Search Results (81)

Background and Objectives: Crohn’s Disease (CD) is a chronic inflammatory condition often treated with anti-TNF agents such as infliximab (IFX) and adalimumab (ADA). This study compares the efficacy, immunogenicity, and pharmacokinetics of IFX and ADA over a 54-week period. Materials and Methods: A prospective, multicentre cohort study was conducted involving 72 patients with active CD (Crohn’s disease activity index, CDAI > 150), who received treatment with either IFX (n = 42) or ADA (n = 30). Results: By week 54, treatment discontinuation occurred in 31% of IFX-treated patients (13/42) and 37% of ADA-treated patients (11/30), with no significant difference between groups (p = 0.612). Among those who completed the study, clinical remission (CDAI ≤ 150) was achieved in 65% of the IFX group and 95% of the ADA group (OR = 8.10; 95% CI = 1.10–20.11; p = 0.049). Loss of clinical response was more frequent in the IFX group (31%) than in the ADA group (10%), with an OR of 0.25 (95% CI: 0.06–0.97; p = 0.045). Fibrinogen levels declined in both groups, with a greater reduction observed in ADA-treated patients. The area under the ROC curve (AUC) for fibrinogen in distinguishing remission from active disease was 0.608 for IFX and 0.711 for ADA. Anti-drug antibodies were detected more frequently in IFX-treated patients (16.7%, 7/42) compared to those receiving ADA (6.7%, 2/30). Conclusions: Treatment with ADA demonstrated superior efficacy compared to IFX in maintaining clinical remission in CD, which was paralleled by a more effective normalization of fibrinogen levels (Clinical trial: GET-CRO-2010-01). Full article

Objective: To determine whether oral vitamin D supplementation reduces the risk of glucocorticoid (GC)-associated severe adverse events (SAEs) in patients with giant cell arteritis (GCA) included in the Spanish ARTESER registry. Methods: The ARTESER registry collected data from patients diagnosed with GCA across 26 Spanish public hospitals between June 2013 and March 2019. SAEs were defined as fatal, life-threatening, or requiring hospitalization. Patients were categorized according to the use or non-use of oral vitamin D supplements. Incidence rates (IRs) of SAEs were expressed per person-year with 95% confidence intervals (CIs). Cox proportional hazards models assessed vitamin D supplementation and its interaction with cumulative glucocorticoid dose. Results: Of 1568 patients (mean age 76.9 ± 8.1 years; 70.1% women) receiving GC, 120 (7.6%) experienced SAEs (IR 0.039; 95% CI 0.033–0.047). Vitamin D supplementation was documented in 1186 (75.6%) compared with 382 (24.4%) non-supplemented patients. SAE incidence was similar in supplemented (n = 89; 7.5%; IR 0.038, 95% CI 0.030–0.046) and non-supplemented patients (n = 31; 8.1%; IR 0.045, 95% CI 0.031–0.064) (p = 0.387). Multivariable Cox regression showed a significant interaction between vitamin D supplementation and cumulative glucocorticoid dose (interaction term HR 0.90; p = 0.033), consistent with a dose-dependent protective effect. Conclusions: Vitamin D supplementation was not independently associated with a lower incidence of GC-related SAEs, likely due to residual confounding factors. However, the interaction with cumulative GC exposure suggests a modulatory effect. Prospective studies incorporating stratified baseline vitamin D assessments are warranted. Full article

Background: Drug combinations with complementary mechanisms of action are able to achieve effective analgesia at lower doses, thereby reducing the risk of adverse effects (AEs). This study evaluated the analgesic efficacy and tolerability of two fixed-dose combinations (FDCs) of ibuprofen/tramadol (IBU/TRA) compared with tramadol and a placebo. Methods: This multicenter, randomized, double-blind, dose-finding, pilot clinical trial compared IBU/TRA (400/37.5 mg and 400/75 mg) with 100 mg of tramadol and a placebo in patients with moderate-to-severe pain following dental surgery. The primary endpoints were pain intensity at 6 h (PI_6h) and the pain intensity difference from baseline to 6 h (PID_6h). PID_7h, the sum of pain intensity differences from baseline to 7 h (SPID_0–7h), pain relief (PAR_7h), total pain relief (TOTPAR_7h), the use of rescue medication and AEs were also assessed. Results: Seventy-two patients were randomized and evaluated. Both FDCs showed superiority over the placebo for PI_6h and PID_6h (p < 0.05) but were not significantly different from 100 mg of tramadol. The statistical superiority of FDCs over the placebo was observed for PID_7h, SPID_0–7h, PAR_7h and TOTPAR_7h. The percentage of patients receiving rescue medication was higher in the placebo (94.1%) and tramadol (52.6%) groups than the FDC groups (35.3% and 36.8% for 400/37.5 mg and 400/75 mg, respectively). A post hoc analysis showed that the FDCs had a superior analgesic efficacy to 100 mg of tramadol in the SPID_0–4h (p < 0.005). The incidence of AEs was comparable between treatment groups. Conclusions: Both FDCs of IBU/TRA provided superior analgesic efficacy compared to the placebo. We propose using SPID_0–4h as the preferred variable for evaluating the efficacy of this type of drug combination. Full article

Background/Objectives: Like many other countries, the management of pancreatic cancer in Spain has developed in a fragmented manner. This study analyzes clinical outcomes related to patient volume at different centers after left pancreatectomy (LP). Our goal is to determine whether our practices align with the standards established in the literature and assess whether centralization’s advantages significantly outweigh its disadvantages. Methods: The SPANDISPAN Project (SPANish DIStal PANcreatectomy) is an observational, prospective, multicenter study focused on LP conducted in Spanish Hepato-Pancreato-Biliary (HPB) Surgery Units from 1 February 2022 to 31 January 2023. HPB units were defined as high volume if they performed more than 10 LPs annually. Results: This study included 313 patients who underwent LP at 42 centers across Spain over the course of a year. A total of 40.3% of the procedures were performed in high-volume centers. Significant differences in preoperative variables were only observed in ASA scores, which were higher in the high-volume group. Intraoperatively, minimally invasive surgical techniques were performed more frequently in high-volume centers. Postoperatively, the administration of somatostatin, major complications, and B and C postoperative pancreatic fistula (POPF) were more frequent in low-volume hospitals. Conclusions: The findings revealed that high-volume centers had a higher rate of minimally invasive surgery, lower intraoperative bleeding, fewer complications, and reduced POPFs compared to low-volume centers. However, it is important to note that low-volume centers still demonstrated acceptable outcomes. Thus, the selective referral of more complex laparoscopic procedures could initiate a gradual centralization of surgical practices. Full article

Background: Hip fractures represent a major clinical challenge, particularly in elderly and frail patients, where postoperative pain control must balance effective analgesia with motor preservation to facilitate early mobilization. Various regional anesthesia techniques are used in this setting, including the pericapsular nerve group (PENG) block, fascia iliaca compartment block (FICB), femoral nerve block (FNB), and quadratus lumborum block (QLB), yet optimal strategies remain debated. Objectives: To systematically review the efficacy, safety, and clinical applicability of major regional anesthesia techniques for pain management in hip fractures, including considerations of fracture type, surgical approach, and functional outcomes. Methods: A systematic literature search was conducted following PRISMA 2020 guidelines in PubMed, Scopus, Web of Science, and the virtual library of the Hospital Central de la Defensa “Gómez Ulla” up to March 2025. Inclusion criteria were RCTs, systematic reviews, and meta-analyses evaluating regional anesthesia for hip surgery in adults. Risk of bias in RCTs was assessed using RoB 2.0, and certainty of evidence was evaluated using the GRADE approach. Results: Twenty-nine studies were included, comprising RCTs, systematic reviews, and meta-analyses. PENG block demonstrated superior motor preservation and reduced opioid consumption compared to FICB and FNB, particularly in intracapsular fractures and anterior surgical approaches. FICB and combination strategies (PENG+LFCN or sciatic block) may provide broader analgesic coverage in extracapsular fractures or posterior approaches. The overall risk of bias across RCTs was predominantly low, and certainty of evidence ranged from moderate to high for key outcomes. No significant safety concerns were identified across techniques, although reporting of adverse events was inconsistent. Conclusions: PENG block appears to offer a favorable balance of analgesia and motor preservation in hip fracture surgery, particularly for intracapsular fractures. For extracapsular fractures or posterior approaches, combination strategies may enhance analgesic coverage. Selection of block technique should be tailored to fracture type, surgical approach, and patient-specific functional goals. Full article

Renal function refers to the combined actions of the glomerulus and tubular system to achieve homeostasis in bodily fluids. While the glomerulus is essential in the first step of urine formation through a coordinated filtration mechanism, the tubular system carries out active mechanisms of secretion and reabsorption of solutes and proteins using specific transporters in the epithelial cells. The assessment of renal function usually focuses on glomerular function, so the tubular function is often underestimated as a fundamental part of daily clinical practice. Therefore, it is essential to properly understand the tubular physiological mechanisms and their clinical association with prevalent human pathologies. This review discusses the primary solutes handled by the kidneys, including glucose, amino acids, sodium, potassium, calcium, phosphate, citrate, magnesium and uric acid. Additionally, it emphasizes the significance of physicochemical characteristics of urine, such as pH and osmolarity. The use of a concise methodology for the comprehensive assessment of urine should be strengthened in the basic training of nephrologists when dealing with problems such as water and electrolyte balance disorders, acid-base disorders, and harmful effects of commonly used drugs such as chemotherapy, antibiotics, or diuretics to avoid isolated replacement of the solute without carrying out comprehensive approaches, which can lead to potentially severe complications. Full article

Background: Brain metastases are a common and devastating complication of non-small cell lung cancer (NSCLC), severely affecting prognosis and quality of life. Despite increasing interest in the role of platelets in tumor progression and dissemination, the potential impact of antiplatelet therapy on brain metastasis in NSCLC remains underexplored. Methods: In this retrospective observational study, we analyzed data from 650 patients diagnosed with NSCLC over a four-year period to evaluate whether prior or subsequent exposure to antiplatelet agents correlates with a reduced incidence of brain metastases. Results: Patients exposed to antiplatelet therapy, predominantly aspirin, presented with more comorbidities and were generally older. Despite these differences, they showed a significantly lower risk of developing brain metastases during the disease course (6.9% vs. 20.0%, p < 0.001), particularly among those with advanced-stage disease at diagnosis. A longer time to metastasis development was also observed in antiplatelet users (77.5 vs. 62.6 months, p < 0.001), along with improved progression-free survival. Additionally, patients on antiplatelets before diagnosis had a lower probability of presenting brain metastases at the time of diagnosis (3.9% vs. 12.1%, p = 0.014), and no cases of brain metastases occurred in patients who started antiplatelet therapy shortly after diagnosis. These findings highlight the potential of antiplatelet agents to interfere with key mechanisms of metastatic spread, including immune evasion and premetastatic niche formation. Conclusions: Importantly, this study provides one of the first real-world analyses suggesting a consistent and stage-dependent association between antiplatelet use and reduced brain metastatic burden in NSCLC. By bridging the gap between preclinical insights and clinical outcomes, our work offers a novel and clinically relevant perspective that supports further research into the integration of antiplatelet therapy in NSCLC management. Full article

Background: The COVID-19 pandemic clearly posed a global challenge to healthcare systems, where the allocation of limited resources had important logistical and ethical implications. Detecting and prioritizing the population at risk of intensive care unit (ICU) admission is the first step to being able to care for the most vulnerable people and avoid unnecessary consumption of resources by mildly ill patients. Objective: To create a model, using machine learning techniques, capable of identifying the risk of admission to the ICU throughout the hospital stay of the COVID patient and to evaluate the performance of the model. Methods: A retrospective cohort design was used to develop and validate a classification model of adult COVID-19 patients with or without risk of ICU admission. Data from three hospitals in Spain were used to develop the model (n = 1272) and for subsequent external validation (n = 550). Sensitivity, specificity, positive and negative predictive value, accuracy, F1 score, Youden index and area under the curve of the model were evaluated. Results: The LightGBM model, incorporating 40 variables, was used. The area under the curve obtained by the model when the test dataset was used was 1.00 (0.99–1.0), specificity 0.99 (0.97–1.00) and sensitivity 0.92 (0.86–0.98). Conclusions: A model for predicting ICU admission of hospitalized COVID-19 patients was created with very good results. The identification and prioritization of COVID-19 patients at risk of ICU admission allows the right care to be provided to those who are most in need when the healthcare system is under pressure. Full article

Background: Remote symptom monitoring via electronic platforms may identify patients at risk for unplanned acute care visits after surgery. Since 2016, the Memorial Sloan Kettering Cancer Center (MSKCC) has employed the Recovery Tracker (RT), a patient-reported outcome (PRO) system, for symptom monitoring after ambulatory procedures. In 2021, RT was extended to patients undergoing inpatient colorectal surgery. Objective: To evaluate the impact of RT implementation on urgent care utilization and readmission rates in patients undergoing elective inpatient colorectal surgery and to determine whether patient engagement with RT influences these outcomes. Methods: In this retrospective observational study at MSKCC, we compared patients undergoing elective colorectal surgery during the RT implementation period (March 2021–December 2022) to a historical control cohort (February 2019–February 2020). The primary outcome was a potentially unnecessary urgent care center (UCC) visits—defined as a visit not requiring inpatient admission. Secondary outcomes included 30-day readmission and survey engagement. Multivariable logistic regression was used for adjusted comparisons. Results: A total of 1941 patients in the RT cohort and 1206 in the control group met the inclusion criteria. The RT cohort had higher rates of UCC visits without admission (4.43% vs. 1.6%) and 30-day readmissions (9.74% vs. 6.88%). RT period surgery was independently associated with increased odds of UCC visits (OR 2.80, 95% CI 1.71–4.58, p < 0.0001) and readmissions (OR 1.43, 95% CI 1.09–1.88, p = 0.0098). Notably, RT users who completed at least one survey (70.2%) had significantly lower odds of readmission (OR 0.56, 95% CI 0.41–0.77, p = 0.0003) compared to non-responders. Discussion: Engagement with the RT system was associated with a 44% reduction in readmission risk, identifying non-responders as a vulnerable subgroup. While the overall rates of post-discharge care utilization increased after RT implementation, active participation in PRO reporting emerged as a protective factor. Conclusions: These findings highlight the need for strategies to promote engagement and support patients less likely to interact with remote monitoring tools. Non-response may signal barriers such as technological challenges or increased vulnerability, warranting proactive engagement strategies. Full article

Sunflower Verticillium Wilt and Leaf Mottle (SVW), caused by Verticillium dahliae Kleb., is a globally prevalent disease affecting sunflower production. In this study, we identified a major quantitative trait locus (QTL) on chromosome 10 and other genomic regions associated with SVW resistance by integrating biparental and association mapping in sunflower populations from the National Institute of Agricultural Technology. Nine replicated field trials were conducted in highly infested V. dahliae reservoirs to assess disease incidence and severity. Both mapping populations were genotyped using double-digest restriction-site-associated DNA sequencing (ddRADseq). Association mapping with 18,161 SNPs and biparental QTL mapping with 1769 SNPs identified a major QTL on chromosome 10 explaining up to 30% of phenotypic variation for disease incidence at flowering and for the area under the disease progress curve for disease incidence, and which contributes to a lesser extent to disease severity reduction. Additional QTLs on chromosomes 17, 8, 9, 14, 13, and 11 were associated with reduced disease incidence, severity, or both. Candidate genes were identified within these associated regions, 39 of which are in the major QTL on Chromosome 10. These findings demonstrate the value of integrating complementary QTL mapping strategies for validating resistance loci and advancing sunflower breeding for SVW resistance. Full article

The transition of agriculture towards sustainability faces significant obstacles, such as increased demand for food, food insecurity, climate variability, biodiversity loss, and food waste, among others. Moreover, agricultural activities must address ethical practices within sustainable development. The literature frequently mentions two approaches to meet these challenges: agroecology and sustainable agriculture. This study aims to delineate the conceptual boundaries of agroecology and sustainable agriculture while elucidating their interconnection. It seeks to clarify the scope and limitations inherent in these agricultural practices, which is critical given the centrality of sustainable agriculture in agrarian studies. By establishing these boundaries, the research outlines the methodologies to identify the relevant variables and indicators required for effective stakeholder engagement within agricultural systems. A systematic literature review was conducted using the PRISMA method. The databases searched were Science Direct, Scopus, Nature, and Google Scholar. The inclusion criteria were (i) written in English or Spanish, (ii) published in a peer-reviewed academic journal, and (iii) related to the conceptualization of agroecology and sustainable agriculture. Publications were selected following the method’s identification, screening, eligibility, and inclusion guidelines. The main distinctions between the concepts are the scale and the scope. Agroecology reveals limitations to achieving impacts on food security and agriculture’s challenges in a large-scale system better suited for rural communities and small farms seeking locally adapted solutions. On the other hand, the literature reveals that it is crucial to adopt a multi-scale systems approach to meet the growing food demands of the global population, for which sustainable agriculture may be more effective. Full article

Catalytic reactor engineering bridges the active-site scale and the industrial-reactor scale, with kinetics as the primary bottleneck in scale-up. The main challenge in kinetics is conceptualizing the active site and formulating the reaction mechanism, leading to multiple approaches without clear guidance on their reliability for industrial-reactor design. This work assesses different approaches to active-site conceptualization and reaction-mechanism formulation for selective oxidation over a complex multi-metal catalyst. It integrates atomistic-scale insights from periodic Density Functional Theory (DFT) calculations into kinetic-model development. This approach contrasts with the macroscopic classical method, which treats the catalyst as a black box, as well as with alternative atomistic methods that conceptualize the active site as a single metal atom on different catalytic-surface regions. As a case study, this work examines ethane oxidative dehydrogenation to ethylene over the multi-metal oxide catalyst MoVTeNbO, which has a complex structure. This analysis provides insights into the ability of DFT to accurately describe reactions on such materials. Additionally, it compares DFT predictions to experimental data obtained from a non-idealized MoVTeNbO catalyst synthesized and assessed under kinetic control at the laboratory scale. The findings indicate that while the black-box active-site conceptualization best describes observed trends, its reaction mechanism and parameters lack reliability compared to DFT calculations. Furthermore, atomistic active-site conceptualizations lead to different parameter sets depending on how the active site and reaction mechanism are defined. Unlike previous studies, our approach determines activation-energy profiles within the range predicted by DFT. The resulting kinetic model describes experimental trends while maintaining phenomenological and statistical reliability. The corrections required for primary parameters remain below 20 kJ mol${}^{-1}$, consistent with the inherent uncertainties in DFT calculations. In summary, this work demonstrates the feasibility of integrating atomistic insights into kinetic modeling, offering different perspectives on active-site conceptualization and reaction-mechanism formulation, paving the way for future studies on rational catalyst and industrial-reactor design. Full article

Adult B-cell acute lymphoblastic leukemia (B-ALL) is characterized by genetic heterogeneity and a high relapse rate, affecting over 40% of adults. However, the mechanisms leading to relapse in adults are poorly understood. Forty-four adult B-ALL patients were studied at both diagnosis and relapse by next-generation sequencing (NGS). Four main genetic pathways leading to relapse in adults were identified: IKZF1^plus genetic profile, RAS mutations and TP53 alterations in Ph-negative B-ALL and acquisition of ABL1 mutations in Ph-positive patients. The most frequently deleted gene at diagnosis was IKZF1 (52%), and 70% of these patients had IKZF1^plus profile. Notably, 88% of patients with IKZF1^plus at diagnosis retained this genetic profile at relapse. Conversely, the acquisition of RAS mutations or the expansion of subclones (normalized variant allele frequency < 25%) present from diagnosis were observed in 24% of Ph-negative patients at relapse. In addition, 24% of relapses in the Ph-negative cohort could potentially be driven by TP53 alterations. Of these cases, five presented from diagnosis, and four emerged at relapse, mostly as “double-hit” events involving both TP53 deletion and mutation. In Ph-positive B-ALL, the main genetic finding at relapse was the acquisition of ABL1 mutations (86%). Three clonal evolution patterns were identified: the persistent clone trajectory (25%), the expanding clone trajectory (11%) and the therapy-boosted trajectory (48%). Our results reveal the presence of preferential biological pathways leading to relapse in adult B-ALL. These findings underscore the need for personalized therapeutic strategies to improve clinical outcomes in adult patients with B-ALL. Full article

Magnetite nanoparticles were synthesized using the green chemistry technique; ferric chloride was used as a precursor agent and Moringa oleifera extract was used as a stabilizer agent. A black powder, characteristic of magnetite, was obtained. X-ray diffraction was performed on the synthesis product and identified as magnetite (Fe₃O₄). Scanning electron microscopy characterization shows that nanoparticles have a spherical morphology, with sizes ranging from 15 nm to 35 nm. The synthesis of carbon nanotubes was carried out by the pyrolytic chemical deposition technique, from which multiwalled carbon nanotubes were obtained with diameters of 15–35 nm and of varied length. The decoration was carried out using the wet and sonification technique, where a non-homogeneous coating was obtained around the nanotubes. The thermal decomposition for both decorated and undecorated nanotubes presents two mass losses but with different slopes, where the activation energy for the decorated carbon nanotubes was 79.54 kJ/mol, which shows that the decoration gives more stability to the nanotubes since the activation energy of the undecorated nanotubes is 25.74 kJ/mol. Full article

This work introduces a boost converter with quadratic gain. Its main advantage compared to well-known similar quadratic boost converters is that it requires capacitors with a relatively small capacitance and inductors with small inductance, leading to a reduction in the size or stored energy while performing a power conversion of similar power rating and the same switching ripples in both the input current and the output voltage. It is inspired by the recently introduced ISB converter and uses a specific PWM method. This results in achieving switching ripple constraints while using smaller energy storage elements (capacitors and inductors). The updated converter offers the same voltage gain compared to the conventional quadratic boost topology with the benefit of compact component sizes. While it has more passive elements, they are of reduced size. An analysis of energy storage revealed that this new converter uses only half the energy in inductors and 14% in capacitors when compared to specific design parameters. Full article