Presurgical Use of Hypoxic Mixture for Systemic Perfusion Improvement in Neonates With Complex Congenital Heart Disease: A Systematic Review and Meta-Analysis.

Oxygen therapy is essential for the survival of preterm babies and critically ill newborns; however, it has the potential to cause harm through hypoxemia or hyperoxemia. Newborns with complex congenital heart diseases (CHD) suffer from oxygen fluctuations due to the disease and its treatments, altering pre and postnatal development. The objective of this study is to evaluate the evidence for using a hypoxic mixture to decrease pulmonary over-circulation and improve systemic perfusion before surgical interventions in newborns with complex CHD that course with pulmonary over-circulation and systemic hypoperfusion. A search was conducted in PubMed, EMBASE, LILACS, Scielo, Taylor and Francis, SAGE, and Science Direct databases from 2000 to 2022 by two independent authors, including articles with hypoxic mixture treatment in observational studies or trials, with pre-treatment and post-treatment measurements in the same patient, or two groups or more comparisons. Six articles were selected, with a total of 75 patients. The primary outcome was improved systemic circulation and decreased pulmonary over-circulation measured directly with Qp/Qs and indirectly with oxygen saturation and cerebral near-infrared spectroscopy (NIRS). In addition, we performed a meta-analysis for oxygen saturation and cerebral NIRS. Oxygen saturation was the value uniformly reported; three studies reported a significantly lower oxygen saturation after the hypoxic mixture. The cerebral NIRS was measured in 4 studies, with inconsistent results. After using the hypoxic mixture, the Qp/Qs calculation was lower in the two studies but was not statistically significant. The meta-analysis for oxygen saturation showed a fixed effect post-hypoxic therapy of -0.7 (-1.06; -0.35), p < 0.001. The meta-analysis of two studies that measured cerebral NIRS did not show a statistically significant difference at 12 and 24 hours. In conclusion, this is the first systematic review and meta-analysis regarding the pre-operative use of hypoxic gas mixtures for newborns with complex congenital heart disease. Treatment results in lower oxygen saturations, but there is a lack of evidence of improvement in systemic perfusion. The utilization of this therapy is controversial, and better evidence is necessary.

Assessing bias in GFR estimating equations: improper GFR stratification can yield misleading results.

BACKGROUND: Assessing bias (estimated - measured) is key to evaluating glomerular filtration rate (GFR). Stratification by subgroups can indicate where equations perform differently. However, there is a fallacy in the assessment of two instruments (e.g., eGFR and mGFR) when stratifying on the level of only one of those instruments. Here, we present statistical aspects of the problem and a solution for GFR stratification along with an empirical investigation using data from the CKiD study. METHODS: Compared and contrasted biases (eGFR relative to mGFR) with 95% confidence intervals within strata of mGFR only, eGFR only, and the average of mGFR and eGFR using data from the Chronic Kidney Disease in Children (CKiD) study. RESULTS: A total of 304 participants contributed 843 GFR studies with a mean mGFR of 48.46 (SD = 22.72) and mean eGFR of 48.67 (SD = 22.32) and correlation of 0.904. Despite strong agreement, eGFR significantly overestimated mGFR when mGFR < 30 (+ 6.2%; 95%CI + 2.9%, + 9.7%) and significantly underestimated when mGFR > 90 (-12.2%; 95%CI - 17.3%, - 7.0%). Significant biases in opposite direction were present when stratifying by eGFR only. In contrast, when stratifying by the average of eGFR and mGFR, biases were not significant (+ 1.3% and - 1.0%, respectively) congruent with strong agreement. CONCLUSIONS: Stratifying by either mGFR or eGFR only to assess eGFR biases is ubiquitous but can lead to inappropriate inference due to intrinsic statistical issues that we characterize and empirically illustrate using data from the CKiD study. Using the average of eGFR and mGFR is recommended for valid inferences in evaluations of eGFR biases.

Timing of Kidney Replacement Therapy Initiation and Survival during Pediatric Extracorporeal Membrane Oxygenation: An Extracorporeal Life Support Organization Registry Study.

To characterize kidney replacement therapy (KRT) and pediatric extracorporeal membrane oxygenation (ECMO) outcomes and to identify the optimal timing of KRT initiation during ECMO associated with increased survival. Observational retrospective cohort study using the Extracorporeal Life Support Organization Registry database in children (0-18 yo) on ECMO from January 1, 2016, to December 31, 2020. Of the 14,318 ECMO runs analyzed, 26% of patients received KRT during ECMO. Patients requiring KRT before ECMO had increased mortality to ECMO decannulation (29% vs. 17%, OR 1.97, P < 0.001) and to hospital discharge (58% vs. 39%, OR 2.16, P < 0.001). Patients requiring KRT during ECMO had an increased mortality to ECMO decannulation (25% vs. 15%, OR 1.85, P < 0.001) and to hospital discharge (56% vs. 34%, OR 2.47, P < 0.001). Multivariable logistic regression demonstrated that the need for KRT during ECMO was an independent predictor for mortality to ECMO decannulation (OR 1.49, P < 0.001) and to hospital discharge (OR 2.02, P < 0.001). Patients initiated on KRT between 24 and 72 hours after cannulation were more likely to survive to ECMO decannulation and showed a trend towards survival to hospital discharge as compared to those initiated before 24 hours and after 72 hours.

Improvement of neurogenic urinary dysfunctions in female rats treated with an injection of botulinum toxin A at the epicenter of the spinal cord injured site.

OBJECTIVE: To assess the effect of an injection of botulinum toxin A (BoNT/A) at the epicenter of the spinal cord injury (SCI) site on the recovery of lower urinary tract function in female rats with thoracic SCI. MATERIALS AND METHODS: Twenty-four female Wistar rats with Sham (laminectomy at T8/T9 level) or SCI (at T8/T9; 30 g compression for 5 s) were assigned into Sham-SS (injected with 5 µL of saline solution), Sham-BoNT/A (injected with 15 pg/rat, equivalent to 7.5 Units/kg of BoNT/A in 5 µL volume), SCI-SS (injured and injected with saline), SCI-BoNT/A (injured and injected with BoNT/A), N = 6 per group. Weekly evaluation of stereotyped micturition behavior, hind-limb nociception, and locomotor activity was performed 1 week before and during 6 weeks after surgery. Subsequently, all groups underwent simultaneous electromyography of the external urethral sphincter (EUS-EMG) and cystometric (CMG) studies. RESULTS: A compression SCI at the T8/T9 thoracic level significantly impairs sensory and locomotive functions, as well as stereotyped micturition behavior. However, these impairments were improved by BoNT/A injection after SCI. Neither injections of saline solution nor BoNT/A had an appreciable effect on the same parameters evaluated in the Sham groups. The combined EUS-EMG and CMG evaluations revealed important improvements of lower urinary tract physiology, particularly a reduction in the frequency of non-voiding contractions and the properties of EUS bursting activity indicated as the amplitude of the EUS-EMG signal and duration of burst electrical activity during effective voiding. CONCLUSION: The severe impairments on sensory and locomotive functions as well stereotyped micturition caused by an SCI could be potentially attenuated by an injection of a small amount of BoNT/A directly into the epicenter of the SCI region. A reduction in the release of neurotoxic neurotransmitters requiring the SNARE complex may be the mechanism triggered by BoNT/A to reduce neurotoxicity and hyperexcitability created in the SCI area to improve the survival of spinal cord cells involved in micturition.

Lung mechanics in pediatric acute respiratory distress syndrome associated to acute COVID-19 and MIS-C: implications for therapies and outcomes. / Mecánica pulmonar en el síndrome de distrés respiratorio agudo pediátrico asociado a COVID-19 aguda y MIS-C.

OBJECTIVE: To describe lung mechanics in Pediatric Acute Respiratory Distress Syndrome (PARDS) associated with acute COVID-19 and MIS-C with respiratory failure. METHODS: A concurrent multicenter observational study was performed, analyzing clinical variables and pulmonary mechanics of PARDS associated with COVID-19 in 4 Pediatric intensive care units (PICU) in Peru. The subgroup analysis included PARDS associated with multisystem inflammatory syndrome in children (MIS-C), MIS-PARDS, and PARDS with COVID-19 primary respiratory infection, C-PARDS. In addition, receiver operating characteristic (ROC) curve analysis for mortality and lung mechanics was performed. RESULTS: 30 patients were included. The age was 7.5 (4-11) years, 60% were male, and mortality was 23%. 47% corresponded to MIS-PARDS and 53% to C-PARDS groups. C-PARDS had positive RT-PCR in 67% and MIS-PARDS none (p < 0.001). C-PARDS group had more profound hypoxemia (P/F ratio < 100, 86% vs. 38%, p < 0.01) and higher driving-pressure [14(10-22) vs 10(10-12) cmH2O], and lower compliance of the respiratory system (CRS) [0.5 (0.3-0.6) vs 0.7(0.6-0.8) ml/ kg/cmH2O] compared with MIS-PARDS (all p < 0.05). The ROC analysis for mortality showed that driving pressure had the best performance [AUC 0.91(95%CI0.81-1.00), with the best cut-off point of 15 cmH2O (100% sensitivity and 87% specificity). Mortality in C-PARDS was 38% and 7% in MIS-PARDS (p = 0.09). MV-free days were 12(0-23) in C-PARDS and 23(21-25) in MIS-PARDS (p = 0.02). CONCLUSION: Patients with C-PARDS have lung mechanics characteristics similar to classic moderate to severe PARDS. This was not observed in patients with MIS-C. As seen in other studies, a driving pressure ≥ 15 cmH2O was the best discriminator for mortality. These findings may help guide ventilatory management strategies for these two different presentations.

Estimation of solar resource for vehicle-integrated photovoltaics in urban environments using image-based shade detection.

Vehicle-Integrated Photovoltaics (VIPV) in urban environments face challenges in accurately estimating solar resource due to dynamic shading effects. This research presents a methodology for evaluating VIPV solar resource by analyzing imagery and detecting shade conditions along driving routes. Street image mapping services and obstacle detection algorithms are utilized to determine the shaded or sunny condition of the vehicle at each point. The approach enables the calculation of solar irradiance, considering direct and diffuse components, and identifies energetically optimal driving routes. The methodology provides valuable insights for optimizing MPPT algorithms and assessing VIPV performance in urban settings. It offers a practical tool for sustainable mobility and renewable energy integration.

Recycled PLA for 3D Printing: A Comparison of Recycled PLA Filaments from Waste of Different Origins after Repeated Cycles of Extrusion.

The objective of this work is to evaluate the reprocessing of PLA 3D printing waste from different origins, into filaments and films, and without the addition of any additive. Two types of waste were considered: a blend of different printing wastes (masks, visors, other components) of personal protective equipment coming from an association of Spanish coronamakers, and PLA waste from a single known commercial source. Both types of materials were subjected to repeated extrusion cycles and processed into films by compression molding. Samples were characterized after each cycle and their mechanical and viscosity properties evaluated. Diffusion-ordered NMR spectroscopy (DOSY) experiments were also carried out to estimate molecular weights. The results show a better performance for the PLA waste from the known origin, capable of withstanding up to three re-extrusion cycles per two for the waste blending, without significant degradation. Additionally, a model to address collection and mechanical recycling cycles under two different scenarios (full traceability and not full traceability) was proposed.

DICER1-associated central nervous system sarcoma: A comprehensive clinical and genomic characterization of case series of young adult patients.

Background: DICER1 alterations are associated with intracranial tumors in the pediatric population, including pineoblastoma, pituitary blastoma, and the recently described "primary DICER1-associated CNS sarcoma" (DCS). DCS is an extremely aggressive tumor with a distinct methylation signature and a high frequency of co-occurring mutations. However, little is known about its treatment approach and the genomic changes occurring after exposure to chemoradiotherapy. Methods: We collected clinical, histological, and molecular data from eight young adults with DCS. Genomic analysis was performed by Next-generation Sequencing (NGS). Subsequently, an additional germline variants analysis was completed. In addition, an NGS analysis on post-progression tumor tissue or liquid biopsy was performed when available. Multiple clinicopathological characteristics, treatment variables, and survival outcomes were assessed. Results: Median age was 20 years. Most lesions were supratentorial. Histology was classified as fusiform cell sarcomas (50%), undifferentiated (unclassified) sarcoma (37.5%), and chondrosarcoma (12.5%). Germline pathogenic DICER1 variants were present in two patients, 75% of cases had more than one somatic alteration in DICER1, and the most frequent commutation was TP53. Seven patients were treated with surgery, Ifosfamide, Cisplatin, and Etoposide (ICE) chemotherapy and radiotherapy. The objective response was 75%, and the median time to progression (TTP) was 14.5 months. At progression, the most common mutations were in KRAS and NF1. Overall survival was 30.8 months. Conclusions: DCS is an aggressive tumor with limited therapeutic options that requires a comprehensive diagnostic approach, including molecular characterization. Most cases had mutations in TP53, NF1, and PTEN, and most alterations at progression were related to MAPK, RAS and PI3K signaling pathways.

Flexural Strength of CAD/CAM Lithium-Based Silicate Glass-Ceramics: A Narrative Review.

Amongst chairside CAD/CAM materials, the use of lithium-based silicate glass-ceramics (LSGC) for indirect restorations has recently been increasing. Flexural strength is one of the most important parameters to consider in the clinical selection of materials. The aim of this paper is to review the flexural strength of LSGC and the methods used to measure it. METHODS: The electronic search was completed within PubMed database from 2 June 2011 to 2 June 2022. English-language papers investigating the flexural strength of IPS e.max CAD, Celtra Duo, Suprinity PC, and n!ce CAD/CAM blocks were included in the search strategy. RESULTS: From 211 potential articles, a total of 26 were identified for a comprehensive analysis. Categorization per material was carried out as follows: IPS e.max CAD (n = 27), Suprinity PC (n = 8), Celtra Duo (n = 6), and n!ce (n = 1). The three-point bending test (3-PBT) was used in 18 articles, followed by biaxial flexural test (BFT) in 10 articles, with one of these using the four-point bending test (4-PBT) as well. The most common specimen dimension was 14 × 4 × 1.2 mm (plates) for the 3-PBT and 12 × 1.2 mm (discs) for BFT. The flexural strength values for LSGC materials varied widely between the studies. SIGNIFICANCE: As new LSGC materials are launched on the market, clinicians need to be aware of their flexural strength differences, which could influence the clinical performance of restorations.

Trajectories of eGFR after kidney transplantation according to trajectories of eGFR prior to kidney replacement therapies in children with chronic kidney disease.

BACKGROUND: In children with chronic kidney disease (CKD), certain risk factors are associated with faster eGFR decline and earlier kidney failure. Whether these factors have lingering effects on post-transplant eGFR trajectory remains unclear. We characterized pre- and post-transplant eGFR trajectories in pediatric kidney transplant recipients by their pre-kidney replacement therapy (KRT) risk factors. METHODS: We studied eGFR trajectories before KRT initiation and after transplantation among Chronic Kidney Disease in Children (CKiD) Study participants. We used mixed-effects models to compare pre-KRT versus post-transplant eGFR trajectories within individual participants by 7 pre-KRT risk factors: glomerular/non-glomerular etiology, race, preemptive transplant, proteinuria, albuminuria, and systolic/diastolic blood pressure (SBP/DBP). RESULTS: We analyzed 1602 pre-KRT and 592 post-transplant eGFR measurements from 246 transplant recipients. Mean annual eGFR decline was decreased from 18.0% pre-KRT (95%CI, 16.1-19.8) to 5.0% post-transplant (95%CI, 3.3-6.7). All 7 pre-KRT risk factors showed strong associations with faster pre-KRT eGFR decline, but not with post-transplant eGFR decline; only albuminuria, high SBP, and high DBP reached statistical significance with notably attenuated associations. In our multivariable model of the pre-KRT risk factors, post-transplant eGFR decline was more rapid only when albuminuria and high SBP were both present. CONCLUSIONS: eGFR decline substantially slows down after transplant even among children with rapidly progressing forms of CKD. Nonetheless, those who had albuminuria and high SBP before KRT might continue to show faster eGFR decline after transplant, specifically when both risk factors were present. This subgroup might benefit from intensive pre-transplant management for at least one of the two risk factors. A higher resolution version of the Graphical abstract is available as Supplementary information.

Extracorporeal Membrane Oxygenation Characteristics and Outcomes in Children and Adolescents With COVID-19 or Multisystem Inflammatory Syndrome Admitted to U.S. ICUs.

OBJECTIVES: Extracorporeal membrane oxygenation (ECMO) has been used successfully to support adults with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-related cardiac or respiratory failure refractory to conventional therapies. Comprehensive reports of children and adolescents with SARS-CoV-2-related ECMO support for conditions, including multisystem inflammatory syndrome in children (MIS-C) and acute COVID-19, are needed. DESIGN: Case series of patients from the Overcoming COVID-19 public health surveillance registry. SETTING: Sixty-three hospitals in 32 U.S. states reporting to the registry between March 15, 2020, and December 31, 2021. PATIENTS: Patients less than 21 years admitted to the ICU meeting Centers for Disease Control criteria for MIS-C or acute COVID-19. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The final cohort included 2,733 patients with MIS-C ( n = 1,530; 37 [2.4%] requiring ECMO) or acute COVID-19 ( n = 1,203; 71 [5.9%] requiring ECMO). ECMO patients in both groups were older than those without ECMO support (MIS-C median 15.4 vs 9.9 yr; acute COVID-19 median 15.3 vs 13.6 yr). The body mass index percentile was similar in the MIS-C ECMO versus no ECMO groups (89.9 vs 85.8; p = 0.22) but higher in the COVID-19 ECMO versus no ECMO groups (98.3 vs 96.5; p = 0.03). Patients on ECMO with MIS-C versus COVID-19 were supported more often with venoarterial ECMO (92% vs 41%) for primary cardiac indications (87% vs 23%), had ECMO initiated earlier (median 1 vs 5 d from hospitalization), shorter ECMO courses (median 3.9 vs 14 d), shorter hospital length of stay (median 20 vs 52 d), lower in-hospital mortality (27% vs 37%), and less major morbidity at discharge in survivors (new tracheostomy, oxygen or mechanical ventilation need or neurologic deficit; 0% vs 11%, 0% vs 20%, and 8% vs 15%, respectively). Most patients with MIS-C requiring ECMO support (87%) were admitted during the pre-Delta (variant B.1.617.2) period, while most patients with acute COVID-19 requiring ECMO support (70%) were admitted during the Delta variant period. CONCLUSIONS: ECMO support for SARS-CoV-2-related critical illness was uncommon, but type, initiation, and duration of ECMO use in MIS-C and acute COVID-19 were markedly different. Like pre-pandemic pediatric ECMO cohorts, most patients survived to hospital discharge.

Influence of Thickness of Opaque Porcelain and Alloy Color on the Final Color of Porcelain-Fused-to-Metal Restorations.

Despite the advent of metal-free solutions, porcelain-fused-to-metal restorations (PFM) are still widely used. Particularly for the latest ceramic systems, scarce information is present in the scientific literature about the ideal opaque layer thickness and the alloy color impact to achieve the desired final color of PFM restorations. This study aimed to evaluate the influence of opaque thickness variation layered on different metal alloys on the final color of PFM restorations. Opaque porcelain of one metal−ceramic system (VITA VM13) was layered in four different thicknesses (0.10 mm, 0.15 mm, 0.20 mm, and 0.25 mm) on three differently colored dental alloys: a gold−platinum alloy (yellowish), a gold−palladium alloy (light grayish), and a nickel−chromium alloy (dark grayish). The veneering porcelain layered over the opaque was kept constant (Base Dentine 0.45 mm, Transpa Dentine 0.50 mm, and Enamel 0.20 mm). Sixty specimens were fabricated, five samples for each combination of alloy/opaque thickness. The color difference (ΔE) between specimen and reference was measured using a clinical spectrophotometer. The two-way ANOVA revealed that the thickness of both the opaque (p < 0.001) and the metal alloy (p < 0.001) significantly influenced the ΔE values. Gray-colored alloys covered by a 0.10 mm thick opaque layer enabled the closest color match, whereas this occurred for yellow-color alloys covered by a 0.15 mm thick opaque layer. In contrast, the samples covered by a 0.25 mm thick opaque layer obtained the worst ΔE.

Platelet-rich Plasma Promotes Restoration of the Anterior Vaginal Wall for the Treatment of Pelvic Floor Dysfunction in Rats.

STUDY OBJECTIVE: To determine the efficacy of using platelet-rich plasma (PRP) for vaginal wall repair in rats with vaginal wall impairment induced by vaginal distension (VD). DESIGN: A single-blind, randomized study. SETTING: A certified animal research facility. ANIMALS: Twenty-four female Sprague Dawley rats. INTERVENTIONS: Female Sprague Dawley rats were divided into sham (n = 8), VD (n = 8), and VD + PRP (n = 8) groups. Vaginal tissues from the VD group were dissected at 28-day post injury. VD + PRP rats received vaginal PRP injections on the 1st, 7th, 14th, and 21st day after VD and sacrificed on the 28th day. MEASUREMENTS AND MAIN RESULTS: Urodynamic tests were performed in all rats. Immunohistochemistry was used to evaluate matrix metalloprotease-2 (MMP-2) and matrix metalloprotease-9 (MMP-9). Masson's staining was used to evaluate collagen fibers and calculate collagen volume fraction. Collagen fiber damage was confirmed in the VD group, evidenced by thinner and sparse distribution of collagen fibers, with significantly higher MMP-2 and MMP-9 expression than the sham group (p <.05). The collagen fiber damage in the vaginal wall likely led to pelvic floor dysfunction (PFD), evidenced by significantly decreased bladder leak-point pressure (p <.01) and abdominal leak-point pressure (p <.01) in the VD group compared with the sham group. After completion of the PRP treatment, a significantly higher collagen volume fraction (p <.01) and significantly increased bladder leak-point pressure (p <.05) and abdominal leak-point pressure (p <.01) were achieved in the VD + PRP compared with the VD group, thus indicating repair of the vaginal wall and improvement of PFD. CONCLUSION: PRP injections facilitate the regeneration of vaginal wall tissue, particularly collagen fiber, after VD, leading to functional improvement of PFD. Findings support the feasibility of using PRP as a novel treatment for PFD.

Satisfacción y experiencia de pacientes en tratamiento con sustitutivos opioides en España. Estudio PREDEPO / Patients’satisfaction and experience in treatment with opioid substitution therapy in Spain. The PREDEPO study

El objetivo es comparar la satisfacción, experiencia, objetivos y opinión de los pacientes con trastorno por consumo de opioides (TCO) en base a su tratamiento sustitutivo de opioides (TSO) actual (metadona o buprenorfina/naloxona (B/N)). El estudio PREDEPO es un estudio observacional, transversal, multicéntrico desarrollado en España que incluyó pacientes adultos, diagnosticados de TCO y en TSO, quienes contestaron una encuesta sobre su tratamiento actual. Se incluyeron 98 pacientes (B/N:50%, metadona:50%): edad media de 47 ± 8 años y el 80% varones. A nivel de la satisfacción con su tratamiento, los resultados fueron similares entre grupos. El factor “muy/bastante satisfactorio” que se reportó con mayor frecuencia fue “poder repartir las dosis en varios momentos del día” (44% B/N vs. 63% metadona; p = ,122). Se encontraron diferencias significativas en “tener que recoger la medicación diariamente” donde una menor proporción en el grupo B/N contestaron “muy/bastante molesto” versus el grupo metadona (19% vs. 52%, p = ,032). Los objetivos reportados por la mayoría de los pacientes fueron similares entre grupos (“no sentir más síndrome de abstinencia”, “disminuir o dejar definitivamente mi consumo de drogas”, “mejorar mi estado de salud” y “dejar de pensar en consumir todos los días”) excepto en “no tener más problemas de dinero” (72% B/N vs. 92% metadona; p = ,012). Estos resultados evidencian que existen expectativas no cubiertas con los TSO actuales y la necesidad de nuevos tratamientos que disminuyan la carga de la enfermedad, eviten la necesidad de una dosificación diaria y reduzcan el estigma, mejorando así el manejo del paciente, su adherencia y calidad de vida. (AU)

The aim of this study was to compare patients’ satisfaction, experience, objectives, and opinion based on their current opioid substitution therapy (OST) (buprenorphine/naloxone (B/N) or methadone). The PREDEPO study is an observational, cross-sectional, multicentric study performed in Spain. Adult patients diagnosed with opioid use disorder (OUD) receiving OST were included. They were asked to fill in a questionnaire regarding their current OST. A total of 98 patients were enrolled (B/N: 50%, methadone: 50%). Mean age was 47 ± 8 years old and 80% were male. Treatment satisfaction was similar between groups. The most frequently reported factor for being “very/quite satisfied” was “being able to distribute the dose at different times throughout the day” (44% B/N vs. 63% methadone; p = .122). A significantly lower proportion of patients in the B/N group versus the methadone group reported that having to collect the medication daily was “very/quite annoying” (19% vs. 52%, p = .032). Treatment objectives reported by the majority of patients were similar between groups (“not feeling in withdrawal anymore”, “reduce/definitely stop drug use”, “improve my health”, and “stop thinking about using daily”) except for “not having money problems anymore” (73% B/N vs. 92% methadone; p = .012). These results suggest there are several unmet expectations regarding current OST. There is a need for new treatments that reduce the burden of OUD, avoid the need for daily dosing, and are less stigmatizing which in turn could improve patient management, adherence and, quality of life. (AU)

Prognostic significance of telomerase reverse transcriptase promoter gen mutations in high grade meningiomas / Importancia pronóstica de las mutaciones del gen promotor de la transcriptasa inversa de la telomerasa en los meningiomas de alto grado

Introduction: Mutations in the promoter region of telomerase reverse transcriptase occur frequently in meningiomas. Objective: To estimate the prognostic importance of telomerase reverse transcriptase mutations in Colombian patients with grades II and III meningioma. Materials and methods: This was a multicenter retrospective cohort study of patients diagnosed with refractory or recurrent WHO grades II and III meningiomas, recruited between 2011 and 2018, and treated with systemic therapy (sunitinib, everolimus ± octreotide, and bevacizumab). Mutation status of the telomerase reverse transcriptase promoter was established by PCR. Results: Forty patients were included, of which telomerase reverse transcriptase mutations were found in 21 (52.5%), being C228T and C250T the most frequent variants with 87.5 % and 14.3 %, respectively. These were more frequent among patients with anaplastic meningiomas (p=0.18), with more than 2 recurrences (p=0.04); and in patients with parasagittal region and anterior fossa lesions (p=0.05). Subjects characterized as having punctual mutations were more frequently administered with everolimus, sunitinib and bevacizumab drug series (p=0.06). Overall survival was 23.7 months (CI95% 13.1-34.2) and 43.4 months (CI95% 37.5-49.3; p=0.0001) between subjects with and without mutations, respectively. Multivariate analysis showed that the number of recurrences and the presence of telomerase reverse transcriptase mutations were tthe only variables that negatively affected overall survival. Conclusions: Mutations in telomerase reverse transcriptase allows the identification of high-risk patients and could be useful in the selection of the best medical treatment.

Introducción. En los meningiomas, ocurren con frecuencia mutaciones en la región promotora de la transcriptasa inversa de la telomerasa. Objetivo. Estimar la importancia pronóstica de las mutaciones de la transcriptasa inversa de la telomerasa en pacientes colombianos con meningiomas de grados II y III. Materiales y métodos. Es un estudio de cohorte, retrospectivo y multicéntrico, que incluyó pacientes con diagnóstico de meningioma persistente o recidivante, de grados II y III, según la clasificación de la OMS, reclutados entre el 2011 y el 2018, con tratamiento sistémico (sunitinib, everolimus con octreótido o sin él, y bevacizumab). El estado de la mutación del promotor de la transcriptasa inversa de la telomerasa se determinó por medio de la PCR. Resultados. Se incluyeron 40 pacientes, en 21 (52,5 %) de los cuales se encontraron mutaciones en la transcriptasa inversa de la telomerasa, siendo las variantes más frecuentes la C228T (87,5 %) y la C250T (14,3 %). Estas fueron más frecuentes entre los pacientes con meningiomas anaplásicos (p=0,18), en aquellos con más de dos recurrencias (p=0,04), y en los que presentaron lesiones en la región parasagital y la fosa anterior (p=0,05). Los sujetos caracterizados por tener alteraciones puntuales fueron tratados con mayor frecuencia con la serie de medicamentos everolimus, sunitinib y bevacizumab (p=0,06). Tras el inicio del tratamiento médico, la supervivencia global fue de 23,7 meses (IC95% 13,1-34,2) en los pacientes con mutaciones y, de 43,4 meses (IC95% 37,5-49,3), entre aquellos sin mutaciones (p=0,0001). Los resultados del análisis multivariado demostraron que, únicamente, el número de recurrencias y la presencia de mutaciones en el gen de la transcriptasa inversa de la telomerasa, fueron factores que afectaron negativamente la supervivencia global. Conclusiones. Las mutaciones en el gen promotor de la transcriptasa inversa de la telomerasa permiten identificar los pacientes con alto riesgo, cuya detección podría ser de utilidad para seleccionar el mejor esquema terapéutico.

Importancia pronóstica de las mutaciones del gen promotor de la transcriptasa inversa de la telomerasa en los meningiomas de alto grado / Prognostic significance of telomerase reverse transcriptase promoter gen mutations in high grade meningiomas

Introducción. En los meningiomas, ocurren con frecuencia mutaciones en la región promotora de la transcriptasa inversa de la telomerasa. Objetivo. Estimar la importancia pronóstica de las mutaciones de la transcriptasa inversa de la telomerasa en pacientes colombianos con meningiomas de grados II y III. Materiales y métodos. Es un estudio de cohorte, retrospectivo y multicéntrico, que incluyó pacientes con diagnóstico de meningioma persistente o recidivante, de grados II y III, según la clasificación de la OMS, reclutados entre el 2011 y el 2018, con tratamiento sistémico (sunitinib, everolimus con octreótido o sin él, y bevacizumab). El estado de la mutación del promotor de la transcriptasa inversa de la telomerasa se determinó por medio de la PCR. Resultados. Se incluyeron 40 pacientes, en 21 (52,5 %) de los cuales se encontraron mutaciones en la transcriptasa inversa de la telomerasa, siendo las variantes más frecuentes la C228T (87,5 %) y la C250T (14,3 %). Estas fueron más frecuentes entre los pacientes con meningiomas anaplásicos (p=0,18), en aquellos con más de dos recurrencias (p=0,04), y en los que presentaron lesiones en la región parasagital y la fosa anterior (p=0,05). Los sujetos caracterizados por tener alteraciones puntuales fueron tratados con mayor frecuencia con la serie de medicamentos everolimus, sunitinib y bevacizumab (p=0,06). Tras el inicio del tratamiento médico, la supervivencia global fue de 23,7 meses (IC95% 13,1-34,2) en los pacientes con mutaciones y, de 43,4 meses (IC95% 37,5-49,3), entre aquellos sin mutaciones (p=0,0001). Los resultados del análisis multivariado demostraron que, únicamente, el número de recurrencias y la presencia de mutaciones en el gen de la transcriptasa inversa de la telomerasa, fueron factores que afectaron negativamente la supervivencia global. Conclusiones. Las mutaciones en el gen promotor de la transcriptasa inversa de la telomerasa permiten identificar los pacientes con alto riesgo, cuya detección podría ser de utilidad para seleccionar el mejor esquema terapéutico.

Introduction: Mutations in the promoter region of telomerase reverse transcriptase occur frequently in meningiomas. Objective: To estimate the prognostic importance of telomerase reverse transcriptase mutations in Colombian patients with grades II and III meningioma. Materials and methods: This was a multicenter retrospective cohort study of patients diagnosed with refractory or recurrent WHO grades II and III meningiomas, recruited between 2011 and 2018, and treated with systemic therapy (sunitinib, everolimus ± octreotide, and bevacizumab). Mutation status of the telomerase reverse transcriptase promoter was established by PCR. Results: Forty patients were included, of which telomerase reverse transcriptase mutations were found in 21 (52.5%), being C228T and C250T the most frequent variants with 87.5 % and 14.3 %, respectively. These were more frequent among patients with anaplastic meningiomas (p=0.18), with more than 2 recurrences (p=0.04); and in patients with parasagittal region and anterior fossa lesions (p=0.05). Subjects characterized as having punctual mutations were more frequently administered with everolimus, sunitinib and bevacizumab drug series (p=0.06). Overall survival was 23.7 months (CI95% 13.1-34.2) and 43.4 months (CI95% 37.5-49.3; p=0.0001) between subjects with and without mutations, respectively. Multivariate analysis showed that the number of recurrences and the presence of telomerase reverse transcriptase mutations were the only variables that negatively affected overall survival. Conclusions: Mutations in telomerase reverse transcriptase allows the identification of high-risk patients and could be useful in the selection of the best medical treatment.

Continuous administration of leuprolide acetate improves urinary function in male rats with severe thoracic spinal cord injury.

AIMS: To determine if a continuous administration of leuprolide acetate (LA), a synthetic agonist for the gonadotrophin-releasing hormone receptor, facilitates the recovery of urinary function in spinal cord injured male rats. MAIN METHODS: Male Wistar rats were randomized into spinal cord injury (SCI; n = 7), SCI with continuous administration of LA for two weeks via implantation of a subcutaneous osmotic pump (SCI + LA; n = 7), Sham SCI (SH-SCI; n = 6) or no surgery (Intact; n = 6) groups. Micturition, hind-limb nociception and locomotor behaviors were analyzed before and after surgical procedures on days 7, 14, 21 and 28. After behavioral studies, electromyography of the external urethral sphincter (EUS-EMG) and cystometric (CMG) studies were performed in all groups. KEY FINDINGS: SCI significantly decreased frequency of voids and CMG parameters (p < 0.001), abolished the bursting activity of the EUS during CMG, significantly increased hind limb sensory threshold and decreased locomotor performance in comparison to the other groups (p < 0.001). Continuous LA treatment significantly increased the frequency of voids and improved CMG parameters (p < 0.001), exhibiting bursting EUS activity during CMGs, and enhanced locomotor performance in comparison to SCI rats (p < 0.001). SIGNIFICANCE: SCI severely affected behavioral and functional micturition processes, including sensory and locomotor functions. Systemic and uninterrupted treatment with LA improves the recovery of micturition behavior and the synergistic function of the EUS. Furthermore, sensory and locomotor responses were also improved in SCI rats. This procedure may have a therapeutic potential to facilitate urinary function recovery in patients with SCI.

Evaluation of the hospital care quality perceived by patients with immune-mediated inflammatory diseases from the pharmacy service. SACVINFA study.

WHAT IS KNOWN AND OBJECTIVE: Immune-mediated inflammatory diseases (IMIDs) are a group of chronic and highly disabling diseases. The objective is to evaluate the satisfaction with the health care received by patients with the most prevalent IMIDs in Spain: inflammatory bowel disease (IBD), psoriasis (Ps) psoriatic arthritis (PsA), rheumatoid arthritis (RA) and spondyloarthropathies (SpAs), and to determine the factors that influence patient satisfaction. METHODS: This was an observational, cross-sectional, multicentre study in a real-world evidence context conducted in the Pharmacy Service in four hospital centres of the Community of Madrid that belong to the National Health System. The study included adult patients diagnosed with an IMID who had attended the Pharmacy Service at least three times. The patients were grouped according to the main IMID. Health care satisfaction was evaluated using the chronic patient experience assessment (IEXPAC) questionnaire. The responses to IEXPAC are grouped into three factors: productive interactions, new relational model and patient self-management, with a total score from 0 (worst) to 10 (best experience). Health-related quality of life (HRQoL) was also evaluated using the EQ-5D-5L questionnaire, and pharmacological adherence was evaluated through the Morisky-Green test. RESULTS AND DISCUSSION: A total of 578 patients were analysed (IBD = 25.3%; Ps = 19.7%; SpAs = 18.7%; RA = 18.5%; PsA = 17.8%). The mean age (SD) was 49.8 (12.3) years and 50.7% were male. The average score (SD) for the total IEXPAC sample was 6.6 (1.9). RA was the IMID with the lowest score, at 5.83 (2.0), significantly lower than the scores of Ps (SD) [7.01 (1.7); p = 0.003], IBD [6.83 (1, 9); p = 0.012] and SpAs [6.80 (1.6); p = 0.001]. Productive interactions (SD) [8.5 (1.8)] and patient self-management (SD) [7.3 (2.3)] were the factors with the highest scores, and the new relational model had the lowest score (SD) [3.2 (2.7)]. Male gender, a longer time interval between medication administrations and a higher HRQoL were correlated with better patient satisfaction. Current biological therapy (according to the Anatomical Chemical classification system) also had a significant influence; patients treated with tumour necrosis factor inhibitors and interleukin inhibitors showed greater satisfaction than those treated with selective immunosuppressants. WHAT IS NEW AND CONCLUSION: The IEXPAC results show high general satisfaction with care quality reported by patients with IMIDs treated in the Pharmacy Service. However, there are areas of improvement in care quality specially health professional-patient communication, such as increasing access to information, and promoting and facilitating relationships with patients in similar conditions.