Methylene blue for intractable pain from oral mucositis related to cancer treatment: a randomized phase 2 clinical trial.

BACKGROUND: Oral mucositis (OM) in patients receiving cancer therapy is thus far not well managed with standard approaches. We aimed to assess the safety and effectiveness of methylene blue (MB) oral rinse for OM pain in patients receiving cancer therapy. METHODS: In this randomized, single-blind phase 2 clinical trial, patients were randomized to one of four arms: MB 0.025%+conventional therapy (CTx) (n = 15), MB 0.05%+CTx (n = 14), MB 0.1%+CTx (n = 15), or CTx alone (n = 16). Intervention groups received MB oral rinse every 6 h for 2 days with outcomes measured at days 1-2; safety was evaluated up to 30 days. The primary outcome measured change in the pain numeric rating scale (0-10) from baseline to day 2. Secondary outcome measured change in oral function burden scores from baseline to day 2, World Health Organization OM grades, morphine equivalent daily doses, and adverse events. The trial was registered with ClinicalTrials.gov ID: NCT03469284. RESULTS: Sixty patients (mean age 43, range 22-62 years) completed the study. Compared with those who received CTx alone, those who received MB had a significant reduction of pain scores at day 2 of treatment (mean ± SD); 0.025%: 5.2 ± 2.9, 0.05%: 4.5 ± 2.9, 0.1%: 5.15 ± 2.6) and reduction of oral function burden scores (0.025%: 2.5 ± 1.55, 0.05%: 2.8 ± 1.7, 0.1%: 2.9 ± 1.60). No serious adverse events were noted, but eight patients reported burning sensation of the oral cavity with the first dose, and this caused one patient to discontinue therapy. CONCLUSIONS: MB oral rinse showed significant pain reduction and improved oral functioning with minimal adverse effects. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT03469284.

Ivermectin compared with placebo in the clinical course in Mexican patients with asymptomatic and mild COVID-19: a randomized clinical trial.

BACKGROUND: Despite the development and application of vaccines against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) around the world, the scientific community is still trying to find some therapies to avoid or ameliorate the fatal evolution of the Coronavirus disease 2019 (COVID-19). Since the publication of the potential use of ivermectin as a treatment against the disease, a pleiad of information about it has been published. However, the evidence is not strong or weak enough to conclude its usefulness in the clinical evolution of patients infected with SARS-CoV-2. We evaluate the efficacy and safety of ivermectin in the treatment of Mexican patients with asymptomatic and mild COVID-19 in a three-day administration in comparison to placebo. METHODS: A randomized, double-blind, placebo-controlled trial was carried out in 66 adults with asymptomatic and mild COVID-19. Patients were randomly assigned 1:1 ratio to ivermectin plus acetaminophen or placebo plus acetaminophen. The primary endpoint was the proportion of subjects without a disease progression to severity according to COVID-19 guidelines by the National Institutes of Health (NIH) since randomization to 14 days. RESULTS: None of the participants presented progression to a severe state in either group. Viral load was measured on Days 1, 5, and 14. No significant differences were observed in baseline or 14-day between groups (p = 0.720 and 0.362, respectively). However, on Day 5, a significant difference in viral load was observed between groups (p = 0.039). The frequency of symptoms was similar between groups, and no significant differences were observed. The most frequent symptom was cough. One severe adverse event associated with SARS-CoV-2 infection was observed in the ivermectin group. CONCLUSIONS: At standard doses, ivermectin is not effective to prevent progression to a severe state or reducing symptoms in adults with asymptomatic and mild COVID-19. Trial registration The study was registered with ClinicalTrial.gov (NCT04407507) on May 29, 2020.

[The indirect costs of tension type headache. A systematic literature review]. / Los costes indirectos de la cefalea tensional. Una revisión sistemática de la literatura.

OBJECTIVE: The objective of this work was to systematically review the published literature in relation to the estimated indirect costs associated with TTH. DESIGN: This systematic review followed the Preferred Reporting Items Statement for Systematic Reviews and Meta-analyzes (PRISMA). DATA SOURCES: The review was performed in two main databases, PubMed and EconLit, and was completed with the gray literature search. STUDY SELECTION: The basic criterion for the inclusion of studies was that they present at least one measure of indirect costs specific to TTH. DATA EXTRACTION: 12 studies were finally selected for information extraction. Of all the selected articles, the characteristics of the study design, the types of costs included, as well as the measurement instrument, and the main results were synthesized. RESULTS: The search yielded a total of 568 studies. Heterogeneity was found in the designs and samples/populations of the included studies. Only two studies estimated direct and indirect costs for TTH. Among the most notable results, we find an estimated moderate impact of disability due to TTH (between 0.037 and 0.15 per person, 0.06-0.09% for the population). Productivity and efficiency losses were observed and were very heterogeneous. The willingness to pay for effective treatment would range from $1.32 to $9.20 per month. Quality of life is low, between 28.2 and 28.4 points out of 100, and health-related quality of life seems to improve significantly with treatment. CONCLUSIONS: Despite the high heterogeneity of the results, we can conclude that tension headache is characterized by a moderate impact on disability, on productivity and efficiency at work or school, and on the quality of life of those who suffer it.

Methylene Blue for the Treatment of Intractable Pain From Oral Mucositis Related to Cancer Treatment: An Uncontrolled Cohort.

BACKGROUND: Oral mucositis is a complication of cancer therapy, causing severe pain that affects oral functioning, nutrition, and quality of life, as well as therapy nonadherence or dose-limiting toxicity. Anecdotal experience has suggested that methylene blue (MB) oral rinse may be an effective and safe treatment of this oral pain. METHODS: To evaluate the efficacy and safety of MB oral rinse for the treatment of oral pain due to mucositis in patients with cancer, we retrospectively evaluated patients who experienced refractory pain despite conventional therapy. RESULTS: We identified 281 patients who received MB oral rinse. Most were receiving treatment for leukemia (n=85; 30.3%) and head and neck squamous cell carcinoma (n=84; 29.9%). The most common treatments were radiation therapy alone (n=108; 38.4%) and chemoradiation (n=86; 30.6%). Median duration of symptoms was 14 days. Mean (SD) numeric rating scale pain scores were 7.7 (1.83; median, 8) before MB oral rinse and 2.51 (2.76; median, 2) after MB oral rinse (P<.0001). Most patients achieved pain control within the first 3 doses. The effectiveness of MB oral rinse was independent of patient age, sex, cancer type, cancer stage, MB dilution, and pain duration or baseline pain scores. The lowest response to treatment was reported in individuals with esophageal mucositis. Few patients experienced adverse effects of MB oral rinse (n=13; 4.6%); 10 had a transient burning sensation, 2 had transient blue discoloration of the teeth and mouth, and 1 had increased pain. CONCLUSIONS: MB oral rinse is an effective and safe treatment for refractory pain from oral mucositis related to cancer treatment.

[Statistical literacy and risk communication for COVID-19 vaccination: a scoping reviewLiteracia estatística e comunicação de risco para a vacinação contra a COVID-19: revisão de escopo]. / Alfabetización estadística y comunicación de riesgo para la vacunación contra la COVID-19: una revisión de alcance.

OBJECTIVE: To describe the role of statistical literacy and proper risk communication in communication strategies related to COVID-19 vaccination. METHODS: A scoping review was carried out in January 2021, with the keywords "statistical literacy," "risk communication," "health communication," and "pandemic," in the Pan American Health Organization Virtual Health Library, PubMed, Web of Science, EBSCO, and Google Scholar databases. No filters were applied for dates, language, or publication type. RESULTS: Of the 87 articles identified, four met the inclusion criteria. Four main messages were recognized that relate statistical literacy and risk communication: 1) risk communication and statistical literacy level affect individual and collective decision-making; 2) communication of uncertainty should include what is known and not known with regard to statistics and risks; 3) the use of graphics and visuals is key to appropriately informing the population; and 4) different formats should be used to improve communication, always adjusted to the population's statistical literacy level. CONCLUSIONS: Statistical literacy plays a key role in communicating risks related to health in general and COVID-19 vaccination in particular. In health emergencies, proper communication of risk and associated uncertainty should be clear, transparent, and timely.

OBJETIVO: Descrever o papel da literacia estatística e da comunicação correta de riscos nas estratégias de comunicação relacionadas à vacinação contra a COVID-19. MÉTODOS: Em janeiro de 2021, foi realizada uma revisão de escopo com as palavras-chave "statistical literacy", "risk communication", "health communication" e "pandemic" nos bancos de dados da Biblioteca Virtual em Saúde da Organização Pan-Americana da Saúde, PubMed, Web of Science, EBSCO e Google Scholar. Não foi aplicado filtro de data, idioma ou tipo de publicação. RESULTADOS: Dos 87 artigos identificados, quatro atenderam aos critérios de inclusão. Foram reconhecidas quatro mensagens principais relacionadas à literacia estatística e à comunicação de risco: 1) a comunicação de risco e o nível de literacia estatística afetam a tomada de decisão individual e coletiva; 2) a comunicação da incerteza deve incluir o que é conhecido e desconhecido sobre estatísticas e riscos; 3) o uso de gráficos e visualizações é fundamental para informar adequadamente a população; e 4) devem ser usados diferentes formatos para melhorar a comunicação, sempre ajustados ao nível de literacia estatística da população. CONCLUSÕES: A literacia estatística desempenha um papel fundamental na comunicação dos riscos relacionados à saúde em geral e à vacinação contra a COVID-19 em particular. Em situações de emergência de saúde, a comunicação correta do risco e da incerteza a ele associada deve ser clara, transparente e oportuna.

High-flow oxygen and pro-serotonin agents for non-interventional treatment of post-dural-puncture headache.

OBJECTIVE: Post dural puncture headache (PDPH) is a common complication in patients following diagnostic or therapeutic lumbar puncture, procedures requiring epidural access, and spinal surgery. Epidural blood patch (EBP), the gold standard for the treatment of this pathology requires training not provided to emergency physicians. In addition, the presence of concomitant pathology and abnormal laboratory values are contraindications to perform EBP. In presence of these limitations, we sought for a non-interventional management of PDPH utilizing high-flow oxygen and pro-serotonin agents. We reviewed the mechanism of action of this therapy METHODS: To illustrate our proposal, we report a series of twelve consecutive patients with PDPH treated with high-flow oxygen therapy at 12 L/min via a non-rebreathing mask and intravenous metoclopramide. RESULTS: All patients were treated with this conservative therapy, no adverse reactions were observed. After the intervention, the headache resolved without further indications for PDPH. CONCLUSION: Our series suggests that combining high-flow oxygen and pro-serotonin agents such metoclopramide in the ED might be a feasible option as effective as the invasive methods used in treating PDPH. This therapy appears to be efficient and to minimize risk, cost and side effects. It presents an easily accessible alternative that should be considered when PDPH is not a viable option.

Normal Saline Trigger Point Injections vs Conventional Active Drug Mix for Myofascial Pain Syndromes.

BACKGROUND: Myofascial pain syndrome (MPS) originates in the muscle and fascia. MPS presents with referred pain specific for each muscle and a trigger point that reproduces the symptoms. Trigger-point-injection (TPI) is an effective approach to treating MPS. Some TPI agents, however, are associated with systemic and local side effects. OBJECTIVE: The aim of this study was to evaluate the effectiveness of TPI with a conventional active drug mixture (CADM) vs. that with normal saline solution (NS) alone in patients with MPS presenting to the emergency department (ED). METHODS: Adults with MPS diagnosed in the ED, participants were randomly assigned to receive TPI with NS or with CADM. Pain intensity was scored using a 0-10 numeric rating scale prior to and after TPI, before discharge and 2 weeks after TPI. RESULTS: Among 48 patients analyzed, 23 received TPI with NS. The mean pain scores were as follows: immediately before TPI, 7.59 (NS) and 7.44 (CADM); immediately after TPI, 2.22 (NS) and 1.76 (CADM); prior to discharge, 1.52 (NS) and 1.76 (CADM). At 2-week follow up, the mean pain scores were 4.29 (NS) and 4.14 (CADM). Pain was significantly reduced after TPI in both groups. At 2 weeks, the mean pain scores were similar between the groups. No adverse events were reported. CONCLUSION: In cases of MPS in the ED, pain can be controlled with TPI independent of the injectate. TPI with NS may be preferred over CADM because of its lower cost and more favorable side effect profile.

[Cardiac magnetic resonance imaging in patients with a suspected myocardial infarction and normal coronary arteries]. / Valor de la resonancia magnética cardíaca para el diagnóstico diferencial en pacientes con sospecha de infarto agudo de miocardio con elevación del segmento ST y arterias coronarias normales.

BACKGROUND: Patients hospitalized with suspected ST-segment elevation myocardial infarction (STEMI) who have normal coronary arteries (CAs) on invasive coronary angiography (ICA) may have an AMI or another acute cardiac disease that mimics it. AIM: To evaluate the usefulness of cardiac magnetic resonance imaging (CMRI) for diagnosing conditions resembling AMI with normal CAs. MATERIAL AND METHODS: We studied 424 consecutive patients admitted with suspected STEMI who underwent ICA. Those with normal CAs underwent CMRI involving cine-CMRI sequences to evaluate segmental wall motion, T2-weighted short-tau inversion-recovery imaging to detect oedema and delayed contrast enhancement (DCE) after gadolinium administration to identify necrosis/fibrosis. Patients with previous myocardial infarction were excluded. RESULTS: Twenty-six patients (6.1%) had normal CAs. Definitive diagnosis after CMRI was acute myocarditis in 11 patients (42.3%) whose DCE was localized in the subepicardium or intramyocardially but not in the endocardium, AMI in nine patients (34.6%) who had subendocardial or transmural DCE, and Takotsubo cardiomyopathy (TCM) in six patients (23.1%), whose CMRI showed regional contractility abnormalities of the left ventricle and myocardial oedema but not DCE. CONCLUSIONS: Cardiac magnetic resonance imaging allows a precise diagnosis of acute myocardial infarction in patients with angiographically normal coronary arteries.

Epanorin, a lichen secondary metabolite, inhibits proliferation of MCF-7 breast cancer cells.

BACKGROUND: Epanorin (EP) is a secondary metabolite of the Acarospora lichenic species. EP has been found in lichenic extracts with antimicrobial activity, and UV-absorption properties have been described for closely related molecules; however, its antiproliferative activity in cancer cells has not yet been explored. It has been hypothesized that EP inhibits cancer cell growth. MCF-7 breast cancer cells, normal fibroblasts, and the non-transformed HEK-293 cell line were exposed to increasing concentrations of EP, and proliferation was assessed by the sulforhodamine-B assay. RESULTS: MCF-7 cells exposed to EP were examined for cell cycle progression using flow cytometry, and DNA fragmentation was examined using the TUNEL assay. In addition, EP's mutagenic activity was assessed using the Salmonella typhimurium reverse mutation assay. The data showed that EP inhibits proliferation of MCF-7 cells, and it induces cell cycle arrest in G0/G1 through a DNA fragmentation-independent mechanism. Furthermore, EP's lack of overt cytotoxicity in the normal cell line HEK-293 and human fibroblasts in cell culture is supported by the absence of mutagenic activity of EP. CONCLUSION: EP emerges as a suitable molecule for further studies as a potential antineoplastic agent.

Progression of atherosclerosis versus arterial stiffness with age within and between arteries in systemic lupus erythematosus.

The progression of atherosclerosis versus arterial stiffness with age within and between arteries has not been defined. Systemic lupus erythematosus (SLE) is a human model of accelerated arterial disease that may permit this determination. 76 SLE patients (69 women, age 37 ± 12 years) and 26 age-and-sex-matched controls (22 women, age 34 ± 11 years) underwent transesophageal echocardiography and carotid ultrasonography for assessment of atherosclerosis [plaques and intima-media thickening (IMT)] and arterial stiffness [increased pressure-strain elastic modulus (PSEM)] of the descending thoracic aorta and carotid arteries. Since IMT is highly associated with plaques, IMT was used as a marker of atherosclerosis to assess its progression in relation with age and PSEM. Aortic and carotid plaques, IMT, and PSEM were greater in patients than in controls (all p ≤ 0.05). Within the aorta and within the carotid arteries, the average percent increases per decade of age for IMT versus PSEM were similar in patients (8.55% versus 9.33% and 3.39% versus 2.46%, respectively) and controls (5.53% versus 6.60% and 4.75% versus 3.49%, respectively) (all p ≥ 0.58). However, in SLE patients, the average percent increases per decade of age for IMT and PSEM were higher in the aorta than in the carotid arteries (8.55% and 9.33% versus 3.39% and 2.46%, respectively, both p ≤ 0.03). In patients with SLE, atherosclerosis and arterial stiffness progress with age parallel to each other within arteries, but divergently between arteries with different anatomy and hemodynamics.

Correlation of neurocognitive function and brain lesion load on magnetic resonance imaging in systemic lupus erythematosus.

Neurocognitive dysfunction and brain injury on magnetic resonance imaging (MRI) are common in patients with systemic lupus erythematosus (SLE) and are associated with increased morbidity and mortality. However, brain MRI is expensive, is restricted by payers, and requires high expertise. Neurocognitive assessment is an easily available, safe, and inexpensive clinical tool that may select patients needing brain MRI. In this cross-sectional and controlled study, 76 SLE patients (69 women, age 37 ± 12 years) and 26 age and gender-matched healthy subjects (22 women, age 34 ± 11 years) underwent assessment of attention, memory, processing speed, executive function, motor function, and global neurocognitive function. All subjects underwent brain MRI with T1-weighted, fluid-attenuated inversion recovery (FLAIR), and diffusion-weighted imaging. Hemispheric and whole brain lesion load in cm3 were determined using semi-automated methods. Neurocognitive z-scores in all clinical domains were significantly lower and whole brain and right and left hemispheres brain lesion load were significantly greater in patients than in controls (all p ≤ 0.02). There was significant correlation between neurocognitive z-scores in all domains and whole brain lesion load: processing speed (r = - 0.46; p < 0.0001), attention (r = - 0.42; p < 0.001), memory (r = - 0.40; p = 0.0004), executive function (r = - 0.25; p = 0.03), motor function (r = - 0.25; p = 0.05), and global neurocognitive function (r = - 0.38; p = 0.006). Similar correlations were found for brain hemisphere lesion loads (all p ≤ 0.05). These correlations were strengthened when adjusted for glucocorticoid therapy and SLE disease activity index. Finally, global neurocognitive z-score and erythrosedimentation rate were the only independent predictors of whole brain lesion load (both p ≤ 0.007). Neurocognitive measures and brain lesion load are worse in SLE patients than in controls. In SLE patients, neurocognitive z-scores correlate negatively with and independently predict brain lesion load. Therefore, neurocognitive testing may be an effective clinical tool to select patients needing brain MRI.

Methylene Blue for the Treatment of Intractable Pain Associated with Oral Mucositis.

Oral mucositis is a common and often debilitating complication among cancer patients receiving radiation therapy to the head and neck or chemotherapy agents, or undergoing hematopoietic stem cell transplantation. Pain and decreased oral function associated with oral mucositis may persist long after the conclusion of therapy. Although most patients respond to conservative management, a subset of patients develops intractable pain with severe consequences. For some, the use of total parenteral nutrition with insertion of percutaneous endoscopic gastrostomy feeding tubes is the only alternative. Current recommendations to treat mucositis and its related pain include basic oral care, bland oral rinses, topical anesthetics, and systemic analgesics. We believe that chemical neurolysis of the affected areas with methylene blue used as an oral rinse is a noninvasive, efficient, safe, and cost-effective alternative that can provide prolonged analgesia in patients with intractable pain of oral mucositis. The benefits of this therapy are reflected in its improvement of patients' quality of life by enabling oral feeding and controlling pain. We report a series of 5 consecutive patients with intractable oral mucositis-related pain despite conventional treatment with systemic opiates. All 5 patients responded well to the use of 0.05% methylene blue as mouth rinse, demonstrating sustained analgesia over 3 weeks. The treatment was tolerated well, and overall patient satisfaction was very high. We also observed that methylene blue rinse significantly reduced the total opioid requirement, as demonstrated by reductions in the patients' morphine equivalent daily dose scores after its use. Our case series suggests that 0.5% methylene blue oral rinse therapy is an effective and inexpensive modality that can be used safely to palliate intractable oral pain in patients with mucositis associated with cancer treatment. To our knowledge, this is the first report using this therapy to treat pain from oral mucositis.

Ventricular Septal Defect from Aortic Regurgitation Jet Lesion in Aortic Valve Infective Endocarditis.

Aortic valve infective endocarditis (IE) can be complicated with severe aortic regurgitation (AR) jet-related lesions such as vegetations, pseudoaneurysms, aneurysms or perforations on the anterior mitral leaflet. Herein is reported the case of a 69-year-old male with culture-negative aortic valve endocarditis complicated with aortic valve perforations resulting in severe and eccentric AR and an AR jet-related ventricular septal defect (VSD). Neither transthoracic echocardiography (TTE) nor two-dimensional transesophageal echocardiography (2D-TEE) were unable to clearly discriminate an aorto-right ventricular fistula from a VSD. By contrast, three-dimensional TEE (3D-TEE) demonstrated multiple aortic valve vegetations, aortic valve perforations, severe AR, and an AR jet-related VSD. The 3D-TEE findings were confirmed at surgery, the aortic valve was replaced with a bioprosthetic valve, and the VSD was repaired with a pericardial patch. To the authors' knowledge, this is the first case of a VSD resulting from an AR jet lesion to be detected and characterized using 3D-TEE. The accurate preoperative diagnosis and characterization of the VSD with 3D-TEE contributed to successful surgery and the patient's short- and long-term survival. Video 1A: This four-chamber transthoracic echocardiography (TTE) view with color Doppler shows a color-Doppler jet traversing the basal interventricular septum (IVS) into the right ventricle, predominantly during systole. However, the origin of the jet resulting from an aortic-right ventricular fistula cannot be determined. A mild to moderate degree of tricuspid regurgitation is also noted. Video 1B: Close-up view of the basal IVS demonstrates a color Doppler jet traversing the IVS, predominantly during systole and apparently originating in the left ventricular outflow tract side, as illustrated by a color Doppler acceleration zone. However, and as in Fig. 1A, the origin of the jet resulting from an aortic-right ventricular fistula cannot be determined. Video 1C: Color Doppler two-dimensional TEE view longitudinal to the aortic valve and aortic root, showing a predominantly systolic color Doppler jet originating in the left ventricular outflow tract and/or aorta and crossing the anterior and basal IVS defect into the right ventricle. Videos 1D: These three-dimensional TEE en-face left ventricular outflow tract views of the aortic valve and basal anterior IVS (Video 1D) and medial anterior close up (Video 1E) and lateral en-face (Video 1F) views of the LV outflow tract and IVS clearly define the anterior and basal location of the VSD with irregular borders and a residual mobile tissue fragment. Multiple aortic valve vegetations and a perforation are visible in Video 1D. Videos 1E: These three-dimensional TEE en-face left ventricular outflow tract views of the aortic valve and basal anterior IVS (Video 1D) and medial anterior close up (Video 1E) and lateral en-face (Video 1F) views of the LV outflow tract and IVS clearly define the anterior and basal location of the VSD with irregular borders and a residual mobile tissue fragment. Multiple aortic valve vegetations and a perforation are visible in Video 1D. Videos 1F: These three-dimensional TEE en-face left ventricular outflow tract views of the aortic valve and basal anterior IVS (Video 1D) and medial anterior close up (Video 1E) and lateral en-face (Video 1F) views of the LV outflow tract and IVS clearly define the anterior and basal location of the VSD with irregular borders and a residual mobile tissue fragment. Multiple aortic valve vegetations and a perforation are visible in Video 1D.

Magnetic fields and intrathecal pump malfunction.

Medical technology has impacted the overall life expectancy. Many conditions traditionally considered fatal are now curable. Surviving chronic diseases and aging of the population have increased the number of people with chronic pain. Many devices are also available to manage severe refractory pain. As such, implantable drug-delivery system (IDDS) is a small battery-powered, programmable pump implanted under the subcutaneous tissue of the abdomen and connected to a small catheter tunneled into the spine. Implantable drug-delivery system is used for the administration of morphine, ziconotide, baclofen, or their mixtures into the cerebrospinal fluid. Like many medical devices, IDDS has technical glitch which limits its performance under certain conditions. Implantable drug-delivery system is susceptible to magnetic field such as a magnetic resonance imaging (MRI) which can temporarily stall the rotor of the pump motor and suspend drug delivery. We encountered a patient from out of town seen at emergency department with increased pain and symptoms of opiates withdrawal after intermittent IDDS malfunction. He denied any exposure to magnetic fields or MRI. However, the pump interrogation showed multiple motor stall events in the event log. After a detailed inquiry, the most likely cause of pump malfunction appears to be frequent placement of a laptop computer on his abdomen close to the pump. The magnets in the laptop speakers may have caused the rotor of the pump motor to stall during the computer use, and frequent stall has caused symptoms of withdrawal. No other mechanical failures were found. The patient was discharged home after the symptoms resolved, and the pump was reprogrammed.

Characterization of a novel endothelial biosensor assay reveals increased cumulative serum inflammatory potential in stabilized coronary artery disease patients.

BACKGROUND: Vascular disease is promoted by systemic inflammation that can arise from sites distal to the affected vessels. We sought to characterize the net inflammatory potential of serum from patients with coronary artery disease (CAD) using cultured endothelial cells as a cumulative biosensor. METHODS AND RESULTS: Serum samples from CAD patients (N = 45) and healthy control subjects (N = 48) were incubated with primary human coronary artery endothelial cells at a 1:10 dilution for 4 h, followed by isolation of the cellular RNA. Alteration of inflammation-responsive elements (adhesion molecules and cytokines) was assessed by gene expression. Specific indicators included intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and interleukin-8 (IL-8). Additionally, the cytokine levels in serum samples from all subjects were quantified. Serum from CAD subjects induced greater endothelial ICAM-1, VCAM-1, and IL-8 expression compared to healthy control serum (p < 0.001 for each analysis). The three indicators of inflammatory potential (ICAM-1, VCAM-1, and IL-8 mRNA) trended independently of each other and also of serum inflammatory biomarkers. IL-8 expression correlated negatively with serum HDL levels but positively correlated with VLDL, plasminogen activator inhibitor-1 and C-reactive protein. Interestingly, serum levels of cytokines in CAD patients were not statistically different from healthy control subjects. A year of follow-up in a sub-group of CAD subjects revealed relatively stable measures. CONCLUSIONS: As yet unidentified circulating factors in the serum of CAD patients appear to activate endothelial cells, leading to upregulation of adhesion molecules and chemokines. This cumulative assay performed well in terms of discriminating patients with CAD compared to healthy subjects, with greater range and specificity than specific inflammatory markers.

Lambl's Excrescences: Association with Cerebrovascular Disease and Pathogenesis.

BACKGROUND: Lambl's excrescences (LEx) are detected by transesophageal echocardiography (TEE) and are characterized as thin, elongated, and hypermobile structures located at the leaflets' coaptation point of the heart valves. The association of LEx with cerebrovascular disease (CVD) is still undefined and yet patients with LEx and suspected CVD receive unproven effective antiplatelet or anticoagulant therapy or even undergo valve surgery. Also, the association of LEx with aging and atherogenic, inflammatory, or thrombogenic parameters has not been reported. METHODS: Seventy-seven patients with systemic lupus erythematosus (SLE) (71 women, age 37 ± 12 years) and 26 age- and sex-matched healthy controls (22 women, age 34 ± 11 years) prospectively underwent routine history and physical exam, transcranial Doppler, brain MRI, TEE, carotid duplex, and clinical and laboratory evaluations of atherogenesis, inflammation, platelet activity, coagulation, and fibrinolysis. Subjects without stroke/TIA on enrollment (with and without LEx) had a median follow-up of 57 months. RESULTS: On enrollment, 33 (43%) of 77 patients had CVD manifested as acute stroke/TIA (23 patients), cerebromicroembolism by transcranial Doppler (17 patients), or cerebral infarcts by MRI (14 patients). Mitral or aortic valve LEx were equally frequent in healthy controls (46%) as in patients with and without any CVD (39 and 43%), stroke/TIA (35 and 43%), cerebromicroembolism (41 and 42%), or cerebral infarcts (36 and 43%) (all p ≥ 0.72). Also, other mechanisms for CVD other than LEx such as Libman-Sacks vegetations, patent foramen ovale or interatrial septal aneurysm, aortic or carotid atherosclerosis, or thrombogenesis were found in ≥94% of patients with CVD. In addition, 36 subjects with and 44 without LEx had similar low incidence of stroke/TIA (1 (1.3%) and 2 (2.5%), respectively, p = 1.0) during follow-up. Finally, LEx were not associated with aging, atherogenic risk factors, atherosclerosis, inflammation, or thrombogenesis. CONCLUSIONS: In this study, LEx are similarly prevalent in healthy controls and SLE patients, are not associated with CVD, and are not associated with pathogenic risk factors. Therefore, the study findings suggest that LEx may not be cardioembolic substrates, may not represent pathologic valve structures, and may not require therapy.

Myofascial Pain Syndromes in the Emergency Department: What Are We Missing?

BACKGROUND: Myofascial pain syndrome (MPS), pain originating in the myofascial tissue, is a widely recognized pathology characterized by the presence of referred pain (often distant from its origin and specific to each muscle) that can resemble other pathologies and by the presence of a trigger point, a localized hyperirritable band able to reproduce the pain and its associated symptoms. Patients with acute or chronic MPS are commonly seen in the emergency department (ED), usually complaining of pain of undetermined origin. Traditionally, the emergency physician (EP) is not trained to diagnose and treat MPS, and many patients with MPS have received less than optimal management of this condition in the ED. Many types of treatments are known to be effective against MPS. Among these, trigger point injection (TPI) is considered a practical and rapid approach that can be carried out in the ED by EPs. OBJECTIVE: This article reviews the current diagnostic methods, treatment options, and procedures for MPS patients seen in the ED to enable EPs to diagnose and successfully treat this condition. DISCUSSION: This article discusses the clinical characteristics, etiology, diagnosis, and treatment of MPS in the ED, including a description of performing TPI. CONCLUSIONS: MPS can mimic other clinical conditions commonly seen in the ED. MPS can be diagnosed on the basis of clinical findings; in many cases, no imaging or laboratory testing is needed. Therefore, MPS diagnosis and treatment can be successfully accomplished in the ED by EPs.

Chest pain a manifestation of migraine.

BACKGROUND: Chest pain is an alarming symptom; it justifies many visits to the emergency department (ED). The etiology is often unknown. Chest wall pain in the presence of migraine headache, although not a common occurrence, is intriguing when it resolves with antimigraine treatment. OBJECTIVES: To characterize the manifestations and outcomes and investigate the relationship between chest wall pain and headache as a manifestation of migraine exacerbation. METHODS: Among patients visiting our ED, we identified those individuals whose pain originated in the chest wall in the setting of migraine exacerbation. Patients with clinical indications for specific treatments were dispositioned accordingly. Control of symptoms including chest pain and headache with antimigraine agents was considered the primary outcome. A prospective follow-up via telephone interview and medical records review was performed. RESULTS: We collected a convenience sample of 33 patients. All manifested migraine headache with an earlier onset than the chest pain, and all had taken medications prior to visiting the ED. Twelve patients reported a higher visual analog scale score for the headache than for the chest pain. Still, chest pain was the main complaint. The chest pain originated at the chest wall. Ten patients received sublingual nitroglycerin or opiates, or both; no pain relief was reported. However, all symptoms resolved with metoclopramide. On follow-up, 6 patients reported recurrence of chest pain with subsequent migraines. CONCLUSIONS: Chest pain can be a complication of migraine. The treatment should be focused on migraine control. Migraine should be included in the differential diagnosis of chest pain.

Diagnostic and therapeutic value of intracellular biomarker testing in chronic pain.

Aim: Micronutrient and metabolic compound supplementation as a method of treating chronic pain is not well understood. Case: A 58 year-old woman presented with refractory painful neuropathy. She did not respond to conservative treatment and was seeking spinal cord stimulator implantation. She underwent a biomarker panel that revealed low intracellular levels of multiple compounds. As she supplemented her deficiencies, her symptoms fully resolved, and the implant was no longer indicated. Discussion: Micronutrient and metabolic compound testing could potentially expand non-invasive treatment options for patients with refractory chronic pain. Caution should be exercised given limited regulatory oversight in the supplement industry and actively ongoing nutritional research. Conclusion: Biomarker testing panels may be a useful adjunct in the management of refractory neuropathic pain.