Objective Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a lethal inherited disease characterized by ventricular arrhythmias induced by physical exercise or emotional stress. The major cause of CPVT is mutations in RYR2, which encodes the cardiac ryanodine receptor channel. Recent advances in sequencing technology have yielded incidental findings of RYR2 variants in other cardiac diseases. Analyzing the characteristics of RYR2 variants related to CPVT will be useful for differentiation from those related to other cardiac diseases. We examined the phenotypic characteristics of patients with RYR2 variants.
Methods Seventy-nine probands carrying RYR2 variants whose diagnoses were either CPVT (n=68) or long QT syndrome (LQTS; n=11) were enrolled. We compared the characteristics of the electrocardiogram (ECG) and the location of the RYR2 mutations-N-terminal (NT), central region (CR) or C-terminal (CT)-between the two patient groups.
Results Using the ECGs available from 53 probands before β-blocker therapies, we analyzed the heart rates (HRs). CPVT probands showed bradycardia more frequently (25/44; 57%) than LQTS probands (1/9; 11%; p=0.024). In CPVT patients, 20 mutations were located in NT, 25 in CR and 23 in CT. In LQTS patients, 5 mutations were located in NT, 2 in CR and 4 in CT. There were no significant differences in the locations of the RYR2 mutations between the phenotypes.
Conclusion Bradycardia was highly correlated with the phenotype of CPVT. When a clinically-diagnosed LQTS patient with bradycardia carries an RYR2 mutation, we should be careful to avoid making a misdiagnosis, as the patient may actually have CPVT.
Objective Although life-threatening cardiac complications in influenza infection are rare, subclinical influenza-associated cardiac abnormalities may occur more frequently. We investigated the prevalence of subclinical cardiac findings.
Methods After obtaining their written informed consent, 102 subjects were enrolled in the present study. The study subjects underwent a first set of examinations, which included electrocardiography (ECG), echocardiography, and the measurement of their cardiac enzyme levels. Those with one or more abnormal findings among these examinations were encouraged to undergo a repeat examination 2 weeks later.
Results Among the 102 subjects enrolled, 22 (21.6%) were judged to have cardiac findings, including ST-T abnormalities, pericardial effusion, diastolic dysfunction, and cardiac enzyme elevation. Eighteen of these 20 subjects underwent a second screening at a median of 14 days later, and it was found that 11 of the 18 subjects were free from cardiac findings on this second examination. This suggested that the abnormalities were only transient and they therefore might have been associated with influenza. Approximately 20% of the influenza patients enrolled had cardiac findings, including ST-T segment abnormalities, pericardial effusion, and cardiac enzyme elevation.
Conclusion Among the 102 patients who were studied, the cardiac findings were only mild and transient; however, physicians should be aware of influenza infection-associated cardiac abnormalities because such abnormalities may not be rare.
Objective Although lung squamous cell carcinoma (SCC) accounts for 20-30% of lung cancer cases, new treatment options are limited. The CA031 study showed that nanoparticle albumin-bound-paclitaxel (nab-PTX) plus carboplatin produced a significantly higher overall response rate (41%) than solvent-based paclitaxel plus carboplatin in patients with lung SCC. However, the safety and efficacy of combination chemotherapy of nab-PTX and carboplatin has not yet been established for patients with concurrent lung SCC and idiopathic interstitial pneumonias (IIPs). The aim of this study was to assess the safety and efficacy profiles of nab-PTX and carboplatin in patients with lung SCC and concurrent IIPs.
Methods Eight patients with inoperable-stage lung SCC and IIPs were treated with nab-PTX plus carboplatin in a first-line setting between June 2013 and December 2016. One of the eight was a woman, and the median age was 77 (range=72-80) years. Their clinical outcomes, including chemotherapy-associated acute exacerbation of IIPs, were retrospectively investigated.
Results The overall response rate was 50%, the median progression-free survival time was 5.6 months, and the median overall survival time was 8.1 months. No patients experienced chemotherapy-related exacerbation of IIPs in the first-line treatment with nab-PTX plus carboplatin. However, IIPs worsened in two of four patients who received second-line chemotherapy.
Conclusion Combination chemotherapy of nab-PTX and carboplatin may be an effective and safe treatment option for patients with inoperable lung SCC with IIPs. To confirm this, a large-scale prospective study is needed.
Objectives Fatty acids (FAs) have various roles in pro-inflammatory and anti-inflammatory functions. Hypoalbuminemia is often observed in sepsis patients. An imbalance among these compounds formed from FAs caused by hypoalbuminemia may be related to increased mortality in sepsis patients. The purpose of this study was to investigate the correlations between serum albumin and FAs in sepsis and the outcome.
Methods This study was an observational investigation. The clinical and laboratory data of sepsis patients were recorded and the Sequential Organ Failure Assessment (SOFA) score was calculated at admission. The serum arachidonic acid (AA), eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and dihomo-gamma-linolenic acid (DHLA) levels were also measured as FAs. The body mass index (BMI) was used to determine the general nutrition status.
Results Two hundred sepsis patients were enrolled during the study period. No significant correlations were observed between the BMI and the SOFA score or the serum albumin level at admission. The FA levels of the non-survivors were significantly lower, but there were no significant differences in the EPA/AA levels of the survivors and non-survivors. A low serum albumin level was closely related to low AA (p<0.0001), EPA (p<0.0001), DHA (p=0.0003), and DHLA levels (p<0.0001). A multiple logistic-regression analysis revealed that a high SOFA score [adjusted odds ratio, 1.19; 95% confidence interval (CI), 1.02-1.39, p=0.026] and low AA (adjusted odds ratio, 0.98; 95% CI, 0.978-0.994, p=0.041) were associated with a poor outcome.
Conclusion A lower AA level was an important determinant of the outcome of patients with sepsis. These findings are consistent with the findings of previous studies, which reported that hypoalbuminemia might alter the AA metabolism in sepsis patients.
A 63-year-old woman was admitted with epigastric pain, eosinophilia, and elevated hepatobiliary enzyme levels. An upper gastrointestinal endoscopic examination showed that the mucosa of the gastroduodenal wall was edematous. Eosinophilic gastroenteritis (EGE) was diagnosed based on eosinophilic infiltration of the gastroduodenal mucosa. Computed tomography showed invagination of the duodenal wall into the common bile duct. The invagination of the duodenal wall improved after conservative therapy, while bile duct drainage was impossible due to the narrowing of the duodenal lumen. EGE was successfully treated without recurrence with steroids and antiallergic therapy. We herein report a rare case of EGE with obstructive jaundice.
We herein report the case of 74-year-old man with gastric follicular lymphoma resected by endoscopic submucosal dissection (ESD). A submucosal tumor 7 mm in diameter was detected at the gastric middle body. Endoscopic ultrasonography showed a homogenous hypoechoic tumor localized in the submucosa. The tumor was removed by ESD immediately, before further tumor growth would preclude endoscopic resection. The pathological findings indicated follicular lymphoma (FL) with negative horizontal and vertical margins. The clinical stage of FL was confirmed to be stage I by extensive work-up procedures, including contrast-enhanced computed tomography, fluorodeoxyglucose-positron emission tomography, esophagogastroduodenoscopy, and colonoscopy. The patient remains in complete remission without any treatment.
We herein report a case of simultaneous amebic colitis and cytomegalovirus (CMV) enteritis in an HIV-infected patient. The patient was a 40-year-old man who developed bloody stool and diarrhea. We diagnosed him with severe amebic colitis associated with HIV infection and administered metronidazole. While his symptoms began to improve, the patient then developed CMV enteritis. We administered ganciclovir, and his symptoms improved. However, despite control of the infection, stenosis of the descending colon caused intestinal obstruction, and colostomy was performed. This case shows the importance of considering the possibility of simultaneous infection when gastrointestinal symptoms appear in people infected with HIV.
A 70-year-old woman with hepatitis C cirrhosis underwent balloon-occluded retrograde transvenous obliteration for hepatic encephalopathy due to spleno-renal shunt. Because the shunt was thick, long, and winding, we used a coaxial and double interruption system, which enables the effective occlusion of the drainage route, and shape-memory coils, which are more physically stable than conventional metallic coils because they form three-dimensional loops. The patient was successfully treated with the combined usage of these devices, resulting in a normal serum ammonia level. Thereafter, the patient was treated with direct-acting antivirals, and a sustained virological response was achieved.
We report a case of percutaneous coronary intervention for spontaneous multi-vessel coronary artery dissection including the left main coronary artery. This case suggests that intracoronary imaging is useful for understanding the complex anatomy and for choosing the appropriate management for effective revascularization. Furthermore, cutting balloon angioplasty prior to stenting is useful for preventing the longitudinal extension of the intramural hematoma and avoiding unnecessary stent implantation.
Pheochromocytoma rupture is rare, and emergent adrenalectomy is associated with a high mortality. We herein report a patient with pheochromocytoma rupture who was stabilized by transcatheter arterial embolization (TAE) and subsequently underwent elective surgery. A 45-year-old man presented with the sudden onset of left lateral abdominal pain, headache, chest discomfort, high blood pressure, and adrenal hemorrhaging on enhanced abdominal computed tomography. TAE was performed under a provisional diagnosis of pheochromocytoma rupture. Following oral doxazosin, he underwent elective left adrenalectomy four and a half months after TAE. Stabilizing the hemodynamic status by TAE before adrenalectomy is a viable option for treating pheochromocytoma rupture.
Cryoglobulinemic vasculitis (CV) presents with systemic manifestations, including renal disease, arthritis, peripheral neuropathy, and muscle weakness. We encountered two patients who developed severe nephrotic range proteinuria; however, extrarenal manifestations were not noted during the clinical course. A renal biopsy revealed typical membranoproliferative glomerulonephritis (MPGN) with huge thrombus-like endothelial deposits and predominant IgM positivity, but electron microscopy did not reveal any definite microtubules. Immunosuppressive therapy and plasmapheresis were only partially effective, and the improvement was not durable. Biological therapy with rituximab (RTX) had no effect. Renal-limited CV should be recognized as a subset of essential CV.
Yellow nail syndrome (YNS) pleurisy is often difficult to control, and pathological examinations have rarely been reported. We herein report a case of bucillamine-induced YNS in which histopathology of the parietal pleura revealed hyperplasia of the lymphoid follicles and lymphangiectasia. Even after the discontinuation of bucillamine, the pleurisy and lymphedema showed no change. Based on the histopathological findings showing similarity to rheumatoid pleurisy, we administered corticosteroid treatments, and both the pleurisy and lymphedema improved. The findings in the present case suggest that, in bucillamine-induced YNS, pleurisy may be related to inflammation caused by rheumatoid arthritis in addition to abnormalities in lymphatic vessels.
Nivolumab is a newly introduced promising therapy for treating lung cancer that restores the anti-tumor immunity by disrupting programmed cell death-1-mediated immuno-suppressive signaling. Although "new-onset" autoimmune diseases are well-known immune-related adverse events, whether or not nivolumab exacerbates "pre-existing" autoimmune disease remains unclear. We herein report a patient with "pre-existing" myasthenia gravis in whom nivolumab was administered that flared up after the treatment with nivolumab. Regardless of the disease stability, nivolumab has the potential to exacerbate an autoimmune disease, and we must pay close attention to each patient's medical history before administering this agent.
Although primary central nervous system post-transplant lymphoproliferative disorder (PCNS-PTLD) causes various symptoms depending on the tumor region, there has been no previous report of PCNS-PTLD in the cerebellopontine angle that was diagnosed due to peripheral facial nerve palsy. We herein report a case involving a 62-year-old man with PCNS-PTLD in the cerebellopontine angle who was diagnosed due to peripheral facial nerve palsy. The reduction of immunosuppressive therapy, whole-brain radiotherapy, intrathecal chemotherapy, and rituximab were effective in treating this patient. Physicians should therefore be mindful that PCNS-PTLD can cause peripheral facial nerve palsy in renal transplant recipients.
A 72-year-old Japanese woman suffered from mild pancytopenia 3 years before her initial hospitalization. On admission, the levels of trace elements, particularly copper, and ceruloplasmin were significantly decreased in her blood serum. Abdominal lymphadenopathy and bone marrow dysplasia were detected. Hemosiderin deposition was observed in her lymph nodes and bone marrow, and magnetic resonance imaging suggested its deposition in various organs. A novel missense pathogenic variant (c.T1670G) was detected in the ceruloplasmin gene, resulting in an amino acid change (p.M557R). When copper deficiency is accompanied by cytopenia and dysplasia in a patient, it is worthwhile to consider a differential diagnosis of aceruloplasminemia.
IgG4-related disease (IgG4RD) is a multi-organ disorder characterized by an elevated serum IgG4 level and IgG4-positive plasma cell infiltration of the affected organs, accompanied by tissue fibrosis and sclerosis. Although it can affect any organ, to our knowledge, no cases involving concurrent autoimmune neutropenia and thrombocytopenia have been reported. A 62-year-old man visited our hospital and was diagnosed with IgG4RD accompanied by interstitial pneumonitis, lymphadenopathy, and interstitial nephritis. During his clinical course, he developed autoimmune neutropenia and idiopathic thrombocytopenic purpura. Our case, invoving multiple hematological abnormalities, might help deepen our understanding of the pathophysiology of IgG4RD.
We herein report a 15-year-old girl who developed rapid progressive muscle weakness soon after the third injection of a bivalent human papilloma virus (HPV) vaccine. Although immunotherapies were performed for possible vaccine-related disorders, she died of respiratory failure 14 months after the onset of the disease. A genetic analysis identified a heterozygous p.P525L mutation of the fused in sarcoma (FUS) gene, and a histopathological analysis was also consistent with FUS-associated amyotrophic lateral sclerosis (ALS) without any evidence of neuroinflammation. We concluded the diagnosis to be FUS-ALS, although we cannot completely rule out the possibility that the vaccination worked as a trigger.
A 36-year-old man with a history of irradiation for acute lymphoblastic leukemia developed headache with cortical dysfunction lasting for 4 weeks. The clinical features were consistent with stroke-like migraine attacks after radiation therapy (SMART) syndrome. Six months later, he developed cerebral infarction due to occlusions of the left anterior and middle cerebral arteries. This is the first case report describing SMART syndrome followed by severe cerebral infarction. Although an association between the two episodes was not assumed, this case indicates that protective therapies against infarction might need to be considered for patients with SMART syndrome.
A 67-year-old man with hypertension and type 2 diabetes mellitus was admitted to our hospital because of left hearing loss and vertical diplopia. A neurological examination showed ocular torsion, skew deviation, and sensorineural hearing loss in the left ear. Brainstem and cerebellar neurological signs were not observed. Left middle cerebellar peduncle infarction was evident on magnetic resonance imaging. He was treated with antiplatelet, however, the infarct progressed after this administration. Ocular tilt reaction (OTR) involves the triad of ocular torsion, skew deviation, and head tilt. Ipsiversive OTR components associated with hearing loss can be early diagnostic signs of anterior inferior cerebellar artery infarction.
We report a rare case of a 27-year-old woman with Takayasu arteritis (TAK) complicated by diffuse sclerosing osteomyelitis. She first presented with sclerosing osteomyelitis of the right mandible without evidence of arteritis in the carotid arteries. Eight months later, she complained of left neck pain, and imaging studies revealed the presence of arteritis in the left carotid artery. She was diagnosed with TAK, and immunosuppressive treatment was initiated, which was effective for both the arteritis and the osteomyelitis. Osteomyelitis is an important complication of TAK and bone scintigraphy is useful for its detection.
Patients with clinically amyopathic dermatomyositis (CADM), a subset of dermatomyositis characterized by a lack of muscle involvement, frequently develop rapidly progressive and treatment-resistant interstitial lung disease. We report the case of a 49-year-old man who was diagnosed with CADM. He developed interstitial pneumonia, which did not respond to combination therapy with methylprednisolone pulse therapy, cyclophosphamide, and cyclosporine. We therefore attempted plasma exchange. After 7 courses of therapeutic plasma exchange, the interstitial pneumonia gradually improved. This case suggests that plasma exchange might be an effective therapeutic option for patients with progressive interstitial lung disease in steroid- and immunosuppressive therapy-refractive CADM.
We herein report a case of central diabetes insipidus complicated with thyroid storm. A middle-aged woman who was receiving treatment for Graves' disease suddenly complained of polydipsia, polyuria and general fatigue. Laboratory tests showed hyperthyroidism, hypernatremia, hypoosmolar urine and a decreased plasma vasopressin level. The occurrence of central diabetes insipidus with hyperthyroidism was revealed on the basis of pituitary magnetic resonance imaging, a water deprivation test and a desmopressin test. The clinical co-existence of diabetes insipidus and hyperthyroidism is very rare; however, the complication should be considered when hypernatremia and/or dehydration progress in patients with Graves's disease as a common autoimmune-related etiology.