ABSTRACT
BACKGROUND: Acute pulmonary embolism (PE) is a serious condition that needs quick and effective treatment. Anticoagulation therapy is the usual care for most PE patients but may not work well for higher-risk ones. Thrombolysis breaks the clot and improves blood flow. It can be given systemically or locally. Ultrasound-assisted catheter-directed thrombolysis (USAT) is a new technique that boosts clot-busting drugs. This network meta-analysis compares death, bleeding, and benefits of four treatments in acute submassive PE. METHODS: We comprehensively searched relevant databases up to July 2023 for RCTs. The outcomes encompassed all-cause mortality, major and minor bleeding, PE recurrence, and hospital stay duration. Bayesian network meta-analysis computed odds ratios (OR) and 95 % CI estimates. RESULTS: In this network meta-analysis of 23 RCTs involving 2521 PE patients, we found that SCDT had the most favorable performance for mortality, as it had the lowest odds ratio (OR) among the four interventions (OR 5.41e-42; 95 % CI, 5.68e-97, 1.37e-07). USAT had the worst performance for major bleeding, as it had the highest OR among the four interventions (OR 4.73e+04; 95 % CI, 1.65, 9.16e+13). SCDT also had the best performance for minor bleeding, as it had the lowest OR among the four interventions (OR 5.68e-11; 95 % CI, 4.97e-25, 0.386). CONCLUSION: Our meta-analysis suggests that SCDT is the most effective treatment intervention in improving the risks of All-cause mortality and bleeding. Thrombolytic therapy helps in improving endpoints including the risk of PE recurrence and the duration of hospital stay.
Subject(s)
Fibrinolytic Agents , Hemorrhage , Network Meta-Analysis , Pulmonary Embolism , Randomized Controlled Trials as Topic , Recurrence , Thrombolytic Therapy , Humans , Pulmonary Embolism/mortality , Pulmonary Embolism/drug therapy , Pulmonary Embolism/diagnostic imaging , Pulmonary Embolism/therapy , Pulmonary Embolism/diagnosis , Thrombolytic Therapy/adverse effects , Thrombolytic Therapy/mortality , Treatment Outcome , Fibrinolytic Agents/adverse effects , Fibrinolytic Agents/administration & dosage , Hemorrhage/chemically induced , Risk Factors , Male , Female , Aged , Risk Assessment , Middle Aged , Time Factors , Adult , Ultrasonic Therapy/adverse effects , Aged, 80 and over , Length of Stay , Anticoagulants/adverse effects , Anticoagulants/administration & dosageABSTRACT
Health-related quality of life (HRQoL) indicates patients' overall health and is an essential aspect of cancer care. Although multiple studies have addressed the various aspects of HRQoL in cancer patients, few studies have investigated HRQoL in hematologic malignancy patients in the Eastern Mediterranean region (EMR). This review conducted an electronic search using OVID-Medline to identify HRQoL-related articles involving hematologic malignancy patients in the EMR. Eight studies met the inclusion criteria. Two studies validated translated QoL psychometric instruments, three were observational studies, and three were interventional studies. Except for the validation studies, all studies discussed HRQoL in leukemia patients. Our review highlighted a scarcity in the number of studies focusing on patients with hematological malignancies in this region. The included studies demonstrated the negative impact of hematological malignancies and therapies on patients' HRQoL. In addition, the studies displayed the association between physical symptoms and QoL of cancer patients, necessitating the importance of addressing these symptoms. The studies were limited by publication year, the number of patients, geographical locations, and disease entities. Future studies in this area are encouraged to help understand factors affecting HRQoL in the EMR region and ways to improve it. Consequently, further research is needed to establish translated and validated QoL assessment instruments that target patients in the EMR using the most common tools including the Short-Form 36-item Health Survey and the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire.
ABSTRACT
PARP1 is an abundant nuclear protein with many pleiotropic functions involved in epigenetic and transcriptional controls. Abundance of mRNA depends on the balance between synthesis and decay of a particular transcript. PARP1 binds RNA and its depletion results in increased expression of genes involved in nonsense-mediated decay, suggesting that PARP1 might be involved in mRNA stability. This is of interest considering RNA binding proteins play key roles in post-transcriptional processes in all eukaryotes. We tested the direct impact of PARP1 and PARylation on mRNA stability and decay. By measuring the half-lives of two PARP1-mRNA targets we found that the half-lives were significantly decreased in PARP1-depleted cells. PARP1 depletion impacted both the synthesis of nascent mRNA and the stability of mature mRNAs. PARylation impacted the production of nascent mRNA and the stability of mature mRNA, albeit to a lesser extent than PARP1 KD. PARylation enhanced the impact of PARP1 depletion. These studies provide the first direct comparative role of PARP1 and PARylation in RNA stability and decay, adding a new dimension as to how PARP1 regulates gene expression. These studies present a platform to begin to tease out the influence of PARP1 at each step of RNA biogenesis and decay to fine-tune gene expression.
