Determining the Need for Additional Testing With Quantiferon TB Gold in Patients With Positive Tuberculin Skin Tests and a History of BCG Vaccination.

OBJECTIVE:  To determine if the QuantiFERON-TB Gold (QFT) testing can be obviated for the diagnosis of latent tuberculosis infection (LTBI) in patients with a positive tuberculin skin test (TST) and a history of Bacillus Calmette-Guerin (BCG) vaccination by identifying high-risk features in patients with positive TST and a history of BCG vaccination who are associated with positive QFT. METHODS:  Retrospective chart review was done for 76 adult patients by dividing them into two groups. Group 1 consisted of true positive TST patients who had BCG vaccination and were positive for QFT. Group 2 consisted of false positive TST patients who had BCG vaccination but were negative for QFT. The two groups were compared to determine if the high-risk features of TST induration diameter of 15mm and more, TST induration of 20mm and more, recent immigration to the US, the advanced age of more than 65 years, country of origin with high TB burden, known exposure to active TB, and smoking history were more prevalent in Group 1 compared to Group 2. RESULTS:  Group 1 had 23 patients and Group 2 had 53 patients. Group 1 had a higher prevalence of patients with PPD induration of more than 10mm than Group 2, which was statistically significant with a P value of 0.03. Other risk factors of advanced age, exposure to active TB and smoking did not show statistically significant differences between Groups 1 and 2.  Conclusion: This study also confirms that if the TST induration is more than 10mm in patients with a history of BCG vaccination, the TST induration is likely because of LTBI and is less likely because of cross-reaction with BCG vaccination.

An Interesting Case of Congenital Intrahepatic Porto-hepatic Shunt as a Cause of Unexplained Encephalopathy.

Congenital portosystemic shunts can be divided into two types: intrahepatic shunts in which there is an abnormal connection between the branches of the portal vein and either the inferior vena cava or the hepatic veins and less commonly the extrahepatic type in which the portal system is connected to one of the branches of the mesenteric veins. Here we describe a 73-year-old woman who was admitted to the hospital with clinical evidence of encephalopathy and was found to have hyperammonemia. Abdominal computed tomography angiography was performed and revealed a dilated portal vein measuring up to 1.8 cm at the porta-hepatis along with dilated superior mesenteric and splenic veins. Multiple dilated vascular channels were identified within the right hepatic lobe. An intrahepatic portosystemic shunt between an enlarged middle hepatic vein and two separate branches of the right portal vein was demonstrated. A liver biopsy showed normal architecture with no evidence of inflammation or fibrosis. Portosystemic shunts are rare and often detected in adulthood but should be considered as an important cause of unexplained encephalopathy in the absence of cirrhotic liver disease or hepatic trauma. Given that the size of such shunts increases with age, older persons are more prone to the effect of toxic metabolites.This age-associated increase in shunt size may help explain why some patients remain asymptomatic until later in their life which may account for the late presentation in our patient.

A potential role of toll-like receptors, IFN-γ and the phosphatidylinositol 3-kinase pathway in the pathogenesis of acquired mediastinal lymphatic malformation.

Sarcoidosis is a multisystem disorder with non-caseating granulomas in various organs. The etiology of sarcoid granuloma formation is not clear and likely an antigen-induced process. We came across a previously treated sarcoidosis patient who presented with worsening dyspnea on exertion for several months and several days of difficulty swallowing. On Chest CT imaging, large posterior mediastinal mass was found that subsequently diagnosed as macrocystic lymphatic malformation after surgical resection. Pathophysiology of development of acquired lymphatic malformations in a sarcoidosis patient is currently not clear. We hypothesize there might be a complex interplay of Toll-like receptors, IFN-γ and the phosphatidylinositol 3-kinase pathway in the pathogenesis.

Macrophage lipid accumulation in the presence of immunosuppressive drugs mycophenolate mofetil and cyclosporin A.

OBJECTIVE: Mycophenolate (MPA) and cyclosporin A (CsA) are two immunosuppressive agents currently used for the treatment of autoimmune diseases. However, reports regarding their effects on inflammation and lipid handling are controversial. Here, we compare the effect of these two drugs on the expression of proteins involved in cholesterol handling and lipid accumulation in a macrophage cell system utilizing M0, M1 and M2 human macrophages and in murine bone marrow-derived macrophages (BMDM). METHODS: Differentiated M0, M1 and M2 subsets of THP-1 human macrophages were subjected to various concentrations of either MPA or CsA. Expression of proteins involved in reverse cholesterol transport (ABCA1 and 27-hydroxylase) and scavenger receptors, responsible for uptake of modified lipids (CD36, ScR-A1, CXCL16 and LOX-1), were evaluated by real-time PCR and confirmed with Western blot. DiI-oxidized LDL internalization assay was used to assess foam cell formation. The influence of MPA was also evaluated in BMDM obtained from atherosclerosis-prone transgenic mice, ApoE-/- and ApoE-/-Fas-/-. RESULTS: In M0 macrophages, MPA increased expression of ABCA1 and CXCL16 in a concentration-dependent manner. In M1 THP-1 macrophages, MPA caused a significant increase of 27-hydroxylase mRNA and CD36 and SR-A1 receptor mRNAs. Exposure of M2 macrophages to MPA also stimulated expression of 27-hydroxylase, while downregulating all evaluated scavenger receptors. In contrast, CsA had no impact on cholesterol efflux in M0 and M1 macrophages, but significantly augmented expression of ABCA1 and 27-hydroxylase in M2 macrophages. CsA significantly increased expression of the LOX1 receptor in naïve macrophages, downregulated expression of CD36 and SR-A1 in the M1 subpopulation and upregulated expression of all evaluated scavenger receptors. However, CsA enhanced foam cell transformation in M0 and M2 macrophages, while MPA had no effect on foam cell formation unless used at a high concentration in the M2 subtype. CONCLUSIONS: Our results clearly underline the importance of further evaluation of the effects of these drugs when used in atherosclerosis-prone patients with autoimmune or renal disease.

Identifying Different Causes of Hyponatremia With Fractional Excretion of Uric Acid.

BACKGROUND: There is controversy over the prevalence of the syndrome of inappropriate antidiuretic hormone secretion (SIADH) and cerebral or renal salt wasting (RSW), 2 syndromes with identical common clinical and laboratory parameters but different therapies. The traditional approach to the hyponatremic patient relies on volume assessment, but there are limitations to this method. METHODS: We used an algorithm that relies on fractional excretion of urate (FEurate) to evaluate patients with hyponatremia and present 4 illustrative cases. RESULTS: Overall, 2 patients had increased FEurate [normal: 4-11%], as is seen in SIADH and RSW. A diagnosis of SIADH was made in 1 patient by correcting the hyponatremia with 1.5% saline and observing a characteristic normalization of an elevated FEurate that is characteristic of SIADH as compared to FEurate being persistently increased in RSW. A patient with T-cell lymphoma had symmetrical leg edema due to lymphomatous obstruction of the inferior vena cava, postural hypotension, pleural effusion, ascites, decreased cardiac output and urine sodium level of 10mmol/L. Saline-induced excretion of dilute urines and undetectable plasma antidiuretic hormone were consistent with RSW. Furosemide, given for presumed heart failure, induced a profound diuresis that required large volumes of fluid resuscitation. A normal FEurate identified a reset osmostat in a transplant patient with a slowly developing pneumocystis carinii pneumonia. A volume-depleted hyponatremic patient with Addison׳s disease had a low FEurate of 1.4%. CONCLUSIONS: These illustrative cases suggest that an approach to hyponatremia using FEurate may be a useful alternative to traditional volume-based approaches.

Awareness of Chronic Kidney Disease and Depressive Symptoms: National Health and Nutrition Examination Surveys 2005-2010.

BACKGROUND: Depressive symptoms are common in patients with chronic kidney disease (CKD) and may stem from distress associated with CKD awareness. So far, no studies have examined this association. The objective of this study was to evaluate the association between awareness of CKD and depressive symptoms. METHODS: We included adults with stages 1-4 CKD (estimated glomerular filtration rate 15-60 ml/min/1.73 m2 or urine albumin-to-creatinine ratio ≥30 mg/g) using the National Health and Nutrition Examination Surveys from 2005 to 2010. Depressive symptoms were categorized as minimal (9-item Patient Health Questionnaire (PHQ-9) score 0-4), subthreshold (PHQ-9 score 5-14) and severe (PHQ-9 score ≥15). Participants were classified as aware of CKD if they answered yes to the question: 'Have you ever been told you have weak or failing kidneys?' Multivariable logistic regression was used to identify variables independently associated with at least subthreshold depressive symptoms (PHQ-9 ≥5). RESULTS: In 2,500 participants with CKD, the weighted prevalence was 21.4% for subthreshold and 3.1% for severe depressive symptoms. The weighted prevalence of CKD awareness was 6.4%. Independent predictors of depressive symptoms included younger age, female gender, never been married, less than high-school education, annual family income <$20,000, obesity, smoking, cardiovascular comorbidity and mental health visit in the past year. CKD awareness was independently associated with a 1.66 greater odds of depressive symptoms (95% CI 1.01-2.74, p < 0.05). CONCLUSIONS: Awareness of CKD is significantly associated with depressive symptoms independent of known confounding factors. Future studies should examine mediators of this association, especially in light of national efforts to promote CKD awareness.

Predictors of positive immunofixation testing in patients with acute kidney injury.

INTRODUCTION: Acute kidney injury may be the presenting manifestation of multiple myeloma, although optimal use of immunofixation testing in this setting is incompletely defined. The authors attempted to determine clinical and laboratory predictors of positive immunofixation testing in patients with acute kidney injury. PATIENTS AND METHODS: The authors did a retrospective study of hospitalized patients with acute kidney injury who had immunofixation studies done. Various clinical and laboratory variables that may be predictive of the presence of multiple myeloma were evaluated and correlations with immunofixation test results determined. RESULTS: One hundred twenty-eight patients were studied. Thirteen had a monoclonal paraprotein detected by immunofixation testing (positive result). Patients with positive testing had higher total, ionized and corrected calcium levels, although the median total calcium in immunofixation-positive patients was normal at 9.7 mg/dL. Patients with positive testing also had lower hemoglobin and platelet counts. An anion gap of <7 mmol/L and total protein-albumin gap >4 g/dL were also associated with positive results. CONCLUSIONS: In patients with acute kidney injury, relatively higher total, ionized and corrected calcium levels and lower hemoglobin and platelet counts may predict the presence of a monoclonal paraprotein. An anion gap of <7 mmol/L and total protein-albumin gap >4 g/dL may also be predictors. The metabolic consequences of acute kidney injury may attenuate some of these abnormalities as well. These findings may help guide optimal use of immunofixation testing and hence help potentially identify patients who may have multiple myeloma.

Quantifying internal medicine resident clinical experience using resident-selected primary diagnosis codes.

BACKGROUND: While experiential learning is a desirable goal of residency education, little is known regarding the actual clinical experience of internal medicine residents during their training. METHODS: We modified an electronic patient handoff tool to include a system for resident entry of a primary diagnosis for each of their patients. Using the International Classification of Diseases, Ninth Revision (ICD-9) system, we created two methods to select the code: 1) an organ system-based dropdown list containing frequently used codes; and 2) a search option for the complete ICD-9 database. The codes were then grouped using ICD-9 categorization. RESULTS: A total of 7562 resident-patient diagnostic encounters were studied. A wide spectrum of clinical conditions was observed, with symptoms and ill-defined conditions, circulatory disorders, respiratory disorders, neoplasms, genitourinary disorders, digestive disorders, diseases of the blood/blood forming organs, endocrinologic/nutritional/metabolic/immune disorders, and disorders of the skin and subcutaneous tissue accounting for about 86% of resident clinical experience. Symptoms and ill-defined conditions were noted to represent a sizable portion of resident clinical experience. Within this category, the most common conditions were fever; abdominal pain; and chest pain, unspecified. CONCLUSIONS: Analysis of resident-selected ICD-9 codes might serve as a method to attempt to define resident clinical experience, and may be useful in the development of innovative experiential learning-based residency curricula. This might also be used to assess gaps in experiential learning at the program or resident level, and may serve to identify topics that require additional teaching supplementation.

Approach to the pretransplant evaluation of the living kidney donor.

Evaluation of the potential kidney donor is a complex activity that differs substantially from other types of preoperative assessments. The well being of the donor, who derives no medical benefit from this surgery, must be assured in both the short term and long term, and the potential adverse consequences to the recipient must be determined as well. The criteria that must be met for a person to donate a kidney are rigorous and include medical, social, psychosocial, ethical, and legal issues. Donor evaluation can be divided into assessments to protect the health and safety of the donor and assessments to protect the health and safety of the recipient. This article provides an approach to evaluating a donor, focusing on the complex issues that an evaluator is faced with. A careful assessment of risks and benefits to both the donor and recipient can lead to favorable outcomes.

Effect of a CD-ROM-based educational intervention on resident knowledge and adherence to deep venous thrombosis prophylaxis guidelines.

BACKGROUND: CD-ROM-based educational methods are not new to residency training, yet little is known about how they affect resident knowledge and patient care practices. OBJECTIVE: We evaluated the effects of a CD-ROM-based educational tool on residents' knowledge of anticoagulation and their adherence to anticoagulation guidelines. DESIGN, SETTING AND PARTICIPANTS: Residents in the departments of cardiothoracic surgery, emergency medicine, otolaryngology, internal medicine, neurosurgery, dental medicine, neurology, obstetrics and gynecology, orthopedics, surgery, and urology at a university hospital participated in the study. INTERVENTION: Residents were provided with CD-ROM-based training on the proper use of anticoagulation based on the sixth ACCP guidelines for antithrombotic therapy. Multiple choice testing was carried out before and after the CD-ROM intervention to assess resident knowledge, and resident compliance with venous thromboembolism prophylaxis guidelines was assessed via inpatient chart review by an independent committee. MAIN OUTCOME MEASURES: Changes in knowledge were measured via test scores and the rate of compliance with anticoagulation guidelines. RESULTS: Multiple choice test scores of 117 residents increased significantly after reviewing the CD-ROM (from 46.7% +/- 15.1% to 77.8% +/- 15.1%, P < .005). As a control, we administered the same test at the same 2 times at a comparable institution but without the CD-ROM intervention and found that test scores did not significantly increase. Chart review revealed a rate of compliance with anticoagulation guidelines for prophylaxis of venous thromboembolism of 75% before the CD-ROM intervention, which increased to 95% after the intervention, an increase that was sustained for at least 7 months. CONCLUSIONS: These findings suggest that CD-ROM-based interventions might be useful not only in enhancing resident knowledge but also in improving the quality of care by favorably affecting clinical practice.

Vancomycin-induced acute granulomatous interstitial nephritis: therapeutic options.

Drug-induced acute renal failure is a commonly encountered mode of renal injury in the hospitalized patient. Vancomycin is a frequently used antibiotic in patients with Gram-positive bacterial infections. In the present study, we evaluated an index case of a patient who developed severe acute granulomatous interstitial nephritis and provided a review of the reported cases of vancomycin-induced acute renal failure in the literature. A Medline search revealed a total of 11 cases of vancomycin-induced interstitial nephritis. In 2 reported cases, interstitial nephritis has been reported with associated granuloma formation. However, the role of T cells in the formation of interstitial nephritis and in the choice of therapeutic modalities in this scenario has not been evaluated in the past. In the index case, we have evaluated the effect of treatment on the basis of the type of cellular infiltrates and provided a follow-up by carrying out the repeat biopsy.

Lack of physician concordance with guidelines on the perioperative use of beta-blockers.

BACKGROUND: The American College of Physicians recommends perioperative use of beta-blockers for certain patients to improve outcomes after surgery. Study of physician behavior with respect to guidelines and recommended practices have shown that beta-blockers have been underutilized after myocardial infarction. We evaluated physician concordance with the perioperative use of beta-blockers along with a specialty-related difference in the frequency of perioperative beta-blocker use. METHODS: To determine perioperative use of beta-blockers, we retrospectively analyzed the medical charts of adult patients who underwent open cholecystectomy at a tertiary care medical center from December 1997 through December 2001. Patients met criteria for perioperative beta-blocker use if they had a history of coronary artery disease or if they had the presence of 2 or more of the following risk factors: 65 years or older; history of hypertension, diabetes mellitus, or hypercholesterolemia; or current smoking. RESULTS: Among the 336 cases of cholecystectomy reviewed, criteria for beta-blocker use were met in 146 patients (43%) who did not have emergency operations and/or contraindications to beta-blocker use. Of these 146 patients, 123 (84%) had a documented preoperative medical evaluation by a physician in the medical chart. There were 44 patients (30%) receiving beta-blockers prior to admission, and 102 patients (70%) were not receiving beta-blockers. Of those 102 patients not receiving beta-blockers at admission but who meet criteria for their use, 94 (92%) were not started on beta-blocker therapy preoperatively. Of the 18 patients evaluated by a cardiologist, 4 (22%) were started on beta-blocker therapy compared with 3 (6%) of 47 patients evaluated by a noncardiologist physician (P =.08). CONCLUSION: Perioperative beta-blocker therapy is underutilized in patients with risk factors for coronary artery disease despite evidence that its use in appropriate individuals may be lifesaving.

Dexamethasone attenuates oxidation of extracellular matrix proteins by human monocytes.

In response to infection or in immune complex-mediated diseases, inflammatory cells may oxidatively damage extracellular matrix (ECM) proteins. In this study we evaluated whether human monocytes could oxidize ECM and whether this could be modulated by exposure to LPS, IgG complexes, and dexamethasone (DEX). Wells in tissue culture plates were coated with the ECM preparation Matrigel. Porous inserts with or without the human monocyte cell line THP-1 were placed into ECM-containing wells and cells were exposed to control conditions or to LPS (10 ng/ml), IgG complexes (200 and 500 microg/ml), or DEX (10(-7) and 10(-6) M). ECM was then subjected to Western blot analysis using an antibody to oxidized protein. In addition, Western blot analysis was carried out on DEX-treated cells to evaluate expression of the NADPH oxidase components p67-phox and gp91-phox. THP-1 cells enhanced ECM oxidation and this effect was augmented by LPS and by IgG aggregates. Preincubation of cells with DEX attenuated ECM oxidation and was also associated with decreased expression of p67-phox and gp91-phox. These findings suggest that human monocytes can oxidize ECM proteins and that this may be modulated by IgG complexes and LPS. Dexamethasone appears to attenuate ECM oxidation and a better understanding of this mechanism might allow for interventions to minimize oxidative damage to ECM proteins by monocytes in infectious and inflammatory states.

Paradoxical arterial emboli causing acute limb ischemia in a patient with essential thrombocytosis.

Acute arterial occlusion can be the result of acute thrombosis or systemic embolism. Paradoxical embolism of a venous thrombosis through a right-to-left shunt is an important cause of acute limb ischemia. We describe a young patient with acute limb ischemia who was found to have multiple deep venous thromboses causing arterial embolization through a patent foramen ovale. Essential thrombocytosis was found to be the risk factor for venous thromboses in this patient. The patient was managed with embolectomy and anticoagulation along with chemotherapeutic cytoreduction of platelet count. This case illustrates the importance of considering the systemic embolism as a cause of acute arterial occlusion. The presence of a hypercoagulable status such as chronic myeloproliferative disorder does not eliminate the possibility of systemic embolism in the event of acute arterial occlusion. Patients presenting with acute limb ischemia should be evaluated for embolic sources. The presence of deep venous thrombosis in such a patient should prompt the evaluation for a patent foramen ovale.

Metal-catalyzed oxidation of extracellular matrix proteins promotes human mesangial cell apoptosis and is associated with enhanced expression of Bax and caspase activation.

Oxidative injury in glomerular disease may oxidize extracellular matrix proteins which might modulate their interaction with mesangial cells and thereby account for the hypocellularity seen in advanced glomerulosclerosis. In this study we evaluated whether oxidation of extracellular matrix could modulate human mesangial cell apoptosis. Human mesangial cells were seeded onto plates coated with unmodified (control) or oxidized Matrigel, laminin, or type IV collagen. Mesangial cell apoptosis was increased on oxidized Matrigel as well as on oxidized laminin and type IV collagen. Mesangial cells behaved similarly on plates coated with control and oxidized forms of the integrin ligand-containing peptide GRGDSP. Cells on oxidized matrix demonstrated enhanced expression of Bax, increased fragmentation of PARP, and diminished apoptosis in the presence of the interleukin-1 beta converting enzyme inhibitor Ac-Tyr-Val-Ala-Asp-aldehyde. These data suggest that oxidation of extracellular matrix proteins may enhance human mesangial cell apoptosis via a mechanism that appears to involve enhanced expression of Bax and caspase activation. This may account for irreversible mesangial hypocellularity in glomerulosclerosis.