Influenza vaccine showed a good preventive effect against influenza-associated hospitalization among elderly patients, during the 2016/17 season in Japan.

The 2016/17 influenza season in Japan was characterized by a predominance of influenza A (H3N2) activity; with H3N2 accounting for 85% of all detected influenza virus infections. We assessed the vaccine effectiveness (VE) of an inactivated quadrivalent influenza vaccine (IIV4) in adult patients, using a test-negative case-control design study based on the results of a rapid influenza diagnostic test (RIDT). Between November 2016 and March 2017, a total of 1048 adult patients were enrolled: including 363 RIDT positive for influenza A, 9 RIDT-positive for influenza B, and 676 RIDT-negative. During the 2016/17 season, the overall adjusted VE was 28.8% (95% confidence interval [CI]: 6.3-46%). The adjusted VE against influenza A was 27.4% (95%CI: 4.4-45%). The VE against influenza B could not be estimated because of the very low number of influenza B patients. Twenty-nine patients were hospitalized due to influenza-associated illness-during the present study, all of whom were infected with influenza A virus. The adjusted VE, determined using a case-control study, for preventing hospitalization for influenza A infection was 72.6% (95%CI: 30.7-89.1%). In addition, the VE for preventing hospitalization of influenza patients with comorbidities was 78.2% (95%CI: 41.1-92%). Our study showed that, during the 2016/17season, IIV4 was effective for preventing both the onset of influenza and influenza-associated hospitalization.

Influenza vaccine effectiveness in adults based on the rapid influenza diagnostic test results, during the 2015/16 season.

We assessed the influenza vaccine effectiveness (VE) of an inactivated quadrivalent influenza vaccine in adult patients, in our test-negative case-control design study based on the results of a rapid influenza diagnostic test. During the 2015/16 season in Japan, influenza A(H1N1)pdm09 virus and influenza B virus were epidemic. The overall adjusted VE was 44% (95% confidence interval [CI]: 13.6%-63.7%). The adjusted VE was 52.9% (95%CI: 20%-72.3%) against any influenza virus among those < 65 years of age and -5% (95%CI: 136%-53.5%) among the elderly ≧ 65 years of age. The adjusted VE against influenza A was 49.1% (95%CI: 13.9%-69.9%). Although the VE was 55.5% (95%CI: 14.8%-76.8%) among those <65 years of age, it was only 15.3% (95%CI: 120%-67.4%) among the elderly ≧ 65 years of age. The adjusted VE against influenza B was 33.8% (95%CI: 25%-64.8%) among adult patients (≧16 years of age) and 46.8% (95%CI: 13%-75%) among those < 65 years of age, the VE against influenza B could not be estimated in those ≧65 years of age because of the low number of elderly patients with that virus.

[Effectiveness of Influenza Vaccine in Adults Using A Test-negative, Case-control Design ­2013/2014 and 2014/2015 Seasons­].

The influenza vaccine forms the basis of efforts to prevent the occurrence of influenza virus infection. However, vaccine effectiveness (VE) differs every season, which complicates efforts to combat the spread of infection. To develop a robust method to analyse variations in VE, we assessed VE among adult patients with influenza using a test-negative, case-control study design that evaluated vaccination records and the corresponding results of rapid influenza diagnostic tests during the 2013/14 and 2014/15 influenza seasons. During the 2013/14season, the adjusted VEs against influenza A and B viruses were 54.9% (95% confidence interval [CI] = 24.2% - 73.2%) and 56.6% (95% CI = 19.1% - 76.7%), respectively. In contrast, during the 2014/15season, the adjusted VE against the influenza A (H3N2), virus was -2% (95% CI = -66% - 37.5%). Moreover, only a few patients were infected with the influenza B virus, thus, the VE against influenza B could not be assessed. The low VE during the 2014/15 season could be attributed to antigenic drift in the circulating influenza A (H3N2) viruses and mutations in the egg-adapted vaccine strains. Estimation of the VE against the influenza virus using this test-negative, case-control study design was simple and easy, and this study design had a precision similar to that of a randomized control trial. Therefore, this study design could be employed to predict VE through out the influenza season and may be used as the basis of influenza prophylaxis.

Cytomegalovirus enteritis in immunocompetent subjects: a case report and review of the literature.

Cytomegalovirus (CMV) enteritis (or colitis) is generally diagnosed in immunocompromised patients in association with human immunodeficiency virus infection as well as in recipients of solid organ or hematopoietic stem cell transplant. CMV enteritis has been reported only sporadically in immunocompetent individuals. We encountered a 76-year-old woman who developed CMV enteritis without any previously identified immunocompromised states. An extensive literature review of 33 cases of CMV enteritis or colitis diagnosed in immunocompetent individuals, including the present case, revealed that the median age of the patients was 68, the accompanying symptoms were diarrhea (76%), abdominal pain (52%), and hematochezia or melena (27%), and that the outcome was generally favorable, including resolution without any treatment in 24% of the patients. CMV enteritis should be recognized more widely as a disease entity not only in immunocompromised patients but also in immunocompetent individuals, especially in elderly populations.

Mitogen-activated protein kinase (MAPK) regulates leukotriene D4-induced HB-EGF and ADAM12 expression in human airway smooth muscle cells.

BACKGROUND: Cysteinyl leukotriene (LT) induces bronchoconstriction as well as airway inflammation and remodeling. Heparin-binding EGF-like growth factor (HB-EGF) is associated with remodeling in airway smooth muscle (ASM) cells in bronchial asthma. A disintegrin and metalloproteinase (ADAM) 12 is an enzyme implicated in the ectodomain shedding of membrane-anchored proHB-EGF and release of HB-EGF. OBJECTIVE: To determine the role of LTD4 in HB-EGF and ADAM12 expression and the regulatory mechanism in human ASM cells, we analyzed a functioning signaling molecule in LTD4-induced HB-EGF and ADAM12 expression in human ASM cells by focusing on the role of mitogen-activated protein kinase (MAPK) cascades. METHOD: Human ASM cells were stimulated LTD4 in a time-dependent manner. We observed phosphorylation of MAPK by western blot analysis and the expression of HB-EGF and ADAM12 by quantitative PCR analysis of mRNA. Furthermore, we pretreated with specific inhibitors of MAPK and LTD4. RESULTS: LTD4 induced an extracellular-signal regulated kinase (ERK), p38 MAPK and c-Jun-NH2-terminal kinase (JNK) phosphorylation in human ASM cells. LTD4 induced HB-EGF and ADAM12 mRNA expression. Furthermore, the regulation of LTD4-induced HB-EGF and ADAM12 mRNA expression is associated with ERK and p38 MAPK, not but JNK. CONCLUSION: we conclude that p38 MAPK and ERK are capable of regulating LTD4-induced HB-EGF and ADAM12 expression in human ASM cells. In bronchial asthma, the specific inhibitor of p38 MAPK and ERK may produce beneficial effects in controlling airway remodeling and inflammation.

[Three cases of lung cancer presenting with spinal cord paralysis as the initial manifestation-symptom control, nursing care, and coordination of home medical care].

Bone metastasis from lung cancer accounts for approximately 30% of all metastatic bone tumors. The median survival time of patients with stage IV lung cancer with bone metastases is 5.5 months and that of patients without bone metastases is 7.5 months. Here, we report 3 cases of spinal cord paralysis. All cases were assessed according to the Tokuhashi score. As the predicted survival time of these patients was < or = 6 months, we opted for conservative treatment. We administered chemotherapy and radiation therapy, ensured symptom control, provided nursing care (prevention of decubitus, position changing, defecation control, rehabilitation, and mental health care), and coordinated home medical care. Patient management was mediated by a multidisciplinary medical team. However, all 3 patients were unable to return home and died in the hospital within 1-2 months after the onset of spinal cord paralysis. Spinal metastases can be expected not only in patients with lung cancer but also in patients with other types of carcinomas. Early diagnosis and treatment and accurate prognosis prediction are essential. Rapid responses and cooperation from experts are required, and increased awareness regarding spinal metastases among health professionals is essential.

[Difficulty in home care management of a young patient with terminal stage carcinoma--a case report].

A 48-year-old man with no remarkable medical history presented with upper abdominal pain for approximately 1 month. He was diagnosed as having pancreatic carcinoma with liver and lung metastasis and complicating carcinomatous peritonitis. Despite chemotherapy, his performance status worsened, his appetite deteriorated, and his pain became intolerable. The patient opted to return home for palliative care, and his parents, aged over 70 years, supported this decision. Although corticosteroid and opiate administration was attempted to improve appetite loss and pain, oral administration became difficult over a short span of time. Thus, treatment was switched from oxycodone to a fentanyl patch for opioid rotation. We also prescribed risperidone for the treatment of delirium. The patient once opted for "respite hospitalization" at a general hospital to relieve his aged parents' fatigue, and thereafter, he finally died at home. When rapid disease progression is expected, not only should a fully equipped environment for patients be ensured but concern for their caregivers should also be considered. For this purpose, cooperation and communication among multidisciplinary medical staff is indispensable.

[Early diagnosis of metastatic spinal tumor is a key for effective palliative radiotherapy in patients with lung cancer].

Patients with metastatic spinal tumor are the largest in number among the patients with bone tumor. It causes a severe bone pain, pathological fracture and spinal cord compression. Thus it harshly hampers patient's quality of life. We report 3 patients with lung cancer whose initial manifestation was metastatic spinal tumor. We treated the 3 patients with palliative radiotherapy and medication. Although the severe pain has improved on a numerical rating scale(NRS), but performance status(PS)and activity of daily living(ADL)of the 3 patients got worse because the disease was progressed and complicated. Generally, PS of cancer patients found by bone matastasis is low. However, it is difficult to take an effective treatment, which leads to ADL improvement. There are many choices for treating metastatic bone tumors including pain control, bisphosphonate administration, radiation therapy, strontium radiotherapy, bone cement, palliative surgery and orthotics. In addition, a development of molecular target drugs, such as Denosmab, is expected as future modality of palliative care. In conclusion, we should detect a bone metastasis in the patient with lung cancer as early as possible, and select an appropriate treatment in collaboration with each specialist for achieving the ADL and PS improvement.

Apoptosis signal-regulating kinase 1-mediated signaling pathway regulates lipopolysaccharide-induced tissue factor expression in pulmonary microvasculature.

Sepsis remains a life-threatening event and acute lung injury (ALI) is one of the complications induced by it. ALI is characterized by fibrin deposition, an indication of local activation of the coagulation cascade. Tissue factor (TF) expressed in the microvasculature acts as a critical initiator of blood coagulation in ALI. Lipopolysaccharide (LPS), a component of the outer envelope of all Gram-negative bacteria, is a highly proinflammatory molecule that elicits a wide range of endothelial responses, including the upregulation of TF; however, the molecular mechanism in LPS-induced TF expression in the pulmonary microvasculature has not been determined. We analyzed the role of apoptosis signal-regulating kinase (ASK1), an upstream kinase of p38 mitogen-activated protein kinase (p38 MAPK) and c-Jun N-terminal kinase (JNK), in order to clarify the signaling molecule regulating LPS-induced TF expression. The results showed the following: 1) LPS induces hTF mRNA expression in normal human lung microvascular endothelial cells (HMVEC-L); 2) LPS induces ASK1 phosphorylation in HMVEC-L; 3) LPS-induced TF mRNA expression is depressed in the dominant negative form of ASK1 stably-transfected porcine artery endothelial (PAE) cells; 4) LPS stimulation induces p38 MAPK and JNK phosphorylations in HMVEC-L; 5) LPS-induced p38 MAPK and JNK phosphorylations are depressed in the dominant negative form of ASK1 stably-transfected PAE cells; and 6) SB 203580 as a specific inhibitor of p38 MAPK, but not SP 600125 as a specific inhibitor of JNK cascade, attenuates LPS-induced hTF mRNA expression. These results indicate that the ASK1-p38 MAPK cascade may regulate LPS-induced TF expression in pulmonary microvasculature.

[A case with an ovarian cancer patient who could receive anti-cancer therapy and palliative care simultaneously at home through seamless collaboration in healthcare linkage].

A palliative care team provides palliative care in the hospital setting.However, palliative care might be discontinued when a patient was switched to an outpatient from an inpatient or when a patient was being transferred to another hospital.In the present work, we report a case who could receive anti-cancer therapy and palliative care simultaneously at home.The case is a 46-year-old woman.She was diagnosed as left ovary cancer in 1990's and underwent an operation followed by chemotherapy. The tumor relapsed and invaded the sigmoid colon in 2000's.She then developed an intestinal obstruction and was hospitalized.After her conditions were stabilized, she was discharged but still needed a high degree of medical interventions. She was introduced to another hospital providing a home palliative care as well as emergency admission.She could fulfill her desire to receive a palliative care and chemotherapy simultaneously at home through this seamless healthcare linkage.It should be insisted that hospital oncologists and home doctors need to acquire the knowledge of palliative care and close cooperation between them is required.It is also important to establish a comprehensive healthcare linkage system in the society.

An inhibitory effect of A20 on NF-kappaB activation in airway epithelium upon influenza virus infection.

Influenza is a major disease in humans. The reemergence of avian influenza A viruses has indicated that hyperinflammatory responses are closely related to the severity of disease. Influenza virus infection induces nuclear transcription factor kappaB (NF-kappaB) activation. NF-kappaB and NF-kappaB-dependent gene products promote lung inflammation and injury. Therefore, it is important to investigate the means to attenuate NF-kappaB activation. A20 is a cytoplasmic zinc finger protein that inhibits NF-kappaB activity, However, little is known about the role of A20 in influenza virus infection. Here, we have examined the role of A20 in influenza virus infection-induced NF-kappaB promoter activation in human bronchial epithelial cells. The results showed that (1) A20 protein and mRNA are inducible and expressed in the lung from mice and human bronchial epithelial cells upon influenza virus infection; (2) NF-kappaB promoter activation was induced in bronchial epithelial cells upon influenza virus infection; and (3) overexpression by transient transfection of A20 attenuated NF-kappaB promoter activation in bronchial epithelial cells. These results indicate that A20 may function as a negative regulator of NF-kappaB-mediated lung inflammation and injury upon influenza virus infection, thereby protecting the host against inflammatory response to influenza virus infection.

Apoptosis signal-regulating kinase 1 in leukotriene D(4)-induced activator protein-1 activation in airway smooth muscle cells.

Cysteinyl leukotrienes (LTs) are involved in allergic disorders including bronchial asthma. Transcription factor activator protein-1 (AP-1) activation is essential for cell proliferation and differentiation. LTD(4) is shown to promote human airway smooth muscle cell proliferation; however, the effect of LTD(4) on AP-1 activation in airway smooth muscle cells and the molecular mechanism in regulating AP-1 activation have not been determined. We examined the effect LTD(4) on AP-1 activation in human airway smooth muscle cells and analyzed a role of apoptosis signal-regulating kinase1 (ASK1), an upstream kinase kinase of c-Jun-NH(2)-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK) in LTD(4)-induced AP-1 activation to clarify the signaling molecule regulating AP-1 activation. The results showed that LTD(4) induced AP-1 activation determined by AP-1-dependent luciferase gene activity and ASK1 phosphorylation. Transient transfection of the dominant negative form of ASK1 attenuated LTD(4)-induced AP-1 activation. In addition, LTD(4)-induced AP-1 activity was depressed in the dominant negative form of ASK1-stably transfected porcine artery endothelial cells compared to that in the parental porcine artery endothelial cells. These results indicate that LTD(4) is capable of inducing AP-1 activation and ASK1 regulates AP-1 activation in LTD(4)-stimulated airway smooth muscle cells.