Search Results (369)

Background: Epidural motor cortex stimulation (MCS) is an established neuromodulatory option for refractory neuropathic pain; however, structured data on long-term outcomes, stimulation dependency, and real-world device management remain limited, particularly in chronic neuropathic orofacial pain. Methods: This retrospective single-center cohort study included patients with refractory neuropathic orofacial pain treated with epidural MCS at a tertiary neurosurgical center. Clinical data were extracted from medical records and longitudinal follow-up documentation. Pain intensity was assessed using a unified 0–10 numerical rating scale (NRS/VAS) at baseline, best achieved response, and last follow-up. Responder status was defined at the last follow-up (≥50% pain reduction from baseline). Secondary outcomes included stimulation dependency during OFF periods, reprogramming burden, device-related events, and safety. Results: Ten patients (6 women, 4 men; mean age 61.5 ± 8.6 years) were followed for a mean of 7.6 ± 6.3 years (range 2–22 years), with 70% exceeding five years of follow-up. Baseline pain intensity (8.8 ± 0.4) decreased to 4.6 ± 0.8 at the best achieved response and remained lower at last follow-up (5.6 ± 0.9). At the last follow-up, eight patients (80%) were classified as partial responders (30–49% pain reduction), while two (20%) were classified as non-responders. Clinically relevant worsening during stimulator OFF periods occurred in 70% of patients. Reprogramming was required in all patients, and 60% underwent battery replacement. No clinically significant stimulation-related adverse effects were observed. Conclusions: Epidural MCS was associated with sustained pain reduction over extended follow-up. These findings support the interpretation of MCS as a chronic neuromodulatory therapy requiring ongoing stimulation, individualized programming, and long-term device management, contributing clinically relevant long-term evidence to the evolving role of neuromodulation in refractory chronic neuropathic pain. Full article

Background and Clinical Significance: Patients with a left ventricular assist device (LVAD) are at risk of ventricular arrhythmias, which are generally hemodynamically tolerated if they occur. In such cases, patients may experience painful implantable cardioverter-defibrillator (ICD) shocks. Case Presentation: A 71-year-old patient with a history of dilated cardiomyopathy caused by a phospholamban (PLN) gain-of-function mutation, with a primary prevention ICD and an LVAD, presented with multiple ICD shocks which she experienced as painful and traumatic. She was found to have ongoing ventricular fibrillation with apparent hemodynamic stability. Conversion to sinus rhythm was achieved through intravenous administration of antiarrhythmic drugs followed by external defibrillation using stacked shocks. Due to the traumatic nature of the shocks, the shock function of the ICD was turned off. Nearly two months later, the patient presented for a second time and was again found to have ventricular fibrillation which had been present for at least six weeks. Conversion to sinus rhythm was unsuccessful and the patient was discharged to her home with an advanced care plan and her LVAD was deactivated. The patient died two months later. Conclusions: Patients with an LVAD can remain hemodynamically stable for prolonged periods of time during ventricular arrhythmias. ICD shocks are therefore mostly experienced as painful and even traumatic. Therefore, the routine use of ICD shock therapy in patients with an LVAD should be reconsidered. Adjustment of ICD programming to higher rates and longer detection may be warranted. Further investigation is warranted regarding a switch to devices with an alarm function rather than therapies for tachyarrhythmias. Full article

Background and Clinical Significance: Polycythemia vera (PV) is a myeloproliferative neoplasm associated with a markedly increased risk of arterial and venous thrombosis. Superior mesenteric artery (SMA) thrombosis is an exceptionally rare but potentially fatal complication. Case Presentation: We report the case of a 25-year-old man with previously diagnosed, JAK2-negative PV who presented with acute abdominal pain, nausea, vomiting, abdominal distension, and absence of stool and flatus, consistent with clinical features of intestinal obstruction. Laboratory testing revealed marked leukocytosis, elevated inflammatory markers, and subtherapeutic anticoagulation (INR 1.2) despite ongoing oral therapy. Multislice computed tomography demonstrated occlusion of the SMA with developed collateral circulation and features of small-bowel ischemia. Due to progression to an acute abdomen, emergency laparotomy was performed, revealing jejunal perforation with preserved viability of the remaining bowel. Primary closure was carried out, followed by peritoneal lavage and drainage. The postoperative course was uneventful. After correction of anticoagulation and therapeutic INR monitoring, no recurrent thrombotic events were observed during follow-up. Conclusions: This case underscores the importance of strict anticoagulation control, early imaging, and prompt surgical intervention in patients with PV, even in young individuals and in atypical vascular territories. Full article

Botulinum toxin type A (BoNT/A) injection into the bladder wall is a milestone in the treatment of urinary incontinence in patients with neurogenic detrusor overactivity (NDOi) or overactive bladder syndrome (OABi) who are refractory to or unable to tolerate oral or transdermal therapies. However, the efficacy of BoNT/A is hampered by the low long-term adherence of patients to a treatment that requires repeated bladder injections under cystoscopy control. The discontinuation is particularly evident among incontinent patients with spontaneous voluntary voiding, regardless of whether the cause is NDOi or OABi, although clearly more marked among the latter group. In addition to the bother and pain associated with repeated cystoscopies, these patients show low tolerance to the high incidence of urinary tract infections (UTIs) and transient urinary retention, the two most common adverse events. Fewer injection points may render treatments less painful, apparently without reducing efficacy, but will not avoid the need for repeated cystoscopies, and no studies have demonstrated that such modification increases adherence. Eventually, accessing the bladder wall for BoNT/A administration via a transabdominal approach, under real-time ultrasound guidance, may overcome trans-urethral limitations, but the technique’s reproducibility remains unknown. An intensive investigation is ongoing to identify aids that facilitate the passage of the large, fragile BoNT/A molecule across the urothelium to reach the bladder nerves without injections. Electromotive Drug Administration (EMDA) of BoNT/A demonstrated efficacy and safety over a 6-year follow-up in NDOi patients at a single center, but the results were not reproduced at other institutions. The application of shock waves to the bladder using shock waves generated by Extracorporeal Shock Wave Lithotripsy (ESWL) machines to tear the urothelium and facilitate the passage of BoNT/A instilled in the bladder is ingenious, but the experience is very limited. Dimethyl sulfoxide, liposomes, and thermal-reversal hydrogel to deliver the toxin failed in pilot trials. BoNT/A in nano-formulations has high heat stability, resistance to pH changes, and to enzymatic degradation. Extended efficacy in dermal and intramuscular pilot applications is promising but needs to be replicated in the bladder. Full article

Fibromyalgia (FM) is a chronic pain syndrome characterized by central sensitization and impaired pain modulation, involving dysfunctional descending inhibitory pathways and altered nociceptive processing. These processes contribute to persistent musculoskeletal pain, difficulties with sleep, feelings of depression, and ongoing fatigue. Serotonin and norepinephrine are key mediators of pain control, and evidence indicates that dual reuptake inhibition provides superior analgesia compared to single-pathway approaches. Accordingly, serotonin–norepinephrine reuptake inhibitors (SNRIs), including milnacipran and duloxetine, approved for FM treatment, show favorable efficacy and tolerability compared with tricyclic antidepressants. This integrative literature review aimed to evaluate the impact of SNRIs on musculoskeletal pain, fatigue, depression, and quality of life in patients with FM by analyzing randomized clinical trials (RCTs), identified via PubMed/MEDLINE searches (2015–2025) in English/Portuguese using descriptors: “Fibromyalgia”, “Serotonin and Norepinephrine Reuptake Inhibitors”, “Duloxetine” and “Milnacipran”. From 195 records screened, 18 studies met inclusion criteria (9.2% inclusion rate); duloxetine evaluated in 16 studies (88.9%), milnacipran in 2 (11.1%); SNRIs demonstrated superior efficacy vs. placebo: pain reduction 30–40%, fatigue improvement 25%, quality of life enhancement 20%. SNRIs were overall more effective than placebo but did not achieve high levels of analgesia, underscoring the need for further research on long-term efficacy and comparisons with combination pharmacological and non-pharmacological therapies. SNRIs significantly alleviate musculoskeletal pain (30–50% of patients), fatigue, depression symptoms, and improve quality of life in FM versus placebo. Duloxetine showed superior efficacy for pain/depression; milnacipran excelled in sleep quality. Long-term studies and combination therapies warrant further investigation. Full article

Background: Peripheral nerve stimulation (PNS) is increasingly used in selected patients with neuropathic pain, and many individuals seek supplemental online information to clarify procedural expectations and postoperative care. Large language models such as ChatGPT may provide scalable patient education; however, their performance for PNS-related questions has not been evaluated. This study assessed the reliability, accuracy, and comprehensibility of ChatGPT-5.0 responses to common PNS patient questions. Methods: We conducted a cross-sectional evaluation of ChatGPT-5.0 responses to 21 standardized questions derived through expert consensus, spanning pre-implantation, implantation, and post-implantation domains. Sixteen board-certified interventional pain specialists and a nurse educator independently rated each response using validated scales for reliability (1–6), accuracy (1–3), and comprehensibility (1–3). Descriptive statistics were calculated, and domain-level patterns were examined. Results: Clinician ratings demonstrated generally strong performance across all domains. Mean reliability was 4.7 ± 1.4, mean accuracy 2.6 ± 0.6, and mean comprehensibility 2.8 ± 0.5. Foundational questions addressing mechanisms, expectations, and postoperative care received the highest ratings. Lower ratings were observed for implantation-focused items requiring procedural nuance. No response fell below predefined acceptability thresholds, and sensitivity analyses confirmed that including one partial evaluator did not alter the observed trends. Conclusions: ChatGPT-5.0 generated responses to PNS-related patient questions that clinicians rated as generally reliable, accurate, and understandable, particularly for foundational and postoperative topics. Performance was more variable for procedural questions, underscoring the need for clinician oversight and verification. These findings provide a benchmark of current LLM capabilities and highlight the importance of ongoing evaluation as models evolve and as patients access versions with differing functionalities. Full article

Background: Polysubstance use, particularly the combination of opioids and stimulants, represents a growing public health concern due to its high risk of severe multisystem complications and mortality. Here, we present a case illustrating the lethal synergy of opioid–stimulant co-use. Methods: A 37-year-old male with chronic Hepatitis C and documented polysubstance use reported recent use of fentanyl, cocaine, methamphetamine, and cannabis. He presented with generalized weakness, left lower limb pain, tense edema, and anuria. Clinical assessment included monitoring of vital signs, physical examination, capillary blood gas analysis, extended laboratory panels (muscle and cardiac enzymes, electrolytes, and coagulation parameters), urinalysis, and Doppler imaging. Management over five days included intravenous hydration, diuretics, urinary alkalinization, electrolyte correction, anticoagulation, metabolic and vitamin therapy, hemodialysis, and comprehensive supportive care. Results: Laboratory evaluation revealed massive rhabdomyolysis (peak CK 161,050 U/L), severe hyperkalemia (K⁺ 8.4 mmol/L), metabolic acidosis, acute kidney injury with oligoanuria, and left-sided deep vein thrombosis. Despite intensive multidisciplinary interventions, the patient’s repeated refusal of ongoing treatment critically contributed to a fatal outcome. Conclusions: This case underscores the high mortality risk associated with opioid–stimulant co-use and the crucial impact of treatment refusal. Clinicians and public health stakeholders should recognize the rapid progression of multisystem dysfunction in polysubstance users and prioritize early, aggressive interventions combined with patient engagement strategies to mitigate fatal outcomes. Full article

Background/Objectives: Postoperative pain pharmacology is complex. We investigated the sensitivity of analgesic-like effects induced by morphine, ibuprofen, and their combination to peripheral opioid antagonism in a mouse laparotomy model. Methods: Mechanical hypersensitivity was assessed using von Frey filaments, and ongoing pain (abdominal licking and facial expressions) was evaluated using artificial intelligence algorithms. We tested the sensitivity of the analgesic treatments to the opioid antagonist naloxone or its peripherally restricted analog, naloxone methiodide. We also tested the effects of neutrophil depletion using an anti-Ly6G antibody. Gastrointestinal transit and pupillary diameter were measured to assess non-analgesic opioid effects. Results: Morphine reversed all pain-related behaviors; its effect on mechanical hypersensitivity was reversed by peripheral opioid antagonism, whereas its effects on ongoing pain were not. Ibuprofen reduced mechanical hypersensitivity and facial expressions but failed to alter licking. Interestingly, the ibuprofen effect on mechanical hypersensitivity depended on peripheral opioid receptors and neutrophils at the injury site. The morphine–ibuprofen combination produced synergistic analgesia across all endpoints without enhancing opioid-induced gastrointestinal inhibition or mydriasis. Peripheral opioid antagonism reversed the effect of the combination on mechanical hypersensitivity and facial expressions but not on licking. Conclusions: Our results replicate the key clinical phenomena relevant to the postoperative pain context, including the potentiation of morphine analgesia by ibuprofen without the exacerbation of adverse effects. Our results suggest that drug effects on different postoperative pain measures rely on distinct neurobiological mechanisms and are not interchangeable. Therefore, the use of a battery of complementary pain endpoints in preclinical pharmacology studies is advisable. Full article

Pregnancy (HP), defined as the coexistence of intrauterine and ectopic gestations, is a rare condition, especially in spontaneous conception, but it is a life-threatening obstetric emergency when rupture occurs, with a reported maternal mortality rate of 0.03%. Diagnosis is often delayed because confirmation of an intrauterine pregnancy can mask clinical signs of a concurrent ectopic gestation. Early recognition and prompt surgical intervention are therefore critical to maternal safety and preservation of intrauterine viability. This case highlights the diagnostic challenges and successful management of a spontaneous ruptured heterotopic pregnancy. Case presentation: A 34-year-old Middle Eastern woman, gravida 4, with a spontaneous conception, presented with sudden severe lower abdominal pain and signs of acute hemoperitoneum (hypotension, tachycardia, and marked peritoneal signs). Transvaginal ultrasound demonstrated a viable intrauterine pregnancy at 9 weeks 4 days gestation, together with a ruptured left tubal ectopic pregnancy of similar gestational age. The patient underwent urgent laparoscopic left salpingectomy with evacuation of approximately 1200 mL of intraperitoneal blood and clots. Postoperatively, she developed significant anemia (hemoglobin drop from 11.2 g/dL on admission to 6.5 g/dL) requiring transfusion of four units of packed red blood cells. Serial ultrasonographic follow-up confirmed ongoing viability of the intrauterine pregnancy, which ultimately resulted in a live birth at term. Progressive resolution of the postoperative pelvic hematoma was also noted. Conclusions: Ruptured heterotopic pregnancy remains a diagnostic and therapeutic challenge. This case, along with a synthesis of the contemporary literature, demonstrates that a high clinical index of suspicion, timely ultrasound diagnosis, and immediate minimally invasive surgical management are paramount. Furthermore, rigorous postoperative monitoring and resuscitation, including targeted transfusion, are essential to achieve maternal stabilization while allowing continuation of a viable intrauterine pregnancy, with reported live birth rates exceeding 70% following timely intervention. Full article

Background/Objectives: Childhood-onset Sjögren disease (cSjD) is a rare autoimmune disorder with heterogeneous manifestations and ongoing diagnostic challenges, as there are no validated paediatric criteria. Our study aims to characterise the clinical, laboratory, and imaging features of children diagnosed with cSjD at a single Romanian paediatric rheumatology centre between 2015 and 2025 and contextualise these findings within the most recent literature. Methods: A retrospective review of 15 consecutive cSjD patients was conducted, including clinical features, autoantibodies, imaging, biopsy findings, treatment, and outcomes. Results: Our cohort showed a significant female predominance (80%) and a broad age range at disease onset (3–15 years). Extraglandular manifestations were more common at presentation than glandular phenotypes (53.3% vs. 40%). Lupus-like extraglandular presentations frequently led to initial misdiagnosis as childhood-onset systemic lupus erythematosus (SLE) in our cohort. Sicca symptoms were present at diagnosis in only 3 of 15 patients (20%) and developed later during follow-up in an additional 4 patients (26.7%). Notably, the cohort included novel findings, such as an unprecedented presentation with acute exudative pericarditis complicated by cardiac tamponade. Anti-SSA antibodies and salivary gland ultrasound abnormalities were highly prevalent (86.7% and 100%, respectively). Anti-SSB antibodies were detected in seven patients (46.7%), with titres showing more variability than those of anti-SSA, ranging from just above the positivity threshold to mildly elevated levels. The association with macro-creatine kinase type I was another distinctive feature of this series. Chronic musculoskeletal pain and dryness were our patients’ most frequently reported symptoms at the last assessment, affecting up to 5/15 (33.3%) in each domain. One patient showed irreversible ocular damage during our study. Conclusions: Extraglandular presentations of cSjD are highly heterogeneous and diagnostically challenging, often occurring without glandular symptoms. Lupus-like systemic features—including facial vasculitic purpura, with or without arthralgia, and occasional pericarditis, as observed in our cohort—may contribute to frequent initial diagnostic misattribution to SLE. Early salivary gland ultrasonography, targeted autoantibody testing, and selective biopsy are essential for timely diagnosis, underscoring the urgent need for paediatric-specific validated classification criteria. Full article

Background: Sinonasal mucosal melanoma is a rare and aggressive malignancy arising from the nasal cavity and paranasal sinuses, characterized by high local recurrence rates and poor survival. Skull-base and orbital progression can occur rapidly, particularly when preoperative imaging underestimates local extension. This paper reports a case of sinonasal mucosal epithelioid melanoma with fulminant postoperative skull-base breach and orbital invasion, highlighting its clinical course, management challenges, and histopathological features. Methods: A 60-year-old woman with progressive unilateral nasal obstruction, recurrent epistaxis, and headache underwent clinical evaluation, contrast-enhanced head MRI, CT, and PET-CT staging. Preoperative imaging demonstrated no intracranial or orbital invasion. Biopsy confirmed mucosal epithelioid melanoma with high proliferative activity (Ki-67 ~80–85%). The patient underwent extensive image-guided endoscopic resection with intraoperative cerebrospinal fluid leak repair. Results: Definitive histopathology confirmed pigmented epithelioid melanoma with extensive necrosis, bone invasion, and non-assessable resection margins due to specimen fragmentation (pT4a, Rx). Within two weeks postoperatively, CT and MRI demonstrated extensive local recurrence with cribriform plate destruction, anterior skull-base dural infiltration, and rapid orbital progression with optic nerve compression and loss of vision. Despite hemorrhage control and hypofractionated palliative radiotherapy (VMAT, 33 Gy in 11 fractions), the patient experienced progressive neurological decline, refractory pain, and recurrent tumour bleeding, and died approximately 4.5 months after initial presentation. Conclusions: In patients with sinonasal mucosal epithelioid melanoma, fulminant local progression with skull-base and orbital involvement may occur despite apparently limited preoperative imaging. When rapid vision loss, dural infiltration, and refractory nasal bleeding develop, structured palliation, hemorrhage control, and aggressive multimodal analgesia should be prioritized early alongside ongoing multidisciplinary decision-making. Full article

Chronic pain imposes a substantial burden on global health and remains challenging to manage, despite ongoing advances in pharmacologic and interventional therapies. Recognition of chronic pain as a condition driven by central sensitization and neuroimmune dysregulation has prompted interest in therapies that target these mechanisms rather than peripheral nociception alone. Low-dose naltrexone (LDN), administered at doses substantially lower than those used for opioid or alcohol use disorders, has emerged as a repurposed treatment with potential analgesic and anti-inflammatory properties. This review summarizes the pharmacologic characteristics of LDN, with emphasis on its proposed mechanisms involving transient opioid receptor blockade, modulation of microglial activation, Toll-like receptor signaling, and central neuroimmune pathways. Available clinical evidence evaluating LDN across a range of chronic pain conditions, such as fibromyalgia, neuropathic pain syndromes, inflammatory and autoimmune disorders, headache disorders, and other centralized pain states, is critically reviewed. Although early trials, observational studies, and case series suggest potential benefit in selected populations, the overall evidence base remains limited, heterogeneous, and characterized by variability in dosing strategies and outcome measures. Safety, tolerability, and practical considerations relevant to contemporary pain practice are discussed, including interactions with opioid therapy and challenges related to off-label use. Finally, key gaps in the current evidence and priorities for future research are highlighted, underscoring the need for larger, well-designed randomized trials and mechanism-informed studies to better define LDN’s role in multimodal chronic pain management. Full article

Aims: This study aims to assess the effect of a structured universal self-care practices module on improving self-care compliance and health maintenance behaviors among women with endometriosis, and to determine if it reduces pain severity. Design: A quasi-experimental design was used. Methods: A total of 90 women confirmed a diagnosis of endometriosis, who were free from any chronic medical or gynecological comorbidities, and who had not received any pain relief pharmacological interventions. Results: The study and control groups were comparable at baseline regarding socio-demographic and clinical characteristics (p > 0.05). Following the intervention, the study group demonstrated significant improvements in universal self-care practices compared to the control group at one month (M = 69.2 ± 11.6 vs. 58.3 ± 8.83; t = −4.93, p = 0.001) and three months (M = 76.4 ± 16.5 vs. 61.5 ± 12.2; t = −4.89, p = 0.001). A strong negative correlation was found between self-care and symptom severity at one month (r = −0.70, p < 0.001) and three months (r = −0.83, p < 0.001), indicating that improved self-care was associated with reduced symptoms. Conclusions: This study highlights the vital role of nursing-led, WHO-based self-care interventions in improving compliance and reducing pain among women with endometriosis. Integrating such programs into routine care can enhance self-management and overall quality of life. Patient or Public Contribution: Integrating individualized, nursing-led self-care programs into routine endometriosis management can improve symptom control through ongoing education and follow-up. Nurses play a pivotal role in empowering women’s self-management, while adopting the WHO Universal Self-Care Framework can strengthen gynecological care policies and practices. Full article

Long COVID is a complex condition characterized by persistent symptoms following SARS-CoV-2 infection. Understanding its biochemical mechanisms is essential for effective management and treatment strategies. Objective: This study investigated biochemical alterations associated with long COVID in unvaccinated individuals presenting symptoms persisting for more than six months, highlighting the prolonged nature of the condition and its systemic and neurological manifestations. A cross-sectional study was conducted with 60 unvaccinated patients at least six months post-COVID-19 infection. Serum biomarkers, including C-reactive protein (CRP), interleukin-6 (IL-6), N-terminal pro-brain natriuretic peptide (NT-proBNP), and irisin, were analyzed. Correlations between these biomarkers and persistent symptoms were assessed using statistical regression models. Elevated CRP levels were significantly associated with persistent respiratory and musculoskeletal symptoms, suggesting ongoing inflammation. Increased IL-6 levels correlated with fatigue and musculoskeletal complaints. NT-proBNP elevations were linked to cardiovascular manifestations, including dyspnea and chest pain. A positive correlation between irisin and persistent sensory impairments, such as anosmia and dysgeusia, indicates potential neuroinflammatory mechanisms. This study highlights that persistent inflammation plays a critical role in long-term (>6 months) post-COVID manifestations. Monitoring biomarkers such as CRP, IL-6, NT-proBNP, and irisin may enhance understanding and management of prolonged post-COVID conditions. Full article

Phantom limb pain (PLP) is a frequent and often persistent consequence of limb amputation, characterized by pain perceived in the absent limb. Despite decades of research, its biological basis remains incompletely understood, and available treatments often provide inconsistent relief. This reflects the complex and heterogeneous nature of phantom limb pain, which cannot be explained by a single anatomical site or pathological process. Current evidence suggests that phantom limb pain emerges from the interaction of changes occurring at multiple levels of the nervous system. Peripheral nerve injury associated with amputation induces molecular and cellular alterations that may influence early nociceptive signaling. These changes can interact with adaptive and maladaptive responses within the spinal cord, including altered synaptic transmission and neuron–glia interactions, which may facilitate sustained amplification of pain-related signals. At supraspinal levels, long-term adaptations within distributed neural networks involved in sensory, motor, and affective processing may contribute to the persistence of pain perceptions in the absence of ongoing peripheral input. Immune-related signaling and long-term regulation of gene expression further modulate these processes and may contribute to inter-individual variability. In this narrative review, we synthesize current experimental and clinical evidence addressing the molecular and cellular processes associated with phantom limb pain following lower limb amputation. Findings are integrated across peripheral, spinal, and supraspinal levels, with consideration of immune-related and regulatory influences. By highlighting areas of convergence, uncertainty, and existing knowledge gaps, this review aims to provide a coherent biological framework that may support future experimental and translational research in this challenging field. Full article