Cardiac involvement of systemic amyloidosis is preferentially observed in patients with amyloid light chain amyloidosis or transthyretin amyloidosis (ATTR). Owing to the development of diagnostic modalities and changes in recognition by physicians, transthyretin cardiac amyloidosis (ATTR-CA) is now understood to be a more common cause of heart failure than previously thought. Recent progress in disease-modifying therapeutic interventions, such as transthyretin stabilizers, has resulted in ATTR-CA changing from an incurable disease to a curable disease. These interventions are particularly effective in patients with mild symptoms of heart failure, thus indicating that early detection and a precise diagnosis are important for improving the prognosis. In this review article, we summarize the recent reports of early screening of ATTR-CA and describe some important points regarding the making of a precise diagnosis, especially focusing on histological evaluations.
Remarkable progress has been seen in monitoring systems using noninvasive ambulatory electrocardiograms (ECGs). In the Holter ECG system, 12-channel formats have been utilized as diagnostic tools, particularly for the detection of transient or silent myocardial ischemia and dynamic electrical disorders. In patients diagnosed with cryptogenic stroke, despite negative results on standard ECG tests, continuous ambulatory ECG monitoring for up to 30 days has been shown to increase the detection rate of transient atrial fibrillation. At present, a waterproof Holter ECG system is available. Recently, continuous late potential measurements using the time domain method and frequency domain T-wave alternans using the spectral analysis method for 24 hours have been applied to the Holter ECG and developed as novel risk stratification markers. Wearable ECG monitors that are built into belts, vests, wristbands, adhesive patches, and mobile smartphones have been used as fitness products for athletes and healthcare products for the general population. In the future, such devices may be used as remote monitoring tools for the detection of arrhythmias.
Myelodysplastic syndromes (MDS) are clonal hematological disorders arising from hematopoietic stem cells that have accumulated various genetic abnormalities. MDS are heterogeneous in nature but uniformly characterized by chronic and progressive cytopenia from ineffective hematopoiesis, dysplasia in single or multiple lineages, and transformation to acute leukemia in a subset of patients. The genomic landscape revealed by next-generation sequencing has provided a comprehensive picture of the molecular pathways involved in MDS pathogenesis. Recurrent mutational targets in MDS are the genes involved in RNA splicing, DNA methylation, histone modification, transcription, signal transduction, cohesin complex and DNA repair. Sequential acquisition of mutations in these sets of genes serves as a driver for the initiation, clonal evolution and progression of MDS. Based on these findings, novel agents targeting driver mutations of MDS are currently under development and expected to improve the clinical outcome of MDS in the coming decades.
Objective The QRS-T angle has been established as a repolarization marker. In the present study, we determined whether or not newly developed bundle branch block (BBB) affected the QRS-T angle in patients with a narrow QRS.
Methods Twenty-four patients with newly developed BBB and no adverse cardiac events were retrospectively included. The frontal QRS-T angle was defined as the absolute value of the difference between the frontal plane QRS axis and the T-wave axis. These electrocardiogram parameters were serially measured in the settings of narrow QRS and BBB.
Results Twelve patients had newly developed right BBB (RBBB), and 12 had newly developed left BBB (LBBB). The development of RBBB did not affect the QRS axis, T-wave axis of QRS-T angle (41° ±42° to 53° ±65°, p = 0.63). In contrast, the development of LBBB shifted the QRS axis to the left (25° ±29° to -18° ±31°, p = 0.003), resulting in an increased QRS-T angle (72° ±50° to 123° ±39°, p = 0.001). Regarding RBBB, an excellent correlation and agreement were found between the QRS-T angles in the setting of narrow QRS and RBBB (r = 0.88; p <0.001; bias, 2.9° ±20.9°). However, there was a significant bias between the QRS-T angles in the setting of narrow QRS and LBBB (51.9° ±40.4°; p = 0.001).
Conclusion Our data suggested that the QRS-T angle in the setting of RBBB reflected the original QRS-T angle in the setting of narrow QRS well, whereas the QRS-T angle in the setting of LBBB did not.
Objective We aimed to clarify clinical and laboratory characteristics of coronavirus disease 2019 (COVID-19) patients, and further explore the features to detect COVID-19 pneumonia at the first visit to community-based hospitals.
Methods Diagnoses of COVID-19 were based on positive results from real-time reverse-transcription polymerase chain reaction testing of nasopharyngeal-swab specimens. We retrospectively reviewed the medical records of patients showing positive results. The clinical characteristics and results of blood tests were compared between the patients with and without pneumonia. The risk factors associated with pneumonia were then evaluated by a multivariable analysis.
Results The study cohort comprised 154 patients, including 117 patients (76.0%) with pneumonia at first visit. Significant differences were seen in age, the frequency of fever, tachycardia, desaturation (peripheral oxygen saturation ≤95%), any comorbidity, neutrocyte count and fraction, lymphocyte count and fraction, platelet count, lactate dehydrogenase (LDH), C-reactive protein (CRP), and fibrinogen between the patients with and without pneumonia. Using a multivariable analysis, CRP ≥0.3 mg/dL and fibrinogen >400 mg/dL were found to be associated with the presence of pneumonia.
Conclusion Community-based settings for screening COVID-19 patients should perform chest X-ray and blood tests for white blood cell fractions, fibrinogen, LDH, and CRP. Of these, elevations in the CRP and fibrinogen levels could be critically associated with the presence of COVID-19 pneumonia.
Objective Prospective memory (PM) is an important social cognitive function in everyday life. PM is one of the most affected cognitive domains in multiple sclerosis (MS) patients. Gray matter (GM) atrophy and plaques have been attracting attention for various cognitive impairments in MS patients. This study aimed to clarify the atrophic GM regions associated with PM deficits and investigate the relationship between the atrophic GM regions and GM plaques.
Methods Twenty-one MS patients and 10 healthy controls (HCs) underwent neuropsychological tests and MRI. PM was assessed using subtests of the Rivermead Behavioural Memory Test. A lesion symptom analysis was performed using voxel-based morphometry (VBM). We then evaluated GM plaques in the corresponding areas using double inversion recovery (DIR).
Results MS patients showed lower PM scores than HCs (p=0.0064). The GM volume of MS patients tended to be lower than those of HCs. VBM analyses revealed correlations of the PM score with the orbital part of the left inferior frontal gyrus, the left hippocampus, and the right parahippocampus. There was no GM plaque in the orbital part of the left inferior frontal gyrus and the right parahippocampus. Only one patient (4.8%) had GM plaque in the left hippocampus.
Conclusion The left inferior frontal gyrus, the left hippocampus, and the right parahippocampus were associated with PM in MS, whereas these atrophic GM regions were not associated with GM plaque. Regardless of the location of plaques on DIR, both PM deficit and GM atrophy should be detected using neuropsychological tests and VBM in MS patients.
An 84-year-old man was admitted with epigastralgia. Computed tomography showed contrast-enhanced wall thickness in the cystic duct. An endoscopic examination revealed short irregular stricture in the cystic duct, and per-oral cholangioscopy revealed a reddish papillary tumor at the stricture site. Surgical resection revealed high-grade biliary intraepithelial neoplasia (BilIN) at the stricture site of the cystic duct. To our knowledge, this is the first case of a solitary high-grade BilIN epithelium in the cystic duct detected by per-oral cholangioscopy.
Portal vein thrombosis (PVT) while using an angiogenesis inhibitor is relatively rare. A 70-year-old Asian man was diagnosed with PVT two months after initiating 5-fluorouracil/leucovorin, irinotecan, and bevacizumab therapy for rectal cancer with liver metastases. Because the metastases were small and shrinking, we suspected that the thrombosis might have been caused by bevacizumab-containing chemotherapy. We stopped bevacizumab and started apixaban, a direct oral anticoagulant (DOAC). Eight months later, the complete dissolution of the thrombus and recanalization of the portal vein were attained. Our case suggests that PVT can occur during bevacizumab-containing chemotherapy, and DOAC therapy might be beneficial for treating PVT in patients with cancer.
A 40-year-old man was admitted to the hospital due to both a worsening of symptoms associated with ulcerative colitis (UC), which had been diagnosed 3 years previously, and limb paralysis. Colonoscopy revealed severe pancolitis-type UC. He was diagnosed with cerebral vasculitis with multiple white matter infarctions associated with the disease activity of UC by contrast-enhanced head magnetic resonance imaging. Mesalazine at 4,000 mg/day and prednisolone at 60 mg/day were started, and the prednisolone dosage was thereafter gradually reduced and switched to golimumab. He achieved a long-term remission from UC, and thereafter his neurological abnormalities improved significantly. He had no recurrence of cerebral infarction.
We herein report three patients with cardiac angiosarcoma who were directly admitted to the intensive-care unit for hemodynamic instability with circulatory collapse. Using a multidisciplinary cardio-oncologic approach, we diagnosed their condition as angiosarcoma by an invasive biopsy and urgently started weekly paclitaxel administration despite their poor performance status. Their vital signs were soon stabilized, leading to the patients' discharge from the hospital. Although no treatment guidelines for cardiac angiosarcoma have been established, chemotherapy with paclitaxel can be an option for cases presenting with hemodynamic instability.
The case was a 76-year-old man with chronic limb-threatening ischemia. Plain old balloon angioplasty (POBA) was performed on the popliteal artery. Subsequently, he suffered from cellulitis around the POBA site, followed by reocclusion. Staphylococcus aureus was detected in a blood culture. After re-revascularization with POBA, both purulent gonitis and an infected popliteal aneurysm were observed to occur. We performed aneurysmectomy and bypass grafting with the saphenous vein and then continued antibiotic therapy. Although treatment consisted of endovascular therapy (EVT) with nothing left behind, management was difficult because of secondary infectious complications. We conclude that prophylactic antibiotics before EVT should be considered in such cases.
Ophthalmic carteolol is often used to treat glaucoma. Elderly patients with atrial fibrillation (AF) and chronic kidney disease (CKD) are common among the super-elderly in Japan. Because these patients are exposed to polypharmacy, they are at a high-risk of adverse drug interactions. We herein report an elderly patient with CKD who suffered bradycardia shock after the combined use of carteolol eye drops and verapamil for glaucoma and paroxysmal AF. This case highlights the fact that eye drops have a similar systemic effect to oral drugs, and especially in elderly patients with polypharmacy, drug interactions can unwittingly lead to serious events.
A 54-year-old woman had been resuscitated after ventricular fibrillation and her electrocardiogram showed a QT prolongation (QTc=510 ms), and genetic screening revealed a missense variant, R1644C, in the SCN5A gene. She was therefore diagnosed with congenital long-QT syndrome (LQTS) type 3. However, the patient had left ventricular dysfunction, and based on the findings of cardiac magnetic resonance imaging, positron emission tomography and pathological examinations, she was diagnosed with cardiac sarcoidosis. Although both are rare diseases, their overlapping presence in this case may have led to an increased cardiovascular risk compared with either alone. Thus, not only genetic but comprehensive clinical examinations are important for making a correct diagnosis.
As an intrathoracic goiter expands, it causes airway stenosis and phrenic nerve paralysis, and slight respiratory stimuli can trigger sudden life-threatening hypoventilation. A 78-year-old obese woman with a large intrathoracic goiter was found unconscious with agonal breathing in her room early in the morning. Cardiopulmonary resuscitation restored spontaneous circulation. She underwent surgical removal of the goiter; however, she required long-term mechanical ventilation because of atelectasis due to phrenic nerve paralysis. In patients with large intrathoracic goiters, difficulty breathing on exertion and diaphragm elevation on chest X-ray may be significant findings predicting future respiratory failure.
A 44-year-old woman presented with a 3-month history of back pain, gait disturbance, and insomnia. She had moon face and central obesity but no goiter. Cushing's syndrome due to left adrenal adenoma was diagnosed. She also had low triiodothyronine syndrome and central hypothyroidism. Treatment involved adrenalectomy followed by 30 mg/day of hydrocortisone. Inappropriate secretion of thyroid-stimulating hormone occurred postoperatively. She developed Graves' disease nine months postoperatively and was treated with methimazole. Excess glucocorticoids followed by their withdrawal may influence the hypothalamic-pituitary-thyroid axis and immune system. Therefore, a careful evaluation of the thyroid function and antibodies is important after surgery for Cushing's syndrome.
A 40-year-old woman who had a history of recurrent olfactory neuroblastoma presented with full moon face, central obesity, buffalo hump, impaired glucose tolerance and bilateral cervical lymph node swelling. Laboratory tests showed morbidly elevated levels of adrenocorticotropic hormone (ACTH) and cortisol, which were not suppressed by high-dose (8 mg) dexamethasone. Biopsies of the enlarged cervical lymph nodes revealed ACTH-positive metastatic olfactory neuroblastoma, and ectopic ACTH syndrome was diagnosed. Metyrapone was used to suppress cortisol production and resulted in decreased levels of ACTH and cortisol. Bilateral cervical tumor resection further reduced the ACTH and cortisol levels, accompanied by a reduction in the metyrapone dosage. Cushing's syndrome was alleviated through ACTH-producing tumor removal.
We herein report a rare case of pulmonary sarcoidosis leading to chronic respiratory failure with restrictive ventilatory impairment during a 53-year-long observation period. Nine years after the histological diagnosis of stage I sarcoidosis on chest X-ray in a woman in her 20s, she developed bilateral reticular and granular opacities on chest computed tomography and was started on prednisone for 18 years. Seven years after prednisone withdrawal, these persisting opacities around the bronchovascular bundle, including a central-peripheral band, had progressed, forming traction bronchiectasis clusters and peripheral cysts, some of which developed continuously at the distal side of these clusters, with eventual upper lobe shrinkage.
Idiopathic pulmonary hemosiderosis is characterized by repeated alveolar hemorrhaging. We herein report a 52-year-old Japanese woman who had shortness of breath, diffuse small nodules, thin-walled cysts, and bronchiolectasis. A surgical lung biopsy revealed peribronchial hemosiderosis, centrilobular emphysema, and fragile elastic fibers of the alveolar septa and small vessels. She ultimately underwent living-donor lung transplantation five years after the first visit.
Case 1: A 65-year-old man with novel coronavirus infection (COVID-19) complicated with acute respiratory failure. On admission, the patient was started on favipiravir and corticosteroid. However, due to a lack of significant improvement, he was introduced to mechanical ventilation and extracorporeal membrane oxygenation (ECMO). Although iliopsoas hematoma occurred as a complication, the patient recovered. Case 2: A 49-year-old man with COVID-19 had been started on favipiravir and corticosteroid. Due to progressive respiratory failure, the patient underwent mechanical ventilation and ECMO. The patient recovered without complications. We successfully treated these severe cases with a multimodal combination of pharmacological and non-pharmacological supportive therapy.
A 76-year-old woman with dermatomyositis was being treated with prednisolone, tacrolimus, and mycophenolate mofetil. There was a solitary lung nodule in the right middle lobe on chest computed tomography at a routine follow-up examination. A transbronchial lung biopsy was performed, and the histopathologic findings indicated diffuse large B-cell lymphoma. An immunodeficiency-associated lymphoproliferative disorder was suspected, and mycophenolate mofetil was stopped without adding any other therapy. Nine months later, the pulmonary nodule had disappeared on chest computed tomography.
In addition to muscle nicotinic acetylcholine receptor (AChR) and muscle-specific kinase (MuSK), low-density lipoprotein receptor (Lrp4) has recently been discovered to be a novel target antigen among patients with seronegative myasthenia gravis (MG). We herein report the findings of a 62-year-old patient who showed positivity for anti-MuSK, anti-Lrp4, and anti-titin antibodies. The patient developed MG crisis following a 10-year history of intermittent double vision with ptosis, and a 7-year history of dropped head. Our detailed clinical, laboratory, and therapeutic descriptions highlight its unique characteristics of anti-MuSK-antibody positive MG accompanied by anti-Lrp4 and anti-titin antibodies.
Hereditary spastic paraplegia (HSP) is a neurodegenerative disorder clinically characterized by slowly progressing spastic paraparesis. We herein report a 50-year-old Japanese woman who presented with slowly progressing spastic paraplegia and a history of Paget's disease of bone (PDB). Genetic testing revealed a mutation of the Valosin-containing protein (VCP) gene (p.Arg155Cys; c.436C>T). This mutation has not been reported to cause HSP with PDB.
Membranous nephropathy (MN) with anti-neutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis (ANCA-GN) is seen infrequently. Previous reports of patients with ANCA-GN with MN showed that the most frequent ANCA subtype was myeloperoxidase-ANCA. We herein present a 73-year-old woman with scleritis, hematuria, proteinuria, and positive serum proteinase 3 (PR3)-ANCA. She underwent a renal biopsy and was diagnosed with MN and ANCA-GN. Immunofluorescence staining for PR3 colocalized with IgG along the glomerular basement membrane were observed. Oral prednisolone and intravenous rituximab therapy immediately improved her symptoms and urinalysis abnormalities. PR3-ANCA may be involved in the pathogenesis of MN via the formation of immune complexes.
Tetanus is a nervous system disorder characterized by muscular spasms and autonomic hyperactivity, such as unstable blood pressure. We herein report a case of tetanus in a patient in shock complicated with a rectus sheath hematoma caused by rupture of a pseudo-aneurysm of the inferior epigastric artery. A rectus sheath hematoma might be misdiagnosed as unstable blood pressure associated with autonomic hyperactivity, which is usually observed in patients with tetanus. The possibility of the occurrence of bleeding complications should be considered if a patient with tetanus has severe and persistent blood pressure reduction.