Skin staining due to iron leakage into the subcutaneous tissue can sometimes occur during intravenous iron infusion. We describe a case of lateral antebrachial cutaneous nerve (LACN) entrapment due to extravasated iron after an intravenous iron infusion. A 41-year-old woman received an intravenous ferric carboxymaltose infusion for iron deficiency anemia. However, during the infusion, extravasation of iron occurred and brown pigmentation developed on the lateral side of the cubital fossa. Sixteen months later, the patient still had some staining in her anterolateral elbow and proximal forearm. In addition, she complained of tingling pain over her left forearm. Ultrasonography (US) revealed a lateral antebrachial cutaneous nerve (LACN) under the stained area. When we swept the stained area with the US transducer, she reported a tingling pain on her left lateral forearm, the region innervated by the left LACN. Therefore, we considered that the pain resulted from the compression of the left LACN by the leaked iron during the intravenous infusion. Leaked iron can compress the cutaneous nerve and result in neuropathic pain and cosmetic problems. When patients with skin staining after iron infusion have neuropathic pain, clinicians should consider the possibility of entrapment of the cutaneous nerves. Full article

Background: Peripheral arterial disease (PAD) involves arterial blockages in the body, except those serving the heart and brain. We explore the relationship of functional limitation and PAD symptoms obtained from a quality-of-life questionnaire about the severity of the disease. We used a supervised artificial intelligence-based method of data analyses known as machine learning (ML) to demonstrate a nonlinear relationship between symptoms and functional limitation amongst patients with and without PAD. Objectives: This paper will demonstrate the use of machine learning to explore the relationship between functional limitation and symptom severity to PAD severity. Methods: We performed supervised machine learning and graphical analysis, analyzing 703 patients from an administrative database with data comprising the toe–brachial index (TBI), baseline demographics and symptom score(s) derived from a modified vascular quality-of-life questionnaire, calf circumference in centimeters and a six-minute walk (distance in meters). Results: Graphical analysis upon categorizing patients into critical limb ischemia (CLI), severe PAD, moderate PAD and no PAD demonstrated a decrease in walking distance as symptoms worsened and the relationship appeared nonlinear. A supervised ML ensemble (random forest, neural network, generalized linear model) found symptom score, calf circumference (cm), age in years, and six-minute walk (distance in meters) to be important variables to predict PAD. Graphical analysis of a six-minute walk distance against each of the other variables categorized by PAD status showed nonlinear relationships. For low symptom scores, a six-minute walk test (6MWT) demonstrated high specificity for PAD. Conclusions: PAD patients with the greatest functional limitation may sometimes be asymptomatic. Patients without PAD show no relationship between functional limitation and symptoms. Machine learning allows exploration of nonlinear relationships. A simple linear model alone would have overlooked or considered such a nonlinear relationship unimportant. Full article

Background. Hyperuricemia is common in patients with chronic kidney disease (CKD), and this may lead to poor cardiovascular (CV) outcomes. The aim of this cross-sectional study was to assess associations among serum uric acid (UA) and echocardiographic parameters, ankle-brachial index (ABI), and brachial-ankle pulse wave velocity (baPWV) in patients with CKD. Methods. A total of 418 patients with CKD were included. The echocardiographic measurements included left atrial diameter (LAD), left ventricular ejection fraction (LVEF) and the ratio of observed to predict left ventricular mass (LVM). ABI, baPWV and medical records were obtained. Results. Multivariable forward logistic regression analysis showed that a high UA level was significantly associated with LAD > 47 mm (odds ratio [OR], 1.329; p = 0.002), observed/predicted LVM > 128% (OR, 1.198; p = 0.008) and LVEF < 50% (OR, 1.316; p = 0.002). No significant associations were found between UA and ABI < 0.9 or baPWV > 1822 cm/s. Multivariate stepwise linear regression analysis showed that a high UA level correlated with high LAD (unstandardized coefficient β, 0.767; p < 0.001), high observed/predicted LVM (unstandardized coefficient β, 4.791; p < 0.001) and low LVEF (unstandardized coefficient β, −1.126; p = 0.001). No significant associations between UA and low ABI and high baPWV were found. Conclusion. A high serum UA level was associated with a high LAD, high observed/predicted LVM and low LVEF in the patients with CKD. A high serum UA level may be correlated with abnormal echocardiographic parameters in patients with stage 3–5 CKD. Full article

Millions suffer daily from chronic pain diagnosed anatomically and treated with opioids. Research shows that underlying nutritional, metabolic and oxidative stressors, which drive the development or worsening of chronic pain, are not diagnosed despite the fact that treatment of these primary pain pathways relieves pain and increases function. One of the main reasons for this gap in care is the lack of a simple diagnostic assay to help clinicians make these diagnoses. We examined the clinical utility of a urine-based pain biomarker panel. Primary care physicians were randomized into the test group and compared to controls. We measured their ability to make the diagnosis and treat a total of nine standardized patients, with common but challenging cases of chronic pain, over two rounds of data collection in a pre–post design using a fixed-effects model. Intervention doctors received educational materials on a novel pain biomarker panel after the baseline round and had access to biomarker test results. Provider responses were measured against evidence-based criteria. The two study arms at baseline provided similar, poor care for three different primary pain pathways: nutritional deficiencies (5.0% control versus 9.2% intervention treated, p = 0.208), metabolic abnormalities (1.0% control versus 0% for intervention treated, p = 0.314), and oxidative stress (1.2% control versus 0% intervention treated, p = 0.152). After the introduction of the Foundation Pain Index (FPI) biomarker test, physicians in the intervention group were 41.5% more likely to make the diagnosis of a micronutrient deficiency, 29.4% more likely to identify a treatable metabolic abnormality and 26.1% more likely to identify an oxidative stressor. These diagnostic and treatment improvements were seen across all three case types, ranging from a relative +54% (p = 0.004) for chronic neuropathic pain to +35% (p = 0.007) in chronic pain from other causes to +38% (p = 0.002) in chronic pain with associated mental health issues. Intervention doctors were also 75.1% more likely to provide a non-opioid treatment to patients on chronic opioids (O.R. 1.8, 95% C.I. 0.8–3.7), 62% less likely to order unnecessary imaging for their patients with low back pain (O.R. 0.38, 95% C.I. 0.15–0.97) and 66% less likely to order an unnecessary pain referral (O.R. 0.34, 95% C.I. 0.13–0.90). This experimental study showed significant clinical utility of a validated pain biomarker panel that determines nutritional deficiencies, metabolic abnormalities and oxidative stressors that drive underlying treatable causes of pain. When integrated into routine primary care practice, this testing approach could considerably improve diagnostic accuracy and provide more targeted, non-opioid treatments for patients suffering from chronic pain. Full article

Liver diseases are amongst the most common diseases worldwide and manifest as a parenchymatic and/or biliary injury due to several causes as well as focal liver lesions, ranging from benign to malignant ones. The diagnosis of liver diseases is based mainly on biochemical and advanced imaging studies and, when required, on liver biopsy. Endoscopic ultrasound (EUS), which combines endoscopy and ultrasonography, is one of the main examination techniques used in gastroenterology as it is applied to evaluate abnormalities in the lumen of the upper and lower gastrointestinal tract and to define pancreatic and hepato-biliary features, often in chronic patients. Given its high spatial resolution and its proximity to the liver, EUS is gaining popularity in the diagnostic work up of liver diseases. This is a comprehensive overview of the current literature on the diagnostic indications for EUS use in patients with liver diseases. We performed a MEDLINE\PubMed and Embase search, and all articles that were relevant, after reviewing abstracts, were assessed and the full text was analyzed to extract data regarding technical success, diagnostic yield, bioptic characteristics, and complications rate. EUS-guided imaging and biopsy techniques in liver diseases have shown consistent favorable promising results among the reports through the literature, with an excellent diagnostic yield and safety profile, especially in the context of focal lesions and portal hypertension. The application of EUS in the diagnosis of liver diseases is a promising technique and should be considered as a first-line therapeutic option in selected cases. Full article

The chain length of hyaluronan (HA) determines its physical as well as its physiological properties. Results of clinical research on HA eye drops are not comparable without this parameter. In this article methods for the assessment of the average molecular weight of HA in eye drops and a terminology for molecular weight ranges are proposed. The classification of HA eye drops according to their zero shear viscosity and viscosity at 1000 s⁻¹ shear rate is presented. Based on the gradient of mucin MUC5AC concentration within the mucoaqueous layer of the tear film a hypothesis on the consequences of this gradient on the rheological properties of the tear film is provided. The mucoadhesive properties of HA and their dependence on chain length are explained. The ability of HA to bind to receptors on the ocular epithelial cells, and in particular the potential consequences of the interaction between HA and the receptor HARE, responsible for HA endocytosis by corneal epithelial cells is discussed. The physiological function of HA in the framework of ocular surface homeostasis and wound healing are outlined, and the influence of the chain length of HA on the clinical performance of HA eye drops is illustrated. The use of very high molecular weight HA (hylan A) eye drops as drug vehicle for the next generation of ophthalmic drugs with minimized side effects is proposed and its advantages elucidated. Consequences of the diagnosis and treatment of ocular surface disease are discussed. Full article

Apolipoproteins (Apo) are known atherogenic factors that play important roles in many mechanisms related to coronary heart disease. The ApoB/ApoA1 ratio is a promising diagnostic tool for metabolic syndrome (MS) in different populations, though its use is not established in Kazakhstan. This study aimed to assess the relationship between MS and the ApoB/ApoA1 ratio among hypertensive patients and to evaluate its diagnostic use for identifying MS as an alternative to triglycerides (TG) and high-density lipoprotein cholesterol (HDL-C). A cross-sectional study was conducted in 800 eligible men and women with primary hypertension from April 2015 to December 2016. Data were collected on socio-demographics, lifestyle parameters, family history of cardiovascular disease, and hypertension. Dietary Quality Score (DQS), anthropometric data, and blood pressure were recorded; ApoA1 and ApoB levels were measured in blood samples. We found a significant positive association between MS and the ApoB/ApoA1 ratio by multiple logistic regression, as shown by a linear trend of increase of the odds ratio (OR) for MS across the quartiles of ApoB/ApoA1 (p < 0.0001). ROC analysis revealed diagnostic significance of the ApoB/ApoA1 ratio for MS, and comparative ROC analysis demonstrated equal diagnostic value of ApoB/ApoA1 ratio and TG levels (AUC = 0.71 (95% CI 0.69; 0.74) and 0.72 (95% CI 0.69, 0.76), respectively), which was significantly higher than those of HDL, ApoA1, ApoB (AUC = 0.27 (95% CI 0.23; 0.31), AUC = 0.37 (95% CI 0.33; 0.41), AUC = 0.67, (95% CI 0.63; 0.71), respectively). The diagnostic value of the ApoB/ApoA1 ratio in Kazakhs with MS appeared to equal that of TG and was significantly higher than that of HDL-C. Adjusting for gender, smoking, and DQS significantly strengthened the association between MS and the ApoB/ApoA1 ratio in the Kazakh population. Full article

Point-of-care (POC) or near-patient testing allows clinicians to accurately achieve real-time diagnostic results performed at or near to the patient site. The outlook of POC devices is to provide quicker analyses that can lead to well-informed clinical decisions and hence improve the health of patients at the point-of-need. Microfluidics plays an important role in the development of POC devices. However, requirements of handling expertise, pumping systems and complex fluidic controls make the technology unaffordable to the current healthcare systems in the world. In recent years, capillary-driven flow microfluidics has emerged as an attractive microfluidic-based technology to overcome these limitations by offering robust, cost-effective and simple-to-operate devices. The internal wall of the microchannels can be pre-coated with reagents, and by merely dipping the device into the patient sample, the sample can be loaded into the microchannel driven by capillary forces and can be detected via handheld or smartphone-based detectors. The capabilities of capillary-driven flow devices have not been fully exploited in developing POC diagnostics, especially for antimicrobial resistance studies in clinical settings. The purpose of this review is to open up this field of microfluidics to the ever-expanding microfluidic-based scientific community. Full article

The opportunity to encounter and appreciate the range of human variation in anatomic structures—and its potential impact on related structures, function, and treatment—is one of the chief benefits of cadaveric dissection for students in clinical preprofessional programs. The dissection lab is also where students can examine unusual anatomic variants that may not be included in their textbooks, lab manuals, or other course materials. For students specializing in physical medicine, awareness and understanding of muscle variants has a practical relevance to their preparations for clinical practice. In a routine dissection of the superficial chest muscles, graduate students in a human gross anatomy class exposed a large, well-developed sternalis muscle. The exposure of this muscle generated many student questions about M sternalis: its prevalence and appearance, its function, its development, and its evolutionary roots. Students used an inquiry protocol to guide their searches through relevant literature to gather this information. Instructors developed a decision tree to assist students in their inquiries, both by helping them to make analytic inferences and by highlighting areas of interest needing further investigation. Answering these questions enriches the understanding and promotes “habits of mind” for exploring musculoskeletal anatomy beyond simple descriptions of function and structure. Full article

The yield of biochemical analysis of pancreatic cysts fluid obtained via fine needle aspiration (FNA) is limited. We aimed to assess whether biochemical cyst analysis correlates with the endoscopic ultra-sonographic (EUS) diagnosis. A retrospective study including patients who underwent EUS-FNA was performed. Agreement level between EUS diagnosis and biochemical analysis was reported. One-hundred-and-eleven patients were included. For cyst CEA level, 42.4% of patients with endoscopic diagnosis of pancreatic mucinous cystic neoplasm (intraductal papillary mucinous neoplasm (IPMN) and mucinous cystic neoplasms (MCN)) had CEA level >192 ng/mL vs. 15.8% of patients who had another endoscopic diagnosis (chi square = 0.03) with poor agreement level (Kappa = 0.130). For the serous cystadenoma (SCA), the levels of amylase and CEA were defined as <250 unit/L and <5 ng/mL, respectively. Eight patients (57.1%) had amylase of <250 unit/L, while 42.9% had >250 unit/L (chi square = 0.007). The agreement level between EUS diagnosis of SCA and amylase level was poor (Kappa = 0.231). For cyst CEA level, 71.4% had CEA level <5 ng/mL vs. 28.6% who had CEA >5 ng/mL (chi square < 0.001) with fair agreement level (Kappa = 0.495). EUS-FNA for pancreatic cystic lesions poorly correlated with the EUS diagnosis. FNA should be considered in the setting of EUS worrisome findings. Full article

Tracheostomy is a commonly performed intervention in patients requiring ventilatory support. The insertion of inappropriately sized tracheostomy tubes carries a risk of decannulation, tissue damage, ventilatory difficulties, premature tube change or discomfort. Currently, no clear guidelines exist in determining the most appropriate size tube. Imaging of the airway preoperatively could aid clinical judgement and reduce risk. Patients included adult critical care patients who had appropriate preoperative imaging. The computed tomography scans and chest radiographs of patients were reviewed. Measurements of the airway were taken and scaled to the known internal diameter of an endotracheal tube. A four-point scoring system was developed to identify patients better suited to a non-standard sized tracheostomy tube. Data from 23 patients was analyzed using the Statistical Package for Social Sciences™ (SPSS). Four measured points on imaging corresponded to the patients’ appropriate tracheostomy tube size. Appropriate tracheostomy size correlates with tracheal diameter at endotracheal tube tip (r² = 0.135), carina (r² = 0.128), midpoint of larynx to carina (r² = 0.146), bronchial diameter at the left mainstem (r² = 0.323), and intrathoracic tracheal length (r² = 0.23). Among our cohort, a score of 4 predicts the need for a larger tracheostomy tube. Simple imaging provides accurate measurement of patients’ airway dimensions. Our method ensures tube size is selected according to patient airway size, and potentially reduces the risks associated with inappropriate sizing. Full article