Challenging Cases in Cerebrovascular Disease.

Disorders involving the vascular system of the brain are numerous and sundry. Atherosclerotic thromboembolism of large vessels and lacunar infarctions of small vessel disease are well known. Brain infarction due to cardioembolism is common as well, and even more so when diligently sought. Rupture of intracranial blood vessels results in subarachnoid and intraparenchymal hemorrhage. We present four cases of stroke of uncommon cause and remind clinicians to be open minded to the many possible causes of stroke, in particular because early recognition and treatment is often critical. Case 1 discusses a patient with inflammatory cerebral amyloid angiopathy. The presentation, ability to recur, and current treatment considerations are reviewed. Case 2 discusses microangiopathic thrombotic angiopathy. Diagnosis and treatment are considered. An association with interferon therapy and the evolving terminology of this and related conditions are discussed. Case 3 discusses intracranial hemorrhage secondary to acute promyelocytic leukemia. Patients with acute leukemias require aggressive management of their coagulopathy, thrombocytopenia, and the disease itself. Finally, Case 4 discusses ischemic stroke due to a paradoxical embolism in the setting of a patent foramen ovale (PFO). Both medical and surgical management of a PFO for stroke prevention are considered.

Osteoporotic Vertebral Fractures are Common in Hip Fracture Patients and are Under-recognized.

INTRODUCTION: The vertebrae are the most common site for osteoporotic fracture. While they can result in disability and increased mortality, only one-third present clinically. People with multiple fractures are at greater risk of future fractures. Most hip fracture patients are neither diagnosed nor treated for their underlying osteoporosis. Computed tomography (CT) studies are often performed on hospitalised patients, can be used to diagnose osteoporosis and are gaining popularity for opportunistic osteoporosis screening by measuring BMD and other bone strength indices. The aim of this study was to assess the prevalence of vertebral fractures on CT pulmonary angiograms (CTPA) in a cohort of hip fracture patients and whether this increased their diagnosis and treatment rates. METHODS: We retrospectively identified all hip fractures admitted to our institution between 2010 and 2017 to identify those who underwent CTPA scans. An independent, blinded consultant musculoskeletal radiologist reviewed the images for vertebral fractures and quantified severity using Genant criteria. Results were compared to the original radiology report, discharge diagnoses and treatment rates for osteoporosis. RESULTS: Eleven percent (225/2122) of patients had CTPA images available. Seventy percent (158) were female with a mean age of 78 years (SD: 11). The median length of stay for all patients was 16 days (1-301). Forty percent (90) of patients had at least one vertebral fracture present and 20% (46) had more than one fracture. Only one in 5 radiology reports noted the fractures. 24% of subjects had osteoporosis treatment recorded at hospital discharge and there was no difference between those with vertebral fractures to those without. CONCLUSION: Many hip fracture patients have undiagnosed spine fractures. A screening strategy which evaluates CT scans for fractures has potential to increase diagnosis and treatment rates of osteoporosis. However, more work is needed to increase awareness.

What Is the Optimal Irrigation Solution in the Management of Periprosthetic Hip and Knee Joint Infections?

BACKGROUND: Thorough irrigation and debridement using an irrigation solution is a well-established treatment for both acute and chronic periprosthetic joint infections (PJIs). In the absence of concrete data, identifying the optimal irrigation agent and protocol remains challenging. METHODS: A thorough review of the current literature on the various forms of irrigations and their additives was performed to evaluate the efficacy and limitations of each solution as pertaining to pathogen eradication in the treatment of PJI. As there is an overall paucity of high-quality literature comparing irrigation additives to each other and to any control, no meta-analyses could be performed. The literature was therefore summarized in this review article to give readers concise information on current irrigation options and their known risks and benefits. RESULTS: Antiseptic solutions include povidone-iodine, chlorhexidine gluconate, acetic acid, hydrogen peroxide, sodium hypochlorite, hypochlorous acid, and preformulated commercially available combination solutions. The current literature suggests that intraoperative use of antiseptic irrigants may play a role in treating PJI, but definitive clinical studies comparing antiseptic to no antiseptic irrigation are lacking. Furthermore, no clinical head-to-head comparisons of different antiseptic irrigants have identified an optimal irrigation solution. CONCLUSION: Further high-quality studies on the optimal irrigation additive and protocol for the management of PJI are warranted to guide future evidence-based decisions.

Biocompatible conjugation of Tris base to 2-acetyl and 2-formyl phenylboronic acid.

We describe the biocompatible conjugation of the Tris base to 2-formyl and 2-acetylphenylboronic acid (abbreviated as 2-FPBA and 2-APBA respectively), which have emerged as a versatile chemotype for fast biocompatible conjugation reactions. Tris base was found to react with 2-FPBA/APBA to give oxazolidinoboronate (OzB) complexes, analogous to the thiazolidinoboronate (TzB) and imidazolidinoboronate (IzB) complex formation that we recently reported. The Tris conjugations proceed well in complex biological media, and in contrast to the TzB/IzB complexes, the Tris conjugates exhibit superior kinetic stability (dissociation over days) as well as chemical stability against oxidation. We demonstrate the utility of such conjugation chemistries via a small molecule-induced peptide cyclization in blood serum.

Phage Display of Dynamic Covalent Binding Motifs Enables Facile Development of Targeted Antibiotics.

Antibiotic resistance of bacterial pathogens poses an increasing threat to the wellbeing of our society and urgently calls for new strategies for infection diagnosis and antibiotic discovery. The antibiotic resistance problem at least partially arises from extensive use of broad-spectrum antibiotics. Ideally, for the treatment of infection, one would like to use a narrow-spectrum antibiotic that specifically targets and kills the disease-causing strain. This is particularly important considering the commensal bacterial species that are beneficial and sometimes even critical to the health of a human being. In this contribution, we describe a phage display platform that enables rapid identification of peptide probes for specific bacterial strains. The phage library described herein incorporates 2-acetylphenylboronic acid moieties to elicit dynamic covalent binding to the bacterial cell surface. Screening of the library against live bacterial cells yields submicromolar and highly specific binders for clinical strains of Staphylococcus aureus and Acinetobacter baumannii that display antibiotic resistance. We further show that the identified peptide probes can be readily converted to bactericidal agents that deliver generic toxins to kill the targeted bacterial strain with high specificity. The phage display platform described here is applicable to a wide array of bacterial strains, paving the way to facile diagnosis and development of strain-specific antibiotics.

Publisher's Note: Direct Imaging of Dynamic Glassy Behavior in a Strained Manganite Film [Phys. Rev. Lett. 115, 265701 (2015)].

This corrects the article DOI: 10.1103/PhysRevLett.115.265701.

Direct Imaging of Dynamic Glassy Behavior in a Strained Manganite Film.

Complex many-body interaction in perovskite manganites gives rise to a strong competition between ferromagnetic metallic and charge-ordered phases with nanoscale electronic inhomogeneity and glassy behaviors. Investigating this glassy state requires high-resolution imaging techniques with sufficient sensitivity and stability. Here, we present the results of a near-field microwave microscope imaging on the strain-driven glassy state in a manganite film. The high contrast between the two electrically distinct phases allows direct visualization of the phase separation. The low-temperature microscopic configurations differ upon cooling with different thermal histories. At sufficiently high temperatures, we observe switching between the two phases in either direction. The dynamic switching, however, stops below the glass transition temperature. Compared with the magnetization data, the phase separation was microscopically frozen, while spin relaxation was found in a short period of time.

Assessment of previous fracture and anti-osteoporotic medication prescription in hip fracture patients.

INTRODUCTION: Hip fracture prevention is an essential component in elderly patient care. History of prior fracture is a significant risk factor for subsequent hip fracture. There are variable rates of treatment for these groups of patients. The aims of this study were to make an assessment of how many hip fracture patients over a 1 year period had a previous fracture and to assess whether or not these patients were on anti-osteoporotic medication. METHODS: Assessment on whether or not patients had a prior fracture using the national radiology imaging system checking radiology reports for all previous imaging performed. Checking patients bone health status using the hip fracture database for our hospital. RESULTS: There were 225 hip fractures in 221 patients over a 1-year period. About 42.6% of females and 35.9% of males had a history of previous fracture. Vertebral fractures were the most common type of fracture. We found 7% of patients had a contralateral hip fracture. There were 81% of patients with prior fracture, and 71% of those without prior fracture were on anti-osteoporotic medication. DISCUSSION: Vertebral fractures were the most common preceding fracture in hip fracture patients. There were many patients with a history of fragility fractures that were not on preventative medication. Overall there were good prescription rates of anti-osteoporotic medication. There were significantly higher rates of prescription amongst females compared with males.

Imaging of Coulomb-driven quantum Hall edge states.

The edges of a two-dimensional electron gas (2DEG) in the quantum Hall effect (QHE) regime are divided into alternating metallic and insulating strips, with their widths determined by the energy gaps of the QHE states and the electrostatic Coulomb interaction. Local probing of these submicrometer features, however, is challenging due to the buried 2DEG structures. Using a newly developed microwave impedance microscope, we demonstrate the real-space conductivity mapping of the edge and bulk states. The sizes, positions, and field dependence of the edge strips around the sample perimeter agree quantitatively with the self-consistent electrostatic picture. The evolution of microwave images as a function of magnetic fields provides rich microscopic information around the ν=2 QHE state.

Stroke: a modern history.

Prevention and treatment of stroke has changed substantially since the time of Franklin Delano Roosevelt who died of an intracerebral hemorrhage in 1945. As the understanding of stroke pathophysiology advanced, the beneficial effects of antiplatelet and anticoagulant drugs were recognized. Imaging of blood vessels by angiography made surgical therapies possible. Later noninvasive computerized tomography and magnetic resonance imaging distinguished hemorrhagic from ischemic stroke and gave new insight into stroke mechanisms. Stroke prevention became possible by selective management of stroke risk factors. Thrombolytics introduced 15 years ago provided the first actual treatment of ischemic stroke. The field of stroke continues to advance as medical and surgical treatments are refined and indications made clear, organized systems of care become standard, and new imaging techniques and endovascular therapies are developed.

Ultrathin topological insulator Bi2Se3 nanoribbons exfoliated by atomic force microscopy.

Ultrathin topological insulator nanostructures, in which coupling between top and bottom surface states takes place, are of great intellectual and practical importance. Due to the weak van der Waals interaction between adjacent quintuple layers (QLs), the layered bismuth selenide (Bi(2)Se(3)), a single Dirac-cone topological insulator with a large bulk gap, can be exfoliated down to a few QLs. In this paper, we report the first controlled mechanical exfoliation of Bi(2)Se(3) nanoribbons (>50 QLs) by an atomic force microscope (AFM) tip down to a single QL. Microwave impedance microscopy is employed to map out the local conductivity of such ultrathin nanoribbons, showing drastic difference in sheet resistance between 1-2 QLs and 4-5 QLs. Transport measurement carried out on an exfoliated (50 QLs) ribbons. These AFM-exfoliated thin nanoribbons afford interesting candidates for studying the transition from quantum spin Hall surface to edge states.

Neurological complications of cardiovascular drugs.

Cardiovascular drugs are used to treat arterial hypertension, hyperlipidemia, arrhythmias, heart failure, and coronary artery disease. They also include antiplatelet and anticoagulant drugs that are essential for prevention of cardiogenic embolism. Most neurologic complications of the cardiovascular drugs are minor or transient and are far outweighed by the anticipated benefits of treatment. Other neurologic complications are more serious and require early recognition and management. Overtreatment of arterial hypertension may cause lightheadedness or fatigue but often responds readily to dose adjustment or an alternative drug. Other drug complications may be more troublesome as in myalgia associated with statins or headache associated with vasodilators. The recognized bleeding risk of the antithrombotics requires careful calculation of risk/benefit ratios for individual patients. Many neurologic complications of cardiovascular drugs are well documented in clinical trials with known frequency and severity, but others are rare and recognized only in isolated case reports or small case series. This chapter draws on both sources to report the adverse effects on muscle, nerve, and brain associated with commonly used cardiovascular drugs.

The Use of Metaphyseal Cones and Sleeves in Revision Total Knee Arthroplasty.

The burden of revision total knee arthroplasty (rTKA) is expected to increase with the rise in the number of TKA procedures being performed yearly. Management of bone loss during rTKA is challenging and necessitates appropriate surgical planning. Metaphyseal cones and sleeves have emerged as an increasing popular option for addressing metaphyseal femoral and tibial bone loss when performing rTKA. Understanding what cones and sleeves are commercially available and when to use them are critical parts of preoperative evaluation and planning. The purpose of this comprehensive review was to present different design philosophies, types of manufacturing, clinical outcomes, and the versatility and interchangeability of varying cones and sleeves with different TKA revision systems.

Hierarchy of electronic properties of chemically derived and pristine graphene probed by microwave imaging.

Local electrical imaging using microwave impedance microscope is performed on graphene in different modalities, yielding a rich hierarchy of the local conductivity. The low-conductivity graphite oxide and its derivatives show significant electronic inhomogeneity. For the conductive chemical graphene, the residual defects lead to a systematic reduction of the microwave signals. In contrast, the signals on pristine graphene agree well with a lumped-element circuit model. The local impedance information can also be used to verify the electrical contact between overlapped graphene pieces.

Diagnostic Accuracy of Physical Examination Tests in Core Muscle Injury.

BACKGROUND: Core muscle injury (CMI), often referred to as a sports hernia, is a common cause of groin pain in athletes characterized by concomitant injury to the insertion of the adductor longus and the rectus abdominis muscles. Currently, the literature on CMI is sparse with no standardized physical examination tests used in the diagnosis of this type of injury. PURPOSE: To determine the diagnostic accuracy of various physical examination tests in the diagnosis of CMI. STUDY DESIGN: Cohort study (Diagnosis); Level of evidence, 3. METHODS: A consecutive series of patients evaluated by the senior author with symptoms consistent with CMI were included. Four physical examination tests were routinely performed in these patients by the senior author and were noted in each patient's chart as positive or negative: (1) pain with resisted cross-body sit-up in figure-of-4 position, (2) pain with straight-leg sit-up, (3) pain with resisted hip flexion in external rotation (external rotation Stinchfield test), and (4) the presence of an adductor contracture. CMI was independently diagnosed by a reference standard (magnetic resonance imaging [MRI]). All MRI scans were read by a musculoskeletal fellowship-trained radiologist. The sensitivity and specificity of each physical examination test alone and in combination were calculated based on this reference standard. RESULTS: A total of 81 patients were included in this study. MRI was positive for a CMI in 39 patients (48%) overall. Both the cross-body sit-up test and the presence of an adductor contracture were found to have a sensitivity of 100% (specificity, 3% for both). The external rotation Stinchfield test was found to have the highest specificity of 60% (sensitivity, 15%). The sensitivity of all 4 physical examination tests in combination was found to be 100% (specificity, 0%). CONCLUSION: Certain physical examination maneuvers can be used to assist in the diagnosis of a CMI. The cross-body sit-up test and the presence of an adductor contracture are highly sensitive but nonspecific tests for CMI and therefore should be used in conjunction with diagnostic imaging before deciding on an appropriate treatment course.

The Effectiveness of Negative Pressure Wound Therapy Versus Conventional Dressing in the Treatment of Open Fractures: A Systematic Review and Meta-Analysis.

OBJECTIVES: To compare the efficacy of negative pressure wound therapy (NPWT) versus conventional dressings (CD) in the management of open fractures. DATA SOURCES: A systematic search of English articles in the PubMed/MEDLINE, Embase, and the Cochrane Library through April 2019 comparing NPWT versus CD in the management of open fractures. STUDY SELECTION: Inclusion criteria were articles in English language, comparing NPWT with CD in skeletally mature individuals who had sustained an open fracture at any anatomical site, reporting on rates of deep infection, flap frequency, flap failure, nonunion, amputation, length of hospital, or intensive care unit stay. DATA EXTRACTION: Two authors independently extracted data from selected studies, and the data collected were compared with verify agreement. DATA SYNTHESIS: Pooled odds ratios were calculated for dichotomous outcomes, whereas continuous data were analyzed using the standard weighted mean difference. A random or fixed effect model was used depending on the level of heterogeneity between the studies. CONCLUSIONS: NPWT results in decreased likelihood of deep infection and flap failure compared with CD in the management of open fractures not directly amenable to early closure. LEVEL OF EVIDENCE: Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.

The long-term outcomes following internal fixation for intracapsular hip fractures in an Irish tertiary referral centre.

BACKGROUND: The burden associated with hip fractures is increasing worldwide. Arthroplasty procedures are more commonly performed for intracapsular fractures due to increased risk of compromise to the femoral head blood supply. However, we know from the Irish Hip Fracture Database that a significant proportion of these fractures undergo internal fixation. AIMS: We sought to investigate the long-term outcomes for these patients including revision rates, functional outcome and mortality rates. METHODS: All intracapsular fractures treated by internal fixation (IF) from 2005 to 2009 were identified. Pre-operative anatomical fracture location and level of fracture displacement was established. Hospital records were used to record mortality and revision rates. The modified Harris hip score was our primary functional outcome measure. RESULT: One hundred twelve intracapsular fractures underwent IF over a 5-year period. The mean age was 68.6 (range 14-95 years). A mean follow-up time of 8.15 years (range 6.7-10.1 years) was achieved. There was a 5-year mortality rate of 36.6%. There was a significantly higher revision rate in displaced fractures (24.4%) than in undisplaced fractures (11.1%) (p = 0.01). We found no difference in functional outcome between displaced fractures [85.9 (± 16.9)] and undisplaced fractures [86.01 (± 18.8)]. Those aged younger than 65 at the time of surgery had a significantly better MHHS (p = 0.02) at long-term follow-up; however, there was a revision rate of 43.8% in this group. CONCLUSION: Whilst a good functional outcome can be achieved with internal fixation, particularly in younger patients, the risk of requiring revision surgery approaches 50% for these patients.

Chronic Tophaceous Gout Presenting as Bilateral Knee Masses in an Adult Patient: A Case Report.

INTRODUCTION: Gout is a common disorder of uric acid metabolism that leads to the precipitation of monosodium urate crystals. It most commonly affects the first metatarsophalangeal joint but can also affect other joints such as knees, elbows, wrists, and ankles. Chronic gout can present as recurrent episodes of monoarticular or polyarticular inflammatory arthritis, tophaceous soft tissue deposits of monosodium urate crystals, uric acid renal calculi, and/or chronic nephropathy. CASE REPORT: We report the case of a 67-year-old Caucasian male patient with bilateral tophaceous gout to his knees involving the soft tissue and ulcerating skin breakdown to his left knee after an acute traumatic injury. Plain radiographs of the bilateral knees revealed large soft tissue masses anterior to the patella. Magnetic resonance imaging of the left knee was also performed which demonstrated heterogeneous masses consistent with tophi and peripheral enhancement with central necrosis. A diagnostic biopsy was performed to rule out malignancy the results confirmed gouty tophi. We report this case to note the atypical presentation of this disease. CONCLUSION: Chronic tophaceous gout presenting with ulcerating skin breakdown overlying a fungating tophaceous mass is uncommon considering the current availability of effective pharmaceutical treatments for hyperuricemia. Surgical intervention for tophaceous gout is seldom required and is traditionally reserved for atypical cases that present with deformities, severe pain, and joint destruction. Although ulcerative tophi are rare, they can have significant morbidity and greatly impact patients' quality of life. Surgical intervention was indicated in our patient to excise the mass and avoid infective complications.

Incidental Asymptomatic Fibular Stress Fractures Presenting as Varus Knee Osteoarthritis: A Case Report.

Stress fractures are often missed, especially in unusual clinical settings. We report on 2 patients who presented to our orthopedic surgery clinic with incidental findings of asymptomatic proximal fibular tension side stress fractures in severe longstanding varus osteoarthritic knees. Initial plain films demonstrated an expansile deformity of the proximal fibular shaft, and differential diagnosis included a healed or healing fracture versus possible neoplasm. Magnetic resonance imaging with and without gadolinium was utilized to rule out the latter prior to planned total knee arthroplasty.

Pain Control in Total Knee Arthroplasty.

As surgical techniques and pharmacology advance, the management of postoperative pain in patients undergoing total knee arthroplasty (TKA) continues to evolve. The current standards of care are composed of multimodal pain management including opioids, nonsteroidal anti-inflammatory drugs and gabapentinoids, peripheral nerve blocks, and periarticular injections. Newer modalities are composed of delayed release local anesthetics and cryoneurolysis. To summarize the current evidence-based treatment modalities and forecast changes in the management of patients having TKAs, we reviewed available data on: (1) oral analgesics; (2) periarticular injections; (3) peripheral nerve blocks; (4) multimodal regimens; and (5) newer modalities in post-TKA pain management. Multimodal analgesic regimens that target numerous pain pathways may provide the best pain management, rehabilitation, patient satisfaction, and reduce opioid use and related side effects. Periarticular injections of delayed-release local anesthetics may further enhance pain management.