Atul Khasnis

The role of optical coherence tomography in vascular medicine

Abstract Optical coherence tomography (OCT) is an emerging imaging modality that provides high-resolution, microstructural information on atherosclerotic plaques in biological systems. Intracoronary OCT can identify thin-cap fibroatheroma and other vulnerable plaques that may be responsible for acute coronary events. These characteristics make OCT helpful in guiding coronary management and interventions, including stent apposition and early identification of procedure-related complications. OCT is being assessed for its potential role in carotid plaque characterization and in the diagnosis of peripheral arterial atherosclerosis. Its current use in studying carotid and cerebral vasculature and in the diagnosis of peripheral arterial diseases is limited and ill defined, but it is finding increasing application in these areas. Its performance can be further improved by increasing the signal to noise ratio and by using dynamic focus tracking techniques. It can potentially be used to monitor the progression and regression of atherosclerosis in the coronary, cerebral and peripheral vasculature. New indications for its use in vascular medicine are emerging as its technology continues to improve over time.

Levetiracetam for managing neurologic and psychiatric disorders

PURPOSE The role of levetiracetam in different epileptic, nonepileptic, neurologic, and psychiatric disorders is discussed. SUMMARY Levetiracetam, an antiepileptic drug (AED), was first approved as an adjunctive therapy for the treatment of partial epilepsy in adults. It is currently being used in the treatment of multiple seizure disorders, including generalized tonic-clonic; absence; myoclonic, especially juvenile myoclonic; Lennox-Gastaut syndrome; and refractory epilepsy in children and adults. Data are emerging on possible uses of levetiracetam outside the realm of epilepsy because of its unique mechanisms of action. There is preliminary evidence about the efficacy of levetiracetam in the treatment of different psychiatric disorders, including anxiety, panic, stress, mood and bipolar, autism, and Tourettes syndrome. The most serious adverse effects associated with levetiracetam use are behavioral in nature and might be more common in patients with a history of psychiatric and neurobehavioral problems. CONCLUSION Levetiracetam is an effective AED with potential benefits in other neurologic and psychiatric disorders. The benefit-risk ratio in an individual patient with a specific condition should be used to determine its optimal use. Levetiracetams use in nonepileptic conditions is not recommended until more data become available from larger trials.

Vasculitis Involving the Breast : A Clinical and Histopathologic Analysis of 34 Patients

Vasculitis of the breast (VB) may be an isolated finding or a manifestation of systemic vasculitis. In the current study we sought to characterize isolated VB (IVB) and compare it to VB in the setting of systemic vasculitis. We studied VB cases in the literature and patients cared for at our institution. We analyzed clinical, laboratory, and histologic features (including vessel size and type of inflammatory infiltrates); course of illness; biopsy procedure; and treatment. Based on the presence of localized or systemic disease at the time of disease presentation and during the follow-up, we divided patients into 3 groups: IVB (Group 1), VB with proven or indirect evidence of systemic vasculitis (Group 2), and VB with possible systemic involvement (Group 3). We identified a total of 34 cases of VB (30 from PubMed [National Library of Medicine, Bethesda, MD] and 4 from our pathology database). All patients presented with breast lesions, which were the only expression of disease in 16 (47%). Eighteen, 6, and 10 patients belonged to Group 1, 2, and 3, respectively. Constitutional symptoms were present less often in Group 1. Musculoskeletal symptoms occurred only in Groups 2 and 3. Patients in Groups 2 and 3 had higher erythrocyte sedimentation rates and lower hemoglobin levels, and also received corticosteroids more frequently than those in Group 1. No differences were found in the other analyzed parameters between groups. In summary, VB is uncommon, and in about half of the cases, occurs in the form of IVB. Histologic characteristics do not correlate with disease extent. In IVB patients, constitutional and musculoskeletal manifestations are usually absent. Such patients generally do not require systemic therapy and may be cured by resection alone. Abbreviations: ESR = erythrocyte sedimentation rate, IVB = isolated vasculitis of the breast, VB = vasculitis of the breast.

Tumor necrosis factor inhibitors and lung disease: a paradox of efficacy and risk.

OBJECTIVE Tumor necrosis factor inhibitors (TNFi) are being increasingly used for a wide range of indications. There are increasing reports of pulmonary toxicity related to the use of TNFi. In this review, we have attempted to synthesize the available literature regarding noninfectious complications related to TNFi use. METHODS We reviewed case reports, case series, and clinical trials accessed from the PubMed database (www.pubmed.gov), European League Against Rheumatism web archive (http://www.abstracts2view.com/eular/index.php), and the British Society of Rheumatology Biologics Register Newsletter website (http://www.rheumatology.org.uk/publications) using 23 search terms. RESULTS There are increasing data available about use of TNFi in treatment of systemic inflammatory rheumatologic disorders and their attempted use for various pulmonary indications. Currently reported noninfectious pulmonary complications related to TNFi use include most commonly granulomatous disease and pulmonary fibrosis/interstitial lung disease and rarely alveolar hemorrhage and antisynthetase syndrome. De novo granulomatous disease seems to be mostly reversible, whereas pulmonary fibrosis carries the worst prognosis especially in the setting of prior lung fibrosis. CONCLUSIONS Serious and potentially fatal pulmonary toxicity has been reported during the use of TNFi, specifically from pulmonary fibrosis. Increased awareness during trial design and increased postmarketing surveillance is needed to provide more information about the epidemiology of these complications. Early recognition of these complications may help avert therapeutic misadventures.

Testicular vasculitis: findings differentiating isolated disease from systemic disease in 72 patients.

Testicular vasculitis (TV) may be part of systemic (testicular) vasculitis (STV) or may exist as single-organ/isolated (testicular) vasculitis (ITV). In the current study we sought to identify clinical and histologic features that distinguish STV from ITV. The distinction was deemed important because it is already well established that in other forms of single organ vasculitis, surgical therapy alone may be curative. We identified patients with biopsy-proven TV from pathology databases from our institution and from an English-language PubMed search. Patients were included if data were available to determine TV extent confidently. Data recorded included clinical, laboratory, and histologic features; treatment; and clinical follow-up. The study included 72 patients with TV (mean age, 42 yr; range, 4–78 yr) (7 from our institution). About 74% of patients presented with painful testicular swelling/mass, 10% with a painless testicular swelling/mass, and 4% with epididymal swelling/mass. Eleven percent had no testicular complaints and vasculitis was discovered at autopsy or in other surgical interventions. Vasculitis involved the testicle in 80.3% of cases, the epididymis in 44.6%, and the spermatic cord in 30.6%. Thirty-seven (51%) patients had ITV and 35 (49%) had STV. No differences between ITV and STV patients were found in regards to age, presenting testicular features, duration of testicular symptoms, and time of follow-up. Compared to ITV patients, STV patients presented more often with constitutional/musculoskeletal symptoms (74.3% vs. 8.3%, respectively; p = 0.0001), elevated erythrocyte sedimentation rate (94.7% vs. 16%; p = 0.0001), and anemia (50% vs. 0%; p = 0.0001). Neoplasm was more frequently suspected in ITV than in STV (74.2% vs. 31.6%; p = 0.001), but only occurred in 2 ITV patients. Long-term glucocorticoid therapy was given only to STV patients, and 59.1% of them also received cytotoxic agents. ITV was diagnosed more often by orchiectomy (81.1% vs. 42.9%; p = 0.001) and less frequently by testicular biopsy (2.7% vs. 28.6%; p = 0.003) than STV. Nongranulomatous inflammation affecting medium-sized vessels occurred in most patients with both ITV and STV. Among STV, polyarteritis nodosa was the most frequently diagnosed (63%), followed by Wegener granulomatosis (17%). In summary, TV occurs as ITV in men usually presenting with a testicular mass in the absence of systemic symptoms and normal laboratory results. In most ITV patients, a testicular neoplasm is initially suspected, and TV is an unexpected finding. After surgical removal, ITV does not require systemic therapy. Polyarteritis nodosa is the systemic vasculitis most frequently associated with testicular involvement. AbbreviationsACR = American College of RheumatologyANCA= antineutrophil cytoplasmic antibodiesCRP = C-reactive proteinESR = erythrocyte sedimentation rateGC = glucocorticoidsHBV = hepatitis B virusHCV = hepatitis C virusITV = isolated testicular vasculitisMR = magnetic resonancePAN = polyarteritis nodosaSTV = systemic vasculitis with testicular involvementTV = testicular vasculitisWG = Wegener granulomatosis

Left Atrial Appendage Closure in Atrial Fibrillation: A World without Anticoagulation?

Atrial Fibrillation (AF) is a common arrhythmia with an incidence that is as high as 10% in the elderly population. Given the large proportion of strokes caused by AF as well as the associated morbidity and mortality, reducing stroke burden is the most important part of AF management. While warfarin significantly reduces the risk of AF-related stroke, perceived bleeding risks and compliance limit its widespread use in the high-risk AF population. The left atrial appendage is believed to be the “culprit” for thrombogenesis in nonvalvular AF and is a new therapeutic target for stroke prevention. The purpose of this review is to explore the evolving field of percutaneous LAA occlusion. After briefly highlighting the risk of stroke with AF, problems with warfarin, and the role of the LAA in clot formation, this article discusses the feasibility and efficacy of various devices which have been developed for percutaneous LAA occlusion.

Statins and the reduction of sudden cardiac death: antiarrhythmic or anti-ischemic effect?

Sudden cardiac death is an important cause of cardiovascular mortality with the majority of cases occurring in low-risk groups. HMG-CoA reductase inhibitors (statins) have recently been shown to reduce the incidence of ventricular tachycardia (VT)/fibrillation (VF) and sudden cardiac death, and this has been attributed to their pleiotropic effects. However, it is unclear whether this occurs through an ‘indirect’ anti-ischemic or ‘direct’ antiarrhythmic effect. We systematically reviewed articles published on MEDLINE between January 1996 and December 2009 focusing on the reduction of VT/VF and sudden cardiac death by statins and the potential mechanisms. Studies reporting sudden cardiac death or VT/VF outcomes with statin use (n = 23) or the pathophysiology of sudden cardiac death reduction by statins (n = 19) were included. We found that statins have been shown to reduce VT/VF and sudden cardiac death only in subjects with underlying coronary artery disease or ischemic cardiomyopathy. No definite benefits were seen with statins in sudden cardiac death and VT/VF in patients with non-ischemic cardiomyopathy. There is insufficient evidence to point toward a benefit in populations at low risk for VT/VF. In conclusion, an anti-ischemic rather than a primary antiarrhythmic effect emerges as the likely mechanism of sudden cardiac death reduction with statins.

Venous thromboembolism in systemic autoimmune diseases: A narrative review with emphasis on primary systemic vasculitides.

Venous thromboembolism (VTE) is a prevalent multifactorial health condition associated with significant morbidity and mortality. Population-based epidemiological studies have revealed an association between systemic autoimmune diseases and deep venous thrombosis (DVT)/VTE. The etiopathogenesis of increased risk of VTE in systemic autoimmune diseases is not entirely clear but multiple contributors have been explored, especially in the context of systemic inflammation and disordered thrombogenesis. Epidemiologic data on increased risk of VTE in patients with primary systemic vasculitides (PSV) have accumulated in recent years and some of these studies suggest the increased risk while patients have active diseases. This could lead us to hypothesize that venous vascular inflammation has a role to play in this phenomenon, but this is unproven. The role of immunosuppressive agents in modulating the risk of VTE in patients with PSV is not yet clear except for Behçet’s disease, where most of the studies are retrospective. Sensitizing physicians to this complication has implications for prevention and optimal management of patients with these complex diseases. This review will focus on the epidemiology and available evidence regarding pathogenesis, and will attempt to summarize the best available data regarding evaluation and treatment of these patients.

Emerging Viral Infections in Rheumatic Diseases

OBJECTIVES To review the current literature regarding emerging viral pathogens in the context of rheumatic diseases with the intent of increasing awareness among rheumatologists and treating physicians, aiming at early recognition and treatment of these patients. METHODS We reviewed case reports, case series, review articles, and original reports from PubMed (www.pubmed.gov) regarding various aspects influencing spread of infectious diseases including epidemiology and viral and human factors that are potentially responsible for the emergence of new viral pathogens. By consensus, we generated a list of emerging viral pathogens pertinent regarding presentation with rheumatologic manifestations and then short-listed several with particular clinical relevance including hepatitis B, human immunodeficiency virus, and Chikungunya viruses for discussion in greater detail. RESULTS There has been a change in the epidemiology and clinical rheumatic manifestations of previously known viral pathogens as well as the emergence of new viral pathogens as a consequence of factors such as changes in environmental temperature and its consequences, changes in vector and parasite biology, and human influences such as treatment and immunization. CONCLUSIONS Rheumatologists need to be cognizant of the changing landscape of emerging viral pathogens as they may present with myriad clinical features. Recognition of these pathogens is important to guide correct treatment and prognosis. Given the current scenario of global epidemiologic factors that influence viral emergence, we should expect a growing number of future emerging pathogens. Ongoing research directed at understanding pathogenesis and transmission as well as developing better preventive strategies may help counter the threat posed by emerging pathogens.

Rituximab-responsive nephrotic syndrome due to minimal change disease in systemic lupus erythematosus.

CASE We present a 15-year-old African-American adolescent girl who presented with arthralgia, headache, facial rash, and pleuritic chest pain. Her examination was significant for synovitis in metacarpophalangeal and proximal interphalangeal joints, malar rash, and generalized pitting edema. Laboratory tests showed leukopenia (3.2 10 cells/L), elevated erythrocyte sedimentation rate (ESR; 60 mm/hr), low complement 4 (C4) level (10 mg/dL), low albumin (1.9 g/dL), elevated serum cholesterol, and normal creatinine (0.7 mg/dL). Urinalysis revealed significant proteinuria on dipstick with trace hemoglobin and no casts. The 24-hour urine collection showed 3.4 g of protein. Antinuclear antibodies (ANAs) were positive (1:640; speckled), with presence of anti-SSA and anti-SSB antibodies and elevated antiYdouble-stranded DNA antibodies. On the basis of her serology results and clinical presentation, she was diagnosed with systemic lupus erythematosus (SLE). On renal biopsy, pathologic examination showed absence of glomerular proliferation or necrosis with negative immunofluorescence studies. Epithelial foot process fusion and a thickened basement membrane were noted, compatible with minimal change disease (MCD). She was treated with prednisone 40 mg daily and furosemide with rapid resolution of symptoms. She was also started on hydroxychloroquine 200 mg twice daily, and prednisone was tapered to off for the next 2 months. For the next 5 years, her clinical course was complicated by several similar episodes of nephrotic syndrome, highly responsive to high-dose (60 mg daily) prednisone tapers with recurrence off prednisone. Other etiologies of MCD including medications such as anti-inflammatory medications and antibiotics were ruled out based on a detailed history. Additional immunosuppressive therapy was tried to prevent flares, including azathioprine and cyclophosphamide, which failed to prevent recurrences, and mycophenolate mofetil, which she could not tolerate. In November 2009, she developed an erythematous rash involving her face, arms and chest, along with anasarca. Laboratory tests revealed leukopenia (2.97 10 cells/L), elevated creatinine (4.67 mg/dL), low complement levels, and elevatedESR (72mm/hr). Serumalbuminwas 1.8g/dL.Urinalysis showed hematuria, proteinuria, nondysmorphic red cells, and granular casts. Spot urine protein-to-creatinine ratio was greater than 3.5. Skin biopsy revealed interface dermatitis. Renal ultrasound showed enlarged kidneys measuring 15 cm in size. A repeat kidney biopsy showed a moderate amount of epithelial foot process fusion, absence of glomerular crescents or necrosis, and negative immunofluorescence, again compatible with MCD (Figure). She responded quickly to prednisone and furosemide, with resolution of edema and return of creatinine to normal levels in 7 days. With recurrent episodes of nephrotic syndrome now leading to renal failure and inability to use other immunosuppressive medications, the decision was made to administer rituximab (2 doses of 1000 mg 2 weeks apart). Ten days after administration of the first dose, her rash had started fading. Within 4 weeks of administration of her second dose, her complement levels had normalized, ESR had decreased (44 mm/hr), and her proteinuria had resolved. Follow-up ultrasound revealed normal-sized kidneys. Prednisone was tapered off for the next 2 months, and she has been maintained on hydroxychloroquine. She has not had a recurrence since and continues to be symptom free at 24 months.