ABSTRACT
Evidence for the efficacy of denosumab in HD patients is limited. Accordingly, here we report a study on the safety and efficacy of denosumab in these patients. We prospectively followed 324 patients (121 HD and 203 non-HD patients) receiving denosumab between June 2013 and May 2018, assessing changes in bone mineral density (BMD) and bone metabolic markers, and noting side-effects. Annual changes in BMD at the lumbar spine in HD and non-HD patients from baseline were, respectively, 6.7 ± 11.1% and 7.5 ± 10.2% (p = 0.60), those at the femoral neck were 4.3 ± 7.9% and 3.1 ± 9.5% (p = 0.32), and those at the distal radius were -0.5 ± 6.4% and 0.2 ± 13.0% (p = 0.66). The prevalence of hypocalcemia (<8.5 mg/dL) was significantly higher in HD than in non-HD patients (35.6% vs 5.4%, p < 0.001). The median elapsed time between the first injection of denosumab and the occurrence of hypocalcemia was 7 days in HD patients. The decrease of serum calcium was greater in patients with higher TRACP5b, corticosteroid use, and those without CaCO3 supplementation. Our study suggests that denosumab was equally as effective in HD as non-HD patients. However, careful hypocalcemia monitoring, for at least 4 weeks, is recommended for HD patients.
Subject(s)
Bone Density Conservation Agents/therapeutic use , Denosumab/therapeutic use , Hypocalcemia/etiology , Kidney Failure, Chronic/therapy , Osteoporosis/drug therapy , Renal Dialysis/adverse effects , Aged , Bone Density , Bone Density Conservation Agents/administration & dosage , Denosumab/administration & dosage , Female , Humans , Hypocalcemia/epidemiology , Kidney Failure, Chronic/complications , Male , Middle Aged , Osteoporosis/complicationsABSTRACT
A 72-year-old woman presented 9 months ago with skin rash on her bilateral forearms, which was followed by intermittent high fever, and stiffness and swelling of her bilateral fingers. She was diagnosed with seronegative rheumatoid arthritis (RA). She had a past history of breast cancer and had undergone breast preservation surgery 13 years previously. During admission in our hospital, she developed high fever and leukocytosis with a relapsing skin rash, sore throat, polyarthralgia and increased levels of serum ALT/AST and ferritin, all of which fulfilled Yamaguchi's criteria for adult-onset Still's disease (AOSD). While we tried to exclude other diseases that may show AOSD-like manifestations, pancytopenia rapidly developed and bone marrow biopsy strongly suggested the diagnosis of macrophage activating syndrome (MAS). Accordingly, steroid pulse therapy was begun, followed by oral glucocorticoid therapy. Thereafter, all of her symptoms improved, but systemic rash, inflammatory signs and pancytopenia gradually progressed. The results of bone marrow pathology, which returned 2 weeks after the beginning of treatment, revealed hemophagocytosis with CK7-positive/CK20-negative atypical cells that suggested recurrence of breast cancer in the bone marrow, thus all of her AOSD-like symptoms were considered to be paraneoplastic manifestations of late-onset metastatic breast cancer. She was treated successfully with chemotherapy. When we see the patients showing AOSD-like symptoms with a history of malignancy, we should consider the possibility of paraneoplastic syndrome due to cancer recurrence.
Subject(s)
Bone Neoplasms/secondary , Breast Neoplasms/pathology , Paraneoplastic Syndromes/pathology , Still's Disease, Adult-Onset/pathology , Aged , Diagnosis, Differential , Female , HumansABSTRACT
OBJECTIVES: In lupus nephritis, the immune complex plays a very important role in kidney disease progression, and immunoglobulin G subclass 3 (IgG3) may play an important role in endothelial damage as lupus nephropathy progresses. We evaluated the association between IgG3 positivity and lupus nephritis activity. MATERIALS AND METHODS: We identified 71 biopsies taken from 57 patients who had lupus nephritis with enough tissue to allow light and immunofluorescence microscopy. We compared the intensity of IgG subclass staining (on a scale of 0 - 3+) with IgG subclass dominance among lupus nephritis classes as defined by the ISN/RPS 2003 classification. RESULTS: The proportion of IgG3-positive patients with capillary loop lesion was significantly higher in the class IV group compared with other groups (p < 0.01). Interestingly, in most patients IgG1 was the strongest subclass; in class IV groups, IgG3 was the strongest in 21% of the biopsies. IgG3 deposition in capillary loops was significantly associated with C1q deposition in those loops. According to Kaplan-Meier analysis, renal survival rates in the patients with IgG3 deposition was lower (82.2%) than in patients without IgG3 deposition (93.3%), but the difference was not significant. CONCLUSION: Our results suggest that capillary loop deposition of IgG3 is associated with disease activity in lupus nephritis.â©.
Subject(s)
Immunoglobulin G/immunology , Kidney/pathology , Lupus Nephritis/immunology , Adult , Female , Fluorescent Antibody Technique , Humans , Lupus Nephritis/pathology , Male , Middle Aged , Retrospective Studies , Survival AnalysisABSTRACT
The immunohistochemical characteristics of brush cells in the laryngeal mucosa were examined using immunohistochemistry for various immunohistochemical cell markers including villin at the light and electron microscopic levels. Cells that were immunoreactive to villin were barrel-shaped with thick cytoplasmic processes extending toward the lumen of the laryngeal cavity. Immunoelectron microscopic observations revealed thick and short microvilli with long rootlets of microfilaments. Numerous small clear vesicles and small finger-like cytoplasmic processes were observed in the apical process and lateral membrane, respectively. Double immunofluorescence showed villin-immunoreactive cells were not immunoreactive for the markers of solitary chemosensory cells, GNAT3 and phospholipase C, ß2-subunit (PLCß2), or for that of neuroendocrine cells, synaptosome-associated protein 25kD. Furthermore, immunoreactivities for cytokeratin 18 (CK18) and doublecortin like-kinase 1 in the perinuclear cytoplasm of villin-immunoreactive cells. However, some CK18-immunoreactive cells were immunoreactive to GNAT3 but not to villin. Regarding sensory innervation, only a few intraepithelial nerve endings with P2X3, SP, or CGRP immunoreactivity attached to villin-immunoreactive cells. In the present study, brush cells in the rat laryngeal mucosa were classified by immunoreactivity for villin, and were independent of other non-ciliated epithelial cells such as solitary chemosensory cells and neuroendocrine cells.
Subject(s)
Epithelial Cells/ultrastructure , Immunohistochemistry , Larynx/cytology , Microvilli , Animals , Doublecortin Protein , Microfilament Proteins/analysis , Microfilament Proteins/immunology , Mucous Membrane/cytology , RatsABSTRACT
PURPOSE: To evaluate the clinical usefulness of an integrated closed intravenous catheter system (CICS) with a preattached stabilization platform and extension tube (BD Nexiva™; Becton, Dickinson and Company) in Japanese patients. METHODS: In this open, single-center study, patients who required peripheral intravenous (PIV) catheterization for ≥72 hours were quasi-randomized to receive a CICS or a conventional intravenous catheter. Study outcomes included adverse events during catheter insertion, catheter replacements during the initial 72 hours, catheter survival rate at 72 hours after insertion and costs of initial catheterization and catheter replacement. RESULTS: Of 359 patients enrolled, 194 received the CICS and 165 received the conventional catheter. The incidence rates of ≥1 failed insertion attempts, blood leakage and blood exposure were similar in both groups. The survival rate of the CICS group (83.7%) was significantly higher than that of the conventional catheter group (62.6%) in the intention-to-treat analysis (p=0.0085). There were significantly fewer catheter replacements due to catheter-related complications (e.g., catheter failure or extravasation) in the CICS group (p=0.0056). Although the initial cost per patient was greater for the CICS group (US$17.07 vs. US$13.26), the total cost per patient over 72 hours was similar (US$21.00 vs. US$20.30) because of the cost of unplanned replacements of conventional catheters. CONCLUSIONS: Although rates of adverse events at insertion were similar for both catheters, significantly fewer patients required unplanned reinsertion with the CICS. The results suggest that the longer survival rate for the CICS can offset the higher initial catheterization costs.