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Obesity is associated with various metabolic and cardiovascular diseases caused by chronic, low-grade inflammation that is initially observed in obese adipose tissue. In addition, many etiological studies in humans have shown a strong correlation between obesity and inflammatory autoimmune diseases. In this review, we focus on the involvement of apoptosis inhibitor of macrophage (AIM), a macrophage-derived blood protein, in both types of immune response. Through differential mechanisms, AIM thereby plays key roles in the pathogenesis of atherosclerosis, metabolic diseases, and obesity-associated autoimmune diseases. Thus, the regulation of blood AIM levels or AIM function has the potential to serve as a next-generation therapy against these inflammatory diseases brought about by modern lifestyle. [ABSTRACT FROM AUTHOR]

Cell cycle regulation and biochemical responses upon nutrients and growth factors are the major regulatory mechanisms for cell sizing in mammals. Recently, we identified that the death effector domain-containing DEDD impedes mitotic progression by inhibiting Cdkl (cyclin-dependent kinase 1) and thus maintains an increase of cell size during the mitotic phase. Here we found that DEDD also associates with S6 kinase 1 (S6K1), downstream of phosphatidylinositol 3-kinase, and supports its activity by preventing inhibitory phosphorylation of S6K1 brought about by Cdkl during the mitotic phase. DEDD[sup-/-] cells showed reduced S6K1 activity, consistently demonstrating decreased levels in activating phosphorylation at the Thr-389 site. In addition, levels of Cdkl-dependent inhibitory phosphorylation at the C terminus of S6K1 were enhanced in DEDD[sup-/-] cells and tissues. Consequently, as in S6K1[sup-/-] mice, the insulin mass within pancreatic islets was reduced in DEDD[sup-/-] mice, resulting in glucose intolerance. These findings suggest a novel cell sizing mechanism achieved by DEDD through the maintenance of S6K1 activity prior to cell division. Our results also suggest that DEDD may harbor important roles in glucose homeostasis and that its deficiency might be involved in the pathogenesis of type 2 diabetes mellitus. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the treatment outcomes of patients with non-occlusive mesenteric ischemia (NOMI) at our institution, we focused on their post-treatment return to social activities.This study included patients with suspected NOMI who were referred to our department between 2011 and 2023. In-hospital mortality was also investigated as a prognostic factor. The Glasgow–Pittsburgh Outcome Categories (GPOC) score was used to evaluate the return to social activities. The relationship between in-hospital mortality and GPOC scores and patient background and treatment factors was examined.Eighty-two patients were included in the study. Among them, 54 (65.9%) died during hospitalization. Only 9 patients (11%) returned to their social activities. In the multivariate analysis, non-surgical management was found to be the only independent factor for in-hospital mortality. Positive portal venous gas on computed tomography, no open abdomen, no pre-onset catecholamine administration, platelet count < 100,000/µL, lactate level < 5 mmol/L, APTT < 46 s, and Sequential Organ Failure Assessment score < 11 were factors significantly associated with an increased likelihood of return to social activities.This is the first study to assess the post-treatment return to social activities among patients with NOMI. Our findings highlight the concerning reality that survivors may face prolonged dependence on medical care.Methods: To investigate the treatment outcomes of patients with non-occlusive mesenteric ischemia (NOMI) at our institution, we focused on their post-treatment return to social activities.This study included patients with suspected NOMI who were referred to our department between 2011 and 2023. In-hospital mortality was also investigated as a prognostic factor. The Glasgow–Pittsburgh Outcome Categories (GPOC) score was used to evaluate the return to social activities. The relationship between in-hospital mortality and GPOC scores and patient background and treatment factors was examined.Eighty-two patients were included in the study. Among them, 54 (65.9%) died during hospitalization. Only 9 patients (11%) returned to their social activities. In the multivariate analysis, non-surgical management was found to be the only independent factor for in-hospital mortality. Positive portal venous gas on computed tomography, no open abdomen, no pre-onset catecholamine administration, platelet count < 100,000/µL, lactate level < 5 mmol/L, APTT < 46 s, and Sequential Organ Failure Assessment score < 11 were factors significantly associated with an increased likelihood of return to social activities.This is the first study to assess the post-treatment return to social activities among patients with NOMI. Our findings highlight the concerning reality that survivors may face prolonged dependence on medical care.Results: To investigate the treatment outcomes of patients with non-occlusive mesenteric ischemia (NOMI) at our institution, we focused on their post-treatment return to social activities.This study included patients with suspected NOMI who were referred to our department between 2011 and 2023. In-hospital mortality was also investigated as a prognostic factor. The Glasgow–Pittsburgh Outcome Categories (GPOC) score was used to evaluate the return to social activities. The relationship between in-hospital mortality and GPOC scores and patient background and treatment factors was examined.Eighty-two patients were included in the study. Among them, 54 (65.9%) died during hospitalization. Only 9 patients (11%) returned to their social activities. In the multivariate analysis, non-surgical management was found to be the only independent factor for in-hospital mortality. Positive portal venous gas on computed tomography, no open abdomen, no pre-onset catecholamine administration, platelet count < 100,000/µL, lactate level < 5 mmol/L, APTT < 46 s, and Sequential Organ Failure Assessment score < 11 were factors significantly associated with an increased likelihood of return to social activities.This is the first study to assess the post-treatment return to social activities among patients with NOMI. Our findings highlight the concerning reality that survivors may face prolonged dependence on medical care.Conclusion: To investigate the treatment outcomes of patients with non-occlusive mesenteric ischemia (NOMI) at our institution, we focused on their post-treatment return to social activities.This study included patients with suspected NOMI who were referred to our department between 2011 and 2023. In-hospital mortality was also investigated as a prognostic factor. The Glasgow–Pittsburgh Outcome Categories (GPOC) score was used to evaluate the return to social activities. The relationship between in-hospital mortality and GPOC scores and patient background and treatment factors was examined.Eighty-two patients were included in the study. Among them, 54 (65.9%) died during hospitalization. Only 9 patients (11%) returned to their social activities. In the multivariate analysis, non-surgical management was found to be the only independent factor for in-hospital mortality. Positive portal venous gas on computed tomography, no open abdomen, no pre-onset catecholamine administration, platelet count < 100,000/µL, lactate level < 5 mmol/L, APTT < 46 s, and Sequential Organ Failure Assessment score < 11 were factors significantly associated with an increased likelihood of return to social activities.This is the first study to assess the post-treatment return to social activities among patients with NOMI. Our findings highlight the concerning reality that survivors may face prolonged dependence on medical care. [ABSTRACT FROM AUTHOR]

Cell surface scavenger receptors contribute to homoeostasis and the response to pathogens and products associated with damage by binding to common molecular features on a wide range of targets. Apoptosis inhibitor of macrophage (AIM/CD5L) is a soluble protein belonging to the scavenger receptor cysteine-rich (SRCR) superfamily that contributes to prevention of a wide range of diseases associated with infection, inflammation, and cancer. AIM forms complexes with IgM pentamers which helps maintain high-levels of circulating AIM in serum for subsequent activation on release from the complex. The structural basis for AIM recognition of IgM as well as other binding targets is unknown. Here we apply cryogenic electron microscopy imaging (cryo-EM) to show how interfaces on both of AIM's C-terminal SRCR domains interact with the Fcμ constant region and J chain components of the IgM core. Both SRCR interfaces are also shown to contribute interactions important for AIM binding to damage-associated molecular patterns (DAMPs)., (© 2024. The Author(s).)

Background: This study aimed to clarify the characteristics and survival prediction value of transcranial Doppler microembolic signals (MES) in patients with acute cerebral infarction and active cancer., Methods and Results: Between 2017 and 2022, 1089 cases of acute cerebral infarction were recorded within 7 days of disease onset. Among them, transcranial Doppler was successful in 33 patients who had active cancer, and these data were analyzed in this study. The primary outcomes were stroke recurrence and mortality at 3 months. The study population had the following characteristics [median (interquartile range)]: age, 70 years (63-78); body mass index, 21.6 (20-24), National Institutes of Health Stroke Scale 3 (1-6), and modified Rankin Scale score at discharge 1 (1-4). The most common cancer types were lung (24%), pancreatic (24%), and intestinal (18%). MES was present in 16 of 33 patients (48.5%). The presence and number of MES were significantly associated with the levels of D-dimer ( P <0.001) and C-reactive protein ( P =0.012). Moreover, the presence of MES was associated with multiple ischemic lesions and the 3-territory sign on magnetic resonance imaging. Of the 33 patients, 9 died at 3 months, and 1 had stroke recurrence. On Cox multivariate analysis, using the MES-negative group as a reference, the presence of MES was significantly associated with all-cause death (adjusted hazard ratio, 12.19 [95% CI, 1.45-216.85]; P =0.020)., Conclusions: In patients with acute ischemic stroke and active cancer, the presence of MES was associated with D-dimer and C-reactive protein levels and multiple and 3-territory ischemic lesions, and was predictive of short-term survival.

To clarify the differences and similarities in the cytokine profiles of macrophage activating syndrome (MAS) between systemic lupus erythematosus (SLE) and adult-onset Still's disease (AOSD). The study participants included 9 patients with MAS-SLE, 22 with non-MAS-SLE, 9 with MAS-AOSD, and 13 with non-MAS-AOSD. Serum cytokine levels were measured using a multiplex bead assay. Cytokine levels were compared between patients with SLE and AOSD with/without MAS. Moreover, cytokine patterns were examined using principal component analysis (PCA) and cluster analysis. IL-6, IL-8, IL-18, and TNF-α levels were elevated in patients with SLE and AOSD. IFN-α levels were elevated in SLE, whereas IL-1β and IL-18 levels were elevated in AOSD. In SLE, IFN-α and IL-10 levels were higher in MAS than in non-MAS and controls. PCA revealed distinctive cytokine patterns in SLE and AOSD, SLE with IFN-α and IP-10, AOSD with IL-1β, IL-6, and IL-18, and enhanced cytokine production in MAS. PCA and cluster analysis showed no differences in cytokine patterns between the MAS and non-MAS groups. However, serum ferritin levels were correlated with IFN-α levels in SLE. Cytokine profiles differed between SLE and AOSD but not between MAS and non-MAS. MAS is induced by the enhancement of underlying cytokine abnormalities rather than by MAS-specific cytokine profiles. Type I IFN may be involved in MAS development in patients with SLE., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Aims: We aimed to assess the prognostic impact of hyperhomocysteinemia (HHcy) on the recurrent vascular event risk in stroke patients with or without chronic kidney disease (CKD)., Methods: In this prospective observational study, 621 patients (mean age, 69.5 years; male, 62.2%) with ischemic stroke or transient ischemic attack were consecutively enrolled within 1 week of onset and followed-up for 1 year. HHcy was defined as elevated levels of fasting total homocysteine ＞15 µmol/L. CKD was defined as an estimated glomerular filtration rate of ＜60 mL/min/1.73 m 2 or a history of renal replacement therapy. The primary outcome was a composite of major adverse cardiovascular events (MACEs), including nonfatal stroke, nonfatal acute coronary syndrome, major peripheral artery disease, and vascular death., Results: The prevalence of HHcy was 18.5%. Patients with HHcy were more likely to have intracranial (37.4% versus 24.8%; p=0.008) and extracranial (20.9% versus 13.0%; p=0.037) artery stenosis than were those without HHcy. At 1 year, patients with HHcy were at a greater risk of MACE than were those without HHcy (annual rate, 17.8% versus 10.4%; log-rank p=0.033). In the Cox proportional hazard regression models, HHcy was independently associated with an increased risk of MACE in patients with CKD (adjusted hazard ratio [HR], 2.06; 95% confidence interval [CI], 1.02-4.20), whereas HHcy was not predictive of MACE in those without CKD (adjusted HR, 1.00; 95% CI, 0.30-3.32)., Conclusions: Elevated levels of serum homocysteine can be an important modifiable risk factor in stroke patients with CKD, but not in those without CKD.

Background: Alveolar macrophages (AMs) and AM-produced matrix metalloprotease (MMP)-12 are known to play critical roles in the pathogenesis of chronic obstructive pulmonary disease (COPD). The apoptosis inhibitor of the macrophages (AIM)/CD5 molecule-like (CD5L) is a multifunctional protein secreted by the macrophages that mainly exists in the blood in a combined form with the immunoglobulin (Ig)M pentamer. Although AIM has both facilitative and suppressive roles in various diseases, its role in COPD remains unclear., Methods: We investigated the role of AIM in COPD pathogenesis using porcine pancreas elastase (PPE)-induced and cigarette smoke-induced emphysema mouse models and an in vitro model using AMs. We also analyzed the differences in the blood AIM/IgM ratio among nonsmokers, healthy smokers, and patients with COPD and investigated the association between the blood AIM/IgM ratio and COPD exacerbations and mortality in patients with COPD., Results: Emphysema formation, inflammation, and cell death in the lungs were attenuated in AIM -/- mice compared with wild-type (WT) mice in both PPE- and cigarette smoke-induced emphysema models. The PPE-induced increase in MMP-12 was attenuated in AIM -/- mice at both the mRNA and protein levels. According to in vitro experiments using AMs stimulated with cigarette smoke extract, the MMP-12 level was decreased in AIM -/- mice compared with WT mice. This decrease was reversed by the addition of recombinant AIM. Furthermore, an analysis of clinical samples showed that patients with COPD had a higher blood AIM/IgM ratio than healthy smokers. Additionally, the blood AIM/IgM ratio was positively associated with disease severity in patients with COPD. A higher AIM/IgM ratio was also associated with a shorter time to the first COPD exacerbation and higher all-cause and respiratory mortality., Conclusions: AIM facilitates the development of COPD by upregulating MMP-12. Additionally, a higher blood AIM/IgM ratio was associated with poor prognosis in patients with COPD., Trial Registration: This clinical study, which included nonsmokers, healthy smokers, and smokers with COPD, was approved by the Ethics Committee of the Hokkaido University Hospital (012-0075, date of registration: September 5, 2012). The Hokkaido COPD cohort study was approved by the Ethics Committee of the Hokkaido University School of Medicine (med02-001, date of registration: December 25, 2002)., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Purpose: Enzalutamide is a potent inducer of cytochrome P450 substrates. Hence, it induces major metabolizing enzyme effects in some of the concomitant drugs, raising the possibility of decreased efficacy. We investigated the actual status of drugs for which precautions for co-administration are indicated during concomitant use with enzalutamide., Methods: We retrospectively investigated the duration of enzalutamide use, concomitant medications, laboratory values, and events using the medical records of patients prescribed enzalutamide for castration-resistant prostate cancer at the National Cancer Center Hospital from May 2014 to May 2017., Results: The median age of the 107 studied patients was 74 years[range: 53-93], median duration of enzalutamide prescriptions was 120 days[range: 14-1,008], and the median number of concomitant medications(components)was 6[range: 0-16]. Sixty nine patients(64%)were taking drugs that could be affected by enzyme induction. The medications listed in the concomitant use section of the package insert were warfarin(3 patients) and omeprazole(2 patients). In this study, 4 patients(except for 1 on warfarin)were taking other drugs that could be affected by enzyme induction. Events considered to possibly reduce their efficacy during concomitant use with enzalutamide were elevated blood pressure and blood clots., Conclusions: When enzalutamide is used in combination with other drugs, there exists the possibility that the effect of concomitant medications may be weakened by enzyme induction.

Endogenous lipoid pneumonia is an uncommon inflammatory pulmonary disease that is caused by lipids from an endogenous source, the treatment for which has not been established. We report the first case of endogenous lipoid pneumonia presenting as lung consolidation and which was associated with rheumatoid arthritis. Treatment was successful with intensive immunosuppressive therapy. When a physician finds lung consolidation in a patient with active rheumatic disease, lipoid pneumonia should be considered.

AIM is a secreted molecule produced by tissue macrophages, and observed in blood at 5-15microg/mL in both mice and humans. Today, AIM is highlighted as a key molecule in the pathogenesis of multiple metabolic diseases in particular by its lipolytic function in obese adipose tissue, causes chronic inflammation leading to insulin resistance. Furthermore, we recently found that association of AIM with IgM accumulates AIM in blood. Interestingly, this association also strongly supports IgM function in the presentation of self-antigens in the splenic germinal center, which promotes obesity-associated autoantibody production. In this report, we present the current knowledge about AIM, and discuss its important pathological roles, as well as its intriguing molecular behavior.

Purpose: To investigate the visual outcome 2 years after photodynamic therapy (PDT) in patients with exudative age-related macular degeneration (AMD) and polypoidal choroidal vasculopathy (PCV)., Methods: Thirty-six eyes undergoing PDT were retrospectively studied. Seventeen eyes of AMD (AMD group) and nineteen eyes of PCV (PCV group) were evaluated., Results: In the AMD group, the mean pre-PDT visual acuity was 0.19. The mean post-PDT visual acuity was 0.16 two years after the PDT. Two years after PDT, the Log MAR visual acuity improved by 0.2 or more in 3 eyes (17.7%), but it decreased by 0.2 or more in 4 eyes (23.5%). In the PCV group, the mean pre-PDT visual acuity was 0.34. The mean post-PDT visual acuity was 0.20 two years after PDT. The Log MAR visual acuity improved by 0.2 or more in 5 eyes (26.3%), but it decreased by 0.2 or more in 7 eyes (36.8%)., Conclusions: In this series of patients, more than half of the two groups were able to maintain their visual acuity for 2 years after PDT. Although the average visual acuity of the AMD group was worse than that of the PCV group, the AMD group was able to maintain their visual acuity for 2 years after PDT. The average visual acuity of the PCV group decreased 2 years after PDT.

A 51-year-old man was admitted to our hospital with fever, dry cough and dyspnea. He had taken minocycline for 11 days because of urinary tract infection. Chest X-ray on admission showed diffuse reticular shadows in bilateral lung fields with bilateral pleural effusion. Cessation of minocycline led to spontaneous improvement of symptoms and radiographic findings. The lymphocyte stimulation test for minocycline with peripheral blood and pleural effusion were negative. After provocation test with minocycline, he developed fever and dry cough and bilateral ground glass opacity appeared on his chest X-ray. He was diagnosed as minocycline-induced pneumonitis and recovered rapidly following corticosteroid therapy.