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.

A case of IgG4-related autoimmune disease with multiple organ involvement.

A 52-year-old male was admitted with autoimmune pancreatitis (AIP), showing mononuclear cell infiltration in both the pancreas and salivary glands with both normal sialography and anti-SS-A/SS-B antibodies. Although the AIP improved with glucocorticoid treatment, subsequent abdominal computed tomography (CT) revealed a nodular shadow in the bilateral kidneys, which was confirmed as interstitial nephritis by renal biopsy. The patient's serum immunoglobulin G4 (IgG4) level was 10 times higher than the upper limit of the normal range. IgG4-positive mononuclear cell infiltration was detected in the salivary gland, pancreas, and kidney. A new entity proposed as 'IgG4-related autoimmune disease' was considered.

RS3PE syndrome presenting as vascular endothelial growth factor associated disorder.

OBJECTIVES: To characterise serum concentrations of various cytokines and detection by magnetic resonance imaging (MRI) of synovial hypervascularity in patients with remitting seronegative symmetrical synovitis with pitting oedema (RS3PE) syndrome before and after corticosteroid treatment. METHODS: Vascular endothelial growth factor(165) (VEGF(165)), tumour necrosis factor alpha (TNFalpha), and interleukin 1beta (IL1beta) were measured by enzyme linked immunosorbent assay (ELISA) in serum samples from three patients with RS3PE syndrome. As controls, serum samples from 26 healthy volunteers, 12 patients with rheumatoid arthritis, 10 patients with systemic lupus erythematosus, 13 patients with polymyositis/dermatomyositis, 13 patients with vasculitis syndrome, and 6 patients with mixed connective tissue disease were also analysed. Synovial hypervascularity of patients with RS3PE syndrome was estimated by rate of enhancement (E-rate) in a dynamic MRI study. RESULTS: Serum concentrations of VEGF(165) (mean (SD) 2223.3 (156.3) pg/ml) were significantly higher in patients with active RS3PE syndrome than in controls before corticosteroid treatment. TNFalpha and IL1beta levels were similar in patients and controls. Synovial hypervascularity in affected joints and subcutaneous oedema decreased during corticosteroid treatment, in parallel with the fall in serum VEGF(165). CONCLUSIONS: VEGF promotes synovial inflammation and vascular permeability in patients with RS3PE syndrome, suggesting that RS3PE can be classified as a VEGF associated disorder.

Detection of apoptosis-specific autoantibodies directed against granzyme B-induced cleavage fragments of the SS-B (La) autoantigen in sera from patients with primary Sjögren's syndrome.

The objective of this study was to detect autoantibodies against granzyme B cleavage products in sera from patients with primary Sjögren's syndrome (SS). Cell lysates derived from human salivary gland (HSG) cell lines were incubated with granzyme B. The susceptibility to the generation of cleavage fragments of SS autoantigens was assayed by immunoblotting using sera from 57 primary SS patients, 17 primary SS patients with malignant lymphoma (ML), 28 systemic lupus erythematosus (SLE) patients, and 20 healthy controls. A 27 kD protein was recognized by serum autoantibodies in 8 (14.0%) of 57 primary SS patients, 5 (29.4%) of 17 SS patients with ML, 2 (7.1%) of 28 SLE patients, but not in 20 normal subjects. This protein was recognized by anti-SSB (La) monoclonal antibodies. Granzyme B-treated recombinant La protein was also shown to migrate as a discrete 27 kD protein by SDS PAGE. Blocking studies demonstrated the existence of an apoptosis-specific B cell epitope present in sera from 2 of 8 primary SS patients and in 2 of 5 primary SS patients with ML which recognized the 27 kD protein. Granzyme B-induced La fragments are generated during cytotoxicity in vitro. This is the first report describing autoantibodies in sera from primary SS patients that specifically recognize fragments of the La protein that are produced by the granzyme B protease.

Transient shrinkage of a uterine leiomyosarcoma treated with GnRH agonist for a presumed uterine leiomyoma: comparison of magnetic resonance imaging finding before and during GnRH agonist treatment.

We present a case of a premenopausal woman treated with GnRH agonist for a presumed uterine leiomyoma. This tumor reduced at first, but subsequent surgical specimens revealed a leiomyosarcoma. Magnetic resonance imaging (MRI), one of the most useful modalities for distinguishing between uterine leiomyoma and leiomyosarcoma, was undertaken twice, before GnRH agonist administration and then after 6 months of GnRH agonist administration. Apparent differences were observed between these MRI findings. Tumor-size reduction with GnRH agonist treatment does not always mean that the possibility of a leiomyosarcoma should be ruled out.

Lamprey fructose-1,6-bisphosphate aldolase: characterization of the muscle-type and non-muscle-type isozymes.

To study evolutionary aspects of fructose-1,6-bisphosphate (Fru-1,6-P2) aldolase during deuterostomian evolution, we have purified and characterized aldolases from the muscle and liver of lamprey (Entosphenus japonicus). Aldolase from the skeletal muscle and liver was identified to be the muscle-type isozyme and the non-muscle-type isozyme that was encoded by cDNAs M8 and L3, respectively, as described previously (Zhang, R., Yatsuki, H., Kusakabe, T., Iwabe, Miyata, T., Imai, T., Yoshida, M., and Hori, K., J. Biochem. 117, 545-553, 1995). The muscle-type isozyme has properties similar to vertebrate aldolase A, while the non-muscle-type isozyme shows a similarity to bacterial class I aldolase and vertebrate aldolase C but not to aldolase B, the liver-type aldolase, in terms of kinetic parameters: the Kcat values toward Fru-1,6-P2 and Fru-1-P, the Fru-1,6-P2/Fru-1-P activity ratio, and the Km values toward these substrates. The two enzymes have tetrameric forms with a molecular mass of approximately 160,000 and have similar pH optimum. The muscle-type and non-muscle-type isozymes from the tissues show different electrophoretic mobility; the muscle-type isozyme moves much faster than the non-muscle-type isozyme toward anodic side. The recombinant muscle-type and non-muscle-type aldolases gave similar characteristics as those from the tissues. The results presented in this paper, together with the data presented in the previous paper, strongly suggest that in lamprey it is possible to have two types of aldolase isozymes rather than one or three isozymes.

Evaluation of Yucatan micropig skin for use as an in vitro model for skin permeation study.

Skin permeation rates of five non-steroidal anti-inflammatory drugs, three of them lipophilic (ibuprofen, indomethacin and ketoprofen) and two hydrophilic (sodium diclofenac and antipyrine), through Yucatan hairless micropig (YMP) full-thickness skin were determined in vitro using Franz-type diffusion cells, and the usefulness of YMP skin as an animal model skin was investigated. Five-month-old YMP skin showed small variation with respect to drug permeation rates, if the region of skin site was the same. But skin from 6-month-old YMPs showed faster and varied permeation rates due to skin defects. In the case of hydrophilic drugs, no effects on permeation due to the region from which the skin was obtained were observed, although higher permeation rates were observed through the flank than through dorsal skin in the case of ibuprofen and ketoprofen. For YMP skin, the permeation coefficients of drugs were lower than those for hairless rat skin, especially for hydrophilic drugs. Compared with reported human data on permeation coefficients, the permeation coefficients of drugs through YMP skin were 1/2-1/8 of those through human skin, regardless of whether the drugs were hydrophilic or lipophilic. YMP skin could be used as an in vitro animal skin model because of the reproducibility of the permeation rate of drugs through this skin and its similarity to human skin.

[Anti-glomerular basement membrane antibody-mediated glomerulonephritis remarkably improved by pulse therapy with methylprednisolone, plasmapheresis and continuous heparin infusion].

The patient, a 28 year-old-man, was admitted to a hospital because of general fatigue and fever. He was pointed out renal dysfunction and was transferred to Nagasaki University Hospital. The laboratory data on admission showed moderate azotemia (BUN 43 mg/dl, Cr 5.4 mg/dl). A percutaneous renal biopsy on admission revealed a diffuse crescentic glomerulonephritis. A direct immunofluorescence of renal biopsy showed a linear pattern for IgG along the glomerular basement membrane. Radioimmunoassay of his serum for circulating anti-GBM antibody was strongly positive. Aggressive treatment with pulse therapy (methylprednisolone), plasmapheresis, and continuous heparin infusion was performed. He had markedly recovered from renal failure and escaped hemodialysis. The patient is making satisfactory process after 3 years.