AKT signaling modulates latent viral reservoir viability in HIV-1-infected blood-brain barrier pericytes.

Despite antiretroviral therapy (ART), chronic forms of HIV-associated neurocognitive disorders (HAND) affect an estimated 50% of individuals living with HIV, greatly impacting their quality of life. The prevailing theory of HAND progression posits that chronic inflammation arising from the activation of latent viral reservoirs leads to progressive damage in the central nervous system (CNS). Recent evidence indicates that blood-brain barrier (BBB) pericytes are capable of active HIV-1 infection; however, their latent infection has not been defined. Given their location and function, BBB pericytes are poised to be a key viral reservoir in the development of HAND. We present the first transcriptional analysis of uninfected, active, and latent human BBB pericytes, revealing distinct transcriptional phenotypes. In addition, we demonstrate that latent infection of BBB pericytes relies on AKT signaling for reservoir survival. These findings provide insight into the state of reservoir maintenance in the CNS during HIV-1 infection and provide novel targets for reservoir clearance.

Pericyte infection by HIV-1: a fatal attraction.

While HIV-1 is primarily an infection of CD4 + T cells, there is an emerging interest towards understanding how infection of other cell types can contribute to HIV-associated comorbidities. For HIV-1 to cross from the blood stream into tissues, the virus must come in direct contact with the vascular endothelium, including pericytes that envelope vascular endothelial cells. Pericytes are multifunctional cells that have been recognized for their essential role in angiogenesis, vessel maintenance, and blood flow rate. Most importantly, recent evidence has shown that pericytes can be a target of HIV-1 infection and support an active stage of the viral life cycle, with latency also suggested by in vitro data. Pericyte infection by HIV-1 has been confirmed in the postmortem human brains and in lungs from SIV-infected macaques. Moreover, pericyte dysfunction has been implicated in a variety of pathologies ranging from ischemic stroke to diabetes, which are common comorbidities among people with HIV-1. In this review, we discuss the role of pericytes during HIV-1 infection and their contribution to the progression of HIV-associated comorbidities.

Differential diagnosis of T2 hypointense masses in musculoskeletal MRI.

Many soft tissue masses have an indeterminate appearance on MRI, often displaying varying degrees and extent of T2 hyperintensity. However, a subset of neoplasms and tumor-like lesions may exhibit prominent areas of T2 hypointensity relative to skeletal muscle. The hypointensity observed on T2-weighted MRI can be caused by a variety of substances, including evolving blood products, calcifications or other inorganic crystals, or fibrous tissue. Carefully evaluating the presence and pattern of T2 hypointensity in soft tissue masses and considering potential causes in their associated clinical contexts can help to narrow the differential diagnosis among neoplastic and non-neoplastic possibilities. These include endometriosis, aneurysmal bone cysts, tenosynovial giant cell tumor, arteriovenous malformation and pseudoaneurysm, calcium pyrophosphate and hydroxyapatite deposition diseases, tumoral calcinosis, gout, amyloidosis, hemangiomas with phleboliths, low-grade fibromyxoid sarcoma, ossifying fibromyxoid tumor, collagenous fibroma, desmoid-type fibromatosis, myxofibrosarcoma, peripheral nerve sheath tumors, dedifferentiated liposarcoma, and treated sarcoma.

Optimal detection of scapholunate ligament tears with MRI.

Background Scapholunate interosseous ligament (SLIL) injuries can often be difficult to detect using magnetic resonance imaging (MRI), especially with older 1.0 and 1.5 Tesla magnets. Wrist arthroscopy is the gold standard for diagnosis of SLIL injuries, but is an invasive procedure with associated risks. Purpose To assess whether SLIL injuries can be more accurately detected using axial MRI sequences instead of coronal sequences. Material and Methods An institutional review board approved retrospective analysis of arthroscopic wrist surgeries performed at our institution. Patients that had a preoperative MRI performed at our university center using a 1.5 Tesla scanner with a dedicated wrist coil were included in the study. Three fellowship-trained musculoskeletal radiologists reviewed the axial sequences and coronal sequences independently. The accuracy of the coronal and axial sequences was compared with the arthroscopic/surgical findings. Result Twenty-six patients met the inclusion criteria. The sensitivity for SLIL tears was 79% and 65% for the axial and coronal sequences, respectively. The specificity was 82% for the axial and 69% for the coronal sequences, respectively. The positive and negative predictive values for the axial sequences were 76% and 84% respectively, compared to 68% and 71% for the coronal sequences, a statistically significant difference. Conclusion SLIL tears are more readily detectable on axial MRI sequences than coronal. Clinically, patients with radial-sided wrist pain and suspicion for SLIL tears should have the axial sequences scrutinized carefully. An otherwise normal study with the axial sequence being degraded by motion or other MRI artifacts might need repeat imaging.

Incidence of tendon entrapment and dislocation with calcaneus and pilon fractures on CT examination.

OBJECTIVE: To examine the association between tibial pilon and calcaneal fracture classification and tendon entrapment or dislocation. MATERIALS AND METHODS: After institutional review board approval, we retrospectively reviewed consecutive CT scans with calcaneal or pilon fractures from 5 years at a level 1 trauma center. We categorized calcaneal fractures according to the Sanders classification, and pilon fractures according to the Ruedi and Allgower and the Arbeitsgemeinschaft für Osteosynthesefragen-Orthopaedic Trauma Association (AO-OTA) classifications. Ankle tendons were assessed for dislocation or entrapment. Fisher's exact test was used for statistical analysis with significance at p < 0.05. RESULTS: A total of 312 fractures (91 pilon only, 193 calcaneal only, and 14 ankles with ipsilateral pilon and calcaneal fractures) were identified in 273 patients. Twenty-two pilon, 42 calcaneal, and nine combination fractures were associated with 99 occurrences of tendon entrapment or superior peroneal retinacular injury. Such findings were associated with multiple fractures (p = 0.002). Multifragmentary pilon fractures were associated with posterior tibial and flexor digitorum longus tendon entrapment (p < 0.0001 and p = 0.0003 for Ruedi/Allgower and AO-OTA, respectively), and multifragmentary Sanders type 3 or 4 calcaneal fractures were associated with superior peroneal retinacular injury (p = 0.0473) compared to simple fracture patterns. Thirty-nine percent of tendon entrapments or retinacular injuries were prospectively identified, 85 % by musculoskeletal radiologists (p < 0.0001). CONCLUSIONS: Approximately 25 % of calcaneal and pilon fractures were retrospectively identified to contain posteromedial tendon entrapment or superior peroneal retinacular injury. Radiologists should meticulously search for such injuries, particularly when analyzing multifragmentary and multiple fractures.

Benign and malignant tumors of the foot and ankle.

Pain and focal masses in the foot and ankle are frequently encountered and often initiate a workup including imaging. It is important to differentiate benign lesions from aggressive benign or malignant lesions. In this review, multiple examples of osseous and soft tissue tumors of the foot and ankle will be presented. Additionally, the compartmental anatomy of the foot and ankle will be discussed in terms of its relevance for percutaneous biopsy planning and eventual surgery. Finally, a general overview of the surgical management of benign, benign aggressive and malignant tumors of the foot and ankle will be discussed.

"Ilizarov" external fixation: what the radiologist needs to know.

Circular external fixation, including the Ilizarov method, is a complex and often long-term treatment used for various orthopedic conditions. Due to the complexity of the hardware, frequent postoperative complications, and the potential for significant radiographic changes between visits, it is important for the radiologist to have a basic understanding of ring fixators. This publication reviews indications for external fixation versus internal fixation and whether to use a circular or uniplanar construct if external fixation is elected. Indications for and characteristics of static circular frames, intercalary and non-intercalary transport frames, and deformity circular frames will also be discussed. While general similarities exist between frame types, each has unique components of which the radiologist must be aware. An emphasis is placed on the important features and complications that arise during treatment.

Ischiofemoral impingement syndrome: a meta-analysis.

OBJECTIVE: The aims of this article are to review the imaging characteristics of ischiofemoral impingement (IFI), summarize measurement thresholds for radiologic diagnosis based on a meta-analysis of the literature and raise awareness among radiologists and clinicians of this entity. MATERIALS AND METHODS: A PubMed search restricted to the English language containing the keywords "ischiofemoral impingement" and "quadratus femoris MRI" was performed, and citations in these articles were also used to identify a total of 27 studies discussing ischiofemoral impingement. After excluding case reports and non-representative studies, there were five remaining articles including 193 hip MRIs of IFI in 154 subjects (133 female, 21 male) and 135 asymptomatic control hip MRIs from 74 subjects (55 female, 19 male). Additionally, we performed a retrospective database search of pelvic and hip MRI reports from our institution including the terms "quadratus femoris" or "ischiofemoral impingement" from a 9-year period and 24 hip MRIs from 21 patients (18 female, 3 male) with IFI with 5 asymptomatic contralateral control hip MRIs identified. In all, 217 hip MRIs of IFI and 140 control cases were included. A meta-analysis of these hip MRIs was conducted to determine optimal thresholds of the ischiofemoral space (IFS) and quadratus femoris space (QFS) for identifying IFI. RESULTS: Cases of IFI showed significantly smaller IFS and QFS compared to controls (14.91 ± 4.8 versus 26.01 ± 7.98 and 9.57 ± 3.7 versus 15.97 ± 6.07, measured in mm, respectively, p < 0.0001 for both). Pooled analysis revealed that for IFS, using a cutoff of ≤ 15 mm yielded a sensitivity of 76.9%, specificity of 81.0% and overall accuracy of 78.3%. For QFS, a cutoff of ≤ 10.0 mm resulted in 78.7% sensitivity, 74.1% specificity and 77.1% overall accuracy. CONCLUSION: IFI is a potential cause of hip pain that can be accurately diagnosed with MRI in conjunction with clinical findings. Using the proposed measurement thresholds may better identify patients with this impingement syndrome so that optimal treatment options can be pursued.

Fate and distribution of the octyl- and nonylphenol ethoxylates and some carboxylated transformation products in the Back River, Maryland.

The concentrations of nonylphenol (NP), octylphenol (OP), their ethoxylates (NP1-16EO and OP1-5EO respectively) and some of their carboxylated derivatives (NP1-2EC and OP1EC quantitatively; NP3-4EC and OP2EC qualitatively) were measured in water samples from the Back River, MD, a sub-estuary of the Chesapeake Bay that receives effluent from a large municipal wastewater treatment plant. The most abundant of the alkylphenolic compounds (APEs) were the carboxylates (APECs, >95% of the APE-related compounds), followed by NP in September and October, and NP1-2EO in March. Ratios of the different compounds' concentrations provide evidence for the season dependency of two different degradation pathways. NP concentrations found in this study, 0.087-0.69 microg L(-1), were below acute toxicity thresholds, and below US EPA water quality criteria; although in March, concentrations were close to 40% of the chronic exposure limit for saltwater, 1.7 microg L(-1). A simple steady-state model of the Back River suggested that total NPE concentrations in the estuary varied in accordance with concentrations in the wastewater treatment plant effluent, especially in the case of the APECs. This model also suggested that in the fall sampling events, when rain occurred, APEOs present in particulate matter might have originated in the river's tributaries rather than the treatment plant.

Instability of the first metatarsal-cuneiform joint: diagnosis and discussion of an independent pain generator in the foot.

BACKGROUND: First metatarsocuneiform (MC) instability is recognized as a pathologic contributor to hallux valgus. There are no studies identifying the first MC joint as an independent pain generator in the foot that may require surgical arthrodesis for its management. MATERIALS AND METHODS: The authors reviewed the records of all patients with this newly described pathology in the first MC joint. There were 61 patients with 85 feet who underwent a fluoroscopically guided local anesthetic injection into the first metatarsocuneiform joint to assess pain relief. Patient's complaints, physical exam findings, treatment decisions, patient characteristics, and radiographic findings were evaluated. RESULTS: Seventy-nine percent of patients (67/85) injected had relief of their symptoms. Eight or these 67 patients were eventually treated with first MC arthrodesis with complete relief of symptoms. The average time from onset of symptoms to presentation was 21 (range, 1 to 72) months. Eighty-five percent of feet (72/85) had multiple previous diagnoses. Radiographic plantar widening of the first M-C joint on weightbearing views was inconsistent with pathology. CONCLUSION: The first MC joint is an independent pain generator in the foot that can have variable presentations. Radiographic data can often be helpful, but clinical exam findings are paramount in the diagnosis. Fluoroscopically-guided long acting local anesthetic injections of this joint are helpful in the diagnosis, especially in the patient with multiple possible pain generators in the foot and ankle. Failure to recognize the first MC joint as a source of pain may lead to delay in treatment, misdiagnosis, and mistreatment of foot pathology.

Comparison of MRI and local anesthetic tendon sheath injection in the diagnosis of posterior tibial tendon tenosynovitis.

BACKGROUND: The modalities currently available to clinicians to confirm the clinical suspicion of posterior tibial tendinitis include MRI, CT, sonography, tenography, and local anesthetic tendon sheath injections. There are no reports in the literature comparing local anesthetic tendon sheath injection to MRI as tools for diagnosing posterior tibial tenosynovitis. METHODS: The authors reviewed the records of all patients with stage 1 posterior tibial tendon dysfunction between the dates of September 1, 2001, to November 21, 2004. Fifteen patients (17 ankles) had a local anesthetic injection into the posterior tibial tendon sheath and MRI for clinically suspected tenosynovitis of the posterior tibial tendon. RESULTS: Seventeen (100%) of 17 ankles had complete relief of symptoms after the local anesthetic tendon sheath injections. Fifteen (88%) of 17 ankles had abnormally increased fluid signal within the posterior tibial tendon sheath seen on MRI. Two of two ankles (100%), after having negative MRI findings, had complete relief with a local anesthetic tendon sheath injection. In addition, conservative treatment failed in these two patients, and they subsequently had tenosynovectomy with gross confirmation at surgery of inflammatory changes within the tendon sheath. These two patients had complete symptom relief after tenosynovectomy. CONCLUSIONS: Local tendon sheath injections and MRI are both reliable diagnostic tools. Injection of the posterior tibial tendon is an accurate, safe, and sensitive modality useful in patients in whom MRI studies are negative in the face of continued clinical suspicion.

Multimodality Approach to a Stener Lesion: Radiographic, Ultrasound, Magnetic Resonance Imaging, and Surgical Correlation.

The ulnar collateral ligament (UCL) of the thumb metacarpophalangeal joint is a static stabilizer that may rupture from a hyperabduction injury. Although some UCL tears may heal with immobilization, outcomes are worse for Stener lesions, in which the proximal ligament stump slips out from beneath the adductor pollicis aponeurosis and is entrapped proximal and superficial to the aponeurosis, preventing primary healing. We report the case of a patient with a Stener lesion with radiographic, ultrasound, and magnetic resonance imaging correlation, subsequently confirmed with intraoperative photographs. Physicians must be familiar with the regional anatomy to understand the injury pathogenesis and the need for surgical intervention to optimize patient outcomes.

Little Leaguer's shoulder.

A case of Little Leaguer's shoulder (LLS) in a 12-year-old male is presented. Classically, LLS is an overuse injury affecting adolescent pitchers. The diagnosis is the result of a thorough history, physical examination, and radiographic evaluation. Clinicians unfamiliar with LLS may fail to detect this injury and order a magnetic resonance imaging (MRI) study without radiographs. The objective of this case report is to help radiologists become more familiar with the MRI and radiographic findings of LLS.

Value of radiographs in the initial evaluation of nontraumatic adult heel pain.

BACKGROUND: Adult patients with nontraumatic plantar heel pain often present to orthopaedic surgeons for evaluation. A thorough history and physical examination are often sufficient for diagnosis, yet radiographs usually are ordered during the initial evaluation. The purpose of this study was to evaluate the value and cost-effectiveness of these radiographs. METHODS: A retrospective chart and radiographic review of 157 consecutive adults (215 heels) presenting with nontraumatic heel pain was done to evaluate the utility of routine radiographs in the initial evaluation. RESULTS: The most common diagnosis was plantar fasciitis (80.9%, 174 of 215). Radiographs were normal in (17.2%, 37 of 215), and incidental radiographic findings were observed in 81.4% (175 of 215). The most common incidental findings were plantar calcaneal spurs (59.5%, 128 of 215) and Achilles spurs (46.5%, 100 of 215). Only (2%, 4 of 215) of all patients had abnormal findings that prompted further evaluation. CONCLUSIONS: Routine radiographs are of limited value in the initial evaluation of nontraumatic plantar heel pain in adults and were not necessary in the initial evaluation. Radiographs should be reserved for patients who do not improve as expected or present with an unusual history or confounding physical findings.

Carcinoembryonic antigen-immunoglobulin Fc fusion protein (CEA-Fc) for identification and activation of anti-CEA immunoglobulin-T-cell receptor-modified T cells, representative of a new class of Ig fusion proteins.

Chimeric immunoglobulin-T-cell receptor (IgTCR)-modified T cells ("designer T cells") kill tumor cells based on antibody-redirected recognition of tumor-associated antigen. Anti-carcinoembryonic antigen (CEA) designer T cells have been prepared and applied in adoptive cellular immunotherapy regimens for CEA-positive cancers. A CEA-immunoglobulin Fc (CEA-Fc) fusion protein was created from the A3B3 region of CEA and the Fc portion of human IgG for the purposes of activation and detection of anti-CEA designer T cells. CEA-Fc was expressed at high yield in CHO cells and purified to homogeneity in a single step on a protein A affinity column. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis revealed that CEA-Fc formed disulfide-linked dimers with a molecular weight of about 170 kDa and a monomer size of 85kDa. The A3B3 CEA component of the CEA-Fc bound to anti-CEA monoclonal antibody MN-14, as well as to the single-chain Fv (sFv) derived from this antibody that was expressed in the IgTCR on the surface of designer T cells. The Fc portion of CEA-Fc was recognized by anti-human IgG Fc antibody and bound by human monocyte Fc receptors. CEA-Fc activated the anti-CEA designer T cells as plate-bound or monocyte-bound form but not as soluble form, as measured by CD69 expression and T-cell proliferation. Our results indicate that the CEA-Fc fusion protein can be used to detect the expression of the anti-CEA IgTCR chimeric receptors on the modified T cells, as well as to serve as an antigen to activate the anti-CEA IgTCR modified T cells. CEA-Fc is the prototype for a new class of antigen-Fc molecules that may significantly augment the analytic and therapeutic goals of adoptive designer T-cell immunotherapies.

Tip of the iceberg: subtle findings on traumatic knee radiographs portend significant injury.

Despite their low clinical yield, knee radiographs are among the most commonly acquired radiographic trauma studies in the emergency department. Although obvious fractures may be present, several subtler radiographic findings suggest internal derangement and significant injury. In this review, we provide an overview of traumatic knee radiography, including anatomy, acquisition techniques, and pitfalls with associated magnetic resonance imaging correlation when available.

Ischiofemoral impingement and the utility of full-range-of-motion magnetic resonance imaging in its detection.

Ischiofemoral impingement is a cause of hip pain resulting from compression on the quadratus femoris muscle between the ischium and femoral lesser trochanter. The most widely accepted diagnostic criterion is hip pain with isolated edema-like signal in the ipsilateral quadratus femoris muscle on magnetic resonance imaging (MRI). Additional criteria based on measurements of the ischiofemoral and quadratus femoris spaces have recently been suggested. However, because these measurements are positioning-dependent, we used full-range-of-motion MRI to increase the diagnostic yield. By evaluating through a range of motion, we detected a case of impingement involving the ischial tuberosity and the lesser trochanter, with probable contributing impingement between the ischial tuberosity and greater trochanter. In this article, we briefly review the topic of ischiofemoral impingement, provide an example of how range-of-motion MRI can improve diagnostic accuracy, describe our protocol, and propose exploring the need for an expanded definition of the impingement criteria.

Imaging of tarsal navicular disorders: a pictorial review.

The tarsal navicular is a bone within the midfoot that plays a critical role in maintaining the arch of the foot. This bone is clinically relevant because it may be affected by a wide array of pathologies. Our approach includes a detailed description of the imaging characteristics and disorders affecting the tarsal navicular. Organization includes (a) normal imaging, (b) accessory ossicles, (c) coalition, (d) fractures, (e) Kohler's disease, (f) osteonecrosis, (g) osteochondral lesions, (h) arthropathies, and (i) tumors. The purpose of this article is to discuss normal variants and pathological processes that can affect the tarsal navicular, with emphasis on the often-overlooked imaging findings.

Prefemoral fat pad impingement syndrome: identification and diagnosis.

Fat pad impingement syndrome refers to anterior knee pain caused by hemorrhage, inflammation, fibrosis and/or degeneration of the anterior knee fat pads. Symptomatic impingement of the prefemoral fat pad can be clinically significant but easily overlooked on magnetic resonance imaging, unless looked for. It should be evaluated in patients with persistent anterior knee pain, particulary if accompanied with mechanical symptoms and lack of intra-articular pathology.