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Radiotherapy and Oncology : Journal of... Apr 2021Despite the modern advances in treatment techniques, the survival of locally advanced lung cancer patients continues to remain poor. Circulating lymphocytes have an... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Despite the modern advances in treatment techniques, the survival of locally advanced lung cancer patients continues to remain poor. Circulating lymphocytes have an important role to play in local immune response to RT as well as immune checkpoint inhibitors, and radiation related lymphopenia has been associated with inferior survival in various tumors.
METHODS
We undertook this systematic review and meta-analysis to evaluate the literature on risk and impact of lymphopenia in thoracic tumors. A systematic methodology search of the PubMed, Embase and Cochrane library was performed and eligible studies selected based on pre-defined inclusion and exclusion criteria. Review Manager Version 5.4.1 was used for the meta-analysis.
RESULTS
Fourteen studies were included in the final systematic review and 10 in the quantitative analysis. Overall mean incidence of severe lymphopenia (absolute lymphocyte count < 500) was 64.24%. The patients with severe lymphopenia were at increased risk of death with a pooled HR of 1.59 (95% CI: 1.40, 1.81, I = 17%, P < 0.001) and progression with a pooled HR of 2.1 (95% CI: 1.57, 2.81, I = 59%, P < 0.001) compared to patients with no severe lymphopenia. Dosimetric parameters including gross tumor volume, lung V5 and heart V5 were predictive of lymphopenia, while advanced age, lower baseline lymphocyte counts, higher stage and large tumor size were other risk factors. Models predicting estimated radiation dose to lymphocytes were a good surrogate for treatment outcomes.
CONCLUSION
Radiation related lymphopenia is associated with increased hazard of progression and death in lung cancer. Minimizing the lung and heart dose, especially in patients with concurrent other risk factors can reduce lymphopenia and potentially improve treatment outcomes in these patients.
Topics: Humans; Lung; Lung Neoplasms; Lymphocyte Count; Lymphocytes; Lymphopenia
PubMed: 33577865
DOI: 10.1016/j.radonc.2021.01.034 -
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 -
Neurocritical Care Apr 2022Several studies have demonstrated the usefulness of cardiac troponin I (cTn) levels in predicting adverse clinical outcomes of patients with anerusmal subarachnoid... (Meta-Analysis)
Meta-Analysis Review
Several studies have demonstrated the usefulness of cardiac troponin I (cTn) levels in predicting adverse clinical outcomes of patients with anerusmal subarachnoid hemorrhage (aSAH). However, it remains unclear whether cTn levels can be a useful factor in predicting adverse neurologic and cardiovascular outcomes regarding follow-up duration. The study aimed to evaluate the clinical value of cTn elevation among patients with aSAH. A systematic literature search was performed in PubMed and Cochrane to collect original studies that compared the adverse outcomes in patients with aSAH who had elevated cTn levels and those who did not have elevated cTn levels. Data on patient demographics and outcome measurements (mortality, major disability, delayed cerebral ischemia, cardiac dysfunction, and pulmonary edema) were extracted. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were computed by fitting a random effects model. A total of 4,117 patients with aSAH were included in the meta-analysis. Elevated cTn levels was associated with a higher all-cause mortality (OR 3.64; 95% CI 2.68-4.94; I = 22.05%), poor major disability (OR 2.27; 95% CI 1.5-3.37; I = 52.07%), delayed cerebral ischemia (OR 2.10; 95% CI 1.46-3.03; I = 13.80%), cardiac dysfunction (OR 9.20; 95% CI 4.31-19.60; I = 39.89), and pulmonary edema (OR 10.32; 95% CI 5.64-18.90; I = 0.00%). Additionally, elevated cTn levels was associated with higher mortality in prospective studies (OR 3.66; 95% CI 2.61-5.14) as well as when compared with studies with short-term and long-term follow-up periods. Patients with aSAH who had elevated cTn levels also tended to experience poor short-term major disability (OR 2.36; 95% CI 1.48-3.76). Among patients with aSAH, elevated cTn levels was associated with higher mortality and adverse neurologic and cardiovascular outcomes. Given its clinical value, cardiac troponin levels may be included in the assessment of patients withs aSAH.
Topics: Brain Ischemia; Heart Diseases; Humans; Prospective Studies; Pulmonary Edema; Subarachnoid Hemorrhage; Troponin T
PubMed: 34686997
DOI: 10.1007/s12028-021-01368-0 -
Orthopaedics & Traumatology, Surgery &... Apr 2023Direct oral anticoagulants (DOACs) are recommended as a possible pharmacologic venous thromboembolism (VTE) prophylaxis in patients undergoing total hip arthroplasty... (Meta-Analysis)
Meta-Analysis Review
The effectiveness and safety of direct oral anticoagulants compared to conventional pharmacologic thromboprophylaxis in hip fracture patients: A systematic review and meta-analysis of randomized controlled trials.
BACKGROUND
Direct oral anticoagulants (DOACs) are recommended as a possible pharmacologic venous thromboembolism (VTE) prophylaxis in patients undergoing total hip arthroplasty (THA) and total knee arthroplasty (TKA). However, current guidelines did not introduce recommendations for administration of DOACs as an option for pharmacologic VTE prophylaxis in patients undergoing hip fracture surgery (HFS). The purpose of this study is to compare the effectiveness and safety of DOACs administered for pharmacologic VTE prophylaxis in patients undergoing HFS to conventional pharmacologic VTE prophylaxis, as well as mortality between these thromboprophylaxis medications.
METHODS
We performed a systematic review of multiple electronic databases for randomized controlled trials (RCTs) including patients who were subjected to HFS and prescribed either DOACs as pharmacologic VTE prophylaxis or a conventional VTE prophylaxis drug. We conducted a meta-analysis comparing effectiveness, safety and mortality of these agents between the patient groups studied. Three endpoints were studied. The first one regarding the effectiveness of the agents included clinical manifestations of VTE. The second one regarding the safety of the agents included clinical presentation of bleeding. The latter endpoint studied was mortality of patient groups studied. We generated forest plots to depict the relative risk of the above clinical manifestations between the two studied patient groups and to investigate if there is statistical significance for each patient group to present any of these clinical manifestations. Additionally, we calculated the inconsistency (I) statistic and assessed the risk of bias of RCTs included in our meta-analysis by using the modified Cochrane collaboration tool.
RESULTS
We selected 2 RCTs in this review including 279 patients totally. Patients of control groups in both eligible studies were administered enoxaparin, which is a low molecular weight heparin (LMWH). The meta-analysis found no statistically significant difference between patients prescribed DOACs and patients prescribed LMWH for VTE (95% CI 0.19 to 1.13, RR=0.46, p=0.09), deep vein thrombosis (DVT) (95% CI 0.21 to 1.32, RR=0.53, p=0.17) and pulmonary embolism (PE) (95% CI 0.03 to 3.12, RR=0.33, p=0.33), major bleeding events (95% CI 0.57 to 1.78, RR=1.01, p=0.97), minor bleeding events (95% CI 0.72 to 1.64, RR=1.09, p=0.69), all bleeding events (95% CI 0.79 to 1.38, RR=1.05, p=0.74) and mortality (95% CI 0.01 to 8.0, RR=0.33, p=0.5). The major risk of bias of the selected RCTs was the fact that either the researchers or the patients could have knowledge whether the latter were administered DOACs or LMWHs.
DISCUSSION
DOACs are not inferior compared to LMWHs regarding their effectiveness, safety and mortality in patients subjected to HFS. Further studies with larger patient samples should be conducted in the future, so that safer results and conclusions could be reached.
Topics: Humans; Anticoagulants; Venous Thromboembolism; Randomized Controlled Trials as Topic; Heparin, Low-Molecular-Weight; Enoxaparin; Hemorrhage; Hip Fractures
PubMed: 35817368
DOI: 10.1016/j.otsr.2022.103364 -
Journal of Orthopaedic Surgery and... Aug 2023With the increasing prevalence of osteoarthritis of the hip and knee, total joint replacement, the end-stage treatment, provides pain relief and restoration of function,... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
With the increasing prevalence of osteoarthritis of the hip and knee, total joint replacement, the end-stage treatment, provides pain relief and restoration of function, but is often associated with massive blood loss. Tranexamic acid (TXA) has been reported to reduce perioperative blood loss in hip or knee arthroplasty. However, the optimal dose of TXA administration remains controversial. Therefore, we performed a meta-analysis combining data from 5 trials comparing the efficacy and safety of one fixed dose of 1 g intravenously administered TXA with two doses of 1 g each administered intravenously for hip or knee arthroplasty.
METHODS
PubMed, Medline, Embase, Web of Science, and The Cochrane Library were searched from January 2000 to February 2023. Our meta-analysis included randomized controlled trials and cohort studies comparing the efficacy and safety of different doses of intravenous TXA (IV-TXA) for THA or TKA. The observation endpoints included total blood loss, postoperative hemoglobin drop, blood transfusion rate, length of hospital stay, incidence of deep venous thrombosis (DVT), and incidence of pulmonary embolism (PE). Meta-analysis was performed according to Cochrane's guidelines and PRISMA statement. The Danish RevMan5.3 software was used for data merging.
RESULTS
Five cohort studies involving 5542 patients met the inclusion criteria. Our meta-analysis showed that the two groups were significantly higher in total blood loss (mean difference (MD) = - 65.60, 95% confidence interval (CI) [- 131.46, 0.26], P = 0.05); blood transfusion rate (risk difference (RD) = 0.00, 95% CI [- 0.01, 0.02], P = 0.55); postoperative hemoglobin (MD = 0.02, 95% CI [- 0.09, 0.13], P = 0.31); postoperative hospital stay days (MD = - 0.13), 95% CI [- 0.35, 0.09], P = 0.25); DVT (RD = 0.00, 95% CI [- 0.00, 0.01], P = 0.67); PE (RD = 0.00, 95% CI [- 0.01, 0.00], P = 0.79). There was some inherent heterogeneity due to variance in sample size across each major study.
CONCLUSION
1 dose of 1 g and 2 doses of 1 g IV-TXA each time have similar effects on reducing blood loss, blood transfusion rate, postoperative hemoglobin level, and postoperative hospital stay after TKA or THA, without increasing the risk of postoperative complications risk. For patients at high risk of thromboembolic events, one dose of 1 g TXA throughout surgery may be preferred. However, higher-quality RCT is needed to explore the optimal protocol dose to recommend the widespread use of TXA in total joint arthroplasty. Trial registration We conducted literature selection, eligibility criteria evaluation, data extraction and analysis on the research program registered in Prospero (CRD42023405387) on March 16, 2023.
Topics: Humans; Tranexamic Acid; Antifibrinolytic Agents; Arthroplasty, Replacement, Knee; Venous Thrombosis; Blood Loss, Surgical; Arthroplasty, Replacement, Hip; Administration, Intravenous; Pulmonary Embolism; Hemoglobins
PubMed: 37563702
DOI: 10.1186/s13018-023-03929-9 -
Pharmaceuticals (Basel, Switzerland) Jun 2023Levamisole is an anti-helminthic drug with immunomodulatory properties that is added to cocaine to increase its potency and weight. Levamisole-adulterated cocaine (LAC)... (Review)
Review
Levamisole is an anti-helminthic drug with immunomodulatory properties that is added to cocaine to increase its potency and weight. Levamisole-adulterated cocaine (LAC) may cause an antineutrophil cytoplasmic antibody (ANCA)-associated systemic small vessel vasculitis (AAV). We aimed to characterize the phenotype of persons developing pulmonary-renal syndrome (PRS) in LAC-induced AAV and summarize its treatment and outcomes. Pubmed and Web of Science were searched (until September 2022). Reports that described co-existing diffuse alveolar hemorrhage and glomerulonephritis in an adult (age ≥ 18) with confirmed or suspected LAC exposure were included. Reports, demographics, clinical and serologic features, treatment and outcome characteristics were extracted. Of the 280 records identified, eight met the inclusion criteria, including eight unique cases. Persons were aged 22-58 years, and 50% were women. Cutaneous involvement occurred in only half of the cases. Other associated vasculitis findings and serologies were heterogeneous. All patients received immunosuppression with steroids, with cyclophosphamide and rituximab commonly added. We concluded that PRS could occur from LAC-induced AAV. Distinguishing LAC-induced AAV from primary AAV is challenging as clinical and serologic presentations overlap. Asking about cocaine use is requisite in persons presenting with PRS to guide diagnosis and appropriately counsel on cocaine cessation in conjunction with immunosuppression as treatment.
PubMed: 37375793
DOI: 10.3390/ph16060846 -
Orthopaedic Surgery Apr 2023The optimal dose and efficacy of tranexamic acid (TXA) and epsilon-aminocaproic acid (EACA) in total knee arthroplasty (TKA) were under controversial, and we aimed to... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
The optimal dose and efficacy of tranexamic acid (TXA) and epsilon-aminocaproic acid (EACA) in total knee arthroplasty (TKA) were under controversial, and we aimed to make comparisons between different doses of TXA and EACA in intravenous (IV) or intra-articular (IA) applications in patients undergoing TKA.
METHODS
This network meta-analysis was guided by the Priority Reporting Initiative for Systematic Assessment and Meta-Analysis (PRISMA). According to the administrations of antifibrinolytic agents, patients in eligible studies were divided into three subgroups: (i) IA applications of TXA and EACA; (ii) IV applications (g) of TXA and EACA; (iii) IV applications (mg/kg) of TXA and EACA. Total blood loss (TBL), hemoglobin (HB) drops and transfusion rates were the primary outcomes, while drainage volume, pulmonary embolism (PE) or deep vein thrombosis (DVT) risk were the secondary outcomes. A multivariate Bayesian random-effects model was adopted in the network analysis.
RESULTS
A total of 38 eligible trials with different regimens were assessed. Overall inconsistency and heterogeneity were acceptable. Taking all primary outcomes into account, 1.0-3.0 g TXA were most effective in IA applications, 1-6 g TXA and 10-14 g EACA were most effective in IV applications (g), while 30 mg/kg TXA and 150 mg/kg EACA were most effective in IV applications (mg/kg). None of the regimens showed increasing risk for pulmonary embolism (PE) or deep vein thrombosis (DVT) compared with placebo.
CONCLUSION
0 g IA TXA, 1.0 g IV TXA or 10.0 g IV EACA, as well as 30 mg/kg IV TXA or 150 mg/kg IV EACA were most effective and enough to control bleeding for patients after TKA. TXA was at least 5 times more potent than EACA.
Topics: Humans; Administration, Intravenous; Aminocaproic Acid; Antifibrinolytic Agents; Arthroplasty, Replacement, Knee; Bayes Theorem; Blood Loss, Surgical; Network Meta-Analysis; Pulmonary Embolism; Tranexamic Acid; Venous Thrombosis
PubMed: 36878889
DOI: 10.1111/os.13678 -
International Journal of Gynaecology... Sep 2021Hermansky-Pudlak syndrome (HPS) is a rare autosomal-recessive disorder with clinical manifestations of bleeding diathesis, multi-organ disease and variable... (Review)
Review
BACKGROUND
Hermansky-Pudlak syndrome (HPS) is a rare autosomal-recessive disorder with clinical manifestations of bleeding diathesis, multi-organ disease and variable oculocutaneous albinism (OCA). In women, it can cause life-threatening obstetric and gynecological (OB/GYN) bleeding.
OBJECTIVE
To summarize OB/GYN presentations, outcomes, and management strategies in women with HPS.
SEARCH STRATEGY
Main databases (MEDLINE, EMBASE, Cochrane, PubMed, Web of Science Core Collection and Google Scholar) were searched from inception until June 30, 2020.
SELECTION CRITERIA
Case reports/series of women with confirmed HPS.
DATA COLLECTION AND ANALYSIS
A systematic review using PRISMA guidelines. Methodological quality assessment performed using adapted Newcastle Ottawa scale.
MAIN RESULTS
A total 29 pregnancies in 15 women and 2 gynecological patients were identified. Heavy menstrual bleeding (HMB), the most common bleeding symptom, was reported in 8/15 (53%) of women. HMB and post-partum hemorrhage (PPH) led to diagnosis of HPS in 5/17 (29%) women. Primary PPH was reported in 12/27 (44%) of viable pregnancies; half were major PPH. In 17 pregnancies with known HPS diagnosis, 9 had hemostatic cover with desmopressin and 8 with platelet transfusion. Major PPH occurred in 3/9 (33%) pregnancies covered with desmopressin compared with none in the platelet group.
CONCLUSION
Diagnosis of HPS should be considered in women with OCA presenting with HMB or PPH. Hemostatic management options include desmopressin and platelet transfusion. Management should be multidisciplinary with close collaboration between OB/GYN and hematology teams.
Topics: Female; Hemorrhage; Hemorrhagic Disorders; Hemostatics; Hermanski-Pudlak Syndrome; Humans; Obstetrics; Pregnancy
PubMed: 33521972
DOI: 10.1002/ijgo.13632 -
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 -
BMC Pulmonary Medicine Jun 2020In recent years, many studies have discovered that cystatin C (Cys C) may play an important role in respiratory diseases, especially in chronic obstructive pulmonary... (Meta-Analysis)
Meta-Analysis
BACKGROUND
In recent years, many studies have discovered that cystatin C (Cys C) may play an important role in respiratory diseases, especially in chronic obstructive pulmonary disease (COPD). However, the findings of these studies were inconsistent. This systematic review and meta-analysis aimed to assess the relationship between serum Cys C and COPD.
METHODS
We conducted a systematic literature search in PubMed, Embase, Web of Science, Wanfang databases, and the China National Knowledge Infrastructure. The standardized mean difference (SMD), Fisher's Z-value and 95% confidence interval (CI) were calculated to investigate the effect sizes. Subgroup analyses were performed on disease status, ethnicity, assay method, and study design. Sensitivity was performed, and publication bias was assessed.
RESULTS
A total of 15 studies, including 4079 COPD patients and 5949 controls, were included in this meta-analysis. The results showed that serum Cys C levels in patients with COPD were significantly higher than those in controls (SMD = 0.99, 95% CI =0.62-1.37, P < 0.001), especially in AECOPD (SMD = 1.59, 95% CI =1.05-2.13, P < 0.001), and there were statistically different among AECOPD and SCOPD (SMD = 0.35, 95% CI =0.10-0.59, P = 0.005). The serum Cys C levels were negatively correlated with FEV1%pre (Z = - 0.45, 95%CI = -0.58--0.32, P = 0.011) and FEV1/FVC (Z = - 0.32, 95%CI = -0.50--0.14, P = 0.006). The serum Cys C levels were independent of ethnicity, assay method, and study design.
CONCLUSION
Serum Cys C levels were associated with COPD and COPD exacerbation, and they were inversely correlated with FEV1%pre and FEV1/FVC.
Topics: Biomarkers; Cystatin C; Disease Progression; Humans; Pulmonary Disease, Chronic Obstructive
PubMed: 32586317
DOI: 10.1186/s12890-020-01208-5