Objective Infective endocarditis (IE) continues to be associated with high mortality. The aim of the present study was to identify prognostic predictors for short-term mortality in patients with IE. Methods We conducted a retrospective study of 119 consecutive patients with IE (mean age 58±17). Prognostic predictors for mortality at the early phase of admission were determined using a multivariate regression analysis, and a receiver operating characteristic (ROC) analysis was carried out to evaluate the predictive ability. Results Eleven of 119 patients died during hospital admission. In this non-survivor group, the clinical parameters at the time of admission, including serum creatinine (Cr), the estimated glomerular filtration rate (eGFR), the red blood cell count, the white blood cell count, the serum CRP level and heart rate, differed significantly from those observed in the survivors (all; p<0.05). According to a logistic regression analysis, an increase in log-serum Cr per one standard deviation (odds ratio=2.18, 95%CI=1.08-4.41) and a decrease in log-eGFR per one standard deviation (odds ratio=0.51, 95%CI=0.26-0.98) were significantly associated with in-hospital death. The area under the ROC curve for serum Cr to predict the outcome was 0.80, the sensitivity was 64% and the specificity was 85% at a cut-off value of 1.16 mg/dL. For eGFR, the area under the ROC curve was 0.77, the sensitivity was 64% and the specificity was 86% at a cut-off value of 47.5 mL/min./1.73 m2. Conclusion Mild renal dysfunction at the time of admission is an important predictor of early phase mortality in patients with IE.
Objective To investigate the predictive values of placental growth factor (PlGF) and its endogenous antagonist, soluble fms-like tyrosine kinase-1 (sFlt-1), for the long-term prognosis of patients with stable coronary artery disease (CAD). Both PlGF and sFlt-1 play important roles in the pathological mechanisms of atherosclerosis. We recently demonstrated that the plasma levels of these molecules are correlated with the severity of coronary atherosclerosis. Methods We enrolled 464 patients with stable CAD who consecutively underwent coronary angiography. Baseline blood samples were collected from the femoral artery immediately before coronary angiography (after the administration of 20 units of heparin), and the plasma levels of PlGF and sFlt-1 were measured. A Cox proportional hazard regression analysis was performed to evaluate the relationship between these parameters and the occurrence of all-cause death (ACD) and total cardiovascular events (TCVE) during a median follow-up of 3.3 years. Results A total of 31 ACDs and 51 TCVEs occurred. Patients with higher PlGF/sFlt-1 ratios (>4.22×10-2) had a significantly higher risk of both ACD and TCVE than patients with lower ratios (<4.22×10-2) (hazard ratio [HR]: 3.32, 95% confidence interval [CI]: 1.43 to 7.72, p=0.005, and HR: 2.23, 95% CI: 1.23 to 4.03, p=0.008, respectively). A multivariate analysis showed the PlGF/sFlt-1 ratio to be an independent predictor for ACD, but not TCVE. Conclusion The baseline PlGF/sFlt-1 ratio is an independent predictor of long-term adverse outcomes in patients with stable CAD.
Objective To evaluate the effects of six-month liraglutide treatment on body weight, visceral and subcutaneous fat and related markers in Japanese type 2 diabetic patients. Methods A total of 59 patients with type 2 diabetes were treated with liraglutide (0.3 mg/day for ≥1 week and then 0.6 mg/day for ≥1 week, gradually increasing the dose to 0.9 mg/day) for six months. Changes in body weight, body mass index (BMI), HbA1c, the fasting blood glucose level, visceral and subcutaneous fat areas, hepatic and renal CT values and the associated markers proinsulin, adiponectin and pentraxin (PTX) 3 were measured. Results The study included one treatment-naïve patient, 10 patients who were switched from oral antidiabetic drugs and 35 patients who were switched from insulin therapy. At six months after treatment, the preprandial blood glucose levels were higher (148.8±40.5 mg/dL) than the baseline values (130.8±36.7, p<0.05); however, body weight, BMI and abdominal circumference were lower, and the liver/kidney CT ratio improved significantly from 1.64±0.44 at baseline to 1.78±0.42. An analysis of the patients who were not pretreated with insulin resistance ameliorators showed that six months of liraglutide treatment significantly decreased the subcutaneous but not visceral fat areas, significantly decreased the serum adiponectin levels and significantly increased the serum PTX3 levels. Conclusion In addition to its glucose-lowering effects, liraglutide exhibits weight loss promotion actions, reducing subcutaneous fat areas in particular. The weight and total fat area reduction properties of liraglutide are likely to be beneficial when this medication is used in combination with other oral antidiabetic drugs and insulin.
Objective Evidence has demonstrated that Ca2+/calmodulin-dependent protein kinase type IV (CaMKIV) contributes to altered cytokine production by promoting the production of inflammatory cytokines. This study aimed to explore the protective role and underlying mechanisms of CaMKIV inhibition in experimental nephrotic syndrome. Methods BALB/c mice received single intravenous injections of adriamycin (10 mg/kg) then were sacrificed at two, four and six weeks. In the second study, treatment with KN-93, a CaMKIV inhibitor, or vehicle administered via intraperitoneal injection was started five days after adriamycin injection. Functional and pathologic parameters, the presence of inflammatory infiltration and the expressions of pro-inflammatory cytokines were assessed. Results The CaMKIV protein expression levels were upregulated in the mice with adriamycin nephropathy, which was significantly inhibited by KN-93 (p<0.01). As compared with the vehicle-treated controls, KN-93 treatment resulted in marked suppression of proteinuria and serum creatinine at week 6 (p<0.01), but not at two weeks after induction of the disease. KN-93 inhibited glomerulosclerosis and the development of tubulointerstitial lesions. The renal alpha-smooth muscle actin (α-SMA) expression was also significantly suppressed by KN-93 treatment at week 6 (p<0.01). Moreover, KN-93 inhibited the renal monocyte chemoattractant protein-1 (MCP-1) expression, paralleled by a reduction in the interstitial infiltration of macrophages and T-cells (p<0.01). Conclusion Our findings suggest that activation of CaMKIV signaling is involved in the progression of glomerular diseases with a proteinuric state. Our data therefore justify the development of small molecule CaMKIV inhibitors for the treatment of clinical nephrotic syndrome.
Objective We previously reported that the antiplatelet action is intensified with combined use of clopidogrel and cilostazol in ischemic stroke patients using the VerifyNow P2Y12 Assay. In this study, the relationship between the cilostazol dose and the platelet function achieved with combination therapy was investigated. Methods The subjects included 231 patients with noncardiogenic ischemic stroke treated at our hospital (18 patients treated with a combination of clopidogrel (75 mg) and cilostazol (100 mg), 52 patients treated with a combination of clopidogrel (75 mg) and cilostazol (200 mg), 126 patients treated with clopidogrel (75 mg) alone and 35 patients treated with cilostazol (200 mg) alone). The platelet function achieved with 20 μM of adenosine diphosphate was measured using the VerifyNow P2Y12 Assay. Clopidogrel resistance was defined as P2Y12 Reaction Units (PRU) >230 and/or % inhibition <20%. Results The PRU was >230 in 32 patients (25.4%) receiving clopidogrel alone, one patient (5.6%) receiving combination therapy with cilostazol (100 mg) and one patient (1.9%) receiving combination therapy with cilostazol (200 mg). The rate of PRU >230 was significantly lower in both of the cilostazol combination groups than in the clopidogrel alone group. The percent inhibition was <20% in 41 patients (32.5%) receiving clopidogrel alone, one patient (5.6%) receiving a combination with cilostazol (100 mg) and one patient (1.9%) receiving a combination with cilostazol (200 mg). The rate of % inhibition <20% was significantly lower in both of the cilostazol combination groups than in the clopidogrel alone group. Conclusion Clopidogrel resistance was clearly decreased with combination clopidogrel (75 mg) and low-dose (100 mg) cilostazol therapy. The use of combination therapy with clopidogrel and low-dose cilostazol may be one means of overcoming clopidogrel resistance.
A 25-year-old pregnant woman complained of abdominal pain and diarrhea. Total colonoscopy provided a diagnosis of Crohn's disease (CD) of the large intestine (Crohn's colitis). Because the patient was allergic to mesalazine, adalimumab (ADA) was used as maintenance therapy during pregnancy, following prednisolone as remission induction therapy. Remission of the patient's CD was maintained with ADA, and the patient delivered a baby girl without any difficulties. Remission of the patient's CD continued to be maintained with the administration of ADA after childbirth. We believe that this is the first report of the use of ADA therapy in a pregnant CD patient in Japan.
Portal biliopathy is a morphological abnormality of the biliary ductal and gallbladder wall associated with portal hypertension. A patient with essential thrombocythemia was initially diagnosed with extrahepatic portal vein obstruction (EHPVO). The contrast-enhanced computed tomography (CT) findings were similar to those of cholangiocarcinoma or sclerosing cholangitis. However, color Doppler and contrast-enhanced ultrasound (US) were more specific. The paracholedocheal veins around the bile ducts appeared as beads soon after the injection of contrast medium, followed by linear enhancement of the epicholedochal veins and the gradual enhancement of the whole bile ducts. These findings led to a diagnosis of portal biliopathy, which prevented the patient from having to endure hazardous procedures such as bile duct biopsies. Color Doppler and contrast-enhanced US findings are useful for diagnosing or ruling out portal biliopathy in patients who present with EHPVO.
We experienced the case of a 67-year-old man with refractory heart failure. He presented with dyspnea and progressive pitting edema of the lower limbs. Diuretics were insufficient to improve his symptoms. Cardiac catheterization demonstrated pulmonary hypertension. Additional examinations confirmed polyneuropathy, organomegaly, endocrinopathy and monoclonal gammopathy. The plasma vascular endothelial growth factor (VEGF) level was 1,340 pg/mL. The patient was diagnosed with Crow-Fukase (POEMS) syndrome. Echocardiography detected left ventricular hypertrophy and diastolic dysfunction. Polysomnography demonstrated severe sleep-disordered breathing. We herein describe a case of pulmonary hypertension with Crow-Fukase syndrome accompanied by left ventricular diastolic dysfunction and sleep-disordered breathing.
Cardiovascular complications, including cardiomegaly, myocardial ischemia and left ventricular hypertrophy, are some of the major determinants of the mortality rate in patients with Cushing's syndrome. We herein report the case of a patient with Cushing's syndrome caused by an adrenal adenoma who presented with congestive heart failure secondary to dilated cardiomyopathy. Follow-up echocardiography showed a marked improvement in the left ventricular cardiac function, and the plasma B-type natriuretic peptide (BNP) levels regressed after successful treatment. "Reversible" dilated cardiomyopathy is rarely associated with Cushing's syndrome; however, it should be recognized. Administering appropriate treatment in a timely manner can reverse this cardiomyopathy along with the other symptoms of Cushing's syndrome.
We herein present the case of a 53-year-old patient with adrenocorticotropin-independent macronodular adrenocortical hyperplasia (AIMAH), which is a rare form of Cushing syndrome. He had hypercortisolemia and bilateral macronodular adrenal glands with a left side predominance. The administration of vasopressin significantly increased the plasma cortisol level (1.9-fold). Following left adrenalectomy, the patient's hypercortisolemia significantly improved and vasopressin responsiveness was lost, suggesting that the responsiveness originated from the resected left adrenal gland. The marked difference in vasopressin responsiveness between the adrenals corresponded with their asymmetrical size and function. Evaluating the differences in the vasopressin sensitivity may therefore be helpful for understanding the progression of AIMAH.
The case of a 68-year-old woman with purpura nephritis associated with nephrotic syndrome is herein described. The patient's clinical course and the findings of a renal biopsy study revealed purpura nephritis. Following treatment with corticosteroids and intravenous cyclophosphamide accompanied by an angiotensin II type I receptor-blocker, an anti-platelet drug and an hydroxymethylglutaryl (HMG)-CoA, the proteinuria mildly decreased. Additional rituximab therapy led to a complete remission. This report describes our successful experience using rituximab to treat refractory nephrotic syndrome of purpura nephritis. Further studies are required to confirm the efficacy of rituximab as an alternative therapy for nephrotic syndrome.
An 83-year-old man who had been receiving treatment for bronchial asthma since 62 years of age experienced difficulty breathing on exertion and was admitted to the hospital. On admission, computed tomography revealed tracheal wall thickening, while test results for antinuclear antibodies and anti-type II collagen antibodies were positive. Since a saddle nose deformity, malacia of the auricles and sensorineural deafness were also observed, relapsing polychondritis was diagnosed. Measuring the peak expiratory flow rate was useful in the early airway assessment. During the follow-up period, the patient's dyspnea worsened and noninvasive positive-pressure ventilation was introduced. As a result, the subjective symptoms improved.
A 67-year-old hypoxic woman was admitted following two episodes of cerebral infarction. Based on the clinical presentation and radiological findings, a diagnosis of hereditary hemorrhagic telangiectasia was made and the cerebral ischemic complications were considered to have been caused by paradoxical embolizations related to pulmonary arteriovenous malformations (PAVMs). We performed video-assisted thoracoscopic surgery (VATS) and identified turbulent thrombi in one of the PAVMs that were capable of circulating systemically and inducing embolic strokes. The condition of the patient improved immediately following VATS. This case suggests that VATS may be a preferred therapeutic option in the treatment of patients with PAVM accompanying recurrent episodes of life-threatening complications such as strokes.
Myeloperoxidase- and proteinase 3-anti-neutrophil cytoplasmic antibodies (ANCAs) are often negative in cases in which systemic vasculitis is highly suspected. We herein present a case of bactericidal/permeability increasing protein (BPI)-ANCA-positive systemic vasculitis. This case highlights the possible role of BPI-ANCA in the pathogenesis of systemic vasculitis as well as the possible use of BPI as a diagnostic tool. The accumulation of further case-based reports is expected to shed some light on the pathogesis of systemic vasculitis.
A 74-year-old woman with refractory IgG-κ multiple myeloma developed massive melena caused by hemorrhagic submucosal tumors in the duodenum and middle jejunum. A biopsy revealed the tumor to be marked AL amyloid deposition. Treatment with bortezomib did not improve the melena or the underlying disease. The patient also developed multiple amyloidomas in the bilateral femoral heads, which caused a fracture in the left femoral head. Treatment with lenalidomide, as the final therapeutic option, resolved the intractable melena and improved both the intestinal lesions and myeloma. This case shows that successful treatment of multiple myeloma leads to marked improvement of accompanying AL amyloidosis.
A 60-year-old myelodysplastic syndrome patient underwent tandem cord blood transplantation. The primary cord blood graft was rejected, and human herpesvirus 6 (HHV6) encephalitis developed after engraftment of secondary cord blood. Polyuria and adipsic hypernatremia were observed during treatment of the encephalitis. The patient died of bacteremia caused by methicillin-resistant Streptococcus epidermis. HHV6 infection in the posterior pituitary was confirmed on autopsy, as was infection of the hippocampus, but not of the hypothalamus. This is the first case report of central diabetes insipidus caused by an HHV6 posterior pituitary infection demonstrated on a pathological examination.
A 61-year-old woman with recurrent non-small cell lung cancer presented with thrombocytopenia, microangiopathic hemolytic anemia, neurological abnormalities, renal failure and a fever that appeared during chemotherapy with gemcitabine and bevacizumab. She was diagnosed with drug-induced thrombotic thrombocytopenic purpura (TTP). After the discontinuation of chemotherapy, the administration of recombinant human soluble thrombomodulin and fresh-frozen plasma rapidly ameliorated the TTP. Hypertension preceded the onset of TTP and required the administration of quadruple therapy on admission. However, after three months, the hypertension was controllable without anti-hypertensive drugs. Twelve months later, the ninth course of vinorelbine was administered safely, preventing the patient's lung cancer from progressing.
A 55-year-old man presented with vertigo, nystagmus, and gait ataxia followed by left hemiparesis (Opalski syndrome). T2-weighted magnetic resonance imaging revealed vascular compression of the left lateral side of the medulla oblongata by the left vertebral artery. On diffusion tensor imaging, the level of fractional anisotropy (FA) in the left corticospinal fibers caudal to the pyramidal decussation was lower than that observed in the right corticospinal fibers. Opalski syndrome caused by vascular compression is very rare. This is the first reported case of Opalski syndrome that was imaged on FA.
We herein present the case of a 38-year-old woman with left-sided oculomotor paralysis with ocular pain that developed after a respiratory infection. Her serum was positive for IgM against GM2 and GalNAc-GD1a gangliosides and cytomegalovirus. Thin-slice magnetic resonance imaging revealed enhanced abnormal tissue located primarily in the superolateral part of the left-sided cavernous sinus, which corticosteroids subsequently obscured with immediate resolution of the patient's ocular symptoms. These clinical features were consistent with those of Tolosa-Hunt syndrome (THS). Our findings in the present patient suggest that cytomegalovirus may provoke granuloma formation in the cavernous sinus, as reported in other various organs, thereby leading to the development of THS.
A substantial number of patients with lupus nephritis (LN) are refractory to conventional glucocorticoid (GC) treatment. Although many of these patients respond to immunosuppressive drugs such as intravenous cyclophosphamide (IVCY), azathioprine (AZA), mizoribine, tacrolimus, cyclosporine A (CSA) and mycofenolate mofetil (MMF), some remain refractory to such therapies. Recent studies of multi-target therapies have reported effective outcomes for immunosuppression following renal transplantation and refractory LN when therapy consists of two or more immunosuppressive drugs with different mechanisms of action. We herein report a case of LN unresponsive to IVCY that was successfully treated with the addition of tacrolimus and discuss the usefulness of multi-target therapy for LN.
Aminoglycosides are useful antimicrobial agents for treating infective endocarditis; however, they occasionally cause troublesome side effects, such as nephrotoxicity and ototoxicity. We herein report a case of infective endocarditis caused by Enterococcus faecalis that was treated successfully with continuous infusion of ampicillin without adjunctive aminoglycosides. The serum ampicillin concentrations were higher than the minimal inhibitory concentration for the target strain. Although the use of ampicillin monotherapy is currently avoided because double β-lactam therapy is reportedly more effective, continuous penicillin administration remains an effective therapeutic choice for treating infective endocarditis.
We herein report two cases of incidental finding of the sternalis muscle in the right anterior chest wall on multidetector-row computed tomography (MDCT). We emphasize the diagnostic utility and value of additional postprocessed MDCT images, which can be easily created using volume data sets of MDCT, in establishing an accurate diagnosis of the sternalis muscle, an uncommon muscular variant.