TLR Agonists Modify NK Cell Activation and Increase Its Cytotoxicity in Acute Lymphoblastic Leukemia.

Natural killer (NK) cells play a crucial role in innate immunity, particularly in combating infections and tumors. However, in hematological cancers, NK cells often exhibit impaired functions. Therefore, it is very important to activate its endosomal Toll-like receptors (TLRs) as a potential strategy to restore its antitumor activity. We stimulated NK cells from the peripheral blood mononuclear cells from children with acute lymphoblastic leukemia and NK cells isolated, and the NK cells were stimulated with specific TLR ligands (Poly I:C, Imiquimod, R848, and ODN2006) and we evaluated changes in IFN-γ, CD107a, NKG2D, NKp44 expression, Granzyme B secretion, cytokine/chemokine release, and cytotoxic activity. Results revealed that Poly I:C and Imiquimod enhanced the activation of both immunoregulatory and cytotoxic NK cells, increasing IFN-γ, CD107a, NKG2D, and NKp44 expression. R848 activated immunoregulatory NK cells, while ODN2006 boosted CD107a, NKp44, NKG2D, and IFN-γ secretion in cytotoxic NK cells. R848 also increased the secretion of seven cytokines/chemokines. Importantly, R848 and ODN 2006 significantly improved cytotoxicity against leukemic cells. Overall, TLR stimulation enhances NK cell activation, suggesting TLR8 (R848) and TLR9 (ODN 2006) ligands as promising candidates for antitumor immunotherapy.

High-Degree Atrioventricular Block and Torsades De Pointes in Severe Aortic Stenosis Treated With Transcatheter Aortic Valve Replacement.

Severe aortic stenosis (AS) significantly elevates cardiovascular risk, predisposing patients to high-degree atrioventricular (AV) block and life-threatening tachyarrhythmias, including torsades de pointes (TdP). This case report presents a patient with severe AS who developed high-degree AV block and, subsequently, TdP, highlighting the interplay between bradycardia and mechanisms that trigger ventricular tachycardias. The case underscores the importance of identifying and managing these risk factors to improve patient outcomes.

Cross-cultural adaptation and validation of Work Productivity and Activity Impairment questionnaires for caregivers of patients with pediatric inflammatory bowel disease in Spain. A multicenter study. / Adaptación transcultural y validación de cuestionarios WPAI (Work Productivity and Activity Impairment) para cuidadores de pacientes con enfermedad inflamatoria intestinal pediátrica en España. Estudio multicéntrico.

Introduction. The WPAI-UC/CD-Caregiver questionnaires assess the impact of ulcerative colitis (UC) or Crohn's disease (CD) on parents'/caregivers' work life and daily activities. Our objective was to adapt and validate these questionnaires in the Spanish population. Methods. A translation and back-translation were done. The document was assessed by an expert committee and a pilot group of families of patients with pediatric inflammatory bowel disease (p-IBD). For validation, the parents/caregivers of patients with p-IBD (10-18 years old) were recruited. The expert committee and the pilot group conducted a subjective assessment of the format and time necessary to complete the questionnaires. Cronbach's alpha coefficient was estimated and a factor analysis with varimax rotation was done. Kaiser- Meyer-Olkin (KMO) coefficients and Bartlett's sphericity test were estimated to test the adequacy of the factor analysis. Results. A total of 370 patients (median age: 14.1 years) and 263 parents/caregivers of patients with UC or unclassified IBD and 261 parents/caregivers of patients with CD were included. The KMO coefficients (0.6947 and 0.7179) and Bartlett's sphericity test (p < 0.001) confirmed the adequacy of the factor analysis. The 6 items targeted the same domain. The factor model accounted for 99.99% and 94.68% of variance, and Cronbach's alpha coefficients (0.6581 and 0.6968) showed an adequate consistency. The format and the median time of 2 minutes to complete the questionnaires were considered optimal. Conclusions. The versions of the WPAI-Caregiver questionnaires validated in the Spanish population may be used in families whose children have IBD.

Introducción. Los cuestionarios WPAI-UC/CD-Caregiver evalúan la repercusión laboral y en actividades cotidianas de los padres/cuidadores de pacientes con colitis ulcerosa (CU) o enfermedad de Crohn (EC). El objetivo fue adaptar y validar estos cuestionarios en la población española. Métodos. Se realizó la traducción y la retrotraducción. El documento fue evaluado por un comité de expertos y por un grupo piloto de familias de pacientes con enfermedad inflamatoria intestinal pediátrica (EII-p). Para la validación, se reclutaron padres/cuidadores de pacientes con EII-p (10-18 años). El comité de expertos y el grupo piloto evaluaron subjetivamente el formato y el tiempo necesario para completar los cuestionarios. Se calculó el coeficiente alfa de Cronbach y se realizó el análisis factorial con rotación Varimax. Se calcularon los coeficientes de Kaiser-Meyer-Olkin (KMO) y la prueba de esfericidad de Bartlett para comprobar la adecuación del análisis factorial. Resultados. Se incluyeron 370 pacientes (mediana 14,1 años), y 263 padres/cuidadores de pacientes con colitis ulcerosa o EII no clasificada y 261 padres/cuidadores de pacientes con enfermedad de Crohn. Los coeficientes KMO (0,6947 y 0,7179) y la prueba de esfericidad de Barttlet (p <0,001) confirmaron la adecuación del análisis factorial. Los 6 ítems se dirigieron a la misma dimensión. El modelo factorial explicó el 99,99 % y el 94,68 % de la varianza, y los alfa de Cronbach (0,6581 y 0,6968) indicaron buena consistencia. El formato y la mediana de 2 minutos para completarlos se consideraron óptimos. Conclusiones. Las versiones validadas en la población española de los cuestionarios WPAI-Caregiver pueden considerarse para su uso en familias con hijos con EII.

Unusual Presentation of De Winter's Sign Due to Bezold-Jarisch Reflex in a Patient With Severe Aortic Valve Stenosis.

The de Winter electrocardiogram (ECG) pattern, marked by upsloping ST depression in leads V2-V6, ST elevation in lead aVR, and tall symmetric T waves, typically indicates left anterior descending artery (LAD) occlusion. Traditionally linked to LAD occlusion, it is rare in severe aortic stenosis and the Bezold-Jarisch reflex (BJR). We report an 83-year-old man with severe aortic stenosis who developed hypotension due to bleeding and exhibited the de Winter ECG pattern. This case highlights how severe aortic stenosis and BJR can lead to significant hemodynamic instability and ischemic ECG changes, resolving after hemodynamic stabilization.

Changes at small intestine induced by food-fish contaminated with ciguatoxins.

Ciguateric syndrome is a food poisoning associated with the consumption of some species of fish that have accumulated ciguatoxins (CTXs) in their tissues. The effects of the syndrome occur with nervous imbalances which have been described for quite some time, and mentioned in sailing literature for centuries. In the last decade, research has been focused on the implementation of analytical methods for toxin identification and the study of action modes of CTXs to design effective treatments. However, an important aspect is to determine the damage that CTXs caused in the organs of affected individuals. In this work, the damages observed in tissues of mice, mainly in the small intestine, were analyzed. The animals were fed with CTX-contaminated fish muscle at concentrations 10-times below the median lethal dose (LD50) for 10 weeks. The analysis of tissues derived from the oral treatment resulted in an increased occurrence of Paneth cells, presence of lymphoid tissue infiltrating the mucosa and fibrous lesions in the mucosal layer of the small intestine. A decreasing weight in animals fed with toxic muscle was observed.

A Case of Left Ventricular Pseudoaneurysm as a Complication of Late-Presenting ST-Segment Elevation Myocardial Infarction.

This case report delineates the clinical trajectory and management strategies of a 59-year-old Hispanic male diagnosed with a left ventricular pseudoaneurysm (LVPA) following a delayed presentation of ST-segment elevation myocardial infarction (STEMI), for which reperfusion treatment was not administered. Initially, an echocardiogram demonstrated an extensive anterolateral myocardial infarction, severe left ventricular systolic dysfunction, and an early-stage left ventricular apical aneurysm with thrombus, leading to the initiation of warfarin. Metabolic myocardial perfusion imaging via positron emission tomography indicated a substantial myocardial scar without viability, guiding the decision against revascularization. Post discharge, the patient, equipped with a wearable cardioverter defibrillator for sudden cardiac death prevention, experienced symptomatic ventricular tachycardia, which was resolved with defibrillator shocks. Subsequent imaging revealed an acute LVPA adjacent to the existing left ventricular aneurysm. Given the high surgical risk, conservative management was elected, resulting in thrombosis and closure of the pseudoaneurysm after two weeks. The patient eventually transitioned to home hospice, surviving an additional five months. This report underscores the complexities and therapeutic dilemmas in managing post-MI LVPA patients who are ineligible for surgical intervention.

Cardiac Angiosarcoma Presenting as Large Pericardial Effusion With Effusive-Constrictive Pericarditis.

Pericardial angiosarcoma is an extremely rare malignant tumor originating from the endothelial cells of blood vessels within the pericardium. We present a case of a 49-year-old male who presented with symptoms of pericardial effusion and was subsequently diagnosed with pericardial angiosarcoma. This case report highlights the diagnostic challenges and management options associated with this rare entity.

Sinus Venosus Atrial Septal Defect as an Overlooked Source of Shortness of Breath Among Patients With Pulmonary Arterial Hypertension.

Sinus venosus atrial septal defects (SVASD) associated with partial anomalous pulmonary venous return (PAPVR) can be overlooked as a source of dyspnea in adult patients with pulmonary hypertension. We present the case of a 61-year-old male with exertional dyspnea initially attributed to pulmonary hypertension, who was subsequently diagnosed with SVASD and right superior PAPVR. This case underscores the critical importance of maintaining high clinical awareness and utilizing multimodal imaging techniques in cardiology to accurately diagnose and manage pulmonary hypertension secondary to congenital heart disease. Timely surgical correction can significantly improve morbidity and mortality outcomes.

Chiral spin-crossover complexes based on an enantiopure Schiff base ligand with three chiral carbon centers.

The preparation of Fe(II) complexes combining monodentate NCX- (X = S or Se) and the tetradentate Schiff base chiral ligands RR-L1 and SS-L1 = (RR- or SS-L1 = 1R,2R or 1S,2S)-N1,N2-bis(pyridin-2-ylmethylen)cyclohexane-1,2-diamine in acetone results in an unexpected reaction. Thus, four enantiomerically pure compounds of formulas [Fe(RR-S-L2)(NCX)2] and [Fe(SS-R-L2)(NCX)2] (X = S or Se) are formed by the new asymmetrical ligand L2. In L2, one acetone solvent molecule is incorporated into the ligand forming a bond with the C atom of one of the two CN imine groups of L1, which is transformed into an amine (Mannich reaction). This reaction is diastereoselective as the incorporation of acetone leads to an asymmetric C adjacent to the NH group with opposite chirality S- or R- to that of the cyclohexane carbons (RR- or SS-, respectively). Therefore, L2 contains three C chiral centers. Structural and magnetic characterization of these compounds demonstrates that they show in the bulk a gradual spin-crossover behavior and LIESST effect. Interestingly, the presence of an intramolecular hydrogen bond between the integrated acetone molecule and the NH group can trigger a secondary stimuli-responsive behavior in the system. Therefore, by changing the solvent polarity, the color of the complex in solution can be easily tuned.

Serum Metabolites Relate to Mucosal and Transmural Inflammation in Pediatric Crohn Disease.

BACKGROUND AND AIMS: We aimed to identify serum metabolites associated with mucosal and transmural inflammation in pediatric Crohn disease (pCD). METHODS: Fifty-six pCD patients were included through a pre-planned sub-study of the multicenter, prospective, ImageKids cohort, designed to develop the Pediatric Inflammatory Crohn's MRE Index (PICMI). Children were included throughout their disease course when undergoing ileocolonoscopy and magnetic resonance enterography (MRE) and followed for 18 months when MRE was repeated. Serum metabolites were identified using liquid chromatography/mass spectroscopy. Outcomes included: PICMI, the simple endoscopic score (SES), faecal calprotectin (FCP), and C-reactive protein (CRP), to assess transmural, mucosal, and systemic inflammation, respectively. Random forest models were built by outcome. Maximum relevance minimum redundancy (mRMR) feature selection with a j-fold cross validation scheme identified the best subset of features and hyperparameter settings. RESULTS: Tryptophan and glutarylcarnitine were the top common mRMR metabolites linked to pCD inflammation. Random forest models established that amino acids and amines were among the most influential metabolites for predicting transmural and mucosal inflammation. Predictive models performed well, each with an area under the curve (AUC) > 70%. In addition, serum metabolites linked with pCD inflammation mainly related to perturbations in citrate cycle (TCA cycle), aminoacyl-tRNA biosynthesis, tryptophan metabolism, butanoate metabolism, and tyrosine metabolism. CONCLUSIONS: We extend on recent studies, observing differences in serum metabolite between healthy controls and Crohn disease patients, and suggest various associations of serum metabolites with transmural and mucosal inflammation. These metabolites could improve the understanding of pCD pathogenesis and assess disease severity.

Nutritional Issues in Children with Dysphagia.

(1) Background: Pediatric dysphagia presents significant nutritional challenges, often impacting growth and development due to reduced oral intake, increased nutritional needs, and gastrointestinal complications; (2) Methods: This prospective quasi-experimental study assessed 117 children under 14 years old (20 patients were under 1 year old, 80 were aged 1-7 years, and 17 were older than 7 years), diagnosed with swallowing disorders, to analyze their caloric, macro-, and micronutrient intake and identify potential deficiencies. The severity of dysphagia was established using functional oral intake scales, and dietary records were reviewed over a 3-day period; (3) Results: The study revealed that 39.8% of participants did not meet their total energy expenditure (TEE), highlighting a high prevalence of malnutrition among these children. Furthermore, patients using feeding devices exhibited a significantly lower caloric intake, and over half required significantly modified food textures. After individualized speech therapy and nutritional rehabilitation, participants showed significant improvements in caloric intake, with their energy coverage increasing from 958% to 1198% of the daily requirement. Rehabilitation also improved tolerance to a broader range of food textures; (4) Conclusions: This research underscores the importance of multidisciplinary, individualized nutritional strategies to address the specific challenges of pediatric dysphagia, emphasizing the role of enteral nutrition and therapeutic interventions in improving the quality of life and nutritional outcomes of these children. Further studies are recommended to assess the long-term impact of such strategies.

Harmonizing Definitions and Perspectives in Extreme Liver Surgery: A Delphi Experts Consensus.

OBJECTIVE: To propose to our community a common language about extreme liver surgery. BACKGROUND: The lack of a clear definition of extreme liver surgery prevents convincing comparisons of results among centers. METHODS: We used a two-round Delphi methodology to quantify consensus among liver surgery experts. For inclusion in the final recommendations, we established a consensus when the positive responses (agree and totally agree) exceeded 70%. The study steering group summarized and reported the recommendations. In general, a five-point Likert scale with a neutral central value was used, and in a few cases multiple choices. Results are displayed as numbers and percentages. RESULTS: A two-round Delphi study was completed by 38 expert surgeons in complex hepatobiliary surgery. The surgeon´s median age was 58 years old (52-63) and the median years of experience was 25 years (20-31). For the proposed definitions of total vascular occlusion, hepatic flow occlusion and inferior vein occlusion, the degree of agreement was 97%, 81% and 84%, respectively. In situ approach (64%) was the preferred, followed by ante situ (22%) and ex situ (14%). Autologous or cadaveric graft for hepatic artery or hepatic vein repair were the most recommended (89%). The use of veno-venous bypass or portocaval shunt revealed the divergence depending on the case. Overall, 75% of the experts agreed with the proposed definition for extreme liver surgery. CONCLUSION: Obtaining a consensus on the definition of extreme liver surgery is essential to guarantee the correct management of patients with highly complex hepatobiliary oncological disease. The management of candidates for extreme liver surgery involves comprehensive care ranging from adequate patient selection to the appropriate surgical strategy.

Deep learning survival model predicts outcome after intracerebral hemorrhage from initial CT scan.

BACKGROUND: Predicting functional impairment after intracerebral hemorrhage (ICH) provides valuable information for planning of patient care and rehabilitation strategies. Current prognostic tools are limited in making long term predictions and require multiple expert-defined inputs and interpretation that make their clinical implementation challenging. This study aimed to predict long term functional impairment of ICH patients from admission non-contrast CT scans, leveraging deep learning models in a survival analysis framework. METHODS: We used the admission non-contrast CT scans from 882 patients from the Massachusetts General Hospital ICH Study for training, hyperparameter optimization, and model selection, and 146 patients from the Yale New Haven ICH Study for external validation of a deep learning model predicting functional outcome. Disability (modified Rankin scale [mRS] > 2), severe disability (mRS > 4), and dependent living status were assessed via telephone interviews after 6, 12, and 24 months. The prediction methods were evaluated by the c-index and compared with ICH score and FUNC score. RESULTS: Using non-contrast CT, our deep learning model achieved higher prediction accuracy of post-ICH dependent living, disability, and severe disability by 6, 12, and 24 months (c-index 0.742 [95% CI -0.700 to 0.778], 0.712 [95% CI -0.674 to 0.752], 0.779 [95% CI -0.733 to 0.832] respectively) compared with the ICH score (c-index 0.673 [95% CI -0.662 to 0.688], 0.647 [95% CI -0.637 to 0.661] and 0.697 [95% CI -0.675 to 0.717]) and FUNC score (c-index 0.701 [95% CI- 0.698 to 0.723], 0.668 [95% CI -0.657 to 0.680] and 0.727 [95% CI -0.708 to 0.753]). In the external independent Yale-ICH cohort, similar performance metrics were obtained for disability and severe disability (c-index 0.725 [95% CI -0.673 to 0.781] and 0.747 [95% CI -0.676 to 0.807], respectively). Similar AUC of predicting each outcome at 6 months, 1 and 2 years after ICH was achieved compared with ICH score and FUNC score. CONCLUSION: We developed a generalizable deep learning model to predict onset of dependent living and disability after ICH, which could help to guide treatment decisions, advise relatives in the acute setting, optimize rehabilitation strategies, and anticipate long-term care needs.

Bioprocess of Gibberellic Acid by Fusarium fujikuroi: The Challenge of Regulation, Raw Materials, and Product Yields.

Gibberellic acid (GA3) is a tetracyclic diterpenoid carboxylic acid synthesized by the secondary metabolism of Fusarium fujikuroi. This phytohormone is widely studied due to the advantages it offers as a plant growth regulator, such as growth stimulation, senescence delay, flowering induction, increased fruit size, and defense against abiotic or biotic stress, which improve the quality and yield of crops. Therefore, GA3 has been considered as an innovative strategy to improve agricultural production. However, the yields obtained at large scale are insufficient for the current market demand. This low productivity is attributed to the lack of adequate parameters to optimize the fermentation process, as well as the complexity of its regulation. Therefore, this article describes the latest advances for potentializing the GA3 production process, including an analysis of its origins from crops, the benefits of its application, the related biosynthetic metabolism, the maximum yields achieved from production processes, and their association with genetic engineering techniques for GA3 producers. This work provides a new perspective on the critical points of the production process, in order to overcome the limits surrounding this modern line of bioengineering.

Tofacitinib in Pediatric Ulcerative Colitis: A Retrospective Multicenter Experience.

BACKGROUND: Tofacitinib has recently been approved for treatment of moderate-to-severe ulcerative colitis (UC) in adults, yet pediatric data are limited. This international multicenter study describes the effectiveness and safety of tofacitinib in pediatric UC. METHODS: This is a retrospective review of children diagnosed with UC treated with tofacitinib from 16 pediatric centers internationally. The primary outcome was week 8 corticosteroid-free clinical remission (Pediatric Ulcerative Colitis Activity Index <10). Secondary outcomes were clinical response (≥20-point decrease in Pediatric Ulcerative Colitis Activity Index) at week 8, corticosteroid-free clinical remission at week 24, and colectomy rate and adverse safety events through to last follow-up. The primary outcome was calculated by the intention-to-treat principle. RESULTS: We included 101 children with a mean age at diagnosis of 12.8 ±â€…2.8 years and a median disease duration of 20 months (interquartile range [IQR], 10-39 months). All had treatment failure with at least 1 biologic agent, and 36 (36%) had treatment failure with 3 agents. Median follow-up was 24 weeks (IQR, 16-54 weeks). Sixteen (16%) children achieved corticosteroid-free clinical remission at week 8, and an additional 30 (30%) demonstrated clinical response. Twenty (23%) of 88 children achieved corticosteroid-free clinical remission at week 24. A total of 25 (25%) children underwent colectomy by median 86 days (IQR, 36-130 days). No serious drug-related adverse events were reported; there was 1 case of herpes zoster and 2 cases of minor blood test perturbations. CONCLUSIONS: In this largest real-life pediatric cohort to date, tofacitinib was effective in at least 16% of patients with highly refractory UC by week 8. Adverse events were minor and largely consistent with adult data.

Tofacitinib, widely reported in adult ulcerative colitis, has very limited pediatric data. This international collaboration is the largest pediatric study on the efficacy and safety of tofacitinib to date, providing important supportive data to clinicians and regulators.

Transcultural adaptation and validation of IMPACT-III and IMPACT-III-P in Spanish families: a multicenter study from SEGHNP.

IMPACT-III and IMPACT-III-P are health-related quality of life (HRQoL) questionnaires for patients with pediatric inflammatory bowel disease (p-IBD) and their parents/caregivers. We aimed to perform a transcultural adaptation and validation for the Spanish context. Translation, back-translation, and evaluation of the questionnaires were performed by an expert committee and 12 p-IBD families. We recruited p-IBD patients aged 10-17 and their parents/caregivers. Utility, content, and face validity were considered. Validation was performed with Cronbach's alpha coefficient and varimax rotation. We confirmed the adequacy of the factor analysis using Kaiser-Meyer-Olkin (KMO) and Bartlett's sphericity tests. A confirmatory factor analysis was performed using the following goodness indexes: chi-square, Normed Fit Index (NFI), Root Mean Square Error of Approximation index (RMSEA), Standardized Root Mean Square Residual (SRMR), and Comparative Fit Index (CFI). The correlation coefficient between IMPACT-III and IMPACT-III-P was analyzed. We included 370 patients and 356 parents/caregivers (37 hospitals). Both questionnaires had good content and face validity and were considered user-friendly. The KMO measure (0.8998 and 0.9228, respectively) and Bartlett's sphericity test (p-value < 0.001 for both) confirmed the adequacy of the factor analysis. The 4-factor model, complying with Kaiser's criterion, explained 89.19% and 88.87% of the variance. Cronbach's alpha (0.9123 and 0.9383) indicated excellent internal consistency. The CFA showed an adequate fit (NFI 0.941 and 0.918, RMSEA 0.048 and 0.053, SRMR 0.037 and 0.044, and CFI 0.879 and 0.913). The correlation coefficient was excellent (0.92). CONCLUSION: The SEGHNP versions of IMPACT-III and IMPACT-III-P are valid and reliable instruments for Spanish p-IBD families. WHAT IS KNOWN: • IMPACT-III and parent-proxy IMPACT-III (IMPACT-III-P) are useful questionnaires for assessing health-related quality of life (HRQoL) in pediatric inflammatory bowel disease (p-IBD) patients and their parents/caregivers and have been translated and validated in several countries. • To date, no transcultural adaptation and validation of these questionnaires have been published for Spanish patients with p-IBD and their families. WHAT IS NEW: • This is the first transcultural adaptation and validation of IMPACT-III and IMPACT-III-P for Spanish p-IBD families. • These are valid and reliable instruments for assessing HRQoL in Spanish families of patients with p-IBD.

Detection of inflammasome activation in liver tissue during the donation process as potential biomarker for liver transplantation.

Deceased donor liver transplantation (LT) is a crucial lifesaving option for patients with end-stage liver diseases. Although donation after brain death (DBD) remains the main source of donated organs, exploration of donation after circulatory death (DCD) addresses donor scarcity but introduces challenges due to warm ischemia. While technical advances have improved outcomes, challenges persist, with a 13% mortality rate within the first year. Delving into liver transplantation complexities reveals the profound impact of molecular signaling on organ fate. NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome activation play a pivotal role, influencing inflammatory responses. The NLRP3 inflammasome, found in hepatocytes, contributes to inflammation, fibrosis, and liver cell death. This study explores these dynamics, shedding light on potential biomarkers and therapeutic targets. Samples from 36 liver transplant patients were analyzed for ASC specks detection and inflammasome-related gene expression. Liver biopsies, obtained before and after cold ischemia storage, were processed for immunofluorescence, qRT-PCR, and Western blot. One year post-LT clinical follow-up included diagnostic procedures for complications, and global survival was assessed. Immunofluorescence detected activated inflammasome complexes in fixed liver tissues. ASC specks were identified in hepatocytes, showing a trend toward more specks in DCD livers. Likewise, inflammasome-related gene expression analysis indicated higher expression in DCD livers, decreasing after cold ischemia. Similar results were found at protein level. Patients with increased ASC specks staining exhibited lower overall survival rates, correlating with IL1B expression after cold ischemia. Although preliminary, these findings offer novel insights into utilizing direct detection of inflammasome activation in liver tissue as a biomarker. They suggest its potential impact on post-transplant outcomes, potentially paving the way for improved diagnostic approaches and personalized treatment strategies in LT.

Critical review of the evidence for Vojta Therapy: a systematic review and meta-analysis.

Introduction: It is essential to link the theoretical framework of any neurophysiotherapy approach with a detailed analysis of the central motor control mechanisms that influence motor behavior. Vojta therapy (VT) falls within interventions aiming to modify neuronal activity. Although it is often mistakenly perceived as exclusively pediatric, its utility spans various functional disorders by acting on central pattern modulation. This study aims to review the existing evidence on the effectiveness of VT across a wide range of conditions, both in the adult population and in pediatrics, and analyze common therapeutic mechanisms, focusing on motor control modulation. Aim: The goals of this systematic review are to delineate the existing body of evidence concerning the efficacy of Vojta therapy (VT) in treating a broad range of conditions, as well as understand the common therapeutic mechanisms underlying VT with a specific focus on the neuromodulation of motor control parameters. Methods: PubMed, Cochrane Library, SCOPUS, Web of Science, and Embase databases were searched for eligible studies. The methodological quality of the studies was assessed using the PEDro list and the Risk-Of-Bias Tool to assess the risk of bias in randomized trials. Methodological quality was evaluated using the Risk-Of-Bias Tool for randomized trials. Random-effects meta-analyses with 95% CI were used to quantify the change scores between the VT and control groups. The certainty of our findings (the closeness of the estimated effect to the true effect) was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE). Results: Fifty-five studies were included in the qualitative analysis and 18 in the meta-analysis. Significant differences in cortical activity (p = 0.0001) and muscle activity (p = 0.001) were observed in adults undergoing VT compared to the control, as well as in balance in those living with multiple sclerosis (p < 0.03). Non-significant differences were found in the meta-analysis when evaluating gross motor function, oxygen saturation, respiratory rate, height, and head circumference in pediatrics. Conclusion: Although current evidence supporting VT is limited in quality, there are indications suggesting its potential usefulness for the treatment of respiratory, neurological, and orthopedic pathology. This systematic review and meta-analysis show the robustness of the neurophysiological mechanisms of VT, and that it could be an effective tool for the treatment of balance in adult neurological pathology. Neuromodulation of motor control areas has been confirmed by research focusing on the neurophysiological mechanisms underlying the therapeutic efficacy of VT.Systematic Review Registration:https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=476848, CRD42023476848.