Abstract: Internalizing and externalizing problems have been associated with sensory processing (SP) alteration, where severe alterations are equivalent to Sensory Processing Disorder (SPD). Background/Objectives: The present study aims to examine the relationship between childhood problems and the degree of sensory processing alteration in children referred to a Child Mental Health Center (CMHC). Methods: The sample consisted of 64 children (44 boys and 20 girls), aged 6 to 8 years, who were referred by their pediatricians to a Child Mental Health Center (CMHC) in Gipuzkoa, Spain. Data were collected using the parent-report version of the Child Behavior Checklist (CBCL/6–18) and the Child Sensory Profile (CSP-2). Data were collected using the parent-report version of the Child Behavior Checklist (CBCL/6–18) and the Child Sensory Profile, Second Edition (CSP-2). Analyses of variance and qualitative analyses were conducted to compare T-scores of childhood problems across SP alteration groups (no alteration, mild, moderate, and severe). Results: A total of 31.3% (n = 20) of participants in the present study exhibited a severe SP alteration. These children obtained significantly higher scores than those without SP alteration on the Withdrawn/Depressed, Attention, Social and Thought Problems syndrome scales, as well as on the Internalizing Problems and Total Problems scales. Furthermore, children with severe SP alteration scored within the clinical range (T-score ≥ 70) on the Anxious/Depressed and Attention problems scales. Mean scores for Internalizing, Externalizing and Total Problems reached the clinical threshold (T-score ≥ 64) when the SP alteration was classified as moderate or severe. These findings indicate that SP alteration is associated with increased internalizing and externalizing problems in children referred to CMHC, with clinical levels observed particularly in cases of moderate to severe SP alteration. Conclusions: This study highlights the importance of including SP assessment into the diagnostic evaluation of childhood mental health problems.

Abstract: As part of the “2nd Training Conference on Heart Failure and Atrial Fibrillation for Residents”, held in Madrid in November 2024, a collaborative initiative was launched to address the most common practical challenges in the management of heart failure (HF) in daily practice. This document is the result of the joint efforts of residents from various hospitals nationwide, in collaboration with senior physicians with extensive HF expertise and members of the Working Group of the Spanish Society of Internal Medicine. Our aim is to provide a useful tool that promotes learning and collaboration among professionals interested in this field. The structure of this document is based on a compilation of the most interesting and challenging questions raised during the conference. Each question is addressed with a concise and practical response, supported by updated references to ensure scientific rigor and facilitate consultation.

Abstract: Purpose: To analyze the influence of the type of cement, aging, and implant connection regarding the Institute of Excellence in Teaching and Research-IETR Institute of Excellence in Teaching and Research-IETR retention capacity of zirconia crowns cemented onto the Titanium base abutment Material and methods: The specimens was divided into four groups: Ti-Base External Hexagon 5,0x4,7x1,0 mm (n=20) or Ti-Base Morse Taper 5,0x4,7x1,5 mm (n=20), temporary or definitive cement, and mechanical aging (with or without). All the samples underwent a tensile test. Results: Data analysis was assessed using the Shapiro-Wilk, three-way ANOVA with repeated measures, and Tukey's test (P < 0.05). The failure mode was also recorded. The Morse taper implants presented a statisti-cally significantly higher average retention strength than the external hexagon implants. Groups III and IV presented the highest value compared to the other groups (565 and 491 N). Most mixed failures were found for all groups. Conclusion: Mechanical aging imped-ed the retention force of milled zirconia crowns cemented on titanium base abutments with resin cement on Morse taper implants had greater retention force compared to exter-nal hexagon implants.

Abstract: Abstract Background/Objectives. To analyze the factors associated with recurrent choledocholithiasis following endoscopic retrograde cholangiopancreatography (ERCP) with biliary sphincterotomy (BS). Methods. A retrospective, observational, and analytical cohort study was conducted. Patients who underwent ERCP with BS for benign biliary pathology and were followed for a minimum of two years were included. Demographic and clinical data were collected, including the indication for the procedure, endoscopic findings, performance and timing of cholecystectomy (before or after ERCP), and the need for repeat procedures. Episodes of choledocholithiasis were defined as those occurring at least six months after the initial ERCP. Follow-up continued until patient death, loss to follow-up, or the conclusion of the study. Results. A total of 576 patients were included, with a mean age of 71 years and an average follow-up duration of 131 months. Sixty-nine cases of recurrent choledocholithiasis were documented (11.96%). Multivariate analysis identified the following predictive factors for recurrence: age over 50 years, bile duct dilation on initial evaluation, history of biliary surgery, cytology sampling, placement of biliary stents, repeated ERCP, biliary diversion procedures, and cholecystectomy prior to the index ERCP. Conclusions. Biliary duct dilation, advanced age, and any previous manipulation of the biliary tree are associated with an increased risk of recurrent choledocholithiasis. Cholecystectomy performed after the initial ERCP was not associated with a reduced recurrence risk.

Abstract: Background/Objectives: Acne vulgaris (AV), a common dermatological condition in adolescence, has been widely recognized not only for its physical impact but also for its significant psychological and social consequences, particularly the internalization of stigma. This study specifically aimed to evaluate the state of internalized stigma in adolescents with AV and its relationship with quality of life and disease severity. Additionally, we sought to identify and assess the factors associated with internalized stigma. Methods: A total of 179 patients with AV were included in this cross-sectional observational study. We employed a convenience sampling strategy. The Internalized Stigma Scale (ISS) was used to assess patients' stigma. The Acne Quality of Life Scale (AQLS) and the Dermatology Life Quality Index (DLQI) were used to assess patients' quality of life. The Global Acne Grading System (GAGS) was used to assess disease severity. Results: Cronbach's alpha coefficient for the ISS was determined to be 0.79. In our study, the mean total ISS scores for patients with AV were notably high. The ISS was significantly positively correlated with the AQLS score (r = 0.653, p = 0.000), DLQI score (r = 0.487, p = 0.000), and GAGS score (r = 0.257, p = 0.006). Linear regression analysis was performed to predict the ISS variable. Accordingly, the AQLS positively and significantly predicts (ß= 0.521, p = 0.000). Conclusions: AVs often experience high levels of stigma. Internalized stigma is strongly associated with reduced quality of life and increased disease severity. Moreover, the AQLS significantly affects stigma.

Abstract: Background: Prevention of an irreversible sequalae of neurosyphilis patients requires an immediate high-dosage of intravenous benzylpenicillin administered for prolonged periods of time. However, life-threatening neutropenia has been reported as one of the complications following the extended usage of benzylpenicillin. Case presentation: We report a 54-year-old HIV infected male patient, who developed a high-dose benzylpenicillin induced febrile neutropenia during the neurosyphilis treatment. The patient developed fever of up to 39.8°C, severe leukopenia (< 1x10⁹/L), and neutropenia (0.2x10⁹/L). He also presented with slightly elevated C-reactive protein and procalcitonin but had no clear symptoms of infection. The diagnosis was confirmed by excluding other possible causes of neutropenia: flu, measles, sepsis, and HIV-related neutropenia. The 3^rd generation antipseudomonal cephalosporin in combination with vancomycin and granulocyte colony-stimulating factor were administered, and the patient saw a rapid improvement in clinical symptoms and laboratory findings. Conclusions: High-dose benzylpenicillin induced neutropenia should be considered as a complication after prolonged periods of neurosyphilis treatment with high-dose benzylpenicillin, when there is no evidence of other potential causes of neutropenia. Early diagnosis and proper treatment are critical in order to prevent this dangerous condition from deteriorating further.

Abstract: Background: Malignant mesothelioma is a rare and aggressive tumor, primarily affecting the pleural lining of the lungs. Our study aims to assess the survival benefit of chemotherapy rechallenge, in patients with no further chemotherapy options, compared to best supportive care, and to identify predictive factors for response to this strategy.Materials and Methods: We retrospectively analyzed data from 163 patients affected by MPM since November 2018. Of these, 41 patients, with advanced stage of disease and previously treated, were evaluated for chemotherapy rechallenge with platinum-pemetrexed regimen or were candidate only to palliative and supportive care. These two populations were compared in terms of overall survival outcomes.Results: When comparing median survival times, a significant difference was observed between the two study groups, with patients treated with platinum-pemetrexed rechallenge reaching approximately 20 months of median survival, while those receiving palliative care only 3 months. Survival percentages at different time intervals show that five months after the decision to undergo rechallenge or begin palliative care, the survival rate for the latter group was 27.27%, which is significantly lower than the 81.57% survival rate in the rechallenge one. Cox regression analysis confirmed rechallenge as a significant predictor of improved survival (HR 0.12, p < 0.001). Conclusion: Our findings suggest a potential survival benefit associated with the use of platinum-pemetrexed rechallenge in selected patients with advanced-stage, pretreated MPM. Further studies with larger cohorts are needed to validate these results.

Abstract: Background and Objectives Upper tract urothelial carcinoma (UTUC) is one of the most underdiagnosed but at the same time one of the most lethal cancers. In this review article we investigated the application of artificial intelligence and novel technologies in the prompt identification of high grade UTUC to prevent metastases and facilitate timely treatment. Materials and Methods We conducted an extensive search of the literature from the Pubmed and Google scholar databases for studies investigating the application of artificial intelligence for the diagnosis of UTUC. After the exclusion of non-associated and non-English studies, we included 12 articles in our review. Results Artificial intelligence systems have been shown to enhance post radical nephroureterectomy urine cytology reporting, in order to facilitate early diagnosis of bladder recurrence, as well as improve diagnostic accuracy in atypical cells, by being trained in annotated cytology images. Apart from that, data from computed tomography urograms by extracting textural radiomics features, can develop machine learning models to predict UTUC tumors grade and stage in small size and especially high grade tumors. Random forest models have been shown to have the best performance in predicting high grade UTUC, while hydronephrosis is the most significant independent factor for high grade tumors. ChatGPT, although not mature to provide information on diagnosis and treatment, can assist patients' understanding of the disease’s epidemiology and risk factors. Computer vision models in real-time can augment visualisation during endoscopic ureteral tumor diagnosis and ablation. Deep learning workflow can also be applied in histopathological slides to predict UTUC protein- based subtypes. Conclusion Artificial intelligence has been shown to greatly facilitate the timely diagnosis of high-grade UTUC by improving the diagnostic accuracy of urine cytology, CT Urogram and ureteroscopy visualisation. Deep learning systems can become a useful and easily accessible tool in physicians' armamentarium to deal with urothelial cancer diagnostic uncertainties.

Abstract: Background and Objectives: The study aims to evaluate the significance and independence of patient-reported outcomes (PROs) in predicting costs of hospitalized chronic heart failure (CHF) cases. Materials and Methods: This observational cross-sectional study included all adult patients with a physician-confirmed diagnosis of CHF who were randomly admitted to the cardiology department of a university emergency hospital from Bucharest, Romania, between July and September 2024. Upon admission, each patient filled in the validated Romanian version of the 12-item Kansas City Cardiomyopathy Questionnaire (KCCQ), and underwent clinical interview and examination, blood sampling and transthoracic echocardiography. Total hospitalization cost and hospitalization duration were the primary outcomes, while KCCQ Overall Summary Score (KCCQ-OSS) was the primary predictor variable in generalized linear modeling (GLM) with potential confounders. Results: The study included 171 CHF patients with an average age of 73.5 years and a predominance of women (55.0%), with a median total hospitalization cost of 1513 €/patient for a mean hospitalization duration of 8.7 days. Each 10-point decrease in KCCQ-OSS was significantly and independently associated with a 9.5% increase in expected hospitalization duration and each 10-point increase in KCCQ-OSS was significantly and independently associated with a 5.1% increase in expected hospitalization cost. Conclusions: This study demonstrates that KCCQ-OSS is a significant independent predictor of both hospitalization cost and duration in CHF. Incorporating KCCQ assessment may support early identification of high-risk, high-cost patients, guide resource allocation, and ultimately enhance patient-centered and value-based management strategies in CHF.

Abstract: Objective: This study aimed to evaluate the prognostic utility of systemic inflammatory markers, such as the Systemic Immune-Inflammation Index (SII), Systemic Inflammatory Response Index (SIRI), Neutrophil-Lymphocyte Ratio (NLR), Monocyte-Lymphocyte Ratio (MLR), and Platelet-Lymphocyte Ratio (PLR), to identify patients at risk of developing surgically treated Dressler syndrome. Methods: A total of 150 patients were retrospectively analyzed. 75 patients who developed Dressler syndrome requiring surgical drainage constituted the Dressler group, whereas 75 age-and surgically matched non-Dressler patients served as the control group. Blood samples were collected at four time points: preoperative (T1), 24 h postoperative (T2), postoperative day 7 (T3), and 24 h before secondary intervention in the Dressler group and the closest matched outpatient follow-up (T4) in the control group. Inflammatory marker values were compared within and between the groups at the four defined time points. Logistic regression and receiver operating characteristic (ROC) analyses were used to determine the diagnostic and predictive accuracy of each marker. Results: Significant increases in SIRI, MLR, and CRP levels were observed in patients who developed DS and required surgical intervention. MLR on postoperative day 7 showed the highest sensitivity (84%) with a cutoff of 0.575, whereas SIRI demonstrated the highest specificity (81.3%) at a cutoff of 3.34. The SII increased significantly only in the late stage, indicating disease progression. The NLR lacked predictive power across all time points. Conclusion: SIRI and MLR are promising early stage biomarkers for identifying patients at a high risk of developing DS. Their integration into routine postoperative follow-up could facilitate earlier diagnosis and reduce surgical burden. A multimarker approach may enhance the diagnostic precision of DS beyond that of traditional inflammatory measures.

Abstract: Background: The MVA-BN vaccine is considered effective for preventing mpox in key populations, based on observational studies, though its effectiveness remains unconfirmed by randomized trials. Observational studies published to date rely on retrospective analyses of routine data, often missing information on relevant risk factors for mpox. Methods: Multi-country target trial emulation study with prospective data collection. Between September 1, 2022, and June 15, 2023, we recruited individuals eligible for mpox vaccination based on clinical history and exposure behaviors via healthcare centers and social venues in Spain, Peru, Panama, and Chile. Vaccinated individuals were paired with unvaccinated counterparts matched by mpox risk factors, country, recruitment date, and age. Follow-up continued via periodic surveys until March 31, 2024. The primary endpoint was symptomatic mpox occurrence ≥14 days post-vaccination. Results: The primary analysis included 1,028 individuals (514 vaccinated, 514 unvaccinated) with a median follow-up time of 9.3 months (IQR 4.7–13.7). Mpox occurred in 8 participants (0.8%): 3 vaccinated and 5 unvaccinated (HR 0.6; 95% CI 0.21–1.70). Adverse reactions were reported by 731 (49.6%) participants, predominantly skin reactions (703/1,475; 47.7%), while systemic reactions occurred in 107 (7.3%). Long-lasting erythema at the injection site was reported in 1,058 (71.7%) participants, persisting &gt;6 months in 17% (107/1,058). Conclusions: Although not statistically significant, our findings—accounting for key confounders such as exposure behaviors—support the use of MVA-BN as pre-exposure prevention for mpox. The MVA-BN was generally safe, though long-lasting erythema at the injection site, previously unreported, was noted in a substantial proportion of participants.

Abstract: ALK+ Anaplastic Large Cell Lymphoma (ALCL) is an aggressive T-cell lymphoma that is characterized by expression of the Anaplastic Lymphoma Kinase (ALK), which is induced by the t(2;5) chromosomal rearrangement leading to the expression of the NPM-ALK fusion-oncogene. Most previous preclinical models of ALK+ ALCL were based on overexpression of the NPM-ALK cDNA from heterologous promoters. Due to the enforced expression, this approach is prone to artifacts arising from synthetic overexpression, promoter competition and insertional variation. To improve the existing ALCL models and more closely recapitulate the oncogenic events in ALK+ ALCL, we employed CRISPR/Cas-based chromosomal engineering to selectively introduce translocations between the Npm1 and Alk gene loci in murine cells. By inducing precise DNA cleavage at the syntenic loci on chromosome 11 and 17 in a murine IL-3-dependent Ba/F3 reporter cell line, we generated de novo Npm-Alk translocations in-vivo, leading to IL-3-independent cell growth. To verify efficient recombination, we analyzed the expression of the Npm-Alk fusion protein in the recombined cells and could also show the t(11;17) in the IL-3 independent Ba/F3 cells. Subsequent functional testing of these cells using an Alk-inhibitor showed exquisite responsiveness towards Crizotinib, demonstrating strong dependence on the newly generated Alk fusion oncoprotein. Furthermore, a comparison of the gene expression pattern between Ba/F3 cells overexpressing the Npm-Alk cDNA with Ba/F3 cells transformed by CRISPR-mediated Npm-Alk translocation indicated that, while broadly overlapping, a set of pathways including the unfolded protein response pathway was increased in the Npm-Alk overexpression model, suggesting increased reactive changes induced by exogenous overexpression of Npm-Alk. Furthermore, we observed clustered expression changes in genes located in chromosomal regions close to the breakpoint in the new CRISPR-based model, indicating positional effects on gene expression mediated by the translocation event, which are not part of the older models. Thus, CRISPR-mediated recombination provides a novel and more faithful approach to model oncogenic translocations, which may lead to an improved understanding of the molecular pathogenesis of ALCL and enable more accurate therapeutic models of malignancies driven by oncogenic fusion proteins.

Abstract: Toxic Oil Syndrome (TOS) was a major food-borne epidemic in Spain in May 1981, caused by the ingestion of rapeseed oil adulterated with aniline. While somatic sequelae have been widely documented, little is known about the long-term cognitive consequences more than four decades after exposure. This case-control study compared 50 individuals with clinically confirmed TOS to 50 age-, sex-, and education-matched healthy controls. Participants completed a standardized neuropsychological assessment and validated questionnaires for fatigue, anxiety, depression, and health-related quality of life. Multivariate regression models, adjusted for demographic and vascular risk factors, showed that TOS patients had significantly poorer performance in attention, executive function, processing speed, and global cognition. However, when mood symptoms, fatigue, and central nervous system-acting medication use were included in the models, these group differences were no longer significant. Structural equation modeling demonstrated that affective symptoms—particularly fatigue—mediated a substantial portion of the association between TOS and cognitive function. The cognitive profile observed resembles that of disorders with subcortical involvement and disrupted neural connectivity, such as multiple sclerosis and vascular cognitive impairment. While postmortem studies have not revealed overt white matter lesions in early TOS cases, the observed patterns may reflect long-term alterations in neural networks, potentially involving both white and gray matter substrates. These findings underscore the importance of accounting for mood and fatigue symptoms in the cognitive evaluation of TOS survivors and raise questions about the diffuse and possibly persistent neurobiological impact of the original toxic exposure.

Abstract: Background/Objectives: Idiopathic normal-pressure hydrocephalus (iNPH) is a potentially reversible neurological disorder characterized by gait disturbance, cognitive impairment, and urinary incontinence. Its pathophysiology involves impaired cerebrospinal fluid (CSF) absorption, and recent research has highlighted the role of the glymphatic and meningeal lymphatic systems in this process. However, the factors that trigger the clinical manifestations of iNPH in subclinical cases remain poorly understood. Case Presentation: Herein, we report two rare cases of iNPH in which clinical symptoms only became apparent following systemic infections. An 82-year-old man presented with transient neurological deficits during a course of sepsis caused by Klebsiella pneumoniae. Neuroimaging revealed periventricular changes and mild ventricular enlargement. Shunting and a tap test led to significant improvements to both his gait and cognition. An 80-year-old man with a history of progressive gait disturbance and cognitive decline developed worsening urinary incontinence and acute cerebral infarction caused by Staphylococcus haemolyticus bacteremia. Magnetic resonance imaging revealed a ventriculomegaly with features of disproportionally enlarged subarachnoid space hydrocephalus and a corona radiata infarct. Clinical improvement was achieved after a ventriculoperitoneal shunt was placed. Conclusions: Our two present cases suggest that systemic inflammatory states may act as catalysts for the manifestation of iNPH in patients with predisposing cerebral ischemia or subclinical abnormalities in CSF flow, highlighting the need for higher clinical awareness of iNPH in older patients who present with neurological deterioration during systemic infections. Early diagnosis and timely shunting after appropriate infection control may facilitate significant functional recovery in such patients.

Abstract: Keywords: COPD, primary care, audit, disease management.

Abstract: Ischemia/reperfusion (I/R) damage remains a major problem in surgery, primarily based on high oxidative stress generated during the reperfusion process. Mitochondria are significantly affected, their metabolic and energetic processes are impaired and the redox system is out of balance. Regulation and restoration of the redox balance by oxidative preconditioning with ozone is being investigated worldwide in cell and animal models. Selected preclinical trials and their results, with a focus on cardiological and neuronal I/R damage, are presented and discussed. We regularly find an upregulation of antioxidants, demonstrated in SOD (superoxide dismutase) and GSH (glutathione, reduced form, and a decrease in oxidative stress as a result, shown here using the typical stress parameters MDA (malondialdehyde) and TBARS (thiobarbituric acid reactive substances). Mitochondrial biogenesis, comparable to moderate physical activity, is induced by ozone oxidative preconditioning in an I/R model in rats and reviewed in this paper.

Abstract: Introduction: Hypotension following epidural labor analgesia (ELA) is its most common complication, affecting approximately 20% of patients and posing risks to both maternal and fetal health. As digital tools and predictive analytics increasingly shape perioperative and obstetric anesthesia practices, real-world implementation data are needed to guide their integration into clinical care. Current monitoring practices rely on intermittent non-invasive blood pressure (NIBP) measurements, which may delay recognition and treatment of hypotension. The Hypotension Prediction Index (HPI) algorithm uses continuous arterial waveform monitoring to predict hypotension for potentially earlier intervention. This clinical trial evaluated the feasibility, acceptability, and efficacy of continuous HPI-guided treatment in reducing time-to-treatment for ELA-associated hypotension and improving maternal hemodynamics. Methods: This was a prospective randomized controlled trial design involving healthy pregnant individuals receiving ELA. Participants were randomized into two groups: Group CM (conventional monitoring with NIBP) and Group HPI (continuous noninvasive blood pressure monitoring). In Group HPI, hypotension treatment was guided by HPI output; in Group CM, treatment was based on NIBP readings. Feasibility, appropriateness, and acceptability outcomes were assessed among subjects and their bedside nurse using the Acceptability of Intervention Measure (AIM), Intervention Appropriateness Measure (IAM), and Feasibility of Intervention Measure (FIM) instruments. The primary efficacy outcome was time-to-treatment of hypotension, defined as the duration between onset of hypotension and administration of a vasopressor or fluid therapy. This outcome was chosen to evaluate the clinical responsiveness enabled by HPI monitoring. Hypotension defined as a mean arterial pressure (MAP) < 65 mmHg for more than 1 minute in Group CM and an HPI threshold < 75 for more than 1 minute in group HPI. Secondary outcomes included total time in hypotension, vasopressor doses, and hemodynamic parameters. Results: There were 30 patients (Group HPI n=16; Group CM n=14) included in the final analysis. Subjects and clinicians alike rated the acceptability, appropriateness, and feasibility of the continuous monitoring device highly. The cumulative probability of time-to-treatment of hypotension was lower by 75 minutes after ELA initiation in Group HPI (65%) than Group CM (71%), although this difference was not statistically significant (log-rank P = 0.66). Mixed models indicated trends that Group HPI had higher cardiac output (β=0.58, 95% Confidence Interval -0.18 to 1.34, P=0.13) and lower systemic vascular resistance (β= -97.22, 95% Confidence Interval -200.84 to 6.40, P=0.07) throughout the monitoring period. No differences were found in total vasopressor use or intravenous fluid administration. Conclusion: Continuous monitoring and precision hypotension treatment is feasible, appropriate, and acceptable to both patients and clinicians in a labor and delivery setting. HPI-guided treatment was associated with hemodynamic trends that warrant further investigation.

Abstract: Background/Objectives: To develop a nomogram for predicting tumor aggressiveness and the presence of lymphovascular space involvement (LVSI) in patients with endo-metrial cancer (EC), using preoperative MRI and pathology-laboratory data. Methods: This IRB-approved, retrospective, multicenter study included 245 patients with histologically confirmed EC who underwent preoperative MRI and surgery at participating institutions between January 2020 and December 2024. Tumor type and grade, both from preoperative biopsy and surgical specimens, as well as preoperative CA125 and HE4 levels, were retrieved from institutional databases. Preoperative MRI was used to assess tumor morphology (polypoid vs. infiltrative), maximum diameter, presence and depth (< or >50%) of myometrial invasion, cervical stromal invasion (yes/no), and minimal tumor-to-serosa distance. The EC-to-uterus volume ratio was also calculated. Results: Among the 245 patients, 27% demonstrated substantial LVSI, and 35% were classified as aggressive on final histopathology. Multivariate analysis identified inde-pendent MRI predictors of LVSI, including cervical stromal invasion (OR = 9.06; p = 0.0002), tumor infiltration depth (OR = 2.09; p = 0.0391), and minimal tumor-to-serosa distance (OR = 0.81; p = 0.0028). The LVSI prediction model yielded an AUC of 0.834, with an overall accuracy of 78.4%, specificity of 92.2%, and sensitivity of 43.1%. For tumor aggressiveness prediction, significant predictors included biopsy grade (OR = 8.92; p < 0.0001), histological subtype (OR = 12.02; p = 0.0021), and MRI-detected serosal involvement (OR = 14.39; p = 0.0268). This model achieved an AUC of 0.932, with an accuracy of 87.0%, sensitivity of 79.8%, and specificity of 91.2%. Both models showed excellent calibration (Hosmer-Lemeshow p > 0.86). Conclusions: The integration of MRI-derived morphological and quantitative features with clinical and histopathological data allows for effective preoperative risk stratifica-tion in endometrial cancer. The two nomograms developed for predicting LVSI and tumor aggressiveness demonstrated high diagnostic performance and may support in-dividualized surgical planning and decision-making regarding adjuvant therapy. These models are practical, reproducible, and easily applicable in standard clinical settings without the need for radiomics software, representing a step toward more personalized gynecologic oncology.

Abstract: Colorectal cancer (CRC) with liver metastases (LM) and peritoneal metastases (PM) presents a formidable challenge, with poor prognosis despite advances in systemic chemotherapy and combined surgical approaches like cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Median overall survival (OS) for unresactable cases ranges from 12–24 months with mod- ern regimens (e.g., FOLFOX/FOLFIRI + targeted therapies), yet conversion to resectable disease remains limited by disease extent and treatment toxicity. This paper proposes that medicinal mush- room extracts, particularly polysaccharopeptides (e.g., PSK and PSP) from Trametes versicolor and bioactive compounds from species like Ganoderma lucidum, could enhance conversion therapy out- comes in CRC with LM and PM. Evidence from preclinical and clinical studies demonstrates that these extracts exert anticancer effects through multiple mechanisms, including suppression of mul- tidrug resistance, immune checkpoint blockade (e.g., PD-1/PD-L1), regulation of oncogenic signaling pathways (e.g., PI3K/AKT, MAPK, NF-κB), and robust immunomodulation. Clinical trials, including meta-analyses of over 8,000 patients, report improved survival and tolerability when combined with chemotherapy, primarily in postoperative settings. Our own meta-analysis involving a total of 2397 patients finds a 10% relative increase in the probability of survival at 5 years compared to the ref- erence group, with a survival risk ratio (RR) of 1.10 (95% CI: 1.04–1.15). The author hypothesizes that integrating these extracts into preoperative regimens could enhance the efficacy of chemother- apy, increase surgical eligibility (e.g., R0 resection rates), and mitigate toxicity, potentially extending OS beyond current benchmarks (e.g., 26–48 months with CRS-HIPEC). While direct evidence in un- resectable CRC with dual metastases is lacking, the biological plausibility and safety profile of mush- room extracts warrant prospective trials to validate their role in conversion therapy.

Abstract: Background Evidence shows bacterial lysates may participate in the immune response against respiratory infections. However, few studies have been conducted on dendritic cells, and, to our knowledge, none on human dendritic cells, and few have analyzed certain TLRs and cytokines. Materials and Methods Monocytes were obtained from the buffy coat and subsequently differentiated into dendritic cells (moDCs). The protein of commercial bacterial lysate Pulmonarom® was lyophilized and quantified. Ultrastructural changes induced by Pulmonarom® were evaluated in moDC by electron microscopy, and the expression of TLRs and some cytokines in these cells was evaluated by flow cytometry. Results Pulmonarom®-stimulated moDCs showed increased numbers of dendrites and the presence of lysosomes; they also showed increased expression of MHC-II and TLRs 2, 3, 6, and 7, IL-4, IL-6, IL-8, and MCP-1. Major conclusions The effects of Pulmonarom® on moDC correlate with an increased capacity to mobilize to lymph nodes and present antigens, initiating an effective adaptive immune response. Lysosomal activity and maturation of moDC, increased expression of TLR2, TLR3, TLR6, and TLR7 receptors, and increased production of the cytokines IL-8, MCP-1, IL-6, and IL-4, indicate a training process in moDC after their activation with Pulmonarom® bacterial lysate. This suggests that Pulmonarom® could enhance responses against viruses and bacteria by activating moDC. To our knowledge, this is the first study to address the effect of Pulmonarom® on one of the most important cells orchestrating the innate and acquired immune responses.