Search Results (512)

Globally, endometriosis affects almost 10% of reproductive-aged women, leading to chronic pain and discomfort. Endocrine-disrupting compounds (EDCs) seem to play a pivotal role as a causal factor. The current manuscript aims to explain potential molecular pathways, synthesize current evidence regarding EDCs as causative agents of endometriosis, and highlight implications in the general population and clinical work. A thorough review of experimental, epidemiologic, and mechanistic research studies was conducted to explain the association between EDCs and endometriosis. Among the primary EDCs under investigation are polychlorinated biphenyls, dioxins, phthalates, and bisphenol A (BPA). Despite methodological heterogeneity and some discrepancies, epidemiologic evidence supports a positive association between some increased levels of BPA, phthalates, and dioxins in urine or in blood, and endometriosis. Experiments support some effect of EDCs on endometrial cells and causing endometriosis. EDCs function as xenoestrogens, alter immune function, induce oxidative stress, and disrupt progesterone signaling. Epigenetic reprogramming may play a role in mediating EDC-induced endometriosis. Endocrine, immunological, and epigenetic pathways link EDCs and endometriosis. Prevention techniques require deeper comprehension of those factors. Causal linkages and possible treatment targets should be based on longitudinal studies and multi-omics techniques. Restriction of EDCs could be beneficial for endometriosis prevalence limitation. Full article

Fibromyalgia is a complex disorder characterized by chronic widespread pain and a variety of related symptoms. Growing evidence suggests that the central and peripheral nervous systems are involved, with small fiber neuropathy playing a key role in its development. We retrospectively reviewed the medical records of 100 patients diagnosed with primary fibromyalgia. Those showing symptoms indicative of small fiber dysfunction who were treated with L-Acetyl Carnitine (LAC) and Palmitoylethanolamide (PEA) alongside standard care (SOC) were compared to matched controls who received only SOC. To ensure comparable groups, propensity score matching was used. Changes in Fibromyalgia Impact Questionnaire Revised (FIQR) scores over 12 weeks were analyzed using non-parametric tests due to the data’s non-normal distribution. After matching, 86 patients (43 in each group) were included. The group receiving LAC and PEA as add-on therapy experienced a significant median reduction in FIQR scores (−19.0 points, p < 0.001), while the SOC-only group showed no significant change. Comparisons between groups confirmed that the improvement was significantly greater in the LAC+PEA group (p < 0.001). These results suggest that adding LAC and PEA to standard care may provide meaningful symptom relief for fibromyalgia patients with suspected small fiber involvement. This supports the hypothesis that peripheral nervous system dysfunction contributes to the disease burden in this subgroup. However, further prospective controlled studies are needed to confirm these promising findings. Full article

Background and Clinical Significance: Spontaneous renal hematoma, also known as Wunderlich syndrome (WS), is a rare disease characterized by the acute onset of spontaneous renal hemorrhage into the subcapsular, perirenal, and/or pararenal spaces without a history of prior trauma. WS can be a life-threatening condition due to hemorrhagic shock; consequently, prompt diagnosis and a therapeutic approach are essential for favorable outcomes. Treatment ranges from conservative management to surgical intervention. The most common etiologies are neoplasms and vascular diseases, but WS can also be observed in patients undergoing hemodialysis. In patients with end-stage renal disease (ESRD), especially those on hemodialysis, acquired cystic kidney disease and renal cell carcinoma are among the primary causes of WS. Although less common, WS can develop in dialysis patients even in the absence of traditional (primary) risk factors. In general, patients with chronic kidney disease (CKD) have a paradoxical hemostatic profile, likely explaining their higher tendency to bleed, so WS can occur without existing predisposing factors. The multifactorial pathogenesis in these patients includes functional platelet abnormalities, intimal arterial fibrosis, chronic inflammation, and oxidative stress associated with ESRD. The use of hemodialysis-related antithrombotic medications could serve as another contributing factor increasing the risk of bleeding. Case Presentation: We present a case report of a 62-year-old male on chronic dialysis who developed sudden right-sided lumbar pain and hematuria during dialysis without evidence of prior trauma. Imaging revealed a large subcapsular hematoma of the right kidney. Further investigations did not reveal additional risk factors in this instance; however, his routinely used hemodialysis-related antithrombotic medications were potentially a contributing factor. Despite conservative treatment, his condition worsened, and the hematoma enlarged, requiring emergency nephrectomy. Postoperatively, his condition gradually improved. Conclusions: This case highlights the importance of considering WS in hemodialysis patients, even without the presence of traditional risk factors, as well as including WS in the differential diagnosis of acute abdominal pain. Full article

Background: Chronic primary orofacial pain (COFP) affects approximately 7% of the population and often leads to reduced quality of life. Patients frequently undergo multiple assessments and treatments across healthcare disciplines, often without a definitive diagnosis. The 2019 ICD-11 classification of chronic primary pain clusters together COFP subtypes based on chronicity and associated functional and emotional impairment. Objective: This study aimed to evaluate whether these subtypes of COFP share common underlying mechanisms by comparing neuroimaging findings. Methods: A systematic review was conducted in accordance with PRISMA guidelines. Searches were performed using Medline (OVID) and Scopus up to April 2025. Inclusion criteria focused on MRI-based neuroimaging studies of participants diagnosed with COFP subtypes. Data extraction included participant demographics, imaging modality, brain regions affected, and pain assessment tools. Quality assessment used a modified Coleman methodological score. Results: Fourteen studies met the inclusion criteria, all utilising MRI and including two COFP subtypes (temporomandibular disorder and burning mouth syndrome). Resting- and task-state imaging revealed overlapping alterations in several brain regions, including the thalamus, somatosensory cortices (S1, S2), cingulate cortex, insula, prefrontal cortex, basal ganglia, medial temporal lobe, and primary motor area. These changes were consistent across both TMD and BMS populations. Conclusions: The findings suggest that chronic primary orofacial pain conditions (TMD and BMS) may share common central neuroplastic changes, supporting the hypothesis of a unified pathophysiological mechanism. This has implications for improving diagnosis and treatment strategies, potentially leading to more targeted and effective care for these patients. Full article

Background and Objectives: Visceral arterial pseudoaneurysms (VAPAs) are rare vascular lesions characterized by the disruption of partial disruption of the arterial wall, most commonly involving the intima and media. They have an estimated incidence of 0.1–0.2%, with the splenic artery most commonly affected. Their management poses unique challenges due to the high risk of rupture. Timely recognition is crucial, as unmanaged pseudoaneurysms have a mortality rate of 90%. This narrative review aims to synthesize current knowledge regarding the epidemiology, etiology, clinical presentation, diagnostic methods, and management strategies for VAPAs. Materials and Methods: A literature search was performed across Pubmed for articles reporting on VAPAs, including case reports, review articles, and cohort studies, with inclusion of manuscripts that were up to (date). VAPAs are grouped by embryological origin—foregut, midgut, and hindgut. Results: Chronic pancreatitis is a primary cause of VAPAs, with the splenic artery being involved in 60–65% of cases. Other causes include acute pancreatitis, as well as iatrogenic trauma from surgeries, trauma, infections, drug use, and vascular diseases. VAPAs often present as abdominal pain upon rupture, with symptoms like nausea, vomiting, and gastrointestinal hemorrhage. Unruptured pseudoaneurysms may manifest as pulsatile masses or bruits but are frequently asymptomatic and discovered incidentally. Diagnosis relies on both non-invasive imaging techniques, such as CT angiography and Doppler ultrasound, and invasive methods like digital subtraction angiography, which remains the gold standard for detailed evaluation and treatment. A range of management options exists that are tailored to individual cases based on the aneurysm’s characteristics and patient-specific factors. This encompasses both surgical and endovascular approaches, with a growing preference for minimally invasive techniques due to lower associated morbidity. Conclusions: VAPAs are a critical condition requiring prompt early recognition and intervention. This review highlights the need for ongoing research to improve diagnostic accuracy and refine treatment protocols, enhancing patient outcomes in this challenging domain of vascular surgery. Full article

Background/Objectives: Deep brain stimulation (DBS) is an effective surgical treatment for Parkinson’s Disease (PD) and other movement disorders. Despite its benefits, DBS explantation occurs in 5.6% of cases, with costs exceeding USD 22,000 per implant. Traditional statistical methods have struggled to identify reliable risk factors for explantation. We hypothesized that supervised machine learning would more effectively capture complex interactions among perioperative factors, enabling the identification of novel risk factors. Methods: The Medical Informatics Operating Room Vitals and Events Repository was queried for patients with DBS, adequate clinical data, and at least two years of follow-up (n = 38). Fisher’s exact test assessed demographic and medical history variables. Data were analyzed using Anaconda Version 2.3.1. with pandas, numpy, sklearn, sklearn-extra, matplotlin. pyplot, and seaborn. Recursive feature elimination with cross-validation (RFECV) optimized factor selection was used. A multivariate logistic regression model was trained and evaluated using precision, recall, F1-score, and area under the curve (AUC). Results: Fisher’s exact test identified chronic pain (p = 0.0108) and tobacco use (p = 0.0026) as risk factors. RFECV selected 24 optimal features. The logistic regression model demonstrated strong performance (precision: 0.89, recall: 0.86, F1-score: 0.86, AUC: 1.0). Significant risk factors included tobacco use (OR: 3.64; CI: 3.60–3.68), primary PD (OR: 2.01; CI: 1.99–2.02), ASA score (OR: 1.91; CI: 1.90–1.92), chronic pain (OR: 1.82; CI: 1.80–1.85), and diabetes (OR: 1.63; CI: 1.62–1.65). Conclusions: Our study suggests that supervised machine learning can identify risk factors for early DBS explantation. Larger studies are needed to validate our findings. Full article

Background/Objectives: Although biallelic pathogenic variants in different DNAH gene family members have been associated with infertility, the role of DNAH12 in this disorder is still incompletely understood. To date, few patients have been shown to have infertility due to biallelic variants in this gene. Here, we report two more unrelated patients with infertility who carry homozygous variants in DNAH12. Methods: This study included two male patients with primary infertility and oligoasthenoteratozoospermia (OAT). Patient 1 was a 32-year-old with 1.5 years of infertility and no chronic illnesses or prior assisted reproductive technologies (ARTs). Patient 2 was a 49-year-old with 24 years of infertility, a history of varicocelectomy, and the occasional use of PRN analgesics for bone pain. Using genome sequencing, we identified two homozygous variants: c.3757C>A, p. Pro1253Thr, and c.11086-1G>A, p.?, in patients 1 and 2, respectively. Results: Our findings add supportive evidence that DNAH12 is a gene implicated in rare cases of male infertility. The identification of these homozygous variants in two additional patients supports the association between DNAH12 variants and reproductive dysfunction. Conclusions: This study highlights the need for further research on the role of DNAH12, including functional studies to clarify the mechanisms contributing to infertility. Full article

Migraine is a neurovascular paroxysmal disorder characterized by neurogenic inflammation and has a remarkable impact on the quality of life. The Food and Drug Administration (FDA) approved onabotulinumtoxin A in 2010 for the prophylactic treatment of chronic migraine. Today, in its 4th decade, it is approved in 100 countries for 15 main indications. Its mechanism of action, based on the inhibition of neurotransmitter release from primary sensory neurons, is very complex: it affords antinociception, but it also has an analgesic effect on neuropathic pain conditions and reduces the need for rescue medications. Genetic variants have been investigated for their potential role in the pathogenesis and clinical expression of migraine and of the response to treatments. These studies primarily involved genes associated with vascular regulation and cardiovascular pathology, including those encoding angiotensin-converting enzyme (ACE) and methylenetetrahydrofolate reductase (MTHFR). However, epigenetics and, particularly, genetic and epigenetic modifications are still poorly studied in terms of understanding the mechanisms implicated in susceptibility to migraine, aura, chronification and response to symptomatic and preventive treatments. In particular, the aim of the present study is to gather evidence on the genetic variants and epigenetic modifications affecting the pathway of the calcitonin gene-related peptide (CGRP), the target of onabotulinumtoxin A and of all the novel monoclonal antibodies. Full article

Background and Objectives: Arthrogenic muscle inhibition (AMI) is a key neurophysiological barrier to effective rehabilitation in individuals with chronic ankle instability (CAI). The primary objective of this narrative review is to explore the role of arthrogenic muscle inhibition (AMI) in chronic ankle instability (CAI) and to critically appraise neurophysiological and rehabilitative strategies targeting its resolution. Although peripheral strengthening remains a cornerstone of treatment, the roles of spinal and cortical modulation are increasingly recognised. Materials and Methods: A narrative review was conducted to examine recent clinical trials targeting AMI in CAI populations. A structured search of MEDLINE, Web of Science, Scopus, Cochrane Central, and PEDro was performed. Five studies were included, encompassing peripheral, spinal, and cortical interventions. The outcomes were grouped and analysed according to neurophysiological and functional domains. Results: Manual therapy combined with exercise improved pain, strength, and functional mobility. Fibular reposition taping transiently enhanced spinal reflex excitability, while transcranial direct current stimulation (tDCS) over the primary motor cortex significantly modulated corticospinal excitability and voluntary muscle activation. Improvements in subjective stability, dynamic balance, and neuromuscular responsiveness were observed in the majority of the five included studies, although methodological heterogeneity and short-term follow-ups limit generalisability. Conclusions: Multimodal interventions targeting different levels of the neuromotor system appear to be more effective than isolated approaches. Integrating manual therapy, sensorimotor training, and neuromodulation may optimise outcomes in CAI rehabilitation. Future trials should focus on standardised outcome measures and long-term efficacy. Full article

Background: Chronic pain affects one in five youth globally and is frequently accompanied by mental health challenges that extend into adulthood. Caregivers play a vital role in supporting youth with chronic pain, yet their own mental and physical health needs are often overlooked. While caregiver well-being is linked to child outcomes, few interventions directly address caregivers’ health, especially among those facing systemic barriers. This study explored the lived experiences of caregivers to better understand their unmet needs and inform the co-design of a supportive digital health solution. Methods: We conducted a qualitative exploratory study involving 32 caregivers of youth with chronic pain across Canada and Australia. Semi-structured interviews were co-facilitated by caregiver partners. Thematic analysis was applied to interview data. Results: Two overarching themes were identified: (1) bearing the weight and sacrifice of caregiving and (2) deep interrelatedness and blurred boundaries. Caregivers reported profound emotional, physical, and financial burdens; strained relationships; and social isolation. Many struggled with self-neglect, prioritizing their child’s needs over their own. Fathers’ evolving caregiving roles challenged traditional gender norms, though mothers continued to bear a disproportionate load. Despite challenges, caregivers demonstrated resilience and recognized their well-being as interconnected with their child’s health. Conclusions: Findings underscore the need for systemic investment in caregiver well-being. Digital health solutions, including virtual peer networks, mental health resources, and tailored education, offer scalable, accessible pathways for support. These insights will inform the development of Power over Pain for Primary Caregivers, a digital solution and knowledge hub aimed at improving caregiver well-being and family outcomes, aligning with global efforts to enhance family-centred pediatric pain care. Full article

Introduction: Total temporomandibular joint replacement (TMJR) is a well-established surgical solution for patients with severe TMJ disorders. It aims to relieve chronic pain, restore jaw mobility, and significantly enhance quality of life. This systematic review evaluates QoL outcomes following TMJR, analyzes complication profiles, compares custom versus stock prostheses, explores pediatric applications, and highlights technological innovations shaping the future of TMJ reconstruction. Methods: A systematic search of PubMed, Embase, and the Cochrane Library was conducted throughout April 2025 in accordance with PRISMA 2020 guidelines. Sixty-four studies were included, comprising 2387 patients. Results: Primary outcomes assessed were QoL improvement, pain reduction, and functional gains such as maximum interincisal opening (MIO). Secondary outcomes included complication rates and technological integration. TMJR consistently led to significant pain reduction (75–87%), average MIO increases of 26–36 mm, and measurable QoL improvements across physical, social, and psychological domains. Custom prostheses were particularly beneficial in anatomically complex or revision cases, while stock devices generally performed well for standard anatomical conditions. Pediatric TMJR demonstrated functional and airway benefits with no clear evidence of growth inhibition over short- to medium-term follow-up. Complications such as heterotopic ossification (~20%, reduced to <5% with fat grafting), infection (3–4.9%), and chronic postoperative pain (~20–30%) were reported but were largely preventable or manageable. Recent advancements, including CAD/CAM planning, 3D-printed prostheses, augmented-reality-assisted surgery, and biofilm-resistant materials, are enhancing personalization, precision, and implant longevity. Conclusions: TMJR is a safe and transformative treatment that consistently improves QoL in patients with end-stage TMJ disease. Future directions include long-term registry tracking, growth-accommodating prosthesis design, and biologically integrated smart implants. Full article

Endometriosis is a chronic inflammatory disease characterized by the presence of ectopic endometrial tissue, mainly in the pelvic cavity. It primarily affects women of reproductive age and is associated with significant morbidity, particularly chronic pelvic pain and infertility. Despite its high prevalence, diagnosis is often delayed, contributing to prolonged suffering and increased healthcare burden. This review examines the management of endometriosis in Primary Care, focusing on clinical presentation, risk factors, diagnostic approaches, and therapeutic options. A comprehensive bibliographic search was conducted using PubMed, Scopus, and Uptodate, including evidence-based clinical guidelines and literature up to January 2025. Women diagnosed with endometriosis in Primary Care are typically of reproductive age, with symptoms including dysmenorrhea, dyspareunia, and abnormal uterine bleeding. Risk factors include early menarche, low birth weight, short menstrual cycles, and family history. Transvaginal ultrasound is the recommended first-line imaging tool. Treatment includes analgesics, nonsteroidal anti-inflammatory drugs (NSAIDs), and hormonal therapies such as combined oral contraceptives or progestins. Non-pharmacological interventions, including dietary modifications and psychological support, are also relevant. Early identification in Primary Care is key to improving out-comes. Enhancing awareness among healthcare providers and promoting multidisciplinary management are essential to optimize care and reduce diagnostic delays. Full article

Background/Objectives: Sternal pain after cardiac surgery results in considerable discomfort and may contribute to the development of chronic postoperative sternal pain syndrome. Parasternal intercostal plane blocks have been shown to improve postoperative sternal pain and can be an essential part of enhanced recovery after cardiac surgery (ERACS). This cohort study evaluated the postoperative impact of a single-shot deep parasternal intercostal plane block (PIPB) on the requirement of analgesic medication and pain sensation up to 48 h. Methods: This retrospective single-center analysis evaluates the postoperative acute pain in 157 patients undergoing off-pump coronary artery bypass (OPCAB) with median sternotomy. The additive analgesic effects of deep PIPB (38 patients) were compared to a group with standard therapy but without PIPB (119 patients). To strengthen the findings, a propensity score matching analysis was performed. Outcomes included the consumption of emergency pain agents (piritramide), the requirement of the total morphine equivalent (ME), time to extubation, and ICU length of stay. Furthermore, we examined pain sensation with evaluation by using the behavioral pain score (BPS) and numeric rating score (NRS) up to 48 h after extubation. Results: The deep PIPB reduced the piritramide administration 24 h and 48 h after OPCAB surgery. Moreover, the requirement of ME was 24 h and 48 h after bypass surgery also significantly decreased. The one-to-one propensity score matching confirmed our primary findings and showed a decreased requirement for intravenous agents. Additionally, we observed a reduced time for extubation and a decreased NRS rating. However, no significant changes were observed in ICU length of stay, incidence of nausea, and vomiting. Conclusions: Our data suggests that an ultrasound-guided single-shot deep PIPB can be a valuable tool for a multimodal analgesic protocol on patients undergoing OPCAB surgery. Full article

Background/Objective: Non-specific chronic neck pain (CNP) greatly affects the social dynamics, the work performance, and the personal independence of patients. Research emphasizes the significant role of sociological factors, psychological stress, and emotional conflicts in the development, regulation, and endurance of chronic pain. This study aims to explore the influence of emotional conflicts on pain experience among CNP patients, drawing from their experiences. Methods: A phenomenological investigation was conducted, grounded in Heideggerian philosophy, involving CNP patients and healthcare professionals in Madrid, Spain. Participants were recruited from Primary Health Care centers. Data collection methods included semi-structured in-depth interviews, focus groups with patients, focus groups with healthcare providers, participant observation, and reflective diaries. Hermeneutic phenomenology guided the data interpretation. Thematic analysis was applied to transcribed audio recordings. Results: This study included 12 patients with CNP who participated in two in-depth interviews conducted at different time points—before and after receiving physiotherapy treatment. Additionally, 23 CNP patients took part in four focus groups, and 46 healthcare professionals (including physicians, nurses, and physiotherapists) participated in three focus groups. A hermeneutic analysis revealed the following three main categories: “Self-concept and pain experience”, “Daily life obligations and pain perception”, and “Emotional conflicts related to CNP”. Patients described themselves as nervous, having communication difficulties, and often prioritizing family or work tasks, leading to stress. They indicated that their interpersonal conflicts with close relations intensified their perceived pain in the neck, head, shoulders, and arms. Conclusions: From the perspective of the participants in this study, interpersonal and emotional conflicts appear to influence their perception of CNP. Full article

Background: Multiple myeloma (MM) is a heterogeneous plasma cell malignancy with non-specific symptoms and disease heterogeneity at clinical and biological levels. This non-specific set of symptoms, including bone pain, anemia, renal failure, hypercalcemia, and neuropathy, can mislead diagnosis as chronic or benign conditions, resulting in a delay in diagnosis. Timely identification is paramount to prevent organ damage and reduce morbidity. Methods: In this review, we present an overview of recent literature concerning the factors leading to the delayed diagnosis of MM and the impact of delayed diagnosis. This includes factors relevant to physicians and systems, diagnostic processes, primary healthcare services, and laboratory and imaging data access and interpretation. Other emerging technologies to diagnose NCIs include AI-based decision support systems and biomarker-focused strategies. Findings: Delayed diagnosis can lead to presentation at advanced disease stages associated with life-threatening complications and shorter progression-free survival. Patients are often seen by many physicians before they are referred to hematology. Understanding of clinical red flags for MM in primary care is inadequate. Our findings indicate that limited access to diagnostic tests, inconsistent follow-up of MGUS/SMM patients, and a lack of interdepartmental coordination delay the diagnostic process. Conclusions: Multimodal tools for early diagnosis of MM. Educational campaigns to raise awareness of the disease, algorithms dedicated to routine care and novel technologies, including AI and big data analytics, and new biomarkers may serve this purpose, as well as genomic approaches to the premalignant MGUS stage. Full article