A Hemoglobinopathy That Produces an Array of Different Hemoglobin A1c Values.

Hemoglobin A1c (HbA1c) refers to non-enzymatically glycated hemoglobin and reflects the patient's glycemic status over approximately 3 months. An elevated HbA1c over 6.5% National Glycohemoglobin Standardization Program (NGSP) (48 mmol/mol the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC)) can be used to diagnose diabetes mellitus. In our laboratory, HbA1c is determined by ion-exchange chromatography which has the advantage of detecting common Hb variants such as Hb S, C, E and D without adversely affecting the HbA1c determination. Certain homozygous or compound heterozygous hemoglobinopathies such as homozygous sickle disease and Hb SC disease can significantly lower the HbA1c by reducing red cell lifespan. Occasionally however, rare and mostly benign hemoglobinopathies can interfere with this technique resulting in an apparent elevation of HbA1c in an otherwise non-diabetic patient. In this report, we describe such a hemoglobinopathy termed Hb Wayne that resulted in a significant HbA1c elevation in a normoglycemic individual. HbA1c was determined by multiple methods including immunoassay, a modified capillary electrophoresis and an alternative ion-exchange system. These techniques yielded significantly lower A1c results, more in keeping with the patient's clinical background. The alternative ion-exchange system resulted in a low A1c that was qualified by warning flags on the chromatogram that indicated the result was not reportable. The hemoglobinopathy in question, Hb Wayne, is a frameshift mutation in the alpha globin gene that results in an extended alpha globin polypeptide that can form two variants Hb Wayne I and Wayne II. Hb Wayne is a clinically silent asymptomatic disorder with no hematologic consequences. The artifactual elevation of HbA1c is, in contrast, very significant because it may result in a misdiagnosis of diabetes mellitus leading to unnecessary treatment. In this report, we compare our findings with other descriptions of Hb Wayne in the literature and corroborate a number of previous observations and conclusions.

Iatrogenic Pseudoaneurysm-Associated Cerebral Hemorrhage: A Rare Complication of Burr Hole Drainage - A Case Report.

BACKGROUND: Nontraumatic intracranial hemorrhage occurs most commonly due to hypertension and is treated nonoperatively. Iatrogenic pseudoaneurysm from prior neurosurgical therapy represents a rarely described etiology for intracranial hemorrhage that may require emergent surgical therapy. CASE REPORT: An elderly female patient was brought to the emergency department with fatigue but no recent trauma. Subsequent computed tomography of the brain revealed a right-sided intraparenchymal hematoma. Her history included burr hole drainage of a subdural hematoma near the site, so additional imaging was performed and revealed an arteriovenous malformation, later discovered on operative findings to be a pseudoaneurysm, as the cause of the current bleeding episode. Why Should an Emergency Physician Be Aware of This? Awareness of prior neurosurgical treatment, even including minor procedures, in patients with apparent spontaneous intracranial bleeding should prompt angiographic evaluation for arteriovenous malformation. If found, these lesions are more likely to benefit from surgical treatment.

Revision Dual Mobility Constructs With Unmatched Acetabular and Femoral Components Do Not Increase Failure Rate.

BACKGROUND: Dual mobility (DM) constructs for revision total hip arthroplasty (THA) have continued to grow in popularity to mitigate instability. This benefit comes at the cost of potential unique modes of failure, and there are theoretical concerns that combining femoral and acetabular components from different manufacturers could lead to increased failure rates. We aimed to investigate rates of reoperation between matched and unmatched DM implants used in revision THA. METHODS: We retrospectively reviewed 217 revision THAs performed with DM constructs between July 2012 and September 2021 at a single institution. Dual mobility (DM) constructs were classified as "matched" if the acetabular and femoral components were manufactured by the same company. They were classified as "unmatched" if the acetabular and femoral components were manufactured by different companies. The primary outcome was reoperation for any reason. RESULTS: There were 136 matched DM constructs and 81 unmatched constructs. Average follow-up was 4.6 years (range, 2.0 to 9.6 years). There was no difference in reoperation rate between matched and unmatched groups (11.0 versus 13.6%, P = .576). The most common reasons for reoperation in both groups were instability and periprosthetic joint infection. There was 1 revision for intraprosthetic dislocation in the matched group. CONCLUSIONS: The use of unmatched DM components in revision THA was common and did not increase the risk of reoperation at an average of 4.6-year follow-up. This information can be helpful in operative planning, but further research on long-term survival will be necessary.

Staphylococcus aureus genotype variation among and within periprosthetic joint infections.

Staphylococcus aureus is a common organism in orthopedic infections, but little is known about the genetic diversity of strains during an infectious process. Using periprosthetic joint infection (PJI) as a model, a prospective study was designed to quantify genetic variation among S. aureus strains both among and within patients. Whole genome sequencing and multilocus sequence typing was performed to genotype these two populations at high resolution. In nasal cultures, 78% of strains were of clonal complexes CC5, CC8, and CC30. In PJI cultures, only 63% could be classified in these common clonal complexes. The PJI cultures had a larger proportion of atypical strains, and these atypical strains were associated with poor host status and compromised immune conditions. Mutations in genes involved in fibronectin binding (ebh, fnbA, clfA, and clfB) systematically distinguished later PJI isolates from the first PJI isolate from each patient. Repeated mutations in S. aureus genes associated with extracellular matrix binding were identified, suggesting adaptive, parallel evolution of S. aureus during the development of PJI.

Emergency Department management of rib fractures

Rib fractures resulting from blunt thoracic trauma are often associated with life-threatening complications of injury to cardiorespiratory systems. Given the risk for morbidity and mortality, the emergency clinician must be swift and thorough in diagnosing and managing these injuries. Society guidelines have been published to assist in determining best-practice approaches to pain control, imaging, and treatment. This issue reviews the recent studies and evidence for multimodal pain control, decision tools for diagnostic imaging, ventilatory support, and operative fixation. Scoring systems to determine disposition of patients are evaluated, with particular attention given to the special risks to the elderly patient.

Increased Medial Displacement of the Humeral Shaft of at Least 40% Correlates With an Increased Incidence of Nerve Injury in Proximal Humerus Fractures.

BACKGROUND: Peripheral nerve and infraclavicular brachial plexus injury following proximal humerus fractures are commonplace, but diagnosing a concomitant nerve injury in the acute setting is challenging. Fracture displacement has been identified as a qualitative risk factor for nerve injury, and additional attention should be paid to the neurologic exams of patients with proximal humerus fractures with significant medial shaft displacement. However, a quantitative relationship between the risk of nerve injury and medialization of the humeral shaft has not been shown, and additional risk factors for this complication have not been assessed. The aim of this study was to identify the risk factors for a neurologic deficit following a proximal humerus fracture, with particular interest in the utility of the magnitude of medial shaft displacement as a predictor of neurologic dysfunction. METHODS: A retrospective chart review was performed on all proximal humerus fractures in a 3-year period (2012-2015) at a level one trauma center. Isolated greater tuberosity fractures (OTA 11-A1) were excluded. Fracture displacement was measured on initial injury AP shoulder radiograph and expressed as a percentage of humeral diaphyseal width. All orthopedic inpatient documentation was assessed to identify clinical neurologic deficits. RESULTS: We identified 139 patients for inclusion. There were 22 patients (16%) with new neurologic deficits at presentation (8 axillary nerve, 2 radial nerve, 12 infraclavicular brachial plexus or multiple nerve injuries). The average shaft medial displacement in patients with neurologic injuries was 59% vs. 21% without nerve deficits (p=0.03). Using a 40% medial displacement threshold, the odds ratio for a nerve injury was 5.24 (95% CI 1.54 - 17.77, p=.008). CONCLUSION: Increased medial displacement of the humeral shaft following proximal humerus fracture is associated with an increased incidence of nerve injury at the time of initial presentation. This finding is not meant to be a surrogate for a high-quality neurologic exam in all patients with proximal humerus fractures. However, improved knowledge of the specific risk factors for an occult neurologic injury will improve the clinician's ability to accurately diagnose and properly treat proximal humerus fractures and their sequelae.Level of Evidence: III.

Oxyhemoglobin concentrations do not support hemoglobinopathy in COVID-19.

Based on computerized modeling studies, it has been postulated that the severe hypoxemia in COVID-19 may result from impaired oxygen carrying capacity on hemoglobin. Standard pulse oximetry may not detect hypoxemia resulting from hemoglobinopathy, therefore hemoglobin co-oximetry is needed to evaluate this divergence. In a clinical data analysis of a multicenter cohort of hospitalized patients with COVID-19, we found a minimal effect, less than 1%, on the correlation between oxyhemoglobin concentration and predicted oxygen saturation in the presence of COVID-19 infection. This effect is unlikely to explain the clinically significant hypoxia in COVID-19 patients.

Monitoring of COVID-19-Associated Coagulopathy and Anticoagulation with Thromboelastometry.

INTRODUCTION: Thrombosis occurs frequently in COVID-19. While the exact mechanism is unclear, 3 processes seem to play important roles in sepsis-related thrombosis and mortality: tissue factor expression on circulating monocytes and microparticles, hypercoagulability (increased clot firmness), and hypofibrinolysis. Rotational thromboelastometry is a point-of-care viscoelastic technique that uses the viscoelastic properties of blood to monitor coagulation. Using various assays, viscoelastometry could monitor this triad of changes in severely ill, COVID-19-positive patients. Similarly, with the increased incidence of coagulopathy, many patients are placed on anticoagulants, making management more difficult depending on the agents utilized. Viscoelastometry might also be used in these settings to monitor anticoagulation status and guide therapy, as it has in other areas. CASE PRESENTATION: We present a case series of 6 patients with different stages of disease and different management plans. These cases occurred at the height of the pandemic in New York City, which limited testing abilities. We first discuss the idea of using the NaHEPTEM test as a marker of tissue factor expression in COVID-19. We then present cases where patients are on different anticoagulants and review how viscoelastometry might be used in a patient on anticoagulation with COVID-19. CONCLUSION: In a disease such as COVID-19, which has profound effects on hemostasis and coagulation, viscoelastometry may aid in patient triage, disease course monitoring, and anticoagulation management.

Development of a large animal rabbit model for chronic periprosthetic joint infection.

AIMS: Periprosthetic joint infections (PJIs) and osteomyelitis are clinical challenges that are difficult to eradicate. Well-characterized large animal models necessary for testing and validating new treatment strategies for these conditions are lacking. The purpose of this study was to develop a rabbit model of chronic PJI in the distal femur. METHODS: Fresh suspensions of Staphylococcus aureus (ATCC 25923) were prepared in phosphate-buffered saline (PBS) (1 × 109 colony-forming units (CFUs)/ml). Periprosthetic osteomyelitis in female New Zealand white rabbits was induced by intraosseous injection of planktonic bacterial suspension into a predrilled bone tunnel prior to implant screw placement, examined at five and 28 days (n = 5/group) after surgery, and compared to a control aseptic screw group. Radiographs were obtained weekly, and blood was collected to measure ESR, CRP, and white blood cell (WBC) counts. Bone samples and implanted screws were harvested on day 28, and processed for histological analysis and viability assay of bacteria, respectively. RESULTS: Intraosseous periprosthetic introduction of planktonic bacteria induced an acute rise in ESR and CRP that subsided by day 14, and resulted in radiologically evident periprosthetic osteolysis by day 28 accompanied by elevated WBC counts and histological evidence of bacteria in the bone tunnels after screw removal. The aseptic screw group induced no increase in ESR, and no lysis developed around the implants. Bacterial viability was confirmed by implant sonication fluid culture. CONCLUSION: Intraosseous periprosthetic introduction of planktonic bacteria reliably induces survivable chronic PJI in rabbits. Cite this article: Bone Joint Res 2021;10(3):156-165.

Volar Carpus Dislocation Following Proximal Row Carpectomy for Scapholunate Advanced Collapse: A Rare Complication.

Scapholunate advanced collapse (SLAC) is a frequently encountered cause of wrist arthritis. For stage 2 disease, proximal row carpectomy (PRC) is an accepted treatment for which the literature has documented satisfactory outcomes and generally low complication rates. However, we report a case of SLAC wrist treated with PRC complicated by postoperative volar dislocation of carpus, to our knowledge a complication not yet reported in the literature. The patient developed atraumatic volar carpus dislocation after a routine PRC. This was treated with subsequent return to the operating room with closed reduction and percutaneous pinning of the wrist. Adequate reduction of the carpal dislocation was achieved and maintained after removal of pins. This case shows that closed reduction and percutaneous pinning is a valid option in this rare complication.

Squamous epithelial cell presence reduces accuracy of urinalysis for prediction of positive urine cultures.

BACKGROUND: Diagnostic value of urinalysis specimens contaminated with squamous epithelial cells (SEC) from the genital surfaces is assumed to be limited compared to clean-catch samples. However, no studies have quantified the change in predictive value in the presence of SECs for individual urinalysis markers. METHODS: In a retrospective, single center cohort study, we analyzed all urine cultures sent from the ED over a 26-month period with corresponding urinalysis results. Cultures were classified as positive with growth of >104 colony forming units of pathogenic bacteria, negative if no growth, or contaminated for all other results. UA specimens were classified as contaminated or clean based on SEC presence. Accuracy of urinalysis markers for prediction of positive cultures was calculated as an area under the curve (AUC) and was compared between contaminated and clean UA specimens. RESULTS: 6490 paired UA and urine cultures were analyzed, consisting of 3949 clean and 2541 contaminated samples. SEC presence was less common with male gender, older age, and smaller BMI. Urine cultures were 19.2% positive overall, and SECs were more common in contaminated cultures. AUCs for individual markers ranged from 0.557 to 0.796, with pyuria, bacteriuria, and leukocyte esterase having higher AUC in clean samples over contaminated. CONCLUSION: Analysis of AUC for individual urinalysis markers showed reduced diagnostic accuracy in the presence of SECs. SEC presence also reflected much higher rates of contaminated cultures. These results support the reduced reliance on contaminated UA specimens for ruling in UTI in ED patients.

Determinants of empiric transfusion in gastrointestinal bleeding in the emergency department.

INTRODUCTION: Current guidelines for the management of GI bleeding (GIB) recommend restrictive transfusion triggers unless patients have shock or specific comorbidities. However, these studies may not be applicable to Emergency Department (ED) patients. Factors determining transfusion decisions in the ED are poorly understood. We compared baseline characteristics and outcomes between ED patients with GI bleeding transfused at lower or higher empiric hemoglobin levels. METHODS: Single center, retrospective analysis of hospital records from a large tertiary care center of ED patients diagnosed with GIB who underwent red blood cell transfusion in the ED. A pre-transfusion hemoglobin cutoff of 7 g/dl was used to divide patients into restrictive and empirically transfused groups. Demographics, mortality, hospital length-of-stay, and mortality risk estimates were compared between groups. RESULTS: 175 patients met inclusion criteria, with 120 restrictive patients (68.5%) and 55 liberal patients (31.4%). The sample was 49.7% male, with mean age 67.2 years, similar between groups. Patients in the empiric transfusion group had more acute emergency severity index scores (2.09 vs. 2.3). No difference was found between groups in triage vital signs, pre-endoscopy Rockall scores or mortality estimates, or length of stay. Most common reasons for empiric transfusion from chart review were hypotension and witnessed large hemorrhage. CONCLUSIONS: Patients that were empirically transfused had similar presentations to patients meeting restrictive guidelines, based on review of triage data. Transfusions above restrictive thresholds occurred frequently in our population. Additional studies are required to clarify appropriate criteria to guide transfusions for GIB in the ED.

Emergency department management of patients taking direct oral anticoagulant agents.

Direct oral anticoagulant (DOAC) agents have become commonly used over the last 9 years for treatment and prophylaxis for thromboembolic conditions, following approvals by the United States Food and Drug Administration. These anticoagulant agents, which include a direct thrombin inhibitor and factor Xa inhibitors, offer potential advantages for patients over warfarin; however, bleeding emergencies with DOACs can present diagnostic and therapeutic challenges because, unlike traditional anticoagulants, their therapeutic effect cannot be easily monitored directly with common clotting assays. This review examines the growing body of evidence on the uses and risks of DOACs in the emergency department, including initiation of therapy and reversal strategies.

Emergency department utilization by a jail population.

BACKGROUND: Incarcerated individuals represent a significant proportion of the US population and face unique healthcare challenges. Scarce articles have been published about emergency department (ED) care of these patients. We studied the ED visits from one urban jail to better describe this population. METHODS: A cohort study design was used, identifying patients who were sent to the ED from a city jail in 2015. Demographics, triage information, length of stay, number of studies, billing codes, diagnoses, and disposition data were collected. These were compared to the overall ED patient population in the same year. RESULTS: 868 ED visits by jail patients occurred, representing 1.3% of the ED census. Compared to the general population, incarcerated patients were younger (32.1 years vs. 44.0 years, p < .01), healthier based on Elixhauser comorbidity scores (0.71 vs. 0.98, p < .01), and had lower admission rates (11.29% vs. 21.54%, p < .01). An abnormal vital sign was noted in 25% of incarcerated patients. Laboratory (61% vs. 57%, p < .02) and radiologic (63% vs 45%, p < .001) testing was more frequent for inmates and length of stay was longer (271 vs. 225 min, p < .01). CONCLUSION: ED visits from jail were common, involving a relatively young and healthy population with a low incidence of abnormal vital signs and admission. Given the high costs associated with ED care and the medical resources available at some jails, further study should evaluate if increased jail medical capabilities could improve care and decrease costs by decreasing ED visits.

Daily muscle stretching enhances blood flow, endothelial function, capillarity, vascular volume and connectivity in aged skeletal muscle.

KEY POINTS: In aged rats, daily muscle stretching increases blood flow to skeletal muscle during exercise. Daily muscle stretching enhanced endothelium-dependent vasodilatation of skeletal muscle resistance arterioles of aged rats. Angiogenic markers and capillarity increased in response to daily stretching in muscles of aged rats. Muscle stretching performed with a splint could provide a feasible means of improving muscle blood flow and function in elderly patients who cannot perform regular aerobic exercise. ABSTRACT: Mechanical stretch stimuli alter the morphology and function of cultured endothelial cells; however, little is known about the effects of daily muscle stretching on adaptations of endothelial function and muscle blood flow. The present study aimed to determine the effects of daily muscle stretching on endothelium-dependent vasodilatation and muscle blood flow in aged rats. The lower hindlimb muscles of aged Fischer rats were passively stretched by placing an ankle dorsiflexion splint for 30 min day-1 , 5 days week-1 , for 4 weeks. Blood flow to the stretched limb and the non-stretched contralateral limb was determined at rest and during treadmill exercise. Endothelium-dependent/independent vasodilatation was evaluated in soleus muscle arterioles. Levels of hypoxia-induced factor-1α, vascular endothelial growth factor A and neuronal nitric oxide synthase were determined in soleus muscle fibres. Levels of endothelial nitric oxide synthase and superoxide dismutase were determined in soleus muscle arterioles, and microvascular volume and capillarity were evaluated by microcomputed tomography and lectin staining, respectively. During exercise, blood flow to plantar flexor muscles was significantly higher in the stretched limb. Endothelium-dependent vasodilatation was enhanced in arterioles from the soleus muscle from the stretched limb. Microvascular volume, number of capillaries per muscle fibre, and levels of hypoxia-induced factor-1α, vascular endothelial growth factor and endothelial nitric oxide synthase were significantly higher in the stretched limb. These results indicate that daily passive stretching of muscle enhances endothelium-dependent vasodilatation and induces angiogenesis. These microvascular adaptations may contribute to increased muscle blood flow during exercise in muscles that have undergone daily passive stretch.

Frictional Magneto-Coulomb Drag in Graphene Double-Layer Heterostructures.

Coulomb interaction between two closely spaced parallel layers of conductors can generate the frictional drag effect by interlayer Coulomb scattering. Employing graphene double layers separated by few-layer hexagonal boron nitride, we investigate density tunable magneto- and Hall drag under strong magnetic fields. The observed large magnetodrag and Hall-drag signals can be related with Laudau level filling status of the drive and drag layers. We find that the sign and magnitude of the drag resistivity tensor can be quantitatively correlated to the variation of magnetoresistivity tensors in the drive and drag layers, confirming a theoretical formula for magnetodrag in the quantum Hall regime. The observed weak temperature dependence and ∼B^{2} dependence of the magnetodrag are qualitatively explained by Coulomb scattering phase-space argument.