Lupus autoantibodies initiate neuroinflammation sustained by continuous HMGB1:RAGE signaling and reversed by increased LAIR-1 expression.

Cognitive impairment is a frequent manifestation of neuropsychiatric systemic lupus erythematosus, present in up to 80% of patients and leading to a diminished quality of life. In the present study, we used a model of lupus-like cognitive impairment that is initiated when antibodies that crossreact with excitatory neuronal receptors penetrate the hippocampus, causing immediate, self-limited, excitotoxic death of hippocampal neurons, which is then followed by a significant loss of dendritic complexity in surviving neurons. This injury creates a maladaptive equilibrium that is sustained in mice for at least 1 year. We identified a feedforward loop of microglial activation and microglia-dependent synapse elimination dependent on neuronal secretion of high mobility group box 1 protein (HMGB1) which binds the receptor for advanced glycation end products (RAGE) and leads to microglial secretion of C1q, upregulation of interleukin-10 with consequent downregulation of leukocyte-associated immunoglobulin-like receptor 1 (LAIR-1), an inhibitory receptor for C1q. Treatment with a centrally acting angiotensin-converting enzyme inhibitor or with an angiotensin-receptor blocker restored a healthy equilibrium, microglial quiescence and intact spatial memory.

Tongue necrosis secondary to giant cell arteritis, successfully treated with tocilizumab: a case report.

BACKGROUND: Giant Cell Arteritis (GCA) is a large vessel vasculitis that most commonly presents with headache, scalp tenderness, jaw claudication, and vision changes. Various other, less common, manifestations have been reported in the literature such as scalp and tongue necrosis. Though most patients respond to corticosteroids, some cases of GCA are refractory to the high doses of corticosteroids. CASE PRESENTATION: We present a 73-year-old female with GCA refractory to corticosteroids presenting with tongue necrosis. This patient significantly improved with a dose of tocilizumab, an IL-6 inhibitor. CONCLUSION: To the best of our knowledge, this is the first case report of a patient with refractory GCA presenting with tongue necrosis that had rapid improvement with tocilizumab. Prompt diagnosis and treatment can prevent severe outcomes such as tongue amputation in GCA patients with tongue necrosis, and tocilizumab may be effective for corticosteroid-refractory cases.

TUBERCULOUS CHOROIDITIS IN PATIENT WITH VOGT-KOYANAGI-HARADA DISEASE.

PURPOSE: To describe a novel case of intraocular tuberculosis (TB) arising in a patient undergoing treatment for Vogt-Koyanagi-Harada disease, and to highlight the use of spectral domain optical coherence tomography for helping confirm the diagnosis and monitor treatment response. METHODS: Case report of a patient with Vogt-Koyanagi-Harada disease on prednisone, with acute clinical changes suspicious for bilateral tuberculous choroiditis. Spectral optical coherence tomography, fundus photography, and B-scan ultrasonography were all used to capture the acute lesions, and to monitor their responses after initiation of anti-TB therapy. RESULTS: New subretinal lesions arose bilaterally, as characterized by spectral domain optical coherence tomography, and appeared to regress after a first round of anti-TB therapy, thereby helping confirm the presumed diagnosis of intraocular TB. A new peripheral choroidal lesion arose shortly after temporary cessation of antimicrobial treatment, and again regressed once four-drug therapy was instituted, with no recurrent lesions thereafter. CONCLUSION: The use of multimodal imaging was instrumental in the management of a rare case of intraocular TB arising in the setting of underlying Vogt-Koyanagi-Harada disease.

Using the Mouse to Model Human Diseases: Cognitive Impairment in Systemic Lupus Erythematosus.

In this 2020 Dunlop-Dottridge Lecture, the authors discuss cognitive impairment (CI), one of the most prevalent neuropsychiatric syndromes in systemic lupus erythematosus (SLE). Patients often report CI as the most bothersome disease-related manifestation, with a great effect on their quality of life. Nevertheless, studies focusing on CI remain scarce and no effective targeted therapy has been identified. We herein present murine models of CI in SLE with insights into the pathogenesis of this condition as well as the role of the renin angiotensin system in microglial activation. We will discuss the role of neuroimaging as a useful objective assessment tool, describing our experience in previous and ongoing clinical trials of CI in patients with SLE.

Orbital compartment syndrome as the first manifestation of SLE.

The occurrence of orbital compartment syndrome is a rare and unusual complication of systemic lupus erythematosus (SLE). Patients will present with symptoms of ocular pain and diplopia and visible signs of proptosis. The condition is considered an ophthalmological emergency because the myositis involving the ocular muscles can cause irrevocable damage to the retina and optic disk, potentially leading to blindness. We report a case of a young African American male who developed orbital myositis with compartment syndrome as his initial manifestation of SLE. The patient underwent an emergent orbital decompression, followed by prompt initiation of immunosuppressant medications. To our knowledge, this is the first report of a case of myositis secondary to SLE complicated by compartment syndrome of the orbit.

Inflammatory arthritis: a unique presentation of human anaplasmosis.

Human granulocytic anaplasmosis (HGA) is a tickborne rickettsial disease caused by the bacterium Anaplasma phagocytophilum. Reported cases have increased with the highest incidence in the Northeast. To our knowledge, this is the first report of anaplasmosis associated with an inflammatory arthritis. A 64-year-old man, with a history of Crohn's disease controlled on budesonide, presented to the emergency room in August 2017 with a week history of headache, sore throat, fever, myalgias, rash, and joint pain. There was no clinical evidence of active Crohn's disease. He lives in Nassau County and participates in outdoor activities. His exam was notable for a maculopapular rash over the trunk, arms, and thighs as well as synovitis of several proximal interphalangeal joints. Lab tests revealed transaminitis and elevated inflammatory markers. When evaluated by rheumatology, he had marked polyarthritis of wrists and hands as well as extremely painful motion of the shoulders, elbows, hips, knees, and ankles despite ibuprofen. Prednisone 20 mg daily resulted in significant improvement in his arthritis. Because of an Anaplasma phagocytophilum IgM of 1:320 (normal < 1:20; IgG < 1:64; normal < 1:64) that returned few weeks after presentation, he was prescribed 4 weeks of doxycycline. Convalescent Anaplasma serologies revealed negative IgM and IgG > 1:320. He fully recovered and was able to discontinue steroids. HGA presents acutely with a spectrum of manifestations ranging from a flu-like illness to severe complications such as respiratory failure. Myalgias and arthralgias are common, but an inflammatory arthritis has not been described.

Cutaneous Necrotizing Vasculitis and Leukopenia in a Cocaine User: Is Levamisole the Culprit?

Levamisole is an antihelminthic drug banned by the US Food and Drug Administration (FDA) in 2000 because of its dangerous side effects. Over the past few years, it has been identified as an adulterant in cocaine and reported to cause cutaneous vasculitis in cocaine users. The health burden of levamisole is serious since it is estimated that over 5 million Americans use cocaine and that 70% of the cocaine used in the USA contains levamisole. In this paper we report the case of a 23-year-old female cocaine user that presented with purpuric rash and skin necrosis, found to have positive c-ANCA and anti-proteinase 3 antibodies. Her skin biopsy showed fibroconnective tissue with signs of necrosis, acute and chronic inflammation, and thrombus formation. She was diagnosed with levamisole-induced vasculitis and successfully treated with withdrawal of cocaine use and local wound care.

Incidence and prevalence of hepatitis B and hepatitis C viruses in hemodialysis patients in Lebanon.

AIM: To determine the incidence and the prevalence of hepatitis B and C viral infections in patients on hemodialysis (HD) across Lebanon. METHODS: We reviewed the data registry at the Lebanese Ministry of Public Health where records of monthly hepatitis B surface antigen (HBsAg) and hepatitis C virus (HCV) serology are reported from 60 affiliated HD centers across Lebanon. All patients who were on HD or who started HD between October 2010 and July 2012 were included in the study. Patients from seven HD centers were excluded due to inadequate and incomplete results reporting. During the selected period, HBsAg and HCV serology were available for 3769 patients from 53 HD centers distributed at all Lebanese governorates. The prevalence was calculated by dividing the number of patients with positive HBsAg or HCV serology to the total number of patients. The Incidence was calculated by dividing the number of newly acquired infection to number of patients-years (p-y). Incidence rates at different governorates were compared to each other using two tailed Z test and a P value of < 0.05 was considered significant. RESULTS: Sixty out of 3769 HD patients were found to have positive HBS Ag and 177 out of 3769 were positive for HCV Antibodies. The prevalence of hepatitis B virus (HBV) and HCV in HD patients across Lebanon was 1.6%, and 4.7%, respectively. The comparison of prevalence according to geographic distribution could not be done accurately due to the frequent shift of patients between dialysis centers at different governorates. The incidence rate was 0.27 per 100 p-y for HBV and 0.37 per 100 p-y for HCV. There was no significant difference concerning the incidence of HBV between HD centers at different governorates (all P values > 0.1), but this difference was highly significant concerning the incidence rates of HCV which occurred predominantly in the southern centers (1.47 per 100 p-y) with a P value of 0.00068 and 0.00374 when compared to Mount Lebanon (0.21 per 100 p-y) and the Northern centers (0.19 per 100 p-y), respectively. CONCLUSION: The incidence rate of HBV and HCV is very low in the Lebanese HD centers and their prevalence is decreasing over the last two decades.

Warburg's effect on solid tumors.

Lactic acidosis is the result of imbalance between the systemic formation of lactate and its hepatic metabolism. In cancer patients, lactic acidosis is mainly associated with hematologic malignancies (leukemia and lymphomas) and the mechanism is known as Warburg's effect. We report a 76-year-old male known to have hypertension and coronary artery disease, who presented with abdominal distension and lactic acidosis. His initial evaluation showed multiple liver masses that were biopsied and the patient was diagnosed with undifferentiated carcinoma of unknown primary, involving the liver. The patient had progression of lactic acidosis leading to his death on day-15. As the lactic acidosis was not in the setting of hypoxia or hemodynamic instability, we made the diagnosis of malignancy-associated type B lactic acidosis, also known as the Warburg's effect. Warburg's effect can occur in solid cancer if the tumor involves the liver. It has bad prognostic implications. The use of intravenous bicarbonate as a temporary measure is of controversial benefit, as it can potentially worsen the metabolic acidosis and its use should be limited to patients with very low pH. In cancer patients, the use of lactatebased intravenous fluids can be potentially harmful and can increase the risk of tumor metastasis, at least in animal malignancy models.

Impact of a 3-day OSCE workshop on Iraqi physicians.

BACKGROUND AND OBJECTIVES: Following a severe hardship for the past 4 decades, the Iraqi Ministry of Health initiated many activities to enhance the knowledge and skills of health professionals. The American University of Beirut was approached to deliver a workshop to update the skills of Iraqi physicians in constructing an Objective Structured Clinical Examination (OSCE). METHODS: This is a descriptive study of the 3-day workshop delivered to Iraqi physicians as train the trainer. The participants were given reading material and participated in interactive hands-on exercises. Performance was determined by direct observation of participants performing a mock OSCE. Pretests and posttests were conducted to assess change in knowledge. RESULTS: The participants demonstrated a significant improvement in their mean score of the posttest in comparison to pretest (8.6 versus 6.4, respectively). Moreover, they revealed mastery of the OSCE in the final mock OSCE activity. The participants highly evaluated the workshop and were positive in their future ability to conduct an OSCE. CONCLUSIONS: Adopting an interactive hands-on workshop to train the trainer is feasible and appears to be effective.

Performances of a bent-crystal spectrometer adapted to resonant x-ray emission measurements on gas-phase samples.

We describe a bent-crystal spectrometer adapted to measure x-ray emission resulting from core-level excitation of gas-phase molecules in the 0.8-8 keV energy range. The spectrometer is based on the Johann principle, and uses a microfocused photon beam to provide high-resolution (resolving power of approximately 7500). A gas cell was designed to hold a high-pressure (300 mbar) sample of gas while maintaining a high vacuum (10(-9) mbar) in the chamber. The cell was designed to optimize the counting rate (2000 cts/s at the maximum of the Cl Kalpha emission line), while minimizing self-absorption. Example of the Kalpha emission lines of CH(3)Cl molecules is presented to illustrate the capabilities of this new instrument.