Assessing the feasibility of digital keypress statistics to detect seizures and capture cognitive impairment in patients with epilepsy: A pilot study.

BACKGROUND: Efficient, non-invasive monitoring may provide a more accurate and comprehensive understanding of seizure frequency and the development of some comorbidities in people with epilepsy. Novel keyboard technology measuring digital keypress statistics has demonstrated its practical value for neurodegenerative diseases including Parkinson's Disease and Dementia. Smartphones integrated into daily life may serve as a low-burden longitudinal monitoring system for patients with epilepsy. OBJECTIVE: This study aimed to assess the feasibility of keyboard statistics as an objective measure of seizure frequency for patients with epilepsy, in addition to tracking differences between cognitively normal and cognitively impaired patients. METHODS: Six adult patients admitted to the Epilepsy Monitoring Unit (EMU) at Mayo Clinic in Rochester, Minnesota were studied. The keyboard was installed on the patient's smartphone. In the EMU, typing statistics were correlated to electroencephalogram (EEG) confirmed seizures. After discharge, participants continued using their keyboards and kept a seizure log. We also analyzed the key press/release times and usage of participants' keyboards for adherence. RESULTS: Keyboard sessions during and after seizures assessed for key press/release differences versus baseline showed no statistically significant difference (p = 0.44). Using one-way ANOVA, cognitive impairment's potential impact on keyboard statistics was explored in patients who had neuropsychological testing (N = 3). Significant differences were found between patients with and without cognitive impairment (p < 0.001). No significant difference was noted between patients with mild intellectual disability and normal cognitive function (p = 0.55).

A bioelectronic device for electric field treatment of wounds reduces inflammation in an in vivo mouse model.

Electrical signaling plays a crucial role in the cellular response to tissue injury in wound healing and an external electric field (EF) may expedite the healing process. Here, we have developed a standalone, wearable, and programmable electronic device to administer a well-controlled exogenous EF, aiming to accelerate wound healing in an in vivo mouse model to provide pre-clinical evidence. We monitored the healing process by assessing the re-epithelization rate and the ratio of M1/M2 macrophage phenotypes through histology staining. Following three days of treatment, the M1/M2 macrophage ratio decreased by 30.6% and the re-epithelization in the EF-treated wounds trended towards a non-statically significant 24.2% increase compared to the control. These findings provide point towards the effectiveness of the device in shortening the inflammatory phase by promoting reparative macrophages over inflammatory macrophages, and in speeding up re-epithelialization. Our wearable device supports the rationale for the application of programmed EFs for wound management in vivo and provides an exciting basis for further development of our technology based on the modulation of macrophages and inflammation to better wound healing.

Exploring Variable Approaches in Complex Hernia Repair: A Comprehensive Literature Review.

Surgeons have long grappled with categorizing complex hernias, leading to varied interpretations and fluctuating incidence rates. Complex Abdominal Wall Reconstruction (CAWR) addresses repairs for large hernias, with defined factors including size, previous repairs, mesh placement, infections, and comorbidities. This review explores pivotal surgical techniques for complex hernia repair, starting with Preoperative Progressive Pneumoperitoneum (PPP) and progressing to innovative methods like Botulinum Toxin Type A. Mesh fixation, both open and laparoscopic, plays a crucial role, with synthetic and biological mesh options discussed. Hybrid techniques and the "sandwich" approach are proposed for intricate cases. Each technique presents advantages and limitations, emphasizing the ongoing quest for optimal outcomes.

Human Microglia-Like Cells Differentiated from Monocytes with GM-CSF and IL-34 Show Phagocytosis of α-Synuclein Aggregates and C/EBPß-Dependent Proinflammatory Activation.

Microglia, the main resident immune cells in the central nervous system, are implicated in the pathogenesis of various neurological disorders. Much of our knowledge on microglial biology was obtained using rodent microglial cultures. To understand the role of microglia in human disease, reliable in vitro models of human microglia are necessary. Monocyte-derived microglia-like cells (MDMi) are a promising approach. This study aimed to characterize MDMi cells generated from adult human monocytes using granulocyte-macrophage colony-stimulating factor and interleukin-34. To this end, 49 independent cultures of MDMI were prepared, and various methodological and functional studies were performed. We show that with this protocol, adult human monocytes develop into microglia-like cells, a coating is unnecessary, and high cell density seeding is preferable. When compared to monocytes, MDMi upregulate the expression of many, but not all, microglial markers, indicating that, although these cells display a microglia-like phenotype, they cannot be considered bona fide human microglia. At the functional level, MDMi phagocytose α-synuclein aggregates and responds to lipopolysaccharide (LPS) by nuclear translocation of the transcription factor nuclear factor-kappaB (NFkappaB) and the upregulation of proinflammatory genes. Finally, a long-lasting silencing of the transcription factor CCAAT/enhancer protein ß (C/EBPß) was achieved by small interfering RNA, resulting in the subsequent downregulation of proinflammatory genes. This supports the hypothesis that C/EBPß plays a key role in proinflammatory gene program activation in human microglia. Altogether, this study sheds new light on the properties of MDMi cells and supports these cells as a promising in vitro model for studying adult human microglia-like cells.

Estrogens prevent the hypothalamus-periphery crosstalk induced by olanzapine intraperitoneal treatment in female mice: Effects on brown/beige adipose tissues and liver.

Olanzapine (OLA) is a highly obesogenic second-generation antipsychotic (SGA). Recently we demonstrated that, contrarily to OLA oral treatment, intraperitoneal (i.p.) administration resulted in weight loss and absence of hepatic steatosis in wild-type (WT) and protein tyrosine phosphatase 1B (PTP1B)-deficient (KO) male mice. This protection relied on two central-peripheral axes connecting hypothalamic AMPK with brown/inguinal white adipose tissue (BAT/iWAT) uncoupling protein-1 (UCP-1) and hypothalamic JNK with hepatic fatty acid synthase (FAS). Herein, we addressed OLA i.p. treatment effects in WT and PTP1B-KO female mice. Contrarily to our previous results in WT females receiving OLA orally, the i.p. treatment did not induce weight gain or hyperphagia. Molecularly, in females OLA failed to diminish hypothalamic phospho-AMPK or elevate BAT UCP-1 and energy expenditure (EE) despite the preservation of iWAT browning. Conversely, OLA i.p. treatment in ovariectomized mice reduced hypothalamic phospho-AMPK, increased BAT/iWAT UCP-1 and EE, and induced weight loss as occurred in males. Pretreatment of hypothalamic neurons with 17ß-estradiol (E2) abolished OLA effects on AMPK. Moreover, neither hypothalamic JNK activation nor hepatic FAS upregulation were found in WT and PTP1B-KO females receiving OLA via i.p. Importantly, this axis was reestablished upon ovariectomy. In this line, E2 prevented OLA-induced phospho-JNK in hypothalamic neurons. These results support the role of estrogens in sex-related dimorphism in OLA treatment. This study evidenced the benefit of OLA i.p. administration in preventing its obesogenic effects in female mice that could offer clinical value.

Time is of the essence: Age at autism diagnosis, sex assigned at birth, and psychopathology.

LAY ABSTRACT: Previous research has shown that girls/women are diagnosed later than boys/men with autism. Individuals who are diagnosed later in life, especially girls/women, have greater anxious and depressive symptoms. Previous research has been limited due to narrow inclusionary criteria for enrollment in studies. The present study uses two samples-one clinic-based, large "real-world" sample and another research-based sample with strict criteria for autism diagnosis-to understand the relationships between diagnostic age, sex assigned at birth, and symptoms of anxiety/depression. In both samples, those who were diagnosed later had greater anxious/depressive symptoms, and anxiety was not predicted by sex. In the clinic-based but not research-based sample, those assigned female at birth were diagnosed later than those assigned male at birth. In the clinic-based sample only, individuals assigned female at birth and who were later diagnosed experienced greater symptoms of anxiety/depression compared to those assigned male who benefited from earlier diagnostic timing. Within the research-based sample, those assigned female at birth had greater depressive symptoms than those assigned male. These findings highlight the importance of timely identification of autism, especially for girls/women who are often diagnosed later. Community-based samples are needed to better understand real-world sex-based and diagnostic age-based disparities in mental health.

A pro-reparative bioelectronic device for controlled delivery of ions and biomolecules.

Wound healing is a complex physiological process that requires precise control and modulation of many parameters. Therapeutic ion and biomolecule delivery has the capability to regulate the wound healing process beneficially. However, achieving controlled delivery through a compact device with the ability to deliver multiple therapeutic species can be a challenge. Bioelectronic devices have emerged as a promising approach for therapeutic delivery. Here, we present a pro-reparative bioelectronic device designed to deliver ions and biomolecules for wound healing applications. The device incorporates ion pumps for the targeted delivery of H+ and zolmitriptan to the wound site. In vivo studies using a mouse model further validated the device's potential for modulating the wound environment via H+ delivery that decreased M1/M2 macrophage ratios. Overall, this bioelectronic ion pump demonstrates potential for accelerating wound healing via targeted and controlled delivery of therapeutic agents to wounds. Continued optimization and development of this device could not only lead to significant advancements in tissue repair and wound healing strategies but also reveal new physiological information about the dynamic wound environment.

Non-response to ACE items is associated with demographic variables and health indicators in the 2021 Behavioral Risk Factor Surveillance System.

Background: Adverse childhood experiences (ACE) encompass traumatic events occurring before age 18, with lasting impacts on health. While ACE disclosure is important for understanding these effects, some individuals decline to respond to ACE-related survey items due to sensitivity, privacy concerns, or psychological distress. This study explores the relationship between non-response to ACE items and health outcomes, shedding light on the implications for those who choose not to disclose. Methods: We performed a secondary analysis of the 2021 Behavioral Risk Factor Surveillance System (BRFSS)-a national telephone survey querying health behaviors and conditions. Sociodemographic factors, ACE exposure, and non-response to ACE items were analyzed. Results: Individuals who decline to respond to ACE items exhibit similar patterns of health behaviors and conditions as those reporting ACE exposure. Non-response is linked to both healthier behaviors (lifetime HIV testing) and riskier behaviors (higher odds of smoking and e-cigarette use). Moreover, non-responders have higher odds of being underweight or obese, experiencing concentration difficulties, reporting poor self-rated health, and reporting multiple health diagnoses including depression, diabetes, high blood pressure, heart attack, and stroke. Conclusions: The study underscores the need to address health disparities associated with ACE, regardless of disclosure status. Healthcare interventions should target respondents and non-respondents of ACE screeners, tailoring strategies to promote healthier coping mechanisms and mitigate maladaptive behaviors. These results emphasize the importance of trauma-informed care, early intervention, and targeted public health initiatives for individuals affected by ACE, irrespective of their disclosure choices.

Pierre Robin Sequence: An Updated Evidence-Based Treatment Proposal.

BACKGROUND: The Pierre Robin sequence (PRS) is characterized by the presence of micrognathia, glossoptosis, and respiratory obstruction during the neonatal period, its prompt recognition allows to mitigate the associated morbidity and mortality. A diagnosis and treatment algorithm was previously proposed based on data from the literature to guide therapeutic efforts; therefore, it was proposed to carry out a new search for relevant evidence to update or complement it. METHODS: A literature review of the subject was conducted in PubMed, Embase, and Cochrane databases, corresponding to the period between November 2016 and September 2021. Using the GRADE methodology, 38 articles from different clinical studies that discussed diagnostic tests or therapeutic approaches, directly or indirectly compared, were selected and evaluated. RESULTS: After evaluating and analyzing the selected articles, the new information was incorporated into an updated algorithm according to the most recent evidence found for the diagnosis and comprehensive management of patients with PRS. CONCLUSION: To date, there is no consensus in the literature on the treatment of patients with PRS nor are there multicenter studies comparing different management modalities. The indications to proceed with surgical strategies do not present changes with respect to the previous article. Nutritional monitoring is the main objective, and the study of oral feeding is essential in all scenarios.

Genetic variation in UGT1A1 is not associated with altered liver biochemical parameters in healthy volunteers participating in bioequivalence trials.

Introduction: Bioequivalence clinical trials are conducted in healthy volunteers whose blood tests should be within normal limits; individuals with Gilbert syndrome (GS) are excluded from these studies on suspicion of any liver disease, even if the change is clinically insignificant. GS is a benign genetic disorder characterized by elevated bilirubin levels, the primary cause of which is the presence of polymorphisms in UGT1A1 gene. In this work, subjects with UGT1A1 intermediate (IM) or poor (PM) metabolizer genotype-informed phenotypes were investigated to determine whether they have a higher incidence of liver disease or other biochemical parameters. Methods: The study population comprised 773 healthy volunteers who underwent biochemical analysis at baseline and at the end of the study which were genotyped for UGT1A1*80 (rs887829), as an indicator of UGT1A1*80+*28 (rs887829 and rs3064744), and UGT1A1*6 (rs4148323). Results: Bilirubin levels were higher in subjects IMs and PMs compared to normal metabolizers (NMs). Decreased uric acid levels was observed in PMs compared to NMs. No associations were observed in liver enzyme levels according to UGT1A1 phenotype. Discussion: Considering that there is no hepatic toxicity in subjects with UGT1A1 IM or PM phenotype, who are more likely to develop GS, this study suggests that they could be included in bioequivalence clinical trials as their biochemical parameters are not affected outside normal ranges.

Course on Breeding, Handling, and Experimental Procedures of Zebrafish (Danio rerio): Training, Refinement, Paradigm Shift, and Dissemination of Knowledge from Brazil to the World.

Currently, in Brazil, all researchers involved in animal experimentation must undergo training in laboratory animal science to stay updated on biology, methodology, ethics, and legal considerations related to the use of animals. The training program presented in this study not only aims to fulfill a legal obligation but also intends to train students and professionals to effectively care for their biomodels. It seeks to help them understand the importance of this care, both for the welfare of the animals and for the results of their projects. In total, 58 participants were present at the event (pre-event and full-time course). These participants consisted students and professionals from 11 institutions and 5 different countries. These numbers demonstrate the successful attainment of the desired capillarity in the scientific community and the posterior dissemination of knowledge. Through this course, it was possible to train the participants and raise their awareness about the importance of applying scientific knowledge in their daily practices to maintain the animals, ensuring the welfare of the models and refining the research. Finally, the program presented in this study, as well as the strategies adopted, can serve as a model for other institutions aiming to achieve similar results.

Critical pathway for deceased donors: An analysis in three regions of Colombia / Ruta crítica de donantes fallecidos: un análisis de tres regiones en Colombia

Introduction. The critical pathway for deceased donation offers a methodical framework for guiding the donation process. It not only serves to assess performance but also to identify areas of potential improvement. Therefore, the identification and selection of potential organ donors (POD) is a key process. This study aims to describe the critical pathway for deceased donation in a cohort of POD in three regions (CRT1, CRT2, and CRT5) of Colombia. Methods. We retrospectively reviewed data of POD assessed from January 2022 to December 2022. General characteristics of POD, diagnosis, contraindication causes, and organ procurement were described. Analysis was conducted using the Chi-squared test for categorical variables and the Mann-Whitney test for quantitative variables. Results. Within the cohort of 1451 assessed POD, 441 (30.3%) were diagnosed with brain death. Among potential donors after brain death, 198 (44.9%) were eligible donors (medically suitable). Of these, 157 donors (79.3%) became actual donors (undergoing operative incision for organ recovery), with 147 (93,6 %) having at least one organ recovered (actual donors with organ recovery). Ultimately, 411 utilized organs were utilized. Additionally, there were observed differences in the characteristics of donors from different regions. Conclusion. This study reports the critical pathway for deceased donation in a cohort of POD in three regions of Colombia. This provides useful information and helps to gain insight and understanding into the process of organ donation and organ procurement in order to take actions that could improve the donation rates.

Introducción. La ruta crítica de donantes fallecidos permite un enfoque sistemático para la donación de riñón, y, proporciona una herramienta para evaluar el rendimiento de áreas de mejora potencial. La selección de posibles donantes de órganos (PDO) es un proceso clave. El objetivo de este estudio fue describir la ruta crítica para la donación de fallecidos en una cohorte de PDO en tres regiones de Colombia. Métodos. Estudio retrospectivo de PDO evaluados durante 2022. Se describieron las características generales de los PDO, el diagnóstico y las causas de contraindicación. El análisis se llevó a cabo utilizando la prueba de Chi-cuadrado para las variables categóricas y la prueba de Mann-Whitney para las variables cuantitativas. Resultados. Entre los 1451 POD evaluados, 441 (30,3 %) fueron diagnosticados con muerte cerebral. De los posibles donantes después de la muerte cerebral, 198 (44,9 %) fueron donantes elegibles (adecuados desde el punto de vista médico). Entre ellos, 157 donantes (79,3 %) fueron donantes reales (en quienes se realizó una incisión operatoria con la intención de recuperar órganos) y 147 (93,6 %) tuvieron al menos un órgano recuperado (donantes reales con recuperación de órganos). Finalmente, se identificaron 411 órganos utilizados. Conclusión. Este estudio reporta la ruta crítica para la donación de fallecidos en una cohorte de POD en tres regiones de Colombia. Esto proporciona información útil, ayuda a obtener conocimientos y comprender el proceso de donación y obtención de órganos, para tomar medidas que puedan mejorar las tasas de donación.

Structural characterization of two nanobodies targeting the ligand-binding pocket of human Arc.

The activity-regulated cytoskeleton-associated protein (Arc) is a complex regulator of synaptic plasticity in glutamatergic neurons. Understanding its molecular function is key to elucidate the neurobiology of memory and learning, stress regulation, and multiple neurological and psychiatric diseases. The recent development of anti-Arc nanobodies has promoted the characterization of the molecular structure and function of Arc. This study aimed to validate two anti-Arc nanobodies, E5 and H11, as selective modulators of the human Arc N-lobe (Arc-NL), a domain that mediates several molecular functions of Arc through its peptide ligand binding site. The structural characteristics of recombinant Arc-NL-nanobody complexes were solved at atomic resolution using X-ray crystallography. Both anti-Arc nanobodies bind specifically to the multi-peptide binding site of Arc-NL. Isothermal titration calorimetry showed that the Arc-NL-nanobody interactions occur at nanomolar affinity, and that the nanobodies can displace a TARPγ2-derived peptide from the binding site. Thus, both anti-Arc-NL nanobodies could be used as competitive inhibitors of endogenous Arc ligands. Differences in the CDR3 loops between the two nanobodies indicate that the spectrum of short linear motifs recognized by the Arc-NL should be expanded. We provide a robust biochemical background to support the use of anti-Arc nanobodies in attempts to target Arc-dependent synaptic plasticity. Function-blocking anti-Arc nanobodies could eventually help unravel the complex neurobiology of synaptic plasticity and allow to develop diagnostic and treatment tools.

Adalimumab as treatment for neurosarcoidosis: A case series.

Sarcoidosis is a disease characterized by non-caseating granulomas that can involve the central nervous system as neurosarcoidosis. This challenging disease is currently managed with high dose steroids, and sometimes the addition of infliximab. Other TNA-alpha inhibitors have not been studied as rigorously. We discovered ten neurosarcoidosis patients who were on an alternative TNA-alpha inhibitor, adalimumab. Eight patients had a positive response clinically and radiographically to adalimumab.

Understanding the dynamics of deceased organ donation and utilization in Colombia.

Objective: To obtain a comprehensive overview of organ donation, organ utilization, and discard in the entire donation process in Colombia. Methods: A retrospective study of 1 451 possible donors, distributed in three regions of Colombia, evaluated in 2022. The general characteristics, diagnosis, and causes of contraindication for potential donors were described. Results: Among the 1 451 possible donors, 441 (30.4%) fulfilled brain death criteria, constituting the potential donor pool. Families consented to organ donation in 141 medically suitable cases, while 60 instances utilized legal presumption, leading to 201 eligible donors (13.9%). Of those, 160 (11.0%) were actual donors (in whom operative incision was made with the intent of organ recovery or who had at least one organ recovered). Finally, we identified 147 utilized donors (10.1%) (from whom at least one organ was transplanted). Statistically significant differences were found between age, sex, diagnosis of brain death, and donor critical pathway between regions. A total of 411 organs were transplanted from 147 utilized donors, with kidneys being the most frequently procured and transplanted organs, accounting for 280 (68.1%) of the total. This was followed by 85 livers (20.7%), 31 hearts (7.5%), 14 lungs (3.4%), and 1 pancreas (0.2%). The discard rate of procured deceased donors was 8.1%. Conclusions: About one-tenth of donors are effectively used for transplantation purposes. Our findings highlight areas of success and challenges, providing a basis for future improvements in Colombia.

Understanding the dynamics of deceased organ donation and utilization in Colombia / Examen de la dinámica de la donación y utilización de órganos de personas fallecidas en Colombia / Entendendo a dinâmica da doação e do aproveitamento de órgãos de pessoas falecidas na Colômbia

[ABSTRACT]. Objective. To obtain a comprehensive overview of organ donation, organ utilization, and discard in the entire donation process in Colombia. Methods. A retrospective study of 1 451 possible donors, distributed in three regions of Colombia, evaluated in 2022. The general characteristics, diagnosis, and causes of contraindication for potential donors were described. Results. Among the 1 451 possible donors, 441 (30.4%) fulfilled brain death criteria, constituting the potential donor pool. Families consented to organ donation in 141 medically suitable cases, while 60 instances utilized legal presumption, leading to 201 eligible donors (13.9%). Of those, 160 (11.0%) were actual donors (in whom operative incision was made with the intent of organ recovery or who had at least one organ recovered). Finally, we identified 147 utilized donors (10.1%) (from whom at least one organ was transplanted). Statistically significant differences were found between age, sex, diagnosis of brain death, and donor critical pathway between regions. A total of 411 organs were transplanted from 147 utilized donors, with kidneys being the most frequently procured and transplanted organs, accounting for 280 (68.1%) of the total. This was followed by 85 livers (20.7%), 31 hearts (7.5%), 14 lungs (3.4%), and 1 pancreas (0.2%). The discard rate of procured deceased donors was 8.1%. Conclusions. About one-tenth of donors are effectively used for transplantation purposes. Our findings high- light areas of success and challenges, providing a basis for future improvements in Colombia.

[RESUMEN]. Objetivo. Presentar una descripción integral de la donación, utilización y descarte de órganos en todo el proceso de donación en Colombia. Métodos. Estudio retrospectivo de 1 451 donantes posibles, distribuidos en tres regiones de Colombia, que fueron evaluados en el 2022. Se describen las características generales, el diagnóstico y las causas de contraindicación de los donantes potenciales. Resultados. De los 1 451 donantes posibles, 441 (30,4%) cumplían con los criterios de muerte encefálica y constituyeron el conjunto de donantes potenciales. Las familias consintieron la donación de órganos en 141 casos aptos desde el punto de vista médico, mientras que en 60 casos se recurrió a la presunción legal, con lo que se llegó a 201 donantes aptos (13,9%). De estos, 160 (11,0%) fueron donantes reales (en los que se les practicó una incisión quirúrgica para la extracción de órganos o se obtuvo al menos un órgano). En última instancia, hubo 147 donantes utilizados (10,1%) (de los que se trasplantó al menos un órgano). Se observaron diferencias estadísticamente significativas entre las regiones en cuanto a edad, sexo, diagnóstico de muerte encefálica y vía crítica del donante. Se trasplantaron un total de 411 órganos procedentes de 147 donantes utilizados; los riñones fueron los órganos obtenidos y trasplantados con mayor frecuencia, ya que supusieron 280 (68,1%) del total de órganos, seguidos del hígado (85, 20,7%), el corazón (31 , 7,5%), los pulmones (14, 3,4%) y el páncreas (1, 0,2%). La tasa de descarte de los donantes fallecidos disponibles fue del 8,1%. Conclusiones. Aproximadamente una décima parte de los donantes son utilizados, de hecho, para realizar trasplantes. Estos datos destacan las áreas en las que se han obtenido buenos resultados y aquellas en las que se presentan desafíos, lo cual proporciona una base para futuras mejoras en Colombia.

[RESUMO]. Objetivo. Obter uma visão geral e abrangente da doação, do aproveitamento e do descarte de órgãos em todo o processo de doação na Colômbia. Métodos. Estudo retrospectivo de 1 451 possíveis doadores em três regiões da Colômbia que foram avalia- dos em 2022. Foram descritas as características gerais, o diagnóstico e os motivos para a contraindicação de potenciais doadores. Resultados. Dentre os 1 451 possíveis doadores, 441 (30,4%) preencheram os critérios de morte encefálica, formando o grupo de potenciais doadores. Em 141 casos considerados clinicamente aptos, as famílias con- sentiram com a doação de órgãos, e em 60 casos utilizou-se o princípio da presunção legal, resultando em 201 doadores elegíveis (13,9%). Desses, 160 (11,0%) foram doadores efetivos (ou seja, doadores nos quais foi feita uma incisão cirúrgica com a intenção de remover um órgão ou pessoas com pelo menos um órgão removido). Por fim, foram identificados 147 doadores utilizados (10,1%) (ou seja, que doaram pelo menos um órgão que foi transplantado). Foram encontradas diferenças estatisticamente significantes entre idade, sexo, diagnóstico de morte encefálica e itinerário crítico de doação entre as regiões. Um total de 411 órgãos foram transplantados de 147 doadores utilizados. Os rins foram os órgãos mais frequentemente removidos e transplantados, representando 280 (68,1%) do total, seguido de 85 fígados (20,7%), 31 corações (7,5%), 14 pulmões (3,4%) e 1 pâncreas (0,2%). A taxa de descarte de doadores falecidos com órgãos removidos foi de 8,1%. Conclusões. Cerca de um décimo dos doadores são efetivamente usados para fins de transplante. Nossos achados destacam áreas de sucesso e desafios, oferecendo uma base para futuras melhorias na Colômbia.

Relación entre la compatibilidad del HLA y la pérdida del injerto en trasplante renal de donante cadavérico: Un análisis por propensity score matching en Colombia / Relationship between HLA compatibility and graft loss in renal transplant from a deceased donor: An analysis by propensity score matching in Colombia

Introducción. En Colombia, solo un 24 % de los pacientes en lista recibieron un trasplante renal, la mayoría de donante cadavérico. Para la asignación de órganos se considera el HLA A-B-DR, pero la evidencia reciente sugiere que el HLA A-B no está asociado con los desenlaces del trasplante. El objetivo de este estudio fue evaluar la relevancia del HLA A-B-DR en la sobrevida del injerto de los receptores de trasplante renal. Métodos. Estudio de cohorte retrospectivo que incluyó pacientes trasplantados renales con donante cadavérico en Colombiana de Trasplantes, desde 2008 a 2023. Se aplicó un propensity score matching (PSM) para ajustar las covariables en grupos de comparación por compatibilidad y se evaluó la relación del HLA A-B-DR con la sobrevida del injerto renal por medio de la prueba de log rank y la regresión de Cox. Resultados. Se identificaron 1337 pacientes transplantados renales, de los cuales fueron mujeres un 38,7 %, con mediana de edad de 47 años y de índice de masa corporal de 23,8 kg/m2. Tras ajustar por PSM las covariables para los grupos de comparación, la compatibilidad del HLA A-B no se relacionó significativamente con la pérdida del injerto, con HR de 0,99 (IC95% 0,71-1,37) para HLA A y 0,75 (IC95% 0,55-1,02) para HLA B. Solo la compatibilidad por HLA DR fue significativa para pérdida del injerto con un HR de 0,67 (IC95% 0,46-0,98). Conclusión. Este estudio sugiere que la compatibilidad del HLA A-B no influye significativamente en la pérdida del injerto, mientras que la compatibilidad del HLA DR sí mejora la sobrevida del injerto en trasplante renal con donante cadavérico

Introduction. In Colombia, only 24% of patients on the waiting list received a renal transplant, most of them from cadaveric donors. HLA A-B-DR is considered for organ allocation, but recent evidence suggests that HLA A-B is not associated with transplant outcomes. The objective of this study was to evaluate the relevance of HLA A-B-DR on graft survival in kidney transplant recipients. Methods. Retrospective cohort study that included kidney transplant recipients with a cadaveric donor in Colombiana de Trasplantes from 2008 to 2023. A propensity score matching (PSM) was applied to adjust the covariates in comparison groups for compatibility, and the relationship of HLA A-B-DR with kidney graft survival was evaluated using the log rank test and Cox regression. Results. A total of 1337 kidney transplant patients were identified; of those, 38.7% were female, with median age of 47 years, and BMI 23.8 kg/m2. After adjusting the covariates with PSM for the comparison groups, HLA A-B matching was not significantly related to graft loss, with HR of 0.99 (95% CI 0.71-1.37) and 0.75 (95% CI 0.55-1.02), respectively. Only HLA DR matching was significant for graft loss with an HR of 0.67 (95% CI 0.46-0.98). Conclusions. This study suggests that HLA A-B matching does not significantly influence graft loss, whereas HLA DR matching does improve graft survival in renal transplantation with a cadaveric donor.

[Incidence and causes of hospitalization in patients with transthyretin (ATTR-CA) and light chain (AL-CA) cardiac amyloidosis]. / Incidencia y causas de hospitalización en pacientes con amiloidosis cardiaca por transtiretina (AC-ATTR) y por cadenas ligeras (AC-AL).

INTRODUCTION AND OBJETIVES: Cardiac amyloidosis (CA) is a disorder associated with high number of hospital admissions. Given the scarce information available, we propose an analysis of the incidence and causes of hospitalization in this disease. MATERIAL AND METHODS: One hundred and forty-three patients [128 by transthyretin (ATTR-CA) and 15 by light chains (AL-CA)] included in Registro de Amiloidosis Cardiaca de Galicia (AMIGAL) were evaluated, including all hospitalizations. RESULTS: During a median follow-up of 959 days there were 179 unscheduled hospitalizations [incidence rate (IR) 512.6 admissions per 1000 patients-year], most common due to cardiovascular reasons (n=109, IR 312.2). Most frequent individual cause of hospitalization was heart failure (n=87, TI 249.2). AL-CA was associated with a higher IR of unscheduled hospitalizations than ATTR-CA (IR 781 vs. 483.2; HR 1.62; p=0,029) due to non-cardiovascular admissions (IR 376 vs. 181.2; HR 2.07; p=0.027). Unscheduled admission-free survival at 1 and 3 years in AL-CA was inferior than in ATTR-CA (46.7% and 20.0% vs. 73.4% and 35.2%, respectively; p=0.021). CONCLUSIONS: CA was associated with high incidence of hospitalizations, being heart failure the most frequent individual cause; unscheduled admission-free survival in AL-CA was lower than in ATTR-CA due mostly to non-cardiovascular admissions.

Use of Exposure Data to Establish Causality in Drug-Adverse Event Relationships: An Example with Desvenlafaxine.

Causality algorithms help establish relationships between drug use and adverse event (AE) occurrence. High drug exposure leads to a higher likelihood of an AE being classified as an adverse drug reaction (ADR). However, there is a knowledge gap regarding what concentrations are predictive of ADRs, as this has not been systematically studied. In this work, the Spanish Pharmacovigilance System (SEFV) algorithm was used to define the relationship between the AE occurrence and drug administration in 178 healthy volunteers participating in five desvenlafaxine single-dose clinical trials, a selective serotonin and norepinephrine reuptake inhibitor that may cause dizziness, headache, nausea, dry mouth, constipation and hyperhidrosis. Eighty-three subjects presented 172 AEs that were classified as possible (101), conditional (31), unrelated (24) and probable (16). AUC∞ and Cmax were significantly higher in volunteers with vs. without ADRs (5981.24 ng·h/mL and 239.06 ng/mL and 4770.84 ng·h/mL and 200.69 ng/mL, respectively). Six of 19 subjects with conditional AEs with an SEFV score of 3 points presented an AUC∞ ≥ 6500 ng·h/mL or a Cmax ≥ 300 ng/mL (i.e., above percentile 75) and were summed one point on their SEFV score and classified as "possible" (4 points), improving the capacity of ADR detection.

Frailty is an independent predictor of postoperative rescue medication use after endoscopic sinus surgery.

INTRODUCTION: The modified five-item frailty index (mFI-5) is a validated risk stratification tool with the ability to predict adverse outcomes following surgery. In this study, we sought to use mFI-5 to assess the potential relationship between unhealthy aging and postoperative endoscopic sinus surgery (ESS) outcomes. METHODS: Patients who underwent sinus surgery at Vanderbilt between 2014 and 2018 were identified and assessed using the mFI-5, which is calculated based on the presence of five comorbidities: diabetes mellitus, hypertension requiring medication, chronic obstructive pulmonary disease, congestive heart failure, and non-independent functional status. Multivariate regression analyses were performed to quantify the association of mFI-5 score on need for rescue oral antibiotics, oral steroids, and antibiotic irrigations within 1 year following ESS, adjusting for relevant potential confounders. RESULTS: Four hundred and three patients met inclusion criteria.  Within 6 months of surgery, 312 (77%) required rescue antibiotics, 243 (60%) required oral corticosteroids (OCS), and 31 (8%) initiated antibiotic irrigations. Increasing mFI-5 scores were significantly associated with higher postoperative use of rescue antibiotics (p < 0.0001), OCS (p = 0.032), and antibiotic irrigation (p < 0.0001). Frailty scores remained as an independent predictor of these outcomes after adjustment for age, polyp status, preoperative sinonasal outcomes test (SNOT-22) score, and revision surgery status. CONCLUSIONS: Modified frailty scores may be a useful clinical tool to predict the need for postoperative rescue medication use after ESS.