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1.
Eur J Prev Cardiol ; 2024 Sep 20.
Article in English | MEDLINE | ID: mdl-39298680

ABSTRACT

AIM: The 2023 ESC guidelines for acute coronary syndrome note that contemporary data are heterogenous regarding beta-blockers (BB) use post-myocardial infarction (MI) in patients without reduced ejection fraction (EF) or heart failure (HF). We aimed to address the heterogeneity in contemporary data around BB post-MI in this population. METHODS: We searched 6 databases from Jan 1, 2000 to Sep 1, 2024 to identify contemporary studies enrolling MI patients without reduced EF (≤40%) or history of HF receiving BB at index MI, and comparing outcomes between BB users and non-users. The primary outcome was all-cause mortality. Secondary outcomes included major adverse cardiac and cerebrovascular events (MACCE) and cardiovascular (CV) mortality. Random-effects meta-analysis was conducted using the restricted maximum likelihood method. RESULTS: There were 24 studies including 290,349 patients enrolled in the contemporary era. Overall, BB use was associated with a significant 11% reduction in all-cause mortality (HR, 0.89; 95% CI, 0.81 to 0.97; I2 = 40%; Figure 1), however with moderate-to-high statistical heterogeneity. Prespecified subgroup analyses demonstrate comparable all-cause mortality (HR, 0.99; 95% CI, 0.94 to 1.06; I2 = 0%), CV mortality (HR, 0.99; 95% CI, 0.85 to 1.15; I2 = 0%), and MACCE (HR, 1.24; 95% CI, 1.01 to 1.52; I2 = 0%) in patients with a 1-year event-free period, defined as no death, recurrent MI, or HF while on BB following index MI. In patients with no event-free period, meta-regression revealed that BB mortality benefits were modified by the study inclusion period (P = 0.01), reflecting a temporal trend of decreasing BB mortality benefits over time. Based on the temporal trend, in patients with preserved EF post-2010, BB exhibited no reduction in all-cause mortality (HR, 0.97; 95% CI, 0.90 to 1.04; I2 = 0%), but a non-significant trend towards increased CV mortality (HR, 1.29; 95% CI, 0.96 to 1.72; I2 = 0%) and a significant increase in MACCE (HR, 1.24; 95% CI, 1.01 to 1.52; I2 = 0%). CONCLUSION: In the contemporary reperfusion era, BB may not confer additional mortality benefits beyond a 1-year event-free period post-MI in patients without reduced EF. Moreover, post-MI BB use was associated with detrimental effects in patients with preserved EF.


Our study aimed to synthesize current evidence around post-myocardial infarction (MI) beta-blocker (BB) use in patients without reduced ejection fraction (EF) or heart failure (HF). We reveal that the mortality benefits of BB are modified by 3 factors, namely an event-free period, study inclusion period, and EF.In patients on BB post-MI with 1 year free of death, recurrent MI, or HF, there may not be additional mortality benefit to continuing the BB.For patients included after 2010, BB did not offer mortality benefits and may even be harmful in those with preserved EF.In contrast to those with preserved EF, patients with mildly reduced EF derive mortality benefits from BB.

2.
Front Genet ; 15: 1292249, 2024.
Article in English | MEDLINE | ID: mdl-39268080

ABSTRACT

Background: Ubiquitination, a major post-translational modification, significantly impacts tumorigenesis, progression, and prognosis. This study aims to classify colon cancer at the molecular level and create a reliable signature using ubiquitination-related genes (URGs) to assess the immune microenvironment and prognosis. Methods: We employed non-negative matrix factorization to subtype colon cancer based on ubiquitination-related gene (URG) expression patterns. Quantitative scores for 28 immune cell infiltrates and the tumor microenvironment were computed using single-sample gene set enrichment analysis (ssGSEA) and the Estimate algorithm. Subtype feature genes were selected through Lasso logistic regression and SVM-RFE algorithm. The ubiquitination-related signature was constructed using univariate Cox, Lasso, and stepwise regression methods to categorize patients into high and low-risk groups. Validation included log-rank tests, receiver operating characteristic (ROC) analysis, decision curve analysis (DCA), and external dataset validation. Immune therapy response was compared using Tumor Immune Dysfunction and Exclusion (TIDE), Immunophenoscore (IPS), and submap analyses. Clinical variables and risk scores were integrated into an enhanced nomogram. The early diagnostic value of four URGs was confirmed via quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry. The cell proliferation was assessed through colony formation, EdU staining, and xenograft tumorigenesis assays. Results: Prognostic ubiquitination-related genes (URGs) stratified patients into subtypes, revealing differences in survival, immune cell infiltration, and pathological staging. A signature of 6 URGs (ARHGAP4, MID2, SIAH2, TRIM45, UBE2D2, WDR72) was identified from 57 subtype-related genes. The high-risk group exhibited characteristics indicative of enhanced epithelial-mesenchymal transition, immune escape, immunosuppressive myeloid-derived suppressor cells, regulatory T cell infiltration, and lower immunogenicity. In contrast, the low-risk group demonstrated the opposite trend but showed a better response to CTLA4 checkpoint inhibitors. The predictive performance of the nomogram significantly improved with the integration of risk score, stage, and age. ARHGAP4 and SIAH2 exhibit promising early diagnostic capabilities. Additionally, WDR72 knockdown significantly inhibited CRC cell proliferation both in vitro and in vivo. Conclusion: Our developed ubiquitination-related signature and genes serve as promising biomarkers for colon cancer prognosis, immune microenvironment, and diagnosis.

5.
Br J Haematol ; 205(2): 473-477, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38981737

ABSTRACT

There are limited data on the optimal choice of anticoagulation in multiple myeloma (MM) patients receiving immunomodulatory drugs (IMiDs). We conducted a propensity score-matched cohort study using the TriNetX database to compare the efficacy and safety of factor Xa inhibitors and warfarin in this patient population. Compared to warfarin, factor Xa inhibitors had a similar risk of deep vein thrombosis (hazard ratio [HR]: 1.11 [95% CI: 0.50-2.46]) or pulmonary embolism (HR: 1.08 [95% CI: 0.59-2.00]). There were no differences in the risk of gastrointestinal or intracranial bleeding. Factor Xa inhibitor-treated patients had lower all-cause mortality (HR: 0.56 [95% CI: 0.36-0.86]) compared with warfarin. These data suggest that factor Xa inhibitors had similar safety and efficacy compared with warfarin for MM patients on IMiDs.


Subject(s)
Anticoagulants , Factor Xa Inhibitors , Multiple Myeloma , Warfarin , Humans , Warfarin/therapeutic use , Warfarin/adverse effects , Multiple Myeloma/drug therapy , Multiple Myeloma/complications , Multiple Myeloma/mortality , Factor Xa Inhibitors/therapeutic use , Factor Xa Inhibitors/adverse effects , Female , Male , Aged , Middle Aged , Anticoagulants/therapeutic use , Anticoagulants/adverse effects , Venous Thrombosis/prevention & control , Venous Thrombosis/etiology , Immunomodulating Agents/therapeutic use , Immunomodulating Agents/adverse effects , Aged, 80 and over , Pulmonary Embolism/prevention & control , Pulmonary Embolism/etiology
6.
World J Gastroenterol ; 30(5): 512-515, 2024 Feb 07.
Article in English | MEDLINE | ID: mdl-38414589

ABSTRACT

We are writing in response to the paper published in the World Journal of Gastroenterology by Zhou et al. The authors identified higher serum immunoglobulin (Ig) G4 levels and age over 55 years as independent risk factors for disease relapse. Despite notable strengths, it is crucial to address potential biases. Firstly, the cohort study included 189 patients with autoimmune pancreatitis (AIP) type 1 (with higher IgG4 seropositivity and higher relapse) and 24 with type 2 (with lower IgG4 seropositivity and lower relapse). Consequently, most, if not all, AIP type 2 patients were assigned to the normal group, possibly inflating the association of higher serum IgG4 levels with relapse and potentially exaggerating the association of older age with relapse. Secondly, the authors did not provide sufficient details regarding AIP diagnosis, such as the ratio of definitive vs probable cases and the proportion of biopsies. In cases where histological evidence is unavailable or indeterminate, AIP type 2 may be misdiagnosed as definitive type 1, and type 1 may also be misdiagnosed as probable type 2, particularly in cases with normal or mildly elevated serum IgG4 levels. Lastly, in this retrospective study, approximately one-third of the consecutive patients initially collected were excluded for various reasons. Accordingly, the impact of non-random exclusion on relapse outcomes should be carefully considered. In conclusion, the paper by Zhou et al offers plausible, though not entirely compelling, evidence suggesting a predictive role of elevated serum IgG4 levels and advanced age in AIP relapse. The foundation for future investigations lies in ensuring a reliable diagnosis and accurate disease subtyping, heavily dependent on obtaining histological specimens. In this regard, endoscopic ultrasound-guided fine-needle biopsy emerges as a pivotal component of the diagnostic process, contributing to mitigating biases in future explorations of the disease.


Subject(s)
Autoimmune Diseases , Autoimmune Pancreatitis , Pancreatitis , Humans , Middle Aged , Autoimmune Pancreatitis/diagnosis , Retrospective Studies , Cohort Studies , Chronic Disease , Immunoglobulin G , Recurrence
7.
Cancers (Basel) ; 15(21)2023 Oct 25.
Article in English | MEDLINE | ID: mdl-37958308

ABSTRACT

There have been many clinical questions regarding whether the use of proton pump inhibitors (PPIs) could deteriorate the effects of cyclin-dependent kinase inhibitors (CDKIs) in HR+/HER2- advanced breast cancer patients. We performed a systematic review and meta-analysis of this clinical question, including studies enrolling HR+/HER2- metastatic breast cancer patients treated with CDKIs (Palbociclib or Ribociclib) and reporting at least one comparative survival outcome, either overall survival (OS) or progression-free survival (PFS), between concomitant PPI users and non-users. Eight studies met the eligibility criteria, with a total of 2584 patients included (PPI users: 830, PPI non-users: 1754), demonstrating that concomitant PPI use was associated with significantly higher risks of all-cause mortality (HR = 2.03; 95% CI, 1.49 to 2.77; I2 = 0%) and disease progression (HR = 1.75; 95% CI, 1.26 to 2.43; I2 = 59%) in breast cancer patients taking Palbociclib. In contrast, there were no significant survival impacts of PPIs on Ribociclib (HR = 1.46; 95% CI, 0.91 to 2.34; I2 = 36%). Additionally, there was no significant difference in the risk associated with CDKI dose reduction due to drug toxicity (RR = 1.12; 95% CI, 0.97 to 1.29). Therefore, when HR+/HER2- advanced breast cancer patients require the use of PPIs, it may be reasonable to consider using Ribociclib.

8.
J Autoimmun ; 140: 103121, 2023 Oct 10.
Article in English | MEDLINE | ID: mdl-37826920

ABSTRACT

Autoimmune pancreatitis (AIP) is an uncommon fibro-inflammatory disorder precipitated by autoimmune/inflammatory reactions. Currently, there are two clinical subtypes of AIP (type 1 [AIP-1] and type 2 [AIP-2]) that correspond to two histologic descriptors (lymphoplasmacytic sclerosing pancreatitis and idiopathic duct-centric pancreatitis, respectively). While our understanding of AIP-1 has evolved considerably over the years, little is known about AIP-2 due to its rarity, often leading to misdiagnosis, delayed treatment, and even unnecessary surgical resection. Compared to AIP-1, AIP-2 exhibits distinct clinical and histologic features. Because AIP-2 is a pancreas-restricted disease without a specific serum marker, the evaluation of histologic features (e.g., granulocytic epithelial lesions) is essential for an accurate diagnosis. Patients with AIP-2 respond well to glucocorticoids, with anti-tumor necrosis factor-alpha antibodies as a promising alternative therapy. The prognosis of AIP-2 is generally favorable and relapse is uncommon. Here, we provide an overview of our current knowledge on the clinical features, diagnosis, therapeutic regimens, prognosis, and putative mechanisms underlying AIP-2. Notably, the diagnostic differentiation between AIP-2, especially the mass-forming/focal type, and pancreatic cancer is important, but challenging. In this regard, endoscopic ultrasound-guided core biopsy has a key role, but novel diagnostic markers and modalities are clearly needed.

9.
Pain Physician ; 26(5): 437-447, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37774178

ABSTRACT

BACKGROUND: Intraarticular steroid injections are a commonly used and proven treatment for frozen shoulder; however, there is no scientific basis for a certified dose. OBJECTIVES: This study aimed to identify the difference between high- and low-dose steroid injections treatments and suggest an appropriate dose. STUDY DESIGN: Systematic review and meta-analysis. METHODS: The MEDLINE, EMBASE, and Cochrane electronic databases were searched through February 15, 2023 for eligible randomized controlled trials. The effects of high- and low-dose steroid injections were calculated as standardized mean differences (SMD) in pain, shoulder range of motion (ROM), and functional improvement. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to evaluate evidence quality. RESULTS: Four studies with 274 patients were included in the final analysis. The meta-analysis showed that improvement in pain (SMD, 0.10; 95% CI, -0.12 to 0.32), ROM (SMD, 0.07; 95% CI, -0.05 to 0.19), and functional improvement (SMD, 0.08; 95% CI, -0.10 to 0.26) did not differ significantly between the high- and low-dose steroid injections. Subgroup follow-up analyses also showed no clinically significant differences in SMD for pain, ROM, and functional scale measurement in any subgroups (after 3 weeks, 6 weeks, and one year). One article described that, although there was no significant difference in adverse events frequency between the high- and low-dose groups, flushing tended to occur more frequently in the high-dose group. LIMITATIONS: Limitations are the small number of studies included in the meta-analysis, no disease stage considered, and a short follow-up period. CONCLUSIONS: This meta-analysis suggests there are no significant differences between the high- and low-dose steroid groups in pain, ROM, or functional improvement. Therefore, considering the side effects of high-dose steroids, starting with low-dose steroids is recommended. However, further studies are needed to establish exact protocols according to disease severity. KEY WORDS: Frozen shoulder, adhesive capsulitis, steroids, triamcinolone acetonide, injections, intraarticular, optimal dose, meta-analysis, randomized controlled trial.

10.
Lab Anim ; : 236772231181658, 2023 Sep 20.
Article in English | MEDLINE | ID: mdl-37728936

ABSTRACT

The reproducibility crisis across animal studies jeopardizes the credibility of the main findings derived from animal research, even though these findings are critical for informing human studies. To clarify and improve transparency among animal studies, the ARRIVE reporting guidelines were first announced in 2010 and upgraded to version 2.0 in 2020. However, compliance with and awareness of those reporting guidelines has remained suboptimal. Journal editors should encourage the authors to adhere to those guidelines. Authors, editors, referees, and reviewers should be aware of the ARRIVE guideline 2.0 when assessing and evaluating the methodology and findings of animal studies. However, we should also question whether reporting guidelines alone can change a research culture and improve the reproducibility of animal investigations. Reported research may not reflect actual research. Large segments of animal research efforts are wasted because of poor design choices and because of non-publication rather than suboptimal reporting. Better training of the scientific workforce, interventions at improving animal research at the design stage, registration practices, and alignment of the reward system with the publication of rigorous animal research may achieve more than reporting guidelines alone.

12.
Am J Gastroenterol ; 118(3): 553-560, 2023 03 01.
Article in English | MEDLINE | ID: mdl-36734654

ABSTRACT

INTRODUCTION: The management of childhood constipation is challenging. Pelvic floor dysfunction (PFD) is one of the most common causes of childhood constipation. Percutaneous tibial nerve stimulation (PTNS) with pelvic floor exercises (PFE) has achieved a satisfactory outcome in the elderly individuals and women with PFD. The efficacy of PTNS with PFE in childhood constipation has not been established. METHODS: A randomized, double-blind, controlled trial with 84 children who met the inclusion criteria was conducted. All participants were randomly assigned to PTNS with PFE or sham PTNS with PFE groups and received their individual intervention for 4 weeks with a 12-week follow-up evaluation. The spontaneous bowel movements (SBM) ≥3 per week were the main outcomes, and the risk ratio (RR) with 95% confidence interval (CI) were calculated. High-resolution anorectal manometry and surface electromyography were used for the assessment of pelvic floor function, and the adverse effects were assessed based on symptoms. RESULTS: At the end of the follow-up period, 26 patients (61.9%) in the PTNS with PFE group and 15 patients (35.7%) in the sham group had ≥3 SBM per week compared with baseline (net difference 26.2%, 95% CI 5.6%-46.8%; RR 2.750, 95% CI 1.384-5.466; P < 0.05). PFD remission occurred in 49 children, 33 (78.6%) in the PTNS with PFE group and 16 (38.1%) in the sham group (RR 2.063, 95% CI 1.360-3.128, P < 0.05). No adverse effects occurred. DISCUSSION: PTNS with PFE is a safe and effective method in the treatment of childhood constipation, particularly in children with PFD or dyssynergic defecation.


Subject(s)
Drug-Related Side Effects and Adverse Reactions , Transcutaneous Electric Nerve Stimulation , Child , Humans , Female , Aged , Pelvic Floor , Constipation/therapy , Tibial Nerve/physiology , Exercise Therapy , Treatment Outcome
13.
Aging Clin Exp Res ; 35(3): 479-495, 2023 Mar.
Article in English | MEDLINE | ID: mdl-36637774

ABSTRACT

BACKGROUND AND AIM: We aimed to capture the breadth of health outcomes that have been associated with the presence of Urinary Incontinence (UI) and systematically assess the quality, strength, and credibility of these associations through an umbrella review and integrated meta-analyses. METHODS: We assessed meta-analyses of observational studies based on random-effect summary effect sizes and their p-values, 95% prediction intervals, heterogeneity, small-study effects, and excess significance. We graded the evidence from convincing (Class I) to weak (Class IV). RESULTS AND DISCUSSION: From 3172 articles returned in search of the literature, 9 systematic reviews were included with a total of 41 outcomes. Overall, 37 out of the 41 outcomes reported nominally significant summary results (p < 0.05), with 22 associations surviving the application of a more stringent p-value (p < 10-6). UI was associated with worse scores than controls in female sexual function (Class II), while it was also associated with a higher prevalence of depression (odds ratio [OR] = 1.815; 95% confidence interval [CI]: 1.551-2.124), and anxiety (OR = 1.498; 95% CI: 1.273-1.762) (Class IV). UI was associated with poorer quality of life (QoL), higher rate of mortality (hazard ratio = 2.392; 95% CI: 2.053-2.787) an increase in falls, frailty, pressure ulcers, diabetes, arthritis, and fecal incontinence (Class IV). CONCLUSIONS: UI is associated with female sexual dysfunction, with highly suggestive evidence. However, the evidence of other adverse outcomes including depression, anxiety, poorer QoL, higher mortality, falls, pressure ulcers, diabetes, arthritis, fecal incontinence, and frailty is only weak. A multidimensional approach should be taken in managing UI in the clinical setting.


Subject(s)
Arthritis , Diabetes Mellitus , Fecal Incontinence , Frailty , Pressure Ulcer , Urinary Incontinence , Humans , Female , Quality of Life , Urinary Incontinence/epidemiology
14.
J Med Virol ; 95(2): e28522, 2023 02.
Article in English | MEDLINE | ID: mdl-36691933

ABSTRACT

As coronavirus variants are constantly occurring, we tried to understand more about the omicron and delta variants that have hit the world. We provided dynamic information on the case fatality rate (CFR) of the Omicron variant over time and to compare it with that of the Delta variant through meta-analysis. Twenty-four countries were selected by submission counts, submission dates, and confirmed cases. We defined the Delta or the Omicron epidemic period for individual countries as when each variant is over 90%. We further analyzed the Omicron period by dividing it into the initial plateau, increasing, and decreasing phases according to the number of newly confirmed daily cases. Finally, the meta-analysis examined the summary and between-study heterogeneity. The CFR of COVID-19 during the Omicron epidemic was lower than that during the Delta epidemic (odds ratio [OR]: 0.252, 95% confidence interval [CI] 0.205-0.309). The CFR of COVID-19 during the initial plateau phase of Omicron was higher than during other phases. (OR: 1.962, 95% CI 1.607-2.397). The CFR of COVID-19 during the increasing phase was lower than during the decreasing phases (OR: 0.412, 95% CI 0.342-0.498). The Omicron variant had lower CFR compared to the Delta variant, and the initial plateau phase had higher CFR compared to the noninitial phases. These results can help establish global health policies for COVID-19 in the future.


Subject(s)
COVID-19 , Epidemics , Humans , SARS-CoV-2 , Health Policy
15.
Rev Med Virol ; 33(3): e2408, 2023 05.
Article in English | MEDLINE | ID: mdl-36420676

ABSTRACT

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Delta variant (B.1.617.2) was the predominant variant behind the surges of COVID-19 in the United States, Europe, and India in the second half of 2021. The information available regarding the defining mutations and their effects on the structure, transmission, and vaccine efficacy of SARS-CoV-2 is constantly evolving. With waning vaccine immunity and relaxation of social distancing policies across the globe driving the increased spread of the Delta variant, there is a great need for a resource aggregating the most recent information for clinicians and researchers concerning the Delta variant. Accordingly, this narrative review comprehensively reviews the genetics, structure, epidemiology, clinical course, and vaccine efficacy of the Delta variant. Comparison with the omicron variant is also discussed. The Delta variant is defined by 15 mutations in the Spike protein, most of which increase affinity for the ACE-2 receptor or enhance immune escape. The Delta variant causes similar symptoms to prototypical COVID-19, but it is more likely to be severe, with a greater inflammatory phenotype and viral load. The reproduction number is estimated to be approximately twice the prototypical strains present during the early pandemic, and numerous breakthrough infections have been reported. Despite studies demonstrating breakthrough infection and reduced antibody neutralisation, full vaccination effectively reduces the likelihood of severe illness and hospitalisation.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , SARS-CoV-2/genetics , COVID-19/epidemiology , COVID-19/prevention & control , Vaccine Efficacy , Breakthrough Infections , Immunity
16.
Autoimmun Rev ; 22(2): 103239, 2023 Feb.
Article in English | MEDLINE | ID: mdl-36464226

ABSTRACT

Posterior reversible encephalopathy syndrome (PRES) is a clinical syndrome characterized by acute or subacute onset of neurological symptoms (e.g., headache, seizure, confusion, vomiting, and diminished eyesight) and impaired endothelial barrier function of the cerebral circulation that leads to bilateral subcortical vasogenic edema, while exhibiting a "reversible" feature in most cases. Clinically, various predisposing or precipitating conditions have been identified, such as hypertension, autoimmune diseases, renal dysfunction/failure, preeclampsia/eclampsia, post-transplantation conditions, and certain therapeutic agents. Among several putative mechanisms, the immune activation hypothesis prevails, as up to 50% of patients with PRES harbor abnormalities related to autoimmunity, such as concurrent systemic lupus erythematosus. In this Review, we summarize the clinical and laboratory evidence that places PRES in the context of autoimmunity.


Subject(s)
Hypertension , Lupus Erythematosus, Systemic , Posterior Leukoencephalopathy Syndrome , Pre-Eclampsia , Female , Pregnancy , Humans , Posterior Leukoencephalopathy Syndrome/complications , Posterior Leukoencephalopathy Syndrome/therapy , Autoimmunity , Magnetic Resonance Imaging
17.
Int J Soc Psychiatry ; 69(3): 523-531, 2023 05.
Article in English | MEDLINE | ID: mdl-36511141

ABSTRACT

BACKGROUND: Suicide is one of the most important causes of deaths in the United Kingdom, and the numbers are currently increasing. AIM: There are numerous identified determinants of suicidality, and physical multimorbidity is potentially important but is currently understudied. Thus, this study aims to investigate the association of physical multimorbidity with suicidality. METHODS: Cross-sectional data from the Adult Psychiatric Morbidity Survey 2007, which was conducted in England between October 2006 and December 2007 by the National Center for Social Research and Leicester University were analyzed. Respondents were asked about 20 physical health conditions, and suicidal ideation and suicide attempts were assessed. RESULTS: Out of 7,403 individuals aged 16 years or over, the prevalence of physical multimorbidity, suicidal ideation, and suicide attempts were 35.1%, 4.3%, and 0.7%, respectively. After adjustment for potential confounders, compared to no physical conditions, 1, 2, 3, and ⩾4 conditions were associated with significant 1.79 (95% CI [1.25, 2.57]), 2.39 (95% CI [1.63, 3.51]), 2.88 (95% CI [1.83, 4.55]), and 6.29 (95% CI [4.12, 9.61]) times higher odds for suicidal ideation. Mediation analysis showed that cognitive problems (mediated percentage 39.2%) and disability (37.5%) explained the largest proportion between multimorbidity and suicidal ideation. Pain (38.0%) and cognitive problems (30.7%) explained the largest proportion between multimorbidity and suicide attempts. CONCLUSION: In this large sample of UK adults, physical multimorbidity was associated with significantly higher odds for suicidal ideation and suicide attempts. Moreover, several potential mediators were identified, and these may serve as future targets for interventions that aim to prevent suicidality among people with physical multimorbidity.


Subject(s)
Suicidal Ideation , Suicide, Attempted , Adult , Humans , Multimorbidity , Mediation Analysis , Cross-Sectional Studies , Risk Factors , England/epidemiology
19.
Clin Rev Allergy Immunol ; 63(3): 431-446, 2022 Dec.
Article in English | MEDLINE | ID: mdl-36251242

ABSTRACT

Mast cells originate from the CD34+/CD117+ hematopoietic progenitors in the bone marrow, migrate into circulation, and ultimately mature and reside in peripheral tissues. Microbiota/metabolites and certain immune cells (e.g., Treg cells) play a key role in maintaining immune tolerance. Cross-linking of allergen-specific IgE on mast cells activates the high-affinity membrane-bound receptor FcεRI, thereby initiating an intracellular signal cascade, leading to degranulation and release of pro-inflammatory mediators. The intracellular signal transduction is intricately regulated by various kinases, transcription factors, and cytokines. Importantly, multiple signal components in the FcεRI-mast cell-mediated allergic cascade can be targeted for therapeutic purposes. Pharmacological interventions that include therapeutic antibodies against IgE, FcεRI, and cytokines as well as inhibitors/activators of several key intracellular signaling molecues have been used to inhibit allergic reactions. Other factors that are not part of the signal pathway but can enhance an individual's susceptibility to allergen stimulation are referred to as cofactors. Herein, we provide a mechanistic overview of the FcεRI-mast cell-mediated allergic signaling. This will broaden our scope and visions on specific preventive and therapeutic strategies for the clinical management of mast cell-associated hypersensitivity reactions.


Subject(s)
Hypersensitivity , Mast Cells , Humans , Receptors, IgE/metabolism , Immunoglobulin E , Allergens , Cytokines/metabolism
20.
J Sex Med ; 19(11): 1616-1624, 2022 11.
Article in English | MEDLINE | ID: mdl-36115787

ABSTRACT

BACKGROUND: Lichen sclerosus (LS) is a common autoimmune dermatological condition that is often under-diagnosed in women and has been documented to affect quality of life and sexual function. AIM: To determine the prevalence of sexual dysfunction among women with vulvar lichen sclerosus. METHODS: The authors conducted a systematic review and meta-analysis of the existing research on LS and sexual function in database including PubMed using search terms: lichen sclerosus OR vulvar lichen sclerosus OR vulvar lichen sclerosus et atrophicus OR kraurosis vulvae) AND (sexual function OR sexual functions OR sexual disorder OR sexual disorders OR sexual activity OR sexual activities OR sexual dysfunction OR sexual dysfunctions OR dyspareunia OR vaginismus). OUTCOMES: Nearly 60% of women with lichen sclerosus suffer from sexual dysfunction. RESULTS: Two hundred and ten studies were initially identified. Twenty-six articles met inclusion criteria and 3 were excluded as they did not relate to sexual function, were regarding a surgical or medical intervention and sexual dysfunction and one was a review article. Therefore, 23 studies were included in the final analysis resulting in a cumulative 486 participants with LS with 208 patients experiencing any kind of sexual dysfunction. Meta-analysis presented prevalence of sexual dysfunction among LS patients as 59% (95% CI: 48 - 70%). Dyspareunia or generalized pain with intercourse was the most commonly reported type of dysfunction. CLINICAL IMPLICATIONS: Discussing sexual concerns with women with LS could empower them to seek treatment. STRENGTHS AND LIMITATIONS: Few articles met criteria for inclusion. CONCLUSION: A large proportion of women with LS experience sexual dysfunction. More research is needed, especially that which includes biopsy-proven LS and validated tools on sexual function. Pope R, Lee MH, Myers A, et al. Lichen Sclerosus and Sexual Dysfunction: A Systematic Review and Meta-Analysis. J Sex Med 2022;19:1616-1624.


Subject(s)
Dyspareunia , Lichen Sclerosus et Atrophicus , Sexual Dysfunction, Physiological , Vulvar Lichen Sclerosus , Humans , Female , Lichen Sclerosus et Atrophicus/complications , Lichen Sclerosus et Atrophicus/therapy , Vulvar Lichen Sclerosus/complications , Vulvar Lichen Sclerosus/surgery , Dyspareunia/epidemiology , Dyspareunia/etiology , Quality of Life , Sexual Dysfunction, Physiological/epidemiology , Sexual Dysfunction, Physiological/etiology
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