Mortality risk factors and fulminant sub-phenotype in anaerobic bacteremia: a 10-year retrospective, multicenter, observational cohort study.

PURPOSE: During the last decade, the incidence of anaerobic bacteremia (AB) has been increasing. Patients with AB may develop complex underlying diseases, which can occasionally be accompanied by fatal or fulminant outcomes. However, the risk factors for AB-related mortality remain unclear. Herein, we sought to elucidate the risk factors for AB-related mortality. METHODS: In this multicenter, retrospective, observational study, we enrolled patients with culture-proven AB from six tertiary hospitals in Japan, between January 2012 and December 2021. Data on patient and infection characteristics, laboratory findings, treatment, and outcome were collected, and their associations with mortality were analyzed. RESULTS: A total of 520 participants were included. The 30-day mortality in the study cohort was 14.0% (73 patients), and malignant tumors were frequently observed comorbidities in 48% of the entire cohort. Multivariable logistic regression analysis showed a Charlson comorbidity score of > 6, serum creatinine level of > 1.17 mg/dL, and hypotension to be independent risk factors for 30-day mortality in AB (odds ratios [ORs] 2.12, 2.25, and 5.12, respectively; p < 0.05), whereas drainage significantly reduced this risk (OR, 0.28; p < 0.0001). Twelve patients (2.3% of the whole cohort and 16.4% of the deceased patients) presented with extremely rapid progression leading to fatal outcome, consistent with "fulminant AB." CONCLUSIONS: This study identified acute circulatory dysfunction and performance of drainage as independent predictive factors for 30-day AB-related mortality and revealed the existence of a fulminant AB sub-phenotype. Our findings could serve as a practical guide to predict the clinical outcomes of AB.

An extremely energetic cosmic ray observed by a surface detector array.

Cosmic rays are energetic charged particles from extraterrestrial sources, with the highest-energy events thought to come from extragalactic sources. Their arrival is infrequent, so detection requires instruments with large collecting areas. In this work, we report the detection of an extremely energetic particle recorded by the surface detector array of the Telescope Array experiment. We calculate the particle's energy as [Formula: see text] (~40 joules). Its arrival direction points back to a void in the large-scale structure of the Universe. Possible explanations include a large deflection by the foreground magnetic field, an unidentified source in the local extragalactic neighborhood, or an incomplete knowledge of particle physics.

Effectiveness of patient and staff cohorting to reduce the risk of vancomycin-resistant enterococcus (VRE) acquisition: a retrospective cohort study during a VRE outbreak in Japan.

BACKGROUND: Patient and staff cohorting is part of a bundle approach in the response to multi-drug-resistant organisms, but its effectiveness is not fully clarified. This study compared the risks of acquiring vancomycin-resistant Enterococcus faecium (VREfm) at a hospital during a VREfm outbreak based on contact characteristics in order to better understand the effectiveness of cohorting. METHODS: Exposure came from contact with patients with VREfm (infectors), including existing patients with VREfm and patients who acquired VREfm during the study period. Contact was defined as length of contact time, degree of sharing space, and care by the same nurses as those caring for infectors between January and March 2018. The outcome was VREfm acquisition as determined through monthly stool or rectal screening cultures. Incidence rates were calculated based on contact patterns, and incidence rate ratios (IRRs) were compared. FINDINGS: Among 272 inpatients (4038 patient-days), 43 patients acquired VREfm with the same or similar pulsotype. Incidence rates were 8.45 per 1000 patient-days when susceptible inpatients were on the same ward as an infector but cared for by different nurses (reference), 16.96 when susceptible inpatients were on the same ward as an infector and cared for by the same nurses [IRR 2.01, 95% confidence interval (CI) 0.62-10.28], and 52.91 when susceptible inpatients shared a room with an infector (IRR 6.26, 95% CI 1.61-35.40). CONCLUSION: Compared with susceptible inpatients in a different room from infectors and not being cared for by the same nurses, the risk of VREfm acquisition could be six times higher for susceptible inpatients who are in the same room as infectors, and could be double for susceptible inpatients cared for by the same nurses as infectors.

Incidence and risk factors for hospital-acquired cholecystitis.

BACKGROUND: Acute cholecystitis can occur both inside and outside hospital settings. However, little is known about the clinical characteristics of hospital-acquired cholecystitis (HAC). AIM: To investigate the clinical characteristics of HAC in a tertiary academic hospital. METHODS: This retrospective cohort study included hospitalized patients who were found to have gallstones without cholecystitis or cholangitis on admission between January 2018 and December 2021. Multi-variate logistic regression analysis was used to make comparisons between patients with and without HAC. FINDINGS: In total, 890 patients met the inclusion criteria and were evaluated in this study. Forty-one patients (4.6%) developed HAC during the study period. Multi-variate logistic regression analysis showed that a history of cholecystitis or cholangitis, fasting for ≥1 day, and gallstones in the gallbladder neck were independently associated with increased risk of HAC. HAC occurred most frequently after several weeks of admission, and only four patients (9.8%) had bacteraemia. CONCLUSIONS: HAC was relatively common among hospitalized patients. Physicians should be aware of the possibility of HAC in symptomatic hospitalized patients with certain risk factors.

Favorable clinical response and drug retention of anti-IL-6 receptor inhibitor in rheumatoid arthritis with high CRP levels: the ANSWER cohort study.

OBJECTIVE: Currently, biological disease-modifying anti-rheumatic drugs (bDMARDs) with different modes of action [tumour necrosis factor inhibitor (TNFi), interleukin-6 receptor inhibitor (IL-6Ri), or cytotoxic T-lymphocyte antigen 4-immunoglobulin (CTLA4-Ig)] are used in clinical practice to treat rheumatoid arthritis (RA). However, it is unclear which type of bDMARD is the most efficacious for a specific clinical situation. C-reactive protein (CRP) is an acute-phase reactant driven by IL-6 signalling. Here, we aimed to establish whether therapeutic efficacy differs between IL-6Ri and other bDMARDs with alternative modes of action in RA patients according to their CRP level. METHOD: RA patients treated with bDMARDs were enrolled from an observational multicentre registry in Japan. Patients were classified into three groups according to baseline CRP tertiles. The overall 3 year retention rates of each bDMARD category were assessed. The Clinical Disease Activity Index (CDAI) was also assessed before and 3, 6, and 12 months after bDMARD initiation. RESULTS: A total of 1438 RA patients were included and classified into three groups according to tertiles of baseline CRP levels (CRP1, 0-0.3; CRP2, 0.3-1.8; CRP3, 1.8-18.4 mg/dL). In CRP3, the overall 3 year drug retention rates were significantly higher for IL-6Ri than for TNFi and CTLA4-Ig (77.5 vs 48.2 vs 67.3, respectively). No significant difference was evident in terms of CDAI 12 months after bDMARD initiation in CRP1-CRP3. CONCLUSION: IL-6Ri may be a favourable therapeutic option over TNFi and CTLA4-Ig in RA patients with high CRP levels.

Cholesterol 25-hydroxylase is a metabolic switch to constrain T cell-mediated inflammation in the skin.

Interleukin-27 (IL-27) is an immunoregulatory cytokine whose essential function is to limit immune responses. We found that the gene encoding cholesterol 25-hydroxylase (Ch25h) was induced in CD4+ T cells by IL-27, enhanced by transforming growth factor­ß (TGF-ß), and antagonized by T-bet. Ch25h catalyzes cholesterol to generate 25-hydroxycholesterol (25OHC), which was subsequently released to the cellular milieu, functioning as a modulator of T cell response. Extracellular 25OHC suppressed cholesterol biosynthesis in T cells, inhibited cell growth, and induced nutrient deprivation cell death without releasing high-mobility group box 1 (HMGB1). This growth inhibitory effect was specific to actively proliferating cells with high cholesterol demand and was reversed when extracellular cholesterol was replenished. Ch25h-expressing CD4+ T cells that received IL-27 and TGF-ß signals became refractory to 25OHC-mediated growth inhibition in vitro. Nonetheless, IL-27­treated T cells negatively affected viability of bystander cells in a paracrine manner, but only if the bystander cells were in the early phases of activation. In mouse models of skin inflammation due to autoreactive T cells or chemically induced hypersensitivity, genetic deletion of Ch25h or Il27ra led to worse outcomes. Thus, Ch25h is an immunoregulatory metabolic switch induced by IL-27 and dampens excess bystander T effector expansion in tissues through its metabolite derivative, 25OHC. This study reveals regulation of cholesterol metabolism as a modality for controlling tissue inflammation and thus represents a mechanism underlying T cell immunoregulatory functions.

Observation of nuclear-spin Seebeck effect.

Thermoelectric effects have been applied to power generators and temperature sensors that convert waste heat into electricity. The effects, however, have been limited to electrons to occur, and inevitably disappear at low temperatures due to electronic entropy quenching. Here, we report thermoelectric generation caused by nuclear spins in a solid: nuclear-spin Seebeck effect. The sample is a magnetically ordered material MnCO3 having a large nuclear spin (I = 5/2) of 55Mn nuclei and strong hyperfine coupling, with a Pt contact. In the system, we observe low-temperature thermoelectric signals down to 100 mK due to nuclear-spin excitation. Our theoretical calculation in which interfacial Korringa process is taken into consideration quantitatively reproduces the results. The nuclear thermoelectric effect demonstrated here offers a way for exploring thermoelectric science and technologies at ultralow temperatures.

Observation of Coulomb-Assisted Nuclear Bound State of Ξ

In an emulsion-counter hybrid experiment performed at J-PARC, a Ξ^{-} absorption event was observed which decayed into twin single-Λ hypernuclei. Kinematic calculations enabled a unique identification of the reaction process as Ξ^{-}+^{14}N→_{Λ}^{10}Be+_{Λ}^{5}He. For the binding energy of the Ξ^{-} hyperon in the Ξ^{-}-^{14}N system a value of 1.27±0.21 MeV was deduced. The energy level of Ξ^{-} is likely a nuclear 1p state which indicates a weak ΞN-ΛΛ coupling.

Quantification of Oscillatory Shear Stress from Reciprocating CSF Motion on 4D Flow Imaging.

BACKGROUND AND PURPOSE: Oscillatory shear stress could not be directly measured in consideration of direction, although cerebrospinal fluid has repetitive movements synchronized with heartbeat. Our aim was to evaluate the important of oscillatory shear stress in the cerebral aqueduct and foramen magnum in idiopathic normal pressure hydrocephalus by comparing it with wall shear stress and the oscillatory shear index in patients with idiopathic normal pressure hydrocephalus. MATERIALS AND METHODS: By means of the 4D flow application, oscillatory shear stress, wall shear stress, and the oscillatory shear index were measured in 41 patients with idiopathic normal pressure hydrocephalus, 23 with co-occurrence of idiopathic normal pressure hydrocephalus and Alzheimer-type dementia, and 9 age-matched controls. These shear stress parameters at the cerebral aqueduct were compared with apertures and stroke volumes at the foramen of Magendie and cerebral aqueduct. RESULTS: Two wall shear stress magnitude peaks during a heartbeat were changed to periodic oscillation by converting oscillatory shear stress. The mean oscillatory shear stress amplitude and time-averaged wall shear stress values at the dorsal and ventral regions of the cerebral aqueduct in the idiopathic normal pressure hydrocephalus groups were significantly higher than those in controls. Furthermore, those at the ventral region of the cerebral aqueduct in the idiopathic normal pressure hydrocephalus group were also significantly higher than those in the co-occurrence of idiopathic normal pressure hydrocephalus with Alzheimer-type dementia group. The oscillatory shear stress amplitude at the dorsal region of the cerebral aqueduct was significantly associated with foramen of Magendie diameters, whereas it was strongly associated with the stroke volume at the upper end of the cerebral aqueduct rather than that at the foramen of Magendie. CONCLUSIONS: Oscillatory shear stress, which reflects wall shear stress vector changes better than the conventional wall shear stress magnitude and the oscillatory shear index, can be directly measured on 4D flow MR imaging. Oscillatory shear stress at the cerebral aqueduct was considerably higher in patients with idiopathic normal pressure hydrocephalus.

Histopathological study of carcinoma showing thymus-like differentiation (CASTLE).

INTRODUCTION: Carcinoma showing thymus-like differentiation (CASTLE) is a rare tumour that mainly arises from the thyroid gland, or occasionally, from the head and neck. Although the 10-year survival rate of patients with CASTLE is approximately 80%, local recurrence and distant metastasis are observed in some cases. A recent systematic review for CASTLE indicated that the prognostic factors are treatment-dependent, and postoperative radiotherapy significantly improves patient survival. CASE REPORT: Herein, we describe and compare three cases of CASTLE, including a case with distant metastasis despite administering postoperative chemotherapy. Thus, the mechanisms underlying metastasis of CASTLE are unclear. This case study helps to elucidate the histopathological risk factors of metastasis in CASTLE. DISCUSSION: We found that prominent lymphovascular invasion and higher proliferative activities might be risk factors of metastasis in CASTLE. In addition, we have summarised the cytological, morphological, and immunohistochemical features of CASTLE for an accurate diagnosis.