Effect of combined tobacco use and type 2 diabetes mellitus on prevalent fibrosis in patients with MASLD.

BACKGROUND: Several studies have investigated the independent effect of cigarette smoking or type 2 diabetes mellitus (T2DM) on MASLD. However, the interaction effect between tobacco consumption and T2DM on MASLD severity remains underexplored. In this study, we assessed the combined effect of tobacco use and T2DM on hepatic fibrosis in MASLD. METHODS: We conducted a single-center retrospective cross-sectional analysis of eligible participants from the Mass General Brigham Fibroscan© database. The participants were divided into 3 groups: those with T2DM and a history of tobacco use (primary exposure group), those with T2DM but no history of tobacco use (secondary exposure group), and those without T2DM and no history of tobacco use (reference group). An additional model was developed, which included a fourth group, participants with a history of tobacco use but no T2DM. The likelihood of fibrosis was determined using a defined fibrosis-4 index cutoff value of 1.3. In addition, we computed the estimated marginal means for liver stiffness measurement and compared the values among the exposure groups. Bivariable and multivariable logistic regression models were used to explore the associations between the exposure groups and the risk for hepatic fibrosis. RESULTS: Overall, 598 individuals were enrolled in the study. The bivariable logistic regression model revealed a significant independent association between T2DM, combined smoking and T2DM, and the outcome of interest, fibrosis. Age, sex, metabolic syndrome, aspirin use, statin use, hemoglobin A1C (A1C), and total bilirubin level were also significantly associated with fibrosis. In the adjusted fibrosis-4 multivariable model (comparing exposure groups to controls), cigarette smoking and T2DM interaction had higher odds of prevalent fibrosis (aOR, 3.04; 95% CI, 1.62-5.76), compared to those with T2DM alone (aOR 2.28; 95% CI, 1.37-3.85). The continuous liver stiffness measurement comparison across the exposure group showed an estimated marginal means of 6.26 (95% CL: 5.58-6.94), 7.54 (95% CL: 6.78-8.30), and 7.88 (6.78-8.99) for the reference group, T2DM only group, and tobacco-T2DM group, respectively. The diabetes-only group and the combined tobacco-T2DM group had statistically significant associations with liver stiffness measurement (p values: 0.013 and 0.014, respectively). CONCLUSION: Although diabetes is independently associated with hepatic fibrosis in patients with MASLD, the combination of tobacco consumption and diabetes is associated with a higher prevalence of fibrosis. Therefore, lifestyle change through tobacco use cessation in patients with diabetes could be beneficial in reducing the incidence of liver fibrosis among individuals with MASLD.

Is Surfer's myelopathy an acute hyperextension-induced myelopathy? A systematic synthesis of case studies and proposed diagnostic criteria.

BACKGROUND: Surfer's myelopathy is a rare complication of spinal hyperextension originally described in novice surfers. However, reports from patients practicing different activities had risen. AIM: To systematically synthesize the epidemiological and clinical evidence on acute hyperextension-induced myelopathy ("Surfer's myelopathy") and propose new diagnostic criteria. METHODS: We systematically searched four databases for all observational and case studies on the topic. We performed a narrative synthesis to propose diagnostic criteria and tested the criteria retrospectively on the included cases. A case report is also presented. RESULTS: Forty-two articles reporting 104 cases (median age 19 years, slightly male predominance) were included. All cases reported a nontraumatic hyperextension event (58% after surfing). All of the cases presented pain of hyperacute onset. The most frequent clinical feature was bladder or bowel dysfunction (84%). The thoracic region was the most frequently affected (87%) with longitudinal involvement until the conus (67%). At discharge or follow-up, 52% partially recovered. We propose five diagnostic criteria with three levels of certainty (definite, probable, and possible): (1) nontraumatic spine hyperextension activity (in individuals with no pre-existent spinal disease); (2) hyperacute onset (with acute pain onset); (3) spinal cord injury clinic (motor, sensory, or autonomic deficit); (4) MRI findings with central spinal cord abnormalities (multiple segments); and (5) no other alternative diagnosis. We identified 88% definite and 12% probable/possible cases. CONCLUSION: The acute hyperextension-induced myelopathy could occur not only during surfing but also during other activities. Therefore, increased awareness and education among sports communities and general physicians are needed.

Recruitment characteristics and non-adherence associated factors of fibromyalgia patients in a randomized clinical trial: A retrospective survival analysis.

INTRODUCTION: Fibromyalgia is a complex pain condition that affects mostly women. Given the disease's lack of understanding, patients report poor adherence to medication and mistrust of medical services. This study aims to describe the recruitment characteristics and non-adherence associated factors of fibromyalgia patients to an RCT. METHODS: We performed a retrospective longitudinal analysis with data from our ongoing RCT. We investigated characteristics of subjects recruited, consented, and randomized. Adherence was studied using survival analysis techniques, and its associated factors were identified using Cox proportional hazards regression model. RESULTS: 524 subjects were contacted, 269 were eligible, 61 consented and 40 subjects were randomized. Thirty-eight percent were non-adherent to the protocol with a median of visits of five. The recruitment survey reported that 90% would likely participate in RCTs, 52% had previous participation, and 19% were aware of RCTs by their physicians. Some barriers were investigator-related (staff's friendliness and receiving the results of their trial participation) and center-related (privacy-confidentiality issues and the institution's reputation), without difference between adherent and non-adherent participants. We report significant factors for non-adherence as VAS anxiety score of 5 or more (5.3 HR, p = 0.01), Body Mass Index (BMI) (0.91 HR, p = 0.041) and Quality of Life (QoL) - Personal development subdomain (0.89 HR, p = 0.046). CONCLUSION: Recruitment and adherence of fibromyalgia patients is a challenge; however, they seem eager to participate in RCTs. We recommend creating a comfortable, friendly and trusting environment to increase the recruitment rate. Higher anxiety, lower BMI and lower quality of life were associated with a higher attrition rate.

Barriers and facilitators for clinical trial participation of underrepresented and non-underrepresented fibromyalgia patients: A cross-sectional internet survey.

BACKGROUND: There is a need of well-powered randomized clinical trials in fibromyalgia. However, challenges for recruitment are presented. This study aims to describe and assess the perception of barriers and facilitators and the associated factors for the participation of underrepresented and non-underrepresented fibromyalgia patients. METHODS: We performed an online survey through REDCap (Research Electronic Data Capture) targeting fibromyalgia patients from April 7 to July 3, 2020 during the COVID-19 stay home mandate and it was restricted to the United States of America. We described and compared the survey characteristics between underrepresented and non-underrepresented participants, and we performed logistic regression models to assess the associated factors with clinical trial participation. RESULTS: In total, 481 completed the survey including 168 underrepresented fibromyalgia patients. Only (1) 11.09 % reported previous participation in clinical trials and the significant perceived barriers were investigator-related (lack of friendliness of research staff and the opportunity to receive the results) and center-related (privacy and confidentiality policies, and the institution's reputation); (2) the participation rate and perceived barriers and facilitators were similar between underrepresented and non-underrepresented patients; and was positively associated with low income, higher age, and clinical trial awareness from their physician; and negatively associated with the perception of investigator-related barriers; and (4) for the underrepresented population, the presence of emotional support. CONCLUSION: Our findings suggest low rates of participation, regardless of underrepresented population status. Strategies as involving their physician as liaison to increase the awareness of clinical trials, as well as improving patient-researcher communication should be considered in this population.

Current updates on various treatment approaches in the early management of acute spinal cord injury.

Spinal cord injury (SCI) is a debilitating condition which often leads to a severe disability and ultimately impact patient's physical, psychological, and social well-being. The management of acute SCI has evolved over the couple of decades due to improved understanding of injury mechanisms and increasing knowledge of disease. Currently, the early management of acute SCI patient includes pharmacological agents, surgical intervention and newly experimental neuroprotective strategies. However, many controversial areas are still surrounding in the current treatment strategies for acute SCI, including the optimal timing of surgical intervention, early versus delayed decompression outcome benefits, the use of methylprednisolone. Due to the lack of consensus, the optimal standard of care has been varied across treatment centres. The authors have shed a light on the current updates on early treatment approaches and neuroprotective strategies in the initial management of acute SCI in order to protect the early neurologic injury and reduce the future disability.

The Emerging Role of Magnetic Resonance Imaging-Guided Focused Ultrasound in Functional Neurosurgery.

Functional disorders of the central nervous system (CNS) are diverse in terms of their etiology and symptoms, however, they can be quite debilitating. Many functional neurological disorders can progress to a level where pharmaceuticals and other early lines of treatment can no longer optimally treat the condition, therefore requiring surgical intervention. A variety of stereotactic and functional neurosurgical approaches exist, including deep brain stimulation, implantation, stereotaxic lesions, and radiosurgery, among others. Most techniques are invasive or minimally invasive forms of surgical intervention and require immense precision to effectively modulate CNS circuitry. Focused ultrasound (FUS) is a relatively new, safe, non-invasive neurosurgical approach that has demonstrated efficacy in treating a range of functional neurological diseases. It can function reversibly, through mechanical stimulation causing circuitry changes, or irreversibly, through thermal ablation at low and high frequencies respectively. In preliminary studies, magnetic resonance imaging-guided high-intensity focused ultrasound (MRgHIFU) has been shown to have long-lasting treatment effects in several disease types. The technology has been approved by the FDA and internationally for a number of treatment-resistant neurological disorders and currently clinical trials are underway for several other neurological conditions. In this review, the authors discuss the potential applications and emerging role of MRgHIFU in functional neurosurgery in the coming years.

Decreased neural inhibitory state in fibromyalgia pain: A cross-sectional study.

OBJECTIVES: Chronic pain is one of the most common and challenging symptoms in fibromyalgia (FM). Currently, self-reported pain is the main criterion used by clinicians assessing patients with pain. However, it is subjective, and multiple factors can affect pain levels. In this study, we investigated the neural correlates of FM pain using conditioned pain modulation (CPM), electroencephalography (EEG), and transcranial magnetic stimulation (TMS). METHODS: In this cross-sectional neurophysiological analysis of a randomized, double-blind controlled trial, 36 patients with fibromyalgia were included. We analyzed CPM, EEG variables and TMS measures and their correlation with pain levels as measured by a visual analog scale. Univariate and multivariate linear regression analyses were performed to identify the predictors of pain severity. RESULTS: We found: (1) no association between pain levels and CPM; (2) an association between reduced alpha and beta power over the central region in resting-EEG and higher pain levels; (3) an association between smaller event-related desynchronization (ERD) responses in theta and delta bands over the central region and higher pain levels; (4) an association between smaller ERD responses in theta and delta bands and smaller intracortical inhibition and higher intracortical facilitation ratios; (5) an association between smaller ERD responses in delta band and reduced CPM. CONCLUSIONS: Our results do not support CPM as a biomarker for pain intensity in FM. However, our specific EEG findings showing the relationship between pain, CPM and TMS measures suggest that FM leads to a disruption of inhibitory neural modulators and thus support CPM as a likely predictive marker of disrupted pain modulation system. These neurophysiological markers need to be further explored in potential future trials as to find novel targets for the treatment of FM.

Exercise-induced pain threshold modulation in healthy subjects: a systematic review and meta-analysis.

BACKGROUND: The use of exercise is a potential treatment option to modulate pain (exercise-induced hypoalgesia). The pain threshold (PT) response is a measure of pain sensitivity that may be a useful marker to assess the effect of physical exercise on pain modulation. AIM: The aim of this systematic review and meta-analysis is to evaluate the PT response to exercise in healthy subjects. METHODS: We searched in MEDLINE, EMBASE, Web of Science, Lilacs, and Scopus using a search strategy with the following search terms: "exercise" OR "physical activity" AND "Pain Threshold" from inception to December 2nd, 2019. As criteria for inclusion of appropriate studies: randomized controlled trials or quasi-experimental studies that enrolled healthy subjects; performed an exercise intervention; assessed PT. Hedge's effect sizes of PT response and their 95% confidence intervals were calculated, and random-effects meta-analyses were performed. RESULTS: For the final analysis, thirty-six studies were included (n=1326). From this we found a significant and homogenous increase in PT in healthy subjects (ES=0.19, 95% CI= 0.11 to 0.27, I2=7.5%). According to subgroup analysis the effect was higher in studies: with women (ES=0.36); performing strength exercise (ES=0.34), and with moderate intensity (ES=0.27), and no differences by age were found. Confirmed by the meta-regression analysis. CONCLUSION: This meta-analysis provides evidence of small to moderate effects of exercise on PT in healthy subjects, being even higher for moderate strength exercise and in women. These results support the idea of modulation of the endogenous pain system due to exercise and highlight the need of clinical translation to chronic pain population.