Search Results (607)

Aim: There is an urgent need for systematic and well-designed studies to clarify the role of systemic inflammatory parameters, especially the neutrophil–lymphocyte-ratio (NLR), in the pathophysiology and clinical management of unregulated substance addiction. This review aims to synthesize current evidence on the relationship between unregulated substance addiction and systemic inflammatory parameters, focusing specifically on the NLR as a potential biomarker. Methods: To ensure a transparent approach in the collection of evidence, this review was carried out following the recommendations of the PRISMA 2020 guidelines and registered in PROSPERO (CRD420251151136). We searched the PubMed and Scopus databases in July2025 using combinations of MeSH terms and keywords related to unregulated substance use and inflammatory biomarkers. The strategy included terms such as “cocaine,” “cannabis,” “opioids,” “heroin,” “fentanyl,” “methadone,” “buprenorphine” “nitazene”, “MDMA”, and “methamphetamine,” combined with “neutrophil-to-lymphocyte ratio.” Filters were applied to limit results to human studies published between 2015 and 2025 in English. The methodological quality of the studies included was assessed using the STROBE 22-item checklist. Results: Fifteen studies were included in this review. Methamphetamine and opioid users showed higher NLR and MLR values. For cocaine abuse, although the evidence is limited to a single population-based study, a significant increase in NLR was reported. Controversial results were observed for cannabis use. Conclusions: Systemic inflammation markers are related to unregulated substance abuse disorders; however, the sparse available evidence encourages the need for well-designed large, prospective clinical trials. Full article

Criminal justice system (CJS) involvement is common among individuals with opioid use disorder (OUD), yet limited research examines retention in medications for OUD (MOUD) within community settings. This study assessed whether CJS involvement predicted retention on buprenorphine/naloxone and explored related demographic and clinical factors. A retrospective cohort included adults (n = 367) enrolled in a low-barrier outpatient MOUD program in Texas (January 2022–April 2024). CJS involvement was identified from program records. Retention was measured as the number of continuous days with buprenorphine/naloxone prescriptions. Analyses used univariate tests, logistic regression, and nonparametric kernel regression. Nearly one-quarter (24.8%) were CJS-involved. Retention at 180 days was similar between CJS and non-CJS groups (38%). CJS participants initiated substance use earlier and reported higher heroin and injection drug use. Behavioral health sessions were associated with both CJS involvement (OR = 1.10, p ≤ 0.001) and longer retention (β = 10.81 days/session, p = 0.001). With comprehensive, low-barrier services, individuals involved with CJS achieved MOUD retention comparable to their peers. Early behavioral health engagement was a strong predictor of retention, suggesting a key intervention point to enhance outcomes and advance equity for justice-involved populations. Full article

This systematic review examines chronic kidney disease-associated pruritus (CKD-aP) as a complex clinical manifestation in patients undergoing hemodialysis. Traditionally considered a secondary symptom of end-stage renal disease, emerging evidence now positions CKD-aP as a multidimensional disorder with substantial pathogenic influence on patient outcomes. Using the PRISMA 2020 methodology, we critically evaluated 54 peer-reviewed studies published between 2020 and 2025. Our synthesis highlights a convergence of five mechanistic frameworks underpinning CKD-aP: elevated levels of uremic toxins originating from gut microbial dysbiosis, immune activation driven by IL-31 and other pro-inflammatory cytokines, heightened peripheral and central neural sensitization, dysregulation of endogenous opioid receptor pathways favoring μ-receptor activation, and xerosis-related epidermal barrier dysfunction. These mechanisms contribute to a systemic cycle of microinflammation, pruritogenic signaling, and neural hyperexcitability. We also identified and compared validated assessment tools—including the NRS, VAS, Skindex-10, and the UP-Dial scale—that facilitate standardized quantification of disease burden. While available treatments such as gabapentinoids and phototherapy offer partial relief, targeted therapies—including κ-opioid receptor agonists—represent a major advancement, although long-term effectiveness and accessibility remain under investigation. Growing scientific consensus establishes CKD-aP as a priority therapeutic target in hemodialysis care, underscoring the need for integrated, mechanism-based management strategies to improve quality of life and clinical outcomes. This work represents a narrative systematic review, integrating evidence from mechanistic, translational, and clinical studies to critically examine the biological pathways underlying CKD-associated pruritus. Full article

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and fibromyalgia (FM) are debilitating disorders with overlapping symptoms such as chronic pain and fatigue. Dysregulation of the endogenous opioid system, particularly µ-opioid receptor function, may contribute to their pathophysiology. This study examined whether epigenetic modifications, specifically µ-opioid receptor 1 gene (OPRM1) promoter methylation, play a role in this dysfunction. Using a repeated-measures design, 28 ME/CFS/FM patients and 26 matched healthy controls visited the hospital twice within four days. Assessments included blood sampling for epigenetic analysis, a clinical questionnaire battery, and quantitative sensory testing (QST). Global DNA (hydroxy)methylation was quantified via liquid chromatography–tandem mass spectrometry, and targeted pyrosequencing was performed on promoter regions of OPRM1, COMT, and BDNF. ME/CFS/FM patients reported significantly worse symptom outcomes. No differences in global (hydroxy)methylation were found. Patients showed significantly higher OPRM1 promoter methylation, which remained after adjusting for symptom severity and QST findings. Across timepoints, OPRM1 methylation consistently correlated with BDNF Promoter I and Exon III methylation. This is, to the best of our knowledge, the first study examining OPRM1 methylation in ME/CFS/FM. Increased OPRM1 methylation in patients, independent of symptoms or pain sensitivity measures, supports the hypothesis of dysregulated opioidergic signaling in these conditions. Full article

Codeine, an opioid analgesic present in many over-the-counter (OTC) formulations, is frequently misused through non-medical extraction techniques such as cold water extraction (CWE). These practices carry substantial risks, including incomplete removal of hepatotoxic co-formulants, contamination, and highly unpredictable dosing. We report a fatal case of a 29-year-old man who ingested codeine extracted from Antidol^® tablets in combination with energy drinks and psychotropic medications. Post-mortem LC–MS/MS analysis revealed the presence of codeine (0.66 µg/mL), morphine (0.02 µg/mL), hydroxyzine (2.52 µg/mL), alprazolam (0.15 µg/mL), paracetamol (30.64 µg/mL), and additional substances in blood samples. Concentrations of codeine and hydroxyzine exceeded therapeutic ranges and were consistent with values reported in fatal intoxications, confirming a poly-drug poisoning. This case highlights the danger associated with non-medical codeine use, particularly when combined with central nervous system (CNS) depressants, and underscores the need for stricter regulation of OTC codeine-containing products as well as improved public awareness of the risks associated with domestic extraction methods. Full article

Acute pancreatitis (AP) is an inflammatory condition with varying severity, ranging from mild self-limiting episodes to life-threatening complications. The incidence, clinical presentation, and outcomes of AP differ significantly across age groups, with elderly patients demonstrating distinct challenges. Biliary pancreatitis is more prevalent in older adults, whereas alcohol-induced AP dominates in younger populations. Elderly patients frequently present with atypical or less pronounced abdominal symptoms, which may delay diagnosis. Comorbidities such as kidney failure, cardiovascular disease, diabetes mellitus and arterial hypertension are significantly more common in the elderly and are associated with increased risk of organ dysfunction, systemic complications such as organ failure, multiple organ dysfunction syndrome (MODS), and prolonged hospitalization. The higher incidence of intensive care unit admissions and mortality is noted in the elderly, particularly in those over 80 years, in particular. Evidence on age-related differences in local pancreatic complications is inconsistent, with a possible trend toward lower rates in older adults. Early identification and individualized treatment planning are essential. Abundant fluid administration should be limited in older patients due to frequent cardiac insufficiency but should be carefully monitored due to the present or threatening renal insufficiency. Pain control with opioids may cause severe CNS complications for elderly patients. In contrast, ERCP, when indicated, is usually well tolerated in older patients. Personalized management in elderly patients is strongly recommended. Full article

A wound has been defined as a disruption of tissue integrity. Pain, bleeding, and the risk of infection are inherent features of wounds, while chronic wounds are often accompanied by serous exudate. Pain associated with chronic wounds is usually underestimated and inadequately addressed in routine clinical care, despite being considered by patients as one of the most burdensome factors affecting their quality of life. Traditionally, management of wound-related pain has relied primarily on systemic analgesics, commonly administered orally. However, recently, there has been accumulated interest in the potential of topical analgesics. Unfortunately, both systemic and local administrations of conventional analgesics (e.g., NSAIDs, opioids) might carry risks of adverse effects, including delayed wound healing and systemic absorption. In this review, we summarize current research on the use of local analgesia for painful wounds and explore the potential of topically applied peptides with analgesic activity as a promising alternative to conventional pain management strategies. We also discuss recent innovations in the development of therapeutic peptides, including those with anti-inflammatory and regenerative activities, which might further enhance outcomes in the wound healing process. Finally, we address challenges associated with topical peptide delivery across compromised skin barriers and examine strategies to overcome these limitations, while outlining future directions for formulation and clinical application of peptide-based wound therapies. Full article

Background: Opioids and nonsteroidal anti-inflammatory drugs (NSAIDs) for clavicle fracture pain management carry significant adverse effect and allergic reaction risks. This study assessed ultrasound-guided nerve block (USNB) efficacy for acute clavicle fracture pain in emergency department (ED) patients, providing an alternative to NSAIDs and opioids with fewer adverse effects. Methods: This retrospective, single-center observational study was conducted in accordance with Methods of Medical Record Review Studies in Emergency Medicine Research guidelines. Adult patients (≥20 years) who presented to the ED with traumatic clavicle fractures between 1 January 2015 and 30 November 2023 were included. Of the 343 eligible patients, 12 received ultrasound-guided nerve blocks (USNB) and 331 received standard care. To improve exchangeability, 1:10 matching with replacement was performed according to patients’ characteristics, such as age, sex, initial pain score, and comorbidities. The primary outcome was pain relief, assessed via the pain intensity difference (PID) on the Numerical Rating Scale within 360 min post-intervention. Meaningful pain relief was defined as a PID ≥ 4. Secondary outcomes included rescue opioid use, ED length of stay, hospital length of stay, and USNB-associated complications, such as vascular puncture, nerve injury, or local anesthetic systemic toxicity. Data were analyzed using time-course, time-to-event (time to meaningful pain relief), and linear regression analyses. Results: A total of 12 patients in the USNB group and 85 matched patients in the standard care group were analyzed after baseline characteristics matching with replacement. Compared to standard care, USNB was associated with significantly greater pain relief (p < 0.001). In the time-to-event analysis, USNB led to a 3.41-fold faster achievement of meaningful pain relief compared with that achieved with standard care (HR = 3.41; 95% CI, 1.47–7.90; p = 0.004). No significant differences were observed between groups in rescue opioid use, ED length of stay, or hospital length of stay. No USNB-associated complication developed in the USNB group. Conclusions: In patients with traumatic clavicle fractures, USNB provides more rapid and sustained pain relief than standard analgesic care in the ED, without increasing the ED length of stay. Large prospective studies are needed to confirm these findings. Full article

Background/Objectives: Uremic pruritus is a common complication in patients with end-stage kidney disease undergoing maintenance hemodialysis. Despite its high prevalence and substantial impact on sleep, psychological well-being, and overall quality of life, its pathophysiology remains multifactorial and incompletely understood. This narrative review summarizes contemporary evidence (2015–2025) on therapeutic strategies for uremic pruritus, with an emphasis on emerging treatments and evolving mechanistic insights. Methods: A PubMed search was conducted for original clinical studies published between 1 January 2015, and 31 October 2025, evaluating treatments for uremic pruritus in adult hemodialysis patients. Eligible study designs included randomized controlled trials and observational interventional studies. Non-English articles, pediatric studies, peritoneal dialysis studies, reviews, case reports, and studies of mixed-etiology pruritus were excluded. Earlier literature was reviewed to contextualize epidemiology and pathophysiology. Results: The review identifies multiple interacting mechanisms—including uremic toxins, immune dysregulation, mineral abnormalities, xerosis, neuropathic changes, and dysregulated opioid signaling—contributing to itch generation. Topical therapies, especially emollients and humectants, consistently improved symptoms with excellent safety profiles. Optimization of dialysis adequacy and membrane selection showed benefit in selected patients. Among systemic therapies, gabapentinoids demonstrated the most robust efficacy but required cautious dosing. Sertraline, nalbuphine, and difelikefalin showed significant antipruritic effects in controlled trials. Emerging therapies, including AST-120, omega-3 fatty acids, and the biologic dupilumab, demonstrated promising but preliminary results. Conclusions: Management of uremic pruritus requires a multifaceted, individualized approach integrating skin-directed therapies, dialysis optimization, and targeted systemic treatments. Ongoing research is needed to identify reliable biomarkers and to develop safer, more effective, mechanism-based therapies. Full article

A large and growing empirical literature documents that privatization, deregulation, financialization, and under-regulation of harmful industries are associated with adverse health outcomes in the United States. However, this evidence remains fragmented across sectors and rarely articulates a unifying causal framework. This paper advances the literature by integrating findings across health care, harmful-product industries, and economic and social policy to demonstrate that corporate profit maximization functions as a cross-cutting driver of health disparities and premature mortality in the United States. We synthesize evidence showing that profit-driven incentives shape insurance markets, hospital and physician practice ownership, pharmaceutical marketing, and the aggressive promotion of tobacco, alcohol, ultra-processed foods, opioids, firearms, and fossil fuels—together contributing to more than one million deaths annually. We further document how corporate influence over public policy has increased poverty, economic inequality, and discrimination, all of which are powerful social determinants of health. In contrast to sector-specific analyses, this paper presents a unified, systems-level account of how profit-first governance undermines population health. We conclude by describing how a social movement to achieve a single payer system that provides Medicare for All would not only vastly improve public health, it would be a catalyst for numerous other reforms that enhance the general wellbeing. Full article

Background: Xylazine, an adulterant in the illicit opioid supply, heightens the risks of overdose, withdrawal severity, and severe wounds among people who use opioids (PWUO). Despite increasing prevalence, gaps remain regarding xylazine awareness in the drug supply and effective harm reduction interventions to address it. Methods: We conducted a cross-sectional survey of 703 PWUO in Baltimore, MD (2023–2025), to assess xylazine awareness, perceptions, and experiences. Multivariable logistic regression models examined correlates of xylazine awareness and self-reported xylazine-attributed wounds. Results: 84.8% of White participants, 48.6% Black participants, 64.3% of males, and 51.4% females had heard of xylazine. Nearly half (45%) of those who used xylazine reported that it caused more severe withdrawal symptoms. In the multivariable model of xylazine awareness, the largest odds ratios were year of survey administration (2024 vs. 2023: aOR = 4.30, 95% CI = 2.91–6.37; 2025 vs. 2023: aOR = 6.32, 95% CI = 3.31–12.07) and White race (aOR = 3.22, 95% CI = 1.85–5.57). Other significant demographic variables included education and gender. In the multivariable model of xylazine-attributed wounds, survey year 2025 vs. 2023 (aOR = 2.65, 95% CI = 1.06–6.61) and injection drug use in the prior year (aOR = 17.74, 95% CI = 5.58–56.39) were statistically significant. Conclusions: Awareness of xylazine in the drug supply remains incomplete among PWUO, with differences by race, age, and gender. The finding of a strong association of xylazine-attributed wounds and injection drug use should be the focus of future research. These findings underscore the need for enhanced surveillance systems, peer education, and community-based harm reduction strategies. Real-time monitoring and rapid response strategies are essential to protect against health risks of toxic adulterants, such as xylazine, medetomidine, and BTMP, in the drug supply. Full article

Substance use disorder (SUD) is a chronic and clinically complex condition, frequently complicated by significant organic and psychiatric comorbidities. Most patients are polymedicated and require opioid substitution programs (OSPs). This complexity is further exacerbated by drug–drug interactions, therapeutic duplication, and fragmentation of the healthcare system. This retrospective observational study analyses the prevalence of polypharmacy and associated pharmacotherapeutic risks in a cohort of 1050 patients with SUD treated at Drug Care Units (DCUs) in Tenerife (Canary Islands, Spain). Prescriptions were dominated by methadone (62%), antidepressants, and antipsychotics, often in combination with benzodiazepines. Significant polypharmacy (>10 active prescriptions) was observed in 2.3% of patients, while 8.1% received 6–10 medications and 37.2% were using 2–5 medications. Women showed a higher pharmacological burden, with 3.5% experiencing significant polypharmacy (>10 different prescriptions) compared with 1.1% of men. Overall, 31% of patients received antidepressants, 31% were treated with antipsychotics—frequently with concurrent use of multiple agents—and 6.4% received opioids outside the OSP. Therapeutic duplication was observed in 15.6% of patients for psycholeptics, 14.2% for psychoanaleptics, and 3.2% for antiepileptics. Additionally, 25.2% of patients reported self-medication, predominantly with benzodiazepines. These findings underscore the need for integrated pharmaceutical care programs incorporating individualized therapeutic review and deprescribing strategies to enhance the safety and efficacy of SUD treatment. Full article

Background and Objectives: Surgical stress during robotic-assisted radical prostatectomy (RARP) elicits a measurable systemic inflammatory response despite the minimally invasive approach. Intravenous lidocaine has been increasingly investigated for its potential anti-inflammatory, analgesic, and immunomodulatory benefits, but evidence in robotic urologic oncology remains limited. This study aimed to evaluate whether intraoperative lidocaine infusion attenuates postoperative inflammation, improves analgesic outcomes, and accelerates early recovery following RARP. Materials and Methods: This prospective non-randomized observational study included 80 patients undergoing elective RARP, divided into a Lidocaine Group (n = 40) receiving an intraoperative bolus and continuous infusion, and a Control Group (n = 40) receiving standard anesthesia without lidocaine. Serum IL-6, TNF-α, CRP, and fibrinogen were measured at baseline, end of surgery, and 24 h postoperatively. Postoperative pain scores, opioid consumption, gastrointestinal recovery, ambulation, and length of stay were recorded. Statistical analyses included repeated-measures ANOVA, correlation testing, and between-group comparisons. Results: Baseline characteristics were similar between groups. At 24 h postoperatively, lidocaine administration was associated with a significantly attenuated inflammatory response, with lower levels of IL-6 (45.7 ± 10.8 vs. 68.9 ± 12.6 pg/mL, p < 0.01) and TNF-α (20.5 ± 5.1 vs. 27.2 ± 6.4 pg/mL, p < 0.01) compared with controls. Patients receiving lidocaine reported lower postoperative pain scores and required significantly less opioid analgesia, with a total 24 h consumption of 8.9 ± 3.4 vs. 14.8 ± 5.2 mg morphine milligram equivalents (p < 0.001). Lidocaine was also associated with faster recovery, including earlier oral intake and a shorter length of hospital stay (2.9 ± 0.7 vs. 3.6 ± 0.9 days, p = 0.003). No lidocaine-related adverse events were observed. Conclusions: In this prospective observational study, intraoperative intravenous lidocaine was associated with attenuated early postoperative inflammation, improved analgesic outcomes, and enhanced early recovery following RARP. These findings support the potential role of intravenous lidocaine as a safe adjunct in multimodal perioperative management; however, given the non-randomized observational design, causal inferences should be interpreted with caution. Further randomized controlled trials are warranted to confirm causality and to validate long-term clinical and mechanistic effects. Potential residual confounding inherent to the observational design should be considered when interpreting these findings. Full article

Background/Objectives: Alcohol Use Disorder (AUD) and Substance Use Disorders (SUDs) can affect both the liver, where clotting factors are synthesized, and the coagulation system, which prevents acute bleeding. Methods: This study included 451 inpatients undergoing addiction detoxification and 150 healthy controls. Patients were stratified by substance type: Alcohol (n = 110), Cannabinoid (n = 71), Methamphetamine (n = 110), Multiple-Substance (Methamphetamine + Cannabinoid, n = 110), and Opioid (n = 50) users. Age-matched control groups (mean ages 45, n = 50; 30, n = 100) were used. Serum levels of Ca, INR, PT, APTT, PLT, AST, and ALT, alongside sociodemographic variables, were assessed. Results: Significant group differences were observed in ALT, AST, PT, APTT, and PLT (p < 0.001). Notably, PT was lower in Multiple Substance and Methamphetamine users; APTT was elevated in Cannabinoid users; AST was higher in Alcohol users; and Methamphetamine and Opioid users exhibited both decreased AST and ALT. Post hoc analyses confirmed substance-specific effects (p < 0.001). Regular cigarette use was significantly more prevalent among alcohol and substance user groups compared to controls; however, smoking did not exert a significant effect on the evaluated biochemical or coagulation parameters. Conclusions: These findings demonstrate that liver enzymes and coagulation parameters can vary significantly by substance type. Observed alterations in AST, ALT, PT, APTT, and PLT suggest that substance use may exert substance-specific effects on hepatic and haemostatic function, highlighting potential risks for bleeding or thrombotic complications. Monitoring these parameters in AUD and SUD patients could provide valuable clinical insights, allowing for more tailored and proactive management strategies. While the underlying mechanisms remain to be fully elucidated, these results emphasize the importance of considering substance-specific physiological impacts when assessing liver and coagulation health in addicted populations. Full article

Fast-track extubation has emerged as a vital component of Enhanced Recovery After Surgery pathways, designed to optimize recovery and resource utilization after cardiac surgery, contrasting with traditional prolonged ventilation. This review explores the evidence supporting fast-track extubation, detailing patient selection criteria based on preoperative risk factors and functional status and outlining perioperative management strategies. It synthesizes findings from various studies, including randomized controlled trials, retrospective studies, and meta-analyses, focusing on intraoperative techniques such as low-dose opioids, neuromuscular blockade reversal, controlled cardiopulmonary bypass duration, judicious inotrope use, and minimal transfusion, alongside structured postoperative protocols emphasizing early sedative weaning and spontaneous breathing trials. Results demonstrate that fast-track extubation decreases intensive care unit stay, reduces costs and ventilator-associated complications, with a safety comparable to conventional care. Prolonged cardiopulmonary bypass time, dependency on inotropes, and intraoperative blood transfusions are identified as critical predictors of fast-track extubation failure. In conclusion, the successful implementation of fast-track extubation protocols requires a collaborative, multidisciplinary approach, proving essential for improving patient outcomes, minimizing complications such as postoperative delirium, and enhancing hospital efficiency in cardiac surgery. Further research should aim to refine patient selection and standardize protocols across healthcare systems. Full article