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Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer (BC) with limited treatment options. Paclitaxel (PTX) is commonly used, but its effectiveness is hampered by resistance and metastasis. The c-Met receptor, which is often upregulated in TNBC, promotes tumor progression via the HGF/c-Met axis and downstream PI3K/AKT and MAPK pathways. This study explored whether Capmatinib (CAP), a selective c-Met inhibitor, can enhance PTX efficacy in TNBC. MDA-MB-231 and 4T1 TNBC cell lines were treated with PTX and CAP, alone and in combination. Cytotoxicity, apoptosis, and cell cycle effects were assessed via MTT assays and flow cytometry. Cell migration was evaluated via scratch assays. The expression of epithelial-mesenchymal transition (EMT) markers (E-cadherin, vimentin, and Snail) was measured via real-time PCR. In vivo studies in BALB/c mice have evaluated hematological parameters, poor prognostic gene expression (BCL11, FOXC1, FOXM1), histopathology, and survival. In MDA-MB-231 cells, combination therapy increased PTX cytotoxicity, induced G2/M arrest, increased apoptosis, and suppressed migration. Co-treatment upregulated E-cadherin and downregulated vimentin and Snail. A weak synergistic effect was observed in 4T1 cells. In vivo, co-treatment improved hematological indices, reduced the expression of genes related to poor prognosis, inhibited angiogenesis and necrosis, increased lymphocyte infiltration, and prolonged survival. CAP enhances the antitumor activity of PTX in TNBC by targeting c-Met-mediated pathways. This combination therapy shows potential to overcome resistance and improve treatment outcomes in TNBC.

Lead (Pb(ii)) exposure poses significant health risks to various organ systems, including the hematological, renal, neurological, and cardiovascular systems. In this study, nano-hydroxyapatite (nano-HAp) was prepared via an ultrasonication-assisted hydrothermal method to remove Pb(ii) from an aqueous solution. The nano-HAp adsorbent was characterized using X-ray diffraction (XRD), Fourier transform infrared (FTIR) spectroscopy, scanning electron microscopy (SEM), Brunauer-Emmett-Teller (BET) surface area, and point of zero charge (pHpzc) analyses. The effects of various factors, including pH (2-8), initial Pb(ii) concentration (40-200 mg L-1), adsorbent dose (0.01-0.07 g L-1), and contact time (30-130 min), were investigated, with the residual Pb(ii) concentrations measured via atomic absorption spectroscopy (AAS). The highest removal efficiency of 99.84% was achieved at an optimum pH of 5, an initial Pb(ii) concentration of 40 mg L-1, an adsorbent dose of 0.03 g L-1, and a contact time of 110 min. Based on the coefficients of determination (R 2), the pseudo-second-order kinetic (R 2 = 0.9912) and Langmuir isotherm (R 2 = 0.9993) models best described the adsorption process. The maximum monolayer adsorption capacity was determined to be 133.33 mg g-1. Thermodynamic analysis confirmed that the process was spontaneous and endothermic, as indicated by positive ΔH and negative ΔG values. Furthermore, reusability studies demonestrated that the nano-HAp adsorbent maintained a removal efficiency above 86% after five successive cycles. Therefore, the prepared nano-HAp adsorbent represents a promising, eco-friendly adsorbent for Pb(ii) removal.

Sufficient safety data on juvenile development is not available for Xiao'er Xiexieting Keli (XXTK), a Chinese herbal formula for pediatric diarrhea. Considering the challenges associated with clinical trials of XXTK, this study was aimed at evaluating its toxicity in juvenile rats to obtain a basis for assessing its safety and dosage in children. In acute toxicity study (Study 1), postnatal day (PND) 24 rats were orally administered 253.13 g/kg XXTK and observed over 14 days. In subacute toxicity study (Study 2), PND21 rats were administered 1.74, 8.71, or 32.66 g/kg XXTK daily for six consecutive weeks and allowed to recover for 4 weeks. Clinical signs, body weight, food intake, and timing of vaginal opening and preputial separation were recorded during the dosing period. Hematological, serum biochemical, and histopathological examinations, Irwin's test, and assessment of growth hormone levels, skeletal development, and immune-related indicators were performed mid-administration, and at culmination of dosing and recovery. Urinalysis, ophthalmological assessment, and Morris water maze test were conducted at the end of dosing and recovery periods. No deaths or significant findings occurred in Study 1; maximum tolerated dose was 253.13 g/kg. In Study 2, all changes were reversible, mild, and without toxicological significance. The no-observed-adverse-effect level was 32.66 g/kg/day. XXTK demonstrated a favorable toxicological safety profile in juvenile rats, supporting its potential for extended clinical use in children. Further evaluation of child development-related indicators and validation in pediatric clinical cohorts are recommended.

δβ-Thalassemia and hereditary persistence of fetal hemoglobin (HPFH) are uncommon hemoglobinopathies. This study aimed to define the molecular epidemiological features of δβ-thalassemia and HPFH in the childbearing-age population of Quanzhou, China, to inform precise prevention strategies and genetic counseling. From a free pre-pregnancy thalassemia screening cohort (n = 19,154), 92 individuals with elevated HbF (≥2%) and 11 control groups with normal HbF (≤2%) were included. DNA analysis of common deletion-type δβ-thalassemia/HPFH mutations (SEA-HPFH, Chinese type Gγ+(Aγδβ)0, Taiwan type β0) and non-deletion-type HPFH mutations was performed by gap-PCR, PCR-reverse dot hybridization, and Sanger sequencing. The correlation between hematological parameters and genotypes was also analyzed. The results suggest that the detection rate of deletion-type HPFH/δβ-thalassemia was 0.063% (12/19154), mainly SEA-HPFH and Chinese Gγ+(Aγδβ)0. The detection rate of γ-globin gene mutations and non-deletion-type HPFH was 0.329% (63/19154). 9 different γ-globin promoter mutations were identified. The most frequently detected variants were HBG2:c.-211C>T, HBG1:c.-29G>A, and HBG1:c.-272_-275dupAGCA. However, based on functional relevance, three key variants were highlighted: HBG1:c.-211C>T, HBG1:c.-249C>T, and the novel HBG2:c.-253_-254dup. The remaining variants (HBG1:c.-29G>A, HBG1:c.-272_-275dupAGCA, HBG1:c.-404A>G, HBG1:c.-417G>C, HBG1:c.-420C>A) are described as benign polymorphisms or variants in strong linkage disequilibrium with HBG2:c.-211C>T. Deletion-type δβ-thalassemia/HPFH is rare in Quanzhou. SEA-HPFH and Chinese Gγ+(Aγδβ)0 are more common. Non-deletion-type HPFH, especially the double heterozygous state HBG1:c.-29G>A/HBG2:c.-211C>T, is significantly more common. These findings reveal the unique molecular epidemiological characteristics of δβ-thalassemia and HPFH in this region, providing important data for genetic counseling and prenatal diagnosis.

6-Mercaptopurine (6-MP) is a potent chemotherapeutic and immunosuppressive agent; however, its oral administration is limited by poor bioavailability and dose-dependent hepatotoxicity. This study aimed to develop and optimize a colon-targeted, pH-responsive delivery system for 6-MP using Eudragit S100-coated thiolated chitosan/casein microbeads (Eu-S100@TCh/CS) to enhance site-specific release and minimize systemic exposure. The microbeads were fabricated via emulsion cross-linking followed by solvent evaporation and optimized using a central composite design. Physicochemical characterization (FTIR spectroscopy, DSC/TGA, PXRD, and SEM) confirmed efficient drug incorporation in a molecularly dispersed state, thermal stability, and a uniform spherical morphology (541-672 µm). Swelling and dissolution studies demonstrated a clear pH-dependent behavior, with minimal swelling and negligible drug release at pH 1.2 and 6.8, and enhanced release (84.5% at 24 h) at colonic pH 7.4, corresponding to the dissolution of the Eudragit S100 coating and hydration of the polymeric core. Drug-release kinetics indicated Higuchi diffusion for uncoated beads (R 2 = 0.9852; n = 0.624) and anomalous (non-Fickian) transport for the coated beads (R 2 = 0.9994; n = 0.741), governed by combined diffusion and polymer relaxation mechanisms. Acute oral toxicity studies in rats revealed no significant alterations in the biochemical, hematological, or histopathological parameters, confirming systemic safety. In vitro cytotoxicity studies (MTT assay) showed enhanced antiproliferative activity of the 6-MP-loaded microbeads against HCT-116 cells compared to the free drug, attributed to improved solubility and sustained drug availability following release rather than whole-particle internalization. Blank microbeads exhibited high cell viability, confirming carrier biocompatibility. Overall, the Eu-S100@TCh/CS microbead system represents a rationally designed colon-targeted delivery platform with potential to improve local therapeutic efficacy and reduce systemic toxicity. Further studies are warranted to evaluate selectivity using normal colonic cell lines.

The role of anti-neutrophil cytoplasmic antibodies (ANCA) in systemic lupus erythematosus (SLE) remains unclear. ANCA positivity has been linked to more severe disease and possible overlap with ANCA-associated vasculitis, but available data are inconsistent. We conducted a retrospective single-center study of SLE patients treated at the University Hospital in Kraków (2012-2022). Patients fulfilled the 2019 EULAR/ACR criteria. ANCA positivity (anti-MPO or anti-PR3) was confirmed by ELISA. Clinical features, laboratory findings, treatment, and outcomes were analyzed. Among 1039 SLE patients, 18 (1.73%) were ANCA-positive (anti-MPO, 72.22%; anti-PR3, 27.78%). Most ANCA-positive SLE patients were female (88.89%), with a median age at disease onset of 35.5 years. The most common manifestations in ANCA-positive cases were hematological abnormalities (100%), constitutional symptoms (88.89%), and joint involvement (88.89%). Renal involvement was observed in 72.22% (n = 13) of ANCA-positive SLE patients; however, lupus nephritis was confirmed by kidney biopsy in only seven cases. Vasculitis was rare (5.56%). Anti-dsDNA (61.11%) and anti-SSA (50%) were the most frequent autoantibodies. No significant differences were found between anti-MPO and anti-PR3 subgroups. Most ANCA-positive patients received glucocorticoids (94.44%), cyclophosphamide (61.11%), and antimalarials (61.11%). No statistically significant differences were observed between the ANCA-positive and ANCA-negative groups (p > 0.05 for all parameters). ANCA positivity in SLE is rare and predominantly associated with anti-MPO antibodies. It is linked to frequent renal involvement but infrequent vasculitis. No differences were observed between ANCA subtypes, suggesting no distinct clinical phenotype. Key Points • ANCA positivity was rare in this systemic lupus erythematosus cohort (1.73%) and was predominantly associated with anti-MPO antibodies rather than anti-PR3 antibodies. • No significant differences in demographic characteristics, clinical manifestations, comorbidities, or autoantibody profiles were observed between ANCA-positive and ANCA-negative patients. Similarly, no significant differences were identified between the anti-PR3-positive and anti-MPO-positive groups. • ANCA-positive SLE was commonly associated with the need for intensive immunosuppressive treatment, highlighting its potential relevance as a marker of severe disease course.

δ-Aminolevulinic acid dehydratase deficient porphyria (ADP) is an exceedingly rare form of acute porphyria, with only fifteen published cases worldwide. This disorder has historically been considered an hepatic porphyria, as it was thought the overproduction of the toxic metabolite δ-Aminolevulinic acid (ALA) solely occurred in the liver. This case report demonstrates that treatments focused on reducing the hepatic ALA production had limited effect on this patient's symptoms. An earlier published hypothesis that patients with ADP also produce substantial levels of bone marrow derived ALA, was retested. We describe a Dutch patient in his early 60s, who has suffered from ADP since birth. His medical history mentions acute neurovisceral attacks, contractures of hand and feet, severe polyneuropathy, developmental delay, and renal insufficiency (eGFR 30-40 ml/min). For over a decade he was treated with weekly heme prophylaxis to reduce the frequency of neurovisceral attacks. Despite continuation, his chronic neurological symptoms aggravated and, in an attempt to suppress erythroid ALA production, weekly erythrocyte transfusions combined with hydroxyurea was started. The patient's symptoms improved and stabilized during this treatment. Oral chelation therapy was started to limit secondary iron overload caused by both heme and erythrocyte infusions. Years later we could trial givosiran, an ALAS1-siRNA to suppress the hepatic ALA production. After starting givosiran the heme infusions could be stopped without an increase in symptoms, but discontinuation of erythrocyte transfusions led to new onset neurovisceral attacks. His current schedule consists of continued givosiran and erythrocyte transfusions. This case report illustrates that ADP can be treated successfully with both hepatic and erythroid suppression. It also illustrates the challenges of treating a patient with a rare, complex and poorly understood disease, and the difficulty to balance the complications, side effects and the benefits of treatments.

Acquisition of laparoscopic psychomotor skills is essential for safe minimally invasive surgery but is associated with a steep learning curve. Simulation-based training improves proficiency; however, additional strategies to accelerate skill acquisition are sought. Transcranial direct current stimulation (tDCS) has been shown to facilitate motor learning, but its effect on laparoscopic training remains uncertain. In this prospective, sham-controlled trial, 33 medical students without prior laparoscopic experience were allocated to active tDCS (n&#x2009;=&#x2009;16) or sham stimulation (n&#x2009;=&#x2009;17) during laparoscopic simulation training. Stimulation was delivered using the Halo Sport system (1.4&#xa0;mA, 20&#xa0;min) over bilateral primary motor cortices. Baseline psychomotor abilities were assessed using the Vienna Test System (Motor Performance Series, 2HAND, and 3D spatial ability tests). Laparoscopic skills were evaluated using the Laparoscopic Skills Testing and Training (LASTT) model, including camera navigation (CN), hand-eye coordination (HE), and bimanual coordination (Bi), on days 1, 3, 5, and 7. Group differences in final performance (day 7) were analyzed using linear models and ANCOVA, adjusting for baseline performance and prespecified covariates. Both groups demonstrated significant improvement across all laparoscopic tasks over time (all p&#x2009;<&#x2009;0.001). Active tDCS was independently associated with higher final bimanual coordination performance compared with sham stimulation (adjusted ANCOVA: F (1,13)&#x2009;=&#x2009;14.92, p&#x2009;=&#x2009;0.002). No independent effect of tDCS was observed for camera navigation (p&#x2009;=&#x2009;0.581) or hand-eye coordination (p&#x2009;=&#x2009;0.439). Baseline visuospatial ability (3D test) was an independent predictor of final performance in camera navigation and hand-eye coordination (both p&#x2009;<&#x2009;0.01). Positive correlations were found between 3D scores and CN (r&#x2009;=&#x2009;0.397) and HE (r&#x2009;=&#x2009;0.390), as well as between 2HAND and HE (r&#x2009;=&#x2009;0.341). Bihemispheric tDCS applied during laparoscopic simulation selectively enhanced acquisition of bimanual coordination, while performance in camera navigation and hand-eye coordination was primarily determined by baseline visuospatial ability. These findings support a task-specific role for neuromodulation as an adjunct to simulation-based laparoscopic training and highlight the importance of visuospatial profiling for personalized training strategies.

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Even with new drugs available, how best to treat unfit adults with acute myeloid leukemia (AML) remains uncertain. In a previous trial in such patients, we found high-dose cytarabine-based therapy with CLAG-M yielded higher response rates but no more toxicity than lower-intensity therapy with dose-attenuated CLAG-M. Here, we conducted a single-institution phase 2 trial (NCT04195945) randomizing 60 adults with untreated AML and medical unfitness with Treatment-Related Mortality (TRM) score of &#x2265;13.1 (68% with ECOG performance status 3-4) 1:1 to standard-dose CPX-351 or CLAG-M. Primary endpoint was 3-month overall survival (OS); key secondary endpoints included overall response rate, rate of measurable residual disease (MRD) negativity, toxicity/mortality rates, and survival estimates. Only CLAG-M met the primary endpoint of &#x2265;63% 3-month OS (70% vs. 60%; P&#x2009;=&#x2009;0.41), and CLAG-M therapy was associated with a non-significantly higher complete remission (CR) plus CR with incomplete hematologic recovery rate (73% vs. 47%, P&#x2009;=&#x2009;0.064). Nonetheless, there was no statistically significant difference in relapse-free survival following CLAG-M vs. CPX-351 (median 37.6 vs. 19.9 months; P&#x2009;=&#x2009;0.80) or OS (median 10.5 vs. 5.8 months; P&#x2009;=&#x2009;0.76). In patients with proliferative disease, however, OS following CLAG-M was longer (median 18.5 vs. 3.9 months; P&#x2009;=&#x2009;0.02) suggesting a role for intensive therapy in this patient subset.

of the study is to evaluate the efficacy, safety, and immunogenicity of divozilimab (DIV), anti-CD20 monoclonal antibody, in patients with systemic sclerosis (SS). . Patients with SS according to ACR/EULAR (American College of Rheumatology/European Alliance of Associations for Rheumatology) 2013 criteria with modified Rodnan skin score (mRSS) &#x2265;10 and &#x2264;20 and forced vital capacity (FVC) &#x2265;40% from the due took part in the study. Infusions of DIV 250 mg were administered on weeks 0 and 2, and DIV 500 mg on week 24 with the subsequent use in open mode, starting from week 48. This publication presents data obtained for 48 weeks of trial (before the DIV infusion at week 48). Primary endpoint was the change in the mRSS from baseline to week 48. The dynamic of FVC was estimated as the secondary endpoint. The safety evaluation included the frequency and profile of adverse events and adverse reactions (ARs). Immunogenicity was assessed by detection of binding and neutralizing anti-drug antibodies on weeks 2, 24, and 48. : The patients (151) were randomized into two groups: DIV (n = 76) and placebo (n = 75). The most were female; the median duration of the disease was about 3-4 years. The initial value of the mRSS was 14 and 13 points in DIV and Placebo groups, respectively. The change of mRSS from baseline to week 48 was -5.8 &#xb1; 1.1 points in DIV group and -2.7 &#xb1; 1.0 points in placebo group (adjusted mean difference (AMD) with 95% confidence interval -3.1 (-4.5; -1.7); p < 0.0001). The lung function was stable in patients treated with DIV. A comparable safety profile of DIV and placebo was demonstrated. The most frequent ARs were infusion reactions and a decrease in the number of lymphocytes. There were no severe and serious ARs in DIV group. All infusion reactions were mild and moderate. 5.3% (4/76) patients in DIV group had binding antibodies without neutralizing activity. : Divozilimab has demonstrated a significant decrease in severity of skin fibrosis, a positive effect on the respiratory function, and a favorable safety profile, which allows it to be considered as a promising therapeutic option for SS.

Squamous cell carcinoma antigen (SCC-Ag) and carcinoembryonic antigen (CEA) are routinely monitored after definitive chemoradiotherapy (dCRT) for esophageal squamous cell carcinoma (ESCC) in Japan, but their clinical significance remains unclear. We analyzed data from patients with resectable ESCC treated with dCRT in the JCOG0502 and JCOG0909 trials, who underwent intensive protocolized surveillance with computed tomography (CT), esophagogastroduodenoscopy (EGD), SCC-Ag, and CEA. Tumor marker positivity was defined as exceeding the cut-off value at least once, at two consecutive measurements, or at three consecutive measurements during follow-up. Sensitivity and specificity were calculated for SCC-Ag and CEA at 0.1-ng/mL increments to determine whether any cut-off met the predefined performance criteria (sensitivity &#x2265;60% and specificity &#x2265;70%). This study included 239 patients (stage I/II/III&#x2009;=&#x2009;147/58/34 [UICC 6th edition]), among whom 38% (91/239) experienced disease progression or recurrence. The median baseline SCC-Ag and CEA levels were 1.0&#xa0;ng/mL (interquartile range [IQR], 0.8-1.5) and 2.3&#xa0;ng/mL (IQR, 1.6-3.6), respectively, with a median of 16 measurements each (IQR, 8-19 for SCC-Ag; 8-20 for CEA). The highest specificities with sensitivity &#x2265;60% were 19.6% for SCC-Ag (cut-off, 1.5&#xa0;ng/mL) and 20.3% for CEA (cut-off, 2.2&#xa0;ng/mL), but neither met the predefined criteria. In this pooled cohort of patients with resectable ESCC who underwent dCRT and intensive protocolized CT and EGD surveillance, routine SCC-Ag and CEA monitoring showed limited incremental diagnostic value. The relevance of these findings to higher-risk cohorts and less intensive surveillance settings warrants further study.

Gastrointestinal bleeding (GIB) is a major cause of morbidity in von Willebrand disease (vWD), most commonly resulting from angiodysplasia. Current obscure gastrointestinal bleeding (OGIB) algorithms are primarily anatomy-based and often overlook underlying hemostatic disorders, delaying diagnosis and promoting recurrent bleeding. This review summarizes current evidence on the molecular basis, diagnosis, and management of vWD-associated GIB and proposes a mechanism-oriented diagnostic framework. A comprehensive narrative review of experimental, translational, and clinical studies was conducted, focusing on inherited vWD, acquired von Willebrand syndrome (AvWS), gastrointestinal angiodysplasia, endothelial biology, and diagnostic and therapeutic strategies. Deficiency or dysfunction of high-molecular-weight von Willebrand factor (vWF) multimers promotes angiodysplasia by disrupting Weibel-Palade body homeostasis, enhancing Ang-2/Tie2 and VEGF signaling, impairing integrin &#x3b1;v&#x3b2;3 function, and fostering pro-inflammatory endothelial activation. Genetic and epigenetic modifiers, including FLI1, STXBP5, ABO blood group, and miR-24, further influence vascular susceptibility. Based on these mechanisms, we propose a four-stage diagnostic framework integrating bleeding assessment, platelet function screening, and targeted vWF testing with conventional endoscopic evaluation to facilitate earlier recognition of vWD/AvWS in patients with recurrent or obscure GIB. This strategy supports mechanism-based treatment combining hemostatic replacement therapies with selected anti-angiogenic approaches. vWD-associated GIB should be regarded as a systemic vascular-hemostatic disorder rather than an isolated structural gastrointestinal disease. Integrating hemostatic evaluation into OGIB pathways may improve diagnostic accuracy, reduce unnecessary procedures, and enable personalized management of patients with recurrent bleeding.

Epstein-Barr virus (EBV) infects more than 90% of the population and establishes a lifelong persistence in memory B cells, passing through several latency stages (I-III). In immunocompromised patients, EBV infections and reactivations can lead to severe complications, such as post-transplant lymphoproliferative disorder (PTLD), a malignant B cell lymphoproliferation. The EBV latent membrane protein 2A (LMP2A) induces activation and proliferation of infected B cells and is expressed in latency stages II/III, that are associated with several EBV malignancies. Here, T cell receptor (TCR)-engineered T cells based on a TCR recognizing the clinically relevant HLA-A&#x2217;02:01-restricted LMP2A-derived peptide CLGGLLTMV (A&#x2217;02_LMP2ACLG) and equipped with a TCR-inducible cassette for IL-18 release (iIL-18_LMP2A_TCR-T cells) aiming to prevent exhaustion and promote remodeling of the immunosuppressive tumor microenvironment (TME) were developed. The iIL-18_LMP2A_TCR-T cells exhibited improved cytotoxicity against HLA-A&#x2217;02:01+ EBV-infected B-lymphoblastoid cell lines (EBV+ B-LCLA&#x2217;02:01) serving as in vitro PTLD model, when compared to LMP2A_TCR-T cells without iIL-18. The superior functionality of iIL-18_LMP2A_TCR-T cells was further confirmed in multicellular tumor spheroid (MCTS) models, where they mediated sustained control of EBV+ B-LCLA&#x2217;02:01 growth, highlighting their potential as an effective therapeutic approach for the immune-mediated eradication of EBV-associated malignancies, including PTLD.

Cellular genomic DNA is continuously exposed to endogenous and exogenous factors that induce various forms of DNA damage. In mammalian cells, the daily burden of DNA damage may reach 104-105 lesions per cell. DNA damage that persists into the S phase can lead to mutations. When such mutations occur in oncogenes, tumor suppressor genes, or genes involved in cell proliferation, they may promote cellular transformation and carcinogenesis. Therefore, DNA damage repair plays a critical role in maintaining genomic stability and preventing cancer development. Assessment of DNA repair capacity is best achieved by measuring the functional activity of DNA repair systems. DNA damage repair pathways and their repair efficiencies are highly relevant to chemotherapeutic drug development, gene function validation, and cancer therapy. Accordingly, investigation of the repair efficiency of individual DNA damage repair pathways has important theoretical and practical significance. This review summarizes the major DNA damage repair pathways, methods used to assess repair efficiency, and the advantages and limitations of these approaches.

Two eosinophil subtypes, resident (rEos) and inflammatory (iEos), have been identified, first in mice and later in asthmatic patients. The effects of different biologics on these subpopulations remain unclear. This study evaluates the impact of mepolizumab, dupilumab and omalizumab on the proportion of rEos and iEos in asthmatic patients over 52 weeks. We conducted a prospective study with 1-year follow-up of 82 patients with severe asthma: 28 were not receiving biologic therapy, 24 were treated with mepolizumab, 20 with dupilumab and 10 with omalizumab. Clinical variables included Asthma Control Test, exacerbation history and lung function. Blood samples underwent flow cytometry to classify eosinophils into (Siglec-8+CD62Llo+CD11bhi) for iEos and (Siglec-8+CD62Lhi+CD11blo) for rEos. Interleukin (IL)-5 receptor expression and levels of free IL-5 and eotaxin I/II were also assessed. Mepolizumab significantly reduced eosinophil concentrations compared with other groups (p<0.001). Patients without biologics had a high iEos proportion (23.4&#xb1;13.7%), comparable with the omalizumab and dupilumab groups (31.3&#xb1;12.8% and 27.6&#xb1;10.1%). Mepolizumab-treated patients had markedly lower iEos proportions (2.4&#xb1;4.0%, p<0.001). Stratifying iEos by quartiles, there was a significant relation between the highest quartile and lower FEV1 % predicted (-15.6%, 95% CI 5.5-25.7) and a higher exacerbation rate (OR 2.24, 95% CI 1.02-4.91). After 1 year, iEos proportions correlated with higher systemic steroid use in mepolizumab and dupilumab groups. At 1-year follow-up, IL-5 levels were higher in omalizumab and dupilumab groups but lower in mepolizumab (p<0.01). Biological therapies differentially affect eosinophil subtypes, correlating with lung function and steroid use. Monitoring iEos and rEos may serve as a marker of asthma control.

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Subtotal petrosectomy (STP) is a radical otologic procedure aimed at complete eradication of diseased temporal bone air cells and creation of a closed, sterile cavity. While well established in adult otology, its role in pediatric patients remains insufficiently described. To analyze current indications, outcomes and complication rates of subtotal petrosectomy in a pediatric population, with particular emphasis in age - related patterns of indications. A retrospective review was conducted of 20 children (<18 years) who underwent STP between 2010 and 2024&#x202f;at two tertiary referral centers. Patients were analyzed according to age groups (&#x2264;6 years vs. >6 years) and etiology, categorized as congenital (including congenital malformations, CHARGE syndrome and congenital CSF leaks) or acquired (cholesteatoma, chronic otitis media, traumatic and oncological lesions). Major and minor complications were recorded and analyzed using non - parametric statistical methods. The cohort included 15 boys and 5 girls with a mean follow-up of 4.3&#x202f;&#xb1;&#x202f;1.2 years. Congenital indications predominated in children &#x2264;6 years, whereas acquired pathologies were significantly more common in older children (>6 years) (Fisher's exact test, p&#x202f;=&#x202f;0.018). Patients treated for congenital indications were significantly younger than those with acquired pathologies (p&#x202f;=&#x202f;0.0095). Major complications occurred in 2 of 20 patients (10%, 95% confidence interval 1,2-31,7%), including cholesteatoma recurrence requiring revision surgery and conversion to an open technique. Minor complications were observed in one patient (5%) and consisted of an abdominal hematoma). No cases of implant loss, permanent facial nerve palsy or wound dehiscence were observed. STP is a safe and effective procedure in selected pediatric patients, with low rates of major complications. Indications differ significantly by age, with congenital pathology predominating in younger children and acquired in older patients. In children, STP should be regarded not as salvage procedure but as a reconstructive strategy providing a stable anatomical foundation for long term hearing rehabilitation and disease control.

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