Search Results (1,543)

Extracellular vesicles (EVs) are membrane-bound nanoparticles released by almost all cell types into the extracellular space, acting as important mediators of intercellular communication by transferring proteins, lipids, and nucleic acids horizontally. EVs are generally classified into small EVs (<200 nm), medium/large EVs (>200 nm), microvesicles, and apoptotic bodies, with current classification methods focusing on physical properties, molecular composition, and cellular origin, as detailed in the MISEV2023 guidelines. EVs are highly promising for diagnostic and therapeutic applications due to their intrinsic biocompatibility, stability in biological fluids, capacity to carry diverse molecular cargo, and potential for drug delivery and functionalization to enable targeted delivery and tissue repair. This narrative review discusses the emerging roles of EVs across various medical fields, including obstetrics and gynecology, ophthalmology, otorhinolaryngology, urology, oncology, orthopedics, neurology, immunology, wound healing, chronic pain management, dermatology, and cardiology. In each discipline, EVs show potential as biomarkers for diagnosing physiological or pathological conditions and as carriers for targeted drug delivery and regenerative treatments. Exosomes, a major type of small EVs, have especially attracted attention as versatile nanocarriers for precision medicine. However, translation into clinical practice requires addressing key pitfalls, including the standardization of isolation and characterization protocols, dose definition, GMP-compliant large-scale production, and regulatory approval. Ongoing interdisciplinary collaboration across disciplines and thorough clinical testing will be essential to unlock the full biomedical potential of EVs and establish them as transformative tools in personalized healthcare. Full article

Intervertebral disc degeneration (IVDD) initiates a cascade of structural and biological changes that compromise mechanical function, often leading to chronic pain. While small animal models have provided insight into inflammatory and nociceptive mechanisms of IVDD, translational studies require large animal models that more closely replicate human spine anatomy and physiology. This study induced cervical disc degeneration via intradiscal chondroitinase ABC (ChABC) injection in a large animal model and evaluated the associated disc pathology and neuroinflammatory responses across IVDs and within spinal cord and dorsal root ganglia (DRG) tissues. Results confirmed structural degeneration at ChABC-injected levels and revealed additional evidence of adjacent segment degeneration. Neuroinflammatory analyses revealed innervation, via deposition of PGP9.5 and NFH, throughout both ChABC-injected and adjacent IVDs. Monocyte markers were significantly increased in ChABC-degenerated IVDs. Across experimental groups, the level of monocyte (Ly6C) and macrophage (CD68) markers correlated with worsened histological scores and with reduced mechanical integrity. Similarly, increased production of the neuropeptide, Substance P, in IVDs was significantly positively correlated with compromised IVD mechanical function. Finally, we observed elevated production of the microglia marker, Iba1, and Substance P production in the spinal cord, with similar trends in DRGs, in degenerative spines. By establishing quantitative relationships between disc pathology, immune responses, and neural activation, this work established possible disease-contributing neuroinflammatory activation and further validated a clinically relevant model for preclinical evaluation of regenerative and therapeutic strategies. Full article

Background/Objectives: Non-atherosclerotic pathological findings on coronary arteries involve various disorders that might lead to myocardial ischemia, independent of plaque complications and consequent lumen narrowing and obstruction. These patients often present with non-specific symptoms such as shortness of breath, rapid fatigue, and exertional chest tightness. When the underlying causes are non-atherosclerotic, these findings are frequently overlooked in radiology reports as a possible differential diagnosis. Therefore, the objective of this paper is to present the role of multidetector computed tomography (MD CT) coronary angiography in the diagnostic work-up of patients with rare but clinically valuable non-atherosclerotic pathological conditions of coronary arteries. Methods: We performed a literature search on Medline (via PubMed) for works presenting data on rare, non-occlusive, pathological findings on coronary arteries. Results: The review of the collected literature was performed in a narrative manner, intended to summarize mainly findings of imaging characteristics of non-occlusive pathologies: myocardial bridge, coronary aneurysm, ectasia, fistula, stenosis, and dissection. MD CT images of selected cases that were examined at our department, showing non-occlusive pathological changes in the coronary arteries, are displayed in planar and/or volume-rendered formats. Conclusions: Non-atherosclerotic abnormalities of the coronary vessel wall should be considered in the differential diagnosis of coronary causes of chest pain, dyspnea, and arrhythmias, as they may lead to both acute and chronic myocardial ischemia. Based on the presented literature and specific cases from our clinical practice, MD CT is shown to be an important tool for the rapid, non-invasive evaluation of non-atherosclerotic pathologies. Full article

Background/Objectives: Oral health-related quality of life (OHRQoL) is a complex topic, encompassing the medical, functional and psychosocial aspects of well-being, especially in the context of systemic conditions that can trigger oral cavity impairment. While this subject has been extensively investigated in adults, evidence remains limited in pediatric populations, particularly in children with leukemia who are at high risk for oral complications related to the disease itself and its treatment. Moreover, children and parent perceptions of oral health are essential for guiding preventive and personalized therapeutic strategies, yet they are poorly explored in this clinical context. The objective of this study was to assess OHRQoL in children with leukemia and gingival inflammation, and compare it with that of children without this systemic condition. Methods: This observational, cross-sectional, case–control study was conducted on 99 subjects, divided into two groups: the study group n = 49 leukemia subjects and the control group n = 50 subjects without oncologic pathology. Clinical examination of all subjects was performed and oral health status was evaluated using Oral Health Index-Simplified (OHI-S) and Gingival Index (GI). Parents filled out a personalized exploratory questionnaire, adapted after established scales, designed to capture the child’s perceived impact of certain leukemia-related gingivo-periodontal alterations, including pain, ulcerations, gingival bleeding and xerostomia. Data were analyzed using descriptive statistics, Pearson’s Chi-square test and comparative graphical analyses (IBM SPSS Statistics 26). Results: Children with leukemia reported higher frequencies of xerostomia, ulcerations and gingival bleeding compared to children in the control group, with xerostomia showing a suggestive association to gingival inflammation. Oral hygiene status of children in the leukemia group was generally better among children receiving parental assistance during brushing or those practicing dental flossing. Comparative graphical analyses showed differences in symptom reporting and oral hygiene support between groups. Conclusions: The results suggest that xerostomia seemed to align with gingival inflammation in children with leukemia, while parental assistance and dental flossing seemed to be associated with better oral hygiene status. Our findings also support the need for developing standardized, disease-oriented scales of evaluating OHRQoL, as well as individualized oral care and continuous monitoring in order to improve oral health-related quality of life in this vulnerable pediatric population. Full article

Patients presenting with abdominal pain require expedited diagnosis and treatment. Computed tomography (CT) scans, which are frequently ordered in the inpatient and emergency departments, have high diagnostic sensitivity and specificity. However, CTs are costly, have radiation exposure, can create hospital workflow inefficiencies, and create a potential safety risk with patient transport. Point-of-care ultrasound (POCUS) use is growing as an efficient, safe, and bedside assessment tool for diagnosing and treating gastrointestinal (GI) pathologies. This manuscript synthesizes key sonographic findings and techniques for a series of important GI pathologies that physicians should recognize: diverticulitis, hernia, appendicitis, intussusception, and intra-abdominal mass. Full article

(1) Background: Endometriosis and chronic endometritis (CE) are pathologies that are positively correlated and have similar paracrine and immunological alterations. This leads us to wonder whether their interrelationship plays a role in the etiopathogenesis or progression of endometriosis. The purpose of this study is to evaluate whether patients with endometriosis and CE have a more advanced stage of the disease, higher rates of pain, a poorer response to treatment, and a greater association with other pathologies compared to women with endometriosis without CE. (2) Methods: This is a cross-sectional pilot design study of 37 women with endometriosis who underwent endometrial aspiration for the diagnosis of CE and were followed up at the Puerta de Hierro Hospital. (3) Results: All patients with CE in this study had adenomyosis (p = 0.004). There was a relatively homogeneous distribution of CE in the different endometriosis phenotypes. The group of patients with endometriosis and CE indicated higher rates of pain during ovulation and less pain during defecation and sexual intercourse. (4) Conclusions: A high prevalence of CE was observed in patients with endometriosis, as well as a trend suggesting a relationship between CE and adenomyosis that should be studied. The following article attempts to reflect a link found between endometriosis and chronic endometritis, which would be important when prescribing personalized medicine, as it forces us to look for a specific disease in a specific patient profile. Full article

Objective: Inferior alveolar (IAN) and lingual nerve (LN) injuries are known complications of impacted mandibular third molar surgery and may result in persistent neurosensory deficits. This exploratory, non-randomized clinical study evaluated the clinical and electrophysiological effects of low-level laser therapy (LLLT) and transcutaneous electrical nerve stimulation (TENS) on neurosensory recovery following trigeminal nerve injury. Methods: Twenty-seven patients with postoperative IAN or LN injury received LLLT, TENS, or placebo therapy according to institutional clinical protocols. Clinical outcomes were assessed using Visual Analog Scale (VAS) scores, and electrophysiological evaluation was performed using electromyography by measuring cutaneous silent period (CSP) duration. Non-parametric statistical analyses were conducted using the Wilcoxon signed-rank and Mann–Whitney U tests. Results: LLLT was associated with statistically significant improvements in several neurosensory symptoms, including pain, burning sensation, speech difficulty, biting, and taste disturbance. In contrast, TENS and placebo treatment did not demonstrate a consistent or generalized improvement across neurosensory outcomes. CSP durations differed significantly between healthy and pathological sides both before and after treatment. Although CSP duration showed a tendency to increase following LLLT, these changes did not reach statistical significance. Subgroup analysis revealed greater clinical improvement in LN injuries compared with IAN injuries within the LLLT group. Conclusions: Within the limitations of this exploratory study, LLLT was associated with more pronounced clinical improvement than TENS or placebo in patients with third molar-related trigeminal nerve injury. CSP measurements provided supportive objective information, although electrophysiological recovery remained limited. Full article

We report a rare case of primary renal adenosarcoma in a 26-year-old woman presenting with right flank pain. Contrast-enhanced computed tomography demonstrated a large, mixed solid and cystic mass confined to the renal pelvocalyceal system, closely mimicking a malignant renal tumor. Histopathologic examination revealed a biphasic tumor with phyllodiform architecture. Immunohistochemistry showed benign epithelial positivity for cytokeratin and focal malignant stromal positivity for smooth muscle actin and CD10; however, the tumor was negative for CD99, Wilm’s tumor protein, SS18-SSX, BCOR, and estrogen/progesterone receptors. These findings led to the diagnosis of primary renal adenosarcoma. This case highlights the diagnostic challenge of distinguishing this rare tumor from more common renal malignancies and underscores the importance of imaging–pathologic correlation. Full article

Knee osteoarthritis (KOA) is a leading cause of disability in older adults, characterized by persistent pain and reduced physical function. Beyond localized joint pathology, many individuals with knee osteoarthritis experience multisite pain and live with multiple comorbidities, reflecting a heterogeneous and multifactorial pain condition. Prognostic models based primarily on biomedical variables have shown limited ability to explain long-term outcomes, partly due to insufficient integration of pain chronicity, comorbidity count and psychosocial determinants such as treatment expectations and pain self-efficacy. While exercise and education are commonly recommended as primary non-surgical treatments, people often respond to them very differently. This study protocol describes a secondary longitudinal observational analysis of data from the EPIPHA-KNEE two-arm, multicentre randomized controlled trial. The primary outcomes will be knee OA pain intensity and physical function, assessed using the Western Ontario and McMaster Universities Arthritis Index (WOMAC) questionnaire at baseline, 3, 6 and 12 months. Baseline prognostic factors will include pain duration, pain distribution, comorbidity count and patient expectations, including treatment expectations and pain self-efficacy. Linear mixed-effects models will be used to examine longitudinal associations between these predictors and pain and function trajectories, with particular emphasis on predictor-by-time interactions to characterize differential patterns of change over time. The planned analyses aim to improve understanding of how clinical characteristics and expectancy-related factors jointly shape 12-month pain and physical function trajectories in older adults with knee osteoarthritis receiving education and exercise-based care, thereby informing prognostic stratification within non-surgical management. Full article

Background/Objectives: Quadriceps arthrogenic muscle inhibition (AMI) represents a key impairment following anterior cruciate ligament reconstruction (ACLR), contributing to quadriceps weakness. Although transcutaneous electrical nerve stimulation (TENS) and percutaneous electrical nerve stimulation (PENS) have been primarily investigated for analgesia, their effects on quadriceps strength in the early postoperative period remain underexplored. Methods: This study describes a single-blinded, parallel-group randomized controlled trial investigating the short-term effects of a single high-frequency TENS session and a novel long-term potentiation (LTP) PENS protocol on quadriceps strength and related clinical outcomes after ACLR. Fifty-four participants will be randomly allocated using block randomization in a 1:1:1 ratio to one of three groups: a control group (conventional post-ACLR rehabilitation only), a TENS group (conventional rehabilitation plus a single high-frequency TENS session), or a PENS group (conventional rehabilitation plus a single LTP PENS session). Participants will receive neuromodulatory intervention during the sixth postoperative week. The LTP PENS protocol consists of five 5 s stimulation bursts at 100 Hz and 250 μs pulse width and has only been investigated once in patients with upper limb pathology, underscoring its novelty in a postoperative setting. Results: The primary outcome is quadriceps maximal voluntary isometric contraction, selected as a clinically relevant surrogate of quadriceps activation deficits associated with AMI. Secondary outcomes include pain intensity, pressure pain threshold, knee range of motion, thigh muscle perimeter, knee effusion and swelling, and self-reported function and knee-related quality of life. Outcomes will be assessed at baseline, immediately post-treatment, and 1 and 7 days post-intervention by a blinded assessor. Full article

The blood–brain barrier and blood–spinal cord barrier (BBB/BSCB) are essential protective components for the healthy functioning of the central nervous system (CNS). While these barriers protect the CNS from peripheral factors, such as immune cells and blood products, they can become disrupted in pathological conditions and injury. The neurovascular unit (NVU) is composed of endothelial cells (ECs), pericytes, astrocytes, microglia, and neurons, all of which contribute to proper function and the maintenance of the BBB/BSCB. Tight junctions (TJs) unite cellular components and are modulated by both intrinsic and extrinsic factors. Systemic processes, such as pain (nociceptive activity), inflammation, and blood hemostasis, can impact BBB/BSCB function, often leading to a disrupted barrier and increased peripheral infiltration. This, in turn, can increase neuroinflammation and drive microglia activation, progressive hemorrhagic necrosis (PHN), and matrix metalloproteinase (MMP) activity. Targeting these processes and mitigating the deleterious effects of BBB/BSCB breakdown represents a key therapeutic target after neural injury and other pathological conditions. Full article

Pain is an unpleasant but essential sensory experience that serves as a protective mechanism, yet it can also manifest maladaptively in a wide range of pathological conditions. Current analgesic strategies rely heavily on opioid medications and non-steroidal anti-inflammatory drugs (NSAIDs); however, concerns regarding addiction, tolerance, and dose-limiting adverse effects highlight the urgent need for safer and more effective therapeutics. Voltage-gated sodium (Na_v) channels, which govern the initiation and propagation of action potentials, have emerged as promising targets for mechanism-based analgesic development. In particular, the Na_v1.7–Na_v1.9 subtypes have attracted substantial interest owing to their enrichment in the peripheral nervous system—despite broader expression elsewhere—and their central roles in nociception, offering the potential for non-addictive, subtype-selective pain modulation. This review summarizes the physiological roles of these channels in nociception, examines how disease-associated mutations shape pain phenotypes, and highlights recent advances in drug discovery targeting Na_v1.7 and Na_v1.8. The recent FDA approval of VX-548 (suzetrigine), a first-in-class and highly selective Na_v1.8 inhibitor, marks a major milestone that validates peripheral Na_v channels as clinically actionable targets for analgesia. We also discuss the remaining challenges and emerging opportunities in the pursuit of next-generation, mechanism-informed analgesics. Full article

Hepatocellular injury syndrome represents a pathological process with a broad etiological spectrum, including viral infections, autoimmune diseases, or intoxications. Clinicians must identify the potential cause using both anamnestic data and available paraclinical examinations. We present the case of a 55-year-old female patient, admitted to the Internal Medicine 1 Department at the Clinical County Emergency Hospital Bihor, Oradea, Romania. The patient exhibited nonspecific complaints and insignificant pathological antecedents, but from a biochemical perspective, substantial changes in liver transaminase levels were evident. To establish differential diagnoses, a series of biochemical and immunological tests were performed, along with a thorough medical history. It was concluded that the patient regularly consumes herbal infusions, specifically Laurus nobilis leaves, commonly known as Bay Laurel. Although this might be easily overlooked at first glance, a closer examination could explain the current clinical picture. In April 2024, a 55-year-old female patient with no history of liver pathology was admitted. She complained of asthenia fatigue, anorexia, mixed dyspeptic symptoms, diffuse abdominal pain, and a weight loss of 12 kg. The pathology had insidiously started approximately 3 months prior. On examination, the patient had altered general status, anorexia, and was overweight. Biochemically, the patient had elevated liver transaminase values (AST = 196 U/L and ALT = 357 U/L) that continued to rise during hospitalization, despite hepatoprotective treatment. Various paraclinical examinations were performed to exclude other potential causes of hepatic aggression, having excluded ordinary causes. Consequently, a liver biopsy was performed, and the histopathological examination leaned toward a toxic hepatitis etiology. Application of the updated RUCAM scale yielded a score of eight points (“probable” HILI—Herb-Induced Liver Injury). Clinical and biochemical improvement was observed after complete cessation of bay leaf tea consumption. This case highlights the potential hepatotoxicity of commonly used culinary herbs when consumed in large quantities or as concentrated infusions and emphasizes the importance of detailed anamnesis regarding herbal product use. Full article

Background: Feigned restriction of shoulder joint movement for secondary gain is clinically relevant and may misdirect care, distort disability determinations, and inflate system costs. Distinguishing feigning from structural pathology and from functional or psychosocial presentations is difficult because pain is subjective, performance varies, and no single sign or test is definitive. This comprehensive review hypothesizes that the systematic integration of clinical examination, objective biomechanical and neurophysiological testing, and emerging technologies can substantially improve detection accuracy and provide defensible medicolegal documentation. Methods: PubMed and reference lists were searched within a prespecified time frame (primarily 2015–2025, with foundational earlier works included when conceptually essential) using terms related to shoulder movement restriction, malingering/feigning, symptom validity, effort testing, functional assessment, and secondary gain. Evidence was synthesized narratively, emphasizing objective or semi-objective quantification of motion and effort (goniometry, dynamometry, electrodiagnostics, kinematic sensing, and imaging). Results: Detection is best approached as a stepwise, multidimensional evaluation. First-line clinical assessment focuses on reproducible incongruence: non-anatomic patterns, internal inconsistencies, distraction-related improvement, and mismatch between claimed disability and observed function. Repeated examinations and documentation strengthen inference. Instrumented strength testing improves quantification beyond manual testing but remains effort-dependent; repeat-trial variability and atypical agonist–antagonist co-activation can indicate submaximal performance without proving intent. Imaging primarily tests plausibility by confirming lesions or highlighting discordance between claimed limitation and minimal pathology, while recognizing that normal imaging does not exclude pain. Diagnostic anesthetic injections and electrodiagnostics can clarify pain-mediated restriction or exclude neuropathic weakness but require cautious interpretation. Motion capture and inertial sensors can document compensatory strategies and context-dependent normalization, yet validated standalone thresholds are limited. Conclusions: Feigned shoulder impairment cannot be confirmed by any single test. The desirable strategy combines structured assessment of inconsistencies with objective biomechanical and neurophysiologic measurements, interpreted within the whole clinical context and rigorously documented; however, prospective validation is still needed before routine implementation. Full article

Endometriosis (EDT) is a chronic, estrogen-dependent disease characterized by inflammation, fibrosis, pelvic pain, and infertility. Current therapies show limited long-term efficacy and adverse effects, underscoring the need for novel therapeutic approaches. Elevated copper (Cu) levels have been reported in both patients and animal models of EDT, making Cu chelation a promising strategy. This work aimed to evaluate the impact of ammonium tetrathiomolybdate (TM) on the expression of markers related to the interconnected processes of inflammation, innervation, and fibrogenesis in mice with induced EDT. Twenty-four female C57BL/6 mice were assigned to Sham, EDT, or EDT+TM groups. Treatment with TM began on postoperative day 15, with samples collected one month after EDT induction. Peritoneal fluid cytokines (TNF-α, IL-1β, IL-6, TGF-β1) were quantified by ELISA. Endometriotic-like lesions were examined for mRNA expression of cytokines, neurotrophins (Ngf, Bdnf, Ngfr), neural markers (Uchl1, Gap43), neuropeptides and nociceptive markers (Tac1/Tacr1, Calca/Calcrl/Ramp1, Trpv1), and fibrogenic markers (Vim, Acta2, Col1a1, Fmod) by RT-qPCR. Neurotrophin protein levels were measured by ELISA, and collagen content was assessed through Masson’s staining. TM significantly modulated inflammatory, neural, nociceptive, and fibrogenic markers, reducing most of them along with collagen content. These findings suggest that TM could impact key pathological mechanisms involved in EDT. Full article