Search Results (27,011)

Background: Diabetic retinopathy (DR) and chronic kidney disease (CKD) are among the leading causes of disability in individuals with type 1 diabetes mellitus (T1DM). However, the genetic architecture of these complications remains poorly understood. Genome-wide studies demonstrate significant interpopulation heterogeneity, while candidate gene studies yield conflicting results due to limited power. Independent replication of previously obtained results in separate cohorts, with appropriate intergroup comparisons, is essential for identifying the most significant biomarkers of microvascular complications in T1DM. Purpose: To search for associations of the most significant polymorphic variants rs55703767, rs72831309, rs118124843, rs9344715, rs183937294, rs4293393, rs12917707, rs77924615, rs11864909, rs9622363, rs73885319, rs2523989, rs3825932, rs763361, rs12708716, rs2292239, and rs4948088 with the risk of developing T1DM and its complications—DR and CKD. Methods: The study involved 618 individuals, including 522 patients with T1DM undergoing inpatient treatment at the Endocrinology Research Centre, as well as 96 control individuals without T1DM. Among the T1DM patients, 232 had concurrent CKD and retinopathy, while 80 were free of both microvascular complications. A comparison of allele and genotype frequencies of 17 single-nucleotide polymorphisms (SNPs) was conducted between the T1DM group and the control group, as well as an intergroup comparison between individuals with and without complications. Results: The rs2292239 (ERBB3) locus is associated with an increased risk (p_bonf = 0.001, OR = 2.02), while rs55703767 (COL4A3) is associated with a decreased risk of developing T1DM in general (p = 0.01846, OR = 0.42). rs9344715 (AKIRIN2) is associated with the risk of diabetic nephropathy (p = 0.03996, OR = 1.29), while PDILT variants rs77924615 (OR = 0.57, p_bonf = 0.045) and rs11864909 (OR = 0.41, p_bonf = 0.0105) with DR. Conclusions: The study identified potential genetic markers for the risk of type 1 diabetes and its microvascular complications. The results require further verification in an independent, expanded cohort. Consideration of genetic factors confirmed the independent contribution of the identified variants, supporting their value as promising biomarkers for risk stratification and personalized prevention of T1DM complications. Full article

Background/Objectives: The angiosome concept is widely used to guide infrapopliteal revascularization in patients with chronic limb-threatening ischemia (CLTI). However, clinical outcomes are not always fully explained by anatomical target-artery alignment alone. The present study aimed to revisit a previously published angiosome-based cohort through a wound-oriented conceptual perspective and to explore whether perfusion heterogeneity may help contextualize variability in clinical outcomes. Methods: This retrospective secondary analysis included 51 patients with CLTI who underwent infrapopliteal endovascular revascularization. Patients were originally classified as direct, indirect, or mixed revascularization according to angiosome-based criteria. The present study represents an exploratory conceptual reinterpretation of the original dataset. No new variables were introduced, and the woundosome concept was not operationalized as a measurable patient-level variable. Statistical analyses were exploratory and descriptive in nature. Results: High rates of wound healing and limb salvage were observed across all revascularization patterns at 12 months. Within the limitations of this small exploratory cohort, no consistent detectable differences in clinical outcomes were observed across anatomical revascularization patterns. Stratification according to the number of affected angiosomes did not reveal clear outcome differences. The findings suggest that factors beyond anatomical target-artery alignment may contribute to wound healing variability in CLTI. Conclusions: The present study does not establish a validated wound-oriented perfusion model but highlights the limitations of relying exclusively on anatomical angiosome classification when interpreting clinical outcomes in CLTI. In this context, the woundosome may serve as a descriptive and hypothesis-generating conceptual framework for discussing perfusion heterogeneity and wound-level perfusion complexity. Prospective studies integrating objective perfusion assessment and standardized wound evaluation are required. Full article

Background: Osteoporosis, a chronic disease with a major epidemiologic impact amid menopause might be aggravated by co-ailments such as adrenal tumours, with an increasing incidence due to a larger access to imaging evaluation. The objective was to evaluate bone profile in relationship with adrenal profile in non-functioning adrenal tumours (NFATs), based on menopausal DXA categories (osteoporosis, osteopenia and normal). Methods: A retrospective real-life study was conducted amid a cross-sectional analysis in anti-osteoporotic drugs naïve subjects. Adrenal profile included baseline morning plasma cortisol (base-cortisol), second-day cortisol (DST-cortisol) after 1 mg dexamethasone testing, ACTH, and largest tumour diameter at CT (D-CT). Results: Ninety-five patients (mean age 61.59 ± 7.83 years) had 24.21% osteoporosis, 47.37% osteopenia, and 28.42%—normal DXA. Base-cortisol, DST-cortisol, ACTH and D-CT were similar between the groups. Total serum calcium was lower in osteoporosis versus osteopenia, versus normal DXA (9.26 ± 0.52 versus 9.61 ± 0.41 mg/dL, p = 0.005, respectively, 9.79 ± 0.47 mg/dL, p < 0.001). Osteocalcin, respectively, CrossLaps were elevated in osteoporosis versus osteopenia. MACS prevalence was 27.37% (no between-group difference). Osteoporosis group: CrossLaps correlated with DST-cortisol (r = −0.550, p = 0.019). Multiple linear regression model to predict lumbar BMD explained 47.1% of the variance in lumbar BMD (R² = 0.471). ACTH was an independent variable for lumbar BMD (p = 0.007). BMI represented the main influential contributor to this model having the highest β of 0.490, and it also explained 49.1% (R² = 0.491) of total hip BMD variation. Conclusions: This study emphasises a heterogeneous connection between adrenal profile in NFATs and clinical evaluation of the bone status. More comprehensive prospective studies are mandatory to assess this multifactorial bone–adrenal interplay in order to improve the overall management. Full article

Fibromyalgia is a chronic syndrome associated with pain, fatigue, and cognitive symptoms, often linked to gut microbiota alterations. The Mediterranean Diet (MD), particularly extra-virgin olive oil (EVOO), has antioxidant and anti-inflammatory properties that may beneficially modulate the microbiota. We conducted a prospective, randomized, double-blind, placebo-controlled clinical trial that included 250 women (206 with fibromyalgia, 44 controls). Participants followed a MD supplemented with EVOO or refined olive oil (placebo) for six months. Microbiota composition was analyzed at four time points (T0–T3) by 16S rRNA sequencing (V3–V4). At baseline, fibromyalgia patients exhibited reduced microbial diversity compared to controls. While global diversity did not change after intervention, specific taxa increased significantly with EVOO, including Bacteroides fragilis, Anaerotruncus colihominis, Adlercreutzia equolifaciens, and butyrate producers such as Faecalibacterium prausnitzii, Roseburia intestinalis, and Agathobacter. These shifts suggest EVOO supplementation might promote anti-inflammatory and metabolic bacteria, suggesting diet as a complementary strategy to modulate gut microbiota in fibromyalgia. Full article

Chronic ulcers are characterized by impaired tissue repair and frequently harbor antimicrobial-resistant microorganisms, worsening clinical outcomes. The objective of this study is to identify microbial agents in chronic ulcers treated at the Lauro de Souza Lima Institute Wound Care Outpatient Clinic and to evaluate their antimicrobial susceptibility profiles and β-lactamase production. Samples (swab and biopsy) from patients treated at the Lauro de Souza Lima Institute were analyzed. Susceptibility was assessed by disk diffusion. ESBL and AmpC production were confirmed by PCR targeting blaTEM, blaSHV, blaCTX-M1, and blaCMY-2. In Staphylococcus spp., oxacillin and clindamycin resistance were evaluated and confirmed by mecA and ermAC. From 33 patients (mean age 63.4 years), 116 isolates were obtained, mainly Pseudomonas aeruginosa (27%), Proteus mirabilis (18%), and Staphylococcus aureus (13%). P. aeruginosa showed high resistance, with 48% MDR and 29% PDR. Among Enterobacterales, 19% were ESBL producers and 17% AmpC, with 56% carrying blaCMY-2. In Staphylococcus, 33% were oxacillin-resistant and 50% expressed MLSb phenotype. P. aeruginosa was identified as the most prevalent pathogen, with frequent MDR/PDR phenotypes. Resistance genes exhibited a discrepancy between genotypic and phenotypic profiles, suggesting the presence of unexpressed resistance that may be inducible during treatment. Full article

Background/Objectives: Clostridioides difficile infection (CDI) is the leading cause of colitis and hospital-acquired diarrhea. Patients with Chronic Obstructive Pulmonary Disease (COPD) frequently have infectious exacerbations requiring treatment with antibiotics, which may be predisposing them to CDI. This study examines the prevalence and in-hospital outcomes of CDI in patients with COPD. Methods: Data for hospitalized patients with CDI was extracted from the National Inpatient Sample database for the years 2016 through 2020. Baseline risk factors were identified using the International Classification of Diseases codes. Patients were stratified into two groups: with COPD and without COPD. The primary outcome was in-hospital mortality. The secondary outcomes were septic shock, hypovolemic shock, AKI, cardiac arrest, need for intensive care unit (ICU) level of care and length of stay. Statistical analyses were conducted using SPSS. Results: 290,172 patients were included in this study. Patients with COPD had more comorbidities overall and higher in-hospital mortality rates compared to patients without COPD (7.7% vs. 5.9%, p < 0.001). On multivariate logistic regression analysis, patients with CDI and COPD had higher risk of in-hospital mortality (OR = 1.346, p < 0.001), septic shock (OR = 1.289, p < 0.001), hypovolemic shock (OR = 1.184, p < 0.001), cardiac arrest (OR = 1.362, p < 0.001) and required more ICU level of care. Conclusions: Patients with COPD experience frequent exacerbations, often requiring hospitalizations and broad-spectrum antibiotics, steroids, proton pump inhibitors and antacids. These factors contribute to the higher prevalence of CDI in this patient population. Patients with CDI and COPD are also more likely to require ICU level of care, shedding the light on the significant burden of CDI, long hospital stays and substantial hospital charges. Recognizing mortality outcomes is essential to guide patient-specific therapies and highlights the need for closer monitoring and targeted management of CDI in patients with COPD. Full article

Background: Fibromyalgia syndrome (FMS) is a syndrome that commonly affects the musculoskeletal system and is characterized by fatigue and body aches. Recent studies have demonstrated a relationship between FMS and certain immunological markers. In this study, we investigated the relationship between MMP-3, IL-6, IL-6R, and TNF-α serum levels and disease impact (FIQ score) in FMS patients. Methods: This case–control study consisted of 164 participants, of whom 82 were patients with fibromyalgia syndrome (FMS) and 82 were healthy controls without FMS, chronic pain, or inflammatory diseases. Disease impact was assessed using the Fibromyalgia Impact Questionnaire (FIQ). MMP-3, IL-6, IL-6R, and TNF-α serum levels were detected using enzyme-linked immunosorbent assay (ELISA) kits. Results: In patients diagnosed with FMS, TNF-α, IL-6, IL-6R, and MMP-3 levels were significantly higher than those of the control group (all p < 0.0001). MMP-3, IL-6, IL-6R, and TNF-α levels correlated positively with the FIQ score. Conclusions: This study highlights the involvement of inflammatory processes in FMS, particularly the role of serum IL-6, TNF-α, IL-6R, and MMP-3 levels in the pathophysiology of FMS. The results indicate that inflammatory markers may be associated with the severity of FMS and may have potential as disease markers. Full article

Objective: Electrocorticography can serve as an intraoperative research tool during deep brain stimulation procedure, when patients are awake to participate in behavioral tasks or to allow recordings while awake but at rest. This report aims to describe the electrocorticography methods used in awake patients undergoing deep brain stimulation surgery at a single center and to describe the feasibility, safety, and usefulness of high-density electrocorticography for capturing high-resolution neurophysiological data during deep brain stimulation surgery. We hypothesize that the use of high-density electrocorticography and multi-subject integration of cortical data enables improved spatial resolution and data analysis compared to prior studies employing lower-density electrodes and primarily single-subject analyses. Methods: Data were obtained from patients undergoing awake deep brain stimulation surgery for the treatment of Parkinson’s disease or essential tremor at Johns Hopkins Hospital between March 2022 and September 2024. Electrophysiological and anatomical data were analyzed, with localization in the anterior commissure and posterior commissure and Montreal Neurological Institute coordinate systems. Surgical complications were monitored for at least six months postoperatively. Results: Thirty-six patients (26 with Parkinson’s disease, 10 with essential tremor) were enrolled in the study. In one case, anatomical placement was inadequate for neurophysiological analysis. Postoperative complications included three infections (8.3%) and one chronic subdural hematoma (2.8%), with no permanent neurological deficits. Observed complication rates were within the range reported in the literature for standard deep brain stimulation surgeries without electrocorticography. Anatomical and neurophysiological analysis demonstrated high-resolution cortical mapping. Multiple-subject level analysis using high-density electrocorticography yielded over 1300 electrode positions. Conclusions: Electrocorticography during deep brain stimulation is a valuable research method for movement disorders and, based on a moderate sized consecutive clinic sample, appears safe with risks no greater than those associated with DBS surgery itself. Full article

Background: Lichen planus (LP) is a chronic inflammatory dermatosis with multiple clinical variants involving the skin, mucous membranes, nails, and hair follicles. Methods: We conducted a retrospective, descriptive study of patients diagnosed with LP at a tertiary referral center from January 2011 to December 2024. Inclusion required concordance between clinical presentation and histopathologic findings. Demographic characteristics, LP subtypes, anatomical involvement, comorbidities, therapeutic approaches, and treatment outcomes were extracted from electronic health records. In addition, an exploratory sensitivity analysis restricted to patients with a single LP subtype was performed to allow for independent subgroup comparisons, and a modified Charlson Comorbidity Index (CCI) based on available comorbidity domains was calculated. Pairwise multivariable logistic regression models adjusted for age, sex, and outcome-specific modified CCI were performed for selected comorbidities. Results: A total of 754 patients were included (mean age 53.1 years), with cutaneous LP (cLP), oral LP (oLP), genital LP (gLP), and lichen planopilaris (LPP) being the most frequent subtypes; a total of 620 had a single major LP subtype and were included in the mutually exclusive analysis. In these groups, modified CCI, age-adjusted modified CCI, and overall comorbidity count differed significantly across subtypes (Kruskal–Wallis p < 0.001). After adjustment in pairwise models, cLP-only showed higher odds of malignancy compared with oLP-only, gLP-only, and LPP-only and higher odds of diabetes mellitus compared with all other pure subtypes. Most other comorbidity comparisons were non-significant or imprecise because of low event numbers. Topical glucocorticoids were the most frequently used treatment, and treatment responses varied by subtype, being more effective in cLP and gLP compared to LPP. Topical calcineurin inhibitors demonstrated the highest response rates in gLP. Acitretin was most effective in cLP, whereas isotretinoin showed favorable responses in oLP. Conclusions: This large, histopathologically confirmed cohort highlights distinct differences in comorbidity patterns, anatomical involvement, and therapeutic response across LP subtypes. Treatment outcomes vary substantially by subtype, underscoring the need for individualized management strategies. Prospective studies are warranted to further elucidate subtype-specific disease associations and optimize treatment approaches. Full article

Background/Objectives: Long COVID-19 (LC-19), also known as Post-Acute COVID-19 Syndrome (PACS), is a chronic condition some people experience after an initial SARS-CoV-2 infection. The etiology of this complex, multifactorial disease remains largely unknown, although various theories have been propounded. This study aims to profile and compare the metabolic activity of cells of normal and LC-19 patients. Methods: A cohort of 20 individuals, 10 with LC-19 and 10 without LC-19, was selected based on their post-COVID-19 symptomatology. Saliva was tested for opportunistic viruses like Epstein–Barr virus (EBV) and Human Herpesvirus 6 (HHV-6). Lymphoblastoid cell lines derived from blood were analyzed using the Biolog Phenotype Mammalian Microarrays (PM-M1, PM-M6, and PM-M7) to assess metabolic activity across a wide array of growth substrates and effector molecules. Results: Unique metabolic profiles emerged across the controls and LC-19 groups. The SARS-CoV-2 infection causes an over two-fold enhanced utilization of glycolytic and anaerobic substrates and a reduced response to growth factors and effectors. The increased energy source utilization assessed in PM-M1 is unsustainable, and the LC-19 groups demonstrate this with a clear correlation with the number of LC-19 symptoms, demonstrating a trend consistent with metabolic reprogramming. The infection also results in a reduced response to growth factors and effectors, assessed in PM-M6 and PM-M7, with the level of reduction commensurate with the symptom burden. Conclusions: The data from the patient groups were analyzed and compared to construct a metabolic profile unique to individuals who developed LC-19, which could, in the future, be used for diagnosis and to identify targets for therapeutic intervention. Our study identified an LC-19-specific metabolic profile indicative of adaptive responses to stress, cellular dysfunction, and prolonged inflammation, leading to the reprogramming of bioenergetic pathways. Full article

Background/Objectives: Effective wound antisepsis and infection control remain central challenges in both acute and chronic wound management. pH-controlled sodium hypochlorite solution (HACCP’ER^®) is a novel agent that optimizes the proportion of bactericidal hypochlorous acid (HOCl) by maintaining pH at 6.0–7.3. The present preliminary study aimed to evaluate its broad-spectrum antimicrobial activity in vitro and clinical outcomes in a retrospective cohort of patients with diverse acute and chronic wounds. Methods: A retrospective observational study was conducted, involving 193 consecutive patients who received HACCP’ER-based wound care between May 2022 and February 2023. Wound categories included pressure ulcers (n = 61), foot ulcers (n = 44), burns (n = 42), acute traumatic wounds (n = 29), and other chronic wounds (n = 17). HACCP’ER was applied at a free available chlorine (FAC) concentration of 50–200 ppm at pH = 6.0–7.3. In vitro antimicrobial suspension testing against ten microbial species was performed at 57 ppm (pH = 5.2, 23 °C) according to Japanese Industrial Standards. Results: HACCP’ER at 57 ppm eliminated Escherichia coli, Staphylococcus aureus, methicillin-resistant S. aureus (MRSA), Streptococcus spp., Salmonella spp., and Pseudomonas aeruginosa to below the detection limit (<10 CFU/mL) within 1 min, Candida within 3 min, and black Aspergillus within 5 min. In clinical wound cultures, bacterial burden was reduced in 6 of 10 (60%) patients. The mean patient age was 67.4 years. No adverse events attributable to HACCP’ER were recorded. Progressive wound healing was documented across all wound categories, with representative cases achieving closure at 1–11 months. Conclusions: HACCP’ER demonstrates potent broad-spectrum antimicrobial activity at wound-relevant concentrations and is clinically safe in acute and chronic wound care. Its physiologically aligned mechanism of HOCl generation supports both efficacy and biocompatibility. Prospective randomized controlled trials are warranted to definitively establish clinical efficacy. Full article

High-phenolic extra-virgin olive oil (EVOO) is a chemically dynamic bioactive matrix in which cultivar, ripening stage, processing, storage, and digestion shape the final profile of phenolic alcohols and secoiridoids. In inflammatory bowel disease (IBD), chronic intestinal inflammation is associated with barrier dysfunction, dysbiosis, systemic immune activation, endothelial injury, platelet hyperreactivity, and increased cardiovascular risk. This narrative review evaluates whether EVOO phenolics may intersect the gut–endothelium–platelet axis linking IBD to vascular and thromboinflammatory complications. The review focuses on hydroxytyrosol, tyrosol, oleuropein- and ligstroside-derived secoiridoids, oleocanthal, and oleacein, with emphasis on their biosynthetic origin, processing-driven transformations, bioavailability, metabolism, and biological targets. Current evidence supports plausible effects on epithelial barrier integrity, TLR4/NF-κB signalling, Nrf2-mediated antioxidant defence, oxidised LDL formation, endothelial activation, and platelet-related pathways. Nevertheless, direct clinical evidence in IBD patients remains limited, and most cardiovascular-relevant findings are extrapolated from non-IBD human trials, animal studies, or in vitro models. Chemically characterised, biomarker-anchored intervention trials are needed before high-phenolic EVOO can be considered a validated strategy for modifying cardiovascular risk in IBD. Full article

Background: Chronic limb-threatening ischemia (CLTI) is associated with high morbidity and substantial healthcare utilization. Length of hospital stay (LOS) after lower limb revascularization is influenced by procedural complexity, but patient physiological reserve may also play a role. We evaluated whether CT-derived lean psoas muscle area (LPMA) is independently associated with LOS in patients undergoing revascularization for CLTI. Methods: We retrospectively analyzed 234 consecutive patients treated with endovascular, hybrid, or open revascularization for CLTI (Rutherford 4–5) between 2018 and 2021. Sarcopenia markers were derived from preoperative CT at the L3 level, including psoas muscle area (PMA), muscle density (PMD), and LPMA. Multivariable linear regression models with log-transformed LOS were used to estimate relative effects on hospitalization duration. Results: Median age was 68 years and 65.4% were male; 76.5% of admissions were urgent. Median LOS was 6 days (IQR 4–9). Procedure type was the strongest determinant of LOS: hybrid (β = 0.69, p < 0.001) and open surgery (β = 0.73, p < 0.001) were associated with approximately 99% and 108% longer LOS compared with endovascular treatment. Higher LPMA was independently associated with shorter LOS (β = −0.00049, p = 0.004). Smoking (β = −0.21, p = 0.003) and history of myocardial infarction (β = −0.19, p = 0.030) were associated with shorter LOS, whereas dialysis showed a non-significant trend toward longer hospitalization (β = 0.36, p = 0.056). Conclusions: In patients undergoing lower limb revascularization for CLTI, CT-derived LPMA demonstrated a modest but independent association with hospital stay duration after adjustment for procedural and clinical factors. Given the exploratory nature of this study, these hypothesis-generating findings support further evaluation of imaging-based muscle assessment as an adjunct marker of physiological reserve in this high-risk population. Full article

Background/Objectives: Migraine may be associated with structural changes in the brain, including the cerebellum and brainstem. Some of these changes reflect the brain’s plasticity in adapting to migraine-related alterations, but others may influence the severity of migraines and resistance to treatment. Some studies report changes in cortical thickness among migraine patients, and focal cortical dysplasia (FCD) has been considered a possible cause of these changes. We argued that FCD could contribute to the development of migraine and the severity of its symptoms. To date, there has been no consistent report of FCD occurring in migraine patients. Case: A 29-year-old woman presented with a history of at least 19 years of high-frequency episodic migraine without aura. She experienced motion sickness during childhood and adolescence. Her condition worsened last year, evolving into chronic migraine, which was partially controlled by medications such as amitriptyline and rizatriptan, leading to high-frequency episodic migraines. An MRI conducted in 2024 showed a small area of signal abnormality in the left occipital lobe, believed to represent cortical dysplasia. A follow-up MRI after three months showed no changes in this area. She is currently diagnosed with high-frequency episodic migraine and demonstrated severe migraine-related disability, with a MIDAS score of 25, and a severe impact on daily functioning, with a HIT-6 score of 65. Conclusions: The case involves a worsening migraine that was somewhat alleviated by a pharmacological intervention. FCD may contribute to brain hyperexcitability in this case and her motion-related problems during childhood and adolescence. FCD could also play a role in the increasing severity of her migraines and her partial resistance to medication. Full article

Myalgic Encephalomyelitis (ME) is a chronic, multisystem disease characterized by systemic metabolic dysfunction and post-exertional malaise (PEM). In this study, we investigated the dysregulation of irisin, an exercise-induced myokine, and its potential antagonism by thrombospondin-1 (TSP-1). In a cross-sectional study (92 ME patients vs. 44 sedentary healthy controls), plasma irisin and TSP-1 levels were measured at baseline and after a 90 min mechanical stress challenge applied to induce PEM. ME patients exhibited significantly lower baseline irisin (p < 0.05) and a blunted exertional response (p < 0.05). Paradoxically, baseline irisin was an independent predictor of fatigue severity (β = 0.728, p = 0.018), with moderate-to-severe patients showing elevated levels of both irisin and TSP-1 (p < 0.05), suggesting a compensatory but ineffective response. Functional cellular dielectric spectroscopy indicated that TSP-1 inhibits irisin signaling in a concentration-dependent manner. Irisin signaling was markedly reduced by both αvβ5 blockade and HSP90α inhibition in this experimental system, consistent with a diminished ability to counteract TSP-1. Collectively, these findings support a model in which dysregulation of the irisin–TSP-1 axis contributes to metabolic dysfunction in ME. Elevated circulating TSP-1 levels are associated with symptom severity and are linked to impaired irisin signaling in an HSP90α- and αvβ5-dependent context. This interaction is consistent with defective metabolic adaptation and highlights a potential therapeutic target that warrants further validation to restore energy homeostasis. Full article