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Clinical Immunology (Orlando, Fla.) Nov 2023Antiphospholipid syndrome (APS) is a systemic autoimmune disease clinically associated with thrombotic and obstetric events. Additional manifestations have been...
Clinical features, risk factors, and outcomes of diffuse alveolar hemorrhage in antiphospholipid syndrome: A mixed-method approach combining a multicenter cohort with a systematic literature review.
BACKGROUND
Antiphospholipid syndrome (APS) is a systemic autoimmune disease clinically associated with thrombotic and obstetric events. Additional manifestations have been associated with APS, like diffuse alveolar hemorrhage (DAH). We aimed to summarize all the evidence available to describe the presenting clinical features, their prognostic factors, and short- and long-term outcomes.
METHODS
We performed a mixed-method approach combining a multicenter cohort with a systematic literature review (SLR) of patients with incident APS-associated DAH. We described their clinical features, treatments, prognostic factors, and outcomes (relapse, mortality, and requirement of mechanical ventilation [MV]). Kaplan-Meier methods were used to estimate relapse and mortality rates, and Cox and logistic regression models were used to assess the factors associated as appropriate.
RESULTS
We included 219 patients with incident APS-associated DAH (61 from Mayo Clinic and 158 from SLR). The median age was 39.5 years, 51% were female, 29% had systemic lupus erythematosus, and 34% presented with catastrophic APS (CAPS). 74% of patients had a history of thrombotic events, and 26% of women had a history of pregnancy morbidity; half of the patients had a history of thrombocytopenia, and a third had valvulopathy. Before DAH, 55% of the patients were anticoagulated. At DAH onset, 65% of patients presented hemoptysis. The relapse rate was 47% at six months and 52% at one year. Triple positivity (HR 4.22, 95% CI 1.14-15.59) was associated with relapse at six months. The estimated mortality at one and five years was 30.3% and 45.8%. Factors associated with mortality were severe thrombocytopenia (< 50 K/μL) (HR 3.10, 95% CI 1.39-6.92), valve vegetations (HR 3.22, 95% CI 1.14-9.07), CAPS (HR 3.80, 95% CI 1.84-7.87), and requirement of MV (HR 2.22, 95% CI 1.03-4.80). Forty-two percent of patients required MV on the incident DAH episode. Patients presenting with severe thrombocytopenia (OR 6.42, 95% CI 1.77-23.30) or CAPS (OR 4.30, 95% CI 1.65-11.16) were more likely to require MV.
CONCLUSION
APS-associated DAH is associated with high morbidity and mortality, particularly when presenting with triple positivity, thrombocytopenia, valvular involvement, and CAPS.
Topics: Humans; Female; Adult; Male; Antiphospholipid Syndrome; Hemorrhage; Lung Diseases; Lupus Erythematosus, Systemic; Leukopenia; Risk Factors; Recurrence; Thrombocytopenia; Retrospective Studies; Multicenter Studies as Topic
PubMed: 37722463
DOI: 10.1016/j.clim.2023.109775 -
Journal For Immunotherapy of Cancer Jan 2024Immune checkpoint inhibitor (ICI) treatment has become an important therapeutic option for various cancer types. Although the treatment is effective, ICI can...
Immune checkpoint inhibitor (ICI) treatment has become an important therapeutic option for various cancer types. Although the treatment is effective, ICI can overstimulate the patient's immune system, leading to potentially severe immune-related adverse events (irAEs), including hepatitis, colitis, pneumonitis and myocarditis. The initial mainstay of treatments includes the administration of corticosteroids. There is little evidence how to treat steroid-resistant (sr) irAEs. It is mainly based on small case series or single case reports. This systematic review summarizes available evidence about sr-irAEs. We conducted a systematic literature search in PubMed. Additionally, we included European Society for Medical Oncology, Society for Immunotherapy of Cancer, National Comprehensive Cancer Network and American Society of Clinical Oncology Guidelines for irAEs in our assessment. The study population of all selected publications had to include patients with cancer who developed hepatitis, colitis, pneumonitis or myocarditis during or after an immunotherapy treatment and for whom corticosteroid therapy was not sufficient. Our literature search was not restricted to any specific cancer diagnosis. Case reports were also included. There is limited data regarding life-threatening sr-irAEs of colon/liver/lung/heart and the majority of publications are single case reports. Most publications investigated sr colitis (n=26), followed by hepatitis (n=21), pneumonitis (n=17) and myocarditis (n=15). There is most data for mycophenolate mofetil (MMF) to treat sr hepatitis and for infliximab, followed by vedolizumab, to treat sr colitis. Regarding sr pneumonitis there is most data for MMF and intravenous immunoglobulins (IVIG) while data regarding infliximab are conflicting. In sr myocarditis, most evidence is available for the use of abatacept or anti-thymocyte globulin (ATG) (both with or without MMF) or ruxolitinib with abatacept. This review highlights the need for prompt recognition and treatment of sr hepatitis, colitis, pneumonitis and myocarditis. Guideline recommendations for sr situations are not defined precisely. Based on our search, we recommend-as first line treatment-(1) MMF for sr hepatitis, (2) infliximab for sr colitis, followed by vedolizumab, (3) MMF and IVIG for sr pneumonitis and (4) abatacept or ATG (both with or without MMF) or ruxolitinib with abatacept for sr myocarditis. These additional immunosuppressive agents should be initiated promptly if there is no sufficient response to corticosteroids within 3 days.
Topics: Humans; Abatacept; Adrenal Cortex Hormones; Colitis; Hepatitis; Immunoglobulins, Intravenous; Infliximab; Mycophenolic Acid; Myocarditis; Neoplasms; Nitriles; Pneumonia; Pyrazoles; Pyrimidines
PubMed: 38233099
DOI: 10.1136/jitc-2023-007409 -
American Journal of Obstetrics and... Apr 2024This study aimed to provide procedure-specific estimates of the risk of symptomatic venous thromboembolism and major bleeding in the absence of thromboprophylaxis,... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
This study aimed to provide procedure-specific estimates of the risk of symptomatic venous thromboembolism and major bleeding in the absence of thromboprophylaxis, following gynecologic cancer surgery.
DATA SOURCES
We conducted comprehensive searches on Embase, MEDLINE, Web of Science, and Google Scholar for observational studies. We also reviewed reference lists of eligible studies and review articles. We performed separate searches for randomized trials addressing effects of thromboprophylaxis and conducted a web-based survey on thromboprophylaxis practice.
STUDY ELIGIBILITY CRITERIA
Observational studies enrolling ≥50 adult patients undergoing gynecologic cancer surgery procedures reporting absolute incidence for at least 1 of the following were included: symptomatic pulmonary embolism, symptomatic deep vein thrombosis, symptomatic venous thromboembolism, bleeding requiring reintervention (including reexploration and angioembolization), bleeding leading to transfusion, or postoperative hemoglobin <70 g/L.
METHODS
Two reviewers independently assessed eligibility, performed data extraction, and evaluated risk of bias of eligible articles. We adjusted the reported estimates for thromboprophylaxis and length of follow-up and used the median value from studies to determine cumulative incidence at 4 weeks postsurgery stratified by patient venous thromboembolism risk factors. The GRADE approach was applied to rate evidence certainty.
RESULTS
We included 188 studies (398,167 patients) reporting on 37 gynecologic cancer surgery procedures. The evidence certainty was generally low to very low. Median symptomatic venous thromboembolism risk (in the absence of prophylaxis) was <1% in 13 of 37 (35%) procedures, 1% to 2% in 11 of 37 (30%), and >2.0% in 13 of 37 (35%). The risks of venous thromboembolism varied from 0.1% in low venous thromboembolism risk patients undergoing cervical conization to 33.5% in high venous thromboembolism risk patients undergoing pelvic exenteration. Estimates of bleeding requiring reintervention varied from <0.1% to 1.3%. Median risks of bleeding requiring reintervention were <1% in 22 of 29 (76%) and 1% to 2% in 7 of 29 (24%) procedures.
CONCLUSION
Venous thromboembolism reduction with thromboprophylaxis likely outweighs the increase in bleeding requiring reintervention in many gynecologic cancer procedures (eg, open surgery for ovarian cancer and pelvic exenteration). In some procedures (eg, laparoscopic total hysterectomy without lymphadenectomy), thromboembolism and bleeding risks are similar, and decisions depend on individual risk prediction and values and preferences regarding venous thromboembolism and bleeding.
Topics: Adult; Humans; Female; Anticoagulants; Venous Thromboembolism; Postoperative Complications; Hemorrhage; Thrombosis; Neoplasms
PubMed: 37827272
DOI: 10.1016/j.ajog.2023.10.006 -
Journal of Cancer Research and Clinical... Aug 2023A comprehensive appraisal of published meta-analyses incorporating Mendelian randomization studies was performed to map the different risk factors and assess the...
INTRODUCTION
A comprehensive appraisal of published meta-analyses incorporating Mendelian randomization studies was performed to map the different risk factors and assess the causality for lung cancer.
METHODS
Systematic reviews and meta-analyses of observational and interventional studies were reviewed based on PubMed, Embase, Web of Science, and Cochrane Library. Mendelian randomization analyses were conducted to validate the causal associations of those various exposures with lung cancer using summary statistics from 10 genome-wide association studies (GWAS) consortia and other GWAS databases in MR-Base platform.
RESULTS
In the review of meta-analyses, 105 risk factors associated with lung cancer were identified from 93 articles. It was found that 72 risk factors were nominally significant (P < 0.05) associated with lung cancer. Mendelian randomization analyses were performed to analyze 36 exposures based on 551 SNPs and 4,944,052 individuals, finding that 3 exposures had a consistent risk/protective effect on lung cancer with the results of the meta-analysis. In Mendelian randomization anaylses, smoking (OR 1.44, 95% CI 1.18-1.75; P = 0.001) and blood copper (OR 1.14, 95% CI 1.01-1.29; P = 0.039) significantly associated with increased risk of lung cancer, whereas aspirin use (OR 0.67, 95% CI 0.50-0.89; P = 0.006) showed protective effects.
CONCLUSION
This study mapped putative associations of risk factors for lung cancer, revealing the causal hazard effect of smoking, blood copper, and the protective effect of aspirin use in the development of lung cancer.
CLINICAL TRIAL REGISTRY
This study is registered with PROSPERO (CRD42020159082).
Topics: Humans; Copper; Genome-Wide Association Study; Lung Neoplasms; Mendelian Randomization Analysis; Polymorphism, Single Nucleotide; Risk Factors; Smoking; Meta-Analysis as Topic
PubMed: 36809502
DOI: 10.1007/s00432-023-04606-4 -
Sleep Medicine Reviews Feb 2024Sleep disordered breathing is extremely common in pregnancy and is a risk factor for maternal complications. Animal models demonstrate that intermittent hypoxia causes... (Meta-Analysis)
Meta-Analysis Review
Sleep disordered breathing is extremely common in pregnancy and is a risk factor for maternal complications. Animal models demonstrate that intermittent hypoxia causes abnormal fetal growth. However, there are conflicting data on the association between maternal sleep disordered breathing and offspring growth in humans. We investigated this association by conducting a systematic review and meta-analysis. Sixty-three manuscripts, and total study population of 67, 671, 110 pregnant women were included. Thirty-one studies used subjective methods to define sleep disordered breathing, 24 applied objective methods and eight used international codes. Using a random effects model, habitual snoring, defined by subjective methods, and obstructive sleep apnea, diagnosed by objective methods, were associated with an increased risk for large for gestational age (OR 1.46; 95%CI 1.02-2.09 and OR 2.19; 95%CI 1.63-2.95, respectively), while obstructive sleep apnea, identified by international codes, was associated with an increased risk for small for gestational age newborns (OR 1.28; 95%CI 1.02-1.60). Our results support that maternal sleep disordered breathing is associated with offspring growth, with differences related to the type of disorder and diagnostic methods used. Future studies should investigate underlying mechanisms and whether treatment of sleep disordered breathing ameliorates the neonatal growth.
Topics: Female; Humans; Infant, Newborn; Pregnancy; Fetus; Pregnancy Complications; Sleep Apnea Syndromes; Sleep Apnea, Obstructive; Snoring
PubMed: 37956482
DOI: 10.1016/j.smrv.2023.101868 -
Medicine Sep 2023The study aimed to evaluate survival rates and prognosis in systemic lupus erythematosus (SLE) patients with pulmonary hypertension (PH) using meta-analysis. (Meta-Analysis)
Meta-Analysis
BACKGROUND
The study aimed to evaluate survival rates and prognosis in systemic lupus erythematosus (SLE) patients with pulmonary hypertension (PH) using meta-analysis.
METHODS
PubMed, EMBASE, Cochrane central register of controlled trials, China National Knowledge Infrastructure, China Science and Technology Journal Database, Wan-Fang Database, and Chinese biomedical database were searched. Information and data were screened and extracted by 2 researchers. The obtained data were analyzed using the R software meta package. Quality assessment was conducted using Newcastle-Ottawa Scale. The causes of heterogeneity were analyzed using subgroup analysis and sensitivity analysis. Publication bias was evaluated using Begger funnel plots and Egger test.
RESULTS
The search strategy yielded a total of 21 studies involving 875 patients included in the final analysis. The pooled 1-, 3- and 5-year survival rates of patients with SLE-PH were 0.9020 (95%CI: 0.8576; 0.9397), 0.8363 (96%CI: 0.7813; 0.8852), 0.7301 (95%CI: 0.6327; 0.8181). The 1-, 3- and 5-year survival rates of echocardiography subgroup were 0.9000 (95%CI: 0.8480; 0.9551), 0.8435 (95%CI: 0.7744; 0.9187), 0.6795 (95%CI: 0.5746; 0.8035), respectively; and there were 0.9174 (95%CI: 0.8951; 0.9402), 0.8529 (95%CI: 0.8255; 0.8812), 0.7757 (95%CI: 0.7409; 0.8121) at right heart catheterization subgroup in the meantime. Multivariate analysis for predicting mortality in SLE-PH patients revealed that diminishing left ventricular ejection fraction, New York Heart Association classification, lupus nephritis, lower cardiac index, and higher red blood cell distribution width level were significantly associated with a higher mortality rate. Treatment with huge doses of cyclophosphamide, tricuspid annular plane systolic excursion/pulmonary artery systolic pressure, and Raynaud phenomenon signaled favorable outcomes.
CONCLUSION
The 1-, 3-, and 5-year survival rates of SLE-PH patients in recent years (0.9020, 0.8363, 0.7301) were estimated in this study. SLE-PH patients diagnosed by echocardiography have a worse long-term prognosis than those diagnosed by right heart catheterization. Studies after 2015 have shown significantly better survival than earlier studies.
Topics: Humans; Hypertension, Pulmonary; Stroke Volume; Ventricular Function, Left; Prognosis; Lupus Erythematosus, Systemic
PubMed: 37682181
DOI: 10.1097/MD.0000000000034947 -
Chinese Medicine Sep 2023Age-related hearing loss (ARHL) is one of the main illnesses afflicting the aged population and has a significant negative impact on society, economy, and health.... (Review)
Review
BACKGROUND
Age-related hearing loss (ARHL) is one of the main illnesses afflicting the aged population and has a significant negative impact on society, economy, and health. However, there is presently no appropriate therapeutic treatment of ARHL due to the absence of comprehensive trials.
OBJECTIVES
The goal of this review is to systematically evaluate and analyze recent statistics on the pathologic classifications, risk factors, treatment strategies, and drug candidates of ARHL, including that from traditional Chinese medicine (TCM), to provide potential new approaches for preventing and treating ARHL.
METHODS
Literature related to ARHL was conducted in databases such as PubMed, WOS, China National Knowledge Infrastructure (CNKI), and Wanfang from the establishment of the database to Jan, 2023. The pathology, causal factor, pathophysiological mechanism, treatment strategy, and the drug candidate of ARHL were extracted and pooled for synthesis.
RESULTS
Many hypotheses about the etiology of ARHL are based on genetic and environmental elements. Most of the current research on the pathology of ARHL focuses on oxidative damage, mitochondrial dysfunction, inflammation, cochlear blood flow, ion homeostasis, etc. In TCM, herbs belonging to the kidney, lung, and liver meridians exhibit good hearing protection. Seven herbs belonging to the kidney meridian, 9 belonging to the lung meridian, and 4 belonging to the liver meridian were ultimately retrieved in this review, such as Polygonum multiflorum Thunb., Panax ginseng C.A. Mey, and Pueraria lobata (Willd.) Ohwi. Their active compounds, 2,3,4',5-Tetrahydroxystilbene-2-O-D-glucoside, ginsenoside Rb1, and puerarin, may act as the molecular substance for their anti-ARHL efficacy, and show anti-oxidative, neuroprotective, anti-inflammatory, anti-apoptotic, or mitochondrial protective effects.
CONCLUSION
Anti-oxidants, modulators of mitochondrial function, anti-inflammation agents, vasodilators, K channel openers, Ca channel blockers, JNK inhibitors, and nerve growth factors/neurotrophic factors all contribute to hearing protection, and herbs are an important source of potential anti-ARHL drugs.
PubMed: 37730634
DOI: 10.1186/s13020-023-00825-6 -
Public Health Nov 2023The study aimed to identify, appraise and update evidence on the association between cold temperatures (i.e. <18°C) within homes (i.e. dwellings) and health and... (Review)
Review
OBJECTIVE
The study aimed to identify, appraise and update evidence on the association between cold temperatures (i.e. <18°C) within homes (i.e. dwellings) and health and well-being outcomes.
STUDY DESIGN
This study was a systematic review.
METHODS
Seven databases (MEDLINE, Embase, Cochrane Database of Systematic Reviews, CINAHL, APA PsycInfo, Applied Social Sciences Index and Abstracts, Coronavirus Research Database) were searched for studies published between 2014 and 2022, which explored the association between cold indoor temperatures and health and well-being outcomes. Studies were limited to those conducted in temperate and colder climates due to the increased risk of morbidity and mortality during winter in those climatic zones. Studies were independently quality assessed using the Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies.
RESULTS
Of 1209 studies, 20 were included for review. Study outcomes included cardiovascular (blood pressure, electrocardiogram abnormalities, blood platelet count), respiratory (chronic obstructive pulmonary disease symptoms, respiratory viral infection), sleep, physical performance and general health. Seventeen studies found exposure to cold indoor temperatures was associated with negative effects on health outcomes studied. Older individuals and those with chronic health problems were found to be more vulnerable to negative health outcomes.
CONCLUSION
Evidence suggests that indoor temperatures <18°C are associated with negative health effects. However, the evidence is insufficient to allow clear conclusions regarding outcomes from specific temperature thresholds for different population groups. Significant gaps in the current evidence base are identified, including research on the impacts of cold indoor temperatures on mental health and well-being, studies involving young children, and the long-term health effects of cold indoor temperatures.
Topics: Humans; Cold Temperature; Housing; Health Status
PubMed: 37820536
DOI: 10.1016/j.puhe.2023.09.006 -
Clinical Medicine Insights. Oncology 2023Pulmonary toxicities caused by immune checkpoint inhibitors are a prominent concern for clinicians. Clinical Practice Guidelines (CPGs) are critical for managing these... (Review)
Review
A Systematic Review of Clinical Practice Guidelines for Managing Pulmonary Toxicities Caused by Immune Checkpoint Inhibitors: Quality of Treatment Recommendations and Differences in Management Strategies Between Guidelines.
BACKGROUND
Pulmonary toxicities caused by immune checkpoint inhibitors are a prominent concern for clinicians. Clinical Practice Guidelines (CPGs) are critical for managing these toxicities.
METHODS
A systematic search of CPGs on checkpoint-associated pulmonary toxicities (ca-PT) was conducted in October 2022. PubMed, Embase, Cochrane Library, CINAHL, and Web of Science were searched. AGREE II and AGREE-REX were used to appraise CPGs and recommendations quality, respectively. Descriptive statistics, intraclass correlation coefficient, Kruskal-Wallis (H) test, and Spearman's correlation were used for analyses. P-values < .05 were considered statistically significant. Matrices were used to determine recommendation differences between CPGs. The study's design was based on the PRISMA 2020 checklist for systematic reviews. Protocol registration number: CRD42022358435.
RESULTS
Eight CPGs (two high-quality, three moderate-quality, and three low-quality) were identified. All CPGs covered pneumonitis. One CPG covered pleural effusions and pneumonitis/SARs-CoV-2-infection. Three CPGs covered sarcoidosis-like-reactions. CPGs for pulmonary fibrosis, airway disease, bronchiolitis, and diffuse alveolar damage, were unavailable. No CPG recommendation was based on a prospective study, and none were appraised as high-quality. Also, recommendations were not specific to histopathologic subtypes. AGREE II's "rigor of development," the domain that evaluates a guideline's methodological approach and strategies in gathering scientific evidence, correlated strongly with AGREE-REX's "overall quality" pneumonitis recommendations, r = .952; P < .01. Approximately 73% of recommendations on pneumonitis were similar between high-quality CPGs. About 16% to 74% of low-quality CPGs were similar to those recommended by high-quality CPGs.
CONCLUSION
Prospectively designed research projects focusing on all types of ca-PT and their histopathologic subtypes are urgently needed. Due to the lack of high-quality recommendations in available CPGs, the disparities in treatment recommendations between high-quality CPGs, and the similarities in recommendations that exists between high-quality and low-quality CPGs, clinicians should thoroughly assess and responsibly appraise all available CPG recommendations in formulating treatment strategies for ca-PT.
PubMed: 38033741
DOI: 10.1177/11795549231203153 -
Diagnostics (Basel, Switzerland) Jul 2023(1) Background: The current diagnostic algorithm for acute pulmonary embolism (PE) is associated with the overuse of CT pulmonary angiography (CTPA). An additional... (Review)
Review
(1) Background: The current diagnostic algorithm for acute pulmonary embolism (PE) is associated with the overuse of CT pulmonary angiography (CTPA). An additional highly specific blood test could potentially lower the proportion of patients with suspected PE that require CTPA. The aim was to summarize the literature on the diagnostic performance of biomarkers of patients admitted to an emergency department with suspected acute PE. (2) Methods: Medline and Embase databases were searched from 1995 to the present. The study selection process, data extraction, and risk of bias assessment were conducted by two reviewers. Eligibility criteria accepted all blood biomarkers except D-dimer, and CTPA was used as the reference standard. Qualitative data synthesis was performed. (3) Results: Of the 8448 identified records, only 6 were included. Eight blood biomarkers were identified, of which, three were investigated in two separate studies. Red distribution width and mean platelet volume were reported to have a specificity of ≥ 90% in one study, although these findings were not confirmed by other studies. The majority of the studies contained a high risk of selection bias. (4) Conclusions: The modest findings and the uncertain validity of the included studies suggest that none of the biomarkers identified in this systematic review have the potential to improve the current diagnostic algorithm for acute PE by reducing the overuse of CTPA.
PubMed: 37443693
DOI: 10.3390/diagnostics13132301