Search Results (42,624)

Cervical dystonia (CD) is the most common adult-onset focal dystonia, with heterogeneous clinical presentation and significant functional impairment. Currently, no structured Italian good clinical practice documents specifically addressing CD have been published. Optimizing CD management requires expert-based recommendations to guide diagnosis, treatment, and follow-up. A two-round Delphi process was conducted, involving a scientific board of six neurologists with expertise in CD management and an external panel of 56 Italian experts (neurologists and physiatrists managing CD patients). Fifty-two statements were developed, discussed, and voted using a 5-point Likert scale, with consensus defined as ≥75% agreement (‘strongly agree’ or ‘somewhat agree’). In Round 1, 48 of 52 statements (92.4%) reached consensus; the four remaining statements were revised, and two were re-voted in Round 2, both achieving consensus. Final recommendations emphasize comprehensive patient assessment in multiple postural conditions; individualized botulinum neurotoxin type A (BoNT-A) dosing taking into account tonic and phasic components, pain, and dysphagia; the use of instrumental guidance; standardized outcome measures; and integration of physiotherapy and psychological support. This article provides structured good clinical practice recommendations for CD management and offers clinicians, especially those with limited experience, a practical framework to standardize care, optimize treatment, and improve patient outcomes. Full article

Background and Objectives: Diabetic retinopathy (DR) is a leading microvascular complication of type 2 diabetes (T2D). Fractalkine (CX3CL1), a chemokine involved in inflammation, angiogenesis, and microglial activation, may play a role in DR pathogenesis. This study investigated the association between serum fractalkine levels, the presence of DR, and disease severity. Materials and Methods: In this cross-sectional study, 140 adults with T2D were classified as non-DR (n = 32) or DR (n = 108) according to ICDR and ETDRS criteria; DR cases were further categorized into NPDR (n = 76) and PDR (n = 32), with NPDR staged as mild, moderate, or severe. Serum fractalkine concentrations were measured using ELISA. Results: Serum fractalkine levels were significantly higher in patients with DR than in those without retinopathy (0.7 vs. 0.4 ng/mL, p < 0.001). Within NPDR stages, fractalkine levels were highest in severe NPDR (p = 0.004). No significant fractalkine difference was found between NPDR and PDR groups. In multivariable analysis, serum fractalkine (OR 10.2; 95% CI 1.2–89.6; p = 0.036) remained independently associated with the presence of DR. For identifying DR, fractalkine yielded an AUC of 0.736; the optimal cut-off of 0.455 ng/mL provided 81.5% sensitivity and 56.3% specificity. In distinguishing severe NPDR, fractalkine demonstrated strong diagnostic performance (AUC = 0.784), with a cut-off of 0.720 ng/mL yielding 100% sensitivity and 61.9% specificity. Conclusions: Serum fractalkine is significantly associated with both the presence and severity of DR and remains independently associated with retinopathy after adjustment for traditional risk markers. Serum fractalkine may offer complementary systemic information in automated and AI-based retinal screening. These findings are exploratory and hypothesis-generating, and prospective studies are required to determine the clinical relevance of serum fractalkine in DR. Full article

Background/Objectives: This study evaluated the diagnostic accuracy of cervical cytology, CINtec^® (p16/Ki-67 dual staining), and PD-L1 immunohistochemistry, individually and in combination with high-risk HPV (HR-HPV) testing, for identifying histologically confirmed cervical lesions ranging from CIN1 to invasive carcinoma. Methods: We conducted a prospective cross-sectional study including 114 patients who underwent cervical cytology, CINtec^®, PD-L1 staining, HPV genotyping, and histopathologic confirmation at a tertiary clinical center between September 2024 and September 2025. Sensitivity, specificity, PPV, NPV, and ROC performance were calculated for each test across lesion categories. Multivariable logistic regression models incorporating HR-HPV status were used to assess added predictive value. Results: All tests showed poor performance for CIN1 (cytology AUC 0.488; CINtec^® 0.374; PD-L1 0.366). Diagnostic accuracy improved markedly with lesion severity. For CIN3, CINtec^® demonstrated the highest discriminative ability (AUC 0.826), with cytology and PD-L1 also performing well (AUC 0.820 and 0.753). Cytology achieved the strongest ROC performance for CIN2+ (AUC 0.937), CIN3+ (0.913), and invasive carcinoma (0.887). PD-L1 consistently showed lower accuracy across categories. Cytology + HR-HPV demonstrated the highest AUC across all lesion categories. Conclusions: Cytology and CINtec^® exhibited strong diagnostic accuracy for high-grade lesions, while PD-L1 showed limited utility as an independent screening marker. Combining cytology with HR-HPV testing enhanced predictive performance across all lesion categories. These findings support the continued use of cytology-based triage and highlight CINtec^® as a valuable adjunct for high-grade disease detection. Because this study used a high-prevalence referral cohort, specificity may be overestimated and not representative of population-based screening. Full article

Background/Objectives: Artificial intelligence (AI) has shown potential in patient education and integration into clinical decision support systems. However, its performance in counseling patients on breast reconstruction currently remains underexplored. This study’s objective is to compare AI-generated answers with expert surgeon responses to common patient questions (derived from clinical scenarios) in domains like oncological justification, reconstructive options, and postoperative care. Methods: We realized an observer-blinded study using five real-world clinical scenarios in the field of oncologic and reconstructive surgery of the breast. Both ChatGPT-5 (October 2025 version) and a senior board-certified plastic surgeon responded to frequently asked questions, which were split into three domains: (1) oncological and surgical justification; (2) reconstruction options and outcomes, respectively; and (3) postoperative period. The answers were evaluated by another senior plastic surgeon using a four-grade ordinal scoring system (1 = unsatisfactory, 4 = excellent), which assessed accuracy, completeness, safety, nuance, and alignment with the current guidelines. Results: Across a total of 40 questions, the average AI response score was 3.1 ± 0.6. Domain-specific items scored lowest values for oncological justification (2.8 ± 0.7) and higher values for reconstruction options/outcomes and postoperative care (both 3.2 ± 0.4). No AI response was graded as unsatisfactory (score 1). Responses graded 4 (15%) were considered comprehensive, accurate, and patient-friendly. Conclusions: Globally, ChatGPT-5 provides satisfactory, readable, and medically accurate answers to basic patient questions on breast reconstruction, with a few limitations in nuanced oncological justification. Full article

Background: Cardiac computed tomographic angiography (CTA) detects patent foramen ovale (PFO) with variable accuracy. This study investigated factors affecting CTA detectability for PFO in patients with suspected PFO-associated stroke. Methods: Consecutive patients with cryptogenic stroke and positive findings on contrast transcranial Doppler (cTCD) examinations were enrolled between November 2020 and April 2023 in this retrospective study. Each participant underwent transesophageal echocardiography (TEE) and cardiac CTA. Patients with confirmed PFO on TEE were categorized into two groups based on CTA detectability: the CTA-positive group (PFO identified by CTA) and the CTA-negative group (PFO missed by CTA). Univariate and multivariate logistic regression analyses were performed to identify predictors of CTA false-negative results. Results: Among 108 patients (mean age 46.7 ± 14.9 years, 47.2% male), the prevalence of PFO by TEE was 94.4% (102/108). Compared to TEE, cardiac CTA had a sensitivity of 70% (95%CI 61–79%), a specificity of 100% (95%CI 54–100%), a positive predictive value of 100% (95%CI 95–100%), and a negative predictive value of 16% (95%CI 6–32%). Among patients with PFO confirmed by TEE (n = 102), the incidence of moderate to large right-to-left shunts (RLS) was significantly higher in the CTA-positive group than in the CTA-negative (77.5% vs. 22.5%, p < 0.001). After adjusting for confounders, patients with moderate to large shunts showed a significantly lower likelihood of a CTA false-negative result compared to those with small shunts (OR 0.113, 95%CI 0.035–0.365, p < 0.001). In patients with moderate to large RLS, the sensitivity of cardiac CTA for diagnosing PFO increased to 90.16% (95% CI 82.69–97.64%). Conclusion: Cardiac CTA could be an effective complementary modality for selected patients with suspected PFO-associated stroke. Its diagnostic performance appears more reliable for identifying PFO in patients with moderate-to-large RLS than in those with small RLS. Full article

Background and Objectives: Mechanical alignment (MA) has long been the gold standard in total knee arthroplasty (TKA), aiming for neutral hip–knee–ankle alignment with proven long-term survivorship. However, up to 20% of patients remain dissatisfied, often due to neglect of individual constitutional limb variation and subsequent soft tissue imbalance. This has driven the development of alternative alignment philosophies. This current concepts review aims to determine the various evolving alignment strategies, elucidate their underlying principles, and demonstrate the available clinical outcomes data. Materials and Methods: This review examines MA and the paradigm shift towards personalized alignment techniques, including Kinematic Alignment (KA), restricted Kinematic Alignment (rKA), inverse Kinematic Alignment (iKA), adjusted mechanical alignment (aMA), and the most recent evolution, Functional Alignment (FA). Results: Kinematic alignment and its derivatives (rKA, iKA) seek to better replicate native joint morphology and tension, often reducing the need for soft tissue releases and improving functional outcomes compared to MA. rKA and iKA introduce protective boundaries to avoid extreme phenotypes and possible instability. FA leverages robotic platforms and integrates these principles with real-time gap balancing, demonstrating promise for consistent, personalized outcomes. Some reports, however, advise caution with adjusted Mechanical Alignment (aMA), particularly those that result in phenotypes such as Coronal Plane Alignment of the Knee (CPAK) VII or VIII, which may increase the risk of revision. Conclusions: The philosophy of TKA has evolved from a uniform mechanical target (MA) to a more nuanced, patient-specific strategy. While promising mid- to long-term outcomes and comparable survival data support the viability of KA and its derivatives, critical needs remain, including standardizing nomenclature (especially for FA) and conducting high-quality comparative trials. Future directions involve leveraging high-volume intraoperative data and Artificial Intelligence (AI) to refine decision-making and further personalize alignment strategies, without compromising long-term implant survivorship. Full article

Background: The monocarboxylate transporter 1 (MCT1) plays a central role in myocardial lactate handling and metabolic adaptation. The functional rs1049434 polymorphism (T1470A; Asp490Glu) affects MCT1-mediated lactate transport and substrate utilization, but its clinical relevance in sarcomere-related hypertrophic cardiomyopathy (HCM) remains poorly defined. Methods: We studied 56 carriers of pathogenic or likely pathogenic sarcomeric variants examined in a familial HCM program. All participants underwent standardized clinical phenotyping, including electrocardiography, transthoracic echocardiography, and cardiac magnetic resonance imaging. Genotyping of MCT1 rs1049434 was performed on genomic DNA. Analyses focused on sex-stratified genotype distribution, phenotypic expression among the 26 individuals who fulfilled diagnostic criteria for HCM, and the influence of habitual vigorous exercise. Septal wall thickness was the primary structural endpoint. Results: Among the 26 patients with established HCM (10 women, 16 men), a marked sex-specific effect emerged. Female carriers of the T-allele (TT/TA) exhibited significantly greater interventricular septal thickness compared with AA homozygotes (23.2 vs. 14.2 mm; p = 0.037). In men, septal thickness did not differ by genotype. However, male patients engaged in vigorous physical activity showed a consistently milder structural phenotype, including lower septal thickness (18.3 vs. 19.9 mm; p = 0.585) and directionally favorable markers of mechanical severity. Phenotypic distribution was predominantly asymmetric septal hypertrophy in both sexes, without genotype-dependent differences. Conclusions: The phenotypic impact of MCT1 rs1049434 in sarcomere-positive HCM is context-dependent. In women, impaired monocarboxylate handling is associated with greater hypertrophic remodeling, whereas in men, exercise-related metabolic conditioning appears to attenuate disease severity. These findings support a genotype–sex–environment interaction relevant to precision medicine approaches in HCM. Full article

Breast cancer (BC) remains one of the most prevalent malignancies worldwide, and genetic factors may influence its development. Approximately 10–15% of all BCs are hereditary and known as Hereditary Breast Cancer (HBC). A remarkable family history and young onset are the strongest risk factors of HBC. The rapid development of genetic testing techniques has increased the detection rate of pathogenic and likely pathogenic variants in several genes associated with high, moderate, or low risk of HBC. This allowed us to identify the whole family at risk of HBC. Among hereditary cases, pathogenic variants (PVs) in the BRCA1 and BRCA2 genes are particularly notable, especially in certain populations where founder mutations (specific genetic variants originating from a common ancestor) are more prevalent. In this article, an overview of the current state of knowledge on HBC is provided, focusing on the frequency of founder mutations in the BRCA1 and BRCA2 genes in HBC in Poland compared to other countries. We will also highlight the role of genetic counseling in the diagnosis and treatment of BC, emphasizing its crucial importance in identifying genetic predispositions, selecting appropriate therapeutic strategies, and supporting patients and their families in making informed medical decisions. Full article

Background/Objectives: Hydroxychloroquine (HCQ) is widely used in the treatment of autoimmune rheumatologic diseases due to its immunomodulatory and anti-inflammatory properties. However, long-term HCQ therapy carries a risk of irreversible retinal toxicity caused by drug accumulation in the retinal pigment epithelium. The early identification of preclinical retinal changes is essential to prevent permanent visual impairment. Optical coherence tomography (OCT) and OCT-angiography (OCT-A) have emerged as key imaging modalities for the detection of structural and microvascular biomarkers of HCQ retinopathy. A narrative review of the literature was conducted using the PubMed database, focusing on studies published between January 2017 and February 2025. Search terms included “hydroxychloroquine” and “optical coherence tomography.” Eligible studies evaluated HCQ-related retinal toxicity using OCT and/or OCT-A in human subjects. Data were extracted regarding study population characteristics, treatment duration, cumulative HCQ dose, daily dose normalized to real body weight, and reported imaging findings. Results: We identified 223 scientific papers of which 88 studies met the inclusion criteria. Structural OCT parameters—particularly alterations in the ellipsoid zone, outer nuclear layer, and retinal pigment epithelium—were consistently associated with early HCQ toxicity, often preceding functional impairment. OCT-A studies demonstrated microvascular alterations, including reduced vessel density and foveal avascular zone enlargement, though interpretation may be confounded by underlying autoimmune-disease-related vasculopathy. Conclusions: HCQ retinopathy is a potentially vision-threatening condition associated with the cumulative dose, treatment duration, and patient-specific risk factors. OCT and OCT-A provide complementary structural and vascular biomarkers that aid in the detection of subclinical retinal toxicity. The integration of quantitative and automated OCT-derived metrics may improve screening strategies, facilitate early diagnosis, and support personalized care in patients receiving long-term HCQ therapy. Full article

Background: The aim of this study is to investigate the potential link between the use of specific medications and oral adverse drug reactions. Methods: The 100 most frequently prescribed drugs in Germany in 2023 were compiled using the “PharMaAnalyst” database. According to the descriptions of adverse drug reactions (ADRs) in the patient information leaflets the ADRs were selected, analyzed and weighted with scores according to a classification system that distinguishes four groups of ADRs by frequency: ‘very common’ (4), ‘common’ (3), ‘uncommon’ (2) and ‘rare’ (1). The objective was to summarize the scores of the oral ADRs and define the ‘oral side effect score’ (OSES). Results: After accounting for duplication due to various brand names, 49 medications were reviewed. A total of 65% of the medications exhibited oral ADRs. The number of oral ADRs per medication ranged from one to seven. Xerostomia and dysgeusia were the most prevalent oral side effects, accounting for 37% of cases. Overall, 34% of side effects were classified as either ‘very common’ or ‘common’. The medication groups with the highest OSES were antidepressants, antibiotics and analgesics. Of the individual medications, azithromycin, gabapentin and pregabalin exhibited the highest OSES. Conclusions: This study provides a comprehensive overview of oral side effects associated with the 100 most frequently prescribed drugs. Patients with polypharmacy are particularly likely to experience oral side effects such as xerostomia and dysgeusia. Due to their high OSES combinations, antibiotics, analgesics or antidepressants may trigger multiple oral ADRs. It is essential that the medical community is continuously updated on pharmacological knowledge to raise awareness of oral ADRs. Full article

Background/Objectives: Diabetes is major metabolic disorder and rapidly increasing public health problem globally. The greatest way to reduce diabetic complications is adequate knowledge about the condition. Hence, the primary objectives of this study were to evaluate the psychometric properties of the Simplified Diabetes Knowledge Test—Arabic version (SDKT-A) among Iraqi insulin-dependent diabetic patients. Additionally, the secondary objectives were to assess the associated independent variables and the risk of atherosclerosis and cardiovascular risk event by using atherogenic indices and lipid ratios with the SDKT-A. Methods: A cross-sectional, descriptive study was conducted in primary healthcare clinics. The SDKT was translated into Arabic using forward–backward translation, reconciliation, and pilot testing. Thereafter, psychometric properties of the SDKT-A were evaluated depending on different criteria. Atherogenic indices of Castelli risk indices I and II (CRI-I and II), triglyceride/HDL ratio, non-HDL-C ratio, atherogenic coefficient (AC), and triglyceride–total cholesterol–body weight index (TCBI) were calculated using specific formulas. Results: The SDKT-A questionnaire showed acceptable readability and validity. Cronbach’s alpha test (95% confidence interval) was 0.662 (0.59–0.73). The Pearson correlation coefficient of reliability for test–retest was found to be 0.659. The item difficulty index for most items was between 0.237 and 0.877. The point biserial correlation values ranged from 0.028 to 0.535 with Ferguson’s sigma value equal to 0.962. The content validation results showed a significant content validity ratio (CVR) value for most of the questions, ranging from 0.8 to 1. The content validity index (CVI) value for SDKT-A was found to be 0.98, which showed good agreement between experts. In addition, the exploratory factor analysis with promax rotation identified four domains for the final 20 items of the SDKT-A that explained 41.83% of the scale total variance. The mean score of the SDKT-A was 11.09 ± 3.40. The total score of the SDKT-A was positively and significantly correlated with education level (r = 0.322, p < 0.01). In addition, the total scores of the SDKT-A were negatively and significantly correlated with glycemic control, age, CRI-I, CRI-II, triglyceride/HDL ratio, AC, non-HDL-C ratio, and TCBI. Furthermore, the glycemic control (HbA1c) was positively and significantly correlated with the preventive measures factor (r = 0.175, p < 0.05), and were negatively and significantly correlated with the lifestyle and modification factor (r = −0.169, p < 0.05), diet and monitoring factor (r = −0.158, p < 0.05), and awareness factor (r = −0.149, p < 0.05). Conclusions: This study showed acceptable psychometric properties for the SDKT-A, with low levels of knowledge of diabetic disease in the sample population. Finally, comprehensive and interactive educational programs regarding lifestyle and modification, diet, and monitoring and awareness in primary healthcare centers in Iraq are warranted. Full article

Background: Cervical intraepithelial neoplasia (CIN) represents a precancerous condition whose effective management is crucial for preventing invasive cervical cancer, a disease that remains a leading cause of cancer-related mortality among women worldwide. The long pre-invasive phase of cervical carcinogenesis and the availability of effective screening and treatment procedures make CIN a largely preventable and curable entity. Objectives: This review aimed to analyze therapeutic options applied in CIN, correlating interventions with lesion grade and guideline recommendations, in order to outline a management model adapted to the Romanian clinical setting. Materials and Methods: A structured narrative review of 20 published articles addressing cervical intraepithelial neoplasia (CIN 1–3) published between 2021 and 2023 was performed. Relevant studies were identified through a targeted literature search and analyzed descriptively. This study synthesized data from the recent literature and international clinical guidelines to identify management trends and context-specific adaptations. Results: Extracted variables included lesion grade, reported therapeutic approach (surveillance, excisional, or ablative treatment), reproductive considerations, and patient compliance, with international guidelines used as reference standards. Across the reviewed studies, excisional procedures (conization and LEEP) were predominantly reported for high-grade neoplasia (CIN 2–3), while low-grade lesions (CIN 1) were managed either conservatively or through close surveillance. Treatment decisions described in the literature were strongly influenced by patient age, fertility preservation needs, and obstetric history. Overall, management approaches reported in Romanian and international studies were broadly aligned with current guideline recommendations, although variations were observed in the expectant management of younger patients. Conclusions: The findings emphasize the importance of individualized management in cervical dysplasia, integrating lesion characteristics with patient-specific factors. While international guidelines provide a robust framework, their adaptation to the Romanian healthcare context should prioritize patient education, compliance, and structured post-treatment follow-up strategies. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD) is defined by hepatic steatosis in individuals with at least one cardiometabolic risk factor, most commonly type 2 diabetes mellitus (T2DM). People with non-alcoholic fatty liver disease, even without other metabolic factors, have a higher risk of T2DM. MASLD includes isolated liver steatosis, metabolic dysfunction-associated steatohepatitis, fibrosis, cirrhosis, and MASH-related hepatocellular carcinoma. MASLD patients are also at a higher risk of developing T2DM than the general population. International guidelines recommend a stepwise approach for identifying those at high risk of fibrotic progression, using the FIB-4 index for initial screening, followed by transient elastography. The link between MASLD and T2DM is notable due to shared pathophysiological mechanisms, some of which are reversible with treatment used in T2DM. Many new glucose-lowering drugs have also proven effective in improving anthropometric and metabolic parameters, as well as the stage of hepatic steatosis and fibrosis. Recent evidence suggests that GLP-1RAs and SGLT2is have beneficial effects in MASLD patients with T2DM. Specifically, GLP-1RAs improve hepatic insulin signaling, modulate lipid metabolism, reduce inflammation, and decrease hepatocyte oxidative stress. European guidelines recommend resmetirom as a MASH-targeted therapy, if locally approved, for adults with non-cirrhotic MASH and significant liver fibrosis (stage ≥ 2) and GLP-1RAs in MASH, including compensated cirrhosis, but they should be used for their respective indications, such as T2DM and obesity. Given the post-COVID burden of MASLD and its high risk of liver fibrosis progression among T2DM patients, this review specifically provides an overview of the complex relationship between MASLD and T2DM. Additionally, it examines current understanding of liver fibrosis evaluation and the effects of novel treatment options, with a particular focus on glucose-lowering therapies and their effects on necroinflammation, hepatic fat accumulation, and fibrosis progression in patients with MASLD and T2DM. Full article

Objective: In Vitro Fertilization (IVF) has revolutionized reproductive medicine, offering hope to individuals and couples facing infertility. However, the psychological impact of IVF varies significantly based on gender, necessitating a systematic review of the existing literature. This review explores the emotional effects of IVF on both men and women, highlighting gender-specific psychological responses throughout the treatment process. Methods: A systematic literature search using various databases (such as PubMed) was made. Studies published in English from the years 2000 to 2023 were included in the review. Results: A total of 47 studies examined the psychological impact of IVF on both women and men, covering the IVF programming period, the initial stages of IVF treatment, and subsequent stages, as well as the long-term psychological distress effects of IVF in both genders. Both female and male infertile patients are dealing with anxiety, depression and low quality of life. However, women were found to experience higher levels of psychological distress, including increased anxiety and depression symptoms, compared to men at nearly all stages of IVF treatment. Conclusions: Understanding these gender-specific differences is crucial for developing targeted psychological support interventions to improve mental well-being during IVF treatments. Full article

Background: Atrial fibrillation (AF) is frequently associated with cardiometabolic comorbidities, and increasing evidence suggests a close relationship between AF and liver disease, particularly metabolic dysfunction-associated steatotic liver disease (MASLD); however, the clinical patterns, hepatic phenotypes, and clinical implications of this association remain insufficiently characterized. Therefore, the aim of the present study was to characterize hepatic involvement in patients with paroxysmal AF by integrating a structured literature review with original clinical data. Methods: We performed a retrospective analysis of 253 patients admitted with paroxysmal AF between 2015 and 2025. Demographic data and associated diagnoses were collected with a specific focus on hepatic pathology. Patients were stratified according to the presence and type of liver disease, and descriptive statistics, bivariate analyses, and multivariate logistic regression were used to identify associations and independent predictors. Results: Liver disease was identified in 65.2% of patients, most commonly hepatic steatosis (46.2%), followed by liver cirrhosis or advanced liver disease (19.0%). Patients with liver disease had higher prevalences of type 2 diabetes mellitus, dyslipidemia, obesity, and alcohol consumption. Dyslipidemia (OR 4.51) and obesity (OR 2.54) were independent predictors of hepatic steatosis, whereas liver cirrhosis was inversely associated with age and serum lipid levels. Conclusions: Liver pathology is highly prevalent among patients with paroxysmal AF and is closely associated with adverse metabolic and clinical profiles. Recognition of distinct hepatic phenotypes may support improved risk stratification and multidisciplinary management in patients with AF. Full article