Objective Low serum cholesterol is associated with a poor prognosis in patients with chronic heart failure (CHF). However, the relationships between the serum cholesterol level, production of monocyte proinflammatory cytokines and long-term prognosis in CHF patients remain unclear. Methods A total of 95 CHF patients who had not been treated with statins and had a mean left ventricular ejection fraction of 26.0±6.0% were examined. Peripheral blood mononuclear cells (PBMCs) were isolated, and the production of monocyte tumor necrosis factor (TNF)-α and interleukin (IL)-6 was measured and expressed as the mean ± SD (pg/mL/106 PBMCs). Results The production of monocyte TNF-α and IL-6 was found to be significantly and negatively associated with the serum low-density lipoprotein (LDL)-cholesterol level (TNF-α: r=-0.515, p<0.001, IL-6: r=-0.419, p<0.001). During a median follow-up of 66.0 months, 49 patients developed cardiac events, including 21 cardiac deaths and 28 readmissions for worsening CHF. A multivariate Cox hazard analysis showed that a monocyte TNF-α level of ≥4.9 pg/mL/106 PBMCs [hazard ratio (HR) 187.38, 95% confidence interval (CI) 7.92-4,434.94, p=0.001] and LDL-cholesterol level of <120 mg/dL (HR 9.41, 95% CI 1.02-86.66, p=0.048) were independently associated with the incidence of cardiac events. Conclusion Low LDL-cholesterol and the upregulation of monocyte proinflammatory cytokine production are both significantly and independently associated with poor outcomes in CHF patients.
Objective Patients with type 2 diabetes mellitus (T2DM) and peripheral arterial disease are classified as having very high cardiovascular risks. We therefore sought to determine whether assessments of the ankle brachial index (ABI) and brachial ankle pulse wave velocity (baPWV) together exhibited a superior association with the outcomes of T2DM. Methods A retrospective analysis of patients receiving ABI and baPWV during the period 2005-2007 was performed. Patients A total of 452 subjects were enrolled and followed-up for a mean 5.8 years after being grouped according to the ABI (<0.9 vs. ≥0.9) and baPWV (<1,700 cm/s vs. ≥1,700 cm/s). Results The outcomes were all-cause mortality and composite events (all-cause mortality, hospitalization for coronary artery disease, stroke, re-vascularization, amputation and diabetic foot). Inter-group differences in the smoking rate, duration of diabetes, systolic and pulse blood pressure, anti-platelet drugs, estimated glomerular filtration rate, and urine albumin excretion were significant. During the follow-up period, 17 (3.7%) individuals died and composite events were recorded in 64 cases (14.1%). A low ABI plus high baPWV was found be associated with poor outcomes compared with a normal ABI plus low baPWV (p<0.001). Meanwhile, a low ABI plus high baPWV was associated with an increased risk of all-cause mortality [hazard ratio (HR) 17.01, 95% confidence interval (CI) 1.57-183.73, p=0.019] and composite events (HR 8.53, 95% CI 3.31-21.99, p<0.001). Conclusion In this study, the outcomes of patients with a low ABI plus high baPWV were the worst, while the subjects with a low ABI plus low baPWV or normal ABI exhibited similar outcomes. Therefore, the ABI plus baPWV exhibits a better association with the outcomes of T2DM.
Objective Galactomannan (GM) and (1, 3)-β-D-glucan (BG) are considered useful seromarkers for the diagnosis of invasive pulmonary aspergillosis (IPA) in patients with neutropenia. However, there is still limited data on these seromarkers for testing non-neutropenic patients who are at the risk of IPA. The aim of this study was to evaluate the value of these two serum antigen assays for the early diagnosis of IPA in patients without neutropenia. Methods Between January 2011 and December 2012, 97 patients with suspected IPA admitted to the department of respiratory diseases and the respiratory intensive care unit were prospectively monitored. Serum GM and BG assays were performed before the patients received antifungal therapy. Results Patients were classified as proven IPA (n=11), probable IPA (n=16), possible IPA (n=4), or non-IPA (n=66). The most common underlying disease of patients with IPA was chronic obstructive pulmonary disease (18.5%), and 22.2% patients with IPA had no known diseases. The sensitivities, specificities, and positive and negative predictive values of the GM and BG assays and at least one positive on both assays were 40.7%/89.4%/61.1%/78.7%, 48.1%/78.8%/48.1%/78.8%, and 70.4%/75.8%/54.3%/86.2%, respectively. Conclusion Compared with the testing of neutropenic patients, the serum GM or BG assay alone was less useful for the diagnosis of IPA in non-neutropenic patients. However, at least one positive result of the two serum assays appeared to be useful in the diagnosis of IPA in non-neutropenic patients.
Objective We conducted a multicenter retrospective survey of patients poisoned by synthetic chemicals (SCs) in Japan. Methods Letters were sent to 467 emergency facilities requesting participation in the study, and questionnaires were mailed to facilities that agreed to participate. Patients The study participants were patients who were transported to emergency facilities between January 2006 and December 2012 after consuming SC-containing products. Results We surveyed 518 patients from 60 (12.8%) facilities. Most patients were male (82.0%), in their 20s or 30s (80.5%), and had inhaled SCs (87.5%) contained in herbal products (86.0%). Harmful behavior was observed at the scene of poisoning for 56 patients (10.8%), including violence to others or things in 32, traffic accidents in seven, and self-injury or suicide attempts in four. Other than physical and neuropsychiatric symptoms, some patients also had physical complications, such as rhabdomyolysis (10.0%). Of the 182 patients (35.1%) admitted to hospitals, including 29 (5.6%) who needed respirators, all of the 21 (4.1%) hospitalized for at least seven days were male, and 20 had physical complications (rhabdomyolysis, 12; liver dysfunction, 5; renal dysfunction, 11; and physical injuries, 3). Most patients (95.6%) completely recovered, although 10 (1.9%) were transferred to a psychiatric department or hospital, and three (0.6%) were handed over to the police due to combative or violent behavior. SCs such as synthetic cannabinoids, synthetic cathinones, or methoxetamine were detected in 20 product samples. Conclusion Consuming products containing SCs can result in physical complications, including rhabdomyolysis, injuries, and physical or neuropsychiatric symptoms, which may require active interventions, such as respirator use or prolonged hospitalization.
Objective The distribution of the Mini-Mental State Examination (MMSE) scores by age and educational level was investigated in subjects that underwent comprehensive brain examinations. Methods This cross-sectional study included 1,414 adults without neurological disorders who underwent health-screening tests of the brain, referred to as the "Brain Dock," in our center. The MMSE scores were compared between age groups (40-44, 45-49, 50-54, 55-59, 60-64, 65-69, or ≥70 years) and educational levels [the low education level group (6-12 years) and the high education level group (≥13 years)]. Results The median age was 59 years, and 763 (54%) were women. There was no significant difference in the MMSE total score between women and men. The stepwise method of the multiple linear regression analysis confirmed that a higher age [β value, -0.129; standard error (S.E.), 0.020; p<0.001], low education level (6-12 years) (β value, -0.226; S.E., 0.075; p=0.003), and women (β values, 0.148; S.E., 0.066; p=0.024) was significantly associated with decreased MMSE score. In general, both the percentile scores and mean scores decreased with aging and were lower in the low education level group than in the high education level group. The degree of decrement in scores with age was stronger in the low education level group than in the high education level group. Conclusion The provided data for age- and education-specific reference norms will be useful for both clinicians and investigators who perform comprehensive brain examinations to assess the cognitive function of subjects.
Objective Short-term mortality rates remain high among critically ill human immunodeficiency virus-1 (HIV-1) patients though long-term mortality rates have dropped. Baseline risk factors for short-term mortality have not yet been determined in China. In this paper, we herein describe clinical characteristics, laboratory findings, causes of clinical deterioration, and risk factors associated with mortality among HIV-1 patients within six months after hospital admission. Methods We carried out a prospective study of hospitalized patients in advanced stages of HIV infection. These patients started antiretroviral therapy three or four weeks after admission. Follow-up was conducted for a period of six months. We used a multivariate logistic-regression analysis to identify risk factors associated with mortality. Results A total of 141 patients met our inclusion criteria. The mean age was 41 years. Fever and weight loss were the most common clinical manifestations of advanced HIV disease. Oral candidiasis, tuberculosis, cytomegaloviremia, and pneumocystis pneumonia were the most common opportunistic infections. Significantly decreased CD4+ T-cell counts, hypoalbuminemia, anemia, hyponatremia, as well as elevated C-reactive protein (CRP) and glutamic alanine transaminase levels were common laboratory test abnormalities. The mortality rate was 21.3%. The patients who died were more likely than the survivors to have low CD4+ T-cell counts as well as low creatinine, hemoglobin, albumin, and serum sodium levels while also having longer intervals of fever and higher CRP levels. A multivariate analysis demonstrated that the independent risk factors for mortality were active tuberculosis [odds ratio (OR): 2.681; 95% confidence interval (CI), 1.006-7.142; p=0.049], hyponatremia (OR: 3.027; 95% CI, 1.238-7.401; p=0.015), and being at clinical stage 4 (as defined by the World Health Organization) (OR: 9.492; 95% CI, 1.200-75.065; p=0.033) within the first six months of admission. Conclusion Special consideration should be given to patients who have active tuberculosis, are at clinical stage 4, and present with hyponatremia upon admission as these were found to be important factors associated with mortality within six months of hospital admission in HIV-1 patients.
Objective There have been no previous studies regarding the relationship between the respiratory function and incident diabetes in East Asian women in whom obesity is not prevalent. Methods Using Cox regression models, hazard ratios (HRs) for incident diabetes for each one SD increase in the percent vital capacity (%VC), a parameter of restrictive pulmonary dysfunction, forced expiratory volume in one second over forced vital capacity (FEV1/FVC), a parameter of obstructive pulmonary dysfunction, and log high-sensitivity C-reactive protein (hs-CRP) were calculated in 1,704 men and 1,016 women among a Japanese health screening population. Results Over the four-year study period (mean of 3.4 years), 54 men (3.2%) and 19 women (1.9%) developed diabetes. The HRs [95% confidence intervals (CIs); p values] for incident diabetes for each one SD increase in %VC and log hs-CRP were 0.81 (0.61-1.06; 0.127) and 1.29 (0.97-1.73; 0.085), respectively in men, and 0.55 (0.35-0.88) 0.012 and 2.50 (1.37-4.57; 0.003), respectively in women adjusted for age, fasting glucose and body mass index. The FEV1/FVC was not found to be significantly associated with incident diabetes in any regression models. The Spearman's correlation coefficients between %VC and hs-CRP was -0.11 (p<0.001) in men and -0.08 (p=0.007) in women. The HRs (95% CIs; p values) for each one SD increase in %VC and hs-CRP were 0.86 (0.65-1.13; 0.278) and 1.26 (0.94-1.70; 0.125), respectively in men, and 0.56 (0.34-0.94; 0.028) and 2.95 (1.49-5.81; 0.002), respectively in women, further adjusted for each other, systolic blood pressure, triglycerides and HDL cholesterol. Conclusion A low %VC was found to be associated with incident diabetes, independent of hs-CRP in women among a Japanese health screening population.
Objective The causes of fever of unknown origin (FUO) vary depending on the region and time period. We herein present a study of patients with classic FUO where we investigated differences based on patient background factors, such as age and causative diseases, and changes that have occurred over time. Methods We extracted and analyzed data from the medical records of 256 patients ≥18 years old who met the criteria for classic FUO and were hospitalized between August, 1994 and December, 2012. Results The median age of the patients was 55 years (range: 18-94 years). The cause of FUO was infection in 27.7% of the patients (n=71), non-infectious inflammatory disease (NIID) in 18.4% (47), malignancy in 10.2% (26), other in 14.8% (38), and unknown in 28.9% (74). The most common single cause was human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) (n=17). NIID and malignancy were more common in patients ≥65 years old than in patients <65 years old. During 2004-2012, compared to 1994-2003, infections and "other" causes were decreased, whereas NIID, malignancy, and unknown causes were increased. Conclusion FUO associated with HIV/AIDS is increasing in Japan. In addition, as in previous studies in Japan and overseas, our study showed that the number of patients in whom the cause of FUO remains unknown is increasing and exceeds 20% of all cases. The present study identified diseases that should be considered in the differential diagnosis of FUO, providing useful information for the future diagnosis and treatment of FUO.
We encountered a rare case of severe diffuse duodenitis associated with ulcerative colitis (UC). A 23-year-old man underwent total proctocolectomy with ileal J-pouch anal anastomosis for UC. He suffered from severe abdominal pain, fever and bloody diarrhea for six months after the surgery. Upper double-balloon enteroscopy disclosed severe diffuse duodenitis, of which the findings were endoscopically and histologically similar to those of colonic lesions of UC. Although the administration of prednisolone was ineffective, treatment with intravenous tacrolimus markedly improved the clinical findings. This is the first report of the successful treatment of severe UC-associated diffuse duodenitis with intravenous tacrolimus.
We recently encountered the case of a patient with a synchronous duodenal gastrointestinal stromal tumor (GIST) and pancreatic neuroendocrine tumor (PNET). This is the first report of this specific combination of multiple primary tumors, although three cases involving both PNET and gastric GIST have previously been reported. Since the duodenal GIST developed close to the pancreatic uncus in this case, we considered the possibility of multiple PNETs in the differential diagnosis. However, a histopathological examination using endoscopic ultrasonography-guided fine-needle aspiration confirmed the diagnosis of multiple primary lesions, involving PNET and duodenal GIST.
Ursodeoxycholic acid (UDCA) is often used to treat cholesterol gallstones. UDCA makes cholesterol stones soluble, thereby improving biliary emptying. Conversely, however, UDCA can also form stones via an unknown mechanism, as shown in a few previous reports of cholangitis caused by the formation of UDCA stones in the common bile duct (CBD). We herein report four cases of recurrent cholangitis resulting from UDCA stones. The withdrawal of UDCA administration was highly effective in these patients. The details of these four cases suggest that clinicians must rethink the indications for UDCA treatment in cases in which cholangitis caused by CBD stones frequently recurs over a short period of time.
We herein report a case of hepatocellular carcinoma (HCC) with lung metastasis that was successfully treated with transcatheter arterial infusion chemotherapy via the hepatic and bronchial arteries. A 64-year-old man diagnosed with HCC in 2003 was treated with locoregional therapy followed by sorafenib for recurrent HCC. Tumor thrombosis and lung metastasis were noted in April 2012. We administered IA-call®, a fine-powder formulation of cisplatin, via the hepatic and bronchial arteries. This therapy resulted in the disappearance of the lung metastases and a partial response to tumor thrombosis. The patient remained alive for 23 months after developing lung metastasis.
A 31-year-old woman with treatment-resistant pregnancy-induced hypertension during her first pregnancy delivered a small-for-gestational-age infant (weight: 1,070 g). After delivery, she was diagnosed with primary aldosteronism (PA) associated with a left adrenal adenoma. Following a thorough examination, she underwent laparoscopic left adrenalectomy, and the diagnosis of an aldosterone-producing adenoma was confirmed based on a pathological examination. Thereafter, the patient's hypertension and hypokalemia completely disappeared. She became pregnant again and successfully delivered her second infant at the 37th week of gestation (weight: 2,720 g) without developing treatment-resistant hypertension. Secondary causes of hypertension should not be overlooked, even in young pregnant women.
Chronic neutrophilic leukemia (CNL) is a rare myeloproliferative neoplasm. We herein describe the case of a 41-year-old woman who was admitted with nephrotic syndrome (NS) and severe neutrophilia and underwent a splenectomy due to splenomegaly. Peripheral blood tests revealed a Janus kinase 2 (JAK2) V617F mutation without the Philadelphia chromosome, BCR-ABL fusion transcripts, or FIP1 L1-platelet-derived growth factor (PDGF)a. A kidney biopsy showed focal segmental glomerulosclerosis (FSGS) with interstitial neutrophil infiltration and with a JAK2 V617F mutation. Hydroxyurea was initiated for first three months, followed by hydroxyurea plus interferon, and a subsequent improvement in leukocytosis and completely remission of FSGS-NS was immediately noted. This is the first case reported in which NS was related to CNL.
Primary bladder amyloidosis is a rare disease, with only 200 cases reported worldwide. This condition is clinically important since it masquerades as a malignancy. We herein present a case of primary bladder amyloidosis presenting as painless hematuria and dysuria. Computed tomography and ultrasound showed thickening of the posterior bladder wall. Cystoscopy revealed abnormal bladder tissue suspicious of malignancy. However, transurethral resection of a bladder tumor showed no evidence of malignant cells. Amyloid was identified on Congo red staining. Therefore, the possibility of secondary amyloidosis was ruled out and a diagnosis of primary bladder amyloidosis was made. Nine months after undergoing primary resection, the patient's amyloidosis recurred at the initial site.
We herein report a patient with clinically amyopathic dermatomyositis (CADM) who developed anti-CADM-140 autoantibody in association with rapidly progressive interstitial lung disease (RP-ILD). Chest high-resolution computed tomography (HRCT) revealed early pulmonary involvement preceding typical cutaneous lesions. Primary lesions of patchy peribronchial opacity developed ground-glass opacity and consolidation with architectural distortion and traction bronchiectasis. The possibility of anti-CADM-140 autoantibody-associated RP-ILD should be considered when patchy peribronchial opacity of an unknown cause is visible on chest HRCT.
A 57-year-old right-handed woman with a history of left frontal lobe stroke had experienced episodes of language-expression difficulty followed by paraphasia lasting for approximately 30 seconds two years earlier. She was diagnosed with left frontal lobe epilepsy, and a lamotrigine regimen was initiated. This treatment had to be stopped five weeks after initiation because she developed a rash, and her drug lymphocyte stimulation test result was positive. Interestingly, she has since remained seizure free without requiring any antiepileptic medications. This adult case with a peculiar clinical course provides support for the hypothesis of immunomodulation process involvement in epilepsy, a phenomenon that was previously mainly seen in pediatric patients.
A 75-year-old man with paroxysmal atrial fibrillation developed a traumatic intracranial hemorrhage during warfarin treatment. The administration of warfarin was stopped and rivaroxaban therapy, a novel oral anticoagulant (NOAC), was started. Immediately, his platelet count decreased to 3.7×104 /μL. The platelet count recovered rapidly after cessation of rivaroxaban administration. Development of thrombocytopenia and its rapid recovery was observed again after another administration, and subsequent cessation, of the drug. A diagnosis of rivaroxaban-induced thrombocytopenia was made. The incidence of thrombocytopenia due to NOACs is rare. Careful attention to thrombocytopenia, which is associated with a higher risk for life-threatening bleeding, is therefore necessary during treatment with NOACs.
A spinal cord lesion is a rare manifestation of neurosarcoidosis. We herein report a case with dysuria and gradually worsening numbness in both lower extremities. Thoracic magnetic resonance imaging (MRI) revealed a long spinal cord lesion with gadolinium enhancement in the lower part of the lesion. Chest computed tomography demonstrated enlarged hilar lymph nodes, and a biopsy revealed sarcoidosis. Methylprednisolone pulse therapy was started, but a follow-up MRI showed aggravation of the spinal lesion. After the addition of methotrexate to the therapy, the patient's aggravation of the spinal lesion and clinical symptoms ceased. Early diagnosis and treatment using combined methylprednisolone and methotrexate therapy may improve this devastating spinal cord disease.
We herein report two cases of acute ischemic stroke associated with iron deficiency anemia (IDA) due to bleeding from uterine fibroids. Anemia is not generally recognized as a risk factor for stroke. The physiological mechanisms that may factor in the development of ischemic stroke in patients with IDA include thrombocytosis, hypercoagulable state, and anemic hypoxia. In our two cases, IDA was considered to be the cause of ischemic stroke because all other known causes of stroke were ruled out. In patients with ischemic stroke due to anemia, early treatment of the anemia is important to prevent stroke recurrence.
Herpes simplex virus has protean manifestations and is an important cause of morbidity in the immunocompromised host. We report a case of recurrent lymphadenopathy and rash in a patient with chronic lymphocytic leukemia. The elusive clinical diagnosis eventually required core biopsy of a lymph node with immunohistochemistry and confirmation by polymerase chain reaction. This case illustrates the challenging clinical and laboratory diagnosis of herpes simplex virus lymphadenitis and the need to maintain a high index of suspicion for infection when treating an immunocompromised patient with unusual and/or persistent symptoms.
Pseudomonas stutzeri (P. stutzeri) is a Gram-negative, non-fermenting rod. It is a rare pathogen; therefore, its isolation is often associated with colonization or contamination. We herein describe the first reported case of necrotizing pneumonia caused by P. stutzeri in a non-HIV infected patient with previously undiagnosed pulmonary tuberculosis. The isolate was found to be antibiotic resistant, which led to the failure of the initial treatment. This case highlights the unique presentation of necrotizing pneumonia caused by P. stutzeri and the importance of emerging antimicrobial resistance in P. stutzeri.