[Determination of Endograft Size in Thoracic Endovascular Aortic Repair for Blunt Thoracic Aortic Injury:Report of a Case].

Although the efficacy of thoracic endovascular aortic repair( TEVAR) for blunt thoracic aortic injury (BTAI) has been reported, the determination of the proper endograft size for TEVAR in BTAI cases is yet to be established. The management of BTAI by TEVAR may not be effective if a wrong endograft size is selected, possibly leading to fatal outcomes. In this case report, a hemodynamically unstable patient with BTAI was saved by TEVAR, and the preoperative and postoperative changes in the aortic diameter were compared. In TEVAR for BTAI, the effects of hemodynamic instability should be considered and the appropriate device size should be determined based on blood pressure, pulse, and inferior vena cava diameter.

Positive attitude toward life, emotional expression, self-rated health, and depressive symptoms among centenarians and near-centenarians.

OBJECTIVES: Favorable attitudes, emotions, personality characteristics, and self-rated health have been associated with successful aging in late life. However, less is known regarding these constructs and their relationships to mental health outcomes in the oldest old persons. This study examined cross-sectional relationships of these psychological factors to depressive symptoms in centenarians and near-centenarians. METHODS: A selected sample of Ashkenazi Jewish older adults aged 98-107 (n = 54, 78% female) without significant cognitive impairment participated. Cognitive function was assessed by Mini-Mental Status Examination, positive attitude toward life and emotional expression by the Personality Outlook Profile Scale (POPS), self-rated health by participants' subjective rating of their present health, and depressive symptoms by the Geriatric Depression Scale. RESULTS: Results demonstrated inverse associations of the positive attitude toward life domain of the POPS and self-rated health with participants' levels of depressive symptoms even after adjusting for the effects of history of medical illnesses, cognitive function, and demographic variables. Additionally, participants with high levels of care showed higher levels of depressive symptoms. Path analysis supported the partially mediating role of positive attitude toward life in the relationship between self-rated health and depressive symptoms. CONCLUSION: These findings emphasized the important roles of positive attitudes and emotions as well as self-rated health in mental health outcomes in the oldest old. Although, limited by its cross-sectional design, findings suggest these psychological factors may exert protective effects on mental health outcomes in advanced age.

Discovery of furan-2-carbohydrazides as orally active glucagon receptor antagonists.

Furan-2-carbohydrazides were found as orally active glucagon receptor antagonists. Starting from the hit compound 5, we successfully determined the structure activity relationships of a series of derivatives obtained by modifying the acidity of the phenol. We identified the ortho-nitrophenol as a good scaffold for glucagon receptor inhibitory activity. Our efforts have led to the discovery of compound 7l as a potent glucagon receptor antagonist with good bioavailability and satisfactory long half-life.

Exposure-Based CBT for Older Adults After Fall Injury: Description of a Manualized, Time-Limited Intervention for Anxiety.

Fall accidents among older adults can be devastating events that, in addition to their physical consequences, lead to disabling anxiety warranting the attention of mental health practitioners. This article presents "Back on My Feet," an exposure-based cognitive-behavioral therapy (CBT) protocol that is designed for older adults with posttraumatic stress disorder (PTSD), subthreshold PTSD, or fear of falling resulting from a traumatic fall. The protocol can be integrated into care once patients have been discharged from hospital or rehabilitation settings back to the community. Following a brief description of its development, the article presents a detailed account of the protocol, including patient evaluation and the components of the eight home-based sessions. The protocol addresses core symptoms of avoidance, physiological arousal/anxiety, and maladaptive thought patterns. Because older patients face different coping challenges from younger patients (for whom the majority of evidence-based CBT interventions have been developed), the discussion ends with limitations and special considerations for working with older, injured patients. The article offers a blueprint for mental health practitioners to address the needs of patients who may present with fall-related anxiety in primary care and other medical settings. Readers who wish to develop their expertise further can consult the online appendices, which include a clinician manual and patient workbook, as well as guidance on additional resources.

[Efficacy and safety of levofloxacin in patients with nursing and healthcare-associated pneumonia].

Levofloxacin (LVFX) is one of respiratory quinolones with wide spectrum of antimicrobial efficacy for Gram-positive and -negative bacteria and also atypical bacteria, and 500 mg of intravenous LVFX infusion has recently been able to use once daily based on pharmacokinetics-pharmacodynamics in Japan. So far, there had been no reports of the prospective studies evaluating efficacy and safety of LVFX in patients with nursing and healthcare-associated pneumonia (NHCAP). This study was conducted to evaluate prospectively the efficacy and safety of LVFX in patients with NHCAP categories B and C (other antibacterial agents were allowed to use with LVFX) according to Japanese guideline for NHCAP by the Japanese Respiratory Society (JRS). LVFX 500 mg was intravenously administered once daily, and the clinical efficacy and safety were evaluated by clinical symptoms, peripheral blood laboratory findings and chest X-rays. Sixty-two patients (average age was 81.2 years old, female/male was 22/40) were firstly registered and evaluated for the safety of LVFX, and eventually 54 patients were enrolled for the evaluation of clinical efficacy of LVFX. The percentage of these 54 patients aged over 65 years old was 96.3%, NHCAP category B/C was 33/21. The efficacy of LVFX in all 54 patients evaluated was 85.2% (categories B/C of NHCAP was 81.8/90.5%). In addition, the efficacies of LVFX in each pneumonia severity category by A-DROP system by JRS in NHCAP patients were 100% in mild, 86.7% in moderate, 77.8% in severe/very severe. Nine patients (2 with liver dysfunction, 6 with renal dysfunction and 1 with thrombocytopenia) out of 62 patients were reported to have possible adverse effects of LVFX. All of the patients with liver and renal dysfunctions after starting LVFX administration demonstrated mild dysfunctions and continued LVFX treatment, and these dysfunctions normalized soon after cessation of LVFX. LVFX was changed to other antibacterial agent in one patient with thrombocytopenia, and also thrombocytopenia was normalized thereafter. In conclusion, LVFX is effective and relatively safe for categories B and C in patients with NHCAP.

[Early and mid-term outcomes of aortic valve replacement for aortic stenosis in hemodialysis patients].

We carried out a retrospective evaluation of the early and mid-term outcomes of aortic valve replacement (AVR) for aortic stenosis in hemodialysis patients. Between 2004 and 2012, a total of 40 dialysis patients underwent AVR with or without an additional procedure. Hemodialysis was performed routinely the day before and during the operation. At surgery, decalcification was performed using a cavitron ultrasonic surgical aspirator(CUSA) and a high performance mechanical valve was then implanted, with the exception of elderly patients or those in whom use of oral anticoagulation is contraindicated. A mechanical valve was used in 33 patients and a bioprosthetic valve in 7 patients. Hemodialysis was resumed on the 2nd postoperative day in the majority of patients. There was no intra-operative death and in-hospital mortality was 5%, due to sepsis and intestinal ischemia in 2 of the 40 patients. The mean follow-up period was 33 months. There was no structural valve deterioration in patients with the bioprosthetic valve. Of the 8 late deaths, the reason for deaths was cardiac in 4 patients. Overall survival in the 40 patients was 92%, 79%, and 54% at 1, 3, and 5 years, respectively. Our study demonstrated good early and mid-term outcomes for aortic valve replacement in hemodialysis patients. CUSA was useful for patients with a calcified valve and annulus. A bioprosthetic valve was acceptable for use in elderly patients.

[Simplified aortic root replacement in the era of complex operation].

OBJECTIVES: The purpose of the present study is to assess the clinical results of aortic root replacement using the Carbo-Seal composite graft( CS) compared with the other type of homemade composite grafts. Fifty-nine patients who underwent aortic root replacement between January 1998 to December 2010 were retrospectively analyzed. Twenty-six received homemade composite graft( group 1;1998 ~ 2005) and 33 received CS( group 2;2005 ~ 2010). RESULTS: The duration of operation was longer in group 1:469.2±143.5 min versus 380.3±153.9 min (p=0.03). Although there was no statistically significant difference, group 2 had a higher complex operation rate compared with group1(23.1% versus 45.5%, p=0.07). Overall hospital mortality was 11.5% in group1 versus 3.0% in group2. Prevalence of major complication was significantly lower in group 2 (46.2% versus 18.2%, p=0.02).Requirement of intraoperative blood transfusion (group 1;1,130.8±854.7 ml versus group 2;598.2±836.4 ml) and amount of blood loss in the 1st 12 hours post operation (group 1;628.3±474.6 ml versus group 2;447.8±253.2 ml) were significantly lower in group 2. By univariate analysis, duration of operation, duration of cardio-pulmonary bypass (CPB), blood transfusion, acute dissection were independent risk factors and CS use was negative risk factor for major events. Aortic root replacement with use of CS can be performed with a relatively low early mortality and morbidity. Because a complicated operation is increasing in recent years, use of CS graft may simplify a Bentall operation.

Hemophagocytic Lymphohistiocytosis and Anti-neutrophil Cytoplasmic Antibody-associated Vasculitis Possibly Caused by Enterococcus faecalis Infective Endocarditis.

Infection can induce hemophagocytic lymphohistiocytosis (HLH) and anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). We herein report a 52-year-old man who had HLH and AAV simultaneously, possibly caused by Enterococcus faecalis infective endocarditis. The HLH diagnosis was based on the HLH-2004 criteria. AAV was diagnosed based on a positive result for proteinase-3 ANCA and necrotizing vasculitis of the small vessels on a skin biopsy. He eventually died and was sent for autopsy after combination treatment of valve replacement, antibiotics, and immunosuppressants, including corticosteroids. This case involved a challenging diagnosis and treatment of HLH with various complications in an adult.

Change in Liver Fibrosis Associates with Progress of Diabetic Nephropathy in Patients with Nonalcoholic Fatty Liver Disease.

Diabetic nephropathy (DN) is a major complication of diabetes. Nonalcoholic fatty liver disease (NAFLD) is common in diabetes, and liver fibrosis is a prognostic risk factor for NAFLD. The interaction between DN and liver fibrosis in NAFLD remains unclear. In 189 patients with DN and NAFLD who received an education course about diabetic nephropathy, liver fibrosis was evaluated using the fibrosis-4 (FIB-4) index. The association between the outcome of DN and changes in liver fibrosis was examined. The FIB-4 index was maintained at the baseline level in patients with improved DN, while it was increased in other patients. The ΔFIB-4 index was positively correlated with changes in albuminuria and proteinuria (ρ = 0.22, p = 0.004). In a multivariate analysis, changes in albuminuria and proteinuria were associated with the ΔFIB-4 index (p = 0.002). Patients with a progressive FIB-4 index category from baseline to 5 years showed a lower event-free survival rate after 5 years than patients with an improved FIB-4 index category (p = 0.037). The outcome of DN is associated with changes in liver fibrosis in patients with diabetes, NAFLD and DN. Developing a preventive and therapeutic approach for these conditions is required.

Suppression of Airway Allergic Reactions by a Photocatalytic Filter Using Mouse Model.

Photocatalytic filters installed in air purifiers have been used to purify spaces by decomposing allergenic substances. However, we have not found any reports that evaluate the effectiveness of photocatalytic filters in suppressing allergic reactions in living organisms. In this study, we intratracheally instilled ovalbumin (OVA) into OVA-sensitized mice after the OVA was photocatalyzed by a titanium dioxide (TiO2) filter, and verified the experimental model for evaluating the allergy-suppressing effect of photocatalysts. Mice were sensitized to OVA (10 µg/mouse) four times, and were intratracheally instilled with OVA (10 µg/mouse) after photocatalysis three times. Non-sensitized animals were instilled with normal saline following the same exposure schedule. The mice were dissected 24 h after final exposure. The OVA after photocatalysis significantly decreased the number of eosinophils in bronchoalveolar lavage fluid, and the concentration of OVA-specific IgE and IgG1 in serum, which were elevated in untreated OVA. Moreover, our experimental model showed the suppression of allergic reactions in mice, along with the decomposition of OVA after photocatalysis using the photocatalytic filter. Taken together, our experimental model for evaluating allergic reactions in the respiratory tract suggested that the allergy-suppressing effect of the photocatalytic filter can be evaluated.

Autopsy case of a patient with rapidly progressive combined small-cell lung carcinoma with spindle-shaped cell tumor.

A 69-year-old Japanese man visited our hospital because of worsening shortness of breath. His chest computed tomography (CT) showed a giant left lung mass with a massive left pleural effusion. He could not be treated with chemotherapy and eventually died from a rapidly progressive tumor. He was diagnosed with combined small cell lung carcinoma (C-SCLC) with spindle-shaped cell tumor at autopsy. C-SCLC is characterized by pathologically concurrent SCLC and adenocarcinoma or squamous cell carcinoma, or rarely, spindle-shaped cell tumor. The clinical course of C-SCLC with spindle-shaped cell tumor has not previously been determined. Our patient's tumor increased by 2.59-fold in 20 days. The combination of C-SCLC with spindle-shaped cell tumor suggested rapid progression and a poor prognosis.

Effects of caspase inhibitor on angiotensin II-induced abdominal aortic aneurysm in apolipoprotein E-deficient mice.

OBJECTIVE: The presence of apoptotic markers is a prominent histological feature of abdominal aortic aneurysm. To understand the role of apoptosis in the pathogenesis of this common vascular disease, we tested the effect of the pan-caspase inhibitor quinoline-Val-Asp-difluorophenoxymethylketone (Q-VD-OPh) on aneurysm formation using a mouse angiotensin II (Ang II) model. METHODS AND RESULTS: Ang II in apolipoprotein E-deficient mice significantly induced medial cell apoptosis 3 days after infusion at the aortic region, eventually becoming aneurismal. A daily administration of 20 mg/kg per day Q-VD-OPh starting 6 hours before Ang II infusion reduced aneurysm incidence from 83.3% to 16.7% and maximal aortic diameter from 2.43+/-0.29 mm to 1.58+/-0.18 mm. The caspase inhibitor treated mice showed profoundly diminished levels of medial apoptosis and inflammation. In contrast, administration of Q-VD-OPh starting 7 days after Ang II infusion had no significant impact on aneurysm development. In vitro, media conditioned by Ang II-treated smooth muscle cells (SMCs) stimulated macrophage chemotaxis in a caspase-dependent manner. Inhibition of monocyte chemoattractant protein-1 (MCP-1) in the conditioned media via a neutralizing antibody completely blocked the ability of conditioned media to attract macrophages. CONCLUSIONS: These results indicate that medial SMC apoptosis may contribute to vascular inflammation and thus aneurysm formation, in part through production of MCP-1.

Paraneoplastic Sensory Polyneuropathy Related to Anti-PD-L1-including Anticancer Treatment in a Patient with Lung Cancer.

Paraneoplastic neurological syndromes (PNS), such as sensory polyneuropathy, are rare, and serum neuronal antibodies that are used for diagnosing this syndrome are occasionally positive. Similarly, neurological immune-related adverse events due to immune checkpoint inhibitors (ICIs) are also rare. However, their etiologies and the relationship between them remain unclear. We herein report a patient with suspected small cell lung cancer who showed sensory polyneuropathy after treatment with atezolizumab in combination with cytotoxic agents (carboplatin and etoposide) and was doubly positive for serum anti-Hu and anti-SOX-1 antibodies. Treatment with ICI and cytotoxic agents may sometimes lead to the development of PNS.

Spontaneous pulmonary emphysema in mice lacking all three nitric oxide synthase isoforms.

The roles of endogenous nitric oxide (NO) derived from the entire NO synthases (NOSs) system have yet to be fully elucidated. We addressed this issue in mice in which all three NOS isoforms were deleted. Under basal conditions, the triple n/i/eNOSs-/- mice displayed significantly longer mean alveolar linear intercept length, increased alveolar destructive index, reduced lung elastic fiber content, lower lung field computed tomographic value, and greater end-expiratory lung volume as compared with wild-type (WT) mice. None of single NOS-/- or double NOSs-/- genotypes showed such features. These findings were observed in the triple n/i/eNOSs-/- mice as early as 4 weeks after birth. Cyclopaedic and quantitative comparisons of mRNA expression levels between the lungs of WT and triple n/i/eNOSs-/- mice by cap analysis of gene expression (CAGE) revealed that mRNA expression levels of three Wnt ligands and ten Wnt/ß-catenin signaling components were significantly reduced in the lungs of triple n/i/eNOSs-/- mice. These results provide the first direct evidence that complete disruption of all three NOS genes results in spontaneous pulmonary emphysema in juvenile mice in vivo possibly through down-regulation of the Wnt/ß-catenin signaling pathway, demonstrating a novel preventive role of the endogenous NO/NOS system in the occurrence of pulmonary emphysema.

Anti-receptor for advanced glycation end products therapies as novel treatment for abdominal aortic aneurysm.

OBJECTIVE: Rupture of abdominal aortic aneurysms (AAA) is a devastating event potentially preventable by therapies that inhibit growth of small aneurysms. Receptor of advanced glycation end products (RAGE) has been implicated in age related diseases including atherosclerosis and Alzheimer. Consequently, we explored whether RAGE may also contribute to the formation of AAAs. RESULTS: Implicating a role for RAGE in AAA, we found the expression of RAGE and its ligand AGE were highly elevated in human aneurysm specimens as compared with normal aortic tissue. In a mouse model of AAA, RAGE gene deletion (knockout) dramatically reduced the incidence of AAA to 1/3 of control (AAAs in 75.0% of controls vs. 25.0% knockouts). Moreover, aortic diameter was markedly reduced in RAGE knockout animals versus controls. As to mechanism, we found that RAGE was coexpressed in AAA macrophages with MMP-9, a promoter of matrix degradation, which is known to induce AAA. In vitro, AGE induced the production of MMP-9 in macrophages in a dose-dependent manner while blocking RAGE signaling with a soluble AGE inhibitor prevented MMP-9 expression. In vivo, RAGE gene deficiency eliminated MMP-9 activity that was prevalent in aneurismal wall of the wild-type mice. CONCLUSIONS: RAGE promotes the development of AAA by inducing MMP-9 expression. Blocking RAGE in a mouse aneurysm model has a dramatic inhibitory effect on the formation of aneurysms. These data suggest that larger animal and eventually human trials should be designed to test oral RAGE inhibitors and their potential to prevent progression of small aneurysms.

Caspase-mediated protein kinase C-delta cleavage is necessary for apoptosis of vascular smooth muscle cells.

Apoptotic death of vascular smooth muscle cells (SMCs) is a prominent feature of blood vessel remodeling and various vascular diseases. We have previously shown that protein kinase C-delta (PKC-delta) plays a critical role in SMC apoptosis. In this study, we tested the importance of PKC-delta proteolytic cleavage and tyrosine phosphorylation within the apoptosis pathway. Using hydrogen peroxide as a paradigm for oxidative stress, we showed that proteolytic cleavage of PKC-delta occurred in SMCs that underwent apoptosis, while tyrosine phosphorylation was detected only in necrotic cells. Furthermore, using a peptide (z-DIPD-fmk) that mimics the caspase-3 binding motif within the linker region of PKC-delta, we were able to prevent the cleavage of PKC-delta, as well as apoptosis. Inhibition of PKC-delta with rottlerin or small-interfering RNA diminished caspase-3 cleavage, caspase-3 activity, cleavage of poly (ADP-ribose) polymerase, cleavage of PKC-delta, and DNA fragmentation, confirming the previously reported role of PKC-delta in initiation of apoptosis. In contrast, z-DIPD-fmk markedly diminished caspase-3 activity, cleavage of PKC-delta, and DNA fragmentation without affecting cleavage of caspase-3 and poly (ADP-ribose) polymerase. Taken together, our data suggest that caspase-3-mediated PKC-delta cleavage underlies SMC apoptosis induced by oxidative stress, and that PKC-delta acts both upstream and downstream of caspase-3.

Aneurysmectomy and Revascularization of Anterior Tibial Artery Aneurysm: Case Report.

An 86-year-old man presented with a pulsatile mass in the anterior compartment of the right lower leg. He had become aware of it two months earlier. Computed tomography angiography revealed a fusiform 3.2×5 cm aneurysm of the anterior tibial artery. Mural thrombosis in the aneurysm was absent. Peripheral pulse was normal. We performed aneurysmectomy and revascularization using a saphenous vein graft. Histological findings revealed that the mass was a true aneurysm. The clinical course was good, and the graft has remained patent for six months.

Pulmonary Nocardiosis Caused by Nocardia exalbida in a Patient with Lung Cancer and Radiation Pneumonitis: A Case Report and Literature Review.

We report a case of Nocardia exalbida (N.exalbida)-induced pneumonia in a 70-year old Japanese man with lung cancer and radiation pneumonitis. He initially received doripenem (1.5 g/day) for pneumonia treatment, and N.exalbida was identified by a clone library analysis of bronchoalveolar lavage fluid obtained from the pneumonia lesion. The doripenem dosage was therefore increased to 3.0 g/day with adjunctive trimethoprim/sulfamethoxazole, and his pneumonia improved. N. exalbida is susceptible to antibiotics; thus, in nocardiosis, N. exalbida infection might be associated with a good response to treatment, although its clinical findings are non-specific and similar to those of other Nocardia infections.