo: Determinar el efecto de la adición de doxiciclina sobre el perfil de citocinas de pacientes con dengue y valorar la respuesta clínica y el impacto en la severidad de pacientes con Fiebre de Dengue. Materiales y métodos: Estudio aleatorio, doble ciego, placebo controlado con doxiciclina. Ambos grupos recibieron la medicación por 7 días y se controló la evolución clínica, laboratorio y niveles de citoquinas en los días 0, 3 y 7. Resultados: Fueron incluídos en el estudio 61 pacientes, 36 (59%) en el grupo placebo y 25 (41%) en el grupo doxiciclina. Se observó que los pacientes tratados con doxiciclina mostraron menor plaquetopenia en el día 0 y 3 [(170029±47483/mm3 vs 198875±52211/mm3)(p<0,05) y 129545±62840/mm3 vs 165048±51142/mm3)(p<0,05)] al compararlo con el grupo placebo. Los niveles de IL-6, TNF y raIL-1 no mostraron diferencias significativas. Se observó una tendencia a menores niveles de IL-1ß en el grupo tratado con doxiciclina (52,1±97 vs 3,3±7,7)(0,08). Conclusiones: No se constató diferencias en la presentación clínica, hospitalización ni en la mortalidad entre pacientes tratados con doxiciclina comparados con placebo. Hubo una tendencia a menores niveles de IL-1ß en los pacientes tratados con doxiciclina. Debe aumentarse el tamaño de la muestra para confirmar o rechazar los resultados.

Abstract Background: Cytokine levels could be determinant in the severity of Dengue Fever. The suppression of their activity with immunomodulators would modify its evolution. Objective: To determine the effect of doxycycline on the cytokine profile of patients with dengue fever and to assess the clinical response and the impact on the severity of patients with dengue fever. Materials and methods: Randomized, double-blind, placebo-controlled study with doxycycline. Both groups received the medication for 7 days and clinical evolution, laboratory and cytokine levels were monitored on days 0, 3 and 7. Results: 61 patients were included in the study, 36 (59%) in the placebo group and 25 (41%) in the doxycycline group. It was observed that patients treated with doxycycline showed lower thrombocytopenia at day 0 and 3 [(170029±47483/mm3 vs 198875±52211/mm3)(p<0.05) and 129545±62840/mm3 vs 165048±51142/mm3)(p<0.05)] when compared to the placebo group. IL-6, TNF and raIL-1 levels showed no significant differences. A trend to lower IL-1ß levels was observed in the doxycycline treated group (52.1±97 vs 3.3±7.7)(0.08). Conclusions: There was no difference in clinical presentation, hospitalization or mortality among patients treated with doxycycline compared to placebo. There was a trend to lower IL-1ß levels in patients treated with doxycycline. The sample size should be increased to confirm or reject the results.

FKBP51, AmotL2 and IQGAP1 Involvement in Cilastatin Prevention of Cisplatin-Induced Tubular Nephrotoxicity in Rats.

The immunophilin FKBP51, the angiomotin AmotL2, and the scaffoldin IQGAP1 are overexpressed in many types of cancer, with the highest increase in leucocytes from patients undergoing oxaliplatin chemotherapy. Inflammation is involved in the pathogenesis of nephrotoxicity induced by platinum analogs. Cilastatin prevents renal damage caused by cisplatin. This functional and confocal microscopy study shows the renal focal-segmental expression of TNFα after cisplatin administration in rats, predominantly of tubular localization and mostly prevented by co-administration of cilastatin. FKBP51, AmotL2 and IQGAP1 protein expression increases slightly with cilastatin administration and to a much higher extent with cisplatin, in a cellular- and subcellular-specific manner. Kidney tubule cells expressing FKBP51 show either very low or no expression of TNFα, while cells expressing TNFα have low levels of FKBP51. AmotL2 and TNFα seem to colocalize and their expression is increased in tubular cells. IQGAP1 fluorescence increases with cilastatin, cisplatin and joint cilastatin-cisplatin treatment, and does not correlate with TNFα expression or localization. These data suggest a role for FKBP51, AmotL2 and IQGAP1 in cisplatin toxicity in kidney tubules and in the protective effect of cilastatin through inhibition of dehydropeptidase-I.

Role of Glucocorticoid Signaling and HDAC4 Activation in Diaphragm and Gastrocnemius Proteolytic Activity in Septic Rats.

Sepsis increases glucocorticoid and decreases IGF-1, leading to skeletal muscle wasting and cachexia. Muscle atrophy mainly takes place in locomotor muscles rather than in respiratory ones. Our study aimed to elucidate the mechanism responsible for this difference in muscle proteolysis, focusing on local inflammation and IGF-1 as well as on their glucocorticoid response and HDAC4-myogenin activation. Sepsis was induced in adult male rats by lipopolysaccharide (LPS) injection (10 mg/kg), and 24 h afterwards, rats were euthanized. LPS increased TNFα and IL-10 expression in both muscles studied, the diaphragm and gastrocnemius, whereas IL-6 and SOCS3 mRNA increased only in diaphragm. In comparison with gastrocnemius, diaphragm showed a lower increase in proteolytic marker expression (atrogin-1 and LC3b) and in LC3b protein lipidation after LPS administration. LPS increased the expression of glucocorticoid induced factors, KLF15 and REDD1, and decreased that of IGF-1 in gastrocnemius but not in the diaphragm. In addition, an increase in HDAC4 and myogenin expression was induced by LPS in gastrocnemius, but not in the diaphragm. In conclusion, the lower activation of both glucocorticoid signaling and HDAC4-myogenin pathways by sepsis can be one of the causes of lower sepsis-induced proteolysis in the diaphragm compared to gastrocnemius.