Search Results (2,396)

Pain is the most significant and debilitating symptom throughout all stages of pancreatitis, yet the precise mechanisms responsible for it remain only partially understood, and current pain relief methods often prove insufficient. To gain a clearer understanding, it is crucial to consider pancreatitis not as a singular condition but as comprising three distinct clinical types: acute pancreatitis (AP), recurrent acute pancreatitis (RAP), and chronic pancreatitis (CP), each of which may involve different pathways for pain perception. Notably, RAP has historically been overlooked as a distinct entity, resulting in a paucity of phenotype-specific data regarding its pain mechanisms. At the molecular level, pain in pancreatitis involves peripheral and central sensitization, neuroinflammatory signaling, and structural neural remodeling, processes driven by mediators such as substance P, CGRP, NGF, TRP channels, and pro-inflammatory cytokines. However, these mechanisms have been studied largely in isolation and within single phenotypes, leaving a critical gap in our understanding of how they evolve and interact across the full disease spectrum. This review aims to establish a comprehensive framework detailing the molecular mechanisms responsible for pain in all three pancreatitis phenotypes, with a particular focus on RAP as a less-studied clinical condition and to identify phenotype-specific targets for therapeutic development. Full article

Background/Objectives: Lipschutz ulcers were first described in 1912 by the Austrian dermatologist Benjamin Lipschutz. The onset presents with flu-like symptoms with consecutive development of painful vulvar ulcers. The term is currently used to describe painful genital lesions associated with an immunological reaction to an extragenital source of infection, usually viral or bacterial infections or certain vaccines. This disease affects predominantly adolescent non-sexually active females and is usually self-limiting. Methods : We searched PubMed, Research Gate and Google Scholar using the keywords “Lipschutz ulcer”, “Ulcus vulvae acutum Lipschutz”, “Acute genital ulcer”, and “Reactive non-sexually related acute genital ulcers”. A total of 24 articles in English between the years 2000 and 2025 were selected in order to mark the latest advancements towards diagnostic and treatment plans. Only 19 provided thorough information about the treatment and follow-up of the patients, encompassing a total of 69 girls and women. Results: This review synthesizes the most common etiological factors for Lipschutz ulcers and explores the mechanism behind their development. Different treatment approaches were also investigated. Based on our findings, we propose a diagnostic and treatment algorithm depending on the patient’s general condition and severity of the ulcers. We reported a 12-year-old girl’s case, diagnosed and treated at our department. Despite our efforts, conservative therapy proved inefficient. Surgery was performed. Conclusions: Lipschutz’s ulcer is a diagnosis often overlooked. Therefore, further research is needed to address the best treatment strategies. Surgery should be reserved only for patients who show no improvement with conservative treatment. Full article

Background and Objectives: The recent adoption of RATS (robot-assisted thoracic surgery) alongside VATS (video-assisted thoracoscopic surgery) in minimally invasive thoracic surgery highlights the need for comparative evaluation of both techniques regarding postoperative pain and clinical outcomes. This study compared acute postoperative pain within the first 24 h, as well as postoperative complications, 30-day mortality, and length of hospital and ICU stay. Materials and Methods: A retrospective observational study was conducted including all patients scheduled for VATS or RATS at a tertiary hospital between November 2021 and December 2024. Demographic characteristics, surgical procedures, surgical approach, and pain-related outcomes at 24 h (Numeric Rating Scale [NRS], subjective assessment scale, and rescue analgesia) were obtained from the Acute Pain Unit database of the Department of Anesthesiology. Other variables were collected from the electronic medical record. Results: A total of 148 patients were analyzed, of whom 118 underwent VATS and 30 RATS. Surgical duration was significantly longer in the RATS group (130 vs. 218 min, p < 0.05). No significant differences were observed in NRS scores (2.57 ± 1.06 vs. 2.3 ± 0.79, p = 0.195) or subjective pain assessment (good: 78% vs. 83.3%, p = 0.472). RATS required less rescue analgesia in the unadjusted analysis (30.0% vs. 52.5% in VATS, p = 0.022); however, this association was no longer statistically significant after multivariable adjustment (VATS: OR 2.40, 95% CI 0.93–6.25; p = 0.071). There were no significant differences in postoperative complications (17.8% in VATS vs. 16.7% in RATS, p = 0.85), length of hospital stay (4.9 ± 6.2 days in VATS vs. 3.4 ± 3 days in RATS, p = 0.2), or 30-day mortality (0.8% in VATS vs. 0% in RATS, p = 1). ICU length of stay was longer in the RATS group (0.32 ± 0.78 days in VATS vs. 0.73 ± 1.23 days in RATS, p = 0.024). Conclusions: RATS did not demonstrate superiority over VATS in terms of postoperative pain, patient satisfaction, or clinical outcomes. Full article

Background: Chest pain is a leading cause of emergency department (ED) visits, requiring rapid identification of acute coronary syndrome (ACS). The HEART score is widely used for risk stratification, although its ability to identify ACS associated with significant coronary artery stenosis (SCS) remains incompletely studied. This study evaluates its diagnostic performance in patients with acute chest pain. Methods: A retrospective analysis included patients presenting to the ED with non–ST-elevation chest pain triaged as very urgent by the Manchester Triage System. Patients with ACS underwent invasive coronary angiography. Based on the final diagnosis and angiographic findings, patients were classified into two groups: (1) ACS with SCS and (2) non-ACS or ACS without SCS. The HEART score was retrospectively calculated. Diagnostic performance for ACS with SCS was assessed using sensitivity, specificity, and receiver operating characteristic curve analysis. Results: Of 480 patients, 34 had ACS with SCS. The HEART score demonstrated high discriminative performance (AUC = 0.956; 95% CI 0.929–0.983), with sensitivity 88.2% and specificity 87.9% at a cut-off of ≥6. Conclusions: The HEART score showed strong diagnostic performance for ACS with SCS in ED patients with non–ST-elevation chest pain and may support early identification of patients requiring invasive coronary evaluation. Full article

Background: Immunosuppressed patients are at an increased risk for developing odontogenic and orofacial infections, which can present with atypical processes and features that may mimic rare but life-threatening infections such as Ludwig’s angina. Differentiating cellulitis from a deep neck space infection is often challenging in this population in acute settings due to a broad differential diagnosis and blunted inflammatory responses. This diagnostic uncertainty complicates acute risk stratification and may delay recognition of conditions requiring early airway evaluation and intervention. Case Presentation: We present the case of a 28-year-old male with chronic myelogenous leukemia on immunosuppression with dasatinib who developed unilateral facial swelling and severe odontogenic pain that was refractory to empiric antibiotic therapy. The patient’s presentation with rapid clinical progression, early trismus, submandibular involvement, and floor-of-mouth tenderness raised significant concern for evolving Ludwig’s angina. Laboratory evaluation demonstrated elevated inflammatory markers, including erythrocyte sedimentation rate and C-reactive protein, further complicating early assessment. Imaging was promptly obtained to determine the nature of the infection, and the patient was admitted for intravenous antibiotic therapy and airway monitoring. Clinical improvement ensued. Conclusions: This case highlights the diagnostic overlap between facial cellulitis and Ludwig’s angina and underscores the importance of prompt imaging, airway monitoring, and clinical vigilance for risk stratification of immunocompromised patients in the acute setting to prevent life-threatening complications. Full article

Background: Cholangiocarcinoma (CCA) is a rare and aggressive malignancy of the biliary tree. Renal metastasis represents an exceptionally rare event, reported in fewer than 0.5% of cases. Its clinical and imaging presentation may closely mimic benign renal conditions, particularly renal infarction, posing a significant diagnostic challenge. Case Presentation: We report the case of a 72-year-old man who initially presented with intense right-sided flank pain without urinary symptoms. Combined imaging findings, including absent Doppler signal on ultrasound and absent contrast uptake on contrast-enhanced ultrasound (CEUS) in two-thirds of the right renal parenchyma, led to an initial diagnosis of right renal infarction. Seven months later, re-evaluation prompted by macroscopic haematuria, significant weight loss, cholestatic syndrome, and markedly elevated CA 19-9 revealed an invasive renal tumour mass associated with biliary ductal dilatation. Renal biopsy with immunohistochemical analysis (CK7+, PAX8−, c-kit weakly positive) confirmed renal metastasis from extrahepatic cholangiocarcinoma. The patient’s clinical course was complicated by acute cholangitis, Clostridioides difficile enterocolitis, and upper gastrointestinal haemorrhage, requiring endoscopic retrograde cholangiopancreatography (ERCP) with biliary stenting, endoscopic ultrasound (EUS)-guided hepaticogastrostomy, and endoscopic haemostasis. Conclusions: A systematic review of the published literature identified only two previous dedicated case reports of renal metastasis from CCA, making this, to our knowledge, the third such case and the first involving an extrahepatic primary tumour presenting through its renal metastasis. This case highlights the diagnostic pitfall of mistaking hypovascular renal metastasis for renal infarction, the indispensable role of immunohistochemistry, and the importance of early percutaneous biopsy in avascular renal lesions without a confirmed thromboembolic aetiology. Full article

Background: Pharmacological blockade of the NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome has emerged as an attractive pharmacological strategy for a broad range of inflammatory and metabolic disorders. However, translating preclinical efficacy into clinical success remains a major bottleneck. We previously reported the discovery of a novel, potent NLRP3 inhibitor, KBD3536, but its in vivo efficacy across different pathological conditions remains uncharacterized. Here, we systematically evaluated the in vivo efficacy of KBD3536 across diverse preclinical models of NLRP3-related pathologies. Methods: KBD3536 was evaluated in established rodent models of monosodium urate (MSU)-induced acute inflammation (mouse air pouch and rat gouty arthritis models), radiation-induced dermatitis (RID), and high-fat diet (HFD)-induced obesity. Results: In the MSU models, KBD3536 markedly suppressed local interleukin-1β and interleukin-6 secretion in air pouch exudates and dose-dependently alleviated acute arthritis symptoms, including joint swelling and joint pain. In the RID model, KBD3536 significantly attenuated radiation-induced skin injury and ameliorated radiation-induced systemic weight loss. Under HFD challenge, early intervention with KBD3536 mitigated HFD-induced adiposity, early hepatic steatosis and its associated inflammatory responses, and preserved physical performance. Mechanistically, KBD3536 partially restored AMP-activated protein kinase α1 (AMPKα1) mRNA expression in adipose tissue and restored hepatic Cyp3a11 transcriptional activity. Conclusions: NLRP3 inhibitor KBD3536 exhibited broad-spectrum anti-inflammatory efficacy across multiple preclinical models, supporting its potential as a promising candidate for diverse NLRP3-related disorders. Full article

Most patients with chest pain do not have acute myocardial infarction (AMI), yet post-AMI rule-out disposition remains variable. Detectable but sub-99th percentile high-sensitivity cardiac troponin I (hs-cTnI) provides additional prognostic information. We evaluated the economic value of hs-cTnI-guided hospitalizations among non-AMI patients. We analyzed 1481 non-AMI chest pain visits with detectable baseline hs-cTnI across 29 U.S. emergency departments (2014–2016) in the prospective HIGH-US trial using the Atellica IM TnIH assay(Siemens Healthcare Diagnostics, Tarrytown, NY, US). We compared observed standard-of-care admissions with modeled pathways incorporating hs-cTnI thresholds and risk scores, assessing admission rates, costs, and diagnostic accuracy for 30-day death/MI. Overall, 1.0% (n = 15/1481) experienced 30-day death/MI. Standard-of-care admitted 59% of patients with 93% sensitivity and 41% specificity. The modeled pathway using hs-cTnI ≥ 5 ng/L plus non-low risk scores was associated with reduced projected admission of 41%, higher specificity of 60%, and the same 93% sensitivity. Estimated per-patient diagnostic costs were lower under Scenario 1 (noninvasive diagnostic testing only; $1025 vs. $1139) and under Scenario 2 (including inpatient/invasive procedures; $2672 vs. $3536). In subgroups, higher hs-cTnI thresholds conferred further economic benefit without compromising sensitivity. Incorporating sub-99th percentile hs-cTnI thresholds alongside risk scores may support more efficient resource use while maintaining safety, although findings require prospective validation. Full article

Background: Endovascular repair with covered stent is an established minimally invasive treatment for popliteal artery lesions, particularly in elderly or high-risk patients. Infectious complications are exceptionally rare but may result in arterial destruction, limb loss, and death. Salmonella species demonstrate a well-recognized affinity for diseased arterial walls and prosthetic vascular material. Case Presentation: An 82-year-old man with stage G4 chronic kidney disease and previous nephrectomy for renal cell carcinoma, complicated by Salmonella Enteritidis septic shock 20 years earlier, presented with acute left lower limb ischemia caused by a post-traumatic popliteal artery pseudoaneurysm. Urgent endovascular repair was performed using a 6 × 100 mm covered stent (Viabahn) with adjunctive angioplasty of the anterior tibial artery. Two weeks later, he was readmitted with fever, severe popliteal pain, local erythema, and elevated inflammatory markers. Imaging demonstrated early stent occlusion with a large peri-graft abscess and contained arterial rupture. Emergency open conversion included radical debridement, complete graft explantation, and popliteal-to-posterior tibial bypass using an autologous great saphenous vein. Cultures grew Salmonella Enteritidis. Retrospective history revealed a previously undocumented episode of Salmonella Enteritidis bacteremia approximately 20 years earlier. At 2-year follow-up, the patient remained free of recurrent infection with a patent vein graft and preserved ambulatory function. Conclusions: Early Salmonella Enteritidis infection of a popliteal covered stent is an exceptionally rare but life-threatening complication. This case suggests that remote Salmonella bacteremia may represent a potential, hypothesis-generating risk factor for prosthetic graft infection. Prompt graft explantation followed by radical debridement and autologous venous reconstruction remain essential for durable limb salvage. Full article

Per rectum examination (PRE) is commonly used in the triage of horses with acute abdominal pain, despite reports of associated risk factors for both horses and personnel, but its diagnostic accuracy is questionable. This multicenter, observational study aimed to evaluate the agreement between PRE findings and surgical findings obtained via exploratory laparotomy in horses with colic. A total of 201 cases from four equine referral hospitals across Europe were included. Rectal findings were categorized as primary (most likely cause of colic) or additional. Agreement with surgical findings was assessed using kappa statistics. The influence of examiner demographic data (age, gender, and qualification status) on diagnostic accuracy was also evaluated. The agreement between primary rectal and primary surgical diagnosis was 57.2% (115/201; kappa coefficient, 0.490; 95% confidence interval, 0.394–0.586). When both primary and additional findings were considered, agreement increased to 71.6% (144/201, kappa coefficient, 0.720; 95% confidence interval, 0.156–0.927; 65.1–77.4%). The highest agreement was seen in cases of gas-distended large colon (90.3%), small intestinal distension (75.8%), and left dorsal displacement of the large colon (66.7%). Detection of small intestine distension in PRE had the highest sensitivity (85.7%) and negative predictive value (92.8%) among the evaluated parameters. Examiner demographics had no significant impact on diagnostic accuracy. PRE is a valuable but imperfect diagnostic tool. Given the dynamic nature of colic and possible changes between examination and surgery, some discrepancies are expected. Other variables, such as horse size or the examiner’s hand dominance, were not investigated in this study but may have had an impact on the observed outcomes. Overall, PRE remains a practical, accessible technique that provides clinically useful information regardless of examiner experience. Full article

Background and Objectives: Early diagnosis of acute myocardial infarction (AMI) remains challenging due to the “diagnostic blind window” of conventional protein biomarkers and the limited sensitivity of electrocardiograms in non ST-segment elevation myocardial infarction (NSTEMI). Cardiospecific circulating microRNAs, specifically the microRNA-208 (miR-208) family, have emerged as promising candidates to bridge this gap. This systematic review and meta-analysis evaluated the diagnostic accuracy of circulating miR-208 and outlines a proposed conceptual framework to guide its clinical translation. Materials and Methods: PubMed and Embase were systematically searched up to June 24th, 2026, for clinical studies evaluating the diagnostic performance of circulating miR-208a and/or miR-208b against standard reference definitions for AMI. Risk-of-bias assessment using the QUADAS-2 tool was performed independently by two reviewers. Pooled sensitivity and specificity were estimated using bivariate random effects modeling, and sources of heterogeneity were explored via subgroup analyses. Results: Forty-one studies enrolling 6306 participants were included in the qualitative synthesis, of which 14 were eligible for meta-analysis. The pooled sensitivity and specificity of circulating miR-208 for AMI detection were 0.89 (95% CI: 0.81–0.94) and 0.90 (95% CI: 0.83–0.94), respectively. Marked between-study heterogeneity was observed. Subgroup analyses revealed significantly higher diagnostic accuracy in isolated STEMI (sensitivity: 0.95) or NSTEMI (sensitivity: 0.93) cohorts compared to mixed chest pain populations (sensitivity: 0.65; p < 0.0001). Specificity dropped from 0.90 with healthy controls to 0.80 when using non-AMI controls (p = 0.002), indicating spectrum bias. Funnel plots suggested prominent small-study effects. Conclusions: Circulating miR-208 exhibits a powerful biological signal for the early detection of cardiomyocyte injury, but its standalone clinical utility is constrained by methodological heterogeneity and publication bias. Rather than an immediate clinical tool, future prospective translation requires evaluating this biomarker within the standardized miAMI framework—conceptually prioritizing future investigation of the hyper-acute (<2 h) window, absolute quantification to resolve normalization variability, and integration into multi-marker point-of-care panels. Full article

Background: Hyponatraemia is the commonest electrolyte disturbance encountered in older adults admitted with neck of femur (NOF) fracture. It is now recognised both as associated with fragility fracture and as an independent prognostic indicator for adverse post-operative outcomes. Methods: Narrative review of the literature, with emphasis on cohort studies, meta-analyses and mechanistic investigations pertinent to hip fracture in adults. Results: Admission hyponatraemia affects approximately 13–20% of NOF patients, twice the prevalence observed in age-matched community-dwelling elders and broadly comparable to general geriatric inpatients. A further 20–30% develop in-hospital, predominantly post-operative, hyponatraemia. Mild hyponatraemia (130–135 mmol/L) accounts for 75–85% of cases. Pathophysiology is multifactorial: hypovolaemia from the fracture haematoma, fasting and pre-admission “long lie”; drug effects (thiazides, selective serotonin reuptake inhibitors (SSRIs), proton pump inhibitors, carbamazepine, opioids); and non-osmotic arginine vasopressin (AVP) release driven by pain, nausea and peri-operative stress. Chronic hyponatraemia is hypothesised to contribute to fracture risk through three convergent mechanisms, direct sodium-dependent stimulation of osteoclastogenesis with AVP-mediated bone resorption, subtle cerebral dysfunction producing gait and attention deficits, and sarcopenia, although much of this mechanistic evidence derives from animal and in vitro studies rather than from patients with hip fracture. Hyponatraemia is reproducibly associated with longer length of stay, delayed surgery, and an adjusted 30-day mortality hazard of approximately 1.15–1.40. A dose–response relationship with severity is demonstrable; pre-operative correction has not been shown to improve outcomes in any randomised trial. Conclusions: Hyponatraemia in NOF fracture is consistently a consequence of the acute event and, at minimum, a robust marker of frailty and adverse prognosis. Whether it also causally contributes to fracture risk remains unproven, since the supporting human evidence is entirely observational and mechanistic, each contributing study carries methodological weaknesses that warrant caution, and no interventional study has established causality. Where hyponatraemia is mild and isolated, current evidence does not support delaying surgery; moderate and severe hyponatraemia warrant individualised assessment, with cautious correction proceeding alongside surgical planning rather than postponing it. Given the absence of interventional evidence, no correction strategy can yet be recommended to improve fracture or surgical outcomes. Prospective trials of targeted correction strategies and rehabilitation outcomes are overdue. Full article

Medicinal cannabis has gained increasing attention from both the scientific community and clinical practice, due to the therapeutic potential of its major phytocannabinoids, particularly cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC), for pain management. This review compiled and analyzed the available evidence regarding the antinociceptive effects of nanoencapsulated cannabinoids compared to free compounds. The published works have explored some pharmaceutical formulations and administration routes on different acute, chronic and neuropathic pain experimental models. The findings indicated that cannabinoids exhibited promising analgesic effects, while nanoencapsulation could enhance its stability and bioavailability. Despite these advances, the number of reports investigating nanostructured cannabinoid-based systems remains limited, with a predominance of preclinical research. A recurrent lack of structural information and quality control data for such works was also noted. Furthermore, there were not identified any research regarding the nanoencapsulation of full-spectrum cannabis oils or whole cannabis extracts, highlighting a significant gap in the current literature. Overall, nanoencapsulation emerges as a versatile strategy to overcome the intrinsic limitations of cannabinoids and expand its clinical applicability for pain treatment. Nevertheless, further efforts are required to determine standardized methodologies, facilitating the translation of preclinical findings into clinical practice, in order to provide stable, safe, effective and more accessible cannabinoid-based therapies. Full article

Background and Clinical Significance: Streptococcus pyogenes (group A Streptococcus, GAS) can cause rapidly progressive invasive infections, including necrotizing soft tissue infection (NSTI) and streptococcal toxic shock syndrome (STSS). Although invasive GAS disease is often associated with skin barrier disruption, severe infection may also follow blunt trauma without visible skin injury. Case Presentation: A 22-year-old woman presented with persistent right hip and groin pain four days after a blunt fall during recreational sports activity, without disruption of skin integrity. On admission, she was hypotensive, tachycardic, and intermittently hypoxemic, with local hematoma, swelling, and inflammatory infiltration of the right groin. Laboratory tests showed marked inflammation, acidosis, acute kidney injury (AKI), elevated lactate, creatine kinase, and myoglobin levels. She was admitted to the intensive care unit with septic shock. Empirical antimicrobial therapy was initiated with piperacillin/tazobactam, clindamycin, and linezolid. Computed tomography showed inflammatory changes extending from the right groin to the thigh fascia. On day 3, the patient’s condition deteriorated with respiratory failure necessitating endotracheal intubation and mechanical ventilation. Surgical incision revealed inflamed and necrotic subcutaneous tissue with superficial muscle involvement. Deep tissue cultures yielded GAS, whereas blood and urine cultures remained negative; probable STSS was diagnosed. Therapy was de-escalated to penicillin plus clindamycin. Continuous renal replacement therapy with an adsorptive acrylonitrile 69 surface-treated (AN69ST) membrane was initiated for AKI. The patient gradually improved and was transferred to the surgical ward on day 16. Conclusions: Minor blunt trauma without skin disruption may precede life-threatening invasive GAS infection. Rapid recognition, surgical source control, antitoxin antimicrobial therapy, and intensive organ support are essential in suspected STSS. Full article

Introduction: Isolated peroneus longus (PL) tendon tears are rare injuries and an often-overlooked cause of chronic lateral ankle pain. Evidence regarding optimal conservative management, especially in elite athletes, remains limited. Focused extracorporeal shockwave therapy (F-ESWT) has shown promising results in tendinopathies, yet its application in acute tendon tears is poorly documented. Methods: We present the case of a professional football player in his late twenties who sustained an isolated longitudinal PL tear. The player underwent a combined conservative protocol including F-ESWT, physiotherapy, and custom orthotics. Pain (Visual Analog Scale, VAS) and function (AOFAS Ankle–Hindfoot Score) were assessed at baseline, three months, and in an 18-month follow-up. MRI scans were obtained at diagnosis and after six weeks to evaluate tendon healing. Results: The conservative treatment protocol, including eight sessions of ultrasound-guided F-ESWT (2500–4000 impulses per session, 50–550 µJ/mm²) led to marked pain relief and functional improvement. VAS decreased from 7/10 to 1/10, while AOFAS improved from 57 to 95 points, maintained at 18 months. MRI after six weeks of treatment demonstrated decreased intratendinous hyperintensity, reduced lesion length, and re-establishment of normal tendon architecture. The player returned to training after eight weeks and full competition after 12 weeks, remaining asymptomatic thereafter. Conclusions: A multimodal treatment consisting of F-ESWT, physiotherapy with progressive loading and orthotic correction resulted in rapid and durable healing of an isolated PL tear in a professional athlete. This case supports the potential role of a multimodal conservative treatment strategy including F-ESWT as a first-line, non-invasive option for acute peroneal tendon tears. Full article