Search Results (1,894)

Background: Functional Neurological Disorder (FND) encompasses conditions with neurological symptoms inconsistent with structural pathology, arising instead from complex interactions between psychological, biological, and social factors. Despite growing research, the etiological and risk factor landscape remains only partially understood, complicating diagnosis and treatment. Objective: This systematic review maps risk factors for major FND subtypes such as functional seizures (psychogenic non-epileptic seizures or PNES), functional cognitive disorder (FCD), functional movement disorders (FMD), functional weakness and sensory disturbances, functional visual symptoms, and functional gait abnormalities by categorizing predisposing, precipitating, and perpetuating influences. Methods: A systematic search of PubMed, PsycINFO, Scopus, and Web of Science initially identified 245 records. After removal of 64 duplicates, 181 studies were screened by title and abstract. Of these, 96 full texts were examined in detail, and finally 23 studies met the predefined inclusion criteria. Data were extracted and analyzed thematically within a biopsychosocial framework, with results summarized in subtype-specific profiles. Results: Childhood adversity, especially emotional, physical, or sexual abuse, emerged as a robust and consistent predisposing factor across PNES cohorts. Psychiatric history (notably anxiety, depression, and PTSD), neurodevelopmental traits (more frequent in FCD), and personality patterns such as alexithymia and somatization also contributed to vulnerability. Precipitating influences included acute psychological stress, intrapersonal conflict, or concurrent medical illness. Perpetuating factors comprise maladaptive illness beliefs, avoidance behaviors, insufficient explanation or validation by healthcare providers, and secondary gains related to disability. While several risk factors were shared across subtypes, others appeared subtype-specific (trauma was especially associated with PNES, whereas neurodevelopmental traits were more characteristic of FCD). Conclusions: FND arises from a dynamic interplay of predisposing, precipitating, and perpetuating factors, with both shared and subtype-specific influences. Recognizing this heterogeneity can enhance diagnostic precision, guide tailored intervention, and inform future research into the neurobiological and psychosocial mechanisms underlying FND. Full article

Background and Objectives: Limb–girdle muscular dystrophies (LGMDs) are a group of muscular dystrophies characterized by predominantly proximal-muscle weakness, with a highly heterogeneous genetic etiology. Despite recent efforts, the epidemiology of LGMDs is still under-evaluated. However, a better understanding of the distribution and genetic characteristics of LGMDs is required to optimize the diagnostic process and to address future research. Therefore, the aim of the present study is to investigate and identify new pathogenic variants, to better characterize LGMDs in Sicily. Methods: We enrolled patients with genetic and clinical diagnosis of LGMD referred to our clinic between the years 2019 and 2025. A targeted next-generation-sequencing (NGS) panel was performed, based on the reported disease frequency. A retrospective analysis of the clinical, laboratory, electrophysiological, and histological features was performed. Results: A total of 28 LGMDs patients aged 56.6 years (47.2–60.5 IQR) were identified (16 males, 57%). A molecular diagnosis was achieved in 24 (85.7%) of patients, most commonly carrying mutations in CAPN3 (14 patients, 50%), followed by DYSF, LAMA2, ANO5, FKTN and TTN genes. Pathogenic variants in CAPN3 and LAMA2 were associated with earlier onset and longer disease duration, whereas ANO5 presented later with a milder course. Cardiac involvement was observed more frequently in patients with LAMA2 and FKTN mutations. Association between heterozygous mutations in the CAPN3 and DYSF, as well as between CAPN3 and DMD variants were reported. Discussion: The findings of this study provide valuable insights into the epidemiology of LGMDs in the Western Sicily, offering important contributions to genotype–phenotype correlations. Our analysis highlights the role of genetic diagnosis in achieving accurate classification of the disease and optimizing clinical management. Full article

Background: Non-variceal upper gastrointestinal bleeding (NVUGIB) remains a critical medical–surgical emergency associated with significant morbidity, mortality, and healthcare burden worldwide. Despite advances in diagnostic and therapeutic modalities, NVUGIB continues to pose complex clinical challenges, particularly in resource-limited settings. Methods: This retrospective observational study analyzed 364 consecutive adult patients diagnosed with NVUGIB and hospitalized at the First Surgical Clinic of the County Emergency Clinical Hospital Craiova between January 2009 and December 2014. Inclusion criteria required a confirmed diagnosis based on clinical presentation, laboratory findings, and upper gastrointestinal endoscopy (UGIE). Demographic variables, etiology, comorbidities, drug-induced triggers, laboratory parameters, onset-to-admission and onset-to-surgery intervals, endoscopic findings, therapeutic interventions (medical, endoscopic, surgical), rebleeding rates, and mortality were recorded and analyzed. Results were descriptively compared with historical data from the national and international literature. Due to the retrospective and aggregate nature of the data, survival analysis (Kaplan–Meier) was not applicable. Results: Peptic ulcers, erosive gastritis, Mallory–Weiss syndrome, and gastric neoplasms were the predominant etiologies. NSAID use, oral anticoagulation, and alcohol consumption emerged as major risk factors. Endoscopic hemostasis was achieved in the majority of cases; surgical intervention was required in 11.5% of patients, mainly for refractory or recurrent bleeding. The overall mortality rate was 10.9%, consistent with historical benchmarks. Comparative analysis revealed trends in etiology and management reflecting evolving clinical practice standards. Conclusions: NVUGIB remains a significant clinical challenge with persistent mortality and rebleeding risks. This cohort highlights the need for timely diagnosis, risk stratification, and an evidence-based therapeutic strategy integrating modern endoscopic and surgical options. An updated diagnostic and management algorithm is proposed to guide practical decision-making and optimize outcomes in similar tertiary care settings. Full article

Background and Clinical Significance: Zoledronic acid (ZA) is a widely used bisphosphonate for the prevention of skeletal-related events in patients with metastatic bone disease. While it is generally well tolerated, rare immune-mediated complications may be underrecognized. To date, myocarditis has not been reported in association with ZA. Case Presentation: A 35-year-old woman with metastatic pheochromocytoma developed acute, non-exertional chest pain approximately 36 h after receiving her first intravenous ZA infusion. Laboratory testing revealed elevated high-sensitivity troponin T, peaking at 1182 ng/L. Cardiac magnetic resonance imaging (CMR) demonstrated myocardial edema and subepicardial late gadolinium enhancement, consistent with acute myocarditis per the 2018 revised Lake Louise criteria. An extensive diagnostic workup excluded infectious, autoimmune, and ischemic causes. Symptoms and troponin levels improved following ZA discontinuation and supportive care. In the absence of alternative etiologies, and given the close temporal association with ZA administration, the diagnosis of presumed ZA-associated myocarditis was supported by clinical presentation, biochemical markers, and CMR findings, recognizing that histopathological confirmation is rarely pursued in clinically stable patients. Conclusions: To our knowledge, this is the first reported case of presumed zoledronic acid–associated myocarditis confirmed by cardiac MRI. This report highlights the diagnostic utility of CMR in suspected drug-related cardiac inflammation and the importance of considering myocarditis in patients presenting with unexplained chest pain following ZA infusion, particularly when other causes have been excluded. Full article

Background/Objectives: Granulomatous lesions of the head and neck arise from diverse infectious and non-infectious causes, with tuberculosis (TB) being a predominant etiology. This retrospective study analyzed 42 cases from the archives of university of Baghdad, College of Dentistry (1975–2025). This study aimed to characterize the clinicopathological features of these lesions and to assess the diagnostic performance of histochemical stains and real-time PCR in identifying infectious etiologies—particularly Mycobacterium tuberculosis—in formalin-fixed, paraffin-embedded (FFPE) tissue samples. Methods: Definitive diagnoses included 25 TB cases confirmed through clinical, microbiological, and therapeutic follow-up at the Baghdad Tuberculosis Institute, and 17 non-TB cases classified by predefined clinicopathological criteria supported by relevant clinical data. Zieh–Neelsen (ZN), Periodic acid–Schiff (PAS), and Grocott methenamine silver (GMS) stains were employed to identify acid-fast bacilli and fungal organisms. Statistical analysis was performed using SPSS version 26, with significance set at p ≤ 0.05. Results: The mean patient age was 36.28 years (SD = 20.6), with a female predominance (59.5%). Necrotizing granulomas were identified in 69% of cases and were strongly associated with tuberculosis, which was detected in 59.5% of specimens. ZN staining showed a sensitivity of 16.7% for tuberculosis, while PCR sensitivity was highly dependent on sample age. The detection rate was 33.3% in samples archived for less than 10 years but only 10% in older samples, resulting in an overall sensitivity of 24.0% for tuberculous cases. Langhans-type giant cells were significantly more frequent in necrotizing granulomas and strongly associated with tuberculosis infection (p = 0.001). Fungal infections, predominantly aspergillosis, were confirmed by PAS and GMS in 11.9% and 9.5% of cases, respectively, and were confined to non-necrotizing granulomas. The mandible was the most commonly affected site, and soft tissue lesions were significantly associated with necrotizing granulomas (p = 0.004). Conclusions: These findings underscore the complementary role of histopathology, histochemical stains, and molecular diagnostics in improving the evaluation and diagnosis of granulomatous inflammation in head and neck lesions. Full article

Hypersomnia may be classified as primary or secondary, with secondary hypersomnia arising from a variety of underlying causes. Thus, according to ICSD3-TR classification, the diagnosis of idiopathic hypersomnia (IH) is established based on (1) excessive daytime sleepiness (EDS); (2) electrophysiological findings including either a mean sleep latency of less than 8 min on the Multiple Sleep Latency Test (MSLT) or increased total sleep (≥11 h) on 24 h polysomnography; and (3) systematic elimination of other potential etiologies, including sleep deprivation, substances, and medical, psychiatric (notably mood disorders), or sleep disorders. Nevertheless, the clinical heterogeneity observed in IH fuels an ongoing debate, reflecting the limited understanding of its underlying pathophysiological mechanisms. This report describes the case of a patient presenting with a clinical and polysomnographic phenotype of IH (MSLT < 8 min). A comprehensive psychopathological evaluation was performed to explore the possibility of secondary hypersomnia, which revealed features consistent with complex post-traumatic stress disorder (c-PTSD). Psychotherapy focused on c-PTSD was administered with positive and objective results in hypersomnolence/EDS. This clinical improvement suggests a potential relationship between psychological trauma and hypersomnia, a connection that is rarely described in the literature and warrants further investigation. This case highlights the need for a comprehensive assessment of secondary factors, particularly complex trauma, even in the presence of a clinical and polysomnographic phenotype consistent with IH. Full article

The jaw bones can manifest various cysts and tumors of different origins and etiologies. Any bone lesions lacking any potential odontogenic origin might require more accurate diagnostics, adequate investigation, and careful patient anamnesis. In cases of sharply demarcated radiolucency or mixed radiolucent–radiopaque radiological appearance lesions, they can sometimes extend between the displaced tooth roots or cause their resorption. The scope of cortical bone in radiographic studies might have a different status, and lesions can spread outside of the bone. If no odontogenic feature is present, an additional blood examination for bone markers and calcium–phosphate markers is useful to establish any endocrine-related pathologies. In the primary hyperparathyroidism (PHP), bone blood markers and bone scintigraphy are very useful to establish the possible occurrence of brown tumor. On the other hand, in central giant cell granuloma (CGCG), only a direct tumor lesion biopsy might confirm the diagnosis, where in microscopic evaluation, mostly fibroblasts and secondary cells have multinucleated giant cells along with some accessory cells like macrophages, dendrocytes, and other endothelial cells. Because both lesions can have similar clinical and radiological appearances and unclear borders, with different shapes, sizes, and symptoms, it is quite important to compare both clinical and radiological patient characteristics. The authors aim to present how radiological studies alone can easily lead to lesion misdiagnosis. They also aim to emphasize how local treatment methods without advanced microsurgical reconstruction can, in some cases, improve patient outcomes. Full article

Liver cirrhosis represents the end-stage of chronic hepatic injury, arising from a diverse range of etiologies including viral hepatitis, alcohol abuse and non-alcoholic fatty liver disease. A key driver of cirrhosis is hepatic fibrogenesis, a multifaceted process involving hepatic stellate cell activation, inflammatory signaling and extracellular matrix accumulation. MicroRNAs (miRNAs), a class of small non-coding RNAs, have emerged as pivotal regulators in this context, modulating gene expression networks that govern inflammation, fibrosis and hepatocarcinogenesis. This review synthesizes current evidence on the role of miRNAs in liver cirrhosis, emphasizing specific miRNAs such as miR-21, miR-122, miR-125, miR-146 and miR-155. These miRNAs influence pathways involving TGF-β, NF-κB and PI3K/Akt signaling, contributing to either fibrogenic progression or its suppression. The unique expression profiles and stability of miRNAs in biological fluids position them as promising non-invasive biomarkers for cirrhosis diagnosis and monitoring. Moreover, therapeutic modulation of miRNA activity through mimics or inhibitors holds future potential, though delivery and safety challenges remain. Advancing our understanding of miRNA-mediated regulation in cirrhosis could transform current diagnostic and therapeutic strategies, enabling more precise and personalized liver disease management. Full article

Alzheimer’s disease (AD) is a complex neurodegenerative condition which, despite its high prevalence and socioeconomic impact on the world, has an etiology that remains poorly understood. The genetic causes of AD are complex and have been continuously studied for decades. They range from rare pathogenic, highly penetrant mutations in early-onset (EOAD) forms, which account for 5% of the cases to multiple-risk alleles across different genes in late-onset (LOAD) forms. Monogenic causes of EOAD allocate within APP, PSEN1, and PSEN2 genes in 10–15% of cases. The most significant risk factor in LOAD heritability is the APOE ε4 allele, as well as numerous loci within genes involved in immunity, endocytosis, lipid metabolism, and amyloid and tau processing. LOAD can also be attributed to the accumulation of somatic mutations, which may be detected by analysis of brain-derived cell-free DNA (cfDNA) in plasma. This review offers a comprehensive overview of the genetic architecture of Alzheimer’s disease, with particular focus on the molecular mechanisms underlying both early- and late-onset forms of the condition. An improved understanding of the genetic etiology of AD can aid better prevention, earlier diagnosis, and novel therapeutic approaches. This can be achieved by analyzing understudied populations, performing case-control studies with appropriately matched controls, and surveying brain-derived cell-free DNA in plasma, with the latter having the potential to contribute to the implementation of liquid biopsy in dementology. Full article

Introduction: Shoulder pain is one of the leading causes of medical consultation, highlighting the need to identify the most frequently affected tissues to improve diagnosis. This study aims to determine the most common shoulder soft tissue injuries in young adults using musculoskeletal ultrasound (US). Methods: An observational cross-sectional study was conducted with 66 individuals aged 18 to 45 years; 35 participants reported shoulder pain and 31 did not. All participants received shoulder US by a specialist. Structures analyzed included the rotator cuff tendons, the long head of the biceps tendon (LHBT), and the subacromial–subdeltoid bursa. Results: The supraspinatus tendon was the most frequently affected structure, accounting for 65.1% of clinical findings, and its involvement was strongly associated with subscapularis tendinitis (OR = 18.45). The subscapularis tendon represented 31.8%, tenosynovitis of the LHBT occurred in 7.6%, and the subacromial–subdeltoid bursa was affected in 1.5%. Cluster analysis revealed three distinct profiles based on age, pain status, and tendon involvement: Cluster 1 (n = 23; mean age 21.6 ± 3.8 years) included younger individuals with minimal pain and tendinopathy (21.7%); Cluster 2 (n = 21; mean age 33.6 ± 2.6) consisted of intermediate-age participants with moderate pain and predominant supraspinatus tendinitis (71.4%); and Cluster 3 (n = 22 mean age 42.1 ± 1.6) comprised older individuals with the highest prevalence of pain and combined tendon lesions (81.8%). Conclusions: This study confirms the clinical value of musculoskeletal US in detecting soft tissue injuries, including subclinical findings. The supraspinatus tendon was the most frequently affected structure, often associated with subscapularis tendinitis and other combined lesions in older individuals. US proved useful in identifying distinct injury profiles based on age and pain status, supporting its role in early diagnosis and tailored management strategies. Full article

The incidence of mood disorders in the general population is quite high. Among the most common is bipolar disorder (BD), often associated with severe mood disorders, psychotic changes (e.g., delusions, hallucinations), impulsivity, and self-harm. However, its correct diagnosis is challenging, primarily due to the heterogeneity of clinical and symptomatic features, as well as individual differences among patients, such as comorbidity with other disorders (e.g., borderline personality disorder). Therefore, to improve understanding of its etiology and pathogenesis, refining the diagnosis must be a priority. Given the breadth and complexity of the evidence in the literature, we believe it is useful to provide a clear and comprehensive summary of the neuroanatomical and dysfunctional alterations observed, with particular attention to the prefrontal cortex, anterior cingulate cortex, cerebral ventricles, amygdala, hippocampus, cerebellum, and white matter. Through functional neuroimaging investigations it is possible to distinguish two main forms of bipolarism: the first (BD-I) is the most severe form, both in terms of manifested symptoms and in the structural and functional alterations detected; the second (BD-II) is the less severe form, which presents attenuated symptoms and mild or medium-severe alterations compared to the normotype criteria. Literature highlights the need to identify a precise study model, whether neuro-evolutionary or neuro-progressive or mixed, capable of offering clinical therapists greater scientific basis on which to anchor their diagnostic interpretations, and certainly the use of functional neuroimaging technology can be a good option even if it still presents costs that are not easily and freely sustainable by patients. Full article

Background: The etiology of liver disease remains unidentified in approximately 30% of patients, presenting a persistent diagnostic challenge. While whole-exome sequencing (WES) is well established for identifying rare genetic conditions in pediatric populations, its utility in adult hepatology is less defined. This study aimed to evaluate the diagnostic value of WES in adults with unexplained liver disorder. Methods: Fifty-three Turkish adult patients with idiopathic liver disease underwent a comprehensive clinical evaluation and WES at Gazi University Ankara in 2024–2025. The cohort included individuals with idiopathic cholestasis (6/53, 11%), hepatic steatosis (28/53, 53%), unexplained elevated liver enzymes (12/53, 23%), and cryptogenic cirrhosis (7/53, 13%). All patients had inconclusive results from prior standard investigations. Results: ES yielded a definitive molecular diagnosis in 11% (6/53) of cases. Definitive diagnoses were distributed across the following disease categories: idiopathic cholestasis (n = 1), hepatic steatosis (n = 1), elevated liver enzymes (n = 2), and cryptogenic cirrhosis (n = 2). Pathogenic variants were detected in the ABCB4, AGL, APOB, CP, and MTTP genes. One patient was identified with mosaic Turner syndrome. Conclusions: This study highlights the role of rare genetic variants in the etiology of unexplained liver disease in adults. Integrating whole-exome sequencing into hepatology practice can uncover novel disease mechanisms and improve diagnostic yield, informing more precise patient care. Full article

Background and Clinical Significance: Cocaine-induced vasculitis (CIV), especially when associated with PR3-ANCA positivity, can be very similar both clinically and serologically to idiopathic granulomatosis with polyangiitis (GPA). The distinction between these entities is crucial due to the different etiologies, treatment strategies, and prognoses. We present a unique case of CIV that manifested exclusively in a previously dissected neck area—an example of the locus minoris resistance phenomenon—and was initially misinterpreted as skin melanoma recurrence. Case presentation: A 59-year-old man with a history of skin melanoma (pT4b, left pectoral region) and a previous modified radical neck dissection presented in 2024 with new onset of painful subcutaneous nodules and ulcerative lesions at the surgical site. The imaging procedures (CT and PET-CT) raised the suspicion of locoregional malignant recurrence. However, histology revealed necrotizing granulomatous inflammation without tumor cells. Extensive infectious and autoimmune investigations ruled out alternative causes. Subsequently, the patient developed a perforation of the nasal septum and ulcers on the oral mucosa. PR3-ANCA was strongly positive (up to 49 U/mL). Urine toxicology revealed intranasal cocaine use. A diagnosis of cocaine-induced PR3-ANCA vasculitis was made. After immunosuppressive therapy (high-dose glucocorticoids and methotrexate) and substance withdrawal counseling, the patient showed significant clinical improvement. Conclusions: This case highlights the importance of including CIV in the differential diagnosis of granulomatous or ulcerative lesions, especially when they are localized to previous surgical sites. The presentation illustrates the concept of locus minoris resistentiae and highlights the role of toxicological testing in atypical ANCA-positive disease. Full article

Background: Subacromial impingement or pain syndrome (SAPS) is the most common diagnosis for chronic shoulder pain. Current surgeries do not reduce long-term pain, suggesting they miss the root etiology. Previously, we described the Human Disharmony Loop (HDL), where the unique lower trunk innervation to the pectoralis minor (PM) causes scapular dyskinesis and deforms its connections, including tugging the acromion down and impinging the subacromial structures. We hypothesize that SAPS patients who meet HDL criteria would benefit significantly from PM tenotomy with infraclavicular brachial plexus neurolysis (PM + ICN) alone. Methods: SAPS patients who met HDL diagnostic criteria were treated with PM + ICN, with secondary distal neurolysis if needed. Outcomes included pain and shoulder abduction ROM. Six-month follow-up minimum was required. Results: N = 140 patients were included. Median age was 49. Prior surgeries included 27% subacromial decompression/acromioplasty, 21% rotator cuff repair, 16% biceps tenodesis, 4% SLAP repair, 2% labral repair, 7% distal clavicle resection, 10% reverse total shoulder arthroplasty (rTSA), 1% rib resection with scalenectomy, 16% cervical spine fusion, 28% distal neurolysis. Median pain decreased from 8 to 2 and median shoulder ROM increased from 90 to 180 degrees. Positive impingement signs on exam decreased from 100% to 11%. (p < 0.01) Conclusions: In a large series of SAPS patients, evaluation and treatment for the HDL significantly reduced pain and restored motion. These findings suggest that in many patients SAPS may be a subset of the HDL: the ventral PM disturbing the scapula constitutes the anatomic basis and optimal surgical target behind SAPS. Full article

Background: Numerous studies have demonstrated the beneficial effects of sodium-glucose cotransporter-2 (SGLT2) inhibitors on cardiovascular and renal outcomes in patients with heart failure and chronic kidney disease. However, whether SGLT2 inhibitors are also associated with a reduced risk of tinnitus has not been investigated. Objective: This study aimed to investigate the association between SGLT2 inhibitor therapy and the incidence of tinnitus in patients with type 2 diabetes. Methods: This retrospective cohort study was based on data from a nationally representative database of primary care practices in Germany from 2012 to 2023. Patients with type 2 diabetes who were treated with metformin and additionally received either an SGLT2 inhibitor or a dipeptidyl peptidase-4 (DPP4) inhibitor were included. Patients with a previous diagnosis of tinnitus were excluded. The primary outcome was the first tinnitus diagnosis documented by a primary care physician. The SGLT2 and DPP4 cohorts were compared for tinnitus incidence using Kaplan–Meier analysis and multivariable Cox regression. Results: 66,750 patients with SGLT2 inhibitors and 82,830 with DPP4 inhibitors were analyzed. The cumulative 5-year incidence of tinnitus was 1.9% in both groups. The multivariable regression analysis did not show a significant association between SGLT2 therapy and the occurrence of a tinnitus diagnosis (HR: 1.04; 95% CI: 0.89–1.21). Conclusion: There was no difference in tinnitus incidence between patients with SGLT2 or DPP4 inhibitors. The causes could lie in the heterogeneous, not purely vascular, etiology of tinnitus in general practitioners’ practices. Future studies should include further clinical data, including confirmed hearing impairments. Full article