Implications of sedation during the use of noninvasive ventilation in children with acute respiratory failure (SEDANIV Study).

BACKGROUND: The objective of this study was to analyze the effects of sedation administration on clinical parameters, comfort status, intubation requirements, and the pediatric intensive care unit (PICU) length of stay (LOS) in children with acute respiratory failure (ARF) receiving noninvasive ventilation (NIV). METHODS: Thirteen PICUs in Spain participated in a prospective, multicenter, observational trial from January to December 2021. Children with ARF under the age of five who were receiving NIV were included. Clinical information and comfort levels were documented at the time of NIV initiation, as well as at 3, 6, 12, 24, and 48 h. The COMFORT-behavior (COMFORT-B) scale was used to assess the patients' level of comfort. NIV failure was considered to be a requirement for endotracheal intubation. RESULTS: A total of 457 patients were included, with a median age of 3.3 months (IQR 1.3-16.1). Two hundred and thirteen children (46.6%) received sedation (sedation group); these patients had a higher heart rate, higher COMFORT-B score, and lower SpO2/FiO2 ratio than did those who did not receive sedation (non-sedation group). A significantly greater improvement in the COMFORT-B score at 3, 6, 12, and 24 h, heart rate at 6 and 12 h, and SpO2/FiO2 ratio at 6 h was observed in the sedation group. Overall, the NIV success rate was 95.6%-intubation was required in 6.1% of the sedation group and in 2.9% of the other group (p = 0.092). Multivariate analysis revealed that the PRISM III score at NIV initiation (OR 1.408; 95% CI 1.230-1.611) and respiratory rate at 3 h (OR 1.043; 95% CI 1.009-1.079) were found to be independent predictors of NIV failure. The PICU LOS was correlated with weight, PRISM III score, respiratory rate at 12 h, SpO2 at 3 h, FiO2 at 12 h, NIV failure and NIV duration. Sedation use was not found to be independently related to NIV failure or to the PICU LOS. CONCLUSIONS: Sedation use may be useful in children with ARF treated with NIV, as it seems to improve clinical parameters and comfort status but may not increase the NIV failure rate or PICU LOS, even though sedated children were more severe at technique initiation in the present sample.

Thigh ultrasound monitoring identifies muscle atrophy in mechanically ventilated pediatric patients.

Over the last decade, ultrasonography has taken on an increasingly important role in the daily management of critically patients and has recently been proposed as a means of measuring muscle volume and architecture. This study had two main aims: to monitor for the onset of muscle atrophy in mechanically ventilated pediatric patients during stays in a pediatric intensive care unit based on quadriceps femoris muscle thickness measurements and to study whether demographic and clinical variables have an impact on muscle loss in critically children. The study followed a prospective, observational, single-center design. The sample included all children admitted to our pediatric intensive care unit (PICU) who required mechanical ventilation for more than 48 h. Two trained clinicians measured the thickness of the quadriceps using a 12-MHz linear ultrasound transducer within 24 h of initiating invasive mechanical ventilation and again at 72 h, 1 week, and weekly thereafter until extubation. For the entire cohort, quadriceps femoris muscle thickness decreased by 4.67% on average (IQR = -13.4 to -0.59) between the first two assessments and 13% by the time of the final measurement (IQR = -24 to -0.5%) or 1.57%/day (p < 0.001). Approximately half of all the children (23/41; 56%) experienced muscle atrophy (defined a priori as a decrease in thickness of 10% or more). Bivariate analyses revealed that increasing age, being a child (vs. infant), cumulative energy and protein deficit, highest C-reactive protein value, exposure to neuromuscular blockers, and a longer stay in the PICU were all predictive of a greater decrease in thickness. In a multivariate model, exposure to neuromuscular blockers was linked with greater muscle loss.       Conclusion: In mechanically ventilated children, point-of-care ultrasonography can identify skeletal muscle atrophy. Muscle atrophy of limbs is strongly associated with the use of neuromuscular blockers. Ultrasound-based monitoring of the quadriceps femoris is a clinically useful tool for assessing muscle mass that can provide information on nutritional status and guide rehabilitation. What is Known: • ICU-acquired muscle atrophy is common and has a deleterious effect on adult outcomes. The prevalence and severity of muscular atrophy in critically ill children, however, are poorly understood. • Point-of-care ultrasonography has been put forward as an accurate, reliable method for monitoring variations in muscle mass.. What is New: • The quadriceps femoris muscle tends to suffer an intense loss of thickness early on in most critically ill children. • Quadriceps femoris ultrasound monitoring is a helpful tool for measuring muscle thickness and could lead to the development of novel therapies for critically ill children.

Understanding pediatric palliative care within interdisciplinary palliative programs: a qualitative study.

PURPOSE: To describe the process of delivery of pediatric palliative care from the perspective of a pediatric interdisciplinary team and the children's parents. METHODS: A qualitative descriptive case study was conducted. Purposeful sampling took place within a specialized pediatric palliative care Unit in Madrid (Spain), located at the Niño Jesus Hospital. The study participants included a specialized pediatric palliative care team from Madrid's pediatric palliative care program, other professional teams involved in interdisciplinary care and parents of children under pediatric palliative care. Data were collected via semi-structured interviews, focus groups and researchers' field notes. A thematic analysis was performed. RESULTS: This study included 28 participants (20 women, 8 men), of whom 18 were professionals who belonged to the pediatric palliative care interdisciplinary team, 4 professionals were from other units that collaborated with the pediatric palliative care, and 6 were parents (5 women, 1 man). The mean age of the pediatric palliative care members was 38.2 years (SD ± 7.9), that of the collaborating professionals was 40.5 (SD ± 6.8), and that of the parents was 44.2 (SD ± 5.4). Two main themes emerged: a) Pediatric palliative care has a distinct identity, associated with life. It represents the provision of special care in highly complex children, in the context of the home, far from the hospital environment; b) The team is key: its interdisciplinary organization provides a more comprehensive view of the child and their family, fosters communication among professionals, and improves coordination with other services involved in the care of children. The mindset shift experienced by ID-PPC professionals towards a palliative approach makes them more sensitive to the needs of their patients and leads them to develop specific skills in areas such as communication, decision-making, and adaptability that were identified as differentiating aspects of pediatric palliative care. CONCLUSIONS: Describing pediatric palliative care from the professional and parental perspective helps to establish realistic and comprehensive goals for the care of children and their parents. The findings of this study may help with the establishment of a pediatric palliative care team, as a necessary organizational change in a health care system that cares for children with complex and life-threatening conditions. Promoting training in pediatric palliative care, prioritizing more horizontal organizations, providing tools and spaces for coordination and communication between professionals from different services, together with the creation of a position of case coordinator in the care process of children could enhance the understanding of pediatric palliative care services.

Analysis of complications in intraventricular neuroendoscopy in children: proposal for a standardization system.

Although intraventricular neuroendoscopy is considered a minimally invasive technique with good results, there is nevertheless a risk of developing certain complications. As no agreement apparently exists concerning the classification of these complications, we aim to propose a form of classification based on the results of our series, comparing them with recent publications. We undertook a retrospective study of 170 children who underwent intraventricular neuroendoscopy between 2003 and September 2020 at our center. Data were recorded on demographic and clinical variables: age, gender, presenting symptoms, etiology, number of procedures, type of procedure, and complications. Complications were divided into two main groups, intraoperative and postoperative, and in subgroups. The intraoperative complications included one group of systemic alterations and another group of surgical problems. The postoperative complications were divided into six groups: systemic, neurologic, hormone, fluid, hemorrhagic and death. A total of 202 neuroendoscopic procedures were performed in 170 children. The mean age at first surgery was 71 months (22-122). The most common etiology of the hydrocephalus was intraventricular tumors (32.9%), followed by aqueductal stenosis (13.5%). The most usual presenting sign was intracranial hypertension. The procedure most used was third ventriculostomy (62.9%). During the procedures, we experienced 5 surgical intraoperative complications (2.47% per procedure). In the postoperative period, there were 23.7% systemic complications per procedure, 12.87% neurologic, 8.41% hormone, 10.9% fluid, 0.5% hemorrhagic, and 0.99% for postoperative death. The rate of complications associated with intraventricular neuroendoscopy was similar in our series to those already published. Comparative studies require standardization for the analysis of neuroendoscopic complications.

Effects of the lockdown due to the COVID-19 pandemic on alcohol consumption in patients under treatment in an alcohol relapse prevention programme. / Efectos del confinamiento en el hogar debido a la pandemia por COVID-19 en el consumo en pacientes en tratamiento en un programa de deshabituación de alcohol.

During the COVID-19 pandemic, several exceptional measures were put in place in order to avoid virus propagation, such as lockdown and the discontinuation of usual health care assistance services. It was considered that these changes might be associated with an increase in alcohol consumption and a higher risk of relapse for patients under treatment. The aim of this study was to assess changes in alcohol consumption during the lockdown period (between March and May, 2020) in patients following treatment under the Alcohol Use Disorders Programme at the "Hospital 12 de Octubre" in Madrid. A total of 311 patients were assessed through interviews carried out by telephone in accordance with usual clinical practice during that period. 76% of the total number of patients did not experience changes in their alcohol consumption, 9.2% stopped drinking and some experienced severe withdrawal syndrome, while 7.5% relapsed. The risk factors found for worsening the prognosis of the patients were: being female, drinking alcohol alone or at home, binge drinking, concomitant substance misuse and failure to attend therapy groups or self-help groups online during the lockdown. 31.6% of the sample described psychopathological symptoms due to the lockdown, especially those who already had psychiatric comorbidities. For this reason, we can conclude that during the lockdown as a result of the pandemic, most of our alcohol dependent patients did not modify their drinking patterns, but specific factors enabled us to identify a more vulnerable subgroup.

Durante la pandemia producida por la infección por el Covid-19 se produjeron una serie de cambios sociosanitarios excepcionales para evitar su propagación como el confinamiento en el hogar y la supresión de los servicios asistenciales sanitarios habituales. Se consideró que estos cambios podrían implicar un incremento en el consumo de alcohol y un mayor riesgo de recaídas para los pacientes en tratamiento. El objetivo de este estudio fue valorar los cambios en el consumo durante el período de confinamiento (marzo a mayo de 2020) en los pacientes en tratamiento en el programa de alcohol del Hospital Doce de Octubre de Madrid. Fueron valorados 311 pacientes mediante entrevista telefónica dentro de la práctica clínica habitual durante ese período. Un 76 % de los pacientes no presentaron cambios en su situación de consumo, un 9,2% de estos cesaron en el consumo, algunos de ellos con cuadros de abstinencia graves, y un 7,5% recayeron. El sexo femenino, el consumo en solitario o en el hogar, en atracón, o el de otras drogas de forma concomitante y el no estar en terapia grupal o no asistir a grupos de las asociaciones de ayuda mutua por videoconferencia durante el confinamiento fueron factores predictores de mal pronóstico. Un 31,6% presentó alteraciones psicopatológicas debidas al confinamiento, sobre todo, aquellos pacientes con comorbilidad psiquiátrica. Por lo tanto, en situaciones similares a esta, la mayoría de los pacientes en tratamiento no modifican el patrón de consumo, pero, ciertas características identifican un subgrupo de sujetos más vulnerables.

Effect of vitamin D supplementation on asthma control in patients with vitamin D deficiency: the ACVID randomised clinical trial.

BACKGROUND: The relationship between asthma and vitamin D deficiency has been known for some time. However, interventional studies conducted in this regard have shown conflicting results. OBJECTIVE: To evaluate the efficacy of vitamin D supplementation in asthmatic patients in improving the degree of control of asthma. METHODS: Randomised, triple-blind, placebo-controlled, parallel-group study in adult asthmatic patients with serum 25-hydroxyvitamin-D3 <30 ng/mL. The intervention group received oral supplementation with 16 000 IU of calcifediol per week, and the control group had placebo added to their usual asthma treatment. The study period was 6 months. The primary endpoint was the degree of asthma control as determined by the asthma control test (ACT). Secondary endpoints included quality of life measured using the mini Asthma Quality of Life Questionnaire, the number of asthma attacks, oral corticosteroid cycles, the dose of inhaled corticosteroids, number of emergency visits, unscheduled consultations with the primary care physician and hospitalisations for asthma. RESULTS: One hundred and twelve patients were randomised (mean age 55 years, with 87 (78%) being women). Of the 112 patients, 106 (95%) completed the trial. Half the patients (56) were assigned to the intervention group and the other half to the control group. A statistically significant clinical improvement was observed in the intervention group (+3.09) compared with the control group (-0.57) (difference 3.66 (95% CI 0.89 to 5.43); p<0.001) as measured using ACT scores. Among the secondary endpoints, a significant improvement in the quality of life was found in the intervention group (5.34), compared with the control group (4.64) (difference 0.7 (95% CI 0.15 to 1.25); p=0.01). CONCLUSION: Among adults with asthma and vitamin D deficiency, supplementation with weekly oral calcifediol compared with placebo improved asthma control over 6 months. Further research is needed to assess long-term efficacy and safety. TRIAL REGISTRATION NUMBER: NCT02805907.

Registry of patients with congenital bleeding disorders and COVID-19 in Madrid.

INTRODUCTION: We present the first registry of patients with congenital bleeding disorders and COVID-19. The study has been carried out in the Community of Madrid, which has the highest number of cases in Spain. The objective is to understand the incidence of COVID-19, the course of the disease if it occurs and the psychosocial and occupational impact on this population. METHODS: We included 345 patients (246 of haemophilia, 69 of von Willebrand Disease, two rare bleeding disorders and 28 carriers of haemophilia). A telephone survey was used to collect the data. RESULTS: Forty-two patients presented symptoms suggestive of infection by COVID-19, and in six cases, the disease was confirmed by RT-PCR. The cumulative incidence of our series was 1.73%. It is worth noting the complexity of the management of COVID-19 in two patients on prophylaxis with non-factor replacement therapy. Adherence to the prescribed treatment was maintained by 95.5% of patients. Although 94% were independent for daily living activities, 42.4% had a recognized disability and 58% required assistance, provided by the Madrid Haemophilia Association (Ashemadrid) in 75% of cases. Only 4.4% of consultations were held in person. CONCLUSIONS: Patients with congenital bleeding disorders infected with SARS-CoV-2 presented a mild course of the disease that did not require admission. Their identification and treatment by a specialist team from a Haemophilia Treatment Center are essential to make a correct assessment of the risk of haemorrhage/thrombosis. COVID-19 had a major impact on the psychosocial aspects of these patients which must be remedied with recovery plans.

Moderate hyperoxia induces inflammation, apoptosis and necrosis in human umbilical vein endothelial cells: An in-vitro study.

BACKGROUND: Perioperative oxygen (O2) therapy can cause hyperoxia. Extreme hyperoxia can injure the cardiovascular system and remote organs. OBJECTIVE: Our primary objective was to test the hypothesis that exposure to moderate hyperoxia will induce injury to human umbilical vein endothelial cells (HUVECs), a model for studying the vascular endothelium under controlled conditions. DESIGN: In-vitro cell culture study. SETTING: Department of Anaesthesia, General Intensive Care and Pain Management, Medical University of Vienna, Austria. Study period from the beginning of October 2013 to the end of July 2014. CELLS: HUVECs were isolated from fresh umbilical cords. INTERVENTIONS: HUVECs were exposed to constant hyperoxia (40% O2), cyclic hyperoxia/anoxia (40%/0% O2, average 20% O2), constant normoxia (21% O2) and constant anoxia (0% O2) using a cell culture bioreactor. MAIN OUTCOME MEASURES: Cell growth, viability and release of IL-6, IL-8 and macrophage migration inhibitory factor were assessed at baseline and after 6, 12, 24 and 48 h of treatment. A phosphokinase array was performed after 60 min of treatment to identify activated cellular signalling pathways. RESULTS: Constant hyperoxia and cyclic hyperoxia/anoxia impeded cell growth, reduced viability, triggered a proinflammatory response, proven by IL-6, IL-8 and migration inhibitory factor release, and induced apoptosis and necrosis. The inflammatory and cytotoxicity responses were highest in the constant hyperoxia group. Phosphokinase arrays revealed that different O2 concentrations activated distinct sets of cytoprotective and cell death-associated kinases, including mitogen-activated protein kinases, Src kinases, p53, Akt, mitogen-activated and stress-activated kinase, Lyn, Lck, p70S6, signal transducers and activators of transcription 5b and 6, glycogen synthase kinase 3a/b and 5' AMP-activated protein kinases 1/2. CONCLUSION: Continuous moderate hyperoxia and cyclic moderate hyperoxia/anoxia-induced endothelial inflammation, apoptosis and necrosis. Given the large surface area of the vascular endothelium, moderately elevated O2 levels may contribute to cardiovascular inflammation and injury. TRIAL REGISTRATION: This in-vitro study was not registered in a database.

Living in Limbo: Latinas' Assessment of Lower Rio Grande Valley Colonias Communities.

Community asset mapping (CAM) is the collective process of identifying local assets and strategizing processes to address public health issues and concerns and improve quality of life. Prior to implementing a community-based physical activity intervention with Latinas in the Texas Lower Rio Grande Valley, promotoras [community health workers] conducted 16 interactive sessions in 8 colonias. The analysis of the transcribed CAM recordings and on-site observational data resulted in the construction of Living in Limbo as the thematic representation of these Latinas' social isolation and marginalization associated with pervasive poverty, undocumented immigration status or lack of citizenship, their fears emanating from threats to physical and emotional safety, and the barriers created by lack of availability and access to resources.

Argon Preconditioning Protects Airway Epithelial Cells against Hydrogen Peroxide-Induced Oxidative Stress.

BACKGROUND: Oxidative stress is the predominant pathogenic mechanism of ischaemia-reperfusion (IR) injury. The noble gas argon has been shown to alleviate oxidative stress-related myocardial and cerebral injury. The risk of lung IR injury is increased in some major surgeries, reducing clinical outcome. However, no study has examined the lung-protective efficacy of argon preconditioning. The present study investigated the protective effects of argon preconditioning on airway epithelial cells exposed to hydrogen peroxide (H2O2) to induce oxidative stress. METHODS: A549 airway epithelial cells were treated with a cytotoxic concentration of H2O2 after exposure to standard air or 30 or 50% argon/21% oxygen/5% carbon dioxide/rest nitrogen for 30, 45 or 180 min. Cells were stained with annexin V/propidium iodide, and apoptosis was evaluated by fluorescence-activated cell sorting. Protective signalling pathways activated by argon exposure were identified by Western blot analysis for phosphorylated candidate molecules of the mitogen-activated protein kinase and protein kinase B (Akt) pathways. RESULTS: Preconditioning with 50% argon for 30, 45 and 180 min and 30% argon for 180 min caused significant protection of A549 cells against H2O2-induced apoptosis, with increases in cellular viability of 5-47% (p < 0.0001). A small adverse effect was also observed, which presented as a 12-15% increase in cellular necrosis in argon-treated groups. Argon exposure resulted in early activation of c-Jun N-terminal kinase (JNK) and p38, peaking 10- 30 min after the start of preconditioning, and delayed activation of the extracellular signal-regulated kinase 1/2 (ERK1/2) pathway, peaking after 60-90 min. CONCLUSIONS: Argon preconditioning protects airway epithelial cells from H2O2-induced apoptotic cell death. Argon activates the JNK, p38, and ERK1/2 pathways, but not the Akt pathway. The cytoprotective properties of argon suggest possible prophylactic applications in surgery-related IR injury of the lungs.

Transoral ultrasonic total laryngectomy (TOUSS-TL): description of a new endoscopic approach and report of two cases.

The minimally invasive total laryngectomy avoids a wide surgical field and so it has the potential benefit of reducing the local morbidity, especially on radiated patients. This approach has been previously described on a robotic basis, the transoral robotic total laryngectomy (TORS-TL). We have designed a minimally invasive approach for total laryngectomy (TL) using the transoral ultrasonic surgery technique (TOUSS). TOUSS is a transoral, endoscopic, non-robotic approach for laryngeal and pharyngeal tumors, based on the ultrasonic scalpel as a resection tool. Two patients with a laryngeal squamous cell carcinoma with indication for total laryngectomy were surgically treated: one primary TL for a subglottic carcinoma and one salvage TL with partial pharyngectomy for a local relapse after chemoradiotherapy of a glottic carcinoma. The tumors were completely removed with free surgical margin in both patients. The functional recovery was satisfactory in terms of swallowing and speech (a tracheoesophageal puncture and voice prosthesis placement were done in the same procedure). No intraoperative complications were observed. The patient with previous chemoradiotherapy had a pharyngocutaneous fistula which closed spontaneously without additional surgery. We have demonstrated that transoral endoscopic approach to the larynx and pharynx is feasible without a robotic platform. TOUSS-TL can easily spread the transoral endoscopic philosophy as well as the benefits of a minimally invasive way to remove the entire larynx. Further research will show the advantages in terms of complications and functional outcomes.

The high frequency of genetic diseases in hypotonic infants referred by neuropediatrics.

Neonatal hypotonia is a relatively common cause of consultation in daily pediatric practice. It is part of the clinical presentation of a large group of heterogeneous diseases, many of which have an important and classifiable genetic background. Identification of the specific disorder can help optimize the management and treatment of the patient and inform genetic counseling for the family, and therefore input from clinical geneticists is critical at the earliest stages of medical management. Here we present 30 patients with hypotonia of unknown etiology referred by a neuropediatrician to clinical genetics. Clinical, genetic, and molecular evaluation of each patient was performed. Sixty-nine percent of the patients included in the study had a genetic disease, including eight with Prader-Willi syndrome, three with spinal muscular atrophy, one with Rett syndrome, and one with Sotos syndrome harboring a previously undescribed mutation. Our data demonstrate that a multidisciplinary approach used from the outset that includes molecular analysis can help improve diagnosis and management of hypotonic infants.

Enhancing mobile phones for people with visual impairments through haptic icons: the effect of learning processes.

We report the results of a study on the learnability ofhaptic icons used in a system for incoming-call identification in mobile phones. The aim was to explore the feasibility of using haptic icons to create new assistive technologies for people with visual impairments. We compared the performance and satisfaction of users with different visual capacities (visually impaired vs. sighted) and using different learning processes (unimodal vs. multimodal). A better recognition rate and user experience were observed for the visually impaired than for sighted users and for multimodal rather than unimodal learning processes.

Feasibility of Using Rideshare Transportation to Reduce Barriers to Participating in a Clinic-based Food Insecurity Intervention.

BACKGROUND: Few clinic-based food insecurity interventions address transportation barriers to utilizing food resources. OBJECTIVES: We assessed the feasibility of using free rideshare-based transportation to reduce barriers to participating in an ongoing clinic-based food insecurity intervention. METHODS: Our multi-methods pilot study used patient surveys (n = 155), focus groups with clinic and program staff (n = 10), and rideshare usage data. RESULTS: Of the 95 (61.2%) survey respondents who reported transportation barriers, only 34 (21.9%) used rideshare. More than 80% of rideshare users rated their experience as good or excellent. Clinic and program staff reported that the service allowed patients a greater sense of control over their time and health and emphasized the need for staffing and program-level infrastructure. CONCLUSIONS: Free rideshare may address transportation barriers for some patients but multiple options for support and adjustments to how we offer transportation solutions are needed to successfully meet the needs of all program participants experiencing transportation barriers.

Pediatric Palliative Care at Home: A Prospective Study on Subcutaneous Drug Administration.

CONTEXT: The subcutaneous route is a useful alternative for drug administration in palliative care. Although there is scientific evidence on its use in adult patients, the literature in pediatric palliative care is almost nonexistent. OBJECTIVES: To describe the experience of a pediatric palliative care unit (PPCU) with in-home subcutaneous drug administration symptom control. METHODS: Prospective observational study of patients receiving home-based subcutaneous treatment administered as part of a PPCU treatment regimen over 16 months. Analysis includes demographic and clinical variables and treatment received. RESULTS: Fifty-four different subcutaneous lines were inserted in the 15 patients included, mainly in the thigh (85.2%). The median time of needle in situ was 5.5 days (range: 1-36 days). A single drug was administered in 55.7% of treatments. The most frequently used drugs were morphine chloride (82%) and midazolam (55.7%). Continuous subcutaneous infusion was the predominant administration route (96.7%), with infusion rates oscillating between 0.1 mL/h and 1.5 mL/h. A statistically significant relationship was found between the maximum infusion rate and induration onset. Of the 54 lines placed, 29 (53.7%) had an associated complication requiring line removal. The primary cause for removal was insertion-site induration (46.3%). Subcutaneous lines were mainly used to manage pain, dyspnea, and epileptic seizures. CONCLUSION: In the pediatric palliative care patients studied, the subcutaneous route is most frequently used for administering morphine and midazolam in continuous infusion. The main complication was induration, especially with longer dwell times or higher infusion rates. However, further studies are required to optimize management and prevent complications.

Influence of Humoral Response Against GnRH, Generated by Immunization with a Therapeutic Vaccine Candidate on the Evolution of Patients with Castration-Sensitive Prostate Adenocarcinoma.

BACKGROUND AND AIMS: A gonadotropin-releasing hormone (GnRH)-based therapeutic vaccine candidate against hormone-sensitive prostate cancer has demonstrated its safety and signs of efficacy in phase I/II trials. In this study, we characterized the isotype/subclass profiles of the anti-GnRH humoral response generated by the vaccination and analyzed its association with patients' clinical outcomes. METHODS: The immunoglobulin isotypes and IgG subclasses of the antibody responses of 34 patients included in a randomized, open, prospective phase I/II clinical trial were characterized. Every patient included in the study had a diagnosis of locally advanced prostate adenocarcinoma at stages 3 and 4 and received immunization with the vaccine candidate. Additionally, serum testosterone and prostate specific antigen (PSA) concentrations, serving as indicators of tumor response, were determined. The type of anti-GnRH antibody response was correlated to the time elapsed until the first biochemical recurrence in patients and the outcome of the disease. RESULTS: All patients developed strong and prolonged anti-GnRH antibody responses, resulting in a short- to mid-term decrease in serum testosterone and PSA levels. Following immunizations, anti-GnRH antibodies of the IgM/IgG and IgG1/IgG3 subclasses were observed. Following radiotherapy, the humoral response switched to IgG (IgG1/IgG4). Patients who experienced a short-term biochemical relapse were characterized by significantly higher levels of anti-GnRH IgG titers, particularly IgG1 and IgG4 subclasses. These characteristics, along with a high response of specific IgM antibodies at the end of immunizations and the development of anti-GnRH IgA antibody responses following radiotherapy, were observed in patients whose disease progressed, compared to those with controlled disease. CONCLUSION: The nature of the humoral response against anti-GnRH, induced by vaccination may play a key role in activating additional immunological mechanisms. Collectively, these mechanisms could contribute significantly to the regulation of tumor growth.

Altered Arylamine N-acetyltransferase 1 and miR-1290 Levels in Childhood Acute Lymphoblastic Leukemia: A Pilot Study.

BACKGROUND/AIM: Arylamine N-acetyltransferase 1 and 2 (NAT1 and NAT2) are drug-metabolizing enzymes that play a key role in the development of acute lymphoblastic leukemia (ALL). MATERIALS AND METHODS: This study evaluated NAT1 and NAT2 mRNA and protein expression and their enzymatic activity in peripheral blood mononuclear cells (PBMC) from patients with ALL (n=20) and healthy children (n=19) and explored the mechanisms that regulate these enzymes in ALL such as microRNAs (miR-1290, miR-26b) and SNPs. RESULTS: PBMC from patients with ALL showed a decrease in NAT1 mRNA and protein expression. In addition, NAT1 enzymatic activity was decreased in patients with ALL. There was no influence of SNP 559 C>T or 560 G>A on low NAT1 activity. The lower expression of NAT1 might be related to the loss of acetylated histone H3K14 in the NAT1 gene promoter in patients with ALL and the higher relative expression of miR-1290 in the plasma of patients with relapsed ALL compared with healthy controls. There were significantly fewer CD3+/NAT1+ double-positive cells in patients who relapsed compared with control subjects. Based on a t-distributed stochastic neighbor embedding algorithm, CD19+ cells that reappeared in patients with relapse showed low NAT1 expression. In contrast, for NAT2, there were no significant results. CONCLUSION: The expression and function of NAT1 and miR-1290 levels could be involved in modulating immune cells altered in ALL.

Engaging Public Health Critical Race Praxis in Local Social Determinants of Health Research: The Youth Health Equity and Action Research Training Program in Portland, OR-yHEARTPDX.

The social determinants of health (SDH) have long been considered a core mechanism through which racial health inequities are (re)produced and incubated in the U.S. Moreover, scholars have expressly-and appropriately-named structural racism as a precursor to inequities associated with SDH. However, while research on racial health inequities-SDH-related or otherwise-continues to grow, communities of color remain grossly underrepresented as public health researchers and practitioners. Additionally, although SDH are experienced in a very local sense, much research and practice fails to more deeply and thoroughly engage and center local community knowledges. Thus, much work around SDH and racial health inequities presents, ironically, as structurally racist itself-being done/led mostly by White scholars and in ways that do not "center the margins". Moreover, in the context of public health practice, youth perspective is seldom centered within local health department (LHD) community SDH assessment efforts. With these challenges in mind, this paper introduces and discusses the development of the youth health equity and action research training (yHEART) program as a model for public health researchers/practitioners to engage public health critical race praxis (PHCRP) to better understand and respond to local SDH in communities of color. Specifically, we highlight the significance of PHCRP principles of "voice" and "social construction of knowledge" in advancing antiracism in research and LHD practice related to local SDH. First, we articulate core conceptual and theoretical groundings that informed the yHEART program's development and animate its ongoing training and research activities. Second, we outline the program's core training components and overall process, and provide some brief illustrative examples of work completed during the program's first iteration-yHEART PDX, Vol.I: Youth Participatory Research on Local Social Determinants of Health. We then close with a discussion that reflects on program strengths, challenges, and implications for SDH and racial health equity research/practice in light of growing calls for an antiracist public health.