Objective The aim of this study was to determine if direct-acting antiviral (DAA) treatment with daclatasvir (DCV) plus asunaprevir (ASV) for 24 weeks influenced the health-related quality of life (HRQOL) at 12 and 24 weeks after treatment initiation [end of treatment (EOT)].

Methods This was a prospective, longitudinal study comparing the HRQOL of patients receiving DAA treatment at 12 weeks after treatment initiation and EOT with the HRQOL at baseline. We used a Japanese-validated version of the 8-item Short Form Health Survey (SF-8) to assess the HRQOL of patients. This score can be compared to the Japanese normative sample scores of SF-8. Wilcoxon signed-rank tests were used to compare the HRQOL before treatment, 12 weeks after treatment initiation, and at EOT.

Patients We enrolled patients who received 24-week combination therapy using DCV and ASV for HCV at Saga University Hospital between November 2014 and July 2015. Those who discontinued treatment due to relapse or adverse reactions during the treatment period were excluded from the study.

Results There were no significant changes in any of the SF-8 subscales, Physical component scores (PCS) or mental component scores (MCS) during the treatment period for both males and females.

Conclusion Our study makes a significant contribution to the literature because 24-week DAA treatment with DCV plus ASV did not decrease the HRQOL at 12 or 24 weeks after treatment initiation.

Objective Whether or not depression affects the control or severity of asthma is unclear. We performed a cluster analysis of asthma patients with depressive symptoms to clarify their characteristics.

Methods Multiple medical institutions in Niigata Prefecture, Japan, were surveyed in 2014. We recorded the age, disease duration, body mass index (BMI), medications, and surveyed asthma control status and severity, as well as depressive symptoms and adherence to treatment using questionnaires. A hierarchical cluster analysis was performed on the group of patients assessed as having depression.

Results Of 2,273 patients, 128 were assessed as being positive for depressive symptoms [DS(+)]. Thirty-three were excluded because of missing data, and the remaining 95 DS[+] patients were classified into 3 clusters (A, B, and C). The patients in cluster A (n=19) were elderly, had severe, poorly controlled asthma, and demonstrated possible adherence barriers; those in cluster B (n=26) were elderly with a low BMI and had no significant adherence barriers but had severe, poorly controlled asthma; and those in cluster C (n=50) were younger, with a high BMI, no significant adherence barriers, well-controlled asthma, and few were severely affected. The scores for depressive symptoms were not significantly different between clusters.

Conclusion About half of the patients in the DS[+] group had severe, poorly controlled asthma, and these clusters were able to be distinguished by their Adherence Starts with Knowledge (ASK)-12 score, which reflects adherence barriers. The control status and severity of asthma may also be related to the age, disease duration, and BMI in the DS[+] group.

Objective We conducted a study to obtain information that could be used to provide Parkinson's disease (PD) patients with appropriate advice on safe driving.

Methods Consecutive PD patients who visited our office were studied. Among these patients, those who had experienced driving after being diagnosed with PD were interviewed by neurologists and a trained nurse to investigate their previous car accidents, motor function, cognitive function, sleepiness, levodopa equivalent dose (LED), and emotional dysregulation. The rates of major car accidents before and after the onset of PD were compared.

Results Fifteen patients had experienced a major car accident resulting in human injury or serious property damage since the onset of PD. When the rates of major car accidents before and after the onset of PD were compared, the ratio was 4.3 [95% confidence interval (CI) 1.9-9.7]. The incidence of accidents after the onset of PD was correlated with age, disease duration, LED, the cognitive function Mini-Mental Scale Examination (MMSE), Japanese translation of the Montreal Cognitive Assessment (MoCA-J), but not the motor symptom score [Unified Pankinson's disease rating scale (UPDRS) part III at the time of the study]. The Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease (QUIP) score was also higher in patients with major car accidents.

Conclusion The severity of symptoms (Hoehn-Yahr classification), cognitive function, and disease duration were expected to be risk factors for car accidents. However, the motor symptom score (UPDRS part III) was not associated with the incidence of major car accidents. In addition to a low cognitive function and the severity of symptoms, the QUIP score might be an independent factor that can be referenced when advising PD patients to refrain from driving.

Objective This study retrospectively evaluated fungal dissemination due to hospital reconstruction and explored effective methods of predicting an outbreak.

Methods Patients suspected of having invasive aspergillosis were tested for Aspergillus galactomannan antigen before and after reconstruction, and the mean values of three months of testing for positive patients were determined. The characteristics of patients with aspergillosis during this period were also assessed.

Results Forty-five patients were positive for Aspergillus antigen (>0.5 cut-off index) from January 2013 to December 2014. Mean Aspergillus antigen values significantly increased following reconstruction (p<0.05). Three patients developed pneumonia due to Aspergillus and were diagnosed with "probable" invasive aspergillosis according to the European Organization for Research and Treatment of Cancer and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) criteria. We also discovered that the anteroom to contain dust was not prefabricated and a negative pressure system to remove dust was not used. After construction of the unit, no new cases of aspergillosis were diagnosed.

Conclusion Many Aspergillus spores may be transiently floating during hospital reconstruction. Therefore, monthly surveillance with frequent serum galactomannan antigen testing to predict outbreaks is necessary. Surveillance of all patients in the hematology ward is especially important. Reconsideration of prophylactic antifungals may also be necessary during hospital reconstruction.

Objective Almost no Japanese elderly patients have an advance directive (AD). Our aim was to determine whether or not the wish to receive intensive care in elderly patients with respiratory tract infection could be predicted from the prehospital data.

Methods In this retrospective study, we reviewed patients ≥65 years of age with respiratory tract infection who had been transferred to our hospital by ambulance between September 2014 and August 2016. The patients were divided into two groups according to whether or not they wished to receive intensive treatment. We placed patients without a wish to receive intensive treatments (WITs) in Group A and patients with a WITs in Group B. We then analyzed parameters that could be determined in the prehospital phase and compared the findings between the groups.

Results Thirty-seven patients were in Group A, and 67 patients were in Group B. None of the patients in this study had an AD. There were significant differences in the age, rate of residence in an extended care facility, frequency of inability to care for oneself fully, frequency of dementia, number of prescribed drugs, and Glasgow coma scale (GCS) on a univariate analysis. A logistic regression analysis showed that the inability to care for oneself fully [odds ratio (OR): 4.521, 95% confidence interval (CI): 2.024-10.096, p<0.001] and a low GCS (OR 0.885, 95%CI 0.838-0.935, p<0.001) were related to a WITs.

Conclusion Elderly patients who are unable to care for themselves and who have a low GCS in the prehospital stage are likely not to want intensive treatment.

A 69-year-old man was admitted to a hospital with complaints of abdominal pain. Computed tomography showed hepatic portal venous gas and pneumatosis cystoides intestinalis. Conservative treatment was effective; however, after discharge, he developed complaints of vomiting. Fluoroscopic enteroclysis revealed a stricture in the jejunum necessitating admission to our hospital. Transoral balloon-assisted enteroscopy showed a circumferential ulcer with a stricture. The stricture was surgically resected, and a histopathological examination was consistent with ischemic enteritis. Stenotic ischemic enteritis should be considered among the differential diagnoses in a patient presenting with hepatic portal venous gas and pneumatosis cystoides intestinalis showing small intestinal obstruction.

The initial symptoms of Crohn's disease (CD) sometimes present as extraintestinal lesions, which can be a diagnostic challenge for physicians. Painful legs, known as "gastrocnemius myalgia syndrome", are rare complications that often precede abdominal manifestations. We herein report the case of a 38-year-old man who presented with bilateral leg myalgia lasting for 4 months. Magnetic resonance imaging showed abnormal intensity, and a muscle biopsy revealed inflammatory cell infiltration. Abdominal symptoms appeared three months after the myalgia onset, and the diagnosis of CD was confirmed later by endoscopic and radiological findings. To our knowledge, this is the first description of gastrocnemius myalgia syndrome in Japan.

A 45-year old woman who underwent several surgeries for tumors associated with von Hippel-Lindau disease (VHL) was referred to our hospital due to a pancreatic tumor and liver tumors. She was diagnosed with pancreatic neuroendocrine tumor (NET) with a Ki67 index of 40% based on the examination of a biopsy specimen of the liver tumors. She was treated with everolimus for 6 months and sunitinib for 6 weeks as first- and second-line therapies. She survived for 13 months. At autopsy the diagnosis of pancreatic neuroendocrine tumor (NET)-G3 was confirmed. We herein report an aggressive clinical course of VHL-related NET G3. The further accumulation of cases is required to reach a consensus on treatment for this disease.

A 68-year-old woman with liver dysfunction was diagnosed with nonalcoholic steatohepatitis (NASH) stage 1. Three years later, she showed massive ascites and jaundice. A trans-jugular liver biopsy confirmed advanced cirrhosis, suggesting that her liver fibrosis had progressed rapidly. At the same time, she was diagnosed with multiple myeloma (MM). In this case, the plasma levels of osteopontin (OPN), a proinflammatory cytokine that promotes liver fibrosis progression through the hedgehog pathway and is increased in patients with MM, were increased. This increased OPN expression was accompanied by the upregulation of the hedgehog pathway in this patient, suggesting that the MM-associated increase in OPN had promoted the progression of liver fibrosis through the hedgehog pathway. The progression of liver fibrosis should be monitored in patients with NASH if other diseases, such as MM, are present.

Antiphospholipid syndrome (APS) is a cause of chronic thromboembolic pulmonary hypertension (CTEPH) and it is associated with an increased risk of postoperative neurological complications. We experienced a case of reversible parkinsonism after pulmonary endarterectomy (PEA) and subsequent multiple cerebral infarctions under standard anticoagulation therapy in a patient with CTEPH associated with APS. Strict management using a combination of antiplatelet and anticoagulation therapy should be considered in patients with a high titer of triple antiphospholipid antibodies in the perioperative period. We should be aware of the high risk of postoperative neurologic manifestations in patients with APS.

A 19-year-old man was referred due to sudden onset of right foot pain and chest discomfort. Contrast-enhanced computed tomography revealed massive thrombi in the right pulmonary artery and femoral vein. The patient's father had experienced multiple recurrences of venous thromboembolism (VTE) and was diagnosed with inherited antithrombin deficiency by a genetic examination. The patient was administered the oral factor Xa inhibitor rivaroxaban (30 mg). After seven days, the thrombus disappeared. Rivaroxaban (15 mg) was continued for 6 months with no recurrence, indicating the efficacy of this factor Xa inhibitor for the treatment and prevention of VTE in patients with antithrombin deficiency.

An 80-year-old woman with malignant melanoma received 20 cycles of anti-programmed death 1 (PD-1) antibody (nivolumab) treatment and showed normal glucose tolerance. Three weeks after switching to anti-cytotoxic T-lymphocyte associated antigen 4 (CTLA-4) antibody (ipilimumab), her plasma glucose level was elevated to 639 mg/dL, her HbA1c was 7.7%, and her fastening serum C-peptide immunoreactivity was undetectable. Anti-glutamic acid decarboxylase and insulinoma-associated protein-2 antibodies were negative. She was diagnosed with fulminant type 1 diabetes mellitus (F1DM). Remarkably, her anti-insulin antibody was positively converted, and her Sialylated Carbohydrate Antigen, Krebs von den Lungen-6 levels increased after ipilimumab therapy. She possessed F1DM-susceptible Human Leukocyte Antigen-DR4. A fluorescence activated cell sorting analysis showed an altered T-cell population. This case of F1DM highlights specific mechanisms underlying pancreatic beta cell immunity.

Maturity-onset diabetes of the young (MODY) is an autosomal dominant form of early onset diabetes. The hepatocyte nuclear factor-1-beta (HNF1B) gene is responsible for MODY type 5 (MODY5) with distinctive clinical features, including pancreatic atrophy and renal disease. We herein report a Japanese case of young-onset diabetes with typical phenotypes of MODY5 and a novel heterozygous missense mutation (p.L145Q) in the HNF1B gene. The mutation was located in the Pit-Oct-Unc (POU)-specific domain, and the amino acid residue L145 was highly conserved among species. It is strongly suggested that this mutation explains the phenotypes of MODY5.

Quinolones are known to induce hypoglycemia, although there is no written report of garenoxacin-induced hypoglycemia. We herein report a case of garenoxacin-induced hypoglycemia in a patient not taking hypoglycemic drugs. An 89-year-old Japanese woman with type 2 diabetes and chronic renal insufficiency requiring hemodialysis was admitted to the emergency department in a comatose state. Her serum glucose measured 1 mg/dL on arrival. The patient had not taken any hypoglycemic drugs recently and had never experienced a hypoglycemic episode. She had received a four-day course of garenoxacin treatment before the emergency admission. Clinicians should therefore recognize the potential risk of hypoglycemia during garenoxacin therapy.

A 72-year-old man was admitted due to dyspnea on exertion with interstitial shadows and elevated serum creatinine kinase (CK). Despite a close examination, which included magnetic resonance imaging (MRI), we could not diagnose myopathy. Prednisolone was administered and gradually tapered. One year later, anti-signal recognition particle (SRP) antibody was confirmed and he was re-admitted for hypoxemia with elevated CK. MRI revealed muscle edema and a histopathological examination of a muscle biopsy specimen showed necrotizing myopathy. Prednisolone, cyclosporine, and intravenous immunoglobulin were administered. Physicians should carefully monitor muscle symptoms and serum CK levels in cases of interstitial lung disease with anti-SRP antibodies.

A 16-year-old boy, who had been initially examined for bilateral blepharedema and slight eruption, presented with rapidly deteriorating symptoms in associating with headache and consciousness disturbance. He was diagnosed to have primary cutaneous CD8-positive aggressive epidermotropic cytotoxic T-cell lymphoma (PCAE-CTL) by a biopsy of the skin and brain. After whole-brain radiation and some courses of chemotherapy, cord blood transplantation was performed with myeloablative conditioning. After transplantation, the cerebral dysfunction gradually improved. Disease remission was confirmed by the disappearance of any abnormal findings on electroencephalogram and magnetic resonance imaging. PCAE-CTL is reported to be an extremely aggressive disease with a poor prognosis, but the timely performance of cord blood transplantation is considered to be a promising treatment strategy.

Miller Fisher syndrome (MFS) can be difficult to diagnose, particularly in mild cases where some of the standard triad of symptoms (external ophthalmoplegia, ataxia, and loss of deep tendon reflex) are absent. We herein report a case of the incomplete form of MFS diagnosed in a 54-year-old Japanese man who presented only with ataxia symptoms and was positive for the anti-GQ1b antibody. However, the patient also suffered from dysgeusia, a significant impairment of taste perception. We propose that dysgeusia in acute-onset ataxia cases may constitute an important clinical feature to aid in the diagnosis of the incomplete form of MFS.

We herein report a woman with chronic inflammatory demyelinating polyneuropathy (CIDP) in whom positivity for anti-neurofascin 155 antibodies was revealed 23 years after the onset of neuropathy. The patient initially reported numbness in the face at 50 years of age and subsequently manifested features compatible to typical CIDP. Steroid administration initiated at 54 years of age ameliorated her neuropathic symptoms. Although the nerve conduction indices at 59 years of age deteriorated, those at 68, 72, and 73 years of age showed a gradual recovery. The deterioration and subsequent restoration of compound muscle action potential amplitudes was the most dramatic, suggesting that a conduction block can be reversed earlier than other electrophysiological indices.

Lupus nephritis (LN) occurs in up to 60% of systemic lupus erythematosus patients. Combination therapy involving a corticosteroid and cyclophosphamide or mycophenolate mofetil (MMF) has been a standard therapy for LN. However, clinicians generally prefer to minimize steroid use in LN treatment. We herein report the case of a Japanese man with LN whose severe chronic heart failure prevented us from using steroid therapy. Instead, his LN was successfully treated with MMF monotherapy. Based on our experience with this case, we suggest that MMF monotherapy may represent a feasible LN treatment option in patients who cannot tolerate steroid therapy.

The patient was a 74-year-old Japanese woman with rheumatoid arthritis (RA) who developed generalized lymphadenopathy with elevated levels of lactase dehydrogenase (LD), and soluble IL-2 receptor (sIL-2R). She was found to be positive for anti-human T-cell leukemia virus type 1 (HTLV-1) antibodies. Her symptoms and laboratory abnormalities spontaneously regressed after the cessation of methotrexate (MTX), suggesting that she had an MTX-associated lymphoproliferative disorder; however, her lymphadenopathy appeared again approximately 14 months later with LD and sIL-2R elevation. A histopathological analysis and Southern blotting of a lymph node biopsy specimen for HTLV-1 provirus supported the diagnosis of adult T-cell leukemia/lymphoma (ATL) (lymphoma type). These data confirmed that an HTLV-1 positive RA patient may develop ATL.

We herein report a case of recurrent Campylobacter coli bacteremia in a 37-year-old Japanese man with X-linked agammaglobulinemia (XLA). The patient experienced seven episodes of C. coli bacteremia over one year, with an erythematous rash intermittently emerged on the lower limbs. Although hospitalization for intravenous treatment was repeatedly recommended, he obstinately declined it. Following long-term oral antibiotic treatment with tebipenem and faropenem for the persistent infection, C. coli showed elevated minimum inhibitory concentrations to meropenem, a key drug for severe campylobacteriosis. Physicians should note that the overuse of antibiotics can lead to the emergence of carbapenem-non-susceptible Campylobacter strains.

Emphysematous osteomyelitis is a rare but potentially fatal infection. It is caused by gas-forming organisms and is characterized by the presence of intraosseous gas. A 75-year-old woman with untreated diabetes mellitus presented with difficulty in moving and anorexia. Laboratory studies revealed inflammation, a urinary infection, and diabetic ketoacidosis. Klebsiella pneumoniae was detected in both urine and blood cultures. Computed tomography and magnetic resonance imaging revealed emphysematous lesions in the paravertebral soft tissue, spinal canal, and iliopsoas muscle, with intraosseous gas at L1 and L2. These findings led to a diagnosis of emphysematous osteomyelitis. We herein review 35 reported cases of emphysematous osteomyelitis including our case.