Objective Little is known about the relationship between elevated serum α-fetoprotein (AFP) levels and insulin resistance, which adversely influence the clinical course of chronic hepatitis C (CHC). Therefore, we investigated the association between serum AFP and insulin resistance in patients with CHC.
Methods We retrospectively investigated 300 patients with CHC without hepatoma who underwent liver biopsies and oral glucose tolerance tests. Patients taking antidiabetic drugs were excluded. We analyzed factors associated with elevated AFP levels (≥10.0 ng/mL) in 265 eligible patients. Twenty patients with a homeostasis model assessment for insulin resistance value of ≥2.0 and a whole-body insulin sensitivity index of <5.0 received prospective lifestyle intervention.
Results A univariate analysis showed that the body mass index, platelet count, levels of albumin, aspartate aminotransferase, alanine aminotransferase and γ-glutamyl transpeptidase, glucose metabolism, hepatic inflammation, fibrosis and steatosis were associated with elevated AFP levels. In a multivariate analysis, a platelet count of <15×10⁴ /μL, aspartate aminotransferase level of ≥50 IU/L, γ-glutamyl transpeptidase level of ≥35 IU/L, whole-body insulin sensitivity index of <5.0 and stage 3-4 fibrosis were independently associated with an elevated AFP level. A Bayesian Network analysis showed that the aspartate aminotransferase level, whole-body insulin sensitivity index and hepatic fibrosis were directly associated with an elevated AFP level. The lifestyle intervention significantly improved the serum AFP level, homeostasis model assessment for insulin resistance and whole-body insulin sensitivity index.
Conclusion Whole-body insulin resistance is associated with an elevated serum AFP level in patients with CHC. Lifestyle interventions targeting insulin resistance can reduce the serum AFP level and may ameliorate the clinical course of CHC.

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Objective Although both atrial fibrillation (AF) and gastroesophageal reflux disease (GERD) are common diseases, the relationship between these two conditions remains controversial, depending on the study design and type of AF. Therefore, we focused on the relationship between nonvalvular AF and GERD.
Methods A total of 479 consecutive subjects (255 men and 224 women, mean age: 60.4 ± 12.8 years), including outpatients at several hospitals (n=201) and participants of an annual health screening program (n=278), were enrolled. Subjects with valvular AF, malignancy or dementia were excluded. The frequency scale for symptoms of GERD (F-scale) was applied after obtaining each patient's informed consent for screening symptomatic GERD with a total cutoff score of 8 points. The score on the questionnaire was correlated with the baseline characteristics extracted from the patients' medical records.
Results The total F-scale scores were significantly higher in the older patients (≥60 years) than in the younger patients (<60 years) (p=0.017) and increased in the following order: permanent AF > paroxysmal AF > sinus rhythm (p=0.003). The incidence of GERD increased in the same order among the patients with the various heart rhythm classifications (p<0.001). Coronary heart disease, hypertension, diabetes and dyslipidemia were not correlated with the F-scale scores or incidence of GERD. The stepwise discriminant analyses demonstrated that nonvalvular AF alone was significantly associated with symptomatic GERD (Wilks' lambda=0.983, p=0.004).
Conclusion This multicenter study demonstrated that nonvalvular AF is significantly correlated with symptomatic GERD. This small sample survey warrants a future study of a large-scale cohort.

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Objective The management of diabetes mellitus includes controlling the blood glucose level, body weight, blood pressure and serum lipid level. The coexistence of diabetes and a high low-density lipoprotein cholesterol (LDL-C) level promotes atherosclerosis of the coronary arteries and increases the risk of coronary artery disease (CAD). We compared the rates of attainment of LDL-C goals in type 2 diabetes patients receiving primary and secondary prevention therapy, the former without a history of CAD and the latter with a history of CAD. Because patients receiving secondary prevention are at greater risk of coronary events, LDL-C management is especially important in this group. This study was designed to determine how frequently diabetic patients attain their LDL-C goals and identify the reasons for the lack of attainment.
Methods The groups were distinguished according to the patients' medical records. Contributory factors for the patients not achieving their goals were recorded in a questionnaire filled out by each patient's physician.
Results The overall attainment rate in both groups was 61%. The most frequent impediment in both groups was "an LDL-C level above or below the goal at every hospital visit" followed by "continuously sufficient effects of dietary therapy only" and the "management of LDL-C by other departments or hospitals," the latter reflecting the increasing problems of polydisease and polypharmacy in diabetes care.
Conclusion Polydisease and polypharmacy issues in diabetes patients with a history of CAD constitute a growing barrier to medication adherence and the attainment of treatment goals.

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Objective Clinically, the ankle-brachial blood pressure index (ABI) and skin perfusion pressure (SPP) are used to screen for subclinical peripheral artery disease. However, the association between the SPP and mortality in hemodialysis patients has not been previously reported. We investigated these factors and compared the ABI and SPP in patients receiving hemodialysis.
Methods A total of 102 patients receiving maintenance hemodialysis were enrolled in this study. The ABI was determined using an ABI-form (Colin, Japan). The SPP was measured using a SensiLase^TM PAD3000 (Kaneka, Osaka, Japan).
Results The mean follow-up period was 3.2±1.4 years. A multivariate Cox analysis identified a low ABI (p=0.019) and a low SPP (p=0.047) as being independent predictors of mortality. A receiver operating characteristic (ROC) analysis of the ABI revealed a cutoff point of 1.1 and an area under the curve (AUC) of 0.79, with a sensitivity of 90% and a specificity of 62%. A ROC analysis of the SPP revealed a cutoff point of 54.0 mmHg and an AUC of 0.71, with a sensitivity of 55% and a specificity of 84%.
Conclusion Both low ABI and SPP values were found to be independent risk factors for mortality among hemodialysis patients. The cutoff point for ABI as a predictor of mortality was 1.1, while that for SPP was 54.0 mmHg.

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Objective To evaluate the association between vitamin D receptor (VDR) BsmI gene polymorphism and the risk of end-stage renal disease (ESRD).
Methods All eligible studies were included in our meta-analysis of a search of the PubMed, Embase, Cochrane and China National Knowledge Infrastructure (CNKI) databases according to predefined criteria. The fixed-effects or, in the presence of heterogeneity, random-effects models were used to calculate the pooled odds ratio (OR) and corresponding 95% confidence interval (CI).
Materials Six studies including 863 patients and 1,063 controls were recruited for the analysis of the association between the VDR BsmI gene polymorphism and the risk of ESRD.
Results The B allele/BB genotype was not associated with the ESRD risk in the overall population, Caucasians or Asians (overall population: p=0.492 and 0.382, Caucasians: p=0.765 and 0.522, Asians: p=0.607 and 0.481). The Bb/bb genotype was also not associated with the risk of ESRD in the overall population, Caucasians or Asians (overall population: p=0.556 and 0.166, Caucasians: p=0.770 and 0.965, Asians: p=0.411 and 0.098). The exclusion of any single study had little impact on the p value in the overall population. No evidence of publication bias was observed.
Conclusion VDR BsmI gene polymorphism appears to not be associated with the risk of ESRD in the overall population, Caucasians or Asians. However, more studies should be performed in the future.

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Objective Information available on the clinical features and outcomes of pneumonia in diabetic patients is limited. There are no data on the association between glycemic control during hospitalization and mortality in this population. The objective of this study is to examine whether the presence of hyperglycemia on admission and during hospitalization is associated with mortality in diabetic patients admitted to the hospital for pneumonia.
Methods This study is a retrospective observational cohort study of diabetic adults hospitalized for the first time for pneumonia between 2005 and 2011 in a 358-bed community hospital. Univariate and multivariate analyses were performed for 30-day all-cause hospital mortality adjusted for sex, age, type of pneumonia (community-acquired pneumonia or nursing and health care-associated pneumonia), severity of pneumonia according to the A-DROP score and various comorbidities in consideration of the serum glucose and hemoglobin A1c levels on admission and the mean plasma glucose level during hospitalization.
Results Of the 1,499 pneumonia patients evaluated, 185 (12.3%) (mean age 75 years) had diabetes mellitus. Fourteen (7.6%) of the 185 diabetic patients died within 30 days after admission. According to the univariate analysis, 30-day mortality was significantly associated with the A-DROP score (p<0.0001), the admission glucose level (p=0.01) and the mean plasma glucose level during hospitalization (p<0.0001). Even after adjusting for factors related to the severity of pneumonia, the mean plasma glucose level during hospitalization remained significantly associated with 30-day mortality (p=0.004).
Conclusion Hyperglycemia determined according to the mean plasma glucose level during hospitalization is independently associated with 30-day all-cause hospital mortality in diabetic patients admitted for pneumonia.

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An 85-year-old woman was hospitalized with rapidly progressive paraparesis without altered consciousness, although she was not definitively diagnosed. She developed acute drowsiness and disorientation several days later. An intrahepatic portosystemic venous shunt (IPSVS) was observed on enhanced computed tomography, and hyperammonemia suggested leakage of neurotoxins from the shunt as the etiology of the patient's symptoms. Her neurological symptoms and hyperammonemia improved following transcatheter shunt embolization. We diagnosed her with hepatic myelopathy, which is a rare complication of liver cirrhosis and portosystemic venous shunts. Hepatic myelopathy resulting from a congenital IPSVS has not been previously reported. A diagnosis of hepatic myelopathy should be ruled out in diagnostically difficult cases of paraparesis.

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Various laboratory and patient-related factors can affect the measurement of hemoglobin A1c (HbA1c). We herein present the case of a diabetic patient with spuriously low HbA1c values on ion-exchange high-performance liquid chromatography (HPLC). Further investigations revealed that the patient was heterozygous for a rare Hb variant, namely Hb Iraq-Halabja (β10 Ala→Val). This is the second report of this variant published in the literature. Clinicians should be aware of the limitations of HbA1c assays because inaccurate values may lead to the inappropriate management of diabetes. Unusual or discrepant HbA1c test results should prompt further investigations for potentially interfering factors, including rare Hb variants.

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A 62-year-old woman complained of repeated hypoglycemic events. A 75g oral glucose tolerance test (75gOGTT) showed a marked increase in the plasma insulin level and impaired glucose tolerance. The patient exhibited a high titer of plasma anti-insulin autoantibodies. Her diagnosis was insulin autoimmune syndrome (IAS). Following the cessation of loxoprofen-sodium (LOXs), she experienced no further hypoglycemic episodes. However, the hypoglycemic attacks recurred following the accidental readministration of LOXs in an adhesive skin patch. Considering the changes in the titer of anti-insulin autoantibodies, the repeated 75gOGTT and the repeated Scatchard analysis, we determined LOXs to be the cause of the IAS and evaluated the characteristics of the autoantibodies.

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Spontaneous pneumothorax in the elderly commonly occurs due to underlying pulmonary diseases, such as chronic obstructive pulmonary disease, interstitial lung disease, lung cancer, etc. A 73-year-old woman developed pneumothorax for the first time that was a clinical clue to a diagnosis of Birt-Hogg-Dubé syndrome (BHDS), an autosomal dominant condition characterized by fibrofolliculomas of the skin, renal tumors and multiple lung cysts predisposing to pneumothorax. Although BHDS patients frequently develop pneumothorax during their twenties to forties, the present case indicates that BHDS should be considered as an underlying cause of pneumothorax in the elderly with undisclosed BHDS.

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A 47-year-old man diagnosed with pulmonary tuberculosis was referred to our hospital. Rifampicin, isoniazid, pyrazinamide and ethambutol were administered, and the patient's symptoms promptly improved. On the 19th hospital day, he developed acute kidney injury with a fever and chills. Renal biopsy specimens indicated tubulointerstitial nephritis. Suspecting rifampicin-induced acute kidney injury, we discontinued the rifampicin and administered levofloxacin in its place. The patient's serum creatinine level subsequently gradually improved. We herein report this case and review eight cases reported in Japan. We found that the rifampicin toxicity appeared at both the initial administration and readministration. All eight patients presented with proteinuria.

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We herein report a novel compound heterozygous mutation of the acid α-glucosidase (GAA) gene in a 23-year-old man with adult-onset Pompe disease. The patient was admitted for respiratory failure and a highly elevated serum level of creatine kinase (CK). His muscle pathology did not show typical vacuolated fibers; however, globular inclusion bodies with acid phosphatase (ACP) activity was observed. A molecular genetic analysis of the GAA gene revealed a novel compound heterozygous mutation, c.1544 T>A (M515K), combined with a previously reported mutation, c.1309 C>T (R437C). The presence of ACP-positive globular inclusion bodies is a useful diagnostic marker for adult-onset Pompe disease, even when typical vacuolated fibers are absent.

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We herein report the case of a 58-year-old man with advanced esophageal carcinoma who developed posterior reversible encephalopathy syndrome (PRES). He initially presented with a severe consciousness disturbance. A subsequent examination revealed hypercalcemia and an elevated serum parathyroid hormone-related peptide (PTHrP) level. Magnetic resonance imaging performed on admission and 24 days later showed reversible widespread white matter abnormalities, which confirmed a diagnosis of PRES. The patient's clinical and radiological manifestations improved upon normalization of the serum calcium level. To the best of our knowledge, this is the first report describing hypercalcemia-induced PRES occurring in association with elevated PTHrP.

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A woman with rheumatoid arthritis (RA) experienced glottic stenosis approximately two months after switching from etanercept to tocilizumab. Cricoarytenoid joint (CAJ) arthritis due to RA was diagnosed. An awake tracheostomy saved the relievable airway, and the administration of methylprednisolone and infliximab ameliorated the flare-up and glottic stenosis. A follow-up examination revealed the recovery of the patient's normal voice and good control of RA with infliximab and methotrexate. Although general physicians do not frequently encounter patients with symptomatic CAJ arthritis, this condition should be considered as it can be life-threatening. Therefore, when detected, it should be diagnosed and treated immediately.

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