Multifunctionalized Carbon Dots as an Active Nanocarrier for Drug Delivery to the Glioblastoma Cell Line.

Nanoparticle-based nanocarriers represent a viable alternative to conventional direct administration in cancer cells. This advanced approach employs the use of nanotechnology to transport therapeutic agents directly to cancer cells, thereby reducing the risk of damage to healthy cells and enhancing the efficacy of treatment. By approving nanoparticle-based nanocarriers, the potential for targeted, effective treatment is greatly increased. The so-called carbon-based nanoparticles, or carbon dots, have been hydrothermally prepared and initiated by a polymerization process. We synthesized and characterized nanoparticles of 2-acrylamido-2-methylpropanesulfonic acid, which showed biocompatibility with glioblastoma cells, and further, we tested them as a carrier for the drug riluzole. The obtained nanoparticles have been extensively characterized by techniques to obtain the exact composition of their surface by using Fourier transform infrared (FTIR), X-ray photoelectron spectroscopy (XPS), and nuclear magnetic resonance (NMR) spectroscopy, as well as cryo-transmission electron microscopy. We found that the surface of the synthesized nanoparticles (NPs) is covered mainly by sulfonated, carboxylic, and substituted amide groups. These functional groups make them suitable as carriers for drug delivery in cancer cells. Specifically, we have successfully utilized the NPs as a delivery system for the drug riluzole, which has shown efficacy in treating glioblastoma cancer cells. The effect of nanoparticles as carriers for the riluzole system on glioblastoma cells was studied using live-cell synchrotron-based FTIR microspectroscopy to monitor in situ biochemical changes. After applying nanoparticles as nanocarriers, we have observed changes in all biomacromolecules, including the nucleic acids and protein conformation. These findings provide a strong foundation for further exploration into the development of targeted treatments for glioblastoma.

Performance of a vaginal self-collection device versus clinician collected cervical samples for the detection of high-risk human papillomavirus.

Objective: Screening for cervical cancer requires the participation of target women. Human papillomavirus (HPV) testing can be performed on vaginal self-samples and self-sampling can improve this participation. This study aims to validate the performance of the vaginal self-sampling device (Vitroveil®) to detect high risk human papillomavirus (hrHPV) in comparison to clinician collected samples and evaluate the degree of acceptability of the Vitroveil® device. Methods: A cross-sectional observational study was carried out in a cohort of 385 participating women (median age of 44 ± 10.47 years) attending primary care centers and cervical pathology services of Granada, Spain. Two paired samples (vaginal self-sample and clinician collected cervical sample) where collected from each participant to compare the detection of HPV with the Vitro HPV Screening assay (Vitro, Granada, Spain). A questionnaire was also provided to the participants to analyze the degree of satisfaction with the device and the preference for sampling method. Results: Overall concordance for hrHPV detection was substantial (ĸ 0.804). The prevalence of any hrHPV infection was higher in self-collected samples (30.6%) than in clinician-collected samples (24.3%). The participants found the self-sampling device easy to use and preferred self-collection as the collection method. Conclusion: The Vitroveil® self-sampling device enables safe and accruable hrHPV testing, obtaining equivalent results to those of the clinician collected samples. High acceptability of the device has been demonstrated among women in the study. Nevertheless, additional studies are necessary to verify the efficacy and reliability of the device's performance.

Clinical features and predictors of delayed neurological syndrome in carbon monoxide poisoning: the AMICO study. / Caracterización clínica y factores predictivos de desarrollo de síndrome neurológico tardío en la intoxicación por monóxido de carbono: estudio AMICO.

OBJECTIVES: To identify predictors for developing delayed neurological syndrome (DNS) after an initial episode of carbon monoxide (CO) poisoning in the interest of detecting patients most likely to develop DNS so that they can be followed. MATERIAL AND METHODS: Retrospective review of cases of CO poisoning treated in the past 10 years in the emergency departments of 4 hospitals in the AMICO study (Spanish acronym for the multicenter analysis of CO poisoning). We analyzed demographic characteristics of the patients and the clinical characteristics of the initial episode. The records of the cohort of patients with available follow-up information were reviewed to find cases of DNS. Data were analyzed by multivariant analysis to determine the relationship to characteristics of the initial exposure to CO. RESULTS: A total of 240 cases were identified. The median (interquartile range) age of the patients was 36.2 years (17.6-49.6 years); 108 patients (45.0%) were men, and the poisoning was accidental in 223 cases (92.9%). The median carboxyhemoglobin concentration on presentation was 12.7% (6.2%-18.7%). Follow-up details were available for 44 patients (18.3%). Eleven of those patients (25%) developed DNS. A low initial Glasgow Coma Scale score predicted the development of DNS with an odds ratio (OR) of 0.61 (95% CI, 0.41-0.92) and an area under the receiver operating characteristic curve of 0.876 (95% CI, 0.761-0.990) (P .001). CONCLUSION: The initial Glasgow Coma Scale score seems to be a clinical predictor of DNS after CO poisoning. We consider it important to establish follow-up protocols for patients with CO poisoning treated in hospital EDs.

OBJETIVO: Identificar factores pronósticos de desarrollo de síndrome neurológico tardío (SNT) después de un episodio inicial de intoxicación por monóxido de carbono (ICO), con el fin detectar precozmente a la población más susceptible y facilitar su acceso a un seguimiento específico. METODO: Revisión retrospectiva de todos los casos de ICO que acudieron a los servicios de urgencias (SU) de 4 hospitales durante los últimos 10 años. Se analizaron datos demográficos y características clínicas en el momento del episodio. En la cohorte de pacientes con datos de seguimiento disponibles, se evaluó la aparición de SNT y su relación con diferentes variables en la exposición inicial al CO a través de técnicas de análisis multivariante. RESULTADOS: Se identificaron 240 pacientes. La mediana de edad fue de 36,2 años (17,6-49,6). De ellos 108 (45,0%) eran hombres y 223 casos (92,9%) fueron accidentales. El nivel medio de COHb fue del 12,7% (6,2-18,7). En 44 (18,3%) episodios se disponía de datos de un seguimiento específico. En esta cohorte, 11 (25%) pacientes desarrollaron SNT. Una puntuación inicial más baja en la Escala Coma de Glasgow (GCS) (OR: 0,61, IC 95%: 0,41-0,92) fue predictor independiente del desarrollo del SNT, con un ABC en la curva COR de 0,876 (IC 95%: 0,761-0,990, p 0,001). CONCLUSIONES: Una puntuación inicial baja en la GCS parece ser un predictor clínico de desarrollo de SNT en la ICO. Dada la incidencia de SNT, consideramos fundamental establecer protocolos de seguimiento específico de estos pacientes tras su asistencia inicial en los SU.

Intention to use physical restraint in paediatric intensive care units and correlated variables: A multicentre and cross-sectional study.

OBJECTIVES: To determine the intention to use physical restraint (PR) and the relationship with sociodemographic and professional variables of the Paediatric Intensive Care Unit (PICU) nurses. RESEARCH METHODOLOGY/DESIGN AND SETTING: A multicentre and correlational study was carried out from October 2021 to December 2023 in five paediatric intensive care units from five maternal and child hospitals in Spain. The Paediatric Physical Restraint-Theory of Planned Behaviour Questionnaire was provided. Moreover, sociodemographic and employment variables were registered. RESULTS: A total of 230 paediatric nurses participated in the study. A total of 87.7 % were females with an average age of 35.5 ± 9.7 years and working experience of 10.5 ± 8.4 years. The mean scores obtained were 21.1 ± 3.8 for attitude, 13.1 ± 5.0 for subjective norms, 14.4 ± 4.3 for perceived behavioural control and 28.0 ± 6.0 for intention. The nurses apply more physical restraint to anxious patients, with scarce analgesics and sedation, those affected with pharmacological withdrawal symptoms and those with a high risk of accidental removal of vital support devices or fall from bed. The sex (p = 0.007) and type of employment contract (p = 0.01) are the variables that are significantly correlated with the intention to use of PR. CONCLUSION: The paediatric nurses analysed had a moderate attitude, social pressure and perceived behavioural control towards the use of PR. IMPLICATIONS FOR CLINICAL PRACTICE: It is important to know the factors that influence the intention to use physical restraint in order to standardise safe practice for critically ill paediatric and to ensure that patients' rights are respected by obtaining informed consent and assessing the prescription, continuation and removal of physical restraint.

Tumor microenvironment restricts IL-10 induced multipotent progenitors to myeloid-lymphatic phenotype.

Lymphangiogenesis is induced by local pro-lymphatic growth factors and bone marrow (BM)-derived myeloid-lymphatic endothelial cell progenitors (M-LECP). We previously showed that M-LECP play a significant role in lymphangiogenesis and lymph node metastasis in clinical breast cancer (BC) and experimental BC models. We also showed that differentiation of mouse and human M-LECP can be induced through sequential activation of colony stimulating factor-1 (CSF-1) and Toll-like receptor-4 (TLR4) pathways. This treatment activates the autocrine interleukin-10 (IL-10) pathway that, in turn, induces myeloid immunosuppressive M2 phenotype along with lymphatic-specific proteins. Because IL-10 is implicated in differentiation of numerous lineages, we sought to determine whether this pathway specifically promotes the lymphatic phenotype or multipotent progenitors that can give rise to M-LECP among other lineages. Analyses of BM cells activated either by CSF-1/TLR4 ligands in vitro or orthotopic breast tumors in vivo showed expansion of stem/progenitor population and coincident upregulation of markers for at least four lineages including M2-macrophage, lymphatic endothelial, erythroid, and T-cells. Induction of cell plasticity and multipotency was IL-10 dependent as indicated by significant reduction of stem cell markers and those for multiple lineages in differentiated cells treated with anti-IL-10 receptor (IL-10R) antibody or derived from IL-10R knockout mice. However, multipotent CD11b+/Lyve-1+/Ter-119+/CD3e+ progenitors detected in BM appeared to split into a predominant myeloid-lymphatic fraction and minor subsets expressing erythroid and T-cell markers upon establishing tumor residence. Each sub-population was detected at a distinct intratumoral site. This study provides direct evidence for differences in maturation status between the BM progenitors and those reaching tumor destination. The study results suggest preferential tumor bias towards expansion of myeloid-lymphatic cells while underscoring the role of IL-10 in early BM production of multipotent progenitors that give rise to both hematopoietic and endothelial lineages.

Comparison of digitally assessed quality of posterior crown preparations performed with and without previous practice on patient-specific three-dimensional-printed teeth models.

INTRODUCTION: Three-dimensional (3D)-printing technology can provide customizable simulations, but its effects on patient care quality have not been well studied. This study aimed to assess the impact of practicing with patient-specific 3D-printed teeth models on the quality of patients' dental preparations performed by students transitioning to clinical training. Accordingly, the quality of posterior crown preparations was evaluated by objectively analyzing digital scans and grades in two groups: the study group, which practiced beforehand with patient-specific 3D-printed teeth models, and the control group, which did not practice with these models. METHODS: All 78 fourth-year dental students who had just finished their fixed prosthodontics course at the simulation laboratory with training on phantom heads and without previous clinical experience in crown preparations were invited to participate in the study. Sixty-eight agreed to take part and were randomly divided into a study group that practiced crown preparations on 3D-printed models of their own patient's teeth and a control group that did not practice with 3D-printed models and started their clinical work straightforwardly after simulation training. Students completed validated perception questionnaires on self-confidence and clinical skills before and after the protocol, which were compared using a chi-squared test. Crown preparations performed on 3D-printed models and then on patients were digitally scanned and objectively graded by prepCheck software for critical parameters, such as undercuts, taper, and occlusion reduction. Non-parametric tests were used to compare preparations on 3D-printed models and on patients performed by the study group and those on patients made by the control group. RESULTS: Initially, both groups reported similar perceptions of self-confidence and clinical skills levels. The study group significantly improved both aspects after the protocol. Analysis of the scanned preparations demonstrated that the study group removed less tooth structure from actual patients than from the initial 3D-printed models. In contrast, the control group showed excess occlusal clearance in their patients compared to the study group. CONCLUSIONS: Practicing patient-specific 3D-printed teeth before performing procedures clinically appears to enhance preparation quality and minimize unnecessary tooth reduction in early clinical experiences.

Understanding the response of the Western Mediterranean cephalopods to environment and fishing in a context of alleged winners of change.

Increasing impacts of both fisheries and climate change have resulted in shifts in the structure and functioning of marine communities. One recurrent observation is the rise of cephalopods as fish recede. This is generally attributed to the removal of main predators and competitors by fishing, while mechanistic evidence is still lacking. In addition, climate change may influence cephalopods due to their high environmental sensitivity. We aim to unveil the effects of different anthropogenic and environmental drivers at different scales focusing on the cephalopod community of the Western Mediterranean Sea. We investigate several ecological indicators offering a wide range of information about their ecology, and statistically relating them with environmental, biotic and fisheries drivers. Our results highlight non-linear changes of indicators along with spatial differences in their responses. Overall, the environment drivers have greater effects than biotic and local human impacts with contrasting effects of temperature across the geographic gradient. We conclude that cephalopods may be impacted by climate change in the future while not necessary through positive warming influence, which should make us cautious when referring to them as generalized winners of current changes.

Efficacy and safety of sitagliptin with basal-plus insulin regimen versus insulin alone in non-critically ill hospitalized patients with type 2 diabetes: SITA-PLUS hospital trial.

AIMS: To compare the efficacy and safety of basal-plus (BP) insulin regimen with or without sitagliptin in non-critically ill patients with type 2 diabetes (T2D). METHODS: This open-label, randomized clinical trial included inpatients with a previous diagnosis of T2D and blood glucose (BG) between 180 and 400 mg/dL. Participants received basal and correctional insulin doses (BP regimen) either with or without sitagliptin. The primary outcome was the difference in the mean daily BG among the groups. RESULTS: Seventy-six patients (mean age 60 years, 64 % men) were randomized. Compared with BP insulin therapy alone, the sitagliptin-BP combination led to a lower mean daily BG (158.8 vs 175.0 mg/dL, P = 0.014), a higher percentage of readings within a BG range of 70-180 mg/dL (75.9 % vs 64.7 %, P < 0.001), and a lower number of BG readings >180 mg/dL (P < 0.001). Sitagliptin-BP resulted in fewer basal and supplementary insulin doses (P = 0.024 and P = 0.017, respectively) and lower daily insulin injections (P = 0.023) than those with insulin alone. The proportion of patients with hypoglycemia was similar in the two groups. CONCLUSIONS: For inpatients with T2D and hyperglycemia, the sitagliptin and BP regimen combination is safe and more effective than insulin therapy alone. CLINICALTRIALS: gov identifier: NCT05579119.

COVID-19 and Pregnancy: A Dangerous Mix for Bone Turnover and Metabolism Biomarkers in Placenta and Colostrum.

Background: In pregnant women, COVID-19 can alter the metabolic environment, cell metabolism, and oxygen supply of trophoblastic cells and, therefore, have a negative influence on essential mechanisms of fetal development. The purpose of this study was to investigate, for the first time, the effects of COVID-19 infection during pregnancy with regard to the bone turnover and endocrine function of several metabolic biomarkers in colostrum and placenta. Methods: One hundred and twenty-four pregnant mothers were recruited from three hospitals between June 2020 and August 2021 and assigned to two groups: Control group and COVID-19 group. Metabolism biomarkers were addressed in placental tissue and colostrum. Results: Lipocalin-2 and resistin levels were higher in the placenta, revealing an underlying pro-inflammatory status in the gestation period for mothers suffering from COVID-19; a decrease in GLP-1 and leptin was also observed in this group. As for adiponectin, resistin, and insulin, their concentrations showed an increase; a decrease in GLP-1, leptin, and PYY was also reported in the colostrum of mothers suffering from COVID-19 compared with the control group. Conclusions: As for bone turnover, placental samples from mothers with COVID-19 showed lower levels of OPG, while DKK-1 increased compared with the control group. Colostrum samples showed higher levels of OPG, SOST, and PTH in the COVID-19 group, a fact that could have noteworthy implications for energy metabolism, fetal skeletal development, and postnatal bone density and mineralization. Further research is needed to explain the pathogenic mechanism of COVID-19 that may affect pregnancy, so as to assess the short-term and long-term outcomes in infants' health.

Amygdala-liver signaling orchestrates rapid glycemic responses to stress and drives stress-induced metabolic dysfunction.

Behavioral adaptations to environmental threats are crucial for survival and necessitate rapid deployment of energy reserves. The amygdala coordinates behavioral adaptations to threats, but little is known about its involvement in underpinning metabolic adaptations. Here, we show that acute stress activates medial amygdala (MeA) neurons that innervate the ventromedial hypothalamus (MeAVMH neurons), which precipitates hyperglycemia and hypophagia. The glycemic actions of MeAVMH neurons occur independent of adrenal or pancreatic glucoregulatory hormones. Instead, using whole-body virus tracing, we identify a polysynaptic connection from MeA to the liver, which promotes the rapid synthesis of glucose by hepatic gluconeogenesis. Repeated stress exposure disrupts MeA control of blood glucose and appetite, resulting in diabetes-like dysregulation of glucose homeostasis and weight gain. Our findings reveal a novel amygdala-liver axis that regulates rapid glycemic adaptations to stress and links recurrent stress to metabolic dysfunction.

Proteus mirabilis biofilm expansion microscopy yields over 4-fold magnification for super-resolution of biofilm structure and subcellular DNA organization.

Bacterial biofilms form when bacteria attach to surfaces and generate an extracellular matrix that embeds and stabilizes a growing community. Detailed visualization and quantitative analysis of biofilm architecture by optical microscopy are limited by the law of diffraction. Expansion Microscopy (ExM) is a novel Super-Resolution technique where specimens are physically enlarged by a factor of ∼4, prior to observation by conventional fluorescence microscopy. ExM requires homogenization of rigid constituents of biological components by enzymatic digestion. We developed an ExM approach capable of expanding 48-h old Proteus mirabilis biofilms 4.3-fold (termed PmbExM), close to the theoretic maximum expansion factor without gross shape distortions. Our protocol, based on lytic and glycoside-hydrolase enzymatic treatments, degrades rigid components in bacteria and extracellular matrix. Our results prove PmbExM to be a versatile and easy-to-use Super-Resolution approach for enabling studies of P. mirabilis biofilm architecture, assembly, and even intracellular features, such as DNA organization.

A Web-Based Intervention Based on Acceptance and Commitment Therapy for Family Caregivers of People With Dementia: Mixed Methods Feasibility Study.

BACKGROUND: Acceptance and commitment therapy (ACT), as an empirically based third-wave cognitive behavioral therapy, has shown promise in enhancing well-being and functioning across diverse populations. However, in the context of caregiving, the effect size of available ACT interventions remains at best moderate, sometimes accompanied by high dropout rates, highlighting the need for more effective and feasible intervention designs. OBJECTIVE: The objective of our study was to evaluate the feasibility and acceptability of a fully online ACT program designed for family caregivers of people with dementia. This study aimed to boost psychological flexibility and support caregivers, enabling them to realize and prioritize their own life values alongside their caregiving responsibilities. METHODS: A mixed methods feasibility study using an uncontrolled pretest-posttest design was conducted. This intervention included a 9-week web-based self-help program based on ACT incorporating collaborative goal setting and weekly web-based motivational coaching for family caregivers of people with dementia. This study involved 30 informal caregivers recruited through memory clinics and social media platforms in the Netherlands and received approval from the Medical Ethics Committee of the Maastricht University Medical Center+ (NL77389.068.21/metc21-029). RESULTS: A total of 24 caregivers completed the postintervention assessment, indicating a high adherence rate (24/29, 83%). Caregivers reported positive feedback regarding collaborative goal setting, but some found challenges in implementing new skills due to their own habitual responses or the unpredictable context of dementia caregiving. Personalizing the intervention based on individual value preferences was highlighted as beneficial. CONCLUSIONS: Compared to other web-based self-help ACT interventions for family caregivers, this intervention showed a high adherence and sufficient level of feasibility, which underscores the use of personalization in delivering web-based interventions. Moreover, the potential of this ACT-based intervention for family caregivers of people with dementia was demonstrated, suggesting that further research and a larger-scale controlled trial are warranted to validate its effectiveness. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1136/bmjopen-2022-070499.

Intracardiac echography-guided fluoroless ablation versus conventional fluoroscopy-guided ablation for cardiac arrhythmias: a systematic review and meta-analysis

BACKGROUND: Intracardiac echocardiography (ICE) has improved catheter ablation procedures, reducing reliance on fluoroscopy. Yet, the efficacy and safety of zero-fluoroscopy (ZF) procedures remain uncertain. METHODS: We conducted a systematic review and meta-analysis comparing ZF ablation procedures guided by ICE vs. conventional techniques regarding efficacy and safety outcomes. PubMed, Cochrane, and embase were searched. A random-effects model was used to calculate risk ratios (RRs), odds ratios (OR) and mean differences (MDs) with 95% confidence intervals (CI). RESULTS: We includedfourteen studies with 1,919 patients of whom 1,023 (58.72%) performed ZF ablation using ICE. We found a significant reduced ablation time (SMD -0.18; 95% CI -0.31;-0.04; p=0.009), procedure time (MD -7.54; 95% CI -14.68;-0.41; p=0.04), fluoroscopic time (MD -2.52; 95% CI -3.20;-1.84; p<0.001) in patients treated with ZF approach compared with NZF approach. However, there was no significant difference between the two groups in acute success rate (RR 1.00; 95% CI 0.99-1.01; p=0.85), long-term success rate (RR 0.99; 95% CI 0.93-1.05; p=0.77) and complications (RR 0.84, 95% CI: 0.48-1.46; p = 0.54). CONCLUSION: Our findings suggest that among patients undergoing arrhythmia ablation, fluoroscopy-free ICE-guided technique reduces procedure time and radiation exposure with comparable short and long-term success rates and complications.

Complete versus culprit-only revascularization for older adults with acute coronary syndromes: a meta-analysis and systematic review

BACKGROUND: Randomized studies support complete over culprit-only revascularization for patients with acute coronary syndrome (ACS) However,whether these findings extend to elderly patients has not been thoroughly explored. METHODS: We conducted a systematic review and meta-analysis comparing clinical outcomes of elderly individuals (defined as age > 75 years) with ACS and multivessel coronary artery disease submitted to complete vs. culprit-only percutaneous coronary intervention (PCI). PubMed, Embase, and Cochrane were searched. We computed pooled hazard ratios (HRs) with 95% confidence intervals (CI) to preserve time-to-event data RESULTS: We included 7 studies, of which 2 were randomized controlled trials (RCTs), comprising 7,409 patients, of whom 3225 (43.5%) underwent complete revascularization. As compared with culprit lesion only PCI, complete revascularization was associated with a lower risk of all-cause mortality (HR 0.76; 95% CI 0.68-0.85; p<0.001), cardiovascular mortality (HR 0.67; 95% CI 0.54-0.82; p<0.001), and recurrent myocardial infarction (MI) (HR 0.65; 95% CI 0.50-0.85; p=0.002). There was no significant difference between the groups regarding the risk of recurrent revascularizations (HR 0.79; 95% CI 0.54-1.16; p=0.23). CONCLUSION: Among elderly patients with ACS and multivessel CAD, complete revascularization is associated with a lower risk of all-cause mortality, cardiovascular mortality, and recurrent MI.

Cardioneuroablation for reflex syncope: a systematic review and single-arm meta-analysis

BACKGROUND: Reflex syncope reduces quality of life and leads to fall-related injuries, with no highly effective treatment. In this context, cardioneuroablation (CNA) presents as a promising therapy for these patients. METHODS: We searched PubMed, Embase and Cochrane Central for studies that evaluated safety and efficacy outcomes related to CNA procedures. Two reviewers independently performed study selection, data extraction and assessment of bias. Generalized linear mixed models was used. We performed a single-arm meta-analysis using R version 4.2.3. RESULTS: A total of 25 studies comprising 871 patients were included. The mean follow-up ranged from 8 to 40 months. Mean age ranged from 32.9 to 53.9 years and 541 (62.1%) were female. The ablation target was biatrial in 302 patients (34%), left atrium only in 433 (49%), and right atrium only in 136 (15%). The freedom from syncope was 94% (95% confidence interval (CI) 90.13-97.00; P<0.01). Left and right atrial CNA was associated with a significant higher freedom from syncope (96.03%; 95% CI 93.13-97.73) than left atrial ablation only (94.61%; 95% CI 82.88-98.45) and right ablation only (84.53%; 95% CI 74.30-91.18). Peri-procedural adverse event occurred on 1.4% (95% CI 0.44- 4.50). CONCLUSION: Our findings suggest that in patients with reflex syncope, CNA is a procedure associated with a significant reduction in syncope incidence and with low complication rates. Among the procedures used, both right and left ablation were more effective.

Cardiac myosin inhibitors in obstructive hypertrophic cardiomyopathy: a systematic review and meta-analysis of randomized controlled trials

BACKGROUND: Selective cardiac myosin inhibitors (CMI) are promising therapies for obstructive hypertrophic cardiomyopathy (HCM). Yet, the extent of their benefits remains unclear due to the limited population studied. METHODS: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing CMI vs. placebo in patients with obstructive HCM. PubMed, Cochrane, and embase were searched. We calculated risk ratios (RRs), mean differences (MDs) and standardized mean differences (SMDs) with 95% confidence intervals (CI). RESULTS: Four RCTs with 485 patients with obstructive HCM were included, of whom 261 (53.8%) were prescribed CMI (10.7% were aficamten and 89.3% were mavacamten). CMI significantly reduced resting left ventricular outflow tract (LVOT) gradient (SMD -1.4, 95% CI -1.6,-1.2, p<0.001), but also reduced left ventricular ejection fraction (LVEF) (MD -5.1%, 95% CI -7.6,-2.6, p<0,001). Patients receiving CMI had a higher rate of study-defined complete hemodynamic response (RR 16.8, CI 95% 5.5, 51.4, p<0,001; Figure 1A) with a number needed to treat (NNT) of 8; and improvement of at least one point in NYHA functional class (RR 2.29, CI 95% 1.8,2.9, p<0,001; Figure 1B). Conclusion: In this meta-analysis of RCTs including patients with obstructive HCM, CMI led to a significant reduction in LVOT gradient and symptomatic improvement. The NNT to achieve one complete hemodynamic response was 8. There was a significant, albeit modest, decrease in LVEF in the CMI group.

Effects of anabolic androgenic steroids in athletes on left ventricle systolic and diastolic function: a systematic review and meta-analysis

BACKGROUND: The use of anabolic androgenic steroids (AAS) among athletes has been linked to pathological structural and functional cardiac changes. However, the studies are small, and the results are inconsistent. METHODS: We conducted a systematic review and meta-analysis of echocardiographic outcomes comparing athletes with prolonged use of AAS (at least 2 years of use) versus sex and age- matched athletes who were did not use AAS. PubMed, Cochrane, and embase were searched. A random-effects model was used to calculate mean differences (MDs), with 95% confidence intervals (CI). Statistical analyses were performed using Review Manager 5.4.1. RESULTS: We included 17 studies comprising 1,023 athletes, of whom 543 (53%) were AAS users. The mean age ranged to 24.2 to 43 years. Compared with non-AAS users, athletes who used AAS exhibited a significant increase in interventricular septal wall thickness (MD 1.33 mm; 95% CI [0.8,1.89], p<0.001), a reduction in left ventricular ejection fraction (MD 2.77 %; 95% CI [-4.2,-1.34], p<0.001;Figure 1B) , and worsening of global longitudinal strain (MD 3.39%; 95% CI [2.88,3.91], p<0.001;Figure 1B). Additionally, there was a significant reduction in the E/A ratio (MD -0.21; 95% CI [-0.35,-0.07], p=0.003) and an increase in the E/e' ratio (MD 1.71; 95% CI [0.96,2.46], p<0.001). CONCLUSION: Our findings suggest that prolonged use of AAS in athletes is associated with increased left ventricular wall thickness and worsening of systolic and diastolic parameters.

Extensive colitis associated with ixekizumab.

We present the clinical case of a 56-year-old former smoker female, with a family history of maternal ulcerative colitis and personal history of ankylosing spondylitis treated with Ixekizumab for 3 months, who was admitted for fever, left iliac fossa pain and diarrhea without pathological products of 2 weeks of evolution. Abdominopelvic computed tomography scan identified pancolitis. Complete colonoscopy revealed continuous involvement of the proximal colon (right and transverse colon presented deep ulcerations and mucosal friability) with preservation of the terminal ileum. After many complementary tests and according to the clinical context, the diagnosis of extensive colitis associated with IL-17 inhibitor was established.

Auritidibacter ignavus en muestras óticas de pacientes pediátricos. Presentación de 2 casos y revisión de la literatura / Auritidibacter ignavus in ear discharge of paediatric patients: Two cases reports and literature review

Introducción: El desarrollo e investigación de nuevas tecnologías para la identificación de microorganismos, ha permitido la identificación de microorganismos hasta ahora desconocidos. Auritidibacter ignavus es un bacilo grampositivo recientemente descrito, posiblemente asociado con la otitis, aunque su papel como patógeno ótico actualmente es controvertido.Métodos: Presentamos 2 casos de otitis recurrente en pacientes pediátricos en los que se aisló A. ignavus, y revisamos los casos previos descritos en la literatura. Resultados: Todos los aislamientos fueron identificados como A. ignavus por métodos proteómicos y genómicos. En ambos pacientes se resolvieron los síntomas clínicos. Conclusión: A. ignavus se recuperó de las secreciones del oído de los pacientes pediátricos con problemas crónicos del oído. Todos los casos descritos previamente en la literatura eran adultos. Es necesaria más evidencia para asociar A. ignavus con la enfermedad ótica, ya que los datos sobre esta especie aún son escasos.(AU)

Introduction: The development and research of new technologies for identifying microorganisms, has allowed the identification of hitherto unknown bacteria. Auritidibacter ignavus is a newly described Gram-positive rod possibly associated with otitis, although its role as an etiologic agent in otitis is currently controversial. Methods: We report two cases of recurrent otitis in paediatric patients in which A. ignavus was isolated and review the previous cases reported in the literature. Results: All the isolates were identified as A. ignavus by proteomic and genomic methods. Both patients recovered from their symptoms. Conclusion: A. ignavus was recovered from ear discharges of paedriatic patients with chronic ear problems. All the cases previously reported in the literature were adults. More evidence is needed for the association between A. ignavus and otitis, since data regarding this species are still scarce.(AU)