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Circulation May 2024Empagliflozin reduces the risk of heart failure (HF) events in patients with type 2 diabetes at high cardiovascular risk, chronic kidney disease, or prevalent HF... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Empagliflozin reduces the risk of heart failure (HF) events in patients with type 2 diabetes at high cardiovascular risk, chronic kidney disease, or prevalent HF irrespective of ejection fraction. Whereas the EMPACT-MI trial (Effect of Empagliflozin on Hospitalization for Heart Failure and Mortality in Patients With Acute Myocardial Infarction) showed that empagliflozin does not reduce the risk of the composite of hospitalization for HF and all-cause death, the effect of empagliflozin on first and recurrent HF events after myocardial infarction is unknown.
METHODS
EMPACT-MI was a double-blind, randomized, placebo-controlled, event-driven trial that randomized 6522 patients hospitalized for acute myocardial infarction at risk for HF on the basis of newly developed left ventricular ejection fraction of <45% or signs or symptoms of congestion to receive empagliflozin 10 mg daily or placebo within 14 days of admission. In prespecified secondary analyses, treatment groups were analyzed for HF outcomes.
RESULTS
Over a median follow-up of 17.9 months, the risk for first HF hospitalization and total HF hospitalizations was significantly lower in the empagliflozin compared with the placebo group (118 [3.6%] versus 153 [4.7%] patients with events; hazard ratio, 0.77 [95% CI, 0.60, 0.98]; =0.031, for first HF hospitalization; 148 versus 207 events; rate ratio, 0.67 [95% CI, 0.51, 0.89]; =0.006, for total HF hospitalizations). Subgroup analysis showed consistency of empagliflozin benefit across clinically relevant patient subgroups for first and total HF hospitalizations. The need for new use of diuretics, renin-angiotensin modulators, or mineralocorticoid receptor antagonists after discharge was less in patients randomized to empagliflozin versus placebo (all <0.05).
CONCLUSIONS
Empagliflozin reduced the risk of HF in patients with left ventricular dysfunction or congestion after acute myocardial infarction.
REGISTRATION
URL: https://www.clinicaltrials.gov; Unique identifier: NCT04509674.
Topics: Humans; Glucosides; Benzhydryl Compounds; Heart Failure; Male; Female; Myocardial Infarction; Aged; Middle Aged; Double-Blind Method; Sodium-Glucose Transporter 2 Inhibitors; Hospitalization; Treatment Outcome; Stroke Volume
PubMed: 38581389
DOI: 10.1161/CIRCULATIONAHA.124.069217 -
Clinical and Experimental Rheumatology Dec 2023Recent studies have implicated cytotoxic CD4 and CD8 T cells in primary Sjögren's syndrome (pSS) and IgG4-related disease (IgG4-RD), but their association with immune...
OBJECTIVES
Recent studies have implicated cytotoxic CD4 and CD8 T cells in primary Sjögren's syndrome (pSS) and IgG4-related disease (IgG4-RD), but their association with immune aging and organ-specific clinical features remain unclear. CX3CR1 is expressed on cytotoxic CD4 and CD8 T cells. The aim of this study was to determine associations of peripheral CX3CR1+CD4 and CX3CR1+CD8 T cells with aging and clinical features.
METHODS
Whole blood samples were freshly obtained from consecutive patients with active, treatment-naïve pSS (n=57), IgG4-RD (n=54), and healthy individuals (n=40) and analysed by flow cytometry for CX3CR1+CD4 and CX3CR1+CD8 proportions. Associations of those T cells with aging and clinical features were determined.
RESULTS
CX3CR1+CD4 and CX3CR1+CD8 T cells selectively expressed perforin and granzyme B. Proportions of CX3CR1+CD4 and CX3CR1+CD8 T cells were significantly higher in pSS and IgG4-RD than in healthy individuals. Higher proportions of CX3CR1+CD8 T cells were associated with aging in pSS and IgG4-RD but not in healthy individuals. Sex differences were not associated with proportions of CX3CR1+CD8 T cells. Furthermore, patients with pSS with interstitial lung disease showed higher proportions of CX3CR1+CD8 T cells than those without interstitial lung disease. IgG4-RD patients with retroperitoneal fibrosis and/or aortitis exhibited higher proportions of CX3CR1+CD8 T cells compared with those with Mikulicz's disease. Moreover, proportions of CX3CR1+CD8 T cells were decreased following glucocorticoid treatment in paralleled with clinical improvements in IgG4-RD.
CONCLUSIONS
CX3CR1+CD8 T cells might be involved in immune aging and distinct clinical phenotypes of patients with pSS or IgG4-RD.
Topics: Humans; Male; Female; Sjogren's Syndrome; Immunoglobulin G4-Related Disease; CD8-Positive T-Lymphocytes; Aging; Lung Diseases, Interstitial; CX3C Chemokine Receptor 1
PubMed: 37812481
DOI: 10.55563/clinexprheumatol/kfsd65 -
Cells Sep 2023Prolactin-inducible protein (PIP), also referred to as gross cystic disease fluid protein 15 (GCDFP-15), has been a trending topic in recent years due to its potential... (Review)
Review
Prolactin-inducible protein (PIP), also referred to as gross cystic disease fluid protein 15 (GCDFP-15), has been a trending topic in recent years due to its potential role as a specific marker in breast cancer. PIP binds to aquaporin-5 (AQP5), CD4, actin, fibrinogen, β-tubulin, serum albumin, hydroxyapatite, zinc α2-glycoprotein, and the Fc fragment of IgGs, and the expression of PIP has been demonstrated to be modulated by various cytokines, including IL4/13, IL1, and IL6. PIP gene expression has been extensively studied due to its captivating nature. It is influenced by various factors, with androgens, progesterone, glucocorticosteroids, prolactin, and growth hormone enhancing its expression while estrogens suppress it. The regulatory mechanisms involve important proteins such as STAT5A, STAT5B, Runx2, and androgen receptor, which collaborate to enhance PIP gene transcription and protein production. The expression level of PIP in breast cancer is dependent on the tumor stage and subtype. Higher expression is observed in early-stage tumors of the luminal A subtype, while lower expression is associated with luminal B, basal-like, and triple-negative subtypes, which have a poorer prognosis. PIP expression is also correlated with apocrine differentiation, hormone receptor positivity, and longer metastasis-free survival. PIP plays a role in supporting the immune system's antitumor response during the early stages of breast cancer development. However, as cancer progresses, the protective role of PIP may become less effective or diminished. In this work, we summarized the clinical significance of the PIP molecule in breast cancer and its potential role as a new candidate for cell-based therapies.
PubMed: 37759471
DOI: 10.3390/cells12182252 -
BMC Geriatrics Jun 2024IgG4-related diseases are very uncommon, and its diagnosis and treatment are complicated as it encompasses multiple disciplines.
BACKGROUND
IgG4-related diseases are very uncommon, and its diagnosis and treatment are complicated as it encompasses multiple disciplines.
CASE PRESENTATION
A 77-year-old woman was admitted with a jaw mass and nausea and vomiting. Laboratory tests showed elevated serum IgG4, pituitary MRI suggested thickening of the pituitary stalk, and head and neck CT suggested orbital and mandibular masses. Patients with mandibular mass were diagnosed with Mikulicz's disease with IgG4-related hypophysitis. We found no other evidence of causing thickening of the pituitary stalk. She was given oral prednisolone 30 mg daily, and her nausea and vomiting improved significantly, and the mandibular and ocular masses decreased in size.
CONCLUSION
Mikulicz's disease combined with IgG4-related hypophysitis is a rare case of IgG4-RD in elderly women. IgG4-RD is one of the causes of head and neck exocrine gland mass and pituitary stalk thickening in the elderly.
Topics: Humans; Aged; Female; Mikulicz' Disease; Immunoglobulin G4-Related Disease; Autoimmune Hypophysitis; Immunoglobulin G; Prednisolone; Magnetic Resonance Imaging
PubMed: 38880897
DOI: 10.1186/s12877-024-05142-7 -
Arthritis Research & Therapy Sep 2023We investigated sensitivity of the 2020 Revised Comprehensive Diagnostic Criteria (RCD) and the 2019 ACR/EULAR classification criteria across the four identified...
Differential sensitivity of the 2020 revised comprehensive diagnostic criteria and the 2019 ACR/EULAR classification criteria across IgG4-related disease phenotypes: results from a Norwegian cohort.
BACKGROUND
We investigated sensitivity of the 2020 Revised Comprehensive Diagnostic Criteria (RCD) and the 2019 ACR/EULAR classification criteria across the four identified IgG4-related disease (IgG4-RD) phenotypes: "Pancreato-Hepato-Biliary", "Retroperitoneum and Aorta", "Head and Neck-limited" and "Mikulicz' and Systemic" in a well-characterized patient cohort.
METHODS
We included adult patients diagnosed with IgG4-RD after comprehensive clinical assessment at Oslo University Hospital in Norway. We assigned patients to IgG4-RD phenotypes based on pattern of organ involvement and assessed fulfillment of RCD and 2019 ACR/EULAR classification criteria. Differences between phenotype groups were analyzed using one-way ANOVA for continuous variables, and contingency tables for categorical variables.
RESULTS
The study cohort included 79 IgG4-RD patients assigned to the "Pancreato-Hepato-Biliary" (22.8%), Retroperitoneum and Aorta" (22.8%) "Head and Neck-limited" (29.1%), and "Mikulicz' and Systemic" (25.3%) phenotype groups, respectively. While 72/79 (91.1%) patients in total fulfilled the RCD, proportion differed across phenotype groups and was lowest in the "Retroperitoneum and Aorta" group (66.7%, p < 0.001). Among the 57 (72.2%) patients meeting the 2019 ACR/EULAR classification criteria, proportion was again lowest in the "Retroperitoneum and Aorta" group (27.8%, p < 0.001).
CONCLUSION
The results from this study indicate that IgG4-RD patients having the "Retroperitoneum and Aorta" phenotype less often fulfill diagnostic criteria and classification criteria than patients with other IgG4-RD phenotypes. Accordingly, this phenotype is at risk of being systematically selected against in observational studies and randomized clinical trials, with potential implications for patients, caregivers and future definitions of IgG4-RD.
Topics: Humans; Immunoglobulin G4-Related Disease; Norway; Phenotype
PubMed: 37670401
DOI: 10.1186/s13075-023-03155-y -
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 -
BMC Ophthalmology Jul 2023Sjögren's Syndrome (SS) is an inflammatory autoimmune disease, and Mikulicz's disease (MD) is a lymphoproliferative disorder. Both MD and SS are more common in...
BACKGROUND
Sjögren's Syndrome (SS) is an inflammatory autoimmune disease, and Mikulicz's disease (MD) is a lymphoproliferative disorder. Both MD and SS are more common in middle-aged female, and the dry eyes could be presented in both of them with different degree. The MD patients are characterized by symmetrical swelling of the lacrimal glands which also can occur in the early stage of SS. And the imaging findings between early stage of SS and MD are lack of specificity. Therefore, SS and MD have similarities in the clinical manifestations, imaging and pathological findings and are confused in diagnosis.
CASE PRESENTATION
A 51-year-old female patient presented with bilateral swelling of the upper eyelids for 2 years. She also reported having dry mouth and dry eyes which could be tolerated. The Schirmer's test result is positive and the laboratory tests indicate serum total IgG increased. In the bilateral lacrimal gland area could palpate soft masses. The orbital magnetic resonance imaging (MRI) examination showed bilateral lacrimal gland prolapse. While the histopathological result was considered as MD. The immunohistochemical (IHC) staining results were positive for IgG and negative for IgG4. To clarify the diagnosis, SS-related laboratory tests were performed: anti-SSA antibody (+++), anti-SSB antibody (+++), anti-Ro-52 antibody (+++). With a comprehensive consideration, the final diagnosis was SS.
CONCLUSION
When the clinical manifestations are atypical, it is necessary to pay attention to the differential diagnosis of SS and MD.
Topics: Middle Aged; Humans; Female; Mikulicz' Disease; Sjogren's Syndrome; Salivary Glands; Edema; Immunoglobulin G; Diagnostic Errors
PubMed: 37501055
DOI: 10.1186/s12886-023-03090-1 -
Quantitative Imaging in Medicine and... Dec 2023
PubMed: 38106322
DOI: 10.21037/qims-23-563 -
BMC Pulmonary Medicine Mar 2024IgG4-related disease is a systemic fibroinflammatory disease that is mainly seen in older men, and involves multiple organs, such as the pancreas and lungs. However, 75%...
BACKGROUND
IgG4-related disease is a systemic fibroinflammatory disease that is mainly seen in older men, and involves multiple organs, such as the pancreas and lungs. However, 75% of patients with IgG4-related lung disease are asymptomatic (if they are symptomatic, they mainly complain of nasal congestion, rhinorrhoea, chest pain, and cough) and are incidentally diagnosed through chest computed tomograph. Although, nodules in the airway and bronchial wall thickening are criteria for diagnosis, it is important that nodules have been reported in peripheral airways in several cases and rarely in the central airway.
CASE PRESENTATION
A 74-year-old woman previously diagnosed with Mikulicz's disease presented with swelling of the eyelid margin on both sides and visual disturbances. Computed tomography revealed extensive multiple nodules and mucosal oedema of the trachea and both bronchi. On flexible bronchoscopy under local anaesthesia, extensive lesions were observed from the middle of the trachea to the carina, extending into both segmental bronchi. The nodules were continuous with the normal respiratory tract mucosa, and the surfaces were smooth with minimal neovascularisation. Due to the solid nature of the lesion, obtaining an adequate amount of specimen was challenging. Therefore, we used a 1.9 mm cryoprobe under intubation, resulting in minimal bleeding. Subsequently, the patient was diagnosed with IgG4-related lung disease.
CONCLUSIONS
The present case is very rare because of the presence of multiple nodules, severe mucosal edema of the central airway and the absence of mediastinal lymphadenopathy, ground glass nodules, and lung masses. Therefore, it is important to consider differential diagnoses. Thus, we emphasise the importance of endobronchial cryobiopsy for obtaining an adequate number of tissue specimens in such cases to establish a definitive pathological diagnosis.
Topics: Male; Female; Humans; Aged; Trachea; Immunoglobulin G4-Related Disease; Bronchi; Edema; Lung Diseases; Immunoglobulin G
PubMed: 38443819
DOI: 10.1186/s12890-024-02926-w -
World Journal of Orthopedics May 2024Unicompartmental knee arthroplasty (UKA) and high tibial osteotomy (HTO) are well-established operative interventions in the treatment of knee osteoarthritis. However,...
BACKGROUND
Unicompartmental knee arthroplasty (UKA) and high tibial osteotomy (HTO) are well-established operative interventions in the treatment of knee osteoarthritis. However, which intervention is more beneficial to patients with knee osteoarthritis remains unknown and a topic of much debate. Simultaneously, there is a paucity of research assessing the relationship between radiographic parameters of knee joint alignment and patient-reported clinical outcomes, preoperatively and following HTO or UKA.
AIM
To compare UKAs and HTOs as interventions for medial-compartment knee osteoarthritis: Examining differences in clinical outcome and investigating the relationship of joint alignment with respect to this.
METHODS
This longitudinal observational study assessed a total of 42 patients that had undergone UKA ( = 23) and HTO ( = 19) to treat medial compartment knee osteoarthritis. Patient-reported outcome measures (PROMs) were collected to evaluate clinical outcome. These included two disease-specific (Knee Injury and Osteoarthritis Outcome Score, Oxford Knee Score) and two generic (EQ-5D-5L, Short Form-12) PROMs. The radiographic parameters of knee alignment assessed were the: Hip-knee-ankle angle, mechanical axis deviation and angle of Mikulicz line.
RESULTS
Statistical analyses demonstrated significant ( < 0.001), preoperative to postoperative, improvements in the PROM scores of both groups. There were, however, no significant inter-group differences in the postoperative PROM scores of the UKA and HTO group. Several significant correlations associated a more distolaterally angled Mikulicz line with worse knee function and overall health preoperatively ( < 0.05). Postoperatively, two clusters of significant correlations were observed between the disease-specific PROM scores and knee joint alignment parameters (hip-knee-ankle angle, mechanical axis deviation) within the HTO group; yet no such associations were observed within the UKA group.
CONCLUSION
UKAs and HTOs are both efficacious operations that provide a comparable degree of clinical benefit to patients with medial compartment knee osteoarthritis. Clinical outcome has a limited association with radiographic parameters of knee joint alignment postoperatively; however, a more distolaterally angled Mikulicz line appears associated with worse knee function/health-related quality of life preoperatively.
PubMed: 38835690
DOI: 10.5312/wjo.v15.i5.444