With the progress of medical care in recent years, the prognosis of intractable diseases of childhood onset has markedly improved. Young adults with special health care needs require continuous medical support throughout their lifetimes. To provide them with optimal health care services, a smooth transition from the pediatric medical system to the adult one is essential. However, in Japan many adult health providers are not sufficiently prepared to care for these patients, due both to limited opportunities to gain up-to-date medical knowledge on transitional health care and a lack of familiarity with the medical treatment of childhood-onset chronic diseases. In this review, we discuss current issues in transitional health care in Japan from an internist's viewpoint.
Objective Sorafenib is a standard therapy for advanced hepatocellular carcinoma (HCC), whereas radiotherapy is effective for local control of extrahepatic spread (EHS) or macrovascular invasion (MVI). This study investigated the safety and efficacy of this combined therapy to treat advanced HCC.
Methods This retrospective study reviewed 62 patients with advanced-stage HCC with EHS or MVI who received sorafenib therapy, excluding the patients with only lung metastases.
Results Of the 62 patients, 15 were treated using the combined therapy of sorafenib and radiotherapy (group RS), and 47 were treated with sorafenib monotherapy (group S). In group RS, patients were treated using three-dimensional conformal radiotherapy with a total irradiation dose of 30-60 Gy (median, 50 Gy). Irradiation was targeted at the bone, lymph nodes, adrenal gland, and MVI in 6, 5, 1, and 4 patients, respectively. The overall incidence of adverse events was 93.3% in group RS and 91.5% in group S (p=N.S.). Incidences of thrombocytopenia, leukopenia, and skin reaction were significantly higher in group RS (73.3%, 40.0%, and 66.7%, respectively) than in group S (36.2%, 10.6%, and 27.7%, respectively, p=0.02, 0.02, and <0.01, respectively). The incidence of severe adverse events, however, was comparable in the 2 groups: 20% in group RS and 19.2% in group S. The median progression-free survival (PFS) of EHS or MVI, PFS of whole lesions, and overall survival were longer in group RS (13.5, 10.6, and 31.2 months, respectively) than in group S (3.3, 3.5, and 12.1 months, respectively) (p<0.01 for all).
Conclusion Sorafenib in combination with radiotherapy is a feasible and tolerable treatment option for advanced HCC.
Objective Although several pre-endoscopic scoring systems have been used to predict the mortality or the need for intervention for upper gastrointestinal bleeding, their usefulness to predict the failure of endoscopic hemostasis in bleeding gastroduodenal peptic ulcers has not yet been fully investigated. In this study, we evaluated the usefulness of the Glasgow-Blatchford score (GBS), the clinical Rockall score (CRS), and the AIMS65 score in predicting the failure of endoscopic hemostasis in patients with bleeding gastroduodenal peptic ulcers.
Methods We retrospectively evaluated 226 consecutive emergency endoscopic cases with bleeding gastroduodenal peptic ulcers between April 2010 and September 2016. The study outcome was the failure of first endoscopic hemostasis. The GBS, CRS, and AIMS65 scores were assessed for their ability to predict the failure of endoscopic hemostasis using a receiver-operating characteristic curve.
Results Eight cases (3.5%) failed to achieve first endoscopic hemostasis. Surgery was required in six cases, and interventional radiology was required in two cases. The GBS was superior to both the CRS and the AIMS65 score in predicting the failure of endoscopic hemostasis [area under the curve, 0.77 (95% confidence interval, 0.64-0.90), 0.65 (0.56-0.74) and 0.75 (0.56-0.95), respectively]. No failure of endoscopic hemostasis was noted in cases in which the patient scored less than GBS 10 and CRS 2.
Conclusion The GBS was the most useful scoring system for the prediction of failure of endoscopic hemostasis in patients with bleeding gastroduodenal peptic ulcers. The GBS was also useful in identifying the patients who did not require surgery or interventional radiology.
Objective Life-threatening ventricular arrhythmias are recognized in patients with coronary spastic angina. Implantable cardioverter-defibrillators (ICDs) are effective in patients with structural heart disease and ventricular fibrillation. However, the optimal medication for patients with aborted sudden cardiac death (SCD) due to coronary artery spasm after the implantation of ICD remains controversial.
Methods We investigated the medications and the numbers of appropriate ICD shocks in 137 patients with a history of aborted SCD due to coronary spasm.
Results Appropriate ICD shocks were observed in 24.1% (33/137) of patients with aborted SCD due to coronary spasm during 41 months of follow-up. Only 15 (15.6%) of the 96 patients with ICDs received aggressive medical therapy, including two or three calcium-channel antagonists. The rate of appropriate ICD shocks was significantly higher in Western countries than in Asian countries (42.9% vs. 19.3%, p<0.01), whereas the medications did not differ between the two regions. Appropriate ICD shocks successfully resuscitated 33 patients. Three patients died due to second serious fatal arrhythmias.
Conclusion Appropriate ICD shocks were recognized in a quarter of patients with aborted SCD due to coronary spasm and ICD implantation was effective for suppressing the next serious fatal arrhythmia in these patients. We should reconsider prescribing more medications after ICD implantation in patients with aborted SCD due to coronary artery spasm.
Objective Coronary artery disease (CAD) is one of the clinical categories of atherosclerotic diseases. There have been reports indicating that the pathological findings of coronary artery plaque differ between acute coronary syndrome (ACS) and effort angina pectoris (EAP). The brachial-ankle pulse wave velocity (baPWV) has been reported to be a good indicator of atherosclerotic disease. However, the baPWV may not be equally effective for evaluating ACS and EAP. In this study, we compared the baPWV in patients with ACS and those with EAP.
Methods Two hundred and seventy patients were enrolled in this study. All patients underwent coronary angiography, and were separated into normal (CONT), ACS and EAP groups according to the clinical and coronary angiographic findings. The baPWV was evaluated and the results were compared among the groups.
Results The baPWV was significantly higher in the EAP group than in the other groups. The baPWV in the ACS group was almost the same as that of the CONT group and was significantly higher in the EAP group than in the ACS group across almost all age groups.
Conclusion The present study showed that the baPWV is high in patients with EAP. In contrast, the baPWV in the ACS group was almost normal and was similar to that of the CONT group. ACS occurs due to plaque rupture induced by atherosis, which may occur independent of sclerosis in the coronary artery. EAP may occur in proportion to systemic arterial sclerosis. The baPWV is suitable for screening for EAP, but not for ACS.
Objective Cardiovascular disease is a leading cause of sudden unexpected death even in hospitalized patients. Infectious aortitis is a rare disease that has the potential to cause aortic tears and hemorrhage followed by sudden death. The aim of this study was to reveal the clinicopathological features of infectious aortitis that are related to sudden unexpected death.
Methods We retrospectively reviewed 1,310 autopsy cases over 15 years and selected the cases involving patients who died suddenly due to aortic tears. We analyzed the clinical information and pathological findings.
Results One hundred thirty-three of 1,310 cases (10.2%) were autopsied under the clinical diagnosis of unexpected sudden death. Aortic tears were identified in 33 cases (2.5%) and infectious aortitis was diagnosed in 6 (18.2%) of these cases. All cases involved male patients (middle-aged to elderly) with risk factors for atherosclerosis (i.e., hypertension). The laboratory data showed continuous leukocytosis and C-reactive protein elevation, even during the improvement phase, in patients with pre-existing infectious disease. The autopsy findings revealed three types of aortic tears (aneurysms, dissections and penetrating atherosclerotic ulcers with moderate to severe atherosclerosis), and the infiltration of numerous neutrophils at the site of rupture. Gram-positive bacteria were detected in four cases and Gram-negative bacteria were detected in two cases.
Discussion We demonstrated that sudden unexpected death caused by infectious aortitis rarely occurred in hospitalized patients, even in the recovery phase of the preceding infectious disease. We therefore recommend that clinicians pay attention to infectious aortitis in patients with infectious disease, particularly elderly patients with atherosclerotic disease, even those who are in the improvement phase.
Conclusion Unexpected sudden death by infectious aortitis in the recovery phase of antecedent infection.
Objective Insulin glargine [300 U/mL (Gla-300)] achieved better glycemic control and reduced the risk of hypoglycemia in comparison to glargine [100 U/mL; (Gla-100)] in phase 3 trials. This is the first study to retrospectively evaluate the efficacy and safety of Gla-300 in Japanese type 1 and 2 diabetes patients in a routine clinical setting.
Methods We analyzed 20 type 1 diabetes patients and 62 type 2 diabetes patients who switched from Gla-100 to the same dose of Gla-300. Sixty type 2 diabetes patients who continued the use of Gla-100 during the study were included as controls.
Results At three months after switching, the HbA1c levels were decreased in the patients with type 1 diabetes, but not to a significant extent. In the type 2 diabetes patients, the HbA1c levels were significantly decreased after switching (p<0.01). In contrast, there was no change in the HbA1c levels of the type 2 diabetes patients who continued the use of Gla-100 over the same period. The BMI values of the type 1 diabetes patients tended to decrease (p=0.06) and there was a significant decrease in the BMI values of the type 2 diabetes patients (p<0.05). There was no change in the BMI values of the type 2 diabetes patients who continued the use of Gla-100. The rates of hypoglycemia and adverse events did not change during the follow-up period.
Conclusion In the clinical setting, switching from Gla-100 to the same dose of Gla-300 had a favorable effect on glycemic control and body weight control in Japanese type 1 and type 2 diabetes patients, without any increase in adverse events; however, a prospective study should be performed to confirm these findings.
Objective This retrospective cohort study investigated whether the three components of the blood cell count have prognostic implications in HIV-negative Japanese adult inpatients with smear-positive pulmonary tuberculosis.
Methods We reviewed patients who were treated by the isoniazid, rifampicin, pyrazinamide, and ethambutol regimen or by the isoniazid, rifampicin, and ethambutol regimen. The association between the patient data on admission and the survival outcome was evaluated.
Results We reviewed 367 consecutive patients (male, 60.5%) with a median age of 72 [interquartile range (IQR), 54-82] years. While the white blood cell count did not differ between the two groups, (discharged alive: 7,000/μL; IQR, 5,500-9,300; died in hospital: 7,200/μL; IQR, 5,600-9,400; p=0.797), hemoglobin level (discharged alive: 11.5 g/dL; IQR, 10.0-13.1; died in hospital: 9.9 g/dL; IQR, 8.6-11.3; p<0.001) and the platelet count (discharged alive: 275,000/μL; IQR, 206,000-345,000; died in hospital: 149,000/μL; IQR, 93,000-236,000; p<0.001) were lower in patients who died in hospital. After dividing patients into hemoglobin- and platelet-based quantiles, the lower quantile class tended to show poorer survival (log-rank test for trend p<0.001 for both). A multi-variable Cox proportional hazards model revealed that hazard ratio for in-hospital death for every 1,000/μL increase of platelet count was 0.997 (95%CI, 0.995-0.999; p=0.010); the hazard ratio for the hemoglobin level was not significant.
Conclusion A low platelet count was clearly related to a poor life prognosis in HIV-negative Japanese adult inpatients with smear-positive pulmonary tuberculosis.
Objective The aim of this study was to identify predictive factors for bacteremia conveniently and quickly among outpatients diagnosed with pyelonephritis.
Patients All patients who were diagnosed with pyelonephritis at the outpatient clinic in the Department of General Medicine of Juntendo University Hospital from April 1, 2008, to June 30, 2015, were enrolled. Patients from whom blood cultures had not been taken were excluded.
Methods Clinical information was extracted from medical charts. Factors potentially predictive of bacteremia were analyzed using a t-test and Fisher's exact test, followed by a multivariable logistic regression model analysis.
Results Blood cultures were drawn from 116 patients, and 25 (22%) presented with bacteremia. A multivariate analysis with the age, chills, platelet count and urine nitrite test results revealed that older age, positive urinary nitrite test results and chills tended to be associated with bacteremia, respectively. [older age: unit odds ratio (OR) 1.02, p=0.052, 95% confidence interval (CI) 1.00-1.05, positive urinary nitrite test findings: OR 2.5, p=0.092, 95% CI 0.86-7.7, chills: OR 2.5, p=0.096, 95% CI 0.84-7.65]. The area under the receiver operating characteristic (ROC) curve of this model was 0.77. Regardless of age, positive urinary nitrite test findings were significantly associated with bacteremia (OR 3.1, p=0.033, 95% CI 1.1-9.2), and chills tended to be associated with bacteremia (OR 2.7, p=0.07, 95% CI 0.93-7.9) The area under the ROC curve of this model was 0.75.
Conclusion Bacteremia should be considered in pyelonephritis patients with rapidly assessable factors in outpatient clinic. In particular, a model including a urinary nitrite test has the potential to aid in the prediction of bacteremia.
The clinical course of hepatic eosinophilic abscess (HEA) induced by malignant tumors is not well-known; however, it is considered to be a benign hepatic lesion. HEA is difficult to diagnose by imaging alone and a pathological examination is generally needed, particularly in patients with malignant tumors, because the radiological findings can be similar to those of metastasis. We report a case of multiple HEAs with eosinophilia and sigmoid colon cancer that was difficult to diagnose without a pathological examination. After the resection of the sigmoid colon cancer, the patient's eosinophilia was quickly ameliorated and the HEAs disappeared within 6 months.
Cholangiocarcinoma is a devastating cancer with a poor prognosis. Patients are often diagnosed at the advanced stage, and curative surgery is impossible. Radiation therapy is used for cases of advanced cancer. A 50-year-old woman with stage IVb intrahepatic cholangiocarcinoma was diagnosed with unresectable cancer, and had chemotherapy; however, the disease progressed. CyberKnife radiosurgery was performed, which was able to control the symptoms of liver failure and prolong her life. Her symptoms, which included jaundice, ascites, and edema disappeared and her tumor markers became normal. Even though she relapsed and was not able to survive, she was able to stay home with her family until the last days of her life. CyberKnife radiosurgery was useful as a non-invasive palliative treatment and successfully alleviated the symptoms of a patient with advanced cancer.
We herein report the case of a 25-year-old Japanese woman with left-main-trunk acute myocardial infarction (LMT-AMI). She had cardiogenic shock, so emergency percutaneous intervention was performed. Intravascular ultrasound of LMT-AMI showed that the three-layered structure of the intima, tunica media, and adventitia was not clearly visible, and the vessel was concentrically thickened; unstable plaque and calcification were not seen. AMI is rarely seen in young women, but Takayasu's arteritis is one major cause. If a young woman complaining of typical chest pain as acute coronary syndrome is encountered, systemic diseases must be considered.
Left main coronary compression syndrome rarely occurs in patients with severe pulmonary hypertension. A 65-year-old woman with severe pulmonary hypertension due to an atrial septal defect suffered from angina on effort. Cardiac computed-tomography and coronary angiography revealed considerable stenosis of the left main coronary artery (LMA) caused by compression between the dilated main pulmonary artery trunk and the sinus of valsalva. Stenting of the LMA under intravascular ultrasound imaging was effective for the treatment of angina. We herein report the diagnosis and management of this condition with a brief literature review.
Pulmonary embolism (PE) is usually caused by thrombosis or tumor. We report the long-term survival of a patient with PE due to a leiomyosarcoma in the deep vein. A 71-year-old woman complained of dyspnea and swelling of the left lower limb. Computed tomography revealed filling defects in the pulmonary arteries and deep vein. She was diagnosed with PE caused by venous thrombosis and treated with anticoagulant therapy. Her symptoms were prolonged, and D-dimer tests remained negative. Biopsy of the substance in the deep vein revealed leiomyosarcoma. The possibility of PE caused by extravascular or intravascular tumors should be considered when a patient is negative for D-dimer.
We herein report a case of lung metastases with unusual radiological appearances that mimicked those of chronic airway infection, causing diagnostic difficulty. A 60-year-old woman who underwent liver transplantation from a living donor was incidentally diagnosed with bile duct adenocarcinoma after a histopathological analysis of her explanted liver. Six months later, chest computed tomography (CT) revealed bilateral bronchogenic dissemination that had gradually worsened, suggesting chronic airway infection. A biopsy with bronchoscopy from a mass lesion beyond a segmental bronchus revealed adenocarcinoma identical to that of her bile duct adenocarcinoma, leading to the diagnosis of multiple lung metastases from bile duct adenocarcinoma.
Thrombocytopenia, ascites, myelofibrosis, renal dysfunction, and organomegaly (TAFRO) syndrome is a newly recognized but rare disease, and its treatment has not yet been established. We reported a 50-year-old woman with TAFRO syndrome diagnosed 2 years after the initial symptoms of a fever, fatigue, epigastric pain, edema, ascites, lymphadenopathy, thrombocytopenia and renal insufficiency. The patient showed refractory ascites and required hemodialysis under corticosteroid mono-therapy for suspected immune-mediated disease but was successfully treated with additive rituximab, resulting in improvement in her laboratory data, the withdrawal of hemodialysis and the disappearance of ascites. This case underscores the therapeutic utility of rituximab in patients with corticosteroid-resistant TAFRO syndrome, even long after the onset of the disease.
We present the case of a 56-year-old man with an upper respiratory infection followed by fatigue, hypotension, and hyponatremia. Bilateral adrenal hemorrhage was confirmed, based on T2-weighted magnetic resonance imaging. The patient had previously undergone allogeneic hematopoietic stem cell transplantation and had been diagnosed with antiphospholipid syndrome (APS) during the development of chronic graft-versus-host disease. A prompt diagnosis and steroid replacement, in addition to anticoagulant therapy, resulted in a favorable outcome. Once the diagnosis of APS has been confirmed, which might be the sign of bilateral adrenal hemorrhage, the initial manifestations of adrenal insufficiency should never be overlooked.
Patients with mycosis fungoides (MF), the most common subtype of primary cutaneous T-cell lymphoma, have an increased risk of developing secondary malignancies. We herein report two rare cases of MF concurring with diffuse large B cell lymphoma (B lymphoid lineage) and acute myeloid leukemia (myeloid lineage) in two otherwise healthy elderly patients. Potential etiologic factors, including the impact of the therapy-associated inflammatory response on the development of secondary tumors in patients with MF, are discussed. Further clinical, experimental and genetic studies are needed to elucidate possible physiopathogenic associations among the three concurrent malignancies occurring in the cases presented here.
A 37-year-old man with anti-muscle-specific tyrosine kinase (MuSK) antibody-positive myasthenia gravis (MG) presented with subacute progressive dysphagia and muscle weakness of the neck and bilateral upper extremities. Conventional immune-suppressive treatments and high-dose intravenous immunoglobulin were ineffective. He then displayed repeated exacerbations and remissions over the course of two years, despite two to four sessions of plasma exchange (PE) every two months. The patient was successfully treated with outpatient periodic weekly blood purification therapy with alternative PE and double-filtration plasmapheresis using an internal shunt. This case report suggests the benefits of blood purification therapy with an internal shunt against anti-MuSK antibody-positive MG.
Cough headache can be a primary benign condition or secondary to underlying etiologies. We herein describe a case of a 52-year-old woman with cough headache that presented as reversible cerebral vasoconstriction syndrome (RCVS). Some cases of RCVS are caused by an aberrant sympathetic response to activities that cause an intracranial pressure surge. Therefore, cough headache should be recognized as a possible presentation of RCVS, even without thunderclap headache or neurological deficits.
A 65-year-old woman with rheumatoid arthritis (RA) visited our hospital because of right facial sensory hypoesthesia. Cerebral toxoplasmosis was suspected on brain magnetic resonance imaging. We discontinued methotrexate for RA and started a sulfamethoxazole/trimethoprim (ST) mixture. Although ST treatment was interrupted because of adverse reactions, her prognosis was favorable. The Toxoplasma 18S rDNA gene was detected by nested-polymerase chain reaction (PCR) from blood and cerebrospinal fluid. Detecting the Toxoplasma 18S rDNA gene by nested-PCR is useful for the diagnosis and safer than a brain biopsy. In addition, the discontinuation of immunosuppressants may be recommended in patients compromised by those immunosuppressants.
The patient was an 81-year-old man who was found to have bacteremia due to Raoultella planticola, which might have entered the circulation through the bile duct during the passing of a gallbladder stone. In the present case, we screened for malignancies because most cases of R. planticola bacteremia occur after trauma, invasive procedures, or in patients with malignancy (70.6%). Early gastric cancer was detected. Although the association between R. planticola bacteremia and malignancy remains speculative in the present case, it may be useful to scrutinize similar cases involving low-virulence bacteremia for possible malignancies or immune conditions.
A 65-year-old man presented with gradually exacerbating low back pain. Magnetic resonance imaging revealed vertebral osteomyelitis in the Th11-L2 vertebral bodies and discs. The patient showed negative findings on conventional cultures. Direct broad-range polymerase chain reaction (PCR) with sequencing of the biopsied specimen had the highest similarity to the 16S rRNA gene of Helicobacter cinaedi. This case suggests that direct broad-range PCR with sequencing should be considered when conventional cultures cannot identify the causative organism of vertebral osteomyelitis, and that this method may be particularly useful when the pathogen is a fastidious organism, such as H. cinaedi.
A 35-year-old man (height, 169 cm; body weight, 240 kg; BMI, 84) visited the Department of Dermatology due to left leg pain and swelling. Focused enhanced computed tomography (CT) of the left leg ruled out complications of deep venous thrombosis. Surgical exploration of the left leg resulted in a diagnosis of necrotic soft tissue infection, but amputation was ruled out due to his weight. The patient ultimately died of multiple organ failure on the fourth day of hospitalization. A culture of the surgical material revealed Streptococcus dysgalactiae. The present case suggests that super-obese patients should be aggressively treated before lethal complications occur.
Drug-induced pressure ulcer (DIPU), which is a newly recognized adverse drug reaction, is associated with the administration of psychiatric drugs in geriatric patients with dementia. The notification of the causative drugs is crucial to the treatment of DIPU. We herein report the case of a 56-year-old woman with early-stage Parkinson's disease who developed DIPUs after starting olanzapine treatment for depressive symptoms. Our findings illustrate that if an akinetic patient with pressure ulcers is encountered, the patient's medication should be reviewed by a multidisciplinary team, to evaluate whether the development of the pressure ulcer is drug-related, regardless of the patient's age.
Constrictive pericarditis (CP) is defined as impedance to diastolic filling caused by a fibrotic pericardium. The diagnosis of CP is a clinical challenge and requires a high index of clinical suspicion. The signs and symptoms of CP include fatigue, edema, ascites, and liver dysfunction. These can be mistakenly diagnosed as primary liver disease. We present the case of a 69-year-old woman with a 7-year history of leg edema and a 2-year history of ascites who was initially diagnosed with cryptogenic liver cirrhosis and was finally diagnosed with CP.