Resilience in the aftermath of trauma: Classes of adjustment in at-risk youth.

OBJECTIVE: Youth who have been exposed to potentially traumatic events are at risk of developing chronic and severe adjustment problems. However, some youth exposed to potentially traumatic events exhibit better-than-expected adaptation. Person-centered analyses, based on multiple criteria for adaptive behavior and adversity, are well-suited to empirically identifying different patterns of adaptation among high-risk youth. METHOD: Data from 381 youth from three at-risk subgroups in Portugal were collected using self-reported measures of trauma history, trauma-related symptomatology, coping skills, and perceived social support. Distinct classes of adaptation after traumatic experiences were examined with latent class analysis. RESULTS: Four classes were identified: (a) trauma-related psychopathology class (13.6%), (b) adaptive resilience class (36.8%), (c) low resources class (11.4%), and (d) high resources class (38.2%). Trauma-related psychopathology class and low resources class were characterized by high levels of maladjustment. Similarly to the low resources class, the trauma-related psychopathology class reported a significantly higher likelihood of trauma-related psychopathology and higher levels of problem-solving skills. The adaptive resilience class and high resources class also reported lower levels of maladjustment, and the high resources class reported higher levels of coping skills and lower levels of externalizing problems than any other class. CONCLUSION: Clinicians treating children's internalizing mental health or externalizing behavior problems should assess trauma history and trauma-related psychopathology, as well as protective resources that may enhance resilience such as skills for problem solving and social support seeking. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

A minimum data set-Core outcome set, core data elements, and core measurement set-For degenerative cervical myelopathy research (AO Spine RECODE DCM): A consensus study.

BACKGROUND: Degenerative cervical myelopathy (DCM) is a progressive chronic spinal cord injury estimated to affect 1 in 50 adults. Without standardised guidance, clinical research studies have selected outcomes at their discretion, often underrepresenting the disease and limiting comparability between studies. Utilising a standard minimum data set formed via multi-stakeholder consensus can address these issues. This combines processes to define a core outcome set (COS)-a list of key outcomes-and core data elements (CDEs), a list of key sampling characteristics required to interpret the outcomes. Further "how" these outcomes should be measured and/or reported is then defined in a core measurement set (CMS). This can include a recommendation of a standardised time point at which outcome data should be reported. This study defines a COS, CDE, and CMS for DCM research. METHODS AND FINDINGS: A minimum data set was developed using a series of modified Delphi processes. Phase 1 involved the setup of an international DCM stakeholder group. Phase 2 involved the development of a longlist of outcomes, data elements, and formation into domains. Phase 3 prioritised the outcomes and CDEs using a two-stage Delphi process. Phase 4 determined the final DCM minimal data set using a consensus meeting. Using the COS, Phase 5 finalised definitions of the measurement construct for each outcome. In Phase 6, a systematic review of the literature was performed, to scope and define the psychometric properties of measurement tools. Phase 7 used a modified Delphi process to inform the short-listing of candidate measurement tools. The final measurement set was then formed through a consensus meeting (Phase 8). To support implementation, the data set was then integrated into template clinical research forms (CRFs) for use in future clinical trials (Phase 9). In total, 28 outcomes and 6 domains (Pain, Neurological Function, Life Impact, Radiology, Economic Impact, and Adverse Events) were entered into the final COS. Thirty two outcomes and 4 domains (Individual, Disease, Investigation, and Intervention) were entered into the final CDE. Finally, 4 outcome instruments (mJOA, NDI, SF-36v2, and SAVES2) were identified for the CMS, with a recommendation for trials evaluating outcomes after surgery, to include baseline measurement and at 6 months from surgery. CONCLUSIONS: The AO Spine RECODE-DCM has produced a minimum data set for use in DCM clinical trials today. These are available at https://myelopathy.org/minimum-dataset/. While it is anticipated the CDE and COS have strong and durable relevance, it is acknowledged that new measurement tools, alongside an increasing transition to study patients not undergoing surgery, may necessitate updates and adaptation, particularly with respect to the CMS.

Multimethod Analysis of a Novel Multi-coloured Heat-treated Nickel-Titanium Rotary System: Design, Metallurgy, Mechanical Properties, and Shaping Ability.

INTRODUCTION: This study aimed to compare a new multicolored rotary system with four heat-treated rotary instruments using the multimethod approach. METHODS: Three-hundred instruments of RCS Rainbow, Rotate, RaCe EVO, OneCurve, and ProTaper Ultimate systems were evaluated regarding their design (stereomicroscopy, scanning electron microscopy, and 3D surface scanning), metallurgy, and mechanical performance (cyclic fatigue, torsional resistance, bending and buckling resistance, and cutting ability). Unprepared surfaces after canal preparation of maxillary molars were evaluated using micro-computed tomography. Kruskal-Wallis and one-way analysis of variance post hoc Tukey tests were used for statistical comparisons (α = 5%). RESULTS: Instruments exhibited variations in active blade length, number of spirals, and cross-sectional designs. RCS Rainbow showed specific phase transformation temperatures, highest bending (400.5gf) and buckling (286gf) resistance values, and lowest mean angle of rotation (529°) (P < .05). OneCurve exhibited superior cutting ability (8.4 mm) and longer time to fracture (112s). RaCe EVO displayed the lowest time to fracture (51s), maximum torque (1.2 N.cm), buckling (174gf), and bending resistance (261gf) values (P < .05). ProTaper Ultimate showed the highest torque (1.6 N.cm) and angle of rotation (611°) (P < .05), while its bending load (262gf) was comparable to RaCe EVO (P > .05). Rotate instrument showed intermediate values in the mechanical tests. No difference was observed regarding the unprepared canal surfaces (P > .05) CONCLUSIONS: RCS Rainbow demonstrates a trade-off between flexibility and other mechanical properties. Its dimensions exceeded those of other instruments, affording it higher torque resistance, yet concurrently reducing its flexibility, angle of rotation, and cutting ability. OneCurve stands out as a well-balanced choice by integrating geometric design and mechanical performance.

A Virtual Reality Simulation to Examine the Relationship Between Post-Traumatic Stress Symptoms and Decision-Making in First Responders.

First responders (FRs) are continuously exposed to critical incidents, considered traumatic events (TEs). This cumulative exposure increases the risk for post-traumatic stress disorder (PTSD). However, there is no evidence about the relationship between PTSD symptoms and emergency decision-making (EDM). The objective of this study was to examine the EDM of FRs during a virtual reality through the simulation of two emergency scenarios to collect data on the reaction time and the number of incorrect decisions. We also assessed PTSD symptoms, TE, and sociodemographics. The sample included 368 Portuguese FRs, were 295 (80.20%) males and 73 (19.80%) females, with a mean age of 33.96 (SD = 9.38). Considering the probable PTSD diagnosis according to the DSM-5, 85 (23.10%) of the FRs met the criteria. These individuals who meet the criteria exhibited higher EDM scores (M = 19.60, SD = 5.99) compared to those without probable PTSD (M = 17.87, SD = .5.66) (F(1, 360) = 5.32, p = .02, partial η2 = .015). We found that TEs had a direct effect on EDM, ß = -.16, Z = -3.74, p < .001), and the pathway of trauma-PTSD symptoms-decision-making an indirect effect, ß = .02, Z = 3.10, p = .002). Individuals exposed to more TEs demonstrated faster and more accurate decision-making in the context of EDM. However, when these individuals developed PTSD symptoms, their decision-making became slower and less accurate. The inclusion of a trauma-informed approach for FRs to prevent individual and job-related consequences is discussed.

Genetic modifiers of somatic expansion and clinical phenotypes in Huntington's disease reveal shared and tissue-specific effects.

Huntington's disease (HD), due to expansion of a CAG repeat in HTT , is representative of a growing number of disorders involving somatically unstable short tandem repeats. We find that overlapping and distinct genetic modifiers of clinical landmarks and somatic expansion in blood DNA reveal an underlying complexity and cell-type specificity to the mismatch repair-related processes that influence disease timing. Differential capture of non-DNA-repair gene modifiers by multiple measures of cognitive and motor dysfunction argues additionally for cell-type specificity of pathogenic processes. Beyond trans modifiers, differential effects are also illustrated at HTT by a 5'-UTR variant that promotes somatic expansion in blood without influencing clinical HD, while, even after correcting for uninterrupted CAG length, a synonymous sequence change at the end of the CAG repeat dramatically hastens onset of motor signs without increasing somatic expansion. Our findings are directly relevant to therapeutic suppression of somatic expansion in HD and related disorders and provide a route to define the individual neuronal cell types that contribute to different HD clinical phenotypes.

[Management of Cytomegalovirus Infection in Allogeneic Hematopoietic Stem Cell Transplant Recipients]. / Abordagem à Infeção pelo Vírus Citomegálico em Doentes Submetidos a Transplante Alogénico de Progenitores Hematopoiéticos.

Cytomegalovirus (CMV) is a type of double-stranded deoxyribonucleic acid virus belonging to the herpesviridae family. Following a primary infection, the virus becomes latent in various types of white blood cells. Cytomegalovirus infection can remain latent or become active, especially in immunocompromised individuals, such as those undergoing hematopoietic stem cell transplantation (HSCT), where CMV reactivation can occur. In this context, CMV infection is common and associated with high rates of morbidity and mortality. Pneumonia is one of the most serious complications, with mortality rates exceeding 50%. Additionally, even in the absence of organ-specific disease, CMV infection is related to increased mortality unrelated to hematologic neoplasm recurrence. Given the frequency and severity of this infection in HSCT patients, it is crucial to implement effective strategies for monitoring, prevention, and treatment. This guideline was developed to identify patient groups that benefit from a systematic approach to CMV infection and to define the most appropriate strategy for each group. Monitoring CMV viral load in peripheral blood is crucial, especially in patients at moderate to high risk of active infection. Primary prophylaxis with letermovir (an antiviral drug) is recommended to reduce the incidence of active infection, especially in high-risk patients. Secondary prophylaxis with valganciclovir (antiviral drug) is recommended after an episode of active infection, while preemptive and disease treatment is based on monitoring viral load and clinical response. The aim of this guideline is to improve the approach to CMV infection in HSCT patients, ensuring an effective and safe preventive and therapeutic approach.

O vírus citomegálico (CMV) é um tipo de vírus de ácido desoxirribonucleico de dupla cadeia que pertence à família herpesviridae. Após uma infeção primária, o vírus torna-se latente em vários tipos de glóbulos brancos. A infeção por CMV pode permanecer latente ou tornar-se ativa, especialmente em indivíduos imunodeprimidos, como aqueles submetidos a transplantes de células progenitoras hematopoiéticas (TPH), onde a reativação do CMV pode ocorrer. Neste contexto, a infeção por CMV é comum e associada a elevadas taxas de morbilidade e mortalidade. A pneumonite é uma das complicações mais graves, com taxas de mortalidade superiores a 50%. Além disso, mesmo na ausência de doença específica do órgão, a infeção por CMV está relacionada com um aumento da mortalidade não relacionada com a recidiva da neoplasia hematológica. Dada a frequência e gravidade desta infeção em doentes submetidos a TPH, é crucial implementar estratégias eficazes de monitorização, prevenção e tratamento. Este protocolo foi desenvolvido para identificar os grupos de doentes que se beneficiam de uma abordagem sistematizada para a infeção por CMV e definir a estratégia mais adequada para cada grupo. A monitorização da carga viral de CMV no sangue periférico é fundamental, especialmente em doentes com risco moderado a elevado de infeção ativa. A profilaxia primária com letermovir (fármaco antiviral) é recomendada para reduzir a incidência de infeção ativa, especialmente em doentes com alto risco. A profilaxia secundária com valganciclovir (fármaco antiviral) é recomendada após um episódio de infeção ativa, enquanto o tratamento de antecipação e de doença é baseado na monitorização da carga viral e na resposta clínica. Este protocolo visa melhorar a abordagem da infeção por CMV em doentes submetidos a TPH, garantindo uma abordagem preventiva e terapêutica eficaz e segura.

Trueness of Extraoral Digital Impressions for Full-Arch Implant Impressions-In Vitro Study.

Direct scanning of silicone impressions is a valid technique. However, studies in implant-supported rehabilitations are lacking. This in vitro study aims to compare the trueness of impressions obtained with two types of silicone and their corresponding stone casts, using two laboratory scanners in a full-arch implant rehabilitation. A master cast with six dental implants was scanned with a 12-megapixel scanner to obtain a digital master cast. Ten implant impressions were made using two silicones (Zhermack and Coltene) with the open-tray technique. The impressions and stone casts were scanned by two extraoral scanners (Identica T500, Medit; and S600 ARTI, Zirkonzhan). Trueness was assessed by comparing linear and angular distances in digital casts with the master cast. A p < 0.05 significance level was considered. The results showed that for the linear measurements, 72% were higher than the master cast measurements, and no consistent pattern was observed in the angular measurements. The greatest deviations were detected between the most posterior implants, with mean values ranging between 173 and 314 µm. No significant differences were found between scanners. However, differences were observed in the distances between silicones (46.7%) and between impressions and stone casts (73.3%). This work demonstrates that the direct scanning of silicone impressions yields results comparable to those obtained from scanning gypsum casts in full-arch implant-supported rehabilitation.

Identification of genetic modifiers of Huntington's disease somatic CAG repeat instability by in vivo CRISPR-Cas9 genome editing.

Huntington's disease (HD), one of >50 inherited repeat expansion disorders (Depienne and Mandel, 2021), is a dominantly-inherited neurodegenerative disease caused by a CAG expansion in HTT (The Huntington's Disease Collaborative Research Group, 1993). Inherited CAG repeat length is the primary determinant of age of onset, with human genetic studies underscoring that the property driving disease is the CAG length-dependent propensity of the repeat to further expand in brain (Swami et al ., 2009; GeM-HD, 2015; Hensman Moss et al ., 2017; Ciosi et al ., 2019; GeM-HD, 2019; Hong et al ., 2021). Routes to slowing somatic CAG expansion therefore hold great promise for disease-modifying therapies. Several DNA repair genes, notably in the mismatch repair (MMR) pathway, modify somatic expansion in HD mouse models (Wheeler and Dion, 2021). To identify novel modifiers of somatic expansion, we have used CRISPR-Cas9 editing in HD knock-in mice to enable in vivo screening of expansion-modifier candidates at scale. This has included testing of HD onset modifier genes emerging from human genome-wide association studies (GWAS), as well as interactions between modifier genes, thereby providing new insight into pathways underlying CAG expansion and potential therapeutic targets.

Advances in Microfluidic-Based Core@Shell Nanoparticles Fabrication for Cancer Applications.

Current research in cancer therapy focuses on personalized therapies, through nanotechnology-based targeted drug delivery systems. Particularly, controlled drug release with nanoparticles (NPs) can be designed to safely transport various active agents, optimizing delivery to specific organs and tumors, minimizing side effects. The use of microfluidics (MFs) in this field has stood out against conventional methods by allowing precise control over parameters like size, structure, composition, and mechanical/biological properties of nanoscale carriers. This review compiles applications of microfluidics in the production of core-shell NPs (CSNPs) for cancer therapy, discussing the versatility inherent in various microchannel and/or micromixer setups and showcasing how these setups can be utilized individually or in combination, as well as how this technology allows the development of new advances in more efficient and controlled fabrication of core-shell nanoformulations. Recent biological studies have achieved an effective, safe, and controlled delivery of otherwise unreliable encapsulants such as small interfering RNA (siRNA), plasmid DNA (pDNA), and cisplatin as a result of precisely tuned fabrication of nanocarriers, showing that this technology is paving the way for innovative strategies in cancer therapy nanofabrication, characterized by continuous production and high reproducibility. Finally, this review analyzes the technical, biological, and technological limitations that currently prevent this technology from becoming the standard.

The Role of Life Stages in the Sensitivity of Hediste diversicolor to Nanoplastics: A Case Study with Poly(Methyl)Methacrylate (PMMA).

The presence of plastic particles in oceans has been recognized as a major environmental concern. The decrease in particle size increases their ability to directly interact with biota, with particles in the nanometer size range (nanoplastics-NPs) displaying a higher ability to penetrate biological membranes, which increases with the decrease in particle size. This study aimed to evaluate the role of life stages in the effects of poly(methyl)methacrylate (PMMA) NPs on the polychaete Hediste diversicolor, a key species in the marine food web and nutrient cycle. Thus, behavioral (burrowing activity in clean and spiked sediment) and biochemical endpoints (neurotransmission, energy reserves, antioxidant defenses, and oxidative damage) were assessed in juvenile and adult organisms after 10 days of exposure to spiked sediment (between 0.5 and 128 mg PMMA NPs/Kg sediment). Overall, the results show that H. diversicolor is sensitive to the presence of PMMA NPs. In juveniles, exposed organisms took longer to burrow in sediment, with significant differences from the controls being observed at all tested concentrations when the test was performed with clean sediment, whereas in PMMA NP-spiked sediment, effects were only found at the concentrations 8, 32, and 128 mg PMMA NPs/Kg sediment. Adults displayed lower sensitivity, with differences to controls being found, for both sediment types, at 8, 32, and 128 mg PMMA NPs/Kg sediment. In terms of Acetylcholinesterase, used as a marker of effects on neurotransmission, juveniles and adults displayed opposite trends, with exposed juveniles displaying increased activity (suggesting apoptosis), whereas in adults, overall decreased activity was found. Energy-related parameters revealed a generally similar pattern (increase in exposed organisms) and higher sensitivity in juveniles (significant effects even at the lower concentrations). NPs also demonstrated the ability to increase antioxidant defenses (higher in juveniles), with oxidative damage only being found in terms of protein carbonylation (all tested NPs conditions) in juveniles. Overall, the data reveal the potential of PMMA NPs to affect behavior and induce toxic effects in H. diversicolor, with greater effects in juveniles.

How Bacteria Cope with Oxidative Stress Induced by Cadmium: Volatile Communication Is Differentially Perceived among Strains.

Soil is an environment with numerous niches, where bacteria are exposed to diverse conditions. Some bacteria are exposed earlier than others to pressure, and the emission of signals that other bacteria can receive and perceive may allow a better response to an eminent stimulus. To shed light on how bacteria trigger their response and adapt to changes in the environment, the intra- and interspecific influences of volatiles on bacterial strains growing under non-stressed and cadmium-stressed conditions were assessed. Each strain was exposed to its volatiles emitted by cells growing under different conditions to test whether the environment in which a cell grows influences neighboring cells. The five genera tested showed different responses, with Rhizobium displaying the greatest influence. In a second experiment, 13 strains from different genera were grown under control conditions but exposed to volatiles released by Cd-stressed Rhizobium cells to ascertain whether Rhizobium's observed influence was strain-specific or broader. Our results showed that the volatiles emitted by some bacteria under stress are differentially perceived and translated into biochemical changes (growth, alteration of the antioxidant response, and oxidative damage) by other bacteria, which may increase the adaptability and resilience of bacterial communities to environmental changes, especially those with a prooxidant nature. Cadmium (Cd) contamination of soils constitutes a risk to the environment and human health. Here, we showed the effects of Cd exposure on bacteria and how volatile communication influences the biochemistry related to coping with oxidative stress. This knowledge can be important for remediation and risk assessment and highlights that new biological features, such as volatile communication, should be considered when studying and assessing the impact of contaminants on soil ecosystems.

Role of compliance in Helicobacter pylori eradication treatment: Results of the European Registry on H. pylori management.

BACKGROUND: Adherence to Helicobacter pylori (H. pylori) eradication treatment is a cornerstone for achieving adequate treatment efficacy. OBJECTIVE: To determine which factors influence compliance with treatment. METHODS: A systematic prospective non-interventional registry (Hp-EuReg) of the clinical practice of European gastroenterologists. Compliance was considered adequate if ≥90% drug intake. Data were collected until September 2021 using the AEG-REDCap e-CRF and were subjected to quality control. Modified intention-to-treat analyses were performed. Multivariate analysis carried out the factors associated with the effectiveness of treatment and compliance. RESULTS: Compliance was inadequate in 646 (1.7%) of 38,698 patients. The non-compliance rate was higher in patients prescribed longer regimens (10-, 14-days) and rescue treatments, patients with uninvestigated dyspepsia/functional dyspepsia, and patients reporting adverse effects. Prevalence of non-adherence was lower for first-line treatment than for rescue treatment (1.5% vs. 2.2%; p < 0.001). Differences in non-adherence in the three most frequent first-line treatments were shown: 1.1% with proton pump inhibitor + clarithromycin + amoxicillin; 2.3% with proton pump inhibitor clarithromycin amoxicillin metronidazole; and 1.8% with bismuth quadruple therapy. These treatments were significantly more effective in compliant than in non-compliant patients: 86% versus 44%, 90% versus 71%, and 93% versus 64%, respectively (p < 0.001). In the multivariate analysis, the variable most significantly associated with higher effectiveness was adequate compliance (odds ratio, 6.3 [95%CI, 5.2-7.7]; p < 0.001). CONCLUSIONS: Compliance with Helicobacter pylori eradication treatment is very good. Factors associated with poor compliance include uninvestigated/functional dyspepsia, rescue-treatment, prolonged treatment regimens, the presence of adverse events, and the use of non-bismuth sequential and concomitant treatment. Adequate treatment compliance was the variable most closely associated with successful eradication.

Long-term prognosis of idiopathic ventricular fibrillation: An eighteen-year experience from a tertiary center.

INTRODUCTION AND OBJECTIVES: Idiopathic ventricular fibrillation (IVF) is diagnosed in patients who survive sudden cardiac arrest (SCA), preferably with documented ventricular fibrillation (VF), without any identifiable structural or electrical abnormality. Current evidence provides limited guidance on the diagnosis and follow-up of these patients. Our aim was to assess the clinical outcomes of survivors of an aborted SCA attributed to IVF. METHODS: We retrospectively collected clinical data from all patients who survived SCA and implanted a cardiac defibrillator (ICD) between 2005 and 2023. RESULTS: A total of 38 patients, 36.8% female, with a mean age of 44±14 years old were included. Median follow-up time was 8.7 years (interquartile range (IQR) 4.7-14.7 years). All patients underwent a comprehensive diagnostic evaluation that excluded structural and coronary disease. During follow-up, underlying diagnoses were established in 34.2% of the whole cohort. Genetic testing, performed in 37.2%, revealed underlying diagnoses in 57.1% of those tested, compared to only 26.3% of patients who did not undergo genetic testing [p=0.035, OR=5.1 (95% confidence interval (CI) 1.2-21.5)]. Mortality was 10.5% (due to non-arrhythmic causes) and 36.8% patients received appropriate therapies with a median time to first ICD therapy of 39 [5.4-47.3] months. CONCLUSION(S): Etiological diagnosis and recurrence prediction in patients with IVF remains challenging, even with extensive diagnostic evaluation and long-term follow-up. In our study, genetic testing enhanced diagnostic yield. Consistent with previous findings, our cohort experienced a notable arrhythmic recurrence, with no cardiac deaths, underlining the pivotal role of ICD implantation in these patients.

Splice modulators target PMS1 to reduce somatic expansion of the Huntington's disease-associated CAG repeat.

Huntington's disease (HD) is a dominant neurological disorder caused by an expanded HTT exon 1 CAG repeat that lengthens huntingtin's polyglutamine tract. Lowering mutant huntingtin has been proposed for treating HD, but genetic modifiers implicate somatic CAG repeat expansion as the driver of onset. We find that branaplam and risdiplam, small molecule splice modulators that lower huntingtin by promoting HTT pseudoexon inclusion, also decrease expansion of an unstable HTT exon 1 CAG repeat in an engineered cell model. Targeted CRISPR-Cas9 editing shows this effect is not due to huntingtin lowering, pointing instead to pseudoexon inclusion in PMS1. Homozygous but not heterozygous inactivation of PMS1 also reduces CAG repeat expansion, supporting PMS1 as a genetic modifier of HD and a potential target for therapeutic intervention. Although splice modulation provides one strategy, genome-wide transcriptomics also emphasize consideration of cell-type specific effects and polymorphic variation at both target and off-target sites.

Optimized Synthesis of Poly(Lactic Acid) Nanoparticles for the Encapsulation of Flutamide.

Biopolymeric nanoparticles (NPs) have gained significant attention in several areas as an alternative to synthetic polymeric NPs due to growing environmental and immunological concerns. Among the most promising biopolymers is poly(lactic acid) (PLA), with a reported high degree of biocompatibility and biodegradability. In this work, PLA NPs were synthesized according to a controlled gelation process using a combination of single-emulsion and nanoprecipitation methods. This study evaluated the influence of several experimental parameters for accurate control of the PLA NPs' size distribution and aggregation. Tip sonication (as the stirring method), a PLA concentration of 10 mg/mL, a PVA concentration of 2.5 mg/mL, and low-molecular-weight PLA (Mw = 5000) were established as the best experimental conditions to obtain monodisperse PLA NPs. After gelification process optimization, flutamide (FLU) was used as a model drug to evaluate the encapsulation capability of the PLA NPs. The results showed an encapsulation efficiency of 44% for this cytostatic compound. Furthermore, preliminary cell viability tests showed that the FLU@PLA NPs allowed cell viabilities above 90% up to a concentration of 20 mg/L. The comprehensive findings showcase that the PLA NPs fabricated using this straightforward gelification method hold promise for encapsulating cytostatic compounds, offering a novel avenue for precise drug delivery in cancer therapy.

20-year follow-up of rheumatic mitral stenosis patients after percutaneous mitral commissurotomy: invasive transmitral gradient differential as a predictor of events.

Percutaneous mitral valve commissurotomy (PMC) is a viable alternative to mitral valve (MV) surgery in the treatment of patients with rheumatic mitral stenosis (RMS). In this single-center retrospective study of consecutive patients with RMS submitted to PMC from 1991 to 2008, we analyzed clinical, echocardiographic, and hemodynamic data and events during follow-up (FUP) until December 2021. Major adverse cardiovascular events (MACE) were a combined endpoint of all-cause death, cardiovascular hospitalization, and MV re-intervention. A total of 124 patients were enrolled: 108 (87.1%) were female, with a mean age at PMC of 46 [standard deviation (SD) 11] years. PMC was successful in 91.1%, with a mean reduction in invasive transmitral pressure gradient (TMPG) of 8 (SD 7) mmHg at PMC time. During the mean FUP of 20 (SD 6) years, 51 (41.1%) patients had MV re-intervention (86.3% surgery and 13.7% redo-PMC), 37 (29.8%) were hospitalized, and 30 (24.2%) died. Approximately 75% of patients remained MACE-free after 10 years, and this percentage decreased to around 40% after 20 years; at this time mark, about 8 in 10 patients were alive. A reduction of <5 mmHg in TMPG at PMC time was associated with a 2.7-fold greater rate of MACE compared to a reduction of ≥5 mmHg, independent of MV regurgitation after PMC and moderate disease of other valves (adjusted hazard ratio 2,7; 95% confidence interval 1.395-5.298, p=0.003). In this cohort with favorable long-term results after PMC, a reduction of <5 mmHg in TMPG at PMC time was associated with MACE during FUP. More studies are needed to validate this independent predictor.

An Update of a Clinical Practice Guideline for the Management of Patients With Acute Spinal Cord Injury: Recommendations on the Role and Timing of Decompressive Surgery.

STUDY DESIGN: Clinical practice guideline development. OBJECTIVES: Acute spinal cord injury (SCI) can result in devastating motor, sensory, and autonomic impairment; loss of independence; and reduced quality of life. Preclinical evidence suggests that early decompression of the spinal cord may help to limit secondary injury, reduce damage to the neural tissue, and improve functional outcomes. Emerging evidence indicates that "early" surgical decompression completed within 24 hours of injury also improves neurological recovery in patients with acute SCI. The objective of this clinical practice guideline (CPG) is to update the 2017 recommendations on the timing of surgical decompression and to evaluate the evidence with respect to ultra-early surgery (in particular, but not limited to, <12 hours after acute SCI). METHODS: A multidisciplinary, international, guideline development group (GDG) was formed that consisted of spine surgeons, neurologists, critical care specialists, emergency medicine doctors, physical medicine and rehabilitation professionals, as well as individuals living with SCI. A systematic review was conducted based on accepted methodological standards to evaluate the impact of early (within 24 hours of acute SCI) or ultra-early (in particular, but not limited to, within 12 hours of acute SCI) surgery on neurological recovery, functional outcomes, administrative outcomes, safety, and cost-effectiveness. The GRADE approach was used to rate the overall strength of evidence across studies for each primary outcome. Using the "evidence-to-recommendation" framework, recommendations were then developed that considered the balance of benefits and harms, financial impact, patient values, acceptability, and feasibility. The guideline was internally appraised using the Appraisal of Guidelines for Research and Evaluation (AGREE) II tool. RESULTS: The GDG recommended that early surgery (≤24 hours after injury) be offered as the preferred option for adult patients with acute SCI regardless of level. This recommendation was based on moderate evidence suggesting that patients were 2 times more likely to recover by ≥ 2 ASIA Impairment Score (AIS) grades at 6 months (RR: 2.76, 95% CI 1.60 to 4.98) and 12 months (RR: 1.95, 95% CI 1.26 to 3.18) if they were decompressed within 24 hours compared to after 24 hours. Furthermore, patients undergoing early surgery improved by an additional 4.50 (95% 1.70 to 7.29) points on the ASIA Motor Score compared to patients undergoing surgery after 24 hours post-injury. The GDG also agreed that a recommendation for ultra-early surgery could not be made on the basis of the current evidence because of the small sample sizes, variable definitions of what constituted ultra-early in the literature, and the inconsistency of the evidence. CONCLUSIONS: It is recommended that patients with an acute SCI, regardless of level, undergo surgery within 24 hours after injury when medically feasible. Future research is required to determine the differential effectiveness of early surgery in different subpopulations and the impact of ultra-early surgery on neurological recovery. Moreover, further work is required to define what constitutes effective spinal cord decompression and to individualize care. It is also recognized that a concerted international effort will be required to translate these recommendations into policy.

A Clinical Practice Guideline for Prevention, Diagnosis and Management of Intraoperative Spinal Cord Injury: Recommendations for Use of Intraoperative Neuromonitoring and for the Use of Preoperative and Intraoperative Protocols for Patients Undergoing Spine Surgery.

STUDY DESIGN: Development of a clinical practice guideline following the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) process. OBJECTIVE: The objectives of this study were to develop guidelines that outline the utility of intraoperative neuromonitoring (IONM) to detect intraoperative spinal cord injury (ISCI) among patients undergoing spine surgery, to define a subset of patients undergoing spine surgery at higher risk for ISCI and to develop protocols to prevent, diagnose, and manage ISCI. METHODS: All systematic reviews were performed according to PRISMA standards and registered on PROSPERO. A multidisciplinary, international Guidelines Development Group (GDG) reviewed and discussed the evidence using GRADE protocols. Consensus was defined by 80% agreement among GDG members. A systematic review and diagnostic test accuracy (DTA) meta-analysis was performed to synthesize pooled evidence on the diagnostic accuracy of IONM to detect ISCI among patients undergoing spinal surgery. The IONM modalities evaluated included somatosensory evoked potentials (SSEPs), motor evoked potentials (MEPs), electromyography (EMG), and multimodal neuromonitoring. Utilizing this knowledge and their clinical experience, the multidisciplinary GDG created recommendations for the use of IONM to identify ISCI in patients undergoing spine surgery. The evidence related to existing care pathways to manage ISCI was summarized and based on this a novel AO Spine-PRAXIS care pathway was created. RESULTS: Our recommendations are as follows: (1) We recommend that intraoperative neurophysiological monitoring be employed for high risk patients undergoing spine surgery, and (2) We suggest that patients at "high risk" for ISCI during spine surgery be proactively identified, that after identification of such patients, multi-disciplinary team discussions be undertaken to manage patients, and that an intraoperative protocol including the use of IONM be implemented. A care pathway for the prevention, diagnosis, and management of ISCI has been developed by the GDG. CONCLUSION: We anticipate that these guidelines will promote the use of IONM to detect and manage ISCI, and promote the use of preoperative and intraoperative checklists by surgeons and other team members for high risk patients undergoing spine surgery. We welcome teams to implement and evaluate the care pathway created by our GDG.

Analysis of Complications in Multilevel Anterior Cervical Discectomy and Fusion Using Osteobiologics Other than Bone Morphogenetic Protein: A Systematic Review.

STUDY DESIGN: Systematic review. OBJECTIVES: The aim of this study is to analyze the complications related to multilevel anterior cervical discectomy and fusion (ACDF) using osteobiologics other than bone morphogenetic protein (BMP). METHODS: A systematic review of the literature was conducted using PubMed, EMBASE, Cochrane Library, and ClinicalTrials.gov databases. The search to identify studies reporting complications in multilevel ACDF surgery using osteobiologics other than bone morphogenetic protein was performed in August 2020. The study was reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA). RESULTS: A total of 584 articles were found after searching the databases and removing duplicates. Next, screening was performed in a double reviewer process, and 153 eligible articles-with 4 retrospective studies-in full-text were selected; these met all inclusion criteria. A total of 197 patients received 3-level ACDF, while 72 patients received 4-level ACDF. Osteobiologics were used in all selected articles, allograft was used in 4 studies, autologous bone graft was utilized in 3 articles, and hydroxyapatite was used in 1 article. The main complications reported were dysphagia, adjacent segment disease, and pseudarthrosis. CONCLUSIONS: Given the limited evidence, no conclusions on complications in multilevel ACDF using osteobiologics other than BMP could be made. However, descriptively, the most common complications found were dysphagia, adjacent segment disease, and pseudoarthrosis. Further prospective studies separately analyzing complications in multilevel ACDF by osteobiologics and a number of treated levels are needed.