Diseases (Basel, Switzerland)最新文献

Background/objective: Diabetic nephropathy (DN), a key microvascular complication of type 2 diabetes (T2DM), drives significant morbidity, mortality, and healthcare costs. Vitamin D deficiency has been linked to renal dysfunction, but its role in DN remains unclear. This study assessed the association between vitamin D status and DN versus T2DM without nephropathy.

Methods: This cross-sectional hospital-based study included 399 participants (299 DN, 100 T2DM without nephropathy) at a tertiary endocrine clinic. Demographic, clinical, and biochemical data, including serum 25(OH)D, were collected. Chi-square and Mann-Whitney compared categorical and continuous variables, respectively, and multinomial logistic regression assessed the association between vitamin D status and DN (p < 0.05).

Results: Patients with DN were older (58.2 ± 7.95 vs. 51.4 ± 9.94 years, p < 0.001), had more advanced CKD (stages 2-3b: 84.6% vs. 20.0%, p < 0.001), and higher albuminuria (moderate: 80.3% vs. 19.0%; severe: 18.4% vs. 0%, p < 0.001). They also showed poorer glycemic control, elevated urea and creatinine, lower serum albumin, dyslipidemia, elevated liver enzymes, and higher uric acid (all p < 0.05). Vitamin D deficiency was more prevalent in DN (37.7% vs. 8.0%, p < 0.001). Unadjusted multinomial regression indicated that T2DM patients without nephropathy had a 91% lower risk of vitamin D deficiency (RRR 0.09; 95% CI 0.04-0.19, p < 0.001) and an 87% lower risk of insufficiency (RRR 0.13; 95% CI 0.05-0.26, p < 0.001) compared with DN patients. After adjusting for age, HbA1c, creatinine, duration of diabetes and eGFR, the reduced risk of deficiency remained significant (RRR 0.04; 95% CI 0.01-0.16, p < 0.001), while the association with insufficiency was no longer significant (p = 0.310).

Conclusions: This study shows a significant association between vitamin D deficiency and diabetic nephropathy, though its cross-sectional design precludes causal inference. Reverse causality and residual confounding cannot be excluded. Patients with DN had poorer glycemic control, dyslipidemia, and renal function, along with more frequent vitamin D deficiency. Routine vitamin D monitoring may support early detection and risk stratification in T2DM.

Background: Gold nanoparticles (GNPs) are widely used in nanomedicine as drug carriers, including in targeted radionuclide therapy where therapeutic radionuclides are bound to GNPs. Quantitative assessment of their biodistribution is essential. X-ray fluorescence imaging (XFI) is well suited for detecting high-Z elements, but its quantitative accuracy is compromised by strong attenuation effects, particularly in L-shell XFI where low-energy fluorescence (~10 to 12 keV) is heavily absorbed in tissue. Methods: We developed a computed tomography (CT)-guided attenuation correction algorithm for L-shell XFI. The method generates energy-dependent attenuation maps from co-registered CT data and performs voxel-wise corrections along both excitation and emission paths. The approach was tested on an ex vivo murine tumor sample resected three hours after intratumoral injection of 34.7 μg PEG-modified GNPs. Results: Application of the CT-guided correction substantially improved the relative accuracy of L-shell XFI reconstructions compared to uncorrected data. The corrected distribution maps showed consistent mass recovery across different measurement geometries, demonstrating that the algorithm compensates for the theoretically expected attenuation due to heterogeneous biological tissue. Conclusions: This study provides a proof-of-principle that CT-based attenuation correction enables more reliable and quantitative L-shell XFI of GNPs in biological samples. The approach represents a promising step toward accurate nanoparticle biodistribution assessment in biomedical research, including preclinical studies in targeted radionuclide therapy.

Background: Leptin is a hormone that plays a crucial role in regulating energy homeostasis and it is associated with adiposity. Women engaged in work shifts are often exposed to circadian disruption and metabolic changes that may contribute to increased adiposity and hormonal imbalance. Thus, this study aimed to investigate the association between general and abdominal obesity and serum leptin levels among female shift workers.

Methods: This cross-sectional study included a sample of 302 female employees from a group of plastic manufacturing industries in southern Brazil. Serum leptin levels were measured, with values > 15.2 ng/mL classified as elevated. General obesity (body mass index ≥ 30 kg/m²) and abdominal obesity (waist circumference ≥ 88 cm) were assessed. Associations were examined using Poisson regression with robust variance.

Results: The mean age of participants was 35.4 ± 10.1 years. The mean serum leptin concentration in the sample was 33.6 ng/mL (95% Confidence Interval [CI]: 30.6-36.6), and the prevalence of altered serum leptin levels was 78.1% (95% CI: 73.5-82.8). After adjustment for potential confounders, women with obesity showed a 63% higher probability of having elevated leptin levels (Prevalence Ratio [PR] = 1.63; 95% CI: 1.32-2.02; p < 0.001) compared with those without obesity. Additionally, significant associations were observed with work shift and physical activity. However, abdominal obesity was not statistically significant after adjustment.

Conclusions: Obesity was independently associated with elevated serum leptin levels among female shift workers, suggesting that excess adiposity remains a key determinant of leptin dysregulation in this population.

Background: Fluid shear stress (FSS) is a biomechanical force that can produce phenotypic changes in the cells that are directly in contact with the flow of fluid. Accumulating evidence indicates high FSS to possess the potential ability to prevent tumor development and suppress cancer growth. However, the exact mechanism of its antitumorigenic effects is still not clear.

Objective: In this study, we aimed to investigate the effect of FSS on breast cancer microenvironment via macrophage modulation.

Methods: We exposed THP-1 like-macrophages to different levels of FSS. The supernatant from THP1-like-macrophages after exposure to FSS was used as conditioned medium (FSS-CM). Subsequently, we analyzed human breast cancer cells, MCF-7, and endothelial cells, as well as HUVECs cultured with FSS-CM.

Results: Study outcomes have demonstrated that low FSS-CM inhibited apoptosis as well as induced tumor migration in MCF-7 cells. Conversely, high FSS-CM promoted apoptosis, inhibited tumor migration, and induced G1-phase arrest in MCF-7 cells. Furthermore, low FSS-CM was found to promote proliferation of HUVECs.

Conclusions: In conclusion, this study highlights the complex interplay between FSS and cancer cell behavior. Our findings provide in vitro evidence that high FSS exerts an anti-cancer effect by promoting THP-1-like macrophage polarization toward an anti-tumor phenotype, leading to increased apoptosis and reduced migration in MCF-7 cells. These results suggest that the modulation of macrophage polarization may underlie the therapeutic potential of high FSS in suppressing breast cancer progression.

Background: Severe (FIGO grade 3b & c) placenta accreta spectrum (PAS) is potentially a life-threatening condition due to catastrophic haemorrhage at delivery. Consequently, interventional radiology (IR) techniques are often employed to prevent massive blood loss, but this is not always readily available, is costly, and can cause significant morbidity, including distal limb ischaemia due to thrombus formation. We believe that internal iliac ligation under direct vision is a safe option to control bleeding. We sought to evaluate the short- and long-term outcomes relating to this technique compared to IR.

Methods: This is a mixed-methods cohort study of women with severe PAS who underwent hysterectomy with either surgical devascularisation, as part of the Soleymani and Collins (SAC) technique, or IR insertion of internal iliac balloon catheters, in a UK tertiary referral centre for PAS between 2011 and 2022. Only women with intraoperative diagnosis of very severe PAS (FIGO stage 3b & c) were included in this study.

Results: Of the 22 women invited to participate in the long-term component of the study, 59% agreed. Women in the surgical devascularisation group experienced no adverse short or late sequelae related to internal iliac arterial ligation. Pelvic devascularisation (11 patients, 41%) demonstrated a reduction in median estimated blood loss, 1600 millilitres vs. 2500 millilitres in the IR balloon catheter group (p = 0.04).

Conclusions: We have demonstrated that the SAC technique for surgical devascularisation is a safe method for achieving haemorrhage control during caesarean hysterectomy for severe PAS. It also appears to be at least as effective at haemorrhage control as IR balloon occlusion of the internal iliac vessels.

Background/Objectives: Diffuse large B-cell lymphoma (DLBCL) exhibits substantial clinical heterogeneity and poor prognosis in relapsed/refractory (R/R) settings. PRO-MIND is a prospective, multicenter real-world study evaluating tafasitamab-lenalidomide followed by tafasitamab monotherapy in patients with transplant-ineligible R/R DLBCL in Italy. This ad hoc, cross-sectional, baseline analysis aimed to characterize health-related quality of life (HRQoL) and symptom burden before tafasitamab-lenalidomide initiation in the PRO-MIND cohort. Methods: Thirty-eight patients across 30 centers completed the EORTC QLQ-C30 and QLQ-NHL-HG29 questionnaires at pretreatment baseline, prior to starting tafasitamab-lenalidomide. EORTC QLQ-C30 scores (0-100) were compared with age-specific normative values for the Italian general population using Welch's t-test. Differences of ≥5 points were considered clinically meaningful and ≥10 points clearly clinically important. Effect sizes (Cohen's d) were calculated to complement p-values for between-group comparisons. Results: Compared with normative data, the PRO-MIND cohort had significantly lower EORTC QLQ-C30 functioning scores for physical (Δ 12.7, p = 0.0135), role (Δ 16.1, p = 0.0168), social (Δ 15.2, p = 0.0019), and cognitive (Δ 8.5, p = 0.0460) functioning. Symptom scales revealed worse fatigue (Δ 14.8, p = 0.0097), insomnia (Δ 13.9, p = 0.0291), appetite loss (Δ 9.4, p = 0.0435), and pain (Δ 8.7, p = 0.0430) in the PRO-MIND cohort versus normative data, with effect sizes in the small-to-moderate range. EORTC QLQ-NHL-HG29 scores indicated a high prevalence of concerns about future health (84.2%), disease recurrence (81.6%), and dependency (78.9%), as well as physical symptoms, including lack of energy (71.1%), sleep difficulties (63.2%), and pain or discomfort (60.5%). Conclusions: This cross-sectional, baseline-only analysis of the PRO-MIND real-world cohort showed that patients with transplant-ineligible R/R DLBCL scheduled to receive tafasitamab-lenalidomide already had pronounced impairments in physical, role, social, and cognitive functioning, along with substantial fatigue, insomnia, pain, appetite loss, and psychological concerns. These baseline benchmarks underscore the importance of systematic HRQoL assessment and targeted supportive interventions focusing on these domains before and during treatment. Future longitudinal PRO-MIND analyses will complement these findings by describing how HRQoL evolves after tafasitamab-lenalidomide initiation.

Introduction: Although patients with upper gastrointestinal (GI) cancer have an increased risk of developing small intestinal bacterial overgrowth (SIBO) due to disease- and treatment-related factors, SIBO remains underdiagnosed in oncology.

Aim and methods: This prospective study evaluated the prevalence of SIBO and its impact on symptom-related quality of life (QoL) in patients with current or prior upper GI cancer. Between April 2021 and May 2022, patients reporting SIBO-related symptoms like bloating and/or diarrhea completed a standardized symptom questionnaire. QoL impact was scored from 0 (none) to 3 (severe). Patients with scores > 1 and no recent antibiotic use underwent upper endoscopy with duodenal aspirate. SIBO was defined as >10³ CFU/mL.

Results: Ninety patients were enrolled (51% female; median age of 65 years): 35% had pancreatic, 34% gastric, 17% biliary, and 14% esophageal cancer. Sixty reported SIBO-related symptoms: 35% reported bloating, 11% diarrhea, and 54% both. Of these, 36 underwent endoscopy; 53% were diagnosed with SIBO. Among SIBO-positive patients, 95% reported bloating and 58% reported diarrhea. Prior abdominal surgery was recorded in 63% of SIBO cases.

Conclusions: SIBO was identified in more than half of symptomatic upper GI cancer patients, with a strong association with bloating and previous abdominal surgery. These findings emphasize the importance of clinical awareness and appropriate diagnostic evaluation for SIBO in this high-risk group to improve symptom control and quality of life.

Cervicofacial actinomycosis is a well-recognized infectious disease caused by Actinomyces, a Gram-positive filamentous bacterium. In contrast, Nocardia, a morphologically similar, hyphae-forming organism, is an exceedingly rare cause of cervicofacial abscesses, and even more uncommon associated osteomyelitis of mandible. We present such a case involving a kidney transplant recipient who presented with opioid-induced constipation, along with left jaw pain and swelling. CT scan of the soft tissue in the neck revealed a complex cervicofacial abscess with enhancement of underlying mandible. Culture growth and RNA sequencing of USG-guided aspirate identified a Nocardia species closely related to N. beijingensis/exalbida. The patient initially received broad-spectrum antibiotics, including ceftriaxone, imipenem, and trimethoprim-sulfamethoxazole (TMP-SMX). Imipenem was later discontinued in view of new-onset unexplained encephalopathy and replaced with linezolid, which was subsequently switched to minocycline following thrombocytopenia development. Minocycline therapy was intended for a total of 12 months. TMP-SMX was avoided long-term due to avoid nephrotoxicity risk in kidney transplant patients. On six-month follow-up, the patient showed clinical and radiological improvement; minocycline was discontinued after additional six months. This case highlights the importance of considering Nocardia as a differential diagnosis in immunosuppressed patients presenting with cervicofacial symptoms, especially following orofacial surgery or trauma. Early recognition, prompt diagnosis, and appropriate antibiotic therapy with adequate bone penetration seem crucial for optimal management and may help avoid the need for surgical intervention.

Background: Type 2 diabetes mellitus (T2DM) remains one of the most significant public health problems, and its incidence rate is steadily increasing worldwide despite scientific and technological progress in the field of medicine. The focus of research in this area is gradually shifting from classic risk factors-such as obesity, sedentary lifestyle and genetic predisposition-toward additional, potentially modifiable contributors such as micronutrient imbalances; among them are disturbances in zinc homeostasis that may influence glucose metabolism and oxidative stress.

Objective: This systematic review with narrative synthesis aims to examine the bidirectional relationship between zinc status and T2DM and to evaluate whether zinc screening and personalized nutritional support could contribute to comprehensive metabolic management.

Methods: A literature search was conducted in the PubMed database and the Cochrane library for studies published between 2010 and 2024. Studies assessing zinc status or supplementation in relation to the risk, progression, or management of T2DM were included. Data were synthesized narratively, focusing on clinical and mechanistic evidence.

Results: Thirty studies met the inclusion criteria. Evidence indicates that zinc imbalance (both deficiency and excess) is associated with T2DM risk and outcomes. Zinc deficiency may impair insulin synthesis and signaling, promote oxidative stress and inflammation, while excessive zinc intake may induce metabolic disturbances. T2DM itself may lead to reduced zinc status via altered absorption and increased excretion. While some studies suggest modest improvements in glycemic or lipid parameters following zinc supplementation, findings remain inconsistent and context-dependent. The prevalence of suboptimal zinc status in certain populations supports the rationale for targeted screening rather than routine supplementation.

Conclusions: Zinc is mechanistically involved in insulin synthesis, antioxidant defense, and inflammation control, but current clinical evidence does not justify its use as a therapeutic agent in T2DM. Instead, assessment of zinc status and individualized correction of deficiency may represent a component of personalized nutritional support, particularly for patients with long disease duration, poor dietary quality, or genetic predispositions affecting zinc metabolism.

Background:JAK/STAT interferon signaling interacts with the PI3K/AKT/mTOR pathway to drive hepatocellular carcinoma (HCC) progression and metastasis. RSAD2, an interferon-inducible gene, is upregulated by the PI3K/AKT/mTOR pathway and serves as a key factor for metabolic reprogramming to promote stem-like properties of cancer stem cells and tumor proliferation. In patients with resected HCC, RSAD2 upregulation showed an association with microvascular invasion, which is a proven risk factor for developing HCC metastasis. This clinical observation was compatible with preclinical findings. On the other hand, RSAD2 upregulation has been reported to confer poor prognosis in breast and gastric cancers. However, further clinical study of RSAD2 in HCC is lacking. As a result, we investigated the clinical implications of RSAD2 gene expression in HCC patients, in terms of its associations with survival, the presence of extra-hepatic metastasis, and other clinical manifestations. Methods: We studied 309 treatment-naïve HCC patients, as well as data from the TCGA and GTEx databases. Results:RSAD2 gene expression was differentially upregulated in HCC tumors when compared to normal liver tissues (p < 0.01). Elevated RSAD2 mRNA levels in the blood and the presence of extra-hepatic metastasis were independent prognostic factors for poor overall survival (OS) (p < 0.01). The median OS of patients with high RSAD2 expression vs. low expression were 5.4 vs. 14.2 months, respectively (p < 0.01). A high RSAD2 mRNA level was significantly correlated with the presence of extra-hepatic metastasis, nutritional disturbance, and functional impairment after controlling for confounding clinical factors (p < 0.05). Conclusions: High RSAD2 gene expression is associated with poorer OS, the presence of extra-hepatic metastasis, and quality-of-life disturbances in HCC patients.