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Medical Principles and Practice :... 2023Actinium-225 (Ac-225) labelled PSMA RLT has been tested recently in metastatic castration-resistant prostate cancer (mCRPC), with encouraging results. Ac-225, being an... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Actinium-225 (Ac-225) labelled PSMA RLT has been tested recently in metastatic castration-resistant prostate cancer (mCRPC), with encouraging results. Ac-225, being an alpha emitter, is expected to have higher efficacy and fewer side effects compared to the beta-emitters such as Lutetium-177. We have performed a meta-analysis to assess the therapeutic responses, survival effects, and significant side effects of Ac-225 PSMA RLT in patients with mCRPC.
METHODOLOGY
Systematic literature search was carried out from five electronic databases PubMed/MEDLINE, SCOPUS, EMBASE, Web of Science, and Cochrane Library until March 2021. Eight studies were found to be eligible for this metanalysis.
RESULTS
Eight studies with 226 patients were analyzed in this metanalysis. 81% (95% CI 73-89) patients had a decline in PSA levels. 60% of the patients showed more than 50% PSA decline. Two studies assessed survival effects of radioligand naïve patients compared to patients who had received Lu-PSMA therapy previously and the pooled HR for radioligand naïve patients is 0.22. The most common toxicity reported was xerostomia in 167 patients out of 226 patients (73.9%, 95% CI 67.6-79.5%); however, most of them were confined to grade I and II levels. Other reported side effects include hematologic toxicity and nephrotoxicity.
CONCLUSION
Ac-PSMA RLT is a safe and potentially effective treatment option for patients with mCRPC.
Topics: Male; Humans; Actinium; Prostatic Neoplasms, Castration-Resistant; Prostate-Specific Antigen; Prostate; Dipeptides; Treatment Outcome; Retrospective Studies
PubMed: 37247612
DOI: 10.1159/000531246 -
The Cochrane Database of Systematic... May 2023Neonates who have undergone gastrointestinal surgery are particularly susceptible to infectious complications in the postoperative period. This may be due in part to... (Review)
Review
BACKGROUND
Neonates who have undergone gastrointestinal surgery are particularly susceptible to infectious complications in the postoperative period. This may be due in part to disruption of the integrity of the gut and its altered intestinal microflora. Lactoferrin is a whey protein found in milk and is an important innate mammalian defence mechanism. Lactoferrin has been reported to have antimicrobial and anti-inflammatory properties. It has also been reported to help establish a healthy gut microflora and aid in the intestinal immune system. Lactoferrin supplementation has been reported to decrease sepsis in preterm infants. There may be a role for lactoferrin to reduce the incidence of sepsis, thus reducing morbidity and mortality and improving enteral feeding in postoperative term neonates.
OBJECTIVES
The primary objective of this review was to evaluate the efficacy of administering lactoferrin on the incidence of sepsis and mortality in term neonates after gastrointestinal surgery. The secondary objective was to assess the impact of administering lactoferrin on time to full enteral feeds, the intestinal microflora, duration of hospital stay, and mortality before discharge in the same population.
SEARCH METHODS
The Cochrane Neonatal Information Specialist searched the Cochrane Central Register of Controlled Trials (CENTRAL), Ovid MEDLINE, Embase Ovid, CINAHL, the WHO ICTRP and ClinicalTrials.gov trials registries. The date of the last search was February 2023. There were no restrictions to language, publication year or publication type. We checked references of potentially relevant studies and systematic reviews.
SELECTION CRITERIA
We planned to include randomised controlled trials that studied infants born at 37 or more weeks of gestation who had one or more episodes of gastrointestinal surgery within 28 days of birth, and compared administration of lactoferrin with a placebo.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methodological procedures. We planned to use the GRADE approach to assess the certainty of evidence for each outcome.
MAIN RESULTS
We identified no published randomised controlled studies that assessed the efficacy of lactoferrin for the postoperative management of term neonates following gastrointestinal surgery.
AUTHORS' CONCLUSIONS
There is currently no evidence available from randomised controlled trials to show whether lactoferrin is effective or ineffective for the postoperative management of term neonates after gastrointestinal surgery. There is a need for randomised controlled trials to be performed to assess the role of lactoferrin in this setting.
Topics: Animals; Humans; Infant, Newborn; Digestive System Surgical Procedures; Infant, Premature; Lactoferrin; Milk; Sepsis
PubMed: 37233609
DOI: 10.1002/14651858.CD012218.pub2 -
Current Problems in Cardiology Oct 2023Twelve CCI patients were studied with confirmed or suspected COVID-19 infection. The majority of these patients were males (83.3%) with a median age of 55 years from... (Review)
Review
Twelve CCI patients were studied with confirmed or suspected COVID-19 infection. The majority of these patients were males (83.3%) with a median age of 55 years from three geographical locations, constituting the Middle East (7), Spain (3), and the USA (1). In 6 patients, IgG/IgM was positive for COVID-19, 4 with high pretest probability and 2 with positive RT-PCR. Type 2 DM, hyperlipidemia, and smoking were the primary risk factors. Right-sided neurological impairments and verbal impairment were the most common symptoms. Our analysis found 8 (66%) synchronous occurrences. In 58.3% of cases, neuroimaging showed left Middle Cerebral Artery (MCA) infarct and 33.3% right. Carotid artery thrombosis (16.6%), tandem occlusion (8.3%), and carotid stenosis (1%) were also reported in imaging. Dual antiplatelet therapy (DAPT) and anticoagulants were conservative therapies (10). Two AMI patients had aspiration thrombectomy, while three AIS patients had intravenous thrombolysis/tissue plasminogen activator (IVT-tPA), 2 had mechanical thrombectomy (MT), and 1 had decompressive craniotomy. Five had COVID-19-positive chest X-rays, whereas 4 were normal. four of 8 STEMI and 3 NSTEMI/UA patients complained chest pain. LV, ICA, and pulmonary embolism were further complications (2). Upon discharge, 7 patients (70%) had residual deficits while 1 patient unfortunately died.
Topics: Female; Humans; Male; Middle Aged; Anticoagulants; COVID-19; Infarction, Middle Cerebral Artery; Stroke; Thrombectomy; Thrombolytic Therapy; Tissue Plasminogen Activator; Treatment Outcome; Case Reports as Topic
PubMed: 37209804
DOI: 10.1016/j.cpcardiol.2023.101814 -
Lipids in Health and Disease May 2023Many commonly used drugs were evaluated as repurposed treatment options since the emergence of the COVID-19 pandemic. The benefit of lipid-lowering agents has been... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Many commonly used drugs were evaluated as repurposed treatment options since the emergence of the COVID-19 pandemic. The benefit of lipid-lowering agents has been controversial in this regard. In this systematic review, we assessed the effect of these medications as adjunctive therapy in COVID-19 by the inclusion of randomized controlled trials (RCTs).
METHODS
We searched four international databases including PubMed, the Web of Science, Scopus, and Embase for RCTs in April 2023. The primary outcome was mortality, while other efficacy indices were considered secondary outcomes. In order to estimate the pooled effect size of the outcomes, considering the odds ratio (OR) or standardized mean difference (SMD) and 95% confidence interval (CI), random-effect meta-analyses was conducted.
RESULTS
Ten studies involving 2,167 COVID-19 patients using statins, omega-3 fatty acids, fenofibrate, PCSK9 inhibitors, and nicotinamide as intervention compared to control or placebo, were included. No significant difference was found in terms of mortality (OR 0.96, 95% CI 0.58 to 1.59, p-value = 0.86, I = 20.4%) or length of hospital stay (SMD -0.10, 95% CI -0.78 to 0.59, p-value = 0.78, I = 92.4%) by adding a statin to the standard of care. The trend was similar for fenofibrate and nicotinamide. PCSK9 inhibition, however, led to decreased mortality and an overall better prognosis. Omega-3 supplementation showed contradicting results in two trials, suggesting the need for further evaluation.
CONCLUSION
Although some observational studies found improved outcomes in patients using lipid-lowering agents, our study found no benefit in adding statins, fenofibrate, or nicotinamide to COVID-19 treatment. On the other hand, PCSK9 inhibitors can be a good candidate for further assessment. Finally, there are major limitations in the use of omega-3 supplements in treating COVID-19 and more trials are warranted to evaluate this efficacy.
Topics: Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Fenofibrate; PCSK9 Inhibitors; COVID-19; Randomized Controlled Trials as Topic; Hypolipidemic Agents; Fatty Acids, Omega-3; Proprotein Convertase 9; Observational Studies as Topic
PubMed: 37158917
DOI: 10.1186/s12944-023-01828-w -
Frontiers in Endocrinology 2023Intravenous recombinant tissue plasminogen activator (rtPA) thrombolysis is an effective treatment for acute ischemic stroke. Hyperglycemia is a major risk factor for... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND OBJECTIVES
Intravenous recombinant tissue plasminogen activator (rtPA) thrombolysis is an effective treatment for acute ischemic stroke. Hyperglycemia is a major risk factor for the occurrence, development, and prognosis of ischemic stroke. This meta-analysis purposefully estimates the association between hyperglycemia and poor prognosis in acute ischemic stroke patients receiving intravenous rtPA thrombolytic therapy.
MATERIALS AND METHODS
According to the predefined inclusion criteria, we searched PubMed, Web of Science, and Cochrane Library databases. The association of high blood glucose(>140mg/dl) with symptomatic intracranial hemorrhage (sICH), poor clinical outcome and mortality at 90 days post-rtPA thrombolysis was studied using both a common effects model and a random effects model. Odds ratios (ORs) were plotted on forest plots.
RESULTS
Of a total cohort of 2565 patients who received intravenous thrombolytic therapy, 721 had higher blood glucose. High glucose level significantly increased the odds of sICH (OR 1.80; 95% confidence interval(95%CI): 1.30- 2.50) and poor clinical outcome at 90 days (OR 1.82; 95%CI: 1.52-2.19), and all-cause mortality at 90 days (OR 2.51; 95%CI:1.65-3.82).
CONCLUSIONS
In our meta-analysis, high blood glucose was significantly associated with sICH, poor clinical outcome and higher mortality at 90 days.
Topics: Humans; Tissue Plasminogen Activator; Stroke; Blood Glucose; Ischemic Stroke; Brain Ischemia; Fibrinolytic Agents; Prognosis; Thrombolytic Therapy; Intracranial Hemorrhages; Hyperglycemia
PubMed: 37124754
DOI: 10.3389/fendo.2023.1120779 -
European Urology Jul 2023The optimal management for men with prostate cancer (PCa) with unconventional histology (UH) is unknown. The outcome for these cancers might be worse than for...
Impact of Epithelial Histological Types, Subtypes, and Growth Patterns on Oncological Outcomes for Patients with Nonmetastatic Prostate Cancer Treated with Curative Intent: A Systematic Review.
CONTEXT
The optimal management for men with prostate cancer (PCa) with unconventional histology (UH) is unknown. The outcome for these cancers might be worse than for conventional PCa and so different approaches may be needed.
OBJECTIVE
To compare oncological outcomes for conventional and UH PCa in men with localized disease treated with curative intent.
EVIDENCE ACQUISITION
A systematic review adhering to the Referred Reporting Items for Systematic Reviews and Meta-Analyses was prospectively registered on PROSPERO (CRD42022296013) was performed in July 2021.
EVIDENCE SYNTHESIS
We screened 3651 manuscripts and identified 46 eligible studies (reporting on 1 871 814 men with conventional PCa and 6929 men with 10 different PCa UHs). Extraprostatic extension and lymph node metastases, but not positive margin rates, were more common with UH PCa than with conventional tumors. PCa cases with cribriform pattern, intraductal carcinoma, or ductal adenocarcinoma had higher rates of biochemical recurrence and metastases after radical prostatectomy than for conventional PCa cases. Lower cancer-specific survival rates were observed for mixed cribriform/intraductal and cribriform PCa. By contrast, pathological findings and oncological outcomes for mucinous and prostatic intraepithelial neoplasia (PIN)-like PCa were similar to those for conventional PCa. Limitations of this review include low-quality studies, a risk of reporting bias, and a scarcity of studies that included radiotherapy.
CONCLUSIONS
Intraductal, cribriform, and ductal UHs may have worse oncological outcomes than for conventional and mucinous or PIN-like PCa. Alternative treatment approaches need to be evaluated in men with these cancers.
PATIENT SUMMARY
We reviewed the literature to explore whether prostate cancers with unconventional growth patterns behave differently to conventional prostate cancers. We found that some unconventional growth patterns have worse outcomes, so we need to investigate if they need different treatments. Urologists should be aware of these growth patterns and their clinical impact.
Topics: Humans; Male; Prostate; Prostate-Specific Antigen; Prostatectomy; Prostatic Intraepithelial Neoplasia; Prostatic Neoplasms
PubMed: 37117107
DOI: 10.1016/j.eururo.2023.03.014 -
JAMA Oncology Jun 2023Recently, several large, high-quality analyses have shown opposing results regarding the association between 5α-reductase inhibitor (5-ARI) use and prostate cancer... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Recently, several large, high-quality analyses have shown opposing results regarding the association between 5α-reductase inhibitor (5-ARI) use and prostate cancer (PCa) mortality.
OBJECTIVE
To systematically evaluate the current evidence regarding 5-ARI use and PCa mortality.
DATA SOURCES
A literature search began in and was conducted through August 2022 using PubMed/Medline, Embase, and Web of Science databases.
STUDY SELECTION
Studies were deemed eligible if they included male patients of any age who were 5-ARI users and were compared with those who were nonusers if they analyzed PCa mortality in randomized clinical trials and prospective or retrospective cohort studies.
DATA EXTRACTION AND SYNTHESIS
This study was reported in accordance with Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline. Adjusted hazard ratios (HRs) were extracted from published articles. Data analysis was performed in August 2022.
MAIN OUTCOMES AND MEASURES
The primary outcome was PCa mortality among 5-ARI users vs nonusers. The inverse variance method with adjusted HRs and random-effect models were used to determine the association between 5-ARI use and PCa mortality. Two subgroup analyses were performed to assess the effect of 2 main confounders: prostate-specific antigen level and PCa diagnosis at baseline.
RESULTS
Among 1200 unique records screened, 11 studies met the inclusion criteria. A total of 3 243 575 patients were included: 138 477 users of 5-ARI and 3 105 098 nonusers. There was no statistically significant association between 5-ARI use and PCa mortality (adjusted HR, 1.04; 95% CI, 0.80-1.35; P = .79). No significant association was found when the analysis was restricted to studies that excluded patients with a diagnosis of PCa at baseline (adjusted HR, 1.00; 95% CI, 0.60-1.67; P = .99) or the analysis was restricted to prostate-specific antigen-adjusted studies (adjusted HR, 0.76; 95% CI, 0.57-1.03; P = .08).
CONCLUSIONS AND RELEVANCE
This systematic review and meta-analysis, which draws on 2 decades of epidemiologic literature and includes more than 3 million patients, found no statistically significant association between 5-ARI use and PCa mortality but provides important data to inform clinical care.
Topics: Humans; Male; Prostate-Specific Antigen; Prospective Studies; 5-alpha Reductase Inhibitors; Retrospective Studies; Prostatic Neoplasms; Oxidoreductases
PubMed: 37079318
DOI: 10.1001/jamaoncol.2023.0260 -
Clinical and Experimental Medicine Nov 2023Some human polymorphisms of ACE1, ACE2, IFITM3, TMPRSS2 and TNFα genes may have an effect on the susceptibility to SARS-CoV-2 infection and increase the risk to develop... (Meta-Analysis)
Meta-Analysis Review
Genetic polymorphisms of ACE1, ACE2, IFTM3, TMPRSS2 and TNFα genes associated with susceptibility and severity of SARS-CoV-2 infection: a systematic review and meta-analysis.
BACKGROUND
Some human polymorphisms of ACE1, ACE2, IFITM3, TMPRSS2 and TNFα genes may have an effect on the susceptibility to SARS-CoV-2 infection and increase the risk to develop severe COVID-19. We conducted a systematic review of current evidence to investigate the association of genetic variants of these genes with the susceptibility to virus infection and patient prognosis.
METHODS
We systematically searched Medline, Embase and The Cochrane Library for articles published until May 2022, and included observational studies covering genetic association of ACE1, ACE2, IFITM3, TMPRSS2 and TNFα genes with COVID-19 susceptibility or prognosis. We evaluated the methodological quality of included studies, and pooled data as convenient in meta-analysis (MA). Odds ratio (OR) values and 95% confidence intervals were calculated.
RESULTS
We included 35 studies (20 on ACE, 5 each on IFITM3, TMPRSS2, TNFα), enrolling 21,452 participants, of them 9401 were COVID-19 confirmed cases. ACE1 rs4646994 and rs1799752, ACE2 rs2285666, TMPRSS2 rs12329760, IFITM3 rs12252 and TNFα rs1800629 were identifies as common polymorphisms. Our MA showed an association between genetic polymorphisms and susceptibility to SARS-CoV-2 infection for IFITM3 rs12252 CC (OR 5.67) and CT (OR 1.64) genotypes. Furthermore, MA uncovered that both ACE DD (OR 1.27) and IFITM3 CC (OR 2.26) genotypes carriers had a significantly increased risk of developing severe COVID-19.
DISCUSSION
These results provide a critical evaluation of genetic polymorphisms as predictors in SARS-CoV-2 infection. ACE1 DD and IFITM3 CC polymorphisms would lead to a genetic predisposition for severe lung injury in patients with COVID-19.
Topics: Humans; Angiotensin-Converting Enzyme 2; COVID-19; Membrane Proteins; Peptidyl-Dipeptidase A; Polymorphism, Genetic; RNA-Binding Proteins; SARS-CoV-2; Serine Endopeptidases; Tumor Necrosis Factor-alpha
PubMed: 37055652
DOI: 10.1007/s10238-023-01038-9 -
American Journal of Men's Health 2023Prostate cancer (PCa) is the second leading cause of cancer-causing death in the United States. As the most common malignancy in men, it is pertinent to explore whether...
Prostate cancer (PCa) is the second leading cause of cancer-causing death in the United States. As the most common malignancy in men, it is pertinent to explore whether novel immunotherapies may improve the quality of life and overall survival (OS) of patient populations. This systematic review and post hoc analysis curates a patient-by-patient pool of evidence adhering to PRISMA Statement 2020 guidelines. In total, 24 patients were analyzed for treatment history and associated variables including prostate-specific antigen (PSA) levels at diagnosis and post-treatment, Gleason score, secondary tumor locations, success/failure of therapy, and post-immunotherapy outcomes including OS. In total, 10 types of immunotherapies were identified with Pembrolizumab (among 8 patients) followed by IMM-101 (among 6 patients) being the most commonly administered. The mean OS for all patients was 27.8 months (24 patients) with the relatively highest mean OS reported with IMM-101 (56 months) followed by tumor-infiltrating lymphocytes (30 months). This research article provides critical insights into the evolving landscape of immunotherapies being tested for PCa and addresses gaps in oncological research to advance the understanding of PCa.
Topics: Male; Humans; Quality of Life; Prostatic Neoplasms; Immunotherapy; Prostate-Specific Antigen
PubMed: 37002863
DOI: 10.1177/15579883231165140 -
Stroke May 2023Prior systematic reviews have compared the efficacy of intravenous tenecteplase and alteplase in acute ischemic stroke, assigning their relative complications as a... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Prior systematic reviews have compared the efficacy of intravenous tenecteplase and alteplase in acute ischemic stroke, assigning their relative complications as a secondary objective. The objective of the present study is to determine whether the risk of treatment complications differs between patients treated with either agent.
METHODS
We performed a systematic review including interventional studies and prospective and retrospective, observational studies enrolling adult patients treated with intravenous tenecteplase for ischemic stroke (both comparative and noncomparative with alteplase). We searched MEDLINE, Embase, the Cochrane Library, Web of Science, and the www.
CLINICALTRIALS
gov registry from inception through June 3, 2022. The primary outcome was symptomatic intracranial hemorrhage, and secondary outcomes included any intracranial hemorrhage, angioedema, gastrointestinal hemorrhage, other extracranial hemorrhage, and mortality. We performed random effects meta-analyses where appropriate. Evidence was synthesized as relative risks, comparing risks in patients exposed to tenecteplase versus alteplase and absolute risks in patients treated with tenecteplase.
RESULTS
Of 2226 records identified, 25 full-text articles (reporting 26 studies of 7913 patients) were included. Sixteen studies included alteplase as a comparator, and 10 were noncomparative. The relative risk of symptomatic intracranial hemorrhage in patients treated with tenecteplase compared with alteplase in the 16 comparative studies was 0.89 ([95% CI, 0.65-1.23]; I=0%). Among patients treated with low dose (<0.2 mg/kg; 4 studies), medium dose (0.2-0.39 mg/kg; 13 studies), and high dose (≥0.4 mg/kg; 3 studies) tenecteplase, the RRs of symptomatic intracranial hemorrhage were 0.78 ([95% CI, 0.22-2.82]; I=0%), 0.77 ([95% CI, 0.53-1.14]; I=0%), and 2.31 ([95% CI, 0.69-7.75]; I=40%), respectively. The pooled risk of symptomatic intracranial hemorrhage in tenecteplase-treated patients, including comparative and noncomparative studies, was 0.99% ([95% CI, 0%-3.49%]; I=0%, 7 studies), 1.69% ([95% CI, 1.14%-2.32%]; I=1%, 23 studies), and 4.19% ([95% CI, 1.92%-7.11%]; I=52%, 5 studies) within the low-, medium-, and high-dose groups. The risks of any intracranial hemorrhage, mortality, and other studied outcomes were comparable between the 2 agents.
CONCLUSIONS
Across medium- and low-dose tiers, the risks of complications were generally comparable between those treated with tenecteplase versus alteplase for acute ischemic stroke.
Topics: Humans; Tissue Plasminogen Activator; Tenecteplase; Fibrinolytic Agents; Ischemic Stroke; Prospective Studies; Retrospective Studies; Stroke; Intracranial Hemorrhages; Treatment Outcome; Brain Ischemia
PubMed: 36951049
DOI: 10.1161/STROKEAHA.122.042335