Tasnim F. Imran

Lupus nephritis: an update

Lupus nephritis (LN) is an inflammatory condition of the kidneys that encompasses various patterns of renal disease including glomerular and tubulointerstitial pathology. It is a major predictor of poor prognosis in patients with systemic lupus erythematosus (SLE). Genetic factors, including several predisposing loci, and environmental factors, such as EBV and ultraviolet light, have been implicated in the pathogenesis. It carries a high morbidity and mortality if left untreated. Renal biopsy findings are utilized to guide treatment. Optimizing risk factors such as proteinuria and hypertension with renin-angiotensin receptor blockade is crucial. Immunosuppressive therapy is recommended for patients with focal or diffuse proliferative lupus nephritis (Class III or IV) disease, and certain patients with membranous LN (Class V) disease. Over the past decade, immunosuppressive therapies have significantly improved long-term outcomes, but the optimal therapy for LN remains to be elucidated. Cyclophosphamide-based regimens, given concomitantly with corticosteroids, have improved survival significantly. Even though many patients achieve remission, the risk of relapse remains considerably high. Other treatments include hydroxychloroquine, mycofenolate mofetil, and biologic therapies such as Belimumab, Rituximab, and Abatacept. In this paper, we provide a review of LN, including pathogenesis, classification, and clinical manifestations. We will focus, though, on discussion of the established as well as emerging therapies for patients with proliferative and membranous lupus nephritis.

QT Prolongation and Clinical Outcomes in Patients with Takotsubo Cardiomyopathy

Takotsubo cardiomyopathy (TCM) has been associated with repolarization abnormalities including QT prolongation and acquired long QT syndrome. However, the association between QT prolongation and clinical outcomes in patients with TCM remains unclear. The aim of this study is to examine the association between QT prolongation and ventricular arrhythmias, cardiogenic shock, and death in patients with TCM.

Walking and Calcified Atherosclerotic Plaque in the Coronary Arteries

Objective— Studies have reported mixed findings on the association between physical activity and subclinical atherosclerosis. We sought to examine whether walking is associated with prevalent coronary artery calcification (CAC) and aortic calcification. Approach and Results— In a cross-sectional design, we studied 2971 participants of the National Heart, Lung, and Blood Institute Family Heart Study without a history of myocardial infarction, coronary artery bypass grafting, or percutaneous transluminal angioplasty. A standardized questionnaire was used to ascertain the number of blocks walked daily to compute walking metabolic equivalent hours. CAC was measured by cardiac computed tomography. We defined prevalent CAC and aortic calcification using an Agatston score of at least 100 and used generalized estimating equations to calculate adjusted prevalence ratios. Mean age was 55 years, and 60% of participants were women. Compared with the ⩽3.75-Met-h/wk group, prevalence ratios for CAC after adjusting for age, sex, race, smoking, alcohol use, total physical activity (excluding walking), and familial clustering were 0.53 (95% confidence interval, 0.35–0.79) for >3.75 to 7.5 Met-h/wk, 0.72 (95% confidence interval, 0.52–0.99) for >7.5 to 15 Met-h/wk, and 0.54 (95% confidence interval, 0.36–0.81) for >15 to 22.5 Met-h/wk, (P trend=0.01). The walking–CAC relationship remained significant for those with body mass index ≥25 (P trend=0.02) and persisted with CAC cutoffs of 300, 200, 150, and 50 but not 0. When examined as a continuous variable, a J-shaped association between walking and CAC was found. The walking–aortic calcification association was not significant. Conclusions— Our findings suggest that walking is associated with lower prevalent CAC (but not aortic calcification) in adults without known heart disease.Objective— Studies have reported mixed findings on the association between physical activity and subclinical atherosclerosis. We sought to examine whether walking is associated with prevalent coronary artery calcification (CAC) and aortic calcification. Approach and Results— In a cross-sectional design, we studied 2971 participants of the National Heart, Lung, and Blood Institute Family Heart Study without a history of myocardial infarction, coronary artery bypass grafting, or percutaneous transluminal angioplasty. A standardized questionnaire was used to ascertain the number of blocks walked daily to compute walking metabolic equivalent hours. CAC was measured by cardiac computed tomography. We defined prevalent CAC and aortic calcification using an Agatston score of at least 100 and used generalized estimating equations to calculate adjusted prevalence ratios. Mean age was 55 years, and 60% of participants were women. Compared with the ≤3.75-Met-h/wk group, prevalence ratios for CAC after adjusting for age, sex, race, smoking, alcohol use, total physical activity (excluding walking), and familial clustering were 0.53 (95% confidence interval, 0.35–0.79) for >3.75 to 7.5 Met-h/wk, 0.72 (95% confidence interval, 0.52–0.99) for >7.5 to 15 Met-h/wk, and 0.54 (95% confidence interval, 0.36–0.81) for >15 to 22.5 Met-h/wk, ( P trend=0.01). The walking–CAC relationship remained significant for those with body mass index ≥25 ( P trend=0.02) and persisted with CAC cutoffs of 300, 200, 150, and 50 but not 0. When examined as a continuous variable, a J-shaped association between walking and CAC was found. The walking–aortic calcification association was not significant. Conclusions— Our findings suggest that walking is associated with lower prevalent CAC (but not aortic calcification) in adults without known heart disease. # Highlights {#article-title-39}

Vertigo as a predominant manifestation of neurosarcoidosis.

Sarcoidosis is a granulomatous disease of unknown etiology that affects multiple organ systems. Neurological manifestations of sarcoidosis are less common and can include cranial neuropathies and intracranial lesions. We report the case of a 21-year-old man who presented with vertigo and uveitis. Extensive workup including brain imaging revealed enhancing focal lesions. A lacrimal gland biopsy confirmed the diagnosis of sarcoidosis. The patient was initially treated with prednisone, which did not adequately control his symptoms, and then was switched to methotrexate with moderate symptomatic improvement. Our patient had an atypical presentation with vertigo as the predominant manifestation of sarcoidosis. Patients with neurosarcoidosis typically present with systemic involvement of sarcoidosis followed by neurologic involvement. Vertigo is rarely reported as an initial manifestation. This case highlights the importance of consideration of neurosarcoidosis as an entity even in patients that may not have a typical presentation or systemic involvement of disease.

Television Viewing Time, Physical Activity, and Mortality Among African Americans

Background Prolonged television viewing time, a marker of sedentary activity, is independently associated with increased all-cause mortality; however, this association has rarely been studied in African Americans. The objective of our study was to examine the association between television viewing time and mortality among African Americans by using data from the Jackson Heart Study (JHS). Methods We studied 5,289 participants from the JHS study who reported television viewing time (h/day) in the JHS baseline questionnaire from 2000 through 2004. Using multivariable Cox regression models adjusted for age, sex, smoking, alcohol use, physical activity, nutrition, prevalent coronary heart disease, chronic kidney disease, diabetes, and hypertension, we computed hazard ratios to examine the association between television viewing time (≤2 h/day, 2–4 h/day, and ≥4 h/day) and mortality. Results Participants had a mean age of 55 years, and 64% were women. After a median follow-up of 9.9 years (interquartile range, 9.0–10.7), 615 deaths occurred (data analysis conducted in 2017). Hazard ratios for mortality were 1.08 (0.86–1.37) for television time of 2 to 4 hours per day and 1.48 (95% CI: 1.19–1.83) for television time of greater than or equal to 4 hours per day when compared with those who watched television less than 2 hours per day (P trend = .002). When we restricted analyses to those who performed leisure-time activities, the hazard ratios for mortality were 1.10 (95% CI, 0.84–1.45) for television viewing of 2 to 4 hours per day and 1.45 (95% CI, 1.13–1.86) for more than 4 hours per day compared with the less than 2 hours per day. Conclusion Our findings suggest that greater television viewing time, even among those who perform leisure-time physical activities, is associated with increased all-cause mortality among African Americans. Thus, it may serve as an indicator of a sedentary lifestyle with potential for intervention.

Prognostic Significance of Baseline Serum Sodium in Heart Failure With Preserved Ejection Fraction

Background The purpose of this study was to evaluate the relationship between serum sodium at the time of diagnosis and long term clinical outcomes in a large national cohort of patients with heart failure with preserved ejection fraction. Methods and Results We studied 25 440 patients with heart failure with preserved ejection fraction treated at Veterans Affairs medical centers across the United States between 2002 and 2012. Serum sodium at the time of heart failure diagnosis was analyzed as a continuous variable and in categories as follows: low (115.00–134.99 mmol/L), low‐normal (135.00–137.99 mmol/L), referent group (138.00–140.99 mmol/L), high normal (141.00–143.99 mmol/L), and high (144.00–160.00 mmol/L). Multivariable Cox regression and negative binomial regression were performed to estimate hazard ratios (95% confidence interval [CI]) and incidence density ratios (95% CI) for the associations of serum sodium with mortality and hospitalizations (heart failure and all‐cause), respectively. The average age of patients was 70.8 years, 96.2% were male, and 14% were black. Compared with the referent group, low, low‐normal, and high sodium values were associated with 36% (95% CI, 28%–44%), 6% (95% CI, 1%–12%), and 9% (95% CI, 1%–17%) higher risk of all‐cause mortality, respectively. Low and low‐normal serum sodium were associated with 48% (95% CI, 10%–100%) and 38% (95% CI, 8%–77%) higher risk of number of days of heart failure hospitalizations per year, and with 44% (95% CI, 32%–56%) and 18% (95% CI, 10%–27%) higher risk of number of days of all‐cause hospitalizations per year, respectively. Conclusions Both elevated and reduced serum sodium, including values currently considered within normal range, are associated with adverse outcomes in patients with heart failure with preserved ejection fraction.

A phenotyping algorithm to identify acute ischemic stroke accurately from a national biobank: the Million Veteran Program

Background Large databases provide an efficient way to analyze patient data. A challenge with these databases is the inconsistency of ICD codes and a potential for inaccurate ascertainment of cases. The purpose of this study was to develop and validate a reliable protocol to identify cases of acute ischemic stroke (AIS) from a large national database. Methods Using the national Veterans Affairs electronic health-record system, Center for Medicare and Medicaid Services, and National Death Index data, we developed an algorithm to identify cases of AIS. Using a combination of inpatient and outpatient ICD9 codes, we selected cases of AIS and controls from 1992 to 2014. Diagnoses determined after medical-chart review were considered the gold standard. We used a machine-learning algorithm and a neural network approach to identify AIS from ICD9 codes and electronic health-record information and compared it with a previous rule-based stroke-classification algorithm. Results We reviewed administrative hospital data, ICD9 codes, and medical records of 268 patients in detail. Compared with the gold standard, this AIS algorithm had a sensitivity of 91%, specificity of 95%, and positive predictive value of 88%. A total of 80,508 highly likely cases of AIS were identified using the algorithm in the Veterans Affairs national cardiovascular disease-risk cohort (n=2,114,458). Conclusion Our algorithm had high specificity for identifying AIS in a nationwide electronic health-record system. This approach may be utilized in other electronic health databases to accurately identify patients with AIS.

Efficacy of spinal cord stimulation as an adjunct therapy for chronic refractory angina pectoris

INTRODUCTION Patients with chronic refractory angina whose symptoms are not controlled with conventional therapies have a poor quality of life. Adjunctive therapies, such as spinal cord stimulation (SCS) may be considered in these cases. We sought to examine whether SCS is associated with changes in exercise capacity and angina severity in these patients. METHODS We searched Pubmed, Medline and other databases until December 2015. Two reviewers independently extracted data and assessed risk of bias. Exercise capacity included exercise duration and rate pressure product, determined via an exercise test. Angina severity included daily angina frequency and nitrate consumption. RESULTS A total of 518 participants (1048.25 person-years of follow-up), from 14 studies met our inclusion criteria. The mean age was 66.8years and 68.5% were men. SCS implant duration ranged from 3weeks to 5years (median: 6months). Using random effects meta-analysis, we found that SCS was associated with a higher exercise duration (1.90min, 95% CI 1.71, 2.06) and lower angina severity, 1.55 less daily angina episodes, (95% CI -1.75, -1.33), 1.54 less daily nitrates consumed, (95% CI -1.81, -1.26), and a 22 points higher SF-36 angina frequency score (95% CI 10.76, 32.81; p<0.0001) on follow-up. The change in rate pressure product was not significant. CONCLUSION This meta-analysis suggests that SCS, as an adjunct therapy to medical management, may be associated with a longer exercise duration and lower angina frequency and nitrate consumption in patients with chronic refractory angina pectoris who are not candidates for percutaneous intervention or revascularization.

Facial Weakness, Diplopia, and Fever in a 31-Year-Old: An Atypical Case of Tuberculous Meningitis

Tuberculous meningitis (TBM) is an infection of the central nervous system (CNS) meninges that carries high morbidity and mortality. It is important to recognize, as patients may present with atypical symptoms. We describe the case of a 31-year-old man with a history of diabetes who presented with a sub-acute onset of right-sided facial weakness and right gaze difficulty with diplopia. History revealed low-grade fever, right-sided headache, fatigue and moderate weight loss for the past several weeks. The patient did not report neck stiffness, rigidity, fever, chills or cough. The physical exam revealed sixth nerve palsy with a right Horner’s syndrome. Magnetic resonance imaging (MRI) of the brain showed pachymeningeal enhancement. A spinal tap revealed elevated white blood cells (WBCs), glucose and protein; cerebrospinal fluid (CSF) culture showed Mycobacterium tuberculosis. The patient was diagnosed with TBM and treated with isoniazid, rifampin, pyrazinamide, ethambutol and vitamin B6 for 12 months. The timely diagnosis of TBM can be challenging due to a nonspecific clinical presentation. In patients with a sub-acute onset of headache, fever and meningeal signs, TBM should be considered in the differential. If suspected, treatment should be initiated immediately to prevent further neurological impairment and death.

Serial Magnetic Resonance Imaging in Creutzfeldt-Jakob Disease: a Case Report and Literature Review

Creutzfeldt-Jakob disease (CJD) is a rare, degenerative, invariably fatal brain disorder. CJD usually appears in later life and runs a rapid course. Typically, the onset of symptoms occurs about age 60 and about 90% of individuals die within one year. We report a case of 67-year-old male presented with progressive aphasia, confusion, dysphagia and inability to carry out activities of daily life (ADLs) over a period of three to four weeks. The patient had past medical history of chronic atrial fibrillation and hypertension. Prior to admission, the patient was treated for ischemic stroke of left basal ganglia but continued to have worsening encephalopathy. The spinal tap revealed a 14-3-3 protein level of thirteen times the upper limit of normal; electroencephalogram (EEG) showed a diffuse slowing of the background and periodic sharp waves with greater involvement of the left hemisphere. Diffusion-weighted imaging (DWI) magnetic resonance imaging (MRI) at the time of admission showed extensive signal abnormality in the basal ganglia bilaterally and in the cerebral cortex bilaterally, particularly over the left cerebral hemisphere. The persistence of the MRI findings over several weeks was concerning for spongiform encephalopathy. The probable diagnosis of Creutzfeldt-Jakob disease was made based on these imaging findings taken together with the patient’s clinical signs and symptoms of a rapidly progressive encephalopathy. The patient was able to have some quality time with his family as the diagnosis was made earlier than perhaps otherwise and expired peacefully after comfort care measures were chosen. Serial MRI may serve as a clue to the early diagnosis of CJD and potentially provide a better quality of life for the patients.