Background: Immune checkpoint inhibitors (ICI) usage has increased in recent years, along with it the associated adverse effects. Objective: To conduct an observational study on immune checkpoint usage and adverse drug reactions associated with its use in a tertiary care center from coastal South India. Methodology: 228 patients were enrolled in this ambispective study, patient’s data was collected from the year 2020‑2024. Patients were selected based on inclusion criteria. Results: While adverse effects such as pruritus, tachycardia, and thyroiditis occurred infrequently, their clinical significance necessitates careful monitoring. A statistically significant association (p = 0.022) between treatment response and adverse events indicated a potential relationship between therapeutic effectiveness and toxicity. The instance of myocarditis was found to be 0.4%. Conclusion: These findings emphasize the significance of accurate monitoring, management, which includes various fields, and individualized therapies to maximize the outcomes for patients and reduce potential risks associated with Immune Checkpoint inhibitors (ICI).
Outer membrane protein A (OmpA) is an essential part of the Gram-negative bacterial outer membrane, which is essential in the stability of the membrane, the development of biofilm, and resistance to antibiotics. This is a detailed computational analysis involving the use of molecular dynamics (MD) simulations with GROMACS to examine using simulations in a lipid bilayer the structural dynamics, stability, and functional implications of Escherichia coli OmpA. We studied the conformational dynamics, membrane integration patterns, networks of hydrogen bonding, and structural stability of OmpA in physiological conditions through 200 nanoseconds of all-atom MD dynamics. Root mean square deviation (RMSD) was analyzed and showed that, on average the protein remained stable in conformation after 50 ns with average values of 2.8 ± 0.4 A. Root Mean square fluctuation (RMSF) analysis helped locate regions of the protein that are highly flexible (residues 160-180) with fluctuation greater than 4.5 A and the transmembrane 2-barrel domain was rigid (RMSF < 1.5 A). Measurement of radius of gyration was a sign of compact protein structure (17.2 ± 0.3 A) during the simulation. Analysis of secondary structure indicated that 43 percent of the 3D structure was also maintained with few transitions of 3D structures to 43% 3D structure. The analysis of hydrogen bonds showed that there were an average of 185 hydrogen bonds and a standard deviation of 15 intramolecular hydrogen bonds that forms the structure. Calculation of solvent accessible surface area revealed that hydrophobic residues (62) were mostly exposed to the lipid environment with the hydrophilic residues (38) being exposed to the aqueous environment. Three main motion modes with 68% of the total structural variance were obtained by principal component analysis. Analysis of free energy landscape showed that there are two conformational basins which are stable with energy barriers of 4.2 kcal/mol. These results not only give molecular-level information on the correlation between OmpA structure-function relationships, but also provide potential antimicrobial drug targets against Gram-negative pathogens.
BACKGROUND Teratomas are rare congenital tumors arising from pluripotent germ cells and contain tissues derived from all three germ layers: ectoderm, mesoderm, and endoderm. Intracranial teratomas are uncommon, accounting for less than 0.5% of all central nervous system tumors, and typically occur in midline structures such as the pineal or suprasellar regions. Primary involvement of cranial bones with transosseous extension is exceptionally rare. These lesions may lead to progressive cranial deformity and local bone destruction. While isolated cases involving the petrosal bone have been reported, localization at the cranial vault is exceedingly uncommon. To our knowledge, this report describes the first case of a transosseous teratoma involving the frontal and parietal bones. CASE PRESENTATION A 39‑year‑old male presented with persistent headache and vertigo, associated with a subcutaneous swelling at the bregma that progressively enlarged following a hair transplant procedure. Imaging revealed an osteolytic transosseous lesion involving both the external and internal cortical tables, with intraspongious extension and multiple hair follicles embedded within the mass. The patient underwent complete surgical excision, including resection of the outer cortical bone to delineate tumor margins and achieve total removal clearly. Histopathological examination confirmed the diagnosis of a mature teratoma. The postoperative course was uneventful, and the patient was discharged on the third postoperative day without neurological deficits. DISCUSSION Transosseous teratomas of the cranial vault are extremely rare. Their pathogenesis is thought to involve aberrant migration of germ cells during embryogenesis, resulting in ectopic growth within bone. Differential diagnosis includes dermoid and epidermoid cysts, osteolytic skull tumors, and other germ cell neoplasms. Complete surgical excision remains the treatment of choice to prevent recurrence. Given the potential for malignant transformation, long‑term clinical and radiological follow‑up is recommended. CONCLUSION: This case underscores the importance of early diagnosis and complete surgical resection in the management of transosseous cranial teratomas. Further reports are needed to better define optimal management strategies for these rare lesions.
Introduction: Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by periods of relapse and remission, in which gut microbiota imbalance plays a role in triggering and sustaining inflammation through pro‑inflammatory cytokines. Therapeutic approaches targeting the gut microbiota, such as probiotics and synbiotics, have the potential to regulate disease activity by restoring microbial balance and reducing systemic inflammation. Several randomized controlled trials (RCTs) have explored the effects of microbiota‑based interventions in autoimmune diseases; however, comprehensive meta‑analyses summarizing their efficacy remain limited. Objective: To explore the potential benefit of probiotics and synbiotics supplementation in improving SLE disease activity and inflammatory markers. Methods: RCTs relevant to the treatment of SLE with probiotics and synbiotics were systematically retrieved from Pubmed, EMbase, Cochrane, Sinomed in accordance with the PRISMA guideline. The meta‑analysis was performed using RevMan 5.4.1 software. A fixed‑effects model was applied, Cochrane Risk of Bias 2 (ROB 2.0) was used as a bias assessment tool. Results: Seven studies with a total 460 subjects were included in this meta‑analysis. Data consisting of SLEDAI‑2K, IL‑17 and IgG from studies RCTs. The pooled analysis demonstrated that probiotic or synbiotic supplementation significantly reduced disease activity of SLE as assessed by the SLEDAI‑2K score (MD = ‑2.33, 95% CI ‑2.49, ‑2.16; P < 0.00001; I² = 61%). Similarly, the pro‑inflammatory markers of IL‑17 (MD = ‑1.04, 95% CI ‑1.55, ‑0.52; P < 0.0001) and IgG (MD = ‑2.64, 95% CI ‑2.77, ‑2.51; P < 0.00001) revealed a significant reduction compared to control group. Conclusion: Gut microbiota‑based therapies, including synbiotics and probiotics supplementation, demonstrate the potential benefit to reduce systemic inflammation and improve SLE disease activity through modulating gut microbiota composition and function. While promising as an adjunctive treatment for SLE, further studies are required to investigate its mechanisms and therapeutic efficacy.
Background: Cigarette smoking is a major risk factor for cardiovascular disease. Oxidative stress plays a central role in endothelial dysfunction and atherosclerosis. β-hydroxybutyrate (β-OHB), a ketone body, has been proposed to exert antioxidant and vascular protective effects. This study aimed to evaluate the effects of β-OHB on aortic histopathology and von Willebrand Factor (vWF) levels in Wistar rats exposed to cigarette smoke. Methods: This experimental randomized controlled animal study included 25 male Wistar rats divided into five groups: negative control (K−), positive control (K+; cigarette smoke exposure), and three treatment groups receiving β-hydroxybutyrate-(R)-1,3-butanediol monoester (DeltaG®, TDeltaS Global Inc., Orlando, FL, USA) at doses of 1.5 g/kg/day (P1), 3 g/kg/day (P2), and 6 g/kg/ day (P3). Rats were exposed to 40 cigarettes/day for 28 days. Aortic tissues were collected after euthanasia on day 28 for histopathological analysis and vWF measurement using ELISA. Data were analyzed using ANOVA with Fisher’s LSD post-hoc test. Results: β-OHB significantly reduced aortic histopathological alterations compared to the smoke-exposed control group (degeneration p = 0.001, hyperemia p = 0.002, hemorrhage p = 0.001, necrosis p = 0.000). vWF levels differed significantly among groups (p = 0.034), indicating improved endothelial function. Conclusions: β-OHB attenuates cigarette smoke-induced aortic injury and improves endothelial function. These findings support its potential role as a cardiometabolic therapeutic strategy.
Background: Nasal septal perforation (NSP) represents a challenging clinical condition with significant functional impact and heterogeneous presentation. Surgical repair remains the treatment of choice for symptomatic moderate and large perforations, yet optimal techniques are still debated. Objective: To evaluate the effectiveness of the sandwich graft technique using polydioxanone (PDS) plates combined with cartilage graft and platelet‑rich fibrin (PRF) membranes in the surgical treatment of moderate nasal septal perforations. Materials and Methods: A prospective study was conducted on 22 patients with moderate NSPs (1‑2 cm), treated between April 2022 and December 2025. The surgical technique consisted of bilateral PDS plates with interposed cartilage graft and PRF membranes. Patients were followed endoscopically at 1, 3, 6, and 12 months postoperatively. Results: Complete closure of the perforation was achieved in 77% of cases at the first postoperative evaluation, increasing to 91% at 6 and 12 months. Partial closure persisted in 9% of patients, all of whom were smokers. No major complications were reported. Conclusions: The sandwich graft technique using PDS plates and PRF membranes is a safe, effective, and reproducible method for repairing moderate nasal septal perforations, offering high success rates and favorable functional outcomes.
Background: Sarcoidosis is a multisystem inflammatory disorder characterized by non‑caseating granulomas. Skeletal involvement, present in up to 13% of cases, frequently remains underrecognized due to its asymptomatic course and imaging features that closely mimic metastatic disease, creating significant diagnostic challenges. Case Presentation: A 63‑year‑old woman presented for neurological evaluation of potential early cognitive decline prompted by family history. Neuroimaging incidentally revealed multiple osteolytic calvarial lesions. Further imaging demonstrated widespread mixed osteolytic and osteoblastic lesions involving the skeleton, bilateral perilymphatic pulmonary nodules, mediastinal and hilar lymphadenopathy, and hepatic lesions. Laboratory investigation showed elevated CA 15‑3 (43.7 kU/l) with normal CEA and CYFRA 21‑1. Whole‑body FDG PET/CT revealed hypermetabolic osteolytic lesions and metabolically active pulmonary infiltrates. An interdisciplinary tumor board considered carcinoma of unknown primary with suspected breast origin; however, breast MRI revealed no suspicious findings. Multiple myeloma was excluded by negative immunofixation electrophoresis. Percutaneous liver biopsy demonstrated non‑caseating granulomas without malignancy, with negative special stains for acid‑fast bacilli and fungi, establishing sarcoidosis as the underlying diagnosis. Management and Outcome: The patient was initiated on corticosteroids with calcium and vitamin D supplementation. At one‑month follow‑up, symptomatic improvement was noted with normalization of serum ACE levels and decline in CA 15‑3. Pulmonary function remained stable with mild DLCO reduction. The patient was continued on a corticosteroid taper with addition of inhaled corticosteroids for residual bronchial hyperreactivity. Conclusion: This case emphasizes the critical importance of maintaining broad differential diagnosis in multisystem disease with skeletal involvement. Although metastatic malignancy must be considered, sarcoidosis remains a key diagnostic consideration. Definitive histopathological confirmation is essential for accurate diagnosis and prevention of unnecessary oncologic intervention.
Introduction. Viral hepatitis C (VHC) remains a major public health concern in the Republic of Moldova, which records one of the highest prevalence rates in Europe. Understanding the knowledge, attitudes, and practices (KAP) of the population is a prerequisite for designing effective prevention and control strategies. Aim. To assess KAP related to VHC in a mixed cohort from the Republic of Moldova and to identify factors associated with KAP scores. Material and Methods. Cross‑sectional descriptive study (2024‑2025), with 567 participants: 455 healthcare workers and 112 members of the general population. A purpose‑built KAP scale (0‑30 points) assessed knowledge (0‑10), attitudes (0‑10), and practices (0‑10). Statistical analysis included Mann‑Whitney U and Kruskal‑Wallis tests, and Spearman’s correlation. Results. The mean KAP score was 17.82 ± 3.81 points (59.4%), with 63.7% of participants at a moderate level. Healthcare workers scored significantly higher than the general population (18.85 vs 13.62, p < 0.001). A positive correlation was found between knowledge and practices (ρ = 0.336, p < 0.001). Conclusions. Most participants showed a moderate KAP level, with relatively favorable attitudes, while knowledge and practices remained insufficient. Targeted educational programs are needed, particularly for the general population, those with lower education, and residents of rural areas.
Aerial conduction hearing aids (conventional) are the most commonly used devices for the rehabilitation of residual hearing loss after tympanoplasty. Patients with dry, safe ears with mild to moderate conductive hearing loss typically achieve excellent hearing rehabilitation with these devices. Although recent conventional hearing aids have improved technically, there are still shortcomings: distortion of sound and voice, irritation of the external ear canal, acoustic feedback, discomfort and exacerbation of existing conditions of the outer and middle ear. Bone‑anchored hearing aids are excellent devices that have proven their usefulness over time if candidates were properly selected and surgery was performed meticulously. In audiological terms, bone‑anchored hearing devices are clearly superior to conventional aerial conduction devices and passive bone conduction devices. The major drawbacks of this hearing aid are the relatively high financial costs and the need for the implantation surgical procedure. Cochlear implant is one of the most effective rehabilitation methods for sensorineural hearing loss, especially in cases where there is no functional effect with other hearing aids. The benefits of cochlear implantation, including for severe‑profound hearing loss in children and adults, have been significant improvements in post‑implant audiological test scores, cognitive domains, and quality of life, including long‑term. Cochlear implants showed the greatest improvements in speech perception and production, clear speech recognition in noisy environments, and audiometry performance compared to conventional hearing aids.
Background: The emergence of Generative Artificial Intelligence (GenAI) has a significant potential effect on medical education though there is little evidence regarding its use, perceptions, and expectations of medical students in resource‑limited clinical training contexts. Objectives: We aim to explore the experiences and perceptions of medical students regarding the use of GenAI technologies in clinical education with a special focus on the AI trust relationship between advanced age and academic level. Methods: A cross‑sectional observational study was conducted over eight months at Al‑Kindy College of Medicine, University of Baghdad, Iraq. All clinical‑grade students who responded to a 24‑item survey were involved (n=423). Multiple linear regression models and descriptive data analysis were performed. Results: Almost all oura sample students reported a current AI use and most of them showed a prior use (n=405,95.7%). Exam preparation (n=316,74.7%) and clinical case generation (n=249,58.9%) were the main use purposes. They exhibited strong agreement regarding AI’s ability of better learning potential and essential need for regulatory policies, while marked neutrality appeared toward AI’s clinical diagnostic accuracy and long‑term practical effects. Significant skepticism (p<0.001) resulted as AI trust positively correlated with higher clinical experience and negatively related to chronological age. Conclusions: Academic AI adoption was very largely encountered by medical students of resource‑limited settings and professional caution was shown regarding broader clinical applications with demands of AI compliance standards. The higher educational grade the better AI trust, while this was inversed regarding student’s age displaying a distinct skepticism.
Introduction: Recurrent chronic dacryocystitis represents a complex inflammatory condition frequently associated with failure of previous surgical interventions and persistent mechanical obstruction of the lacrimal drainage system. Objective: To present a case of recurrent chronic dacryocystitis after multiple unsuccessful surgical procedures and to highlight the role of laser‑assisted endoscopic dacryocystorhinostomy as a revision technique. Materials and Methods: We report the case of a patient with recurrent symptoms following two previous endoscopic dacryocystorhinostomies with nasolacrimal stent placement. Clinical examination, computed tomography of the paranasal sinuses, endoscopic findings, surgical management, and postoperative course were analyzed. Results: Imaging revealed rhinostomy stenosis associated with lacrimal sac lithiasis, representing a persistent mechanical cause of obstruction. Laser‑assisted endoscopic dacryocystorhinostomy using a diode laser was performed without stent placement, allowing precise removal of fibrotic tissue and obstructive material. The postoperative course was favorable, with complete resolution of epiphora, absence of purulent discharge, and maintained rhinostomy patency at 3‑month follow‑up. Conclusions: Laser‑assisted endoscopic dacryocystorhinostomy may represent an effective revision strategy in recurrent chronic dacryocystitis caused by persistent mechanical obstruction. Accurate identification of the underlying mechanism of surgical failure is essential for achieving durable functional outcomes.
Foreign bodies in the hypopharynx and upper esophagus are frequent emergencies in ENT practice, but their migration outside the aerodigestive lumen is rare and associated with an increased risk of morbidity and mortality. Sharp foreign bodies can perforate the hypopharyngeal or esophageal wall, migrating into the cervical spaces and generating significant diagnostic and therapeutic difficulties. We present the case of ingestion of a sharp foreign body (chicken bone), complicated by its migration initially into the deep spaces of the neck, and later into the peripheral spaces. The diagnosis was established by correlating clinical data with imaging investigations, and the treatment consisted of surgical extraction of the foreign body, associated with antibiotic therapy and careful monitoring. The evolution was favorable. These situations highlight the importance of clinical suspicion, early imaging explorations and individualized therapeutic conduct in the management of migrating foreign bodies of the hypopharynx and upper esophagus.
Vocal fold granuloma is a benign laryngeal lesion located at the vocal processes of the arytenoid cartilages and characterized by the formation of granulation tissue as a response to chronic mucosal irritation. Material and methods. A retrospective analysis of data from 12 patients diagnosed with laryngeal granuloma and treated between 2019 and 2024 at the ENT Clinic of the “Timofei Mosneaga” Republican Clinical Hospital. Results. In the examined series, males predominated (58.33%). Age distribution showed a bimodal pattern: 16–30 years (33.3%) and 41–50 years (33.3%). The clinical presentation was dominated by dysphonia (58.3%), foreign body sensation (41.66%), and irritative cough (50%). Most patients sought medical care more than one month after symptom onset (41.66% of cases). Constant vocal abuse was associated with 41.66% of cases, gastroesophageal reflux disease (GERD) with 33.3%, intubation with 16.6%, and 1 case (8.35%) was idiopathic. Morphologically, medium-sized granulomas predominated (66.6%), followed by microgranulomas (25%) and large granulomas (8.35%). Conservative therapy proved effective in the vast majority of cases, 9 of 12 patients (75%). A favorable outcome after CO₂ laser ablation assisted by jet ventilation was observed in 66.6% of the patients undergoing the procedure (1 recurrence among 3 operated cases). Conclusions. Conservative treatment (proton pump inhibitors, corticosteroids—3 days intramuscularly followed by 7 days inhalation, proteolytic enzymes, NSAIDs, antihistamines, and phoniatric therapy) represents the initial treatment option for laryngeal granulomas. Surgery is reserved for symptomatic, treatment-refractory, or recurrent cases. Late presentation, likely associated with the gradual increase in granuloma size, combined with gastroesophageal reflux disease, increases the probability of conservative treatment failure and the need for surgical intervention.
Introduction: Extracranial arteriovenous malformations (AVMs) are rare but challenging vascular anomalies characterized by direct arteriovenous connections that bypass the capillary network, leading to progressive lesion growth, hemorrhage, and functional impairment. The management of these lesions remains complex due to high recurrence rates and the need for multidisciplinary therapeutic approaches. Case Presentation: We report the case of a 51-year-old female presenting with a left retro-auricular pulsatile mass, headaches, and audible bruits. Magnetic resonance imaging (MRI) revealed an extracranial AVM with a 17 × 30 mm nidus. Surgical resection was performed following preoperative evaluation, involving meticulous dissection, selective vascular control, and complete excision of the malformation. The patient had a favorable postoperative course, with no neurological deficits and early hospital discharge. Discussion: Extracranial AVMs pose significant diagnostic and therapeutic challenges. While embolization serves as an adjunctive measure to reduce intraoperative bleeding, complete surgical resection remains the definitive treatment. However, lesion recurrence is common due to residual microscopic arteriovenous shunts and neovascularization. Advances in molecular pathology have identified key angiogenic pathways involved in AVM progression, opening new avenues for targeted therapies. Conclusion: This case highlights the importance of early diagnosis, comprehensive imaging assessment, and individualized surgical planning for optimal patient outcomes. Multimodal strategies integrating endovascular techniques and surgical resection remain crucial in managing extracranial AVMs. Long-term follow-up is essential to detect potential recurrence and guide future therapeutic decisions.
This study is a multidimensional research of Escherichia coli genetically paralyzed by ampicillin and polymyxin B using optical flow, Gaussian Mixture Model (GMM) clustering, angular profiling and fluorescence estimating. Phase sensitive microscopy and quartz crystal resonators provided an opportunity to efficiently monitor bacterial responses on a mechanical and visual level simultaneously. Optical flow Farneback was used to extract motion vectors that were clustered and discussed in terms of displacement, directionality and angular distribution. The samples treated with ampicillin had a heterogeneous motility in which the clusters have a high speed and directional bias along the Z-axis. In comparison, polymyxin B samples contained uniformly suppressed samples of the low-speed clusters with low angular bias. Motion mapping of HSV visualized forms of movement was done on the basis of color coded and fluorescence analysis was done to determine the metabolism of the motile clusters. The novelty of the given work lies in the fact that it involves the use of both mechanical and optical cues in the process of revealing antibiotic-specific motion patterns and organized angular reactions. These observations suggest that not only motion of bacteria under stress is suppressed but this motion is conditionally and complexly regulated. The proposed approach will deliver the speed of diagnostics and live resistance profiling.
Background: Pakistan exhibits a high global prevalence of vitamin D deficiency (78%) and excessive tea consumption patterns. Tea contains polyphenols and tannins that may interfere with mineral absorption through chelation mechanisms. This study aimed to determine the effects of excessive tea consumption on serum calcium and vitamin D levels among citizens of Nawabshah, Pakistan. Methods: This cross-sectional study was conducted in Nawabshah from January to June 2024. A total of 344 adults aged 18-40 years were recruited using convenience sampling and classified into three groups based on daily tea consumption: 1-2 cups (n=58), 3-4 cups (n=50), and ≥5 cups (n=236). Serum calcium was measured using ethylene-diamine-tetra-acetic acid titration, and vitamin D levels were determined using enzyme-linked immunosorbent assay—statistical analysis employed one-way analysis of variance and independent t-tests with Bonferroni correction. Results: Serum calcium levels decreased significantly across consumption groups: 8.36±0.68 mg/dL (1-2 cups), 7.46±0.72 mg/dL (3-4 cups), and 7.08±0.81 mg/dL (≥5 cups) (P<0.001). Vitamin D levels similarly declined: 20.2±8.4 ng/mL, 18.9±7.8 ng/mL, and 13.9±6.2 ng/mL, respectively (P<0.001). Hypocalcemia prevalence increased from 46.6% to 94.9% across groups, while vitamin D deficiency increased from 48.3% to 94.9%. Conclusions: Excessive tea consumption demonstrates a significant dose-dependent inverse relationship with serum calcium and vitamin D levels. Healthcare providers should counsel patients about optimal tea consumption patterns to prevent mineral deficiencies in populations with endemic vitamin D insufficiency.
Background: Dengue infection caused by dengue virus and transmitted through the bite of Aedes aegypti mosquito causes thrombocytopenia due to bone marrow suppression. Increased Platelet Distribution Width (PDW) and Mean Platelet Volume (MPV) values are associated with platelet activation, destruction, and consumption. Hematocrit levels increase due to hemoconcentration that occurs together with plasma leakage, which is common in dengue infection. Leukopenia occurs due to bone marrow suppression, either directly by the virus or indirectly through the production of proinflammatory cytokines. Objective: Analyzing the relationship between heparanase and hematological parameters in dengue infection patients Method: Observational analytical study with cross-sectional approach and consecutive sampling data collection in 100 patients. Heparanase levels were examined using enzyme link immunoassay (ELISA), platelet counts, PDW values and MPV values were examined using the impedance method. Hematocrit levels and leukocyte counts were examined using the lowcytometry method. Statistical analysis used the Spearman correlation test (p<0.005). Results: Heparanase levels were negatively associated with platelet count (r = -0.405, p = 0.001), and positively with PDW (r = 0.250, p = 0.012), MPV (r = 0.247, p = 0.013), and hematocrit (r = 0.269, p = 0.003). However, there was no significant association with leukocyte count (r = -0.077, p = 0.448). Conclusion: There is a weak positive relationship between heparanase levels and PDW values, MPV values and hematocrit levels. There was a weak negative relationship between heparanase levels and platelet counts and there was no significant relationship between heparanase levels and leukocyte counts.
Recurrent laryngeal papillomatosis (RLP) is a benign but clinically aggressive condition, characterized by frequent recurrences and significant morbidity. Although infection with the human papillomavirus (HPV) represents the main etiological factor, the biological mechanisms underlying the persistence and recurrence of lesions remain incompletely understood. This study aimed to perform a comprehensive histopathological and immuno-histochemical evaluation of recurrent laryngeal papillomatosis, focusing on epithelial proliferation, angiogenesis, the inflammatory microenvironment, and HPV expression. A retrospective tissue-based study was conducted on a cohort of 32 surgically excised laryngeal papilloma specimens obtained from adult patients. Conventional histopathological examination was performed using hematoxylin–eosin staining. Immuno-histochemical analysis included HPV markers, Ki-67, VEGF-A, CD31, and CD68. Proliferative activity, angiogenesis, and inflammatory infiltrates were assessed using semi-quantitative and quantitative methods. Statistical analysis was performed using standard comparative tests, with a p-value < 0.05 considered statistically significant. Histopathological evaluation revealed a typical papillary architecture, with fibrovascular stromal cores, epithelial acanthosis, koilocytic changes, and chronic inflammatory infiltrates. HPV immunopositivity was detected in 21.9% of cases, predominantly in the suprabasal epithelial layers, displaying a mosaic pattern. All lesions showed positivity for Ki-67, with heterogeneous proliferative indices. CD68-positive macrophages were variably distributed within the subepithelial stroma. CD31 immunostaining demonstrated a dense and mature microvascular network in all cases. VEGF-A expression was present in the majority of lesions and showed a moderate positive correlation with microvascular density, indicating active angiogenesis. Recurrent laryngeal papillomatosis is characterized by a complex interaction between epithelial proliferation, angiogenesis, chronic inflammation, and HPV-associated changes. VEGF-A-mediated angiogenesis appears to play a significant role in sustaining lesion growth. Comprehensive immuno-histochemical profiling provides valuable insights into the biological behavior of RLP and may contribute to improved risk stratification and the development of targeted therapeutic strategies.
Background: Adult-onset isolated focal dystonia (AOIFD) is the most common form of dystonia, being the third most common movement disorder. AOIFD has a heterogenous phenotype, etiopathogenesis being incompletely understood, both genetic and environmental factors playing a role. Objective: The objective of this study was to characterize a cohort of Romanian patients with AOIFD and to explore the potential associations between environmental factors and disease progression. Methods: We conducted an observational cross-sectional study on patients with AOIFD evaluated in a tertiary neurology referral centre in Romania, approved by the local Ethics Committee. Demographic, clinical, environmental, and treatment-related data were collected. Associations were assessed using univariable analyses and logistic regression models. Results: 89 patients were included. The most common phenotypes were cervical dystonia (53.9%) and blepharospasm (36.0%). Disease progression was present in 75.3% of cases. No statistically significant associations were observed between disease progression and environmental or lifestyle factors. Isometric occupational activity was associated with acute onset (p=0.023). Evolution to Meige syndrome occurred exclusively in patients with late-onset blepharospasm. Conclusions: AOIFD is a heterogeneous multifactorial disorder. While the assessed environmental factors were not significantly associated with disease progression, certain phenotype-specific patterns were observed.
Dystonia is a rare movement disorder, defined by intermittent or sustained involuntary movements and/or postures. The term can refer both to a clinical syndrome and to a group of primary movement disorders in which dystonia represents the predominant manifestation. Adult-onset isolated focal dystonia is the most common form. The aim of this narrative review is to present the current understanding of adult-onset isolated focal dystonia, focusing on its recently revised classification, pathogenesis, and therapeutic approaches. The updated classification system emphasize a two-axis framework integrating clinical features and aetiology, therefore facilitating improved phenotypic characterization and differential diagnosis. The underlying pathophysiological mechanisms of isolated focal dystonia remain incompletely understood, both genetic and environmental factors playing a role. Contemporary models conceptualise dystonia as a network disorder involving the striato–thalamo–cortical and cerebellar circuitry, with evidence supporting impaired inhibitory control, abnormal sensorimotor integration, and maladaptive neuroplasticity. The treatment remains largely symptomatic, with botulinum toxin representing first-line therapy, although its efficacy may be limited in some cases.
