Context: There is a current knowledge gap regarding spinal cord injured patients' motives and expectations when enrolled in regenerative studies. In addition, the impact of trial participation on daily life and perceived intervention effects remains undescribed.Objective: To describe the experiences of participating in a regenerative randomized controlled trial following traumatic spinal cord injury.Design: Longitudinal qualitative process evaluation.Setting: University hospital and rehabilitation center in Sweden.Participants: Nine participants with a complete chronic traumatic thoracic SCI, included in the SC0806 study.Interventions: Participants were in the SC0806 study allocated to one of two treatment arms: surgical implantation of a biodegradable device followed by robot-assisted gait training (RAGT), or RAGT alone.Outcome measures: Semi-structured interviews were performed four times: before randomization, at six months, 18, and 30 months after randomization. Audio-recorded interviews were transcribed and were analyzed with manifest content analysis, following a pattern-oriented longitudinal approach to inductively describe experiences over time.Results: In total, 32 interviews were conducted. Motives for participating were potential functional recovery and altruism. Surgical implantation resulted in physical symptoms that changed over time; for some participants, neurological pain and spasticity were reduced. The RAGT sessions and traveling were time-consuming and affected various aspects of everyday life. Participants completed the study according to the SC0806 protocol, despite the research burden.Conclusions: Study participation involved a substantial research burden; however, acceptability within the treatment arms, as well as sustainability and participant retention, were satisfactory. None of the participants who underwent surgical implantation experienced neurological deterioration.

Pain has been acknowledged as consisting of both emotional and sensory components. Within constructivist theories of emotion, the ability to make subtle distinctions among emotional states - known as emotional granularity (EG) - has been proposed as a downstream mechanism in chronic pain. However, its role remains empirically unexplored. In the current study, we investigated the concurrent and prospective associations between negative EG and pain intensity, and whether dispositional interoceptive sensibility (IAs) - the tendency to focus on internal sensations - moderates this relationship. Sixty-eight women with neuropathic and nociplastic chronic pelvic pain completed diary entries at each pain episode over one month. We assessed integral EG (across broad emotion families), between- and within-category EG (across and within the anger, fear, and sadness families), using multilevel models to predict concurrent and subsequent pain. Our results showed that higher integral and between-category EG were associated with lower concurrent pain among women with average-to-low IAs. Within-category EG showed no concurrent relationship with pain intensity. Prospectively, fear-specific EG in high-IAs participants was associated with heightened subsequent pain. Overall, our findings suggest that the association between EG and pain intensity is conditional on EG type, temporal frame, and interoceptive focus, thus highlighting its potential role in pain chronification.

Sickle cell disease (SCD) is a hereditary haemoglobin abnormality due to a point mutation in the β-globin gene resulting in the production of haemoglobin S. Polymerization of deoxygenated hemoglobin S results in red cell sickling, hemolysis, endothelial injury, ischemia-reperfusion damage, vaso-occlusion, and, in addition to being a hemolytic anaemia and vaso-occlusive condition, SCD is now considered a chronic inflammatory disease with significant immunological abnormalities. This review explores the pathophysiological and immunological basis of SCD, with particular emphasis on how hemolysis, inflammation, innate and adaptive immunity, vulnerability to infection and their implications for current and emerging therapeutics. SCD is characterised by sustained innate and adaptive immune responses, including leukocytosis; neutrophil and monocyte activation; changes in cytokine profiles; complement activation; and T- and B-cell dysfunction. Danger-associated molecular patterns released during hemolysis, including activate inflammasomes, oxidative stress, and endothelial dysfunction through toll-like receptors. Repeat vaso-occlusion maintains sterile inflammation and facilitates coagulation, immune regulation, and vascular damage. Also present are functional asplenia and defective humoral immunity, which predisposes to infection, particularly that caused by encapsulated bacteria. These disruptions help cause vaso-occlusive crises, acute chest syndrome, stroke, pulmonary hypertension, leg ulcers, nephropathy and long-term organ damage. Immunological dysregulation lies at the core of the pathophysiology and complications of SCD. A more detailed understanding of the immune landscape can enhance disease management and inform treatment, including drug administration, transfusion, hematopoietic stem cell transplantation, and gene-based therapies.

Nonsteroidal anti-inflammatory drugs (NSAIDs) can cause mucosal injury throughout the gastrointestinal tract, yet NSAID-related colonic damage remains underrecognized. We report a rare case of an ulcerated colonic mass mimicking carcinoma in a patient with long-term NSAID exposure. The patient, a 63-year-old man with a history of coronary artery disease and coronary artery bypass grafting more than 25 years earlier, was receiving long-term dual antiplatelet therapy consisting of aspirin (81 mg daily) and clopidogrel (75 mg daily), as well as chronic pantoprazole therapy. He presented with a 4-day history of hematochezia without weight loss. Esophagogastroduodenoscopy revealed no bleeding source, but colonoscopy identified an ulcerated, nonobstructive mass in the cecum and proximal ascending colon. A biopsy revealed colonic mucosa with severe ulceration and granulation tissue. The subsequent right hemicolectomy specimen revealed a 5.5-cm, ill-defined ulcerative mass in the cecum and ascending colon. Microscopically, the cecum and ascending colon showed ulcerated mucosa with fibrosis, reactive changes, and foreign body material deposition, without evidence of malignancy. Immunohistochemical stains for cytomegalovirus (CMV) and herpes simplex virus (HSV) were negative. Following surgery, aspirin and clopidogrel were resumed because of the patient's cardiovascular risk. Approximately 1 year later, his hemoglobin level was 12.0 g/dL (6.7 g/dL before surgery), and no gastrointestinal bleeding, diarrhea, or abdominal pain was documented during that encounter. Because aspirin was continued, a clinical response to medication withdrawal could not be assessed. Based on the medication history, right-sided distribution, and histologic findings, the lesion was considered most consistent with suspected aspirin-associated colopathy presenting as a mass-like lesion. However, the concomitant clopidogrel and pantoprazole use and the absence of a formal aspirin dechallenge limited definitive causal attribution.

Pediatric cases of chronic osteomyelitis that remain asymptomatic for a prolonged period before becoming clinically evident are exceedingly rare. We report a rare case of pediatric chronic osteomyelitis of the left radius, which became clinically evident 1.5 years after an episode of left forearm cellulitis at the same anatomical site in a three-year-nine-month-old girl. The patient presented with fever, left wrist pain, and difficulty in flexing her left fingers. Plain radiography and magnetic resonance imaging (MRI) revealed osteolytic lesions spanning the distal radial metaphysis and epiphyseal nucleus across the epiphyseal line, consistent with a chronic disease course. She underwent emergency surgical debridement and lavage of the radius. Blood culture results revealed methicillin-susceptible Staphylococcus aureus, and antibiotic therapy was adjusted accordingly. Tuberculous osteomyelitis was excluded. The patient completed a six-week course of antibiotic therapy and remained recurrence-free, with no evidence of growth disturbance, during follow-up. The cellulitis resolved promptly with a one-week course of oral antibiotics, and the patient remained asymptomatic in the interim. This case underscores the importance of obtaining a careful history of prior skin infections at the same site when osteomyelitis is suspected, even when the infection appears to have resolved completely, and highlights the value of early MRI to facilitate prompt diagnosis given the potentially prolonged asymptomatic interval.

Myocarditis as the inaugural manifestation of primary Sjögren's syndrome is exceptionally rare, and its occurrence in a seronegative patient without prominent sicca features represents a particularly challenging diagnostic scenario. We report a 20-year-old woman presenting with chest pain and inflammatory polyarthralgia, in whom echocardiography revealed moderate biventricular systolic dysfunction and cardiac MRI confirmed active myocarditis fulfilling the 2018 Lake Louise criteria. In the absence of anti-SSA, anti-SSB, and ANA, the diagnosis of seronegative primary Sjögren's syndrome was established through minor salivary gland biopsy demonstrating stage III chronic sialadenitis and a positive Schirmer's test confirming objective ocular dryness, fulfilling the 2016 ACR/EULAR criteria with a total score of 4. Treatment with hydroxychloroquine, methylprednisolone, bisoprolol, and an ACE inhibitor resulted in complete myocardial recovery at 3 months, with normalization of ejection fraction and global longitudinal strain. This case highlights that in young patients with unexplained myocarditis, systematic autoimmune screening including minor salivary gland biopsy is the decisive diagnostic step when serology alone is unrevealing, and that timely diagnosis enables targeted treatment and full cardiac recovery.

Osteoarthritis (OA) is the most prevalent degenerative joint disease and a leading cause of chronic pain and disability worldwide, particularly among aging populations. It is characterized by progressive degeneration of articular cartilage, synovial inflammation, subchondral bone remodeling, and metabolic alterations in the infrapatellar fat pad, reflecting pathology across the entire joint microenvironment. The onset and progression of OA are driven by complex interactions among mechanical stress, aging, obesity, and metabolic dysregulation, which collectively disrupt joint homeostasis. Mechanical injury and cartilage damage induce the release of damage-associated molecular patterns, activating innate immune receptors on chondrocytes and synovial cells. This promotes the production of pro-inflammatory mediators, including interleukin-1β, tumor necrosis factor-α (TNF-α), interleukin-6, and interleukin-17, which contribute to extracellular matrix degradation and cartilage deterioration. MicroRNAs (miRNAs), small non-coding RNAs that regulate gene expression post-transcriptionally, have emerged as key modulators in OA pathogenesis. They regulate chondrocyte proliferation, apoptosis, extracellular matrix turnover, inflammation, and osteochondral remodeling. Notably, certain miRNAs exhibit mechanosensitive properties, responding to altered biomechanical loading and translating mechanical stimuli into gene regulatory responses. This review synthesizes current evidence on the roles of miRNAs in OA, focusing on their regulatory functions across joint tissues, including cartilage, synovium, subchondral bone, and the infrapatellar fat pad. Key miRNAs such as miR-140, miR-146a, miR-27b, miR-34a, miR-155, and mechanosensitive miR-365 are discussed, along with their interactions with major inflammatory and degenerative signaling pathways. Their potential as diagnostic biomarkers and therapeutic targets is also highlighted.

Retropharyngeal displacement of the internal carotid artery (ICA) is an uncommon anatomical variant with significant procedural safety implications. The vessel deviates medially into the retropharyngeal space, approaching or contacting the posterior pharyngeal mucosa, placing it at immediate risk of injury during routine pharyngeal instrumentation. We report a 54-year-old woman with type 2 diabetes mellitus, hypertension, and hyperlipidemia who experienced a three-year diagnostic delay before this anomaly was identified. Her presentation of unilateral chronic otalgia and burning throat discomfort sequentially mimicked otitis externa and laryngopharyngeal reflux (LPR), both of which failed to respond to empirical treatment. CT of the neck with intravenous contrast revealed the right ICA approaching the pharyngeal mucosa. Flexible laryngoscopy demonstrated pulsatile submucosal bulging of the posterior pharyngeal wall, highly suggestive of an underlying vascular structure Carotid duplex ultrasonography demonstrated no hemodynamically significant stenosis bilaterally. Conservative management was adopted, with provider notification initiated. At six-month follow-up, the patient remained neurologically intact with stable symptoms. This case highlights the importance of vascular anomaly recognition in patients with unexplained, treatment-refractory otolaryngologic symptoms and the potentially fatal consequences of unrecognized aberrant ICA during pharyngeal procedures.

The lymphatic system is a part of the circulatory system, playing a crucial role in fluid balance and immune function. Dysfunction of the lymphatic system can lead to lymphedema, a chronic and progressive condition characterized by the accumulation of lymphatic fluid, resulting in tissue swelling, pain, and functional impairment. Lymphedema is classified as either primary or secondary. Primary lymphedema arises from congenital dysfunction of the lymphatic system and may be associated with various genetic syndromes or occur idiopathically. Secondary lymphedema is associated with damage, obstruction, or removal of previously normal lymphatic vessels or lymph nodes. Traditionally, management strategies for lymphedema have been predominantly conservative, and even now, conservative treatment with complete decongestive therapy remains the gold standard. However, in recent years, lymphatic surgical approaches such as lymphaticovenous anastomosis and vascularized lymph node transfer have been improved by advances in microsurgical techniques, with promising clinical outcomes. Equally important, lymphatic tissue engineering has emerged as a promising new direction in lymphedema treatment, introducing both new challenges and opportunities. The complex tissue and molecular alterations associated with lymphedema remain major obstacles to developing a universally applicable treatment algorithm. As no curative treatment is currently available, this review aims to provide a comprehensive overview of current therapeutic options for lymphedema, highlight key experimental advances in lymphatic tissue engineering, and discuss their potential translational applications.

Abdominal cocoon syndrome (ACS), also known as sclerosing encapsulating peritonitis (SEP), is a rare cause of mechanical small bowel obstruction characterized by partial or complete encasement of the small bowel within a fibrocollagenous membrane. Owing to its nonspecific clinical and radiological presentation, preoperative diagnosis remains challenging. A 38-year-old woman with a history of four previous Caesarean sections presented with one week of progressive colicky abdominal pain, abdominal distension, and absolute constipation that worsened during the preceding 24 hours despite conservative management. She reported a five-year history of recurrent, self-limiting episodes of bowel obstruction beginning two to three months after her last Caesarean section. Contrast-enhanced computed tomography (CT) was initially interpreted as a 6-cm distal jejunojejunal intussusception with a characteristic target sign. Diagnostic laparoscopy, however, revealed partial encapsulation of the small bowel by a dense fibrocollagenous membrane, consistent with secondary type I ACS. Complete laparoscopic membrane excision and adhesiolysis were successfully performed. Retrospective postoperative review of the CT images demonstrated clustering of small bowel loops with partial fibrocollagenous membrane encasement that had been overlooked on the initial interpretation. The postoperative course was uneventful. Oral intake was resumed on postoperative day 3, and the patient was discharged on postoperative day 5. Histopathological examination demonstrated fibrocollagenous tissue with chronic inflammatory infiltrates. After excluding other recognized secondary causes, the patient's history of four previous Caesarean sections was considered the most likely predisposing factor. At two-year follow-up, the patient remained asymptomatic with no recurrence of bowel obstruction. ACS may mimic intussusception on CT, creating an important diagnostic pitfall in patients with recurrent small bowel obstruction. This case highlights the importance of maintaining a high index of clinical suspicion and demonstrates the short-term technical feasibility of laparoscopic diagnosis and management in carefully selected patients when performed by experienced surgeons.