Search Results (180)

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

The gastrointestinal tract mediates the absorption of nutrients from the diet, which is increasingly contaminated with toxic metal(loid) species (TMs) and thus threatens food safety. Evidence in support of the influx of TMs into the bloodstream of the general and vulnerable populations (babies, children, pregnant women, and industrial workers) has been obtained by accurately quantifying their blood concentrations. The interpretation of these TM blood concentrations, however, is problematic, as we cannot distinguish between those that are tolerable from those that may cause the onset of environmental diseases. Since TMs that have invaded the bloodstream may perturb biochemical processes therein that will eventually cause organ damage it is crucial to better understand their bioinorganic chemistry as these processes collectively determine their organ availability. Thus, bioinorganic processes of TMs in the bloodstream represent selectivity filters which protect organs from their influx and ultimately determine the corresponding exposure-response relationships. The need to better understand selectivity filters prompted us to mechanistically disentangle them into the major bioinorganic chemistry processes. It is argued that the detoxification of TMs in the bloodstream and the biomolecular mechanisms, which mediate their uptake into target organs, represent critical knowledge gaps to revise regulatory frameworks to reduce the disease burden. Full article

Although intracranial hypertension (ICH) has traditionally been framed as simply a numerical escalation of intracranial pressure (ICP) and usually dealt with in its clinical form and not in terms of its complex underlying pathophysiology, an emerging body of evidence indicates that ICH is not simply an elevated ICP process but a complex process of molecular dysregulation, glymphatic dysfunction, and neurovascular insufficiency. Our aim in this paper is to provide a complete synthesis of all the new thinking that is occurring in this space, primarily on the intersection of glymphatic dysfunction and cerebral vein physiology. The aspiration is to review how glymphatic dysfunction, largely secondary to aquaporin-4 (AQP4) dysfunction, can lead to delayed cerebrospinal fluid (CSF) clearance and thus the accumulation of extravascular fluid resulting in elevated ICP. A range of other factors such as oxidative stress, endothelin-1, and neuroinflammation seem to significantly impair cerebral autoregulation, making ICH challenging to manage. Combining recent studies, we intend to provide a revised conceptualization of ICH that recognizes the nuance and complexity of ICH that is understated by previous models. We wish to also address novel diagnostics aimed at better capturing the dynamic nature of ICH. Recent advances in non-invasive imaging (i.e., 4D flow MRI and dynamic contrast-enhanced MRI; DCE-MRI) allow for better visualization of dynamic changes to the glymphatic and cerebral blood flow (CBF) system. Finally, wearable ICP monitors and AI-assisted diagnostics will create opportunities for these continuous and real-time assessments, especially in limited resource settings. Our goal is to provide examples of opportunities that exist that might augment early recognition and improve personalized care while ensuring we realize practical challenges and limitations. We also consider what may be therapeutically possible now and in the future. Therapeutic opportunities discussed include CRISPR-based gene editing aimed at restoring AQP4 function, nano-robotics aimed at drug targeting, and bioelectronic devices purposed for ICP modulation. Certainly, these proposals are innovative in nature but will require ethically responsible confirmation of long-term safety and availability, particularly to low- and middle-income countries (LMICs), where the burdens of secondary ICH remain preeminent. Throughout the review, we will be restrained to a balanced pursuit of innovative ideas and ethical considerations to attain global health equity. It is not our intent to provide unequivocal answers, but instead to encourage informed discussions at the intersections of research, clinical practice, and the public health field. We hope this review may stimulate further discussion about ICH and highlight research opportunities to conduct translational research in modern neuroscience with real, approachable, and patient-centered care. Full article

Right ventricular apex (RVA) pacing has historically been the default approach for cardiac pacing; however, it is associated with the development of progressive left ventricular dysfunction and heart failure (HF), particularly in patients with high pacing burdens. While advances in device programming and modern algorithms have sought to mitigate these effects, preserving physiological activation has proven to be more critical than reducing ventricular pacing. Conduction system pacing (CSP) techniques—namely, His-bundle pacing (HBP) and particularly left bundle branch area pacing (LBBAP)—have emerged as superior alternatives, enabling improved left ventricular function and reduced rates of pacing-induced cardiomyopathy (PICM). Nevertheless, despite the clinical advantages of these procedures over RVA, they face limitations including variable implantation success rates, increased pacing thresholds and lead revision rates, technical challenges, and occasional procedure prolongation. Thus, while CSP approaches represent the future of physiological pacing, RVA pacing continues to provide a necessary and reliable option in the current clinical practice. Full article

Heart failure (HF) is a well-known leading cause of mortality, associated with a high symptom burden in advanced stages, frequent hospitalizations, and increasing economic costs. HF is typically classified into three main subgroups, based on left ventricular ejection fraction (LVEF): HF with reduced ejection fraction (HFrEF), HF with mildly reduced ejection fraction (HFmrEF), and HF with preserved ejection fraction (HFpEF). Recently, two additional subgroups have been proposed: HF with improved ejection fraction (HFimpEF) and HF with supernormal ejection fraction (HFsnEF). These five phenotypes exhibit distinct risk factors, clinical presentations, therapeutic responses, and prognosis. However, the LVEF thresholds used to define these subgroups remain a subject of considerable debate, with significant differences in opinions among leading experts. A major criticism concerns the reliability of LVEF in accurately classifying HF subgroups. Due to substantial intra and interobserver variability, determining the appropriate therapy and prognosis can be challenging, particularly in patients with HFmrEF. Additionally, patients classified under HFpEF are often too heterogeneous to be effectively managed as a single group. This narrative review explores these issues, and suggests a possible need for a new approach to HF classification, one that involves revising the LVEF reference values for HF phenotypes and highlighting LVEF trajectories rather than relying on a single measurement. Moreover, in light of the relatively limited therapeutic options for patients with LVEF > 40%, a new, simplified classification may be proposed: HF with reduced EF (LVEF ≤ 40%), HF with below-normal EF (41% ≤ LVEF ≤ 55%), and HF with normal EF (LVEF > 55%). This mindset would better equip clinical cardiologists to manage the diverse spectrum of HF syndromes, always with the patient at the center. Full article

Road traffic accidents (RTAs) are a leading cause of physical injury worldwide, but they also frequently result in post-traumatic stress disorder (PTSD). This systematic review examines the prevalence, predictors, comorbidity, and treatment of PTSD among RTA survivors. Four electronic databases (PubMed, Scopus, EBSCO, and ProQuest) were searched following PRISMA 2020 guidelines. Articles were included if reporting on the presence of post-traumatic stress disorder as a result of a road traffic accident in adults aged 18 years and older. Including peer-reviewed journal articles and awarded doctoral theses across all publication years, and written in English, Macedonian, Serbian, Bosnian, Croatian, and Bulgarian, identified 259 articles, and using Literature Evaluation and Grading of Evidence (LEGEND) assessment of evidence 96 were included in the final review, involving 50,275 participants. Due to the heterogeneity of findings, quantitative data were synthesized thematically rather than through meta-analytic techniques. Findings are reported from Random Control Trial (RCT) and non-RCT studies. PTSD prevalence following RTAs ranged widely across studies, from 20% (using Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, DSM-5 criteria) to over 45% (using International Classification of Diseases, 10th Revision, ICD-10 criteria) within six weeks post-accident (non-RCT). One-year prevalence rates ranged from 17.9% to 29.8%, with persistence of PTSD symptoms found in more than half of those initially diagnosed up to three years post-RTA (non-RCTs). Mild or severe PTSD symptoms were reported by 40% of survivors one month after the event, and comorbid depression and anxiety were also frequently observed (non-RCTs). The review found that nearly half of RTA survivors experience PTSD within six weeks, with recovery occurring over 1 to 3 years (non-RCTs). Even minor traffic accidents lead to significant psychological impacts, with 25% of survivors avoiding vehicle use for up to four months (non-RCT). Evidence-supported treatments identified include Cognitive Behavioural Therapy (CBT) (RCTs and non-RCTs), Virtual Reality (VR) treatment (RCTs and non-RCTs), and Memory Flexibility training (Mem-Flex) (pilot RCT), all of which demonstrated statistically significant reductions in PTSD symptoms across validated scales. There is evidence for policy actions including mandatory and regular psychological screening post RTAs using improved assessment tools, sharing health data to better align early and ongoing treatment with additional funding and access, and support and interventions for the family for RTA comorbidities. The findings underscore the importance of prioritizing research on the psychological impacts of RTAs, particularly in regions with high incident rates, to understand better and address the global burden of post-accident trauma. Full article

Background/Objectives: This study evaluated the efficacy and safety of the ab externo open-conjunctiva (AEO) approach with adjunctive Ologen collagen matrix (OCM) compared to ab interno closed-conjunctiva (AIC) techniques for XEN45 gel stent implantation in patients with refractory open-angle glaucoma. The goal was to determine whether the AEO with OCM approach offers advantages in intraocular pressure (IOP) control and postoperative outcomes. Methods: A retrospective, comparative case series was conducted on 76 eyes from 76 patients with open-angle glaucoma who underwent XEN45 implantation between 2017 and 2022 at a single tertiary center. The patients were divided into Group 1 (AEO with OCM, n = 47) and Group 2 (AIC, n = 29). Postoperative IOP, the number of glaucoma medications, surgical complications, bleb revisions, and failure rates were recorded over 12 months. The AEO technique, supported by OCM, was assessed for its potential to reduce postoperative fibrosis and improve long-term outcomes. Results: Both groups experienced significant IOP reductions over time compared to baseline. However, Group 1 had superior outcomes, requiring fewer glaucoma medications postoperatively (p < 0.05), and demonstrated lower rates of complications (10.6% vs. 31.0%, p = 0.026) and bleb revisions (8.5% vs. 34.5%, p = 0.005). Kaplan–Meier survival analysis showed significantly greater cumulative surgical success in Group 1 compared to Group 2 (p < 0.001). Conclusions: The AEO with OCM approach to XEN45 implantation may provide improved safety and efficacy compared to the AIC approach. It appears to be beneficial in minimizing postoperative fibrosis, reducing the medication burden, and lowering complication and failure rates. Prospective randomized trials are needed to validate these findings. Full article

Background/Objectives: Fast-track (FT) protocols have been developed to reduce the surgical burden and enhance recovery, but they still need to be established for carotid endarterectomy (CEA). In this scenario, carotid stenting has gained momentum by answering the need for a less invasive treatment, despite a still debated clinical advantage. We aim to propose a FT protocol for CEA and to analyze its clinical outcomes. Methods: This retrospective, monocentric study enrolled consecutive patients who underwent CEA for asymptomatic carotid stenosis using an FT protocol between January 2016 and December 2024. Patients undergoing CEA for symptomatic carotid stenosis, carotid bypass procedures, and combined interventions were excluded. Our FT protocol comprises same-day hospital admission, exclusive use of local anesthesia, non-invasive assessment of cardiac and neurological status, and selective utilization of cervical drainage. Discharge criteria were goal-directed and included the absence of pain, electrocardiographic abnormalities, hemodynamic instability, neck hematoma, or cranial nerve injury, with a structured plan for rapid readmission if required. Postoperative pain was assessed using the numerical rating scale (NRS), administered to all patients. The perioperative clinical impact of the protocol was evaluated based on complication rates, pain control, length of hospital stay, and early readmission rates. Results: Among 1051 patients who underwent CEA, 853 met the inclusion criteria. General anesthesia was required in 17 cases (2%), while a cervical drain was placed in 83 patients (10%). The eversion technique was employed in 765 cases (90%). Postoperative intensive care unit (ICU) monitoring was necessary for 7 patients (1%). The mean length of hospital stay was 1.17 days. Postoperatively, 17 patients (2%) required surgical revision. Minor stroke occurred in three patients (0.4%), and acute myocardial infarction requiring angioplasty in two patients (0.2%). Inadequate postoperative pain control (NRS > 4) was reported by five patients (0.6%). Hospital readmission was required for one patient due to a neck hematoma. Conclusions: The reported fast-track protocol for elective carotid surgery was associated with a low rate of postoperative complications. These findings support its clinical value and highlight the need for further validation through controlled comparative studies. Furthermore, the implementation of fast-track protocols in carotid surgery should prompt comparative medico-economic research. Full article

Background: Endometriosis is a chronic, estrogen-dependent inflammatory condition, that not only leads to significant physical symptoms but also exerts a profound psychological and social burden. This study aimed to asjsess the relationship between quality of life (QoL) in women with endometriosis and selected socio-demographic, diagnostic-therapeutic, and psychological factors, emphasizing self-efficacy and dispositional optimism as potential protective resources. Methods: A cross-sectional survey was conducted between 2020 and 2022 in healthcare facilities in eastern Poland. The study included 425 women diagnosed with endometriosis. The research tools were the Endometriosis Health Profile, the General Self-Efficacy Scale, and the Life Orientation Test-Revised, as well as an original socio-demographic and clinical questionnaire. Data were analyzed using descriptive statistics, linear regression, and hierarchical regression to assess the predictive role of psychological resources beyond sociodemographic and clinical variables. Results: A higher number of physicians from various specialties consulted before diagnosis was significantly associated with lower QoL in all EHP-30 domains except infertility (p < 0.05). The perceived economic burden of treatment was significantly related to lower QoL across all domains (p < 0.05). In contrast, higher levels of self-efficacy and dispositional optimism emerged as independent protective factors, positively associated with emotional well-being, social support, sexual functioning, and relationships with medical staff (p < 0.05). Psychological variables accounted for an additional 8.1% of the variance in QoL beyond socio-demographic and clinical predictors. Conclusions: The findings support the relevance of a biopsychosocial framework in managing endometriosis. Psychological resources play a critical role in coping with the disease and should be integrated into personalized care strategies. Full article

Arsenic in drinking water poses a threat to public health world-wide. In March 2001, the EPA revised the maximum contaminant level (MCL) for arsenic in drinking water downward from 50 µg/L to 10 µg/L and required all U.S. small community water systems (CWSs) and non-community water systems (NCWSs) to comply by 23 January 2006. Much of the financial burden associated with complying with and maintaining this new drinking water MCL was shouldered by local community governments. For example, the Walker River Paiute Tribe operated a CWS on the Walker River Paiute Indian Reservation that needed upgrading to meet the new arsenic MCL. In collaboration with the Walker River Paiute Tribe, we conducted a study to assess whether reducing the arsenic concentration in drinking water to meet the new MCL reduced the arsenic body burden in local community members who drank the water. Installing a drinking water treatment to remove arsenic dramatically reduced both the drinking water concentrations (to below the current EPA MCL of 10 µg/L) and the community members’ urinary concentrations of total As, AsIII, and AsV within a week of its full implementation. Additional assistance to small water systems to sustain new drinking water treatments may be warranted. Full article

Background/Objectives: Poor diet is a leading modifiable cause of chronic disease in the US. In addition to targeting nutrients of concern (saturated fat, added sugars, and sodium), nutrients with both inadequate intakes and associations with major health outcomes require identification. We aimed to identify priority nutrients to address both malnutrition and diet-related disease in the US population. Methods: An established method for identifying priority nutrients across multiple demographic groups was adapted for the US population. This method evaluates and scores nutrients consumed at insufficient or excessive levels, with proposed revised requirements, and shows associations with established health priorities, based on the degree of deviation from recommendations and the number of linked health priorities. Priority nutrients were defined as those scoring in the top 25%. For each priority nutrient, a comparison of intake levels against the Dietary Reference Intake (DRI) was conducted. Results: There were 21 of 24 nutrients with consumption below recommended levels in at least one demographic group. Certain nutrients, such as dietary fiber, vitamin D, and choline, exhibited particularly high inadequacy rates, exceeding 90% throughout different life stages. The highest priority nutrients included vitamin D, vitamin E, calcium, magnesium, and dietary fiber, with vitamin D, omega-3 fatty acids, zinc, folate, and potassium showing priority for specific demographic groups. Comparing current intake levels with those known to benefit health priorities indicated that higher intakes of vitamin D, vitamin E, and calcium could be beneficial. Conclusions: Ten essential nutrients play a role in the prevention of diet-related disease, yet are consumed inadequately across the US population, suggesting that the prioritization of these nutrients can help to address the burden of chronic disease. Priority nutrients should be considered in diet and nutrition policies and guidelines. Full article

Background and Objectives: Infection, trauma, skin cancer, foreign substance injections and lymphedema are among the most frequent causes of penile skin defects. Scrotal flaps are a promising reconstructive option for penile resurfacing, offering improved functional and aesthetic outcomes; however, there is no clear consensus on their superiority. Materials and Methods: A review of the literature was performed in PubMed Central and Scopus, and multiple keywords were employed. The initial search retrieved 9181 articles; 32 articles were finally selected, of which 13 were case reports and 19 were case series. Results: A total of 368 patients were included, the majority (71%) consulting for sclerosing lipogranuloma. Seven types of scrotal flaps were used: unilateral scrotal flap (n = 1), bilateral anterior scrotal flaps (n = 149), two-stage scrotal flap (n = 57), bipedicled bilateral anterior scrotal flaps (n = 140), apron-style scrotal flap (n = 1), scrotal pull-up (n = 13), and island dartos musculocutaneous flap (n = 7). Patient satisfaction was high in all studies. Outcome evaluation was typically conducted using subjective questionnaires with 2 or 5 items or visual analog scales. Few studies employed validated sexual function questionnaires, as the IIEF-5 or the EHS. Conclusions: Scrotal flaps provide good quality tissue for penile resurfacing, having the closest resemblance to normal penis skin. For a better understanding of the outcomes of different scrotal flaps, a thorough evaluation of postoperative complications should be made. The LOS and revision surgery rates may serve as surrogates for the financial burden of the procedure. Erectile function should be thoroughly evaluated with a 10-item Likert scale, IIEF-5, EHS, and POSAS. Full article

Surgical site infections (SSIs) are one of the most common causes of hospital-acquired infections worldwide, with significant clinical and economic implications. The aim of this review was to summarize the latest body of evidence on associations between microbial air load and SSIs. The systematic review was conducted using the revised Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA, 2020) method. Pubmed and Scopus databases were searched for the period 2014–2024. English language articles were searched for their reports on the microbial burden of operating room air and its association with surgical site infections. The present review includes a total of 36 articles related to microbial air load as an aggravating factor to air quality in the operating room and its association with SSIs. A direct correlation between microbial air load and the occurrence of SSIs was established through sampling methods and genetic analysis. A lack of consensus on the effectiveness of laminar air flow (LAF) systems was underlined, while temperature-controlled air flow seemed a promising alternative. One study found that each additional person in the operating room increases the number of bacterial colonies by 4.93 CFU/m³ while another did not find significant changes in air quality. More than 20 air changes per hour (ACH) appeared to have better results in improving the quality of the air in the operation room. Airborne microbial contamination is multifactorial, and for some of those factors, a revision of the guidelines seems necessary. Artificial Intelligence (AI) and Next-Generation Sequencing methods show great promise for improving air quality in the future. This review calls for the implementation of international guidelines regarding air contamination limits in operating rooms and standardized air sampling methods, as well as further research for the efficacy assessment of air flow systems and emerging technologies based on AI in order to reduce the burden of SSIs and improve patient outcomes. Full article

Background: Solid organ transplant (SOT) recipients are living longer and, consequently, more of them require elective total hip arthroplasty (THA) to restore mobility and improve quality of life. Because these patients are chronically immunosuppressed and often burdened by multiple comorbidities, their peri-operative risk profile may differ substantially from that of the general THA population. This study aimed to evaluate risk factors associated with acute medical and surgical complications, implant survivorship, and overall mortality in patients with a history of SOT who underwent THA. Methods: A total of 173 THA procedures were reviewed in patients with previous SOT. Among them, 64 had undergone liver transplantation (LT), 83 had received renal transplants (RT), and 26 had experienced more than one type of organ transplant (MT). Kaplan–Meier survival analysis was employed to estimate median survival. Complications were examined using univariate analysis through mixed-effects logistic regression, while Cox regression was utilized to assess mortality risk. The median follow-up period extended to 99 months. Results: The proportion of patients experiencing at least one acute medical event was 27% in the LT group, 33% in the RT group, and 38% in the MT group, with no statistically significant difference between groups (p = 0.5). American Society of Anesthesiologists Class (ASA) 4 (Odds Ratio (OR) = 28; p = 0.006) and treatment with bisphosphonates (OR = 2.25; p = 0.03) were associated with higher risk of acute medical complications. Increased age at the time of SOT was linked to a reduced likelihood of surgical complications (OR = 0.94, p = 0.008), as was older age at the time of undergoing THA (OR = 0.92, p = 0.001). The observed rates of reoperation and implant revision were 3% and 1%, respectively. The estimated patient survivorship rates at 1, 5, and 10 years were 98.6, 82, and 58.4%, respectively. Older age at SOT (Hazard Ratio (HR) = 1.06, p < 0.001), at THA (HR = 1.08, p < 0.001), ASA 4 at THA (HR = 7.57, p = 0.02), and atrial fibrillation (AFib) (HR = 3.13, p = 0.02) were associated with higher mortality. Conclusions: ASA 4 and bisphosphonates were associated with a higher risk of acute medical complications, whereas older age was associated with lower surgical complications. Additionally, older age, ASA 4, and AFib were associated with higher mortality. Full article

Previous research consistently identified depression and anxiety as leading contributors to the global disease burden. Recognizing risk and protective factors that lead to or guard against negative mental health outcomes therefore remains a research priority. The present study examined mediation models for the often-cited association between childhood verbal victimization and adult depression and anxiety symptomatology. Specifically, we investigated whether memories of childhood teasing related to adult adverse mental health outcomes indirectly via the mediated effects of self-esteem and social anxiety. Three hundred sixty-four (64.8% female) adult participants took part in a retrospective study by completing the Teasing Questionnaire—Revised; epidemiological scales of depression, anxiety, stress, social phobia, and social interaction anxiety; and a self-esteem measure. Memories of childhood teasing were indeed positively related to depression, anxiety, stress, social interaction anxiety, and social phobia scores and negatively related to current self-esteem, i.e., the individual’s subjective evaluation of their worth. Self-esteem and recalling being teased for one’s social skills were consistent predictors across all adult outcomes (depression, anxiety, stress, social anxiety, and social phobia). Lastly, self-esteem was found to be a partial mediator of the relationship between the memories of childhood teasing and depression and anxiety in adulthood, while social interaction anxiety partially mediated the relationship between teasing and anxiety, but not depression. These findings highlight the long-term psychological impact of childhood teasing and underscore the critical role of self-esteem and social anxiety as pathways through which early verbal victimization contributes to adult mental health outcomes, emphasizing the need for targeted interventions to foster resilience and mitigate lasting effects. Full article