Search Results (22,338)

Background/Objectives: This study developed a macitentan (MAC)–tadalafil (TAD) dry powder inhalation preparation using suspension-based spray drying to enhance pulmonary delivery and reduce systemic exposure to oral combination therapy in patients with pulmonary arterial hypertension (PAH). Methods: MAC–TAD composite powders were prepared by physically mixing or spray-drying aqueous ethanol suspensions at various MAC:TAD ratios. The lead M2-T8 was co-spray-dried with 5, 25, or 50% (w/w) L-leucine. Results: Spray-dried formulations exhibited narrower and more uniform particle size distributions (Dv50 2–6 µm; Dv90~10 µm) and higher emitted dose values than the physical mixtures. In the M2-T8 spray-dried formulation, TAD exhibited an elevated fine particle dose (FPD) (3073.45 ± 1312.30 μg), demonstrating improved aerosolization relative to the physical mixture, even outperforming the TAD-higher M1-T9 formulation (2896.83 ± 531.38 μg), suggesting that favorable interparticle adhesive interactions were developed during co-drying. The incorporation of 25% L-leucine produced the greatest improvement in dispersibility, increasing the FPD by ~31% for MAC and 17% for TAD, whereas excessive L-leucine (50%) reduced the aerosol performance. Powder X-ray diffraction and differential scanning calorimetry confirmed the retention of the MAC and TAD crystallinities, with L-leucine remaining either amorphous or partially crystalline. Conclusions: Suspension-based spray drying yielded MAC–TAD composite formulations with improved uniformity and aerosol performance. The optimized 2:8 formulation containing 25% L-leucine demonstrated the most efficient pulmonary deposition, supporting its potential as an inhaled combination therapy for the treatment of PAH. Full article

Background: Hashimoto’s thyroiditis (HT) is the result of a complex interplay between genetic, environmental, and epigenetic factors. The role of cellular and humoral immunity in the pathogenesis of the disease is well-established. Inflammatory infiltration of T and B lymphocytes is a key feature identified on ultrasound examination. The lack of data on the effect of L-thyroxine (LT-4) doses on the level of anti-TPO and anti-TG antibodies in Hashimoto’s thyroiditis and the relationship with anthropometric measurements resulted in the desire to fill this niche. Methods: A total of 70 Caucasian patients diagnosed with Hashimoto’s thyroiditis within the past two years were examined. The participants were divided into three groups based on their L-thyroxine dosage (≤50, 50–100, >100 μg). Results: The results revealed no correlation between the dosage of L-thyroxine and anthropometric measurements (age, height, body weight, and body fat content). No correlation was identified between the levels of anti-TPO and anti-TG and the dose of L-thyroxine in patients with Hashimoto’s thyroiditis. Conclusions: The mechanism regulating the levels of anti-TPO and anti-TG appears to be associated with a more advanced thyroid inflammation and disease process. Long-term observation of patients would be advisable. We present evidence of no effect of hormone dose on antibody levels in Hashimoto’s thyroiditis. Regardless of disease severity, immune regulation remains outside the scope of hormonal regulation. Full article

Background/Objectives: The Prognostic Nutritional Index (PNI), which integrates serum albumin and lymphocyte count, reflects both nutritional and inflammatory status. However, its role in early renal function decline among patients with type 2 diabetes (T2D), particularly in relation to glycemic control, remains unclear. This study aimed to: (1) characterize the dose–response relationship between PNI and early renal function decline in type 2 diabetes using restricted cubic splines; (2) identify whether glycemic control (HbA1c) modifies the PNI–renal decline association; and (3) evaluate the clinical utility of combining PNI and HbA1c for risk stratification. Methods: We analyzed data from 1711 community-based participants with T2D who had preserved renal function at baseline. The PNI was calculated as serum albumin (g/L) + 5 × lymphocyte count (×10⁹/L). The primary outcome was a composite of rapid estimated glomerular filtration rate (eGFR) decline (>3 mL/min/1.73 m² per year) or incident chronic kidney disease (CKD) stage 3. Restricted cubic spline models, multivariable regression, and Johnson–Neyman analyses were used to examine non-linearity and effect modification by glycated hemoglobin (HbA1c). Results: A consistent inverse linear association was observed between PNI and the rate of eGFR decline (P for non-linearity > 0.05). Johnson–Neyman analysis further demonstrated that the protective association of PNI was statistically significant within an HbA1c range of 7.24% to 8.71%. Stratification by clinical cut-offs revealed a significant effect modification by glycemic status. The inverse linear association between PNI and renal risk was most pronounced under hyperglycemic stress, as evidenced by the markedly elevated incidence (50.0%) among individuals with both poor glycemic control (HbA1c ≥ 8%) and low PNI (<50). Conversely, under good glycemic control (HbA1c < 8%), this inverse association was substantially attenuated, with a lower incidence observed in the low-PNI subgroup (6.7%) than in the high-PNI subgroup (15.9%). These findings indicate that the protective role of PNI is conditional upon the glycemic milieu. Conclusions: The PNI demonstrates a stable linear association with early renal function decline in T2D, with its protective effect most pronounced at suboptimal HbA1c levels. Combining PNI and HbA1c effectively identifies a high-risk subgroup characterized by synergistic risk, underscoring the need for integrated nutritional and glycemic management. Full article

Background and Objectives: Patients with type 2 diabetes mellitus (T2DM) and ischemic stroke present with endothelial, vascular and left ventricular (LV) myocardial dysfunction. We investigated the effects of treatment with either glucagon-like peptide-1 receptor agonists (GLP-1RA) or sodium-glucose contrasporter-2 inhibitors (SGLT-2i) on endothelial glycocalyx, arterial stiffness, and LV myocardial strain in patients with metformin-treated T2DM and a prior ischemic stroke. Materials and Methods: A total of 54 consecutive patients with T2DM and ischemic stroke who attended a cardiometabolic outpatient clinic in Athens, Greece, and received either GLP-1RA (dulaglutide; n = 27) or SGLT-2i (empagliflozin; n = 27) were enrolled in the study. We measured the perfused boundary region (PBR) of the sublingual microvessels, a marker of glycocalyx thickness, as well as carotid-femoral pulse wave velocity (PWV) and LV global longitudinal strain (GLS), at baseline and at 4 and 12 months of treatment. Results: Twelve months after treatment, all patients had reduced glycosylated hemoglobin and body mass index (BMI) (p < 0.001). Patients treated with dulaglutide showed a greater reduction in BMI (−11.8% vs. −4.8%, p < 0.001) compared to those treated with empagliflozin. Compared to baseline, all patients had reduced PBR, PWV and GLS (p < 0.001) after 12 months of treatment. However, empagliflozin presented a greater decrease in PWV (−14% vs. −10.9%, p = 0.041), while dulaglutide resulted in a greater increase in GLS (14.7% vs. 8.3%, p = 0.024) compared to empagliflozin. In all patients, the reduction in PBR at 12 months was correlated with a decrease in PWV and with an increase in GLS (p < 0.05). Conclusions: Both dulaglutide and empagliflozin improve cardiovascular function in T2DM patients with ischemic stroke. Dulaglutide appears to be more effective in the improvement of LV myocardial strain, whereas empagliflozin is more effective in reducing arterial stiffness. Full article

Background and Objectives: Scalp nerve block (SNB) is hypothesized to attenuate the physiological response to skull pinning more effectively than local anesthetic (LA) infiltration. This study aimed to compare the two techniques using Bispectral index (BIS) as a primary surrogate measure of cortical arousal. Materials and Methods: In this prospective observational study, patients undergoing elective craniotomy received either bilateral SNB (Group S, n = 53) or LA infiltration (Group LA, n = 35) based on anesthesiologist preference. Depth of anesthesia was monitored via BIS. The primary outcome was the change in BIS after skull pin insertion. A ΔBIS > 20% from baseline triggered rescue medication (remifentanil/propofol). Secondary outcomes included hemodynamic parameters and rescue requirements. Results: There was a significant main effect of time on BIS values (p < 0.001), indicating that BIS values changed significantly across measurement points. Post-hoc examination of parameter estimates revealed that the Group LA showed significantly greater increases in BIS values compared to the Group S at T1 (p = 0.030) and T3 (p = 0.024). No significant between-group differences in BIS changes were observed at T5, T10, or T15 time points (p > 0.05). Hemodynamic responses (mean arterial pressure and heart rate) were also transiently but significantly higher in Group LA at these time points (p < 0.001). The most clinically notable finding was that significantly more patients in Group LA required rescue medication (p < 0.001), indicating a greater frequency of clinically significant physiological trespass. Conclusions: Compared to LA infiltration, SNB was associated with statistically significant reductions in immediate BIS and hemodynamic responses to skull pinning. The key potential clinical implication is the corresponding reduction in the need for rescue anesthetic intervention. These findings support SNB as a technique for enhancing physiological stability, though the direct impact on patient-centered outcomes requires further study. BIS may serve as a useful adjunctive indicator of the cortical response to noxious stimuli. Full article

Background: Triple-negative breast cancers (TNBCs) are among the most aggressive breast tumors, due not only to the absence of clinically functional biomarkers used in other molecular subtypes, but also their marked heterogeneity and pronounced migratory and invasive behavior. The search for new molecules of interest for risk prediction, diagnosis and therapy stems from the class of long non-coding RNAs (lncRNAs), which often display context-dependent (“dual”) functions and tissue specificity. Among them, lncRNA LINC01133 stands out for its dysregulation across cancer, although its molecular role in TNBC remains unclear. Methods: In the present study, we used the human TNBC cell line Hs578T to generate a cell panel comprising the parental line (Hs578T_wt), the control line (Hs578T_ctr), and the LINC01133 knockout line (Hs578T_ko). Subsequently, we performed bulk RNA-Seq to identify KO-associated Differentially Expressed Genes (DEGs) using ko_vs_ctr as the primary contrast. Functional interpretation was achieved by Over-Representation Analysis (ORA) using Gene Ontology. We then conducted a comparative patient-cohort analysis using TCGA-BRCA Basal-like/TNBC cases (TCGA/BRCA n = 1098; Basal-like/TNBC n = 199), classified with the AIMS algorithm, and evaluated concordance between KO-associated signatures and patient tumor expression patterns via trend-based analyses across the LINC01133 expression levels and associated genes. Results: A total of 265 KO-dominant DEGs were identified in Hs578T_ko, reflecting transcriptional changes consistent with tumor progression, with enrichment of pathways associated with LINC01133 knockout including cell adhesion, cell–cell interactions, epithelial–mesenchymal transition (EMT), and extracellular matrix (ECM) remodeling. The main DEGs included ITIH5, GLUL, CACNB2, PDX1, ASPN, PTGER3, MFAP4, PI15, EPHB6, and CPA3 with additional candidates, such as KAZN and the lncRNA gene SSC4D, which have been implicated in migration/invasion, ECM remodeling, or signaling across multiple tumor contexts. Translational analyses in TCGA-BRCA basal-like tumors suggested a descriptive association in which lower LINC01133 levels were accompanied by shifts in the expression trends of genes linked to ECM/EMT programs and modulation of genes related to cell adhesion and protease inhibition. Conclusions: These results suggest a transcriptional model in which LINC01133 is associated with TNBC-related gene expression programs in a concentration-dependent manner, with loss of LINC01133 being associated with a transcriptomic shift toward pro-migratory/ECM remodeling signatures. While functional validation is required to establish causality, these data support LINC01133 as a molecule of interest in breast cancer research. Full article

Dynamic contrast-enhancement (DCE) modality of MRI is typically considered secondary in prostate cancer (PCa) diagnostics, due to the common interpretation that its diagnostic power is lower than that of other modalities like T2-weighted (T2W) or diffusion-weighted imaging (DWI). To challenge this paradigm, this study introduces a novel concept of a difference map, which relies exclusively on DCE-MRI for the localization of peripheral zone prostate cancer using functional data analysis-based (FDA) signal processing. The proposed workflow uses discrete voxel-level DCE time–signal curves that are transformed into a continuous functional form. First-order derivatives are then used to determine patient-specific time points of greatest enhancement change that adapt to the intrinsic characteristics of each patient, producing diffmaps that highlight regions with pronounced enhancement dynamics, indicative of malignancy. A subsequent normalization step accounts for inter-patient variability, enabling consistent interpretation across subjects and probabilistic PCa localization. The approach is validated on a curated dataset of 20 patients. Evaluation of eight workflow variants is performed using weighted log loss, the best variant achieving a mean log loss of 0.578. This study demonstrates the feasibility and effectiveness of a single-modality, automated, and interpretable approach for peripheral prostate cancer localization based solely on DCE-MRI. Full article

(1) Purpose: Thoracic ossification of the ligamentum flavum (OLF) is increasingly recognized in East Asian populations, but reliable estimates in clinical settings remain limited. This study aimed to determine the clinic-based, lower thoracic (T8–T12) MRI prevalence of OLF among patients undergoing lumbar spine MRI for low-back pain and to identify radiological features associated with OLF. (2) Materials and Method: A cohort of patients with lower back pain who underwent L-Spine MRI studies in a tertiary medical center from January 2008 to December 2009 was created. Patients with thoracic OLF were identified, and a twice-fold sex-and-age-matched control group of patients without OLF, was randomly extracted. Radiological features in two groups were compared. (3) Results: The lower thoracic prevalence of OLF was 2.7%, significantly increasing in patients aged ≥60 years. OLF was most frequently involved in level T10-T11 (43%), and 23 cases (36%) showed multiple-level involvement. OLF was strongly associated with localized degenerative changes at the affected level, including higher degree of degenerative disc change, disc height loss, and more osteophyte formations. (4) Conclusions: Thoracic OLF is not a rare condition in patients with lower back pain. Patients with thoracic OLF were more likely to show features of focal degenerative changes, such as disc degeneration, osteophyte formation, and disc height loss on the level of OLF. Therefore, if initial plain radiographs of patients with neurologic deficits show evidence of degenerative change in the lower thoracic spine, a higher index of suspicion for thoracic OLF should prompt further evaluation. Full article

Background: Sinonasal undifferentiated carcinoma (SNUC) is an extremely rare, high-grade, and aggressive tumor of the sinonasal tract. Due to the rarity of this malignancy, current treatment guidelines are based on small and often/mainly single-center retrospective datasets. In the absence of a universally accepted standard of care for SNUC, treatment approaches vary across countries and institutions, reflecting real-world clinical practice. The primary aim of this study was to describe real-world treatment and outcomes for patients with confirmed SNUC. Methods: This was an international, multi-center, retrospective, observational cohort study that pooled patients into the largest SNUC dataset to date. Fifteen centers were enrolled to contribute data, including seven from Europe, four from the United States, three from the United Kingdom, and one from Canada. In the absence of a universally accepted standard of care for SNUC, treatment approaches varied across countries and institutions, reflecting real-world clinical practice. Patients included were those with histologically confirmed SNUC who were treated between 1997 and 2021. Results: This study yielded 485 patients treated for SNUC. The median age at diagnosis was 55.6 years (IQR: 44.5–67.6), and 63.7% were male. Most cases presented at advanced stages, with 70.8% as T4a or T4b. Overall survival (OS) outcomes were available for 412 patients, with a median follow-up of 26.0 months. The 5- and 10-year OS were 47.2% (95% CI: 40.8–53.3%) and 39.6% (95% CI: 32.5–46.6%), respectively. Advanced age, dichotomized T-stage (T4a/b vs. T1–3), M-stage, and orbital involvement were significant poor prognostic factors on univariable analysis (p’s < 0.01). On multivariable analysis, orbital involvement (HR: 2.73, 95% CI: 1.42–5.27, p = 0.003) and distance metastasis stage (HR: 3.00, 95% CI: 1.25–7.21, p = 0.014) were both independently associated with worse OS. Conclusions: This observational study presents the largest multi-center cohort analysis of SNUC to date, providing new insights into prognostic factors for a rare cancer treated at global centers of excellence. Orbital involvement and the presence of metastases are candidate independent risk factors associated with poorer OS. Full article

Type 2 diabetes mellitus (T2DM) is characterized not only by chronic hyperglycemia but also by profound adipose tissue dysfunction, including impaired lipid handling, low-grade inflammation, mitochondrial dysfunction, and extracellular matrix (ECM) remodeling. These adipose tissue alterations play a central role in the development of systemic insulin resistance, ectopic lipid accumulation, and cardiometabolic complications. Glucagon-like peptide-1 receptor agonists (GLP-1RAs), particularly semaglutide, have emerged as highly effective therapies for T2DM and obesity. While their glucose-lowering and appetite-suppressive effects are well established, accumulating evidence indicates that semaglutide exerts pleiotropic metabolic actions that extend beyond glycemic control, with adipose tissue representing a key target organ. This review synthesizes current preclinical and clinical evidence on the molecular and cellular mechanisms through which semaglutide modulates adipose tissue biology in T2DM. We discuss depot-specific effects on visceral and subcutaneous adipose tissue, regulation of adipocyte lipid metabolism and lipolysis, enhancement of mitochondrial biogenesis and oxidative capacity, induction of beige adipocyte programming, modulation of adipokine and cytokine secretion, immunometabolic remodeling, and attenuation of adipose tissue fibrosis and ECM stiffness. Collectively, available data indicate that semaglutide promotes a functional shift in adipose tissue from a pro-inflammatory, lipid-storing phenotype toward a more oxidative, insulin-sensitive, and metabolically flexible state. These adipose-centered adaptations likely contribute to improvements in systemic insulin sensitivity, reduction in ectopic fat deposition, and attenuation of cardiometabolic risk observed in patients with T2DM. Despite compelling mechanistic insights, much of the current evidence derives from animal models or in vitro systems. Human adipose tissue-focused studies integrating molecular profiling, advanced imaging, and longitudinal clinical data are therefore needed to fully elucidate the extra-glycemic actions of semaglutide and to translate these findings into adipose-targeted therapeutic strategies. Full article

Background: Pulmonary infarction (PI) is the result of the occlusion of distal pulmonary arteries resulting in damage to downstream lung areas that become ischemic, hemorrhagic, or necrotic, and it is often a complication of an underlying condition such as pulmonary embolism (PE). Since in most of cases it is located peripherally, lung ultrasound (LUS) can be a good evaluation tool. The typical radiological features of PI are well-known; however, there are limited data on its sonographic characteristics and its evolution. Methods: The aim of this study is to evaluate, using LUS, a convenience sample of patients with acute PE with computed tomography (CT) consolidation findings consistent with PI. Patients’ clinical characteristics were collected and LUS findings at baseline and their short-term progression was assessed. LUS was performed within 72 h of PE diagnosis (T0) and repeated after one (T1) and four weeks (T2). Each procedure started with a focused examination of the areas of lesions based on CT findings, followed by an exploration of the other posterior and lateral lung fields. The convex probe was used for initial evaluation integrating LUS evaluation with the linear one was employed for smaller and more superficial lesions and when appropriate. Color Doppler mode was added to study vascularization. Results: From June to October 2023, 14 consecutive patients were enrolled at the Respiratory Unit of the University Hospital of Pisa. The main population characteristics included the absence of respiratory failure and prognostic high-risk PE (100%), the absence of significant comorbidities (79%), and the presence of typical symptoms, such as chest pain (57%) and dyspnea (50%). The average number of consolidations per patient was 1.4 ± 0.6. Follow-up LUS showed the disappearance of some consolidations and some morphological changes in the remaining lesions: the presence of hypoechoic consolidation with a central hyperechoic area (“bubbly consolidation”) was more typical at T1 while the presence of a small pleural effusion often persisted both at T1 and T2. A decrease in wedge/triangular-shaped consolidations was observed (82% at T0, 67% at T1, 24% at T2), as was an increase in elongated shapes, representing a residual pleural thickening over time (9% at T0, 13% at T1, 44% at T2). A reduction in size was also observed by comparing the mean diameter, long axis, and short axis measurements of each consolidation at the three different studied time points: the average of the short axes and the median of the mean diameters showed a statistically significant reduction after four weeks. Additionally, a correlation between lesion size and pleuritic pain was described, although it did not achieve statistical significance. Conclusions: Patients’ clinical characteristics and ultrasound features are consistent with previous studies studying PI at PE diagnosis. Most consolidations detected by LUS change over time regarding size and form, but a minority of them do not differ. LUS is a safe and non-invasive exam that could help to improve patients’ clinical approach in emergency rooms as well as medical and pulmonology settings, clinically contextualized for cases of chest pain and dyspnea. Future studies could expand the morphological study of PI. Full article

Background: Heart failure (HF) affects not only the cardiovascular system but also mental health. The majority of patients with HF experience symptoms of mental disorders, such as depression, which are proportionally related to the severity of HF. This results in a significant comorbidity of HF, which might be associated with poor clinical outcomes, including decreased health-related quality of life (HRQOL). In Türkiye, data concerning the extent of this complication among outpatients with HF are limited. Therefore, the aim of this study was to assess the prevalence of depression in outpatients with HF and consequently the HRQOL; the secondary aim was to identify the related factors contributing to the incidence of depression and HRQOL in patients with HF in Bursa, Türkiye. Methods: An outpatient, descriptive, observational, cross-sectional study was conducted in a cardiology outpatient clinic in Bursa Province, Türkiye, between September and December 2022. The study was conducted via a validated questionnaire consisting of four sections. Depression was measured using the Beck Depression Inventory (BDI) scale, and the HRQOL of HF patients was evaluated using the Turkish version of the Minnesota Living with HF Questionnaire (MLHFQ). Simple linear regression and multiple linear regression analyses were used to determine the effects of variables. Limitations of the study include its design as a descriptive, observational, cross-sectional study from a single center that relies on self-reported data. Results: A total of 166 patients were enrolled, with a mean age of 64.96 ± 11.33 years. Nearly half of the participants had moderate or severe depression (33.1% and 15.7%, respectively). The mean MLHFQ score of the study participants was 54.15 ± 18.20. Patients suffering from severe depression had the lowest HRQOL (71.46 ± 12.4). There was a significant increase in depression level, and a decrease in HRQOL in patients with a duration of HF diagnosis of more than 3 years (p = 0.001), a number of HF hospitalizations (p = 0.001), and those diagnosed with NYHA class IV (p = 0.001). Multiple linear regression analysis revealed a significant relationship between the duration of HF disease, number of comorbidities, number of medications used, and BDI [(0.30 < r: 0.31/0.43/0.43 ≤ 0.70), respectively]. The simple linear regression analysis revealed that the BDI has positive and significant explanatory power for the MLHFQ (F: 168.29; R²: 0.51; t: 12.97; p < 0.001), and 51% of the change in the MLHFQ score is recorded by the BDI (R²: 0.51). Conclusions: The results of this study revealed that comorbid depression and HRQOL are closely related. This was observed in nearly half of the patients with HF, who had comorbid moderate and severe depression, which is associated with poor HRQOL. The factors associated with high depression and poor HRQOL were the duration of HF diagnosis of more than 3 years, an increased number of HF hospitalizations, polypharmacy, and NYHA class IV diagnoses. Full article

Background and Objectives: Celiac disease (CD) is a major global public health problem that can occur at any age. Pediatric CD can be typical, atypical, or even asymptomatic. Early diagnosis and early initiation of treatment are essential for improving patients’ quality of life and preventing serious complications later in life. However, it is impossible to identify asymptomatic children and adolescents without screening. In this systematic review, we attempted to identify different mass screening programs that have been reported for CD in apparently healthy children and adolescents across the world, to highlight the advantages and disadvantages of such strategies, and to collect and synthesize data from these studies reporting the prevalence of CD. In addition, where data were available, we also attempted to evaluate the diagnostic accuracy of the tests used, their cost-effectiveness, the reported clinical benefits, and follow-up data from individuals identified through screening. Materials and Methods: Electronic databases, including PubMed and Scopus, were systematically searched. Initially, a total of 316 studies were retrieved. Finally, 55 studies met all inclusion criteria and were included in this review. The included studies were published between 1996 and 2023. Results: The reported age of participants ranged from 6 months to 23 years. Confirmation of CD by biopsy was reported in all but six studies. According to the studies that provided data, the (tTG IgA) seroprevalence of CD in apparently healthy children and adolescents, detected through different mass screening methods around the world, ranged from 0.20% (Turkey) to 3.11% (Italy). In addition, the prevalence of biopsy-confirmed CD ranged from 0.036% (Vietnam) to 3% (Sweden and Spain). Studies from 17 countries reported mass screening strategies based on finger-prick rapid tests. All rapid tests detected CD antibodies, except two, which detected HLA DQ2/DQ8 haplotypes. Rapid tests appeared to be no less sensitive and specific than other screening tests for CD and were probably less expensive, but further studies are needed for more reliable conclusions. Of the 55 studies in the review, only 10 reported follow-up data. After 3 months of a gluten-free diet, the general condition of the patients improved; after 6 months, tTG IgA and EMA IgA levels decreased and hemoglobin values increased; while after 1 year, tTG IgG levels also decreased, symptoms subsided, the children’s weight and height increased, school performance improved, episodes of upper respiratory tract infections decreased, and thyreoperoxidase antibodies that were positive at screening became negative. Conclusions: Mass screening for CD in asymptomatic children and adolescents is a challenge. Future research should provide more answers regarding the most appropriate target age, the frequency of screening, the optimal screening method, the cost-effectiveness, the clinical utility, and the long-term impact of mass screening on patients’ quality of life. Full article

Background/Objectives: Super-selective intra-arterial chemoradiotherapy (SSIACRT) is an alternatively effective treatment for locally advanced oral cavity cancer although no comparative studies on prognosis between SSIACRT and surgical resection with or without post-operative radiotherapy (S+R) have been reported. This study aimed to compare the 5-year survival rate and Quality of Life (QoL) between S+R and SSIACRT for locally advanced oral cavity cancer. Methods: From a total of 326 patients with stage III and IV oral cavity cancer treated between 2000–2020 at a single institution, 149 patients treated with S+R and SSIACRT were analyzed by using Propensity Score Matching (PSM) method, a pseudo-randomized controlled trial, and the matched cases were retrospectively evaluated. The 5-year survival rate and QoL were evaluated using the Kaplan–Meier method and the University of Washington QoL questionnaire, respectively. Log-rank test and Cox proportional hazards model were used to compare 5-year survival rate and to assess factors affecting survival rates, respectively. Paired t-test was used to compare QoL. Results: To compare the 5-year survival rate and QoL between S+R and SSIACRT, 48 and 15 cases were matched after PSM. The 149 cases were further evaluated for covariates affecting survival rates. The 5-year disease-specific survival rate and 5-year crude survival rate were 52.4% and 44.3% for S+R and 71.3%, and 62.9% for SSIACRT, respectively. There was no statistical difference in survival rates between both treatments, based on Log-rank test analysis. Treatment method was the only independent variable that influenced survival rates. SSIACRT showed better statistical difference in QoL evaluation, specifically in appearance, activity, recreation, swallowing, speech, shoulder, taste, mood, and total score. Conclusions: Propensity score-matched analysis demonstrated survival outcomes that were comparable to, and not inferior to, S+R. However, SSIACRT was associated with superior quality-of-life outcomes compared with S+R, as shown by Cox proportional hazards modeling. These findings suggest that SSIACRT is an effective treatment option and, from a quality-of-life perspective, may be considered a preferable approach in the management of locally advanced oral cavity cancer. Full article

Introduction: The addition of immunotherapy to neoadjuvant treatment for early triple-negative breast cancer (TNBC) has been adopted in clinical practice in France since March 2022, with little real-world data published on the topic. The aim of this study was to evaluate real-world data on treatment feasibility, efficacy, and related toxicities, with a specific focus on immune-related adverse events (irAEs). Methods: We conducted a retrospective analysis of patients who completed at least the neoadjuvant sequence of pembrolizumab combined with chemotherapy for early-stage TNBC at Montpellier Cancer Institute from April 2022 to July 2024. Adverse events were graded according to the Common Terminology Criteria for Adverse Events (CTCAE) v5.0. The pathological complete response (pCR) was defined as the absence of residual invasive disease in the breast and axillary lymph nodes (ypT0/Tis ypN0). Results: We reviewed data from 92 patient records. The median age at diagnosis was 50 years (range: 27–76). The history of autoimmune disease was noted in 3.2% of patients. Grade 3–4 irAEs were observed in 20% of patients and included hepatitis (8.6%), colitis (3.3%), skin toxicity (2.1%), myocarditis (2%), arthralgia (1%), autoimmune hemolytic anemia (1%), hypothyroidism (1%), and adrenal insufficiency (1%). No treatment-related deaths were reported. Immunotherapy was discontinued due to irAEs in 29.3% of patients in the study population. The pCR rate was 61,1%, with no significant association between the number of neoadjuvant pembrolizumab cycles and the pCR rate (p = 0.7). Patients experiencing grade 3–4 irAEs had a pCR rate of 80%, compared to 56.7% in those without such toxicities (p = 0.079). Initial positivity of antinuclear antibodies (ANA) was not associated with an increased incidence of irAEs. Conclusions: The immune-related adverse events and efficacy data observed in our cohort were broadly comparable to those reported in the KEYNOTE-522 trial, with no treatment-related deaths. Patients with grade 3–4 irAEs tended to have higher pCR rates. Full article