Targeting the Unstable Plaque in Acute Coronary Syndromes

Background

Rupture or erosion of an unstable atherosclerotic plaque is the typical pathology and usual cause of acute coronary syndromes. Despite detailed understanding of the processes of lipid accumulation, thinning of the fibrous cap, and inflammation leading to plaque instability, there are no strategies in clinical use that uniquely target the unstable plaque.

Objective

A critical review of recent publications on potential therapies that could be used to stabilize unstable plaque.

Methods

We searched PubMed, other literature databases, drug development sites, and clinical trial registries to retrieve clinical studies on anti-inflammatory and lipid-modulating therapies that could be used to stabilize unstable atherosclerotic plaque.

Results

Multiple experimental targets involving lipid and inflammatory pathways have the potential to stabilize the plaque and expand the armamentarium against coronary artery disease. Randomized clinical trials of darapladib, methotrexate, canakinumab, and colchicine are well advanced to establish if plaque stabilization is feasible and effective in patients with acute coronary syndromes.

Conclusions

Although there are still no agents in clinical use for plaque stabilization, there are important advances in understanding plaque instability and several encouraging approaches are being evaluated in Phase III clinical trials.     

Functional and biomechanical characteristics of foot disease in chronic gout: A case-control study

Objectives

Despite the predilection of gout to the feet, the impact of gout on foot function and biomechanics is currently unknown. The aim of this study was to describe the effects of chronic gout upon function and selected biomechanical parameters associated with gait.

Methods

Twenty-five patients with a history of gout were compared with 25 age and gender matched control participants with no history of gout or other forms of arthritis. General function, foot specific disease activity and lower limb activities were determined using the Health Assessment Questionnaire, Foot Function Index (pain domain), and Leeds Foot Impact Scale respectively. Each patient also underwent a gait assessment that included plantar pressure measurements and an evaluation of temporal–spatial gait parameters.

Findings

Patients with chronic gout had higher levels of general and foot-specific disability, pain and impairment (P ≤ 0.001). Significantly lower peak plantar pressures were observed in the hallux of patients with chronic gout (P ≤ 0.05). Significantly higher pressure–time integrals were observed in the cases at the midfoot (P ≤ 0.05), but lower values were observed at the hallux (P ≤ 0.05). Patients with chronic gout walked slower, with longer step and stride lengths compared to the controls.

Interpretation

Patients with chronic gout experience pain and disability associated with their feet. Different toe-off strategies may account for functional changes and pain associated with foot problems in chronic gout.     

Spontaneous Coronary Artery Dissection in a 27-Year-Old Woman

Background

Spontaneous coronary artery dissection (SCAD) causes acute coronary syndromes or sudden death in young patients who are often lacking classic coronary disease risk factors. Systemic inflammatory and connective tissue diseases have been suggested as risk factors for SCAD.

Objective

To review the risk factors, diagnosis, and management of this uncommon but life-threatening disease.

Case Report

We report a case of a 27-year-old woman with a history of an ill-defined inflammatory arthropathy who presented with an acute ST-elevation myocardial infarction. SCAD was diagnosed by coronary angiography. Percutaneous coronary intervention was attempted but was unsuccessful. The patient recovered uneventfully with medical management and was ultimately diagnosed with systemic lupus erythematosus.

Conclusions

SCAD is a rare but important cause of acute coronary syndromes and sudden death. It commonly occurs in young women. Although pregnancy is the most well-established risk factor, systemic inflammatory and connective tissue diseases have also been suggested as risk factors.     

Why Colchicine Should Be Considered for Secondary Prevention of Atherosclerosis: An Overview

Purpose

Colchicine is a widely available, inexpensive drug with a range of antiinflammatory properties that may make it suitable for the secondary prevention of atherosclerosis. This review examines how past and contemporary approaches to antiinflammatory therapy for atherosclerosis have led to a better understanding of the nature of the disease and sets out the reasons why colchicine has the potential to become a cornerstone therapy in its management.

Intercellular Communication by Extracellular Vesicles and Their MicroRNAs in Asthma

Purpose

Extracellular vesicles (EVs) such as exosomes and microvesicles are phospholipid bilayer–enclosed vesicles that are recognized as novel tools for intercellular communications and as biomarkers for several diseases. They contain various DNAs, proteins, mRNAs, and microRNAs (miRNAs) that have potential diagnostic and therapeutic purposes. Their biological roles have attracted significant interest in the pulmonary field because their vesicle composition and miRNA content have the ability to transfer biological information to recipient cells and play an important role in pulmonary inflammatory and allergic diseases. Asthma is a chronic inflammatory disease of the airways, and it is characterized by variable and recurring symptoms and reversible airflow obstruction. The purpose of this review was to discuss the function of EVs and their miRNAs in asthma, with a focus on the biological properties and biogenesis of EVs, their pathophysiologic roles, and their potential use as biomarkers and therapies for asthma.

Methods

We review the findings from several articles on EVs and their miRNAs in asthma and provide illustrative references.

Findings

A few studies have reported on the biological function of bronchoalveolar lavage fluid–derived EVs in asthmatic progression. In the lungs, EVs might regulate airway inflammation and allergic reactions through their paracrine effects. Furthermore, circulating miRNAs have been found to be associated with EVs.

Implication

EV-mediated miRNAs can be used as biomarkers in asthma.     

Evidence-Based Guidelines for the Chiropractic Treatment of Adults With Neck Pain

Objective

The purpose of this study was to develop evidence-based treatment recommendations for the treatment of nonspecific (mechanical) neck pain in adults.

Methods

Systematic literature searches of controlled clinical trials published through December 2011 relevant to chiropractic practice were conducted using the databases MEDLINE, EMBASE, EMCARE, Index to Chiropractic Literature, and the Cochrane Library. The number, quality, and consistency of findings were considered to assign an overall strength of evidence (strong, moderate, weak, or conflicting) and to formulate treatment recommendations.

Results

Forty-one randomized controlled trials meeting the inclusion criteria and scoring a low risk of bias were used to develop 11 treatment recommendations. Strong recommendations were made for the treatment of chronic neck pain with manipulation, manual therapy, and exercise in combination with other modalities. Strong recommendations were also made for the treatment of chronic neck pain with stretching, strengthening, and endurance exercises alone. Moderate recommendations were made for the treatment of acute neck pain with manipulation and mobilization in combination with other modalities. Moderate recommendations were made for the treatment of chronic neck pain with mobilization as well as massage in combination with other therapies. A weak recommendation was made for the treatment of acute neck pain with exercise alone and the treatment of chronic neck pain with manipulation alone. Thoracic manipulation and trigger point therapy could not be recommended for the treatment of acute neck pain. Transcutaneous nerve stimulation, thoracic manipulation, laser, and traction could not be recommended for the treatment of chronic neck pain.

Conclusions

Interventions commonly used in chiropractic care improve outcomes for the treatment of acute and chronic neck pain. Increased benefit has been shown in several instances where a multimodal approach to neck pain has been used.     

BML-111, a lipoxin receptor agonist, protects haemorrhagic shock-induced acute lung injury in rats

Objectives

The main pathogenesis of acute lung injury induced by haemorrhagic shock is inflammation. BML-111, a lipoxinA₄-receptor agonist, promotes acute inflammatory resolution. We sought to elucidate whether BML-111 protects haemorrhagic shock-induced acute lung injury in rats.

Methods

Thirty two adult male rats were randomized to sham group (sham), haemorrhagic shock/resuscitation (HS), HS plus BML-111 (BML-111), and HS plus BML-111 and BOC-2 (BOC-2). Haemorrhagic shock was induced by blood drawing, and then resuscitation was obtained by infusion of shed blood and two-fold volume saline.

Results

Histological findings, as well as assays of neutrophilic infiltration (myeloperoxidase activity, ICAM-1 expression), inflammatory cytokines and pro-inflammatory factor (IκB-α and NF-κB p65) confirmed that haemorrhagic shock induced acute lung injury. BML-111 significantly mitigated acute lung injury induced by haemorrhagic shock. However, BOC-2, an antagonist of the lipoxinA₄-receptor, partially reversed the protective effect of BML-111 on the haemorrhagic shock-induced the acute lung injury.

Conclusion

BML-111 protects haemorrhagic shock-induced acute lung injury in rats.     

Repeated Episodes of Respiratory Failure Due to Bilateral Vocal Cord Paralysis

Background

Bilateral vocal cord paralysis can produce severe airway obstruction, leading to acute respiratory failure. Discriminating the pathology of the upper airway from chronic obstructive diseases of the lower airways often presents a challenge for clinicians in the Emergency Department.

Objectives

To underlie the value of clinical examination and flow-volume loops in the establishment of diagnosis of upper airway obstruction.

Case Report

We describe the case of a 55-year-old female ex-smoker who presented with a long history of hoarseness and progressive exertional dyspnea. The patient developed repeated episodes of acute respiratory failure and was supported with noninvasive ventilation. The diagnosis of bilateral vocal cord paralysis was finally established by patient’s symptoms and flow-volume loops demonstrating variable extrathoracic obstruction.

Conclusion

Vocal cord paralysis is a rare and often neglected condition, contributing to repeated episodes of acute respiratory failure. Flow-volume loop is a useful tool when symptoms are suggestive of upper airway obstruction.     

Relationship between plasma high-mobility group box-1 levels and clinical outcomes of ischemic stroke

Purpose

High-mobility group box-1 (HMGB1) is regarded as a central mediator of inflammation and involved in many inflammatory diseases. This study aimed to investigate impact of plasma HMGB1 level on 1-year clinical outcomes of ischemic stroke.

Methods

Plasma HMGB1 levels of 338 patients were quantified by enzyme-linked immunosorbent assay. The end points were mortality and unfavorable outcome (modified Rankin Scale score>2) after 1 year.

Results

Plasma HMGB1 level emerged as an independent predictor of 1-year clinical outcomes. Its prognostic value was similar to National Institutes of Health Stroke Scale score's. It improved prognostic value of National Institutes of Health Stroke Scale score.

Conclusion

Plasma HMGB1 level represents a novel biomarker for predicting 1-year clinical outcomes of ischemic stroke.     

Eating a Larger Number of High-Salt Foods is Not Associated with Short-Term Risk of Acute Decompensation in Patients with Chronic Heart Failure

Background

Risk factors for exacerbation of congestive heart failure have not been consistently validated.

Objective

Our objective was to examine the role of short-term dietary sodium intake in acute decompensated heart failure.

Methods

Patients with chronic congestive heart failure presenting to the Emergency Department for either acute decompensated heart failure (cases) or for other reasons (controls) were included in a case-control study. Cases and controls were compared with respect to age, smoking, recent sodium intake, medication nonadherence, coronary artery disease, and hypertension. A food frequency questionnaire was utilized to estimate recent sodium intake, defined as the number of food types consumed in the previous 3 days from the 12 highest-sodium food categories.

Results

There were 182 patients enrolled. One patient was excluded due to uncertainty about the primary diagnosis. When adjusted for age, smoking, medication nonadherence, coronary artery disease, and hypertension, acute decompensated heart failure was not associated with short-term dietary sodium intake. The odds ratio for acute decompensated heart failure for each increase in the number of high-sodium food types consumed was 1.1 (95% confidence interval 0.9–1.3; p = 0.3). Acute decompensated heart failure was associated with medication nonadherence, with an odds ratio for decompensation of 2.5 (95% confidence interval 1.2–5.1; p = 0.01).

Conclusions

Patients with chronic congestive heart failure who presented to the Emergency Department with acute decompensated heart failure were no more likely to report consuming a greater number of high-sodium foods in the 3 days before than were patients with chronic congestive heart failure who presented with unrelated symptoms. On the other hand, those who presented with acute decompensated heart failure were significantly more likely to report nonadherence with medications.     

Acute Calcific Tendinitis of the Wrist

Background

Acute calcific tendinitis, a benign and self-limiting inflammatory condition commonly seen in the shoulder, is also described in many other tendons, including those in the hand and wrist. When involving the wrist, acute calcific tendinitis is often misdiagnosed and mistaken for infection.

Objective

We present this case to increase familiarity with this condition to avoid errors in diagnosis resulting in inappropriate treatment with antibiotics or even surgery.

Case Report

A 27-year-old man presented to the Emergency Department with a 2-week history of volar wrist pain, with sudden increase in pain associated with chills and new onset swelling and redness of the wrist. Plain radiographs showed characteristic soft-tissue calcification overlying the insertion of the flexor carpi ulnaris tendon into the wrist. Treatment with ibuprofen and splinting resulted in complete symptom resolution.

Conclusion

Acute calcific tendinitis is an important consideration in the differential diagnosis of acute wrist pain. Radiographs are helpful in confirming the diagnosis when symptoms and examination findings are characteristic.     

Chronic Neck Pain and Exercise Interventions: Frequency,Intensity, Time,and Type Principle

Objective

To identify the most effective components in an active exercise physiotherapy treatment intervention for chronic neck pain based on the frequency, intensity, time, and type (FITT) exercise method of tailoring physical activity recommendations to the individual needs and goals of patients.

Data Sources

Databases, including the Allied and Complementary Medicine Database, Cumulative Index to Nursing and Allied Health, MEDLINE, SPORTDiscus, Biomedical Reference Collection, and Academic Search Premier, were searched for relevant articles.

Study Selection

Quantitative design studies that included active exercise as part of a multimodal or stand-alone approach were selected. Only studies scoring ≥6 on the Physiotherapy Evidence Database Scale were included in the review because this reflected a good level of evidence.

Data Extraction

Study methodologies and relevant outcome measures, including isometric strength, Neck Disability Index scores, and pain scores, were extracted from relevant articles and grouped together for appraisal and synthesis.

Data Synthesis

Evidence from selected articles was synthesized according to the FITT exercise principal to determine the most effective exercise type, frequency, and intensity in the treatment of chronic neck pain.

Conclusions

Physiotherapy interventions using a multimodal approach appear to produce more beneficial outcomes in terms of increased strength, improved function, and health-related quality of life and reduced pain scores. Active strengthening exercises appear to be beneficial for all of these outcomes; the inclusion of additional stretching and aerobic exercise components appear to enhance the benefits of an exercise intervention.     

Gout: Current Insights and Future Perspectives

Gout is a relatively common inflammatory arthritis that is typically known to occur in middle-aged men. The prevalence of gout appears to be shifting, however, and is increasing in the elderly population. Gout is characterized by severely intense pain and can greatly impact patient quality of life. The study of gout and associated conditions appears to have received research attention in the past, however there is a resurgence in gout interest due to the abundance of novel evidence surrounding its diagnosis, pathophysiology, and treatment. In this review we describe a general overview of gout including its assessment/diagnosis, clinical presentations, predisposing factors, pathophysiology, abortive and prophylactic therapy to control gouty inflammation, and the potential future direction of gout treatment.

Perspective

Gout is an underappreciated and extremely painful condition. Over the last 2 years new thought on pathophysiology of gout taking into account the inflammasome and new therapeutic agents have changed management strategies.     

Eagle Syndrome: An Incidental Finding in a Trauma Patient: A Case Report

Background

Eagle syndrome is a rare condition characterized by an elongated styloid process that occasionally irritates or disrupts adjacent anatomical structures. Although this is well known in the literature, it is rarely on the forefront of the clinician's mind. In the trauma patient, awareness of Eagle syndrome and knowledge of the anatomy associated with it may help differentiate symptoms secondary to acute injury from the chronic symptoms of this syndrome.

Objectives

To review the diagnostic and treatment modalities related to Eagle syndrome and its associated anatomical structures germane to the trauma patient.

Case Report

A 42-year-old African American man presented with neck, face, head, and back pain after being assaulted. The patient noted that he had a long history of foreign body sensation on the right side of his neck with occasional difficulty swallowing. On physical examination, the patient was found to have a solitary, 1-cm laceration in the left parietal scalp. The physical examination was unremarkable other than scalp hematoma and laceration. Computed tomography scans of the head, face, and cervical spine were negative for acute injury other than a small scalp hematoma, and a markedly enlarged right styloid process, measuring approximately 8 cm, with ossification of the stylohyoid ligament to the level of the hyoid bone.

Conclusion

In the trauma patient, awareness of Eagle syndrome and knowledge of the anatomy associated with it may help differentiate symptoms secondary to acute injury from the chronic symptoms of this syndrome.     

High-Level Mobility in Chronic Traumatic Brain Injury and Its Relationship With Clinical Variables and Magnetic Resonance Imaging Findings in the Acute Phase

Objectives

To compare high-level mobility in individuals with chronic moderate-to-severe traumatic brain injury (TBI) with matched healthy controls, and to investigate whether clinical variables and magnetic resonance imaging (MRI) findings in the acute phase can predict high-level motor performance in the chronic phase.

Design

A longitudinal follow-up study.

Setting

A level 1 trauma center.

Participants

Individuals (N=136) with chronic TBI (n=65) and healthy matched peers (n=71).

Interventions

Not applicable.

Main Outcome Measures

High-Level Mobility Assessment Tool (HiMAT) and the revised version of the HiMAT performed at a mean of 2.8 years (range, 1.5–5.4y) after injury.

Results

Participants with chronic TBI had a mean HiMAT score of 42.7 (95% confidence interval [CI], 40.2–45.2) compared with 47.7 (95% CI, 46.1–49.2) in the control group (P<.01). Group differences were also evident using the revised HiMAT (P<.01). Acute-phase clinical variables and MRI findings explained 58.8% of the variance in the HiMAT score (P<.001) and 59.9% in the revised HiMAT score (P<.001). Lower HiMAT scores were associated with female sex (P=.031), higher age at injury (P<.001), motor vehicle collisions (P=.030), and posttraumatic amnesia >7 days (P=.048). There was a tendency toward an association between lower scores and diffuse axonal injury in the brainstem (P=.075).

Conclusions

High-level mobility was reduced in participants with chronic, either moderate or severe TBI compared with matched peers. Clinical variables in the acute phase were significantly associated with high-level mobility performance in participants with TBI, but the role of early MRI findings needs to be further investigated. The findings of this study suggest that the clinical variables in the acute phase may be useful in predicting high-level mobility outcome in the chronic phase.     

Expedited computed tomography perfusion and angiography in acute ischemic stroke: a feasibility study

Background

Acute ischemic stroke diagnosis and treatment are among the most challenging in Emergency Medicine. Perfusion computed tomography (CTP) can increase the sensitivity for detecting ischemic stroke and, especially with the addition of CT angiography (CTA), improve decision-making regarding thrombolytic therapy compared to non-contrast computed tomography (NCCT) alone. However, because acute stroke protocols do not generally include procedures for multimodal imaging, they are not commonly performed. In addition, there is concern that additional studies could delay or preclude therapy in patients otherwise eligible for thrombolytic therapy.

Objectives

To demonstrate the feasibility of perfusion CTP and CTA in addition to NCCT of the brain in the emergency assessment of patients with acute ischemic stroke. Methods: Starting January 2008, multimodal (CTP and CTA) imaging was added to NCCT in the Emergency Department (ED) initial assessment of patients with stroke of ≤ 5 h duration. Over the subsequent 9 months, we measured the time from ED arrival to imaging and to recombinant tissue plasminogen activator (rt-PA) treatment and compared these times to patients evaluated with CT alone.

Results

From January to October 2008, 95 patients had CTP and CTA studies in addition to NCCT for acute ischemic stroke. There were no differences between the average time to CT study or to rt-PA treatment between patients evaluated with multimodal CT imaging and patients assessed with NCCT alone.

Conclusions

Combining CTP and CTA with NCCT is feasible and does not adversely increase the time to CT imaging or rt-PA treatment in patients with acute ischemic stroke.     

Serum procalcitonin level for the prediction of severity in women with acute pyelonephritis in the ED: value of procalcitonin in acute pyelonephritis

Purpose

Predicting medical outcomes for acute pyelonephritis (APN) in women is difficult. Delay in diagnosis and treatment often results in rapid progression to circulatory collapse, multiple-organ failure, and death. The aim of this study was to investigate the value of procalcitonin (PCT) level in women with APN at ED.

Methods

We conducted a prospective study of women with APN presenting to the ED. The authors measured inflammatory biomarkers, and the severity of pyelonephritis was assessed by 4 severity of disease classification system and stage of sepsis. We performed an analysis to assess the value of PCT for the prediction of 28-day mortality and disease severity.

Results

A total of 240 female patients with APN are included. Patients were divided into 4 groups on the basis of systemic inflammatory response syndrome criteria, organ dysfunction, and persistent hypotension. The median PCT level was higher in the septic shock group compared with other groups. Of the other inflammatory markers, only white blood cell count was significantly different among the groups, whereas high-sensitivity C-reactive protein level and erythrocyte sedimentation rate revealed no differences. The area under the curve for PCT in predicting 28-day mortality was 0.68. For predicting mortality, a cutoff value of 0.42 ng/mL had a sensitivity of 80% and a specificity of 50%. However, the disease classification systems were demonstrated to be superior to PCT in predicting 28-day mortality.

Conclusions

Relative to other classic markers of inflammation, by distinguishing the severity of sepsis related to APN, PCT levels can provide additional aid to clinicians in disease severity classification and their decision of treatment at ED.     

Impact of Resistance Training in Chronic Obstructive Pulmonary Disease Patients During Periods of Acute Exacerbation

Objective

To evaluate the effects of whole-body resistance training on exercise capacity, health-related quality of life (HRQOL), and muscle strength in patients hospitalized for exacerbation of chronic obstructive pulmonary disease.

Design

Randomized controlled trial.

Setting

University hospital.

Participants

Patients (N=46) were randomized to either a control group (CG) or training group (TG), and 29 patients completed the study.

Intervention

Training consisted of weight-lifting exercises for 6 muscle groups in the upper and lower limbs (2 sets of 8 repetitions each), and the initial load was set at 80% of the 1-repetition maximum load.

Main Outcome Measures

Patients were evaluated on the second day of hospitalization, at hospital discharge, and 30 days postdischarge. Patients were evaluated on the basis of the 6-minute walking distance (6MWD), HRQOL, muscle strength, systemic inflammatory markers, and level of physical activity in daily life (PADL).

Results

The CG showed a reduction in the strength of lower-limb muscles (P<.05) but not in the 6MWD (P>.05). In contrast, patients from the TG improved strength in the lower-limb muscles and 6MWD during and 30 days after hospitalization (P<.05). The TG also improved the impact domain in HRQOL after hospitalization. No improvement in PADL was observed in the TG. Finally, a reduction in the blood levels of inflammatory markers was observed only in the TG after hospitalization.

Conclusions

Our results suggest that resistance training during hospitalization improves the 6MWD, HRQOL, and lower-limb muscle strength, without altering the levels of systemic inflammation. However, future research should explore this intervention in larger randomized trials.     

Vasculitis Presenting with Myocardial Infarction,Stroke, and Aortitis in a Middle-aged Man

Background

Vasculitis may cause inflammation in any single or group of blood vessels. Traditionally, giant cell arteritis involves the extracranial branches of the carotid, and Takayasu arteritis affects the aorta and its major branches. These diseases are quite rare, but have the potential to be fatal.

Objectives

We describe the spectrum of overlap between these two historically distinct diseases, and use a case of a man with arteritis involving his carotid and vertebral vessels, aorta, and coronary arteries to illustrate this. We posit that large-vessel vasculitis should be considered in the differential for young and middle-aged patients presenting with multiple vascular events.

Case Report

Over a 2-month period, a 46-year-old man presented on four separate occasions to the Emergency Department. Each time, he was diagnosed with a vascular event. His first two visits were for myocardial infarction and unstable angina, his third visit was for a cerebrovascular event, and his fourth visit was for aortitis. He was not diagnosed with the underlying vasculitic process until his last visit. He ultimately succumbed to non-aneurysmal aortic rupture from his aortitis.

Conclusions

In middle-aged persons with multiple vascular events, an underlying inflammatory process should be considered. These diseases are rare, but they are treatable; and missed diagnoses can be catastrophic.