Cs2CO3-Promoted Alkylation of 3-Cyano-2(1H)-pyridones: Anticancer Evaluation and Molecular Docking.

Herein, a Cs2CO3-promoted N-alkylation of 3-cyano-2(1H)-pyridones containing alkyl groups with diverse alkyl halides to synthesize N-alkyl-2-pyridones over O-alkylpyridines is reported. Alkyl dihalides resulted in complex mixtures of N- and O-alkylated products. The primary factor influencing regioselectivity in these reactions is the electronic effects of substituents on the 2(1H)-pyridone ring, as evidenced by the preferential formation of O-alkylpyridines upon the introduction of aryl groups. Remarkably, we efficiently employed CuAAC and Ti(Oi-Pr)4-catalyzed amidation reactions to functionalize N-alkyl-2-pyridones containing propargyl and ester groups, leading to the synthesis of 1,2,3-triazoles and amides, respectively. Moreover, O-alkylpyridines 10b and 10d displayed remarkable selectivity toward the A-498 renal cancer cell line with growth inhibition percentages (%GI) of 54.75 and 67.64, respectively. The binding modes of compounds 10b and 10d to the PIM-1 kinase enzyme were determined through molecular docking studies.

Isolated Optic Nerve Relapse in a Pediatric Patient With T-Cell Lymphoblastic Leukemia: A Brief Report.

Isolated optic nerve (ON) relapse is a rare occurrence in lymphoblastic leukemia (LBL). A 10-year-old boy with T-LBL presented 8 months after diagnosis with blurred vision and thickening of right ON on magnetic resonance imaging consistent with relapse. Cerebrospinal fluid and bone marrow were negative for leukemia. He received reinduction chemotherapy (including nelarabine and craniospinal radiation) followed by a myeloablative matched sibling donor bone marrow transplant. He remains in remission 2 years post-transplant with normal vision. We also review the literature for reports of isolated ON relapse in patients with LBL. Our patient's clinical course demonstrates that disease control can be achieved with early detection of ON relapse before disease progression.

Case report: Efficacy of immunotherapy as conversion therapy in dMMR/MSI-H colorectal cancer: a case series and review of the literature.

Immunotherapy has demonstrated a role in the therapeutic landscape of a small subset of patients with colorectal carcinoma (CRC) that harbor a microsatellite instability (MSI-H) status due to a deficient DNA mismatch repair (dMMR) system. The remarkable responses to immune checkpoint inhibitors (ICIs) are now being tested in the neoadjuvant setting in localized CRC, where the dMMR/MSI-H status can be found in up to 15% of patients, with remarkable results obtained in NICHE2 and 3 trials, among others. This case series aims to report our experience at a tertiary center and provide a comprehensive analysis of the possible questions and challenges to overcome if ICIs were established as standard of care in a neoadjuvant setting, as well as the potential role they may have as conversion therapy not only in locoregional advanced CRC but also in oligometastatic disease.

Dacriocistocele bilateral congénito: reporte de un caso / Congenital bilateral dacryocystocele: case report

Introducción: el dacriocistocele es una malformación congénita rara, secundaria a la obstrucción del conducto nasolagrimal; tiene una incidencia de 0,1 % de pacientes con obstrucción congénita del conducto nasolagrimal y se encuentra bilateralmente hasta en 25 % de casos. Caso clínico: lactante femenina de dos meses con celulitis periorbitaria derecha preseptal no asociada con lesión de entrada y diagnóstico inicial de dacriocistitis derecha. Al examen físico de ingreso, en el ojo derecho se evidencia gran masa abscedada en saco lagrimal; en el ojo izquierdo, un área indurada y leve reflujo a la presión del saco lagrimal. Se realiza tomografía computarizada de órbitas con hallazgos compatibles con dacriocistocele bilateral. Discusión y conclusiones: conocer la presentación y posibles complicaciones asociadas con esta patología previene una morbilidad importante al paciente. La mayoría de los casos de dacriocistocele se pueden manejar médicamente, sin embargo, aquellos asociados con complicaciones requieren de manejo quirúrgico oportuno.

Introduction: Dacryocystocele is a rare congenital malformation secondary to na-solacrimal duct obstruction. It has an incidence of 0.1% of patients with congenital nasolacrimal duct obstruction, being found bilaterally in up to 25% of cases. Case Report: Two-month-old female infant with preseptal right periorbital cellulitis not associated with an entrance lesion, with an initial diagnosis of right dacryocystitis. On physical examination, a large abscessed mass in the lacrimal sac was eviden-ced in the right eye; in the left eye, there was an indurated area and slight reflux to the lacrimal sac pressure. Computed tomography of the orbits was performed with findings compatible with bilateral dacryocystocele. Discussion and conclusions: Knowing the presentation and possible complications associated with this pathology prevents significant patient morbidity. Most cases of dacryocystocele can be mana-ged medically, however, cases associated with complications require timely surgical management.

Análisis de interacciones de los actores de la red de conocimiento en salud ambiental del Observatorio Nacional de Salud de Colombia

Introducción: Las interrelaciones positivas y negativas entre el hombre y el medioambiente impactan en la salud general de la población, por esto, la gestión del conocimiento y la transformación social, orientadas a la prevención de la exposición a factores de riesgo ambiental y a la creación de ambientes propicios, deben realizarse a través de acciones multidisciplinares intersectoriales, como el trabajo colaborativo de redes del conocimiento. Objetivo: Describir las interacciones entre los actores de la Red de Conocimiento de Salud Ambiental del Observatorio Nacional de Salud de Colombia (ONS), con el fin de promover, mejorar y fortalecer la colaboración, intercambio de información y planificación conjunta de acciones. Metodología: Estudio descriptivo transversal de análisis de redes sociales mediante herramientas de minería de texto del lenguaje de programación R. Se analizaron las categorías de agua y saneamiento, clima, calidad del aire, radiaciones electromagnéticas e intoxicaciones químicas de un corpus documental de 99 textos de los actores de la red general de conocimiento en salud pública del ONS. Se calcularon medidas de centralidad y prestigio y se graficaron redes dirigidas multicapa con Power BI. Resultados: Los actores con mayor centralidad en la red fueron: Ministerio de Salud y Protección Social, Superintendencia de Salud, Profamilia, universidades de Antioquia y La Salle, ONS, Observatorio de Salud Ambiental de Bogotá, Organización Panamericana de la Salud y Organización Mundial de la Salud. Las cinco categorías analizadas presentaron bajas centralidades de grado, y las categorías de agua y clima mostraron mayor participación de los actores (más nodos e interacciones). Conclusiones: El análisis de redes sociales permitió identificar temas relevantes de salud ambiental entre los actores de la red del ONS, además de actores clave para desarrollar espacios de interacción y gestión del conocimiento. Acorde con las limitaciones del análisis, se sugiere la inclusión de aproximaciones bibliométricas para la actualización de las interacciones de la red.

Introduction: Positive and negative interactions between the human beings and the environment have an impact on the general health of the population. Therefore, it is necessary to use knowledge management and social transformation, in order to limit exposure to environmental risk factors by creating a favorable environment for healthcare. This should be carried out through multidisciplinary and intersectorial actions, such as the collaborative work of knowledge networks. Objective: To describe the interactions between the actors within the Environmental Health Knowledge Network Colombia's National Observatory of Health (ONS acronym in Spanish), in order to promote, improve and strengthen collaboration, information exchange and planning of collaborative actions. Methodology: Cross-sectional descriptive study to analyze social interactions through text mining tools by R, programmer language. Categories analyzed: Water and sanitation, climate, air quality, electromagnetic radiation and chemical poisoning. Data source: a documentary corpus of 99 texts done by actors of Environmental Health Knowledge Network of Colombia's ONS. We calculated centrality and prestige measures. We used Power BI in order to plot multi-layered directed networks. Results: Actors with greatest centrality in the network: Ministry of Health and Social Protection, Health Superintendency, Profamilia, Antioquia and La Salle universities, National Health Observatory, Bogota's Observatory of Environmental Health, the Pan American Health Organization and the World Health Organization. The five categories analyzed provides a low centrality degree, and water and climate categories presented greater participation by actors (more nodes and links). Conclusions: Social interactions analysis provides the identification of relevant environmental health issues in Colombia and key actors in order to develop interaction spaces for knowledge management. The analysis had limitations that suggest the inclusion of bibliometric approaches for updating the interactions within the network.

Hallazgo incidental de neoplasia primaria de pulmón: blastoma pulmonar en mujer adulta. Reporte de caso / Incidental finding of primary lung neoplasm: pulmonary blastoma in an adult woman, case report

El blastoma pulmonar es una neoplasia poco común y agresiva que se origina en el pulmón; está compuesto por tejido mesenquimal y epitelial inmaduro que imita la configuración pulmonar en etapas embrionarias. Tiene una baja incidencia y una alta tasa de mortalidad, con aproximadamente un 60 %. Este blastoma tiende a desarrollarse con mayor frecuencia entre la cuarta y quinta década de vida, siendo más prevalente en mujeres y generalmente asociado al tabaquismo. Se presenta el caso de una mujer de 23 años sin factores de riesgo conocidos, a quien se le diagnosticó incidentalmente un blastoma pulmonar primario. La paciente experimentaba dolor en la región costal izquierda, tos productiva, disnea y hemoptisis desde hace 30 días. Los hallazgos en las imágenes de rayos X y tomografías de tórax llevaron a la realización de una biopsia del pulmón izquierdo, que reveló fragmentos de tejido con una notable presencia de necrosis tumoral. Cinco días después, la paciente consultó nuevamente debido a un empeoramiento de los síntomas, incluyendo dolor torácico de tipo pleurítico. Se decidió realizar una lobectomía inferior izquierda, durante la cual se encontró un tumor sólido adherido a la pleura visceral, con masas tumorales en la pleura parietal. El estudio histopatológico final confirmó el diagnóstico de un tumor maligno de alto grado compatible con blastoma pulmonar. En conclusión, el blastoma pulmonar es una neoplasia rara que puede presentarse en diferentes etapas de la vida, aunque tiene mayor incidencia entre los 40 y 50 años. Es importante que los patólogos consideren esta enfermedad en sus diagnósticos diferenciales debido a los desafíos que implica su diagnóstico. Detectar el blastoma pulmonar en etapas tempranas es crucial para el tratamiento adecuado, aunque actualmente no se conocen marcadores predictivos confiables y el pronóstico de esta enfermedad es generalmente desfavorable.

Pulmonary blastoma is a rare and aggressive neoplasm that originates in the lung. It is composed of immature mesenchymal and epithelial tissue that mimics the embryonic configuration of the lung. It has a low incidence and a high mortality rate, of approximately 60%. Pulmonary blastoma tends to occur more frequently between the fourth and fifth decades of life, being more prevalent in women and generally associated with smoking. The case of a 23-year-old woman with no known risk factors is presented, who incidentally was diagnosed with a primary pulmonary blastoma. The patient experienced pain in the left costal region, productive cough, dyspnea, and hemoptysis for 30 days. Findings on X-ray and chest tomography led to a biopsy of the left lung, which revealed tissue fragments with significant tumor necrosis. Five days later, the patient consulted again due to worsened symptoms, including pleuritic chest pain. It was decided to perform a left lower lobectomy, during which a solid tumor attached to the visceral pleura with tumor masses in the parietal pleura was found. The final histopathological study confirmed the diagnosis of a high-grade malignant tumor compatible with pulmonary blastoma. In conclusion, pulmonary blastoma is a rare neoplasm that can occur at different stages of life, although it has a higher incidence between the ages of 40 and 50. Pathologists need to consider this disease in their differential diagnoses due to the challenges involved in its diagnosis. Detecting pulmonary blastoma at early stages is crucial for appropriate treatment, although currently there are no reliable predictive markers, and the prognosis of this disease is generally unfavorable.

Prognosis and Treatment Outcomes of Bone Metastasis in Gallbladder Adenocarcinoma: A SEER-Based Study.

BACKGROUND: Gallbladder carcinoma (GBC) is a rare, aggressive malignancy comprising 0.5% of gastrointestinal cancers. It has poor survival outcomes due to its insidious onset, lack of standardized screening, and limited therapies. Advanced-stage diagnosis with liver, lymph node, and peritoneal metastasis is common, while bone metastasis is rare. The knowledge on bone metastasis in GBC is limited to case reports and small series, and its clinical significance is largely unexplored. METHODS: The study extracted the demographic and clinical variables of patients with metastatic (M1) gallbladder adenocarcinoma from the Surveillance, Epidemiology, and End Results (SEER) database between 2011 and 2020. Descriptive statistics were used to analyze the demographic characteristics. The multivariate Cox regression analysis was used to calculate the hazard ratio. The overall survival (OS) was assessed using the Kaplan-Meier method, and the log-rank test was utilized to compare the survival between the groups. RESULTS: A total of 2724 patients were included in the study. A total of 69% of the patients were female, and the median age was 68 (range 24-90+). A total of 7.4% of the patients had bone metastasis on diagnosis. The multivariate Cox analysis identified bone metastasis as an independent mortality risk factor in metastatic GBC (HR 1.50, p < 0.001). The patients were divided into two age groups: a younger age group (18-74 years) and an older age group (75+ years). In the younger group, the median OS with and without bone metastasis was 3 and 5 months, respectively (p < 0.0001). In the older age group, there was no significant difference in the OS between the patients with and without bone metastasis (p = 0.35). In the younger group who were treated with chemotherapy, the patients with bone metastasis had a significantly worse OS (median OS 5 months vs. 8 months, p < 0.0001). In the untreated group, the patients with bone metastasis in the younger age group had a significantly worse OS (median OS 1 month vs. 2 months, p = 0.014). In the patients with bone metastasis, those who did not receive chemotherapy had a significantly worse OS than those who were treated with chemotherapy in both age groups (younger age group: median OS 1 month vs. 5 months, p < 0.0001 and older age group: median OS 1 month vs. 5 months, p = 0.041). CONCLUSIONS: Our findings suggest that the presence of bone metastasis in gallbladder adenocarcinoma is an independent prognostic factor associated with unfavorable survival outcomes in the younger age group (18-74 years). However, in the older age group (75+ years), the presence of bone metastasis did not impact the survival. Treatment with chemotherapy was associated with extended survival in all patients. Thus, early detection and aggressive management of bone metastasis, including the consideration of chemotherapy, may be crucial in improving the OS and quality of life for individuals with gallbladder adenocarcinoma.

Influencia de posición del brazo en adultos para abordaje de plexo braquial costoclavicular: estudio observacional / Influence of arm position in costoclavicular approach for brachial plexus block in adult patient: observational study

Resumen: Introducción: el bloqueo de plexo braquial con abordaje costoclavicular, ofrece ventajas como sitio de inyección único, sitio adecuado para colocación de catéter de analgesia continua. Objetivo: identificar la visibilidad de los tres cordones del plexo braquial en el espacio costoclavicular según la angulación del brazo. Material y métodos: se realizó un estudio observacional descriptivo y transversal; se incluyeron 99 pacientes entre 18 a 90 años de edad, en un período de dos meses. Se describieron variables continuas, se aplicó la prueba no paramétrica de Friedman para K muestras relacionadas, una regresión lineal para confirmar la correlación entre la distancia de la piel a plexo braquial, peso e índice de masa corporal (IMC). Resultados: se encontró una menor profundidad en relación piel plexo bajo abducción del brazo a una angulación de 90o y 110o, que permite la visualización sonoanatómica del plexo braquial a nivel costoclavicular con significancia estadística. El peso es un factor independiente que determina la distancia entre la profundidad piel plexo. Conclusiones: se determinó que el abordaje del bloqueo costoclavicular ecoguiado es anatómicamente factible con elevada eficacia clínica, el cual concluye ser un sitio anatómico innovador y seguro.

Abstract: Introduction: the brachial plexus block with a costoclavicular approach offers advantages as a single injection site, being a suitable site for continuous analgesia catheter placement. Objective: to identify the visibility of the 3 brachial plexus cords in the costoclavicular space according to the angulation of the arm. Material and methods: a descriptive and cross-sectional observational study was carried out; 99 healthy patients between 18 and 90 years of age were included, in a period of two months. Continuous variables were described, the nonparametric Friedman test was applied for K related samples, a linear regression was performed to confirm the correlation between the distance from the skin to the brachial plexus, weight and body mass index (BMI). Results: a smaller depth was found in relation to the skin plexus under abduction of the arm at an angulation of 90o and 110o, which allows an adequate sonoanatomical visualization of the brachial plexus at the costoclavicular level with statistical significance. Weight is an independent factor that determine the distance between the skin plexus depth. Conclusions: it was determined that the ultrasound-guided costoclavicular block approach is anatomically feasible with greater clinical efficacy, which concludes to be an innovative and safe anatomical site.

Plasma D-Dimer Is a Promising Marker to Guide Timing of Reimplantation: A Prospective Cohort Study.

BACKGROUND: Two-stage exchange arthroplasty remains the preferred surgical treatment for chronic periprosthetic joint infection. Currently, there is no single reliable marker to determine the optimal timing for reimplantation. The purpose of this prospective study was to assess the diagnostic utility of plasma D-dimer and other serological markers in predicting successful control of infection following reimplantation. METHODS: This study enrolled 136 patients undergoing reimplantation arthroplasty between November 2016 and December 2020. Strict inclusion criteria were applied including the need for a two-week "antibiotic holiday" prior to reimplantation. A total of 114 patients were included in the final analysis. Plasma D-dimer, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and fibrinogen were measured preoperatively. Treatment success was defined using the Musculoskeletal Infection Society Outcome-Reporting Tool. Receiver operating characteristic curves were used to assess the prognostic accuracy of each biomarker in predicting failure following reimplantation at a minimum 1-year follow-up. RESULTS: Treatment failure occurred in 33 patients (28.9%) at a mean follow-up of 3.2 years (range, 1.0 to 5.7). Median plasma D-dimer was significantly higher in the treatment failure group (1,604 versus 631 ng/mL, P < .001), whereas median CRP, ESR, and fibrinogen were not significantly different between the success and failure groups. Plasma D-dimer demonstrated the best diagnostic utility (area under the curve [AUC] 0.724, sensitivity 51.5%, specificity 92.6%), outperforming ESR (AUC 0.565, sensitivity 93.3%, specificity 22.5%), CRP (AUC 0.541, sensitivity 87.5%, specificity 26.3%), and fibrinogen (AUC 0.485, sensitivity 30.4%, specificity 80.0%). Plasma D-dimer level of ≥1,604 ng/mL was identified as the optimal cutoff that predicted failure following reimplantation. CONCLUSION: Plasma D-dimer was superior to serum ESR, CRP, and fibrinogen in predicting failure after the second stage of a two-stage exchange arthroplasty for periprosthetic joint infection. Based on the findings of this prospective study, plasma D-dimer may be a promising marker in assessing the control of infection in patients undergoing reimplantation surgery. LEVEL OF EVIDENCE: Level II.

Mark Coventry Award: Human Knee Has a Distinct Microbiome: Implications for Periprosthetic Joint Infection.

BACKGROUND: Pathogens causing prosthetic joint infection (PJI) are thought to gain access to the knee during surgery or from a remote site in the body. Recent studies have shown that there is a distinct microbiome in various sites of the body. This prospective study, and first of its kind, was set up to investigate the presence of possible microbiome in human knee and compare the profile in different knee conditions. METHODS: We obtained synovial fluid from 65 knees (55 patients) with various conditions that included normal knee, osteoarthritis (OA), aseptic revision, and those undergoing revision for PJI. The contralateral knee of patients who had a PJI were also aspirated for comparison. A minimum of 3 milliliters of synovial fluid was collected per joint. All samples were aliquoted for culture and next-generation sequencing analysis. RESULTS: The highest number of species was found in native osteoarthritic knees (P ≤ .035). Cutibacterium, Staphylococcus, and Paracoccus species were dominant in native nonosteoarthritic knees, and meanwhile a markedly high abundance of Proteobacteria was observed in the osteoarthritic joints. Moreover, the contralateral and aseptic revision knees showed a similar trend in bacterial composition (P = .75). The sequencing analysis of patients who had PJI diagnosis, confirmed the culture results. CONCLUSION: Distinct knee microbiome profiles can be detected in patients who have OA and other knee conditions. The distinct microbiome in the knee joint and the close host-microbe relationships within the knee joint may play a decisive role in the development of OA and PJI.

Duplicidad intestinal con diagnóstico ecográfico. Presentación de un caso

La duplicación intestinal es una afección poco frecuente que se diagnostica y resuelve durante los dos primeros años de vida. Pueden ser diverticulares, quísticas o tubulares, comunicadas y no comunicadas. Los síntomas varían con el tipo, tamaño, localización y mucosa que los tapiza. Este trabajo tiene como objetivo presentar el caso de una paciente pediátrica con diagnóstico de duplicidad intestinal ileal, en que las pruebas de imagen aportaron al diagnóstico definitivo. Se trata de una paciente femenina de 16 meses, que presentó dolor abdominal tipo cólico difuso, intermitente, heces sanguinolentas, distención abdominal e irritabilidad. En radiografía de abdomen simple se evidenció distensión de asas intestinales como niveles hidroaéreos y presencia de gas en recto. En ultrasonido se constató imagen quística hacia hipocondrio derecho, en íntimo contacto con asa intestinal adyacente, signo de la doble pared y nivel líquido-líquido. Se sugirió el diagnóstico de duplicidad intestinal ileal, que fue confirmado con biopsia, posterior a cirugía realizada. Es la ecografía la prueba de primera opción en el diagnóstico de esta afección. Muestra el signo de la doble pared con una capa ecogénica interna (epitelio) y una capa hipoecogénica externa que corresponde a las capas musculares. Los métodos de estudios imagenológicos son de vital importancia para su diagnóstico, es el ultrasonido abdominal quien proporciona un diagnóstico certero, siendo inocuo para el paciente.

Intestinal duplication is a rare condition that is diagnosed and resolves within the first two years of life. They can be diverticular, cystic or tubular, communicating and non-communicating. The symptoms vary with the type, size, location and mucosa that covers them. This research aims to present the case of a pediatric patient diagnosed with ileal intestinal duplication, in which imaging tests contributed to the definitive diagnosis. This is a 16-month-old female patient who presented with diffuse, intermittent colicky abdominal pain, bloody stools, abdominal distention, and irritability. A simple abdominal X-ray revealed distention of the intestinal loops, such as air-fluid levels and the presence of gas in the rectum. Ultrasound revealed a cystic image towards the right hypochondrium, in close contact with the adjacent intestinal loop, double wall sign and fluid-fluid level. The diagnosis of ileal intestinal duplication was suggested, which was confirmed with a biopsy after surgery. Ultrasound is the test of first choice in the diagnosis of this condition. It shows the double wall sign with an inner echogenic layer (epithelium) and an outer hypoechoic layer corresponding to the muscle layers. The methods of imaging studies are of vital importance for its diagnosis, it is the abdominal ultrasound that provides an accurate diagnosis, being harmless for the patient.

Current Landscape and Potential Challenges of Immune Checkpoint Inhibitors in Microsatellite Stable Metastatic Colorectal Carcinoma.

Colorectal cancer (CRC) is the third most frequent cancer and the second most common cause of cancer-related death in Europe. High microsatellite instability (MSI-H) due to a deficient DNA mismatch repair (dMMR) system can be found in 5% of metastatic CRC (mCRC) and has been established as a biomarker of response to immunotherapy in these tumors. Therefore, immune checkpoint inhibitors (ICIs) in mCRC with these characteristics were evaluated with results showing remarkable response rates and durations of response. The majority of mCRC cases have high levels of DNA mismatch repair proteins (pMMR) with consequent microsatellite stability or low instability (MSS or MSI-low), associated with an inherent resistance to ICIs. This review aims to provide a comprehensive analysis of the possible approaches to overcome the mechanisms of resistance and evaluates potential biomarkers to establish the role of ICIs in pMMR/MSS/MSI-L (MSS) mCRC.

Paranasal Mass in a Healthy Male Toddler.

Head and neck tumors are rare in pediatric patients but should be kept in the differential when a patient presents with a new swelling or mass. One of these tumors is a myxoma, which is an insidiously growing, benign mass originating from the mesenchyme. They most commonly arise in the myocardium but can also develop in facial structures, particularly in the maxilla and mandible. When arising in facial structures, ocular, respiratory, and digestive systems can be affected based on local invasion. Complete surgical resection is curative but can lead to significant morbidity as well. Here, we present a case of a 15-month-old toddler presenting with a paranasal mass, which was ultimately diagnosed as a maxillary myxoma. This tumor is very rare in the pediatric population, especially in the toddler age-group, reminding clinicians to broaden the differential diagnosis when a patient's course is atypical.

Sterile Setup Table in the Operating Room Is Not So Sterile.

BACKGROUND: One of the important factors for surgical site infection prevention is the implementation of an ultraclean operating room. This study was designed to evaluate back-table sterility during total joint arthroplasty. METHODS: This prospective study includes 52 patients undergoing primary total joint arthroplasty between November 2021 and January 2022. A total of 4 swabs (2 air swabs and 2 table swabs) were obtained for each case, at the conclusion of surgery and prior to the takedown of drapes. One swab from each set was sent for culture, and the other was sent for next-generation sequencing (NGS) analysis. RESULTS: Among 104 back-table swabs, a total of 13 (12.5%) organisms were isolated. Of these, 7 organisms were isolated by culture and 6 by NGS. No microorganisms were isolated by both culture and NGS from back-table swabs. Among 104 air swabs, a total of 11 (10.6%) organisms were isolated. Of these, 6 microorganisms were isolated by culture and 5 by NGS. In 4 of the 104 swabs, both culture- and NGS-isolated organisms were from air swabs. Of the 104 (12.5%) back-table and air swabs, 13 were culture positive. While more than 1 pathogen was identified in 2 air swabs, all back-table swabs were monomicrobial by culture. Pathogens were identified from 11 of 104 (10.6%) swabs by NGS, while more than 1 pathogen was identified in 4 swabs (2 air and 2 back table). CONCLUSION: The findings of this study raise an important issue that the surgical field including the sterile table setup for instruments is not "sterile" and can harbor pathogens.

New insights into CC2D2A-related Joubert syndrome.

PURPOSE: In this study, we describe the phenotype and genotype of the largest cohort of patients with Joubert syndrome (JS) carrying pathogenic variants on one of the most frequent causative genes, CC2D2A. METHODS: We selected 53 patients with pathogenic variants on CC2D2A, compiled and analysed their clinical, neuroimaging and genetic information and compared it to previous literature. RESULTS: Developmental delay (motor and language) was nearly constant but patients had normal intellectual efficiency in 74% of cases (20/27 patients) and 68% followed mainstream schooling despite learning difficulties. Epilepsy was found in only 13% of cases. Only three patients had kidney cysts, only three had genuine retinal dystrophy and no subject had liver fibrosis or polydactyly. Brain MRIs showed typical signs of JS with rare additional features. Genotype-phenotype correlation findings demonstrate a homozygous truncating variant p.Arg950* linked to a more severe phenotype. CONCLUSION: This study contradicts previous literature stating an association between CC2D2A-related JS and ventriculomegaly. Our study implies that CC2D2A-related JS is linked to positive neurodevelopmental outcome and low rate of other organ defects except for homozygous pathogenic variant p.Arg950*. This information will help modulate patient follow-up and provide families with accurate genetic counselling.

Diseño y validación de un cuestionario sobre factores de riesgo en niños con parálisis cerebral / Design and Validation of a Questionnaire about Risk Factors in Children with Cerebral Palsy

Objetivo. Diseñar y validar, en su apariencia, un cuestionario para recolectar información sobre factores de riesgo en niños con parálisis cerebral. Metodología. Estudio descriptivo, metodológico, que incluyó una fase de diseño y otra de validación facial de un cuestionario. Esta última se llevó a cabo a través de la participación de 43 madres y 10 profesionales del área de la salud. Resultados. De acuerdo con el modelo teórico de Rutter alrededor de los factores de riesgo, se diseñó un cuestionario que permite recolectar información sobre condiciones pre y perinatales, que puede ser utilizado como parte de la documentación de la historia clínica de los niños con parálisis cerebral. Se realizó la validación facial del instrumento, cuyos resultados sugirieron la aceptación de 17 ítems y la reformulación de 12, equivalentes al 41,4% de la totalidad de preguntas del Cuestionario FR-PC. Limitaciones. El tamaño de la muestra pudo ser superior. De igual forma, no se encontró suficiente literatura que permitiera contrastar los resultados del estudio con otros similares. Valor. El producto de esta investigación es el Cuestionario FR-PC, herramienta que facilita la organización y la integración de los datos de la historia clínica del niño con PC, para la toma de decisiones. Así mismo, su contenido puede ser considerado para el desarrollo de proyectos de investigación en salud. Conclusiones. El Cuestionario FR-PC es una herramienta clara y comprensible para recolectar información sobre factores de riesgo en niños con parálisis cerebral

Objective. To design and validate, in its appearance, a questionnaire to collect in-formation on risk factors in children with cerebral palsy. Methodology. Descriptive, methodological study, which included a design phase and a phase of facial validation of a questionnaire. The latter was carried out through the participation of 43 mothers and 10 health professionals. Results. According to Rutter's theoretical model around risk factors, a question-naire was designed to collect information on pre- and perinatal conditions, which can be used as part of the documentation of the clinical history of children with cerebral palsy and for research processes. The facial validation of the instrument was carried out, whose results suggested the acceptance of 17 items and the reformulation of 12, equivalent to 41.4% of the totality of questions of the FR-PC Questionnaire. Limitations. Sample size could have been bigger. In addition, not enough literature was found to allow us to compare our results with other studies. Value. The product of this research is the RF-PC Questionnaire, a tool that facilitates the organization and integration of data from the clinical history of children with CP, for decision making. Conclusions. The FR-PC Questionnaire is a clear and understandable tool to collect information on risk factors in children with cerebral palsy.

Application of the pulmonary embolism rule-out criteria (PERC rule) and age-adjusted D-Dimer in patients undergoing computed tomography pulmonary angiography for diagnosis of pulmonary embolism / Aplicação dos critérios PERC e do D-Dímero ajustado para idade em pacientes submetidos a angiotomografia pulmonar para o diagnóstico de embolia pulmonar

Abstract Background Diagnosis of pulmonary embolism (PE) constitutes a challenge for practitioners. Current practice involves use of pre-test probability prediction rules. Several strategies to optimize this process have been explored. Objectives To explore whether application of the pulmonary embolism rule-out criteria (PERC rule) and age-adjusted D-dimer (DD) would have reduced the number of computed tomography pulmonary angiography (CTPA) examinations performed in patients with suspected PE. Methods A retrospective cross-sectional study of adult patients taken for CTPA under suspicion of PE in 2018 and 2020. The PERC rule and age-adjusted DD were applied. The number of cases without indications for imaging studies was estimated and the operational characteristics for diagnosis of PE were calculated. Results 302 patients were included. PE was diagnosed in 29.8%. Only 27.2% of 'not probable' cases according to the Wells criteria had D-dimer assays. Age adjustment would have reduced tomography use by 11.1%, with an AUC of 0.5. The PERC rule would have reduced use by 7%, with an AUC of 0.72. Conclusions Application of age-adjusted D-dimer and the PERC rule to patients taken for CTPA because of suspected PE seems to reduce the number of indications for the procedure.

Resumo Contexto O diagnóstico de embolia pulmonar (EP) representa um desafio para o profissional. A prática atual envolve o uso de modelos de previsão de probabilidade pré-teste e, para otimizar esse processo, várias estratégias têm sido exploradas. Objetivos Investigar se a aplicação dos critérios de exclusão de EP (pulmonary embolism rule-out criteria, PERC) e do D-dímero (DD) ajustado para idade diminui o número de angiografias computadorizadas (ATCs) pulmonares realizadas em pacientes com suspeita de EP. Métodos Estudo transversal retrospectivo com pacientes adultos submetidos a ATC pulmonar com suspeita de EP em 2018 e 2020. Foram aplicados os critérios PERC e o DD ajustado para idade. Foi estimado o número de casos não indicados para exames de imagem, e foram calculadas as características operacionais para o diagnóstico de EP. Resultados Foram incluídos 302 pacientes, dos quais 29,8% apresentaram diagnóstico de EP. Apenas 27,2% dos casos não prováveis ​​de acordo com os critérios de Wells apresentaram DD; o ajuste implicou em uma diminuição de ACTs de 11,1%, com área sob a curva de 0,5. Os critérios PERC diminuiriam em 7%, com área sob a curva de 0,72. Conclusões A aplicação do DD ajustado para idade e dos critérios PERC em pacientes submetidos a ATC pulmonar por suspeita de EP parece diminuir a indicação para tais exames.

Exposición a material particulado y su relación con el cáncer de mama. Mecanismos fisiopatológicos / Exposure to particulate matter and its association to breast cancer. Pathophysiological mechanisms

Introducción. El cáncer de mama es el tipo de cáncer que genera más muertes en mujeres en el mundo. Aunque se reconoce el aporte de factores genéticos, hormonales y de estilos de vida como sus principales causas, las hipótesis que señalan que la contaminación del ambiente juega un papel importante en su desarrollo, han tomado mucha fuerza en los últimos años. Estas hipótesis surgen debido a que el aumento en la incidencia del cáncer de mama coincide con procesos de industrialización, además de mayor presencia en regiones urbanas y con altos niveles de contaminación. El objetivo de este artículo fue consolidar información sobre los mecanismos fisiopatológicos que puedan explicar la relación entre cáncer de mama y la contaminación por material particulado. Metodología. Se realizó una búsqueda de literatura en PubMed, Google Académico y Epistemonikos para documentos publicados sobre el tema desde enero de 2016 hasta el 3 de agosto de 2022. Resultados. Se encontró que algunos de los mecanismos que podrían explicar dicha relación incluyen: alteraciones endocrinas que favorecen cambios hormonales, induciendo el crecimiento mamario; cambios en las características histológicas del tejido normal, como involución reducida de unidades lobulares ductales terminales; formación de aductos de hidrocarburos aromáticos policíclicos-ácido desoxirribonucleico (HAP-ADN), con mutación específica del gen TP53; activación de la proliferación en la línea celular MCF-7; y, alteraciones en la metilación del ADN. Conclusión. Si bien órganos distales como la mama no son la primera entrada de los contaminantes ambientales al cuerpo, estos sí pueden verse afectados tras la exposición a largo plazo, a través de diferentes mecanismos de disrupción endocrina y daño al ADN principalmente

Breast cancer is the type of cancer that causes the most deaths in women worldwide. Although the contribution of genetic, hormonal and lifestyle factors are recognized as its main causes, the hypotheses that indicate that environmental pollution has an important role in its development have taken on great strength during the last years. These hypotheses are based on the increase in the incidence of breast cancer that coincides with industrialization processes, in addition to its greater presence in urban regions with high levels of pollution. The aim of this study was to consolidate information on the pathophysiological mechanisms that can explain the relationship between breast cancer and air pollution by particulate matter. Methodology. A literature search was carried out in PubMed, Google Scholar and Epistemonikos for documents published on this topic from January 2016 until August 3rd 2022. Results. Some of the mechanisms that could explain this association include endocrine alterations that favor hormonal changes, inducing breast growth; changes in the histological characteristics of normal tissue such as reduced involution of terminal duct lobular units; formation of polycyclic aromatic hydrocarbons-deoxyribonucleic acid (PAH-DNA) adducts, with specific mutation of the TP53 gene; an increase in cell proliferation in the MCF-7 cell line; and alterations in DNA methylation. Conclusion. Although distal organs such as the breast are not the entry site of environmental pollutants into the body, they can be affected after prolonged exposure, mainly through different mechanisms of endocrine disruption and DNA damage

Factores asociados al desarrollo de polineuropatía, miopatía y polineuromiopatía en pacientes adultos críticos / Development associated factors with polyneuropathy, myopathy and polyneuromyopathy in critically ill adult patients

Introducción. La polineuropatía, la miopatía y la polineuromiopatía son condiciones debilitantes que afectan a pacientes críticamente enfermos. Sin embargo, poco se conoce acerca de los factores relacionados con estos desenlaces en pacientes hospitalizados en las unidades de cuidado intensivo (UCI) y con hospitalización prolongada en el contexto clínico colombiano. Objetivo. Evaluar los factores asociados al desarrollo de polineuropatía, miopatía y polineuromiopatía en pacientes críticos con hospitalización prolongada. Métodos. Estudio analítico, observacional, de casos y controles apareados realizado en 192 pacientes (64 casos y 128 controles) atendidos en una clínica de tercer nivel de atención de Cali, Colombia. Se analizaron diferentes factores de riesgo como falla multiorgánica, sepsis, desnutrición, nutrición parenteral, uso de corticoides, uso de relajantes musculares, entre otros. Se evaluó si los días de estancia en UCI es un modificador del efecto de la relación entre estos factores y los desenlaces. Resultados. Se encontró que la falla multiorgánica (OR: 6,32, IC95%: 2,15-18,58), la desnutrición (OR: 2,25, IC95%: 1,01-5,0) y el uso de relajantes musculares (OR: 2,68, IC95%: 1,04-6,87) estuvieron asociados con el desarrollo de polineuropatía y miopatía. Así mismo, se observó que la asociación entre la falla multiorgánica y estas condiciones se vio afectada por la duración de la estancia en UCI (p<0,05). En pacientes sin falla multiorgánica, el riesgo aumentó mínimamente con cada día adicional de estancia en UCI (OR: 1,004, IC95%: 0,97-1,04); sin embargo, en pacientes con falla multiorgánica, el riesgo se incrementó en un 5% por cada día adicional de estancia en UCI. Conclusiones. Los resultados del presente estudio destacan la importancia de factores como la falla multiorgánica, la desnutrición y el uso de relajantes musculares en el desarrollo de la polineuropatía, la miopatía y la polineuromiopatía en pacientes críticos con hospitalización prolongada.

Introduction. Polyneuropathy, myopathy, and polyneuromyopathy are debilitating conditions that affect critically ill patients. However, little is known about the factors related to these outcomes in patients hospitalized in intensive care units (ICUs) and with prolonged hospitalization in the Colombian clinical context. Objective. To assess the factors associated with the development of polyneuropathy, myopathy and polyneuromyopathy in critically ill patients with prolonged hospitalization. Methods. Analytical, observational, matched case-control study conducted in 192 patients (64 cases and 128 controls) treated at a tertiary care clinic in Cali, Colombia. Different risk factors such as multi-organ failure, sepsis, malnutrition, parenteral nutrition, use of corticosteroids, use of muscle relaxants, among others, were analyzed. We assessed whether the length of stay in the ICU is a modifier of the effect of the relationship between these factors and the outcomes. Results. It was found that multiorgan failure (OR: 6.32, 95%CI: 2.15-18.58), malnutrition (OR: 2.25, 95%CI: 1.01-5.0) and the use of muscle relaxants (OR: 2.68, 95%CI: 1.04-6.87) were associated with the development of polyneuropathy and myopathy. Likewise, it was observed that the association between multi-organ failure and these conditions was affected by the length of stay in the ICU (p<0.05). In patients without multi-organ failure, the risk increased minimally with each additional day of stay in the ICU (OR: 1.004, 95%CI: 0.97-1.04); however, in patients with multi-organ failure, the risk increased by 5% for each additional day of stay in the ICU. Conclusions. The results of the present study highlight the importance of factors such as multi-organ failure, malnutrition and the use of muscle relaxants in the development of polyneuropathy, myopathy and polyneuromyopathy in critically ill patients with prolonged hospitalization.

Advanced Hepatocellular Carcinoma in Adults Without Cirrhosis: A Single-Institution Retrospective Review.

Background: Although up to one in five cases of hepatocellular carcinoma (HCC) occurs in patients without cirrhosis, there is scarce literature characterizing non-cirrhotic HCC (NCHCC). Existing NCHCC research is primarily limited to surgical case series and there is a lack of data on unresectable NCHCC. Aim: The purpose of this retrospective review was to compare the characteristics of unresectable NCHCC and cirrhotic hepatocellular carcinoma (CHCC). Methods: A retrospective chart review of adult patients with unresectable HCC treated from 2007 to 2017 was performed at the University of Florida Shands Hospital. The data set was stratified into two cohorts: NCHCC and CHCC. Continuous variables were compared using Wilcoxon-Mann-Whitney tests and Kruskal-Wallis rank-sum tests. Categorical variables were compared using Pearson's Chi-squared tests and Fisher's exact tests. Overall survival was explored utilizing the Kaplan-Meier and log-rank method. Results: There were 1494 adult patients included in the final analysis, including 264 patients (17.7%) with NCHCC and 1230 patients (82.3%) with CHCC. Median age was 61.0 years old and median follow-up time was 30.2 months. NCHCC patients were older than CHCC patients (66.3 years vs 61.9 years; p < 0.0001). NHCC tumors were larger than CHCC tumors (7.92 ± 4.85 vs 4.38 ± 3.12 cm; p < 0.0001) and more likely to be associated with distant metastases (23.35% vs 15.91%; p = 0.0055). There was no difference in overall survival, with a median of 23.5 months in NCHCC and 22.4 months in CHCC (p = 0.9196). Conclusion: Our findings suggest that unresectable NCHCC and CHCC have unique characteristics but similar overall survival. To the best of our knowledge, this is the largest comparison of CHCC and NCHCC.