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.

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.

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.

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.

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.

[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.

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.

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.

Left colic artery aneurysm rupture after stent placement for abdominal aortic aneurysm associated with neurofibromatosis type 1.

BACKGROUND: Neurofibromatosis type 1 (NF1) is an autosomal dominant disease of the skin and soft tissue. Aneurysms associated with NF1 can occur, but a secondary aneurysm rupture is very rare, with very few cases reported in literature. CASE PRESENTATION: We describe the case of a 67-year-old female with NF1 who underwent endovascular aneurysm repair (EVAR) for an abdominal aortic aneurysm (AAA) rupture. She developed a type Ib endoleak requiring a redo-EVAR. Eighteen days after her primary operation, she was found to have two new left colic artery aneurysms. She required emergency surgery consisting of a left hemicolectomy and transverse colon colostomy. Pathology showed neurofibromatous changes to the peri-vasculature tissue, consistent with her underlying disease. CONCLUSIONS: Although rare, secondary aneurysms can occur following AAA repair. Patients with soft tissue connective tissue disorders, like NF1, may be at an increased risk for development of these secondary aneurysms. Endovascular repair appears to be a safe approach for NF1 patients with AAA, but endovascular management can be challenging in the setting of NF1. Surgeons should be ready to convert to open surgery if the patient displays persistent signs of bleeding or structural changes related to connective tissue disorders like NF1.

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.

Myocardial motion analysis based on an optical flow method using tagged MR images.

We developed a method of velocimetry based on an optical flow method using quantitative analyses of tagged magnetic resonance (MR) images (tagged MR-optical flow velocimetry, tMR-O velocimetry). The purpose of our study was to examine the accuracy of measurement of the proposed tMR-O velocimetry. We performed retrospective pseudo-electrocardiogram (ECG) gating tagged cine MR imaging on a rotating phantom. We optimized imaging parameters for tagged MR imaging, and validated the accuracy of tMR-O velocimetry. Our results indicated that the difference between the reference velocities and the computed velocities measured using optimal imaging parameters was less than 1%. In addition, we performed tMR-O velocimetry and echocardiography on 10 healthy volunteers, for four sections of the heart (apical, midventricular, and basal sections aligned with the short-axis, and a four-chamber section aligned with the long-axis), and obtained radial and longitudinal myocardial velocities in these sections. We compared the myocardial velocities obtained using tMR-O velocimetry with those obtained using echocardiography. Our results showed good agreement between tMR-O velocimetry and echocardiography in the radial myocardial velocities in three short-axial sections and longitudinal myocardial velocities on the midventricular portion of the four-chamber section in the long-axis. In the study conducted on the rotating phantom, tMR-O velocimetry showed high accuracy; moreover, in the healthy volunteers, the myocardial velocities obtained using tMR-O velocimetry were relatively similar to those obtained using echocardiography. In conclusion, tMR-O velocimetry is a potentially feasible method for analyzing myocardial motion in the human heart.

Coronary artery and supra-aortic vessel revascularization without aortic clamping for Takayasu arteritis.

Takayasu arteritis (TA) is a rare idiopathic large-vessel vasculitis involving the aorta and its major branches. Coronary artery disease and its surgical management in patients with TA is also a rare clinical entity. We report the case of a 73-year-old woman with TA and 3-vessel coronary artery disease in whom we performed off-pump coronary artery bypass graft concomitant with supra-aortic vessel revascularization.

Successful Additional Corticosteroid Treatment in a Patient with Mycoplasma pneumoniae Pneumonia in whom a Monobacterial Infection was Confirmed by a Molecular Method Using Bronchoalveolar Lavage Fluid.

A 23-year-old Japanese woman was admitted to A hospital due to pneumonia. IgM for Mycoplasma pneumoniae was positive, and the patient was treated with imipenem/cilastatin, clindamycin, pazufloxacin and minocycline. However, both the chest radiological findings and the symptoms became exacerbated, and she was therefore transferred to our hospital. The bronchoalveolar lavage fluid was obtained, and a 16S rRNA gene sequencing analysis revealed a monobacterial infection of Mycoplasma pneumoniae. Therefore, corticosteroid treatment in addition to minocycline was administered, and the patients symptoms, laboratory data and chest radiographs improved. Corticosteroid therapy may therefore be considered for patients with refractory M. pneumoniae pneumonia.

Efficacy of multidetector computed tomography for diagnosis of unroofed coronary sinus.

The patient was a 62-year-old woman with a chest X-ray abnormality. Transthoracic echocardiography (TTE) showed a dilated right ventricle and right atrium and an enlarged coronary sinus (CS), but definite diagnosis was not possible. Using contrast-enhanced 64-slice multidetector computed tomography (MDCT), curved planar reconstruction along the CS showed a direct connection of the left atrium and CS, in addition to the CS to right atrium connection. Unroofed CS is a rare congenital cardiac anomaly that is difficult to diagnose with TTE alone. Our case indicates that MDCT is useful for determining structural information that cannot be obtained from TTE. .

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.

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.

Posttraumatic stress symptoms in older adults hospitalized for fall injury.

OBJECTIVE: Although unintentional falls may pose a threat of death or injury, few studies have investigated their psychological impact on older adults. This study sought to gather data on early posttraumatic stress symptoms in older adults in the hospital setting after a fall. METHOD: Participants in this study were 100 adults age 65 years or older admitted to a large urban hospital in New York City because of a fall. Men and women were represented approximately equally in the sample; most were interviewed within days of the fall event. The study's bedside interview included the Posttraumatic Stress Symptom Scale, which inquires about the presence and severity of 17 trauma-related symptoms. RESULTS: Twenty-seven participants reported substantial posttraumatic stress symptoms (moderate or higher severity). Exploratory bivariate analyses suggested an association between posttraumatic stress symptom severity and female gender, lower level of education, unemployment, number of medical conditions, and back/chest injury. CONCLUSIONS: A significant percentage of older patients hospitalized after a fall suffer substantial posttraumatic stress. Future investigations are needed to assess the association between the psychiatric impact of a fall and short-term inpatient outcomes as well as longer-term functional outcomes.

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.