First Characterization of Tissue Oxygen Saturation Recovery Patterns in Pediatric Cardiac Surgery Patients Undergoing Remote Ischemic Preconditioning and the Association With Clinical Outcomes.

OBJECTIVE: This study aimed to delineate the recovery patterns of regional oxygen saturation (SrO2) in pediatric cardiac surgery patients subjected to remote ischemic preconditioning (RIPC), utilizing near-infrared spectroscopy (NIRS) for quantification. It also sought to establish the correlation between these perfusion patterns and postoperative clinical outcomes. DESIGN: A prospective longitudinal observational study. SETTING: The study was conducted at Fundación Valle Del Lili, a high-complexity service provider institution in Fundación Valle Del Lili. PARTICIPANTS: Pediatric patients (younger than 18 years of age) scheduled for elective cardiac surgery requiring cardiopulmonary bypass between August 2022 and July 2023. INTERVENTIONS: RIPC was performed after anesthetic induction, involving cycles of ischemia and reperfusion on a lower limb. Monitoring included SrO2 using NIRS. MEASUREMENTS AND MAIN RESULTS: The study identified 4 distinct patterns of SrO2 during RIPC. Findings demonstrated a significant association between the negative SrO2 pattern and increased postoperative adverse events, including extended hospital stays and higher mortality, while a positive pattern was associated with better outcomes. CONCLUSIONS: Specific patterns of SrO2 response to RIPC may serve as important indicators for risk stratification in congenital heart surgery. This study illustrated the potential of NIRS in detecting hypoxic states and predicting postoperative outcomes, emphasizing the need for standardized clinical interpretation of RIPC patterns.

NELF focuses sites of initiation and maintains promoter architecture.

Many factors control the elongation phase of transcription by RNA polymerase II (Pol II), a process that plays an essential role in regulating gene expression. We utilized cells expressing degradation tagged subunits of NELFB, PAF1 and RTF1 to probe the effects of depletion of the factors on nascent transcripts using PRO-Seq and on chromatin architecture using DFF-ChIP. Although NELF is involved in promoter proximal pausing, depletion of NELFB had only a minimal effect on the level of paused transcripts and almost no effect on control of productive elongation. Instead, NELF depletion increased the utilization of downstream transcription start sites and caused a dramatic, genome-wide loss of H3K4me3 marked nucleosomes. Depletion of PAF1 and RTF1 both had major effects on productive transcript elongation in gene bodies and also caused initiation site changes like those seen with NELFB depletion. Our study confirmed that the first nucleosome encountered during initiation and early elongation is highly positioned with respect to the major TSS. In contrast, the positions of H3K4me3 marked nucleosomes in promoter regions are heterogeneous and are influenced by transcription. We propose a model defining NELF function and a general role of the H3K4me3 modification in blocking transcription initiation.

Postoperative Outcomes of Analgesic Management with Erector Spine Plane Block at T5 Level in Pediatric Patients Undergoing Cardiac Surgery with Sternotomy: A Cohort Study.

Introduction: There is limited evidence on the impact of erector spinae plane block (ESPB) as part of multimodal analgesia in pediatric population undergoing cardiac surgery. Methods: A retrospective cohort study was conducted in patients under 18 years of age, who underwent cardiac surgery Risk Adjusted classification for Congenital Heart Surgery (RACHS-1) ≤3 by sternotomy. The study aims to evaluate the effect of ESPB as part of multimodal analgesia in pediatric patients undergoing cardiac surgery compared to conventional analgesia (CA) on relevant clinical outcomes: length of hospital stay, length of ICU stay, opioid consumption, time to extubation, mortality, and postoperative complications. The participants included were treated in a reference hospital in Colombia from July 2019 to June 2022. Results: Eighty participants were included, 40 in the ESPB group and 40 in the CA group. There was a significant decrease (Log rank test p = 0.007) in days to length of hospital stay in ESPB group (median 6.5 days (IQR: 4-11)) compared to the CA group (median 10.5 days (IQR: 6-25)). Likewise, there was a higher probability of discharge from the ICU in the ESPB group (HR 1.71 (95% CI: 1.05-2.79)). The ESPB group had lower opioid consumption (p < 0.05). There were no differences in time to extubation, mortality, and postoperative complications. Conclusion: ESPB as part of multimodal analgesia in pediatric patients undergoing cardiac surgery is feasible and associated with shorter hospital length of stay, faster ICU discharge and lower opioid consumption.

Características y desenlaces clínicos de pacientes menores de 18 años tratados con oxigenación con membrana extracorpórea posterior a cirugía para la reparación o paliación de cardiopatías congénitas / Characteristics and clinical outcomes of patients under 18 years of age treated with extracorporeal membrane oxygenation after surgery for the repair or palliation of congenital heart disease

Resumen: Objetivo: determinar las características y desenlaces clínicos de pacientes menores de 18 años tratados con oxigenación con membrana extracorpórea (ECMO) posterior a cirugía para la reparación o paliación de cardiopatías congénitas en un centro de referencia del suroccidente colombiano entre 2015 y 2020. Método: estudio descriptivo longitudinal con recolección retrospectiva de la información. Resultados: entre enero de 2015 y diciembre de 2020, 77 pacientes requirieron ECMO posterior a cirugía cardiaca pediátrica, con una mediana de edad de < 1 mes, mediana de peso de 4 kg, tiempo de circulación extracorpórea de 202 minutos y tiempo de pinzamiento aórtico de 95 minutos. La cardiopatía congénita más ingresada a ECMO fue el síndrome de corazón izquierdo hipoplásico (19.4%) en su posquirúrgico de Norwood (18.1%). La mediana del tiempo de ECMO fue de 111 horas. La indicación más frecuente fue la disfunción ventricular (80.5%). El 80.5% presentó complicaciones y la reintervención por sangrado fue la más frecuente (46.7%). La sobrevida a la ECMO fue del 48% y la sobrevida general al momento del alta fue de 25.97%. La edad < 1 mes (p = 0.030), el ácido láctico preECMO ≥ 5 mmol/l (p = 0.014) y el tiempo de normalización del lactato ≥ 24 horas (0.021), se asociaron a un mayor riesgo de mortalidad al egreso hospitalario. Conclusiones: la ECMO proporciona un soporte adecuado posterior a la cirugía cardiaca pediátrica. La edad < 1 mes, el ácido láctico preECMO ≥ 5 mmol/L y el tiempo de normalización del lactato ≥ 24 horas fueron las variables que se asociaron con un mal resultado y mortalidad hospitalaria.

Abstract: Objective: to determine the characteristics and clinical outcomes of patients under 18 years of age treated with extracorporeal membrane oxygenation (ECMO) after surgery for the repair or palliation of congenital heart disease. Method: longitudinal descriptive study with retrospective data collection. Results: between January 2015 and December 2020, 77 patients required ECMO after pediatric cardiac surgery with a median age of < 1 month, median weight of 4 kg, ECC time 202 minutes (IQR 125-272 minutes), aortic cross-clamp time 95 minutes. 76.6% were supported with ECMO prior to their return to the ICU. The congenital heart disease most frequently admitted to ECMO was hypoplastic left heart syndrome (19.4%) in the Norwood postoperative period (18.1%). The median time of ECMO was 111 hours. The most frequent indication was ventricular dysfunction (80.5%). 80.5% presented complications and reoperation for bleeding was the most frequent of these (46.7%). ECMO survival was 48% and overall survival at discharge was 25.97%. Age < 1 month (p = 0.030), pre-ECMO lactic acid ≥ 5 mmol/l (p = 0.014), OR 0.260 and time of normalization of lactate ≥ 24 hours (0.021), OR 0.24 were associated with a higher risk of mortality at hospital discharge. Conclusions: ECMO provides adequate support after surgery for the repair or palliation of congenital heart disease. Age < 1-month, pre-ECMO lactic acid ≥ 5 mmol/l, and lactate normalization time ≥ 24 hours were the variables that were associated with poor outcome and hospital mortality.

Bilateral continuous erector spinae plane block for cardiac surgery: case series / Bloqueo bilateral continúo del plano erector de la espina para cirugía cardiaca: serie de casos

Abstract Multimodal analgesia in cardiac surgery sternotomy includes bilateral continuous erector spinae plane block (BC-ESPB). However, the effectiveness of the local anesthetic regimens is still uncertain. The purpose of this study was to assess pain control achieved with a multimodal analgesia regimen including BC-ESPB at the level of T5 with PCA with a 0.125 % bupivacaine infusion and rescue boluses. This is a descriptive case series study which recruited 11 adult patients undergoing cardiac surgery through sternotomy in whom multimodal analgesia including BC-ESPB was used, between February and April 2021, at a fourth level institution. All patients reported pain according to the numeric rating scale (NRS) ≤ 3 both at rest and in motion, at extubation and then 4 and 12 hours after surgery. After 24 hours the pain was NRS ≤ 3 in 100 % of the patients at rest and in 63.6 % in motion. At 48 h 81 % of the patients reported pain NRS ≤ 3 at rest and in motion. At 72h all patients reported pain NRS ≤ 3 at rest and 82 % in motion. The average intraoperative use of fentanyl was 2.35 µg/kg and postoperative hydromorphone was 5.3, 4.1 and 3.3 mg at 24, 48 and 72 hours, respectively. Hence, bilateral ESP block in continuous infusion plus rescue boluses allows for proper control of acute intra and post-operative pain.

Resumen En cirugía cardiaca mediante esternotomía, la analgesia multimodal incluye el bloqueo bilateral continuo del plano erector de la espina (BBC-ESP). Sin embargo, existe incertidumbre sobre la efectividad de los esquemas de dosificación del anestésico local. Se busca evaluar el control del dolor proporcionado por un esquema de analgesia multimodal que incluye el BBC-ESP a la altura de T5 con ACP de bupivacaína 0,125 % en infusión y bolos de rescate. Se trata de un estudio descriptivo, serie de casos. Se reclutaron 11 pacientes adultos sometidos a cirugía cardiaca mediante esternotomía en quienes se usó analgesia multimodal que incluía BBC-ESP entre febrero y abril del 2021, en una institución de cuarto nivel. Todos los pacientes refirieron dolor, según la escala numérica (EN) ≤ 3 tanto en reposo como en movimiento, a la extubación, a las 4 y a las 12 horas. A las 24 horas el dolor fue EN ≤ 3 en el 100 % de los pacientes en reposo y en el 63,6 % en movimiento. A las 48 h el 81 % de los pacientes refirieron dolor EN ≤ 3 en reposo y en movimiento. A las 72 h todos los pacientes presentaron dolor EN ≤ 3 en reposo y 82 % en movimiento. El consumo intraoperatorio promedio de fentanilo fue de 2,35 ug/kg y de hidromorfona posoperatoria de 5,3, 4,1 y 3,3 mg a las 24, 48 y 72 horas. Así, el BBC-ESP en infusión continua más bolos de rescate permiten el control del dolor agudo intra y posoperatorio.

Human Cytomegalovirus Infection Elicits Global Changes in Host Transcription by RNA Polymerases I, II, and III.

How human cytomegalovirus (HCMV) infection impacts the transcription of the host genome remains incompletely understood. Here, we examine the global consequences of infection of primary human foreskin fibroblasts (HFFs) on transcription by RNA polymerase I, II, and III over the course of a lytic infection using PRO-Seq. The expected rapid induction of innate immune response genes is observed with specific subsets of genes exhibiting dissimilar expression kinetics. We find minimal effects on Pol II initiation, but increased rates of the release of paused Pol II into productive elongation are detected by 24 h postinfection and pronounced at late times postinfection. Pol I transcription increases during infection and we provide evidence for a potential Pol I elongation control mechanism. Pol III transcription of tRNA genes is dramatically altered, with many induced and some repressed. All effects are partially dependent on viral genome replication, suggesting a link to viral mRNA levels and/or a viral early-late or late gene product. Changes in tRNA transcription are connected to distinct alterations in the chromatin state around tRNA genes, which were probed with high-resolution DFF-ChIP. Additionally, evidence is provided that the Pol III PIC stably contacts an upstream -1 nucleosome. Finally, we compared and contrasted our HCMV data with results from published experiments with HSV-1, EBV, KSHV, and MHV68. We report disparate effects on Pol II transcription and potentially similar effects on Pol III transcription.

Nuclear export restricts Gdown1 to a mitotic function.

Approximately half of purified mammalian RNA polymerase II (Pol II) is associated with a tightly interacting sub-stoichiometric subunit, Gdown1. Previous studies have established that Gdown1 inhibits transcription initiation through competitive interactions with general transcription factors and blocks the Pol II termination activity of transcription termination factor 2 (TTF2). However, the biological functions of Gdown1 remain poorly understood. Here, we utilized genetic, microscopic, and multi-omics approaches to functionally characterize Gdown1 in three human cell lines. Acute depletion of Gdown1 caused minimal direct effects on transcription. We show that Gdown1 resides predominantly in the cytoplasm of interphase cells, shuttles between the cytoplasm and nucleus, and is regulated by nuclear export. Gdown1 enters the nucleus at the onset of mitosis. Consistently, genetic ablation of Gdown1 is associated with partial de-repression of mitotic transcription, and Gdown1 KO cells present with evidence of aberrant mitoses coupled to p53 pathway activation. Evidence is presented demonstrating that Gdown1 modulates the combined functions of purified productive elongation factors PAF1C, RTF1, SPT6, DSIF and P-TEFb in vitro. Collectively, our findings support a model wherein the Pol II-regulatory function of Gdown1 occurs during mitosis and is required for genome integrity.

Reduction in Vaccine HPV Type Infections in a Young Women Group (18-25 Years) Five Years after HPV Vaccine Introduction in Colombia.

In Colombia, the human papillomavirus (HPV) vaccine was launched in 2012 in the context of a school-based national vaccination program targeting girls ages 9 to 14 and offering catch-up vaccination for girls ages 14 to 17. In this study, we evaluated the program's impact on type-specific HPV infection by comparing HPV cervical prevalence among vaccinated and nonvaccinated women. This is a comparative cross-sectional study conducted 5 years after the quadrivalent HPV vaccination implementation in a sentinel Colombian City. This study included young women (18-25 years old) who had been vaccinated in the catch-up group and were attending universities and technical institutions, and women who attended primary health care facilities for Pap smear screening. The HPV prevalence of 1,287 unvaccinated women was compared with the prevalence of 1,986 vaccinated women. The prevalence of HPV16/18 infections was significantly lower in vaccinated compared with unvaccinated women (6.5% vs. 15.4%; P < 0.001), whereas for HPV6/11 infections, a decrease of 63.7% in vaccinated women (1.02% vs. 2.81%) was observed. The adjusted effectiveness to HPV16/18 was 61.4%; 95% CI, 54.3%-67.6%. However, the effectiveness against HPV16/18 was significantly higher among women vaccinated before their sexual debut 91.5%; 95% CI, 86.8-94.5, compared with effectiveness for vaccination after their sexual debut, 36.2%; 95% CI, 23.6-46.7. Five years after the introduction of HPV vaccines in Colombia, high effectiveness of HPV to prevent HPV16/18 infections is observed in the catch-up cohorts including virgin and sexually active women. PREVENTION RELEVANCE: Monitoring HPV vaccines post-licensure plays an important role in assessing the progress of immunization programs, demonstrating the impact of vaccines on the population, and providing data for policy needs. In Colombia, HPV vaccines showed effectiveness when administered before start of sexual activity, and two doses are sufficient to achieve good protection.

Technique in Cleft Rhinoplasty: The Foundation Graft.

Secondary cleft rhinoplasty represents a particular surgical challenge. The authors have identified the deficit in skeletal projection of the cleft-sided piriform rim as an important contributor to the pathology. A graft is described to augment the piriform crest on the cleft side. This foundation graft is suture fixated to the piriform crest after complete release of all soft tissue attachments to the alar base. The foundation graft is articulated with a long alar strut graft, which allows for powerful projection of the cleft-sided nasal tip. An advancement flap of vestibular skin is described to correct the vestibular stenosis. A transplant of diced cartilage in fascia is added to augment maxillary soft tissue volume. Subjective and objective measures of form and function are presented in a retrospective series of five cases, illustrating the efficacy of the techniques described.

Cleft Lip Nose.

All patients with a cleft lip deformity have an associated nasal deformity that varies in degree of severity. A three-dimensional understanding of the anatomy of the cleft nose aids surgeons in selecting the proper technique for repair. Analysis and performance of orthognathic surgery should be done before nasal surgery to optimize the overall result. Goals of the secondary rhinoplasty include relief of nasal obstruction, creation of symmetry and definition of the nasal base and tip, and management of nasal scarring and webbing. Septal reconstruction in the cleft nose is a key maneuver in cleft rhinoplasty.

Chin Advancement, Augmentation, and Reduction as Adjuncts to Rhinoplasty.

Chin deformities are commonly encountered defects in patients seeking rhinoplasty. Careful preoperative evaluation may identify patients who could benefit from concurrent augmentation or reduction mentoplasty. Alloplastic chin implants and sliding genioplasty represent the main accepted methods of chin augmentation. Although both procedures may be used for retrognathia or microgenia, the sliding genioplasty may also be used in chin asymmetry, prognathia, and vertical height discrepancies. This article outlines the methods to analyze the chin, and discusses the treatment options available for correction of chin deformities as an adjunct to rhinoplasty.

Newer Understanding of Specific Anatomic Targets in the Aging Face as Applied to Injectables: Facial Muscles--Identifying Optimal Targets for Neuromodulators.

The muscular anatomy of the face is complex. Animation patterns of facial muscles vary significantly among individuals. Activity of facial muscles determines expression and emotion and affects the eyes aperture and the amount and extent of facial rhytids. Injection of botulin toxin for facial rejuvenation has become a very popular procedure and allows the practitioner the ability to modulate facial expression and to decrease the amount of facial rhytids. A thorough knowledge of the variant facial anatomy is necessary to maximize the efficiency of botulin toxin injection. This knowledge will also aid in minimizing complication an untoward side effect.

Management of Zygomatic Fractures: Bone and Arch.

Zygomatic bone and arch fractures are among the most common facial fractures treated by facial plastic surgeons. Controversy still remains regarding the optimal management of these fractures. Computed tomographic scanning (including three-dimensional reconstruction) represent a fundamental tool for diagnosis and treatment planning of zygomatic fractures. Main indications for treatment are functional impairment, cosmetic deformity, or both. Fracture reduction can be performed through an open or closed approach depending on the amount of exposure necessary to achieve accurate reduction. The common goal among all treatment plans is the exact three-dimensional restoration of the disturbed anatomy and function while minimizing complications.