You-Bin Lee

Change in Serum Bilirubin Level as a Predictor of Incident Metabolic Syndrome

Aim Serum bilirubin level was negatively associated with the prevalence of metabolic syndrome (MetS) in previous cross-sectional studies. However, bilirubin variance preceding the development of MetS has yet to be investigated. We aimed to determine the effect of change in bilirubin concentration on the risk of incident MetS in healthy Korean adults. Methods We conducted a retrospective longitudinal study of subjects who had undergone at least four yearly health check-ups between 2006 and 2012. Of 24,185 total individuals who received annual check-ups, 11,613 non-MetS participants with a baseline bilirubin level not exceeding 34.2 μmol/l were enrolled. We evaluated the association between percent change in bilirubin and risk of incident MetS. Results During 55,407 person-years of follow-up, 2,439 cases of incident MetS developed (21.0%). Baseline serum bilirubin level clearly showed no association with the development of MetS in men but an independent significant inverse association in women which attenuated (hence may be mediated) by elevated homeostatic model assessment index 2 for insulin resistance (HOMA2-IR). However, increased risk for incident MetS was observed in higher percent change in bilirubin quartiles, with hazard ratios of 2.415 (95% CI 2.094–2.785) in men and 2.156 (95% CI 1.738–2.675) in women in the fourth quartile, compared to the lowest quartile, after adjusting for age, smoking status, medication history, alanine aminotransferase, uric acid, estimated glomerular filtration rate, fasting glucose, baseline diabetes mellitus prevalence, systolic blood pressure, waist circumference, and body mass index. The hazard ratios per one standard deviation increase in percent change in bilirubin as a continuous variable were 1.277 (95% CI 1.229–1.326) in men and 1.366 (95% CI 1.288–1.447) in women. Conclusions Increases in serum bilirubin concentration were positively associated with a higher risk of incident MetS. Serum bilirubin increment might be a sensitive marker for the development of MetS.

Disseminated Talaromyces marneffei and Mycobacterium intracellulare coinfection in an HIV-infected patient

A 25-year-old man with human immunodeficiency virus (HIV) infection presented with fever that had lasted 1 month. The CD4+ T lymphocyte count was 7 cells/μL and computed tomography showed several small lung nodules, splenomegaly, and multiple lymphadenopathy. Talaromyces marneffei was isolated in the initial blood cultures. As the fever persisted despite clearance of fungemia and 10 days of liposomal amphotericin B treatment, cervical lymph node fine-needle aspiration was performed. Mycobacterium intracellulare was isolated from sputum and neck node aspiration cultures. The patient was successfully treated with liposomal amphotericin B, clarithromycin, and ethambutol in addition to antiretroviral therapy. This case suggests that we should consider coinfection of opportunistic pathogens in febrile immunosuppressed patients if the patient does not respond properly to the initial treatment.

Increase in serum albumin concentration is associated with prediabetes development and progression to overt diabetes independently of metabolic syndrome

Aim Serum albumin concentration is associated with both type 2 diabetes and metabolic syndrome (MetS). We sought to investigate whether baseline serum albumin and change in serum albumin could be independent risk factors for prediabetes in subjects without MetS. We further examined the effect of serum albumin on progression to overt diabetes in subjects who developed prediabetes. Methods Among 10,792 participants without diabetes and MetS who consecutively underwent yearly health check-ups over six years, 9,807 subjects without incident MetS were enrolled in this longitudinal retrospective study. The risk of developing prediabetes (impared fasting glucose or hemoglobin A1c) was analyzed according to baseline and percent change in serum albumin concentration using Cox regression analysis. Serial changes in serum albumin concentration were measured from baseline to one year before prediabetes diagnosis, and then from the time of prediabetes diagnosis to progression to overt diabetes or final follow-up. Results A total of 4,398 incident cases of prediabetes developed during 35,807 person-years (median 3.8 years). The hazard ratio for incident prediabetes decreased as percent change in serum albumin concentration (quartiles and per 1%) increased in a crude and fully adjusted model. However, baseline serum albumin concentration itself was not associated with prediabetic risk. Serum albumin levels kept increasing until the end of follow-up in prediabetic subjects who returned to normal glycemic status, whereas these measures did not change in prediabetic subjects who developed type 2 diabetes. Serum albumin concentration measured at the end of follow-up was the highest in the regression group, compared to the stationary (p = 0.014) or progression groups (p = 0.009). Conclusions Increase in serum albumin concentration might protect against early glycemic deterioration and progression to type 2 diabetes even in subjects without MetS.

Relationship Between Relative Skeletal Muscle Mass and Nonalcoholic Fatty Liver Disease: A 7‐Year Longitudinal Study

Nonalcoholic fatty liver disease (NAFLD) has been associated with relative skeletal muscle mass in several cross‐sectional studies. We explored the effects of relative skeletal muscle mass and changes in relative muscle mass over time on the development of incident NAFLD or the resolution of baseline NAFLD in a large, longitudinal, population‐based 7‐year cohort study. We included 12,624 subjects without baseline NAFLD and 2943 subjects with baseline NAFLD who underwent health check‐up examinations. A total of 10,534 subjects without baseline NAFLD and 2631 subjects with baseline NAFLD were included in analysis of changes in relative skeletal muscle mass over a year. Subjects were defined as having NAFLD by the hepatic steatosis index, a previously validated NAFLD prediction model. Relative skeletal muscle mass was presented using the skeletal muscle mass index (SMI), a measure of body weight–adjusted appendicular skeletal muscle mass, which was estimated by bioelectrical impedance analysis. Of the 12,624 subjects without baseline NAFLD, 1864 (14.8%) developed NAFLD during the 7‐year follow‐up period. Using Cox proportional hazard analysis, compared with the lowest sex‐specific SMI tertile at baseline, the highest tertile was inversely associated with incident NAFLD (adjusted hazard ratio [AHR] = 0.44, 95% confidence interval [CI] = 0.38‐0.51) and positively associated with the resolution of baseline NAFLD (AHR = 2.09, 95% CI = 1.02‐4.28). Furthermore, compared with the lowest tertile of change in SMI over a year, the highest tertile exhibited a significant beneficial association with incident NAFLD (AHR = 0.69, 95% CI = 0.59‐0.82) and resolution of baseline NAFLD (AHR = 4.17, 95% CI = 1.90‐6.17) even after adjustment for baseline SMI. Conclusion: Increases in relative skeletal muscle mass over time may lead to benefits either in the development of NAFLD or the resolution of existing NAFLD.

Elevated serum uric acid predicts the development of moderate coronary artery calcification independent of conventional cardiovascular risk factors

BACKGROUND AND AIMS Hyperuricemia was frequently noted in subjects with a high risk of cardiovascular disease (CVD). This study aimed to elucidate whether serum uric acid (SUA) is associated with development of moderate coronary artery calcification in generally healthy adults. METHODS A total of 9297 subjects underwent multidetector CT for the evaluation of CAC at least two times during their annual health examinations. Among them, 4461 participants without CVD history and who had no (scores 0) or minimal CAC (scores 1-10) in their first examination were enrolled. The association between SUA as a continuous and categorical variable and development of moderate coronary artery calcification (CAC score > 100) was assessed by Cox regression analysis. Receiver-operating characteristic (ROC) curves were constructed to investigate the diagnostic efficacy of SUA. RESULTS During a median follow-up of 4.1 years, 131 incident cases of moderate calcification developed. Baseline SUA concentration was significantly higher in subjects with progression to moderate coronary artery calcification (6.6 ± 1.3 vs. 5.8 ± 1.3 mg/dL, p < 0.001). SUA as a continuous variable (per 1 mg/dL) and divided into quartiles was positively associated with a higher risk of development of moderate calcification after adjustment for conventional CVD risk factors. The addition of SUA to the conventional CVD risk factors improved the predictive power for development of moderate coronary artery calcification. CONCLUSIONS SUA was an independent predictor for development of moderate coronary artery calcification in subjects with no or minimal calcification.

Relapsing polychondritis presenting with inflammatory pseudotumor.

To the Editor, Relapsing polychondritis (RP) is an uncommon, chronic multisystem disorder characterized by recurrent episodes of cartilaginous tissue inflammation. It can be life threatening, debilitating, and difficult to diagnose [1]. Cartilaginous tissues are the primary targets of destruction, but immune damage can spread to involve non-cartilaginous tissues such as the kidney and blood vessels [2]. Central nervous system (CNS) involvement is rare, and can manifest as cranial neuropathies, meningitis, or meningoencephalitis [3]. Only a few patients with RP and nervous system involvement have been reported in Korea. In this report, we describe a patient with multiple cranial nerve palsies due to RP related inflammatory pseudotumor. A 60-year-old man was diagnosed with RP when he presented with auricular chondritis, hearing loss, and saddle nose deformity. He had a history of recurrent inflammatory episodes involving auricular and nasal cartilage, as well as a history of conjunctivitis. Laboratory evaluation revealed elevated C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). Autoantibody tests for rheumatoid factor, anti-nuclear antibodies, and anti-neutrophil cytoplasmic antibodies were negative. The diagnosis of RP was established based on typical clinical manifestations, without pathological examination. The patient was treated with 1 mg/kg/day of oral prednisolone and experienced symptomatic improvement. With gradual prednisolone tapering, azathioprine was added. During a 3-month follow-up, he remained well while continuing to receive 5 mg prednisolone and 100 mg azathioprine per day orally. Four months after the diagnosis of RP, the patient began experiencing visual difficulties. He developed ptosis and diplopia in the left eye without any history of head trauma or ocular injury. When he was evaluated in the emergency room, his vital signs were within normal limits. Neurological examinations showed third, fourth, and sixth cranial nerve palsies of the left eye (Fig. 1). Pupils were equal in size and responded normally to light. The patient also complained of paresthesia in the territory of the first division of the left trigeminal nerve. Except for these neurologic abnormalities, his physical findings were non-specific. Figure 1. Extraocular left eye movements were disturbed in all directions. Blood tests showed normal CRP and ESR at 0.08 mg/dL and 10 mm/hr, respectively. Lumbar puncture revealed an opening pressure of 14 cm H2O. The cerebrospinal fluid (CSF) tests results were white blood cell count, 0/mm3; glucose, 70 mg/dL (plasma glucose level 100 mg/dL); protein, 23.7 mg/dL, adenosine deaminase 0.1 IU/L. No organisms were observed on Gram stain and acid-fast bacillus stain. Cryptococcus antigen test and mycobacterium tuberculosis polymerase chain reaction test were negative. The final CSF culture results revealed no organisms. CSF cytology was negative for malignant cells. Magnetic resonance imaging (MRI) of the cranial nerves showed diffuse thickening and enhancement of the bilateral cavernous sinuses, orbital apex, and pachymeninges along with Meckel’s cave (Fig. 2). These findings suggest inflammatory pseudotumor involvement of the cranial nerve pathways. Nerve conduction study, electromyography, and blink test were performed. The results indicated bilateral trigeminal nerve dysfunction. Biopsy of the lesion was not performed because it was difficult to reach and the procedure was considered high risk for complications such as nerve injury. Figure 2. Fat-saturated contrast-enhanced T1-weighted magnetic resonance imaging showing: (A, C) diffuse enhancing thickening involving left orbital apex (arrows); (B) enhancing pachymeningeal thickening, including in left Meckel’s (trigeminal) cave (arrowheads); ... The patient was started on intravenous (IV) methylprednisolone, 1 mg/kg/day. After 4 days, extraocular movements were slightly improved, but the left eye ptosis remained. He was started on IV methylprednisolone, 1 g/day over 5 days followed by oral prednisolone, 60 mg/day. High dose steroid therapy resulted in full neurologic recovery after 3 weeks. The prednisolone dosage was gradually reduced. Few previous cases of RP with CNS involvement have been reported. In most cases, the clinical manifestation was meningoencephalitis. Other associated neurological disorders include impaired cognitive dysfunction, seizure, ptosis, and diplopia. The etiology of CNS involvement in RP patients remains unknown but likely originates from autoimmunity. Wang et al. [3] speculated that vasculitis or non-specific inflammation might involve the leptomeninges and brain parenchyma. Ocular manifestations of RP are diverse. The most common manifestations are scleritis and episcleritis. Iritis may occur in as many as 30% of patients who present with scleritis or keratitis. Proptosis with chemosis simulating an orbital pseudotumor is the uncommon manifestation, but may be the initial presentation of RP [4]. Extraocular muscle palsies have been reported and are probably related to a vasculitis involving muscles or related to nerve insults. The current patient presented with multiple cranial nerve palsies and without any findings of meningoencephalitis or scleritis. MRI revealed diffuse thickening and enhancement of the cranial nerve pathways including bilateral cavernous sinuses, orbital apex, and Meckel’s cave. If an orbital mass is seen, biopsy may be necessary to reveal the type of inflammatory histology and exclude neoplastic causes. In this case, a biopsy was not performed for tissue confirmation because of the lesion location. Lichauco et al. [5] reported an orbital mass in a patient with RP that was confirmed by biopsy as mucosa-associated lymphoid tissue type B cell lymphoma. In the reported case by Lichauco et al. [5], biopsy was performed because the initial steroid treatment was only partially effective. Our patient completely recovered after steroid treatment, but biopsy would be necessary if his symptoms reappear or if any suspicion of malignancy arises. We report our experience with a patient diagnosed with RP and pseudotumor who presented with multiple cranial nerve palsies. In RP patients, CNS and ocular manifestations are diverse. If neurologic or ophthalmologic symptoms develop, careful neurologic examination, imaging, and biopsy should be considered to establish a diagnosis.