Remediation of Mild, Acute Radiation Dermatitis Using a Stem Cell-Based Topical: A Real-World Case Report.

INTRODUCTION: Wounds of the skin induced by irradiation involve a disruption of skin homeostasis and an increase in inflammation. Physiological renormalization treatment strategies using the molecules released from stem cells that restore proteostasis and regulate the immune system and reduce inflammation may be effective in treating skin conditions. Previous studies of severe radiation dermatitis found a significant reduction in symptoms using a combination product of the secretome from adipose mesenchymal stem cells and dermal fibroblasts, but mild radiation dermatitis has yet to be studied using this product. CASE PRESENTATION: This is a case report of radiation dermatitis in a patient with an uncommon cutaneous basosquamous cell carcinoma with perineural invasion that warranted radiation therapy. In this study we used S2RM technology, a proprietary combination of stem cell-released molecules from multiple types of skin stem cells, to renormalize homeostasis of the skin, including a renormalization of proteostasis to treat a mild form of radiation dermatitis induced by Intensity Modulated Radiation Therapy. Dramatic reductions in pain, redness, and inflammation, more rapid and complete wound healing, and an overall enhancement of the appearance of the skin were achieved in this patient. DISCUSSION: The current study demonstrates that as part of the palliative care strategies for cancer patients, the simple topical application of S2RM technology is a powerful means to renormalize homeostasis of the skin and remediate mild radiation dermatitis. The reduction of inflammation in the skin is important to reducing systemic inflammation and related comorbidities.

Systematic review of the measurement properties of performance-based functional tests in patients with neck disorders.

OBJECTIVES: The purpose of this systematic review is to identify and synthesise studies evaluating performance-based functional outcome measures designed to evaluate the functional abilities of patients with neck pain. DESIGN: Systematic review. DATA SOURCES: A literature search using PubMed, Scopus, CINAHL, EMBASE, COCHRANE, Google Scholar and a citation mapping strategy was conducted until July 2019. ELIGIBILITY CRITERIA: More than half of the study's patient population had neck pain or a musculoskeletal neck disorder and completed a functional-based test. Clinimetric properties of at least one performance-based functional tests were reported. Both traumatic and non-traumatic origins of neck pain were considered. DATA EXTRACTION AND SYNTHESIS: Relevant data were then extracted from selected articles using an extraction guide. Selected articles were appraised using the Quality Appraisal for Clinical Measurement Research Reports Evaluation Form (QACMRR). RESULTS: The search obtained 12 articles which reported on four outcome measures (functional capacity evaluations (FCE), Baltimore Therapeutic Equipment Work Simulator II (BTEWS II), Functional Impairment Test-Hand and Neck/Shoulder/Arm (FIT-HaNSA)) and a physiotherapy test package, to assess the functional abilities in patients with mechanical neck pain. Of the selected papers: one reports content validity, five construct validity, four reliability, one sensitivity to change and one both reliability and construct validity. QACMRR scores ranged from 68% to 95%. CONCLUSIONS: This review found very good quality evidence that the FIT-HaNSA has excellent inter and intra-rater reliability and very weak to weak convergent validity. Excellent quality evidence of fair test-retest reliability, weak convergent validity and very weak known groups validity for the BTEWS II test was found. Good to excellent quality evidence exists that an FCE battery has poor to excellent reliability and very weak to strong validity. Good to excellent quality of weak to strong validity and trivial to strong effect sizes were found for a physiotherapy test package. PROSPERO REGISTRATION NUMBER: CRD42018112358.

Long-term retention and reconsolidation of a visuomotor memory.

Visuomotor adaptation is a form of motor learning that enables accurate limb movements in the presence of altered environmental or internal conditions. It requires updating the mapping between visual input and motor output, and can occur when learning a new device/tool or during rehabilitation after neurological injury. In either case, it is desirable to stabilize, or consolidate, this visuomotor memory for long-term usage. However, reactivation of a consolidated memory, whether it is motor-based or not, is thought to render it temporarily fragile again, and thus susceptible to interference or modification. Here, we determined if visuomotor memories demonstrate long-term retention but are fragile once reactivated. We used prism lenses to create a novel visuomotor mapping, which participants learned while having to walk and step to the center of targets. We re-tested this memory after one week and one year. We found that the mapping is retained for at least one year, regardless of whether participants were exposed to an interfering (i.e., opposing) mapping in the first session. We also found that presenting an opposing mapping in a block of trials following reactivation of the memory one year later did not disrupt subsequent performance when we re-tested the original memory. Our results suggest that these visuomotor memories are stored for extended periods of time and have limited fragility. Taken together, our results highlight the robustness of visuomotor memories associated with walking.

Consolidation of visuomotor adaptation memory with consistent and noisy environments.

Our understanding of how we learn and retain motor behaviors is still limited. For instance, there is conflicting evidence as to whether the memory of a learned visuomotor perturbation consolidates; i.e., the motor memory becomes resistant to interference from learning a competing perturbation over time. Here, we sought to determine the factors that influence consolidation during visually guided walking. Subjects learned a novel mapping relationship, created by prism lenses, between the perceived location of two targets and the motor commands necessary to direct the feet to their positions. Subjects relearned this mapping 1 wk later. Different groups experienced protocols with or without a competing mapping (and with and without washout trials), presented either on the same day as initial learning or before relearning on day 2 We tested identical protocols under constant and noisy mapping structures. In the latter, we varied, on a trial-by-trial basis, the strength of prism lenses around a non-zero mean. We found that a novel visuomotor mapping is retained at least 1 wk after initial learning. We also found reduced foot-placement error with relearning in constant and noisy mapping groups, despite learning a competing mapping beforehand, and with the exception of one protocol, with and without washout trials. Exposure to noisy mappings led to similar performance on relearning compared with the equivalent constant mapping groups for most protocols. Overall, our results support the idea of motor memory consolidation during visually guided walking and suggest that constant and noisy practices are effective for motor learning. NEW & NOTEWORTHY: The adaptation of movement is essential for many daily activities. To interact with targets, this often requires learning the mapping to produce appropriate motor commands based on visual input. Here, we show that a novel visuomotor mapping is retained 1 wk after initial learning in a visually guided walking task. Furthermore, we find that this motor memory consolidates (i.e., becomes more resistant to interference from learning a competing mapping) when learning in constant and noisy mapping environments.

Teaching Evidence-Based Physical Diagnosis: Six Bedside Lessons.

Evidence-based physical diagnosis is an essential part of the bedside curriculum. By using the likelihood ratio, a simple measure of diagnostic accuracy, teachers can quickly adapt this approach to their bedside teaching. Six recurring themes in evidence-based physical diagnosis are fully reviewed, with examples, in this article.

Bedside Diagnosis of the 'Red Eye': A Systematic Review.

BACKGROUND: In patients with red eye, traditional teachings suggest that photophobia, visual blurring, and eye pain indicate serious eye disease; in patients with presumed conjunctivitis, the finding of purulent drainage traditionally indicates a bacterial cause. The accuracy of these teachings is unknown. METHODS: A MEDLINE search was performed to retrieve articles published between 1966 and April 2014 relevant to the bedside diagnosis of serious eye disease and bacterial conjunctivitis. RESULTS: In patients with red eye, the most useful findings indicating serious eye disease are anisocoria (with the smaller pupil in the red eye and difference between pupil diameters >1 mm; likelihood ratio [LR], 6.5; 95% confidence interval [CI], 2.6-16.3) and photophobia, elicited by direct illumination (LR, 8.3; 95% CI, 2.7-25.9), indirect illumination (LR, 28.8; 95% CI, 1.8-459), or near synkinesis test ("finger-to-nose convergence test," LR, 21.4; 95% CI, 12-38.2). In patients with presumed conjunctivitis, complete redness of the conjunctival membrane obscuring tarsal vessels (LR, 4.6; 95% CI, 1.2-17.1), observed purulent discharge (LR, 3.9; 95% CI, 1.7-9.1), and matting of both eyes in the morning (LR, 3.6; 95% CI, 1.9-6.5) increase the probability of a bacterial cause; failure to observe a red eye at 20 feet (LR, 0.2; 95% CI, 0-0.8) and absence of morning gluing of either eye (LR, 0.3; 95% CI, 0.1-0.8) decrease the probability of a bacterial cause. CONCLUSIONS: Several bedside findings accurately distinguish serious from benign eye disease in patients with red eye and, in patients with presumed conjunctivitis, distinguish bacterial from viral or allergic causes.

Diagnosing and treating dizziness.

Dizziness is a common presenting concern in primary care practice. The most useful diagnostic approach in distinguishing different types of dizziness is a thorough history and physical examination; additional tests are rarely necessary. Effective treatments exist for many causes of dizziness, and these treatments are often accomplished in the clinic or at home without the need for medication.

Cheyne-stokes breathing and reduced ejection fraction.

BACKGROUND: The accuracy of Cheyne-Stokes breathing as a sign of left ventricular dysfunction and its overall prognostic significance are unknown. METHODS: Between 2001 and 2006, the author examined 386 inpatients at a Department of Veterans Affairs Medical Center and compared the finding of Cheyne-Stokes breathing and its cycle length with the patients' echocardiographic ejection fraction (EF) and 5-year survival. RESULTS: A total of 45 of 386 patients (11.7%) had Cheyne-Stokes breathing. Two variables were independently associated with Cheyne-Stokes breathing: reduced EF (P<.001) and age>80 years (P=.006). The presence of Cheyne-Stokes breathing increased the probability of a markedly reduced EF (ie, EF<40%; likelihood ratio, 5.3; 95% confidence interval, 3.1-9), especially in patients aged≤80 years (likelihood ratio, 7.8; 95% confidence interval, 3.9-15.5). The finding was present in 1 of 3 affected patients (sensitivity=34%). The correlation between cycle length and EF was poor (r=0.23, P=.14). The 5-year survival of patients with Cheyne-Stokes breathing (37.2%) was similar to that of patients without the finding (42.9%, P=.18, log-rank test). CONCLUSIONS: In hospitalized patients, Cheyne-Stokes breathing increases the probability of left ventricular dysfunction. It is present in 1 of 3 patients with markedly reduced EF. When detected during physical examination, Cheyne-Stokes breathing does not indicate worse prognosis.

Etiology and diagnosis of systolic murmurs in adults.

BACKGROUND: It is unknown whether echocardiography can provide insights into the origin of systolic murmurs and the modern value of bedside cardiovascular diagnosis. METHODS: The author examined 376 inpatients and compared their physical findings to transthoracic echocardiography, exploring the associations between echocardiography and systolic murmurs and investigating the diagnostic accuracy of physical examination for pathologic murmurs. RESULTS: Four echocardiographic variables predict the presence of systolic murmurs: peak aortic velocity (P <.001); mitral regurgitation severity (P <.001); mitral valve E-point velocity (P=.09); and absence of pericardial effusion (P=.09). When diagnosing murmurs, the most helpful finding is its distribution on the chest wall with respect to the 3(rd) left parasternal space, a landmark that distinguishes murmurs into 6 patterns. The "apical-base" pattern indicates increased aortic velocity (likelihood ratio [LR] 9.7; 95% confidence interval [CI]; 6.7-14): a delayed carotid upstroke (LR 6.8; 95% CI; 4.0-11.5); absent S2 (LR 12.7; 95% CI; 5.3-30.4); and humming quality to the murmur (LR 8.5; 95% CI; 4.3-16.5) further increase the probability of aortic valve disease. The "broad apical" murmur pattern suggests significant mitral regurgitation (LR 6.8; 95% CI; 3.9-11.9); and the "left lower sternal" murmur pattern indicates significant tricuspid regurgitation (LR 8.4; 95% CI; 3.5-20.3): additional bedside observations refine these diagnoses. Nonetheless, this study shows that some classic physical findings are no longer accurate, that physical examination cannot reliably distinguish severe aortic stenosis from less severe stenosis, and that classic physical findings, despite having proven value, are absent in many patients with significant cardiac lesions. CONCLUSIONS: In the diagnosis of systolic murmurs, physical examination has limitations but also unappreciated value. A simple system using onomatopoeia and classifying systolic murmurs into 1 of 6 patterns is diagnostically helpful.

Does this patient have a hemorrhagic stroke?: clinical findings distinguishing hemorrhagic stroke from ischemic stroke.

CONTEXT: The 2 fundamental subtypes of stroke are hemorrhagic stroke and ischemic stroke. Although neuroimaging is required to distinguish these subtypes, the diagnostic accuracy of bedside findings has not been systematically reviewed. OBJECTIVE: To determine the accuracy of clinical examination in distinguishing hemorrhagic stroke from ischemic stroke. DATA SOURCES: MEDLINE and EMBASE searches of English-language articles published from January 1966 to April 2010. STUDY SELECTION: Prospective studies of adult patients with stroke that compared initial clinical findings with accepted diagnostic standards of hemorrhagic stroke (computed tomography or autopsy). DATA EXTRACTION: Both authors independently appraised study quality and extracted relevant data. DATA SYNTHESIS: Nineteen prospective studies meeting inclusion criteria were identified (N = 6438 patients; n = 1528 [24%] with hemorrhage stroke). Several findings significantly increase the probability of hemorrhagic stroke: coma (likelihood ratio [LR], 6.2; 95% confidence interval [CI], 3.2-12), neck stiffness (LR, 5.0; 95% CI, 1.9-12.8), seizures accompanying the neurologic deficit (LR, 4.7; 95% CI, 1.6-14), diastolic blood pressure greater than 110 mm Hg (LR, 4.3; 95% CI, 1.4-14), vomiting (LR, 3.0; 95% CI, 1.7-5.5), and headache (LR, 2.9; 95% CI, 1.7-4.8). Other findings decrease the probability of hemorrhage: cervical bruit (LR, 0.12; 95% CI, 0.03-0.47) and prior transient ischemic attack (LR, 0.34; 95% CI, 0.18-0.65). A Siriraj score greater than 1 increases the probability of hemorrhage (LR, 5.7; 95% CI, 4.4-7.4) while a score lower than -1 decreases the probability (LR, 0.29; 95% CI, 0.23-0.37). Nonetheless, many patients with stroke lack any diagnostic finding, and 20% have Siriraj scores between 1 and -1, which are diagnostically unhelpful (LR, 0.94; 95% CI, 0.77-1.1). CONCLUSION: In patients with acute stroke, certain findings accurately increase or decrease the probability of intracranial hemorrhage, but no finding or combination of findings is definitively diagnostic in all patients, and diagnostic certainty requires neuroimaging.

Use of corticosteroids in treating infectious diseases.

Clinicians have generally avoided prescribing corticosteroids for active infection because of their known immunosuppressive effects and concern about long-term complications. We conducted a review of the published randomized, double-blind trials comparing corticosteroids and placebo in infections. Except in some trials of viral infections, sore throat, and cerebral cysticercosis, all patients also received active antimicrobial agents in addition to placebo or corticosteroids. For patients with bacterial meningitis, tuberculous meningitis, tuberculous pericarditis, severe typhoid fever, tetanus, or pneumocystis pneumonia with moderate to severe hypoxemia, treatment with corticosteroids improved patient survival (group 1 infections). For patients with bacterial arthritis, corticosteroids were also beneficial and reduced long-term disability (group 2 infections). For about a dozen other infections, corticosteroids significantly relieved symptoms (group 3 infections), and clinicians should consider using them if symptoms are substantial. Corticosteroids were harmful in 2 infections, viral hepatitis and cerebral malaria (group 5 infections). We conclude that corticosteroids are beneficial and safe for a wide variety of infections, although courses longer than 3 weeks should be withheld from patients with concomitant human immunodeficiency virus infection and low CD4 counts.

Analysis of recent vessel arrivals and ballast water discharge in Alaska: toward assessing ship-mediated invasion risk.

Ships are a dominant vector for biological invasions through ballast water discharge (BWD) and hull fouling. Here, we provide a first comprehensive analysis of shipping in Alaska, summarizing (a) the number, type and origin of vessel arrivals to Alaska for 2003 and 2004, (b) the spatial and temporal variation in vessel traffic, and (c) the available data on ballast water discharge in order to prioritize locations for tracking biological invasions. Most arrivals were passenger vessels, followed by ferries and fishing vessels, all of which carried little ballast water. Regional and seasonal patterns in arrivals and BWD were unevenly distributed among vessel types. The majority of vessels reporting BWD were from foreign ports, and most of this ballast was untreated. The largest volumes of ballast were from tankers at Valdez and Kenai Peninsula ports. Although Alaska has few documented invasions, opportunities for ship-mediated transfer now appear high and warrant further scrutiny.

Bedside diagnosis of coronary artery disease: a systematic review.

PURPOSE: To assess the accuracy of bedside findings for diagnosing coronary artery disease and acute myocardial infarction. METHODS: A MEDLINE search was performed to retrieve articles published from January 1966 to January 2003 that were relevant to the bedside diagnosis of coronary disease in adults. RESULTS: In patients with stable, intermittent chest pain, the most useful bedside predictors for a diagnosis of coronary disease were found to be the presence of typical angina (likelihood ratio [LR]=5.8; 95% confidence interval [CI]: 4.2 to 7.8), serum cholesterol level >300 mg/dL (LR=4.0; 95% CI: 2.5 to 6.3), history of prior myocardial infarction (LR=3.8; 95% CI: 2.1 to 6.8), and age >70 years (LR=2.6; 95% CI: 1.8 to 4.0). Nonanginal chest pain (LR=0.1; 95% CI: 0.1 to 0.2), pain duration >30 minutes (LR=0.1; 95% CI: 0.0 to 0.9), and intermittent dysphagia (LR=0.2; 95% CI: 0.1 to 0.8) argued against a diagnosis of coronary disease. In patients with acute chest pain, the most important bedside predictors for a diagnosis of myocardial infarction were new ST elevation (LR=22; 95% CI: 16 to 30), new Q waves (LR=22; 95% CI: 7.6 to 62), and new ST depression (LR=4.5; 95% CI: 3.6 to 5.6). A normal electrocardiogram (LR=0.2; 95% CI: 0.1 to 0.3), chest wall tenderness (LR=0.3; 95% CI: 0.2 to 0.4), and pain that was pleuritic (LR=0.2; 95% CI: 0.2 to 0.3), sharp (LR=0.3; 95% CI: 0.2 to 0.5), or positional (LR=0.3; 95% CI: 0.2 to 0.5) argued against the diagnosis of myocardial infarction. CONCLUSION: The accuracy of bedside predictors depends on the clinical setting. In the evaluation of stable, intermittent chest pain, a patient's description of pain was found to be the most important predictor of underlying coronary disease. In the evaluation of acute chest pain, the electrocardiogram was the most useful bedside predictor for a diagnosis of myocardial infarction. Aside from the extremes in cholesterol values, the analysis of traditional risk factors changed the probability of coronary disease or myocardial infarction very little or not at all.

Simplifying likelihood ratios.

Likelihood ratios are one of the best measures of diagnostic accuracy, although they are seldom used, because interpreting them requires a calculator to convert back and forth between "probability" and "odds" of disease. This article describes a simpler method of interpreting likelihood ratios, one that avoids calculators, nomograms, and conversions to "odds" of disease. Several examples illustrate how the clinician can use this method to refine diagnostic decisions at the bedside.