Medical sciences (Basel, Switzerland)最新文献

Background: In this study, we retrospectively analyzed clinical and toxicity outcomes of 67 prostate cancer (PCa) patients undergoing moderately hypofractionated radiotherapy (RT) after prostatectomy, with adjuvant or salvage intent. Methods: Irradiation was delivered by volumetric modulated arc therapy. The median follow-up was 48 months. The 3- and 5-year biochemical relapse-free survival rates were 80% and 69%. The RT schedule consisted of a median total dose of 67.5 Gy with a median number of 25 fractions and a median fraction dose of 2.7 Gy to the prostate bed (PB) and 60% of patients simultaneously received whole pelvis irradiation (WP; fraction dose: 1.8 Gy, median total dose of 46.8 Gy). Results: The rate of acute toxicity was 54% for gastrointestinal (GI) and 36% for genitourinary (GU). No grade 3 acute toxicity was observed. Late toxicity was as follows: G1, G2, and G3 GI events in 25.5%, 3.6%, and 1.8% of the cases, respectively; G1, G2, and G3 GU events in 37.1%, 11.1%, and 7.4%, respectively. The toxicity-free survival (TFS) curves showed a different trend for acute and late toxicity. TFS was significantly associated with RT volume, except for acute GI toxicity. Specifically, the concomitant irradiation of PB and WP appeared to be a significant risk factor for late GI and GU toxicity (p = 0.029 and p = 0.012, respectively). Conclusions: At the 48-month median timepoint considered by our study, postoperative hypofractionated RT achieved promising results in terms of clinical outcomes with acceptable toxicity. Only the irradiated volume seems to be an important predictor for toxicity.

Objectives: This observational and cross-sectional study investigated differential associations between entero-invasive and non-entero-invasive enteric pathogens and HIV infection, considering socioeconomic, clinical and immunological aspects. In a Ghanaian population with a high prevalence of enteric pathogens, stool samples from people living with HIV (PLWH) were screened for Salmonella spp., Shigella spp./EIEC (enteroinvasive Escherichia coli), and Campylobacter jejuni as entero-invasive bacteria, for enteropathogenic E. coli (EPEC), enterotoxigenic E. coli (ETEC), and enteroaggregative E. coli (EAEC) as non-entero-invasive bacteria. Arcobacter butzleri, with uncertain enteropathogenicity, was also included.

Methods: Stool samples from PLWH (with and without antiretroviral therapy) and HIV-negative controls were analyzed by real-time PCR for the presence and quantity of the selected enteropathogens. Results were correlated with socioeconomic, clinical, and immunological parameters.

Results: The presence of Shigella spp. /EIEC in stool was both qualitatively and quantitatively associated with reduced CD4+ T lymphocyte counts and was qualitatively associated with clinically apparent diarrhea. EAEC showed a weak positive association with HIV infection, supported by a negative correlation between EAEC DNA quantity and CD4+ T lymphocyte counts. EPEC colonization was associated with HIV negativity, higher CD4+ T lymphocyte counts, and lower socioeconomic status. Abundance of Salmonella enterica was associated with clinically apparent diarrhea.

Conclusions: This explorative, hypothesis-forming study suggests species- or pathovar-specific associations between enteric bacterial pathogens and HIV-related immunosuppression. Observed relationships with clinically apparent diarrhea largely align with findings from sub-Saharan African children, except for a more pronounced association between diarrhea and Salmonella in this cohort.

Background. Routine lymphocyte counting requires quality assurance validation using quality controls (QCs) that closely resemble fresh human blood leukocytes. This study aimed to evaluate a novel artificial product designed to mimic leukocyte light scatters and marker expression. Methods. FlowCytes and TruCytes, "artificial cell mimics" (Slingshot Biosciences, Emeryville, CA, USA), were tested on CE-IVD-certified systems, namely FACSCanto, FACSLyric (BD Biosciences), Navios, and DxFlex (Beckman Coulter), using routine staining, lysing, fixation, and no-wash procedures for T, B, and NK counting. Results. FlowCytes and TruCytes provided forward and side scatter profiles comparable to human leukocytes on the FACSCanto, FACSLyric, and DxFlex systems but not on Navios despite adapting the process to be slightly different from the manufacturer's recommendations. TruCytes demonstrated robust immunolabeling of CD3, CD4, CD8, and CD19 on the FACSCanto, FACSLyric, and DxFlex systems, with fluorescence intensities and subset distributions being similar to those usually observed in fresh human blood. However, CD16 and CD56 labeling was inconsistent and depended on the antibody clones used. Regrettably, monocyte and granulocyte mimics lacked expression of CD4, CD16, and CD14. TruCytes also displayed significantly lower concentrations of TBNK lymphocyte subsets compared to healthy human blood. Conclusions. FlowCytes and TruCytes show promises as internal quality controls for T cell and B cell immunophenotyping, but not NK cells. They are compatible with most CE-IVD cytometers, even when using lysis/fixation/no-wash routine diagnosis procedures. Further multicentric studies are warranted to assess their performance relative to existing products, such as stabilized human blood.

Background: Developmental dysplasia of the hip (DDH) encompasses a spectrum of neonatal hip abnormalities that, if not detected and treated early, may lead to long-term orthopedic sequelae. Universal ultrasound screening using Graf's method has been proposed to improve early diagnosis, though its implementation remains heterogeneous in Italy. Objectives: This study aimed to describe the outcomes of a universal ultrasound screening program for DDH conducted in a first-level birth center in northern Italy, evaluating DDH incidence, risk factors, management outcomes, and program feasibility. Methods: A prospective observational study was conducted from February 2024 to October 2025 at the Ivrea birth center (Piedmont region, Italy). All consecutive live-born infants (n = 904) underwent hip ultrasound according to Graf's method, between 0 and 11 weeks of age. Hips were classified as type I (normal), type IIa (physiologically immature), or type IIb-IV (pathological). Infants with type IIa hips were re-evaluated after 2-4 weeks; those with type IIb or worse were referred to pediatric orthopedics. Results: Of 1808 hips examined, 92% were Graf type I and 8% type IIa. After follow-up, 93% of type IIa hips matured spontaneously. Pathological DDH (Graf IIb or worse) was diagnosed in 8 infants (0.88%), of whom 75% were female; 50% had no identifiable risk factors. All affected infants were treated with harness before 12 weeks of age, with complete recovery and no late diagnoses. No infant required surgical treatment. Conclusions: Universal ultrasound screening for DDH was feasible and effective in a first-level birth center, ensuring early diagnosis and absence of late-presenting cases. These findings support universal screening as a safe and equitable approach to reduce DDH-related morbidity and align with national recommendations for standardized early detection programs.

Background: Interpretation of cognitive performance in older patients with depression is challenging considering the association between late-life depression and (early-stage) neurodegenerative disease. The Montreal Cognitive Assessment (MoCA) is widely used to screen for mild cognitive impairment in community-dwelling older adults. Objective: The aim of the present study was to examine the need for and to develop dedicated MoCA norms for older people with depressive disorder. Methods: We used data from the Routine Outcome Monitoring for Geriatric Psychiatry & Science (ROM-GPS) study and the Advanced Neuropsychological Diagnostics Infrastructure (ANDI) database, which consisted of 859 patients with a depressive disorder according to DSM-5 criteria and 320 healthy controls, aged ≥60 years. Linear regression was used to examine the relationship between late-life depression and MoCA scores, adjusted for age, sex, and education. Results: The presence of a depressive disorder was associated with lower MoCA scores, and this effect was larger for persons with 12 years or less of education than for those with more education (B = -0.76 [95% CI -0.61; -0.91] vs. -0.53 [-0.36; -0.70]). Among depressed patients, depressive symptom severity was not associated with the MoCA score. Regression-based normative data for the MoCA were computed and adjusted for age, education, sex, and type of depressive disorder. Conclusions: Our findings demonstrate that depressive disorder, but not symptom severity within depression, is associated with lower MoCA scores. Clinical interpretation of MoCA scores in depressed older persons can be facilitated by using MoCA reference tables stratified by age, sex and level of education.

Background: Chronic heart failure (HF) is a significant public health issue. The principal risk factors for left ventricular diastolic dysfunction (LVDD) include older age, female sex, obesity, hypertension, smoking, and diabetes, among others, all of which can reduce physical activity. Additionally, peripheral factors such as skeletal muscle mass (SMM) abnormalities decrease maximal oxygen consumption. In elderly HF patients, the prevalence of sarcopenia is higher than in those without HF; however, the relationship between sarcopenia and HF remains insufficiently explained, particularly in right HF (RHF). Our objective was to describe the echocardiographic alterations between sarcopenic and non-sarcopenic subjects with RHF.

Methods: A cross-sectional study was conducted. Outpatients aged 18 years or older with a confirmed diagnosis of RHF were included. Sarcopenia was defined according to EWGSOP2.

Results: A total of 183 patients were included; 24.5% had sarcopenia. The mean age was 64.34 ± 13.97 years. Echocardiographic characteristics revealed evidence of LVDD in sarcopenic subjects, as indicated by lower E wave velocity, E/A ratio, and e' lateral and medial values, as well as lower right ventricular (RV) wall thickness compared with non-sarcopenic subjects. The multivariate model showed that sarcopenia subjects had lower RV wall thickness (B: -1.36 mm, 95% CI: -2.30 to -0.42), e' medial (B: -1 cm/s, 95% CI: -1.99 to -0.02), and e' lateral (B: -1.78 cm/s, 95% CI: -2.97 to -0.60).

Conclusions: The prevalence of sarcopenia in RHF patients was 24.6%, which was associated with LVDD and lower RV wall thickness, suggesting a loss of cardiac muscle mass.

Background: The roles of cytokines and chemokines in the pathogenesis of Chagas cardiomyopathy (CC) have been proposed, yet their clinical significance with respect to conduction disturbances and left ventricular ejection fraction (LVEF) remains unclear.

Aim: The objective of this study was to analyze the associations between cytokine levels and systolic function, comparing patients with preserved and reduced ejection fractions. As a secondary objective, we evaluated whether differences were present in cytokine levels within the subgroup with preserved ejection fraction, depending on the presence or absence of intraventricular conduction disturbances.

Methods: We conducted an analytical cross-sectional study involving patients with Chagas disease and a healthy control group. Among patients with Chagas disease, those with preserved (>50%) and reduced (<35%) left ventricular ejection fraction (LVEF) were selected. The preserved-LVEF group included individuals with and without conduction disorders. Cytokines (IFN-γ, IL-1β, IL-6, IL-10, IL-12p70, IL-15, IL-17A, MCP-1, MIP1α, TNF-α, and IL-2) were quantified using a magnetic bead-based multiplex assay.

Results: Forty-four patients with CD (26 men, 59%) and 14 seronegative controls were included. In the CD group, 50% (n = 22) had preserved LVEF (LVEF > 50%), and 50% (n = 22) had decreased LVEF (≤35%). No significant differences in cytokine concentrations were observed between patients with preserved and reduced LVEF for TNF-α (19.74 ± 8.32 vs. 22.23 ± 6.40 pg/mL; p = 0.189), IL-6 (2.17 ± 2.41 vs. 5.40 ± 6.40 pg/mL; p = 0.145), IL-2 (2.61 ± 1.05 vs. 2.97 ± 1.79 pg/mL; p = 0.481), MCP-1 (214.18 ± 96.99 vs. 183.83 ± 63.21 pg/mL; p = 0.481) and IFN-γ (9.04 ± 4.90 vs. 7.64 ± 3.78 pg/mL; p = 0.372). Within the subgroup with preserved LVEF (n = 22), those with conduction disorders (n = 10) exhibited higher levels of IL-10 (24.49 vs. 9.83 pg/mL; q = 0.009), IL-12p70 (13.20 vs. 9.02 pg/mL; q = 0.027), IL-2 (2.70 vs. 2.07 pg/mL; q = 0.023), IL-15 (7.09 vs. 3.36 pg/mL; q = 0.018), MIP1α (10.33 vs. 3.35 pg/mL; q = 0.014) and IFN-γ (10.83 vs. 7.25 pg/mL; q = 0.005), compared to those without conduction disorders (n = 12). Notably, patients with CD and preserved LVEF (>50%) without conduction disturbances presented cytokine profiles similar to those of seronegative healthy controls with LVEF ≥ 50%.

Conclusions: Elevated levels of specific cytokines were associated with conduction disturbances in patients with preserved LVEF. Despite this finding, a causal relationship cannot be established, and future studies are needed to explore their prognostic or therapeutic significance.

PANoptosis is an integrated form of regulated cell death that combines pyroptosis, apoptosis, and necroptosis through a coordinated molecular platform known as the PANoptosome. Autophagy, in parallel, maintains immune homeostasis by controlling cellular stress responses. Although both pathways are essential for innate and adaptive immunity, their functional interplay has only recently been explored. This review summarizes current knowledge on the bidirectional relationship between PANoptosis and autophagy, with emphasis on how autophagy can restrain PANoptotic signaling or, under certain conditions, promote inflammatory cell death. We discuss cell-type-specific aspects of this crosstalk in macrophages, dendritic cells, monocytes, neutrophils, T cells, and B cells, focusing on key PANoptosis mediators and autophagy-related proteins. We then examine how dysregulated autophagy and exaggerated PANoptotic signaling contribute to chronic inflammation and tissue damage in immune-mediated inflammatory disease, including systemic lupus erythematosus, rheumatoid arthritis, Sjögren's syndrome, psoriasis, and inflammatory bowel disease. Finally, we outline shared molecular principles that position the autophagy-PANoptosis axis as a fundamental immunoregulatory mechanism and a promising source of therapeutic targets in chronic inflammatory and autoimmune disorders.

Parkinson's disease (PD) is a multifaceted neurodegenerative disorder characterized by dopaminergic neuronal loss and widespread α-synuclein pathology. Nuclear medicine imaging offers essential in vivo tools for early diagnosis, differential assessment, and monitoring disease progression. This review summarizes key PET and SPECT radiotracers targeting dopaminergic synthesis and transport, vesicular storage, post-synaptic receptors, neuroinflammation, and protein aggregation, highlighting their roles in clinical evaluation and phenotyping. Clinically, these modalities support earlier recognition of PD, distinction from atypical parkinsonian syndromes, and assessment of non-motor involvement. Future directions include the development of selective α-synuclein tracers and multimodal imaging strategies to refine prodromal detection and guide personalized therapeutic interventions.

Background/Objectives: The COVID-19 pandemic limited access to in-person physiotherapy, raising concerns about post-operative rehabilitation outcomes. This prospective observational study, without a control group, evaluated whether a self-rehabilitation protocol following a mini-open Learjet procedure influenced short-term clinical outcomes in active military personnel. Materials and Methods: We prospectively enrolled 18 patients (19 shoulders) undergoing mini-open Latarjet between May and October 2020. Patients performed a standardized self-rehabilitation protocol starting on the first post-operative day, with progressive range-of-motion (ROM) exercises added at two weeks. Pain was assessed using the Visual Analog Scale (VAS), ROM was recorded at each follow-up, complications were noted, and patient satisfaction was evaluated at 12 weeks. Results: A total of eighteen patients were prospectively enrolled in the study. At 12 weeks, mean VAS decreased from 1.2 ± 0.6 at week 1 to 0 at week 4 onward. The mean drug consumption was 2.5 ± 0.7 tablets/day only for the first week. Mean assisted forward flexion improved from 155° ± 10° at week 1 to 180° in all patients by week 4. External rotation reached 60° ± 5°at 4 weeks, 75° ± 4° at 8 weeks, and 80° ± 3°at 12 weeks, with no deficits compared to the contralateral side. Internal rotation improved to the T7 level by week 8 and remained stable in week 12. No complications, recurrent instability, or graft displacements were reported. Patient satisfaction at 12 weeks was assessed using a 0-10 numeric rating scale, with a mean score of 9.5 ± 0.4. Conclusions: Implementation of a self-rehabilitation protocol after mini-open Latarjet surgery was associated with favorable short-term outcomes in young military patients, including early recovery, high satisfaction, and absence of complications. Further validation of these findings will require larger, rigorously controlled studies.