Objective The serum cholinesterase (ChE) level has been used for the evaluation of the nutritional status in daily practice. It has been reported that the serum ChE level is significantly more elevated in patients with three-vessel coronary disease than in normal subjects. Thus, the aim of this study was to assess the influence of serum ChE levels in patients suspected of having stable coronary artery disease (CAD).
Methods The relationship between myocardial ischemia and the serum ChE levels was evaluated in 559 consecutive patients suspected of having stable CAD without a history of cardiovascular disease admitted to our hospitals to undergo coronary angiography.
Results This study revealed that, in patients suspected of having stable CAD, 1) the frequency of myocardial ischemia was significantly increased in accordance with the serum ChE levels (p<0.001); 2) higher ChE levels were associated with a higher body mass index (p<0.001) and the co-existence of dyslipidemia (p<0.001), including higher values of low-density lipoprotein-cholesterol (p<0.001) and triglycerides (p<0.001) and serum albumin (p<0.001), as well as a younger age (p<0.001); 3) the specificity and sensitivity of myocardial ischemia were 0.599 and 0.658 at the ChE level of 286 IU/L, respectively; and 4) an increased serum ChE (OR=1.66, p<0.001) was an independent risk factor for myocardial ischemia, in patients suspected of having stable CAD.
Conclusion The serum ChE level may be an important diagnostic biomarker in patients suspected of having stable CAD.
Objective Glycemic variability is being increasingly recognized as an early indicator of glucose metabolic disorder and may contribute to the development of diabetic vascular complications, such as coronary microvascular dysfunction. The present study sought to investigate the relationship between coronary microvascular function assessed by intracoronary thermodilution method and glycemic variability on a continuous glucose monitoring system (CGMS).
Methods We prospectively enrolled 40 patients with or without known diabetes mellitus who had epicardial coronary artery disease referred for coronary angiography and were not treated with diabetic medications. Of these, two had a significant stenosis in the left main coronary artery and were therefore excluded from the analyses. In the end, 38 patients were equipped with a CGMS and underwent intracoronary physiological assessments in the unobstructed left anterior descending artery. The mean amplitude of glycemic excursion (MAGE) and standard deviation were calculated from the obtained CGMS data as indicators of glucose variability.
Results Coronary flow reserve (CFR) was negatively correlated with MAGE (r=-0.328, p=0.044) and standard deviation (r=-0.339, p=0.037) on CGMS, while the index of microcirculatory resistance showed no such correlation. Multivariable linear regression analyses showed that MAGE on CGMS was significantly associated with CFR after adjusting for age, sex, fractional flow reserve and hemoglobin A1c.
Conclusion Higher MAGE on CGMS was associated with reduced CFR in stable patients with coronary artery disease, suggesting a potential effect of glycemic variability on coronary microvascular flow regulation. A further study with a larger sample size needs to be conducted to confirm our findings.
Objective In Japan, immunosuppressive therapy (IST) with anti-thymocyte globulin (ATG), and cyclosporine A (CsA) is the standard of care in patients with aplastic anemia (AA) who are not indicated for stem-cell transplantation, although some patients may experience relapse. This study assessed the efficacy and safety of eltrombopag in combination with rabbit-ATG/CsA in IST-naïve patients with non-severe or severe AA in Japan.
Methods In this non-randomized, open-label, single-arm, phase II study, rabbit-ATG/CsA and eltrombopag were initiated on Days 1 and 15 (±3 days), respectively, and continued for ≥26 weeks; rabbit-ATG was given for 5 days (Days 1 to 5). The primary endpoint was the overall response rate (ORR) at Week 26.
Patients Patients with AA who were IST-naïve and ≤70 years old or between 71 and 75 years old based on the recommendation of the investigator were enrolled in Japan.
Results Of the 11 enrolled patients, 10 started treatment with eltrombopag. The ORRs at Weeks 26 and 52 were 70.0% and 60.0%, respectively. The ORR at Week 26 was 100% (all 3 patients) in patients with non-severe AA and 57.1% (4/7) in patients with severe AA. Among transfusion-dependent patients, 66.7% (4/6) and 62.5% (5/8) became red blood cell- and platelet-transfusion independent, respectively. The most common adverse events were nausea and headache. No deaths or hematologic malignancies were reported. A cytogenetic abnormality was reported in one patient.
Conclusion This study confirmed the clinical benefit of eltrombopag plus rabbit-ATG/CsA in IST-naïve patients with non-severe or severe AA in Japan.
Objective Patients with hematological malignancies, particularly those with multiple myeloma, often suffer from pathological vertebral compression fractures (VCFs). Consequent and significant spinal pain and paralysis impair the activities of daily living and quality of life and delay subsequent chemotherapy. Balloon kyphoplasty (BKP), which is less invasive than conventional therapies, is a type of percutaneous vertebroplasty in which cement is injected into the broken vertebrae to stabilize the spinal column. The present study assessed the effect of BKP on hematological tumors.
Methods We retrospectively analyzed five myeloma patients and one lymphoma patient who underwent BKP for pathological VCFs in our institution.
Results The median age was 74 years old. The spinal operation level ranged from T2 to L4. BKP was performed at the diagnosis in two cases, after first-line chemotherapy in one case, and after subsequent chemotherapy in three cases. After approximately 1 month, the patients' average Eastern Cooperative Oncology Group performance status score rapidly improved from 3.2 to 1.3. The numeric rating scale score decreased from 8.8 to 2.0, and the Karnofsky Performance Status score increased from 35 to 75. No severe complications were observed. All patients became able to walk unassisted and underwent early subsequent chemotherapy.
Conclusion BKP can be a safe and effective treatment option for pathological VCFs in patients with hematological malignancies and allows for rapid induction with subsequent chemotherapy.
Objective The psychological status is a key factor in smoking continuance. However, details on short-term changes in mild depressive states after smoking cessation (SC) are still unknown. The purpose of the present study was to investigate these short-term changes.
Methods A total of 989 patients who visited our SC Clinic were assessed using the Zung Self-Rating-Depression-Scale (SDS), an official instrument to measure depressive tendencies. The participants were classified into normal and neurotic groups based on their SDS scores during their initial visit; they were assessed again 2, 4, 8, and 12 weeks thereafter.
Results The majority of patients in the neurotic group were women. These patients were also younger, with a higher nicotine dependence, and presented with a lower successful SC rate than the patients in the normal group. A decrease in SDS scores after starting the SC treatment was observed only in the neurotic group, especially during the first two weeks. In patients who continued to smoke, no improvement in depressive tendencies was noted in this period.
Conclusion Depressive tendencies of patients with neurosis improve in the initial stages of the SC treatment (i.e., within two weeks after starting the treatment). This finding fills the mentioned knowledge gap regarding the effects of SC on mild depressive states in the short term.
Objective This study examined the pharmacokinetics, safety and anti-tumor activity of docetaxel at a dose of 100 mg/m2 in Japanese patients with advanced or recurrent breast cancer.
Methods Japanese patients with advanced or recurrent breast cancer received docetaxel at a dose of 100 mg/m2 intravenously every three weeks. The pharmacokinetics were assessed during the first cycle. The patients were allowed to receive supportive care drugs based on the indications and dosages in Japan.
Results Six eligible patients aged 39-65 years old and 27 treatment cycles were analyzed. All patients experienced one or more adverse events (AEs). The common AEs were neutropenia, thrombocytopenia, alopecia, rash, diarrhea, neuropathy (sensory), fatigue, nausea, fever, hypoalbuminemia, alanine transaminase (ALT) increased, constipation, and taste alteration. Grade 3 or 4 AEs included neutropenia, leukopenia, anemia, lymphopenia, decreased appetite, γ-glutamyl transpeptidase (GTP) increased, aspartate transaminase (AST) increased, ALT increased, hypertension and cellulitis which were all reversible. There were no cases of febrile neutropenia, serious AEs or deaths. The median number of cycles was six. Dose reductions were not observed and most cycles were administered at their intended doses. No complete response and three partial responses were observed in four assessable patients with evaluable lesions. The maximum concentration and area under the blood concentration-time curve were 3,417.5 ng/mL and 4.35 μg・hr/mL (mean), respectively.
Conclusion Docetaxel at a dose of 100 mg/m2 was tolerable with acceptable safety profiles and effective for Japanese patients with advanced or recurrent breast cancer with appropriate supportive therapies, and pharmacokinetic (PK) profiles which corresponded approximately with the findings of previous clinical studies.
Objective Sarcopenia and osteoporosis often coexist in older adults. Sarcopenia is diagnosed using the skeletal muscle mass index (SMI), which is calculated as the appendicular skeletal muscle mass (ASM)/(present height)2, although patients with osteoporosis frequently have a loss of body height. We therefore investigated whether the present height or maximum height is more useful for calculating the SMI in the evaluation of physical abilities.
Methods We conducted a cross-sectional study to investigate the association of the SMI with physical abilities, such as the grip strength and gait speed, in 587 postmenopausal women. The SMI was evaluated using whole-body dual-energy X-ray absorptiometry (DXA). The SMI [(ASM)/(present height)2], modified SMI (mSMI) [(ASM)/(maximum height)2], and SMI difference (ΔSMI) (mSMI-SMI) were calculated.
Results Age and body mass index (BMI)-adjusted regression analyses showed that the SMI (β=0.30, p<0.001 and β=0.14, p=0.034) and mSMI (β=0.40, p<0.001 and β=0.29, p<0.001) were positively associated while the ΔSMI was negatively associated with the grip strength and gait speed (β=-0.15, p<0.001 and β=-0.24, p<0.001, respectively). Furthermore, the age, BMI, and presence of osteoporotic fractures-adjusted logistic regression analyses showed that a low mSMI (<5.4 kg/m2) was significantly associated with a low grip strength (<18 kg) and slow gait speed (1.0 m/s) [odds ratio (OR) =2.45, 95% confidence interval (CI) =1.52-3.95 per SD increase, p<0.001; and OR=1.73, 95% CI=1.01-2.96, p=0.042, respectively], although a low SMI showed no such relationship (p=0.052 and p=0.813, respectively).
Conclusion The mSMI using the maximum height is more useful for evaluating physical abilities than conventional SMI estimation in postmenopausal women.
A 73-year-old woman with a history of diarrhea for one year and other various symptoms was admitted to our hospital. Gastrointestinal endoscopy that included enteroscopy with multiple biopsies was performed. However, no significant findings were observed. Electrocardiography showed low voltage in all limb leads, and an echocardiogram showed thickened cardiac walls with granular sparkling pattern. A myocardial biopsy revealed amyloidosis, and a bone marrow biopsy showed multiple myeloma. This case suggests that we should suspect the possibility of amyloidosis in a patient with diarrhea and various symptoms involving multiple organ systems. Additionally, electrocardiograms and echocardiograms should be performed even when gastrointestinal biopsies reveal negative results.
Acute pancreatitis is an extraintestinal manifestation of inflammatory bowel disease. There have been few reports describing acute pancreatitis preceding a diagnosis of inflammatory bowel disease. We herein report a rare case of a 16-year-old boy with presymptomatic Crohn's disease that was newly diagnosed just after the onset of idiopathic acute pancreatitis. Crohn's disease of any stage, much less in the presymptomatic stage, is rarely diagnosed just after the development of acute pancreatitis. The present case suggests that acute pancreatitis without an apparent cause in young or pediatric population can precede a diagnosis of presymptomatic Crohn's disease.
We herein report a rare case of intraductal papillary mucinous neoplasm with a pancreatogastric fistula in an elderly Japanese man admitted to our hospital. The pancreatogastric fistula was confirmed using endoscopic retrograde pancreatography via a cannulated guidewire placed in the stomach. Six months after admission, the patient was diagnosed with intraductal papillary mucinous carcinoma. A pancreatogastric fistula is generally a rare complication of intraductal papillary mucinous neoplasm. It was caused by mechanical penetration in this case. Interestingly, we also observed endoscopic and histochemical mucosal changes in the fistula.
The patient was a 73-year-old man with a history of hypertension, diabetes mellitus, dyslipidemia, rheumatoid arthritis, repeated percutaneous coronary intervention and percutaneous peripheral intervention procedures. He was frequently admitted to our hospital for congestive heart failure with orthopnea. The myocardial washout rate of iodine-123-β-methyl iodophenyl-pentadecanoic acid was defective on scintigraphy. He was diagnosed with triglyceride deposit cardiomyovasculopathy (TGCV). Proton magnetic resonance spectroscopy (1H-MRS) indicated the level of myocardial triglyceride (TG) content to be extremely high (4.92%). This is the first report to confirm a massive accumulation of TG in the myocardium of a patient with TGCV using 1H-MRS noninvasively.
Radiofrequency ablation is an established treatment for atrial fibrillation (AF). However, coronary artery spasm (CAS) is a rare but a potentially lethal complication associated with this procedure. A 54-year-old man with paroxysmal AF underwent pulmonary vein isolation. The procedure was completed and AF could not be induced after burst pacing and the administration of isoproterenol. Suddenly, ST-segment elevation developed in the anterior leads and frequent premature ventricular contractions followed by non-sustained ventricular fibrillation. The diagnosis of CAS was made by urgent coronary angiography. We identified isoproterenol as a potential cause of CAS. Physicians should be aware of this potentially lethal side effect.
We present an extremely rare case of mitral Ebstein's anomaly that resulted in severe mitral regurgitation (MR). A 41-year-old woman with a history of tuberous sclerosis underwent surgery. Preoperatively, it was assumed that MR had occurred due to leaflet tethering related to left ventricular posterior wall motion asynergy due to a scarred rhabdomyoma. However, surgical inspection revealed a dysplastic posterior leaflet adhering to the ventricular wall, which was completely covered by the endocardium. Both congenital mitral Ebstein's anomaly and acquired wall motion abnormality due to a scarred rhabdomyoma may have contributed to the development of severe MR in this case.
Procalcitonin (PCT), a marker of the inflammatory response during infections, can be elevated by diabetic ketoacidosis (DKA). A male patient in his 50s with diabetic nephropathy on hemodialysis presented with vomiting and a reduced level of consciousness and was diagnosed with DKA. His PCT level was markedly elevated, but bacterial cultures (blood, urine, and stool) were negative. The PCT level decreased after DKA improvement. In this patient, DKA probably enhanced the PCT levels. As DKA can increase the PCT levels, an elevation of the PCT levels in DKA patients may not be indicative of infectious diseases, and non-infectious causes of DKA should therefore be considered.
A 74-year-old Japanese woman diagnosed with autosomal dominant polycystic kidney disease (ADPKD) was admitted to our institute for the further examination of right-side groin pain developing in the past week. The patient was diagnosed with polymyositis (PM). Diagnostic imaging showed a mass lesion measuring 8 cm and a renal stone in the right kidney. Immediately following surgical resection of the right kidney, the patient's serum CK decreased to the normal range. A histopathological analysis showed well-differentiated squamous cell carcinoma. In conclusion, this case showed a close relationship between the occurrence of squamous cell carcinoma and the development of PM in an ADPKD patient.
Malignant lymphoma is rarely complicated by secondary IgA nephropathy. We encountered a 74-year-old man with rapidly progressive glomerulonephritis due to IgA nephropathy with predominant deposition of IgA2, instead of IgA1, in the glomerulus that was eventually diagnosed as secondary IgA nephropathy due to mantle cell lymphoma. Renal impairment was improved by chemotherapy for the mantle cell lymphoma. IgA came from the colonic mucosa that was stimulated by the infiltrated lymphoma cells, instead of the tumor itself. We should consider mantle cell lymphoma as a cause of secondary IgA nephropathy, although its prevalence may not be very high.
Allergic bronchopulmonary aspergillosis (ABPA) is a severe form of asthma in which structural airway destruction occurs due to a hypersensitivity reaction to fungi. A 25-year-old man without any major features of asthma had lung infiltration with dilatation of the central bronchus, high-attenuation mucus with histological eosinophilic invasion, fungi detected on cultures, and positive Aspergillus-specific immunoglobulin E (IgE) and precipitating antibody of Aspergillus, with a significant elevation of blood eosinophils and slightly increased total IgE. He recovered rapidly with systemic corticosteroid therapy without recurrence over 1-year follow-up and an increased forced expiratory volume in one second, which supported the possibility of ABPA without any major features of asthma.
A 42-year-old man with a history of surgery for tongue cancer was referred to our hospital due to an abnormal chest shadow. High-resolution computed tomography showed lower lobe reticulation. A physical examination revealed nail dystrophy, oral leukoplakia, and reticulated hypopigmentation. Lung biopsy revealed subpleural and perilobular fibrosis, suggestive of usual interstitial pneumonia. However, multiple pathological findings, including homogenous fibrosis and cell infiltration in the centrilobular region, which were compatible with nonspecific interstitial pneumonia, and bronchiolitis were also seen. Genetic testing showed a hemizygous missense mutation in the DKC1 gene, and the patient was diagnosed with dyskeratosis congenita. Although anti-fibrotic therapy was initiated, the patient's respiratory function has continued to decrease.
We herein report a case of asymmetrical interstitial lung disease (ILD) that remained almost completely asymmetrical over time on chest computed tomography (CT). An open lung biopsy from the right lung showed severe pleural adhesion, obstruction of the pulmonary artery, and dilated systemic arteries in addition to the usual interstitial pneumonia pattern. Three-dimensional CT angiography showed partial defects of pulmonary arteries on the affected side. After excluding other known causes of ILD and gastroesophageal reflux, we suspected that decreased pulmonary artery perfusion in the present case may have been responsible for the observed asymmetrical unilateral fibrosis.
Though adult-onset primary autoimmune pancytopenia (AIP) rarely follows a self-limited course, a standard treatment strategy has not yet been established. We herein report two cases, each involving primary autoimmune neutropenia complicated with autoimmune thrombocytopenia or Evans syndrome. They were refractory to granulocyte-colony stimulating factor, but all lineages of cytopenia promptly recovered with prednisolone (PSL). In case 1, PSL was tapered and discontinued six months after its initiation without AIP relapse. In case 2, PSL has been tapered for five months without relapse. To establish an optimal treatment strategy for AIP, it is necessary to accumulate more cases.
A 70-year-old woman with a human T-cell leukemia virus type 1 infection without any focal neurological symptoms showed age-related atherosclerotic changes in the white matter without any suspicious signal changes suggestive of progressive multifocal leukoencephalopathy (PML) based on the findings of MRI. Viral polymerase chain reaction (PCR) revealed 6,700 copies/mL of the JC virus genome in the cerebrospinal fluid (CSF). An immuno-pathological examination of the autopsied brain revealed JC virus capsid proteins, and in situ hybridization confirmed a JC virus infection, indicating that an active infection begins at the radiologically indistinguishable phase of PML. An early JC virus infection is probably associated with small, scattered demyelinating lesions around the cortico-medullary area of the cortex.
Krabbe disease involves the accumulation of neurotoxic metabolites due to lysosomal galactocerebrosidase enzyme deficiency, which results in widespread demyelination of central and peripheral nerves. Generally, Krabbe disease presents as spastic paraplegia with a slow progressive course; however, some cases may show clinical symptoms similar to those of chronic inflammatory demyelinating polyneuropathy (CIDP). No previously reported studies have investigated the efficacy of intravenous immunoglobulin (IVIg) for treating Krabbe disease, and reporting a case involving IVIg treatment may be informative in the clinical setting. A 14-year-old girl who developed Guillain-Barré syndrome-like limb weakness was administered IVIg, and her limb weakness improved. At 16 years old, she developed abnormal sensory perception and weakness of both upper limbs. A nerve conduction study revealed demyelination, which led us to suspect CIDP. IVIg was administered, and her symptoms gradually improved. A nerve biopsy, enzyme activity, and genetic test results indicated adult Krabbe disease. In some cases, IVIg may be an effective treatment for Krabbe disease.
We herein report a 65-year-old man with progressive multifocal leukoencephalopathy (PML) after 2-year remission from acute myeloid leukemia who developed recurrent episodes of left hemiparesis with gadolinium enhancement on magnetic resonance imaging. Steroid pulse therapy for each exacerbation induced clinical and radiological improvement, suggesting that exacerbations are an excessive immune response to the JC virus and distinct from immune reconstitution inflammatory syndrome (IRIS). Although glucocorticoids are recommended only for IRIS, steroid pulse therapy should be considered as a therapeutic option in cases of exacerbation of hematologic malignancy-associated PML. Importantly, neuroimaging is not sufficient to differentiate excessive inflammation from a controlled inflammatory response, for which steroids are not recommended.
A 65-year-old man presented with a slight headache and transient visual disturbance. Magnetic resonance imaging (MRI) revealed occlusion of the left internal carotid artery (ICA) and acute brain infarctions in both hemispheres, and a blood examination indicated inflammation. Gadolinium enhancement was observed in the walls of the temporal arteries and ICAs. After we diagnosed giant cell arteritis (GCA) by a temporal artery biopsy, aspirin and corticosteroids were administered. The typical symptoms of GCA, such as jaw claudication and temporal artery tenderness, were absent during the entire clinical course, and the findings of contrast-enhanced MRI contributed to the diagnosis.
High-altitude cerebral edema (HACE) is a rare condition of acute mountain sickness that manifests as consciousness disturbance and truncal ataxia. Neuroimaging shows vasogenic edema with microbleeds in the white matter and the corpus callosum. We herein report a case of HACE in which the patient showed widespread hyperintense signals with extensive microbleeds in the white matter and corpus callosum on MRI, as well as cognitive dysfunction. Rehabilitation to improve the higher brain function facilitated the recovery of the patient's cognitive impairment and was accompanied by improved MRI findings.
TAFRO syndrome is a systemic inflammatory, lymphoproliferative disorder, but the pathophysiology of the disease is unknown. It is typically characterized by thrombocytopenia, anasarca, a fever, reticulin fibrosis, renal dysfunction, and organomegaly. However, other manifestations have been also reported. We encountered a 43-year-old man with TAFRO syndrome who showed mediastinal panniculitis, liver damage, and adrenal lesions in addition to the core signs. He achieved complete remission with combination therapy of corticosteroids, tocilizumab, and cyclosporin, and remission was maintained even after drug discontinuation at 15 months. Atypical manifestations and complete remission of TAFRO syndrome were remarkable features of our case.
We herein report a case of aortitis induced by granulocyte colony-stimulating factor (G-CSF) that coincided with lung injury, splenomegaly, and cutaneous manifestations during treatment for recurrent extraosseous mucinous chondrosarcoma. Computed tomography revealed large-vessel vasculitis, splenomegaly, and pulmonary interstitial changes. Treatment with prednisolone was successful. Because sarcoma is a rare disease, this case is valuable for showing clinicians that G-CSF preparations could cause aortitis regardless of the patient's underlying diseases or therapeutic pharmacological backgrounds.