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International Journal of Rheumatology 2012Objectives. The characteristic features of Mikulicz's disease (MD) are diffuse enlargement of the lacrimal and submandibular glands, elevated levels of serum...
Objectives. The characteristic features of Mikulicz's disease (MD) are diffuse enlargement of the lacrimal and submandibular glands, elevated levels of serum immunoglobulin (Ig)G4, and abundant infiltration of IgG4-positive plasmacytes into both glands. No disease index is available to properly evaluate MD, so we developed a functional assessment of MD, the Mikulicz's disease activity questionnaire (MAQ), and evaluated its clinical efficacy. Methods. We selected 18 patients who were either being treated for MD or who had presented with recurrence. The patients completed a self-assessment and were scored according to the MAQ sheet during each visit between December 2009 and August 2011. Assessment items were in regard to increases or decreases in lacrimal and salivary gland enlargement and severity of sicca symptoms. Results. On the first visits, MAQ scores were high, but scores decreased rapidly as treatment progressed. When doses of glucocorticoid were reduced, some patients showed increased scores. Dry-symptom scores increased initially. MAQ scores for patients with recurrent MD gradually increased over several months before relapse. However, some patients displayed no elevation in MAQ scores due to relapses at other sites. Conclusion. MAQ score can be used to quantify flares and treatment response and is useful for functional assessment of MD.
PubMed: 22649453
DOI: 10.1155/2012/283459 -
Journal of the American College of... Jun 2024Empagliflozin reduces the risk of heart failure (HF) hospitalizations but not all-cause mortality when started within 14 days of acute myocardial infarction (AMI). (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Empagliflozin reduces the risk of heart failure (HF) hospitalizations but not all-cause mortality when started within 14 days of acute myocardial infarction (AMI).
OBJECTIVES
This study sought to evaluate the association of left ventricular ejection fraction (LVEF), congestion, or both, with outcomes and the impact of empagliflozin in reducing HF risk post-AMI.
METHODS
In the EMPACT-MI (Trial to Evaluate the Effect of Empagliflozin on Hospitalization for Heart Failure and Mortality in Patients with Acute Myocardial Infarction) trial, patients were randomized within 14 days of an AMI complicated by either newly reduced LVEF<45%, congestion, or both, to empagliflozin (10 mg daily) or placebo and were followed up for a median of 17.9 months.
RESULTS
Among 6,522 patients, the mean baseline LVEF was 41 ± 9%; 2,648 patients (40.6%) presented with LVEF <45% alone, 1,483 (22.7%) presented with congestion alone, and 2,181 (33.4%) presented with both. Among patients in the placebo arm of the trial, multivariable adjusted risk for each 10-point reduction in LVEF included all-cause death or HF hospitalization (HR: 1.49; 95% CI: 1.31-1.69; P < 0.0001), first HF hospitalization (HR: 1.64; 95% CI: 1.37-1.96; P < 0.0001), and total HF hospitalizations (rate ratio [RR]: 1.89; 95% CI: 1.51-2.36; P < 0.0001). The presence of congestion was also associated with a significantly higher risk for each of these outcomes (HR: 1.52, 1.94, and RR: 2.03, respectively). Empagliflozin reduced the risk for first (HR: 0.77; 95% CI: 0.60-0.98) and total (RR: 0.67; 95% CI: 0.50-0.89) HF hospitalizations, irrespective of LVEF or congestion, or both. The safety profile of empagliflozin was consistent across baseline LVEF and irrespective of congestion status.
CONCLUSIONS
In patients with AMI, the severity of left ventricular dysfunction and the presence of congestion was associated with worse outcomes. Empagliflozin reduced first and total HF hospitalizations across the range of LVEF with and without congestion. (Trial to Evaluate the Effect of Empagliflozin on Hospitalization for Heart Failure and Mortality in Patients with Acute Myocardial Infarction [EMPACT-MI]; NCT04509674).
Topics: Humans; Benzhydryl Compounds; Glucosides; Male; Female; Myocardial Infarction; Heart Failure; Middle Aged; Aged; Sodium-Glucose Transporter 2 Inhibitors; Ventricular Function, Left; Stroke Volume; Hospitalization; Double-Blind Method; Follow-Up Studies
PubMed: 38588929
DOI: 10.1016/j.jacc.2024.03.405 -
Internal Medicine (Tokyo, Japan) 2010
Topics: Humans; Immunoglobulin G; Mikulicz' Disease; Ribonucleosides; Treatment Outcome
PubMed: 20647641
DOI: 10.2169/internalmedicine.49.3692 -
Nihon Rinsho Men'eki Gakkai Kaishi =... 2013IgG4-related disease is thought to show good prognosis because of positive responsiveness to corticosteroids. Increased long-term observations of IgG4-related disease... (Review)
Review
IgG4-related disease is thought to show good prognosis because of positive responsiveness to corticosteroids. Increased long-term observations of IgG4-related disease have provided clinical data regarding the functional prognosis of organs. We analyzed the necessity for early intervention based on those findings and our own experience. It is important for the recovery and maintenance of salivary gland function to start corticosteroid treatment within 2 years after onset, and to maintain clinical remission in cases of IgG4-related dacryoadenitis and sialoadenitis (so-called Mikulicz's disease). Early intervention might be useful in cases of IgG4-related kidney disease because recovery of renal function is insufficient when estimated glomerular filtration before treatment is <60 ml/min. Corticosteroid treatment significantly suppresses relapse in patients with autoimmune pancreatitis showing a relatively high rate of spontaneous remission. Long-term observational studies have demonstrated the transformation of autoimmune pancreatitis into chronic pancreatitis presenting with pancreatic atrophy and stone formation. The treatment protocol and timing of initiation should thus be considered. Although organ dysfunction in IgG4-related disease proceeds more slowly than in conventional chronic inflammatory disorders, sustained IgG4-related lesions still cause accumulation of organ damage with expansion of fibrosis. Intervention as soon as possible would favorably impact IgG4-related disease, considering the side effects of treatments such as corticosteroids.
Topics: Diabetes Mellitus, Type 1; Female; Glomerular Filtration Rate; Glucocorticoids; Humans; Immunoglobulin G; Kidney Diseases; Male; Mikulicz' Disease; Pancreatitis; Pancreatitis, Chronic; Prednisolone; Prognosis; Time Factors; Treatment Outcome
PubMed: 24390104
DOI: 10.2177/jsci.36.442 -
Advances in Clinical and Experimental... Oct 2022Cardiovascular disease (CVD) is associated with intestinal barrier dysfunction and increased intestinal permeability. Increased intestinal permeability to gut microbial...
BACKGROUND
Cardiovascular disease (CVD) is associated with intestinal barrier dysfunction and increased intestinal permeability. Increased intestinal permeability to gut microbial metabolites may accelerate the progression of CVD. Plasma citrulline levels are a marker of functional enterocyte mass, and reduced citrulline levels indicate intestinal epithelial damage. Citrulline was reported as a useful prognostic marker in critically ill patients. However, data are lacking on the association of citrulline with long-term mortality in patients with CVD and with the levels of trimethylamine N-oxide (TMAO), a microbiota-derived metabolite which has been implicated in the pathogenesis of CVD.
OBJECTIVES
To assess the effect of citrulline levels, a marker of intestinal barrier disruption, on long-term mortality in patients with CVD. Moreover, the relationship between the concentrations of 2 biomarkers - citrulline and TMAO - was assessed.
MATERIAL AND METHODS
Serum citrulline levels were retrospectively assessed in 1036 consecutive patients with CVD (median age: 62 years; 61% men) hospitalized between 2013 and 2015. Associations of citrulline levels with 5-year mortality rates as well as anthropometric and biochemical parameters were evaluated for the entire study group and in subgroups of patients with acute coronary syndrome (ACS), chronic coronary syndrome, chronic heart failure (chronic HF), and atrial fibrillation (AF). Correlations between serum citrulline and TMAO levels were assessed.
RESULTS
The median citrulline level in the study population was 22.5 μM (interquartile range (IQR): 17.8-27.9). Citrulline levels were not associated with 5-year mortality in patients with CVD (hazard ratio (HR) = 0.99; 95% confidence interval (95% CI): 0.97-1.00; p = 0.49). Median citrulline levels differed significantly between deceased patients and survivors at 5 years in patients with ACS (p = 0.025). There were no significant correlations between citrulline and TMAO levels (Kendall's tau = 0.027).
CONCLUSIONS
Decreasing citrulline levels do not predict long-term mortality of hospitalized patients with CVD. Moreover, they are not associated with the serum levels of TMAO in these patients.
Topics: Male; Humans; Middle Aged; Female; Citrulline; Cardiovascular Diseases; Retrospective Studies; Prognosis; Biomarkers; Acute Coronary Syndrome
PubMed: 35699588
DOI: 10.17219/acem/150475 -
Nihon Rinsho Men'eki Gakkai Kaishi =... Dec 2009Since Hamano et al. have first reported serum IgG4 elevation in sclerosing pancreatitis in 2001, various systemic disorders have been reported to be related to elavated... (Review)
Review
Since Hamano et al. have first reported serum IgG4 elevation in sclerosing pancreatitis in 2001, various systemic disorders have been reported to be related to elavated IgG4, and many names have been proposed from the point of view of the systemic condition. Despite similarities in the organs damaged in IgG4-related Mikulicz's disease and Sjögren's syndrome, there are marked clinical and pathological differences between the two entities. IgG4-related Mikulicz's disease and Küttner's tumor are related diseases and complete differentiation is very difficult. The majority of cases diagnosed with autoimmune pancreatitis in Japan are IgG4-related sclerosing pancreatitis, and it should be recognized that this is distinct from the western type. There is a likelihood that cases once diagnose as Castleman's disease that showed good responsiveness to glucocorticoid treatment may have been IgG4-related lymphadenopathy, and should be re-assessed in light of recent findings. Diagnosis of IgG4-related disease is defined by both 1) Elevated serum IgG4 (>135 mg/dl) and 2) Histopathological features including lymphocyte and IgG4(+) plasma cell infiltration (IgG4(+) plasma cells/IgG(+) plasma cells >50% on a highly-magnified slide checked in five points), however differential diagnosis from other distinct disorders, such as sarcoidosis, Castleman's disease, Wegener's granulomatosis, lymphoma, cancer, and other existing conditions is necessary. To avoid diagnostic confusion, simpler and more scientific names should be used where disease-specific pathogenesis or markers have been ascertained.
Topics: Autoimmune Diseases; Biomarkers; Castleman Disease; Diagnosis, Differential; Granulomatosis with Polyangiitis; Humans; Immunoglobulin G; Lymphatic Diseases; Lymphoma; Mikulicz' Disease; Pancreas; Pancreatitis; Sclerosis; Sjogren's Syndrome
PubMed: 20046015
DOI: 10.2177/jsci.32.478 -
Gut and Liver Jan 2013The objective of this study was to compare the clinical characteristics of patients with autoimmune pancreatitis (AIP) with or without Mikulicz's disease (MD) and with...
BACKGROUND/AIMS
The objective of this study was to compare the clinical characteristics of patients with autoimmune pancreatitis (AIP) with or without Mikulicz's disease (MD) and with MD alone.
METHODS
We investigated the clinical findings in 15 AIP patients with MD (group A+M), 49 AIP only patients (group A), and 14 MD only patients (group M).
RESULTS
The male-female ratio was significantly higher in group A+M (73%, p<0.05) and group A (78%, p<0.01) than group M (21%). Serum immunoglobulin G (IgG) levels were significantly higher in group A+M than in group A (p<0.01) and group M (p<0.05). Serum IgG4 levels were significantly higher in group A+M than in group A (p<0.01). Other organ involvement was observed in 73% (11/15) of patients in group A+M. The number of patients with diabetes mellitus was significantly higher in group A+M (66%, p<0.01) and group A (51%, p<0.05) than in group M (7%). All of the patients responded well to steroid therapy, but the relapse rate in group A+M (33%) was significantly higher than that in group A (3%, p<0.01). Salivary gland function was impaired in all groups compared with the control group, but the degree of dysfunction was less in group A compared with group A+M and group M.
CONCLUSIONS
The relapse rate of AIP in MD patients was significantly higher than that of AIP in patients without MD.
PubMed: 23422705
DOI: 10.5009/gnl.2013.7.1.96 -
Journal of Autoimmunity Jun 2014IgG4-related disease (IgG4-RD) is a systemic disease characterized by the elevation of serum IgG4 and infiltration of IgG4-positive plasma cells in multiple target... (Review)
Review
IgG4-related disease (IgG4-RD) is a systemic disease characterized by the elevation of serum IgG4 and infiltration of IgG4-positive plasma cells in multiple target organs, including the pancreas, kidney, biliary tract and salivary glands. In contrast, Mikulicz's disease (MD) has been considered a subtype of Sjögren's syndrome (SS) based on histopathological similarities. However, it is now recognized that MD is an IgG4-RD distinguishable from SS and called as IgG4-related dacryoadenitis and sialoadenitis (IgG4-DS). Regarding immunological aspects, it is generally accepted that CD4+ T helper (Th) cells play a crucial role in the pathogenesis of SS. Since it is well known that IgG4 is induced by Th2 cytokines such as interleukin (IL)-4 and IL-13, IgG4-DS is speculated to be a unique inflammatory disorder characterized by Th2 immune reactions. However, the involvement of Th cells in the pathogenesis of IgG4-DS remains to be clarified. Exploring the role of Th cell subsets in IgG4-DS is a highly promising field of investigation. In this review, we focus on the selective localization and respective functions of Th cell subsets and discuss the differences between SS and IgG4-DS to clarify the pathogenic mechanisms of these diseases.
Topics: Animals; Cytokines; Dacryocystitis; Humans; Immunoglobulin G; Interleukins; Sialadenitis; Sjogren's Syndrome; T-Lymphocyte Subsets; T-Lymphocytes, Helper-Inducer
PubMed: 23920005
DOI: 10.1016/j.jaut.2013.07.007 -
Viruses Sep 2022There is accumulating evidence on the perinatal aspects of COVID-19, but available data are still insufficient. The reports on perinatal aspects of COVID-19 have been...
There is accumulating evidence on the perinatal aspects of COVID-19, but available data are still insufficient. The reports on perinatal aspects of COVID-19 have been published on a small group of patients. Vertical transmission has been noted. The SARS-CoV-2 genome can be detected in umbilical cord blood and at-term placenta, and the infants demonstrate elevated SARS-CoV-2-specific IgG and IgM antibody levels. In this work, the analysis of clinical characteristics of RT-PCR SARS-CoV-2-positive pregnant women and their infants, along with the placental pathology correlation results, including villous trophoblast immunoexpression status for SARS-CoV-2 antibody, is presented. RT-PCR SARS-CoV-2 amniotic fluid testing was performed. Neonatal surveillance of infection status comprised RT-PCR testing of a nasopharyngeal swab and the measuring of levels of anti-SARS-CoV-2 in blood serum. In the initial study group were 161 pregnant women with positive test results. From that group, women who delivered during the hospital stay were selected for further analysis. Clinical data, laboratory results, placental histomorphology results, and neonatal outcomes were compared in women with immunohistochemistry (IHC)-con SARS-CoV-2-positive and IHC SARS-CoV-2-negative placentas (26 cases). A positive placental immunoprofile was noted in 8% of cases ( = 2), whereas 92% of cases were negative ( = 24). Women with placental infection proven by IHC had significantly different pathological findings from those without. One infected neonate was noted ( = 1; 4%). Infection was confirmed in perinatal autopsy, as there was the intrauterine fetal demise. The potential course of the infection with the risk of vertical transmission and implications for fetal-neonatal condition is critical for proper clinical management, which will involve comprehensive, multidisciplinary perinatal care for SARS-CoV-2-positive patients.
Topics: COVID-19; Female; Humans; Immunoglobulin G; Immunoglobulin M; Infant; Infant, Newborn; Infectious Disease Transmission, Vertical; Placenta; Pregnancy; Pregnancy Complications, Infectious; SARS-CoV-2
PubMed: 36146849
DOI: 10.3390/v14092043 -
Arthritis Research & Therapy Aug 2015The aim of this study was to clarify the effectiveness of various imaging modalities and characteristic imaging features in the screening of IgG4-related dacryoadenitis...
Effectiveness of imaging modalities for screening IgG4-related dacryoadenitis and sialadenitis (Mikulicz's disease) and for differentiating it from Sjögren's syndrome (SS), with an emphasis on sonography.
INTRODUCTION
The aim of this study was to clarify the effectiveness of various imaging modalities and characteristic imaging features in the screening of IgG4-related dacryoadenitis and sialadenitis (IgG4-DS), and to show the differences in the imaging features between IgG4-DS and Sjögren's syndrome (SS).
METHODS
Thirty-nine patients with IgG4-DS, 51 with SS and 36 with normal salivary glands were enrolled. Images of the parotid and submandibular glands obtained using sonography, 2-[(18)F]-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (FDG-PET/CT), computed tomography (CT) and magnetic resonance imaging (MRI) were retrospectively analyzed. Six oral and maxillofacial radiologists randomly reviewed the arranged image sets under blinded conditions. Each observer scored the confidence rating regarding the presence of the characteristic imaging findings using a 5-grade rating system. After scoring various findings, diagnosis was made as normal, IgG4-DS or SS, considering all findings for each case.
RESULTS
On sonography, multiple hypoechoic areas and hyperechoic lines and/or spots in the parotid glands and obscuration of submandibular gland configuration were detected mainly in patients with SS (median scores 4, 4 and 3, respectively). Reticular and nodal patterns were observed primarily in patients with IgG4-DS (median score 5). FDG-PET/CT revealed a tendency for abnormal (18)F-FDG accumulation and swelling of both the parotid and submandibular glands in patients with IgG4-DS, particularly in the submandibular glands. On MRI, SS had a high score regarding the findings of a salt-and-pepper appearance and/or multiple cystic areas in the parotid glands (median score 4.5). Sonography showed the highest values among the four imaging modalities for sensitivity, specificity and accuracy. There were significant differences between sonography and CT (p = 0.0001) and between sonography and FDG-PET/CT (p = 0.0058) concerning accuracy.
CONCLUSIONS
Changes in the submandibular glands affected by IgG4-DS could be easily detected using sonography (characteristic bilateral nodal/reticular change) and FDG-PET/CT (abnormal (18)F-FDG accumulation). Even inexperienced observers could detect these findings. In addition, sonography could also differentiate SS. Consequently, we recommend sonography as a modality for the screening of IgG4-DS, because it is easy to use, involves no radiation exposure and is an effective imaging modality.
Topics: Dacryocystitis; Diagnosis, Differential; Diagnostic Imaging; Female; Fluorodeoxyglucose F18; Humans; Immunoglobulin G; Magnetic Resonance Imaging; Male; Middle Aged; Mikulicz' Disease; Positron-Emission Tomography; Reproducibility of Results; Retrospective Studies; Sensitivity and Specificity; Sialadenitis; Sjogren's Syndrome; Tomography, X-Ray Computed; Ultrasonography
PubMed: 26298875
DOI: 10.1186/s13075-015-0751-x