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Biomedical Papers of the Medical... Mar 2024Oxidative DNA damage markers (8OHdG, comet assay, gammaH2AX) are becoming widely used in clinical cardiology research. To conduct this review of DNA damage in relation... (Meta-Analysis)
Meta-Analysis Review
Oxidative DNA damage markers (8OHdG, comet assay, gammaH2AX) are becoming widely used in clinical cardiology research. To conduct this review of DNA damage in relation to hypertension in humans, we used databases (e.g. PubMed, Web of Science) to search for English-language publications up to June 30, 2022 and the terms: DNA damage, comet assay, gammaH2AX, 8OHdG, strand breaks, and arterial hypertension. Exclusion criteria were: children, absence of relevant controls, extra-arterial hypertensive issues, animal, cell lines. From a total of 79526, 15 human studies were selected. A total of 902 hypertensive patients (pts): (comet: N=418 pts; 8OHdG: N=484 pts) and 587 controls (comet: N=203; 8OHdG: N=384) were included. DNA damage was significantly higher in hypertensive pts than healthy controls (comet 26.6±11.0 vs 11.7±4.07 arbitrary units /A.U./; P<0.05 and="" 8ohdg="" 13="" 1="" 4="" 12="" vs="" 6="" 97="" 2="" 67="" ng="" mg="" creatinine="" i=""> P<0.05) confirmed with meta-analysis for both. Greater DNA damage was observed in more adverse cases (concentric cardiac hypertrophy 43.4±15.4 vs 15.6±5.5; sustained/untreated hypertension 31.4±12.1 vs 14.2±5/35.0±5.0 vs 25.0 ±5.0; non-dippers 39.2±15.5 vs 29.4±11.1 A.U.; elderly 14.9±4.5 vs 9.3±4.1 ng/mg creatinine; without carvedilol 9.1±4.2 vs 5.7±3.9; with coronary heart disease 0.5±0.1 vs 0.2±0.1 ng/mL) (P<0.05) confirmed with meta-analysis. DNA damage correlated strongly positively with serum glycosylated haemoglobin (r=0.670; P<0.05) and negatively with total antioxidant status (r=-0.670 to -0.933; P<0.05). This is the first systematic review with meta-analysis showing that oxidative DNA damage was increased in humans with arterial hypertension compared to controls.
Topics: Child; Animals; Humans; Aged; 8-Hydroxy-2'-Deoxyguanosine; Creatinine; DNA Damage; Comet Assay; Hypertension
PubMed: 37916467
DOI: 10.5507/bp.2023.044 -
Journal of Cancer Research and Clinical... Dec 2023Capecitabine has extensive utilization in the treatment of diverse solid tumors, and its efficacy has been substantiated. Its oral administration and minimal toxicity in... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
Capecitabine has extensive utilization in the treatment of diverse solid tumors, and its efficacy has been substantiated. Its oral administration and minimal toxicity in clinical practice render it advantageous. Nevertheless, uncertainty remains regarding whether capecitabine can substitute anthracycline drugs in chemotherapy regimens to achieve a lower risk of anthracycline-induced degradation. Consequently, we conducted a meta-analysis of randomized controlled trials (RCTs) to assess the potential of capecitabine as a replacement for anthracycline drugs in chemotherapy regimens for breast cancer.
METHODS
We systematically searched PubMed, Embase, Web of Science, and the Cochrane Controlled Trials Register (CENTRAL) to retrieve eligible studies published before July 18, 2023. Two independent reviewers extracted relevant data from the included studies using a pre-established data extraction form. The primary endpoints of interest encompassed overall survival (OS) and progression-free survival (PFS) for postoperative adjuvant therapy, as well as pathological complete response (PCR) following neoadjuvant therapy. Adverse events were considered as secondary outcomes. The statistical analysis was performed using Revman 5.4.1.
RESULTS
A total of six studies involving 2348 breast cancer patients were deemed eligible according to the selection criteria. The pooled meta-analysis revealed that there were no statistically significant differences observed in the primary outcomes of overall survival (OS) (HR 1.06, 95% CI 0.88-1.28) and progression-free survival (PFS) (HR 1.10, 95% CI 0.90-1.34) across the four postoperative adjuvant chemotherapy trials, as well as in the two neoadjuvant chemotherapy trials with respect to the primary outcome of pathological complete response (PCR) (OR 1.65, 95% CI 0.93-2.95) when comparing regimens containing anthracycline drugs to those without. In terms of adverse events, the probability of experiencing diarrhea (OR 3.94, P = 0.004) and hand-foot syndrome (OR 10.89, P = 0.004) was significantly higher in the capecitabine group, attributable to the drug characteristics. Conversely, the likelihood of developing neutropenia (OR 0.50, P = 0.03) was higher in the anthracycline group.
CONCLUSIONS
According to the current evidence, there was no statistically significant difference in the primary outcomes when capecitabine was substituted for anthracycline drugs. Thus, capecitabine can be regarded as a feasible alternative in the subset of patients who necessitate the exclusion of anthracyclines.
Topics: Humans; Female; Capecitabine; Anthracyclines; Taxoids; Breast Neoplasms; Antibiotics, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols
PubMed: 37891407
DOI: 10.1007/s00432-023-05459-7 -
Ecotoxicology and Environmental Safety Nov 2023Oxidative stress (OS) constitutes a pivotal factor in the initiation and progression of lipopolysaccharide (LPS) challenges in broiler chickens. Increasing studies have... (Meta-Analysis)
Meta-Analysis Review
Oxidative stress (OS) constitutes a pivotal factor in the initiation and progression of lipopolysaccharide (LPS) challenges in broiler chickens. Increasing studies have demonstrated that Alleviation of oxidative stress seems to be a reasonable strategy to alleviate LPS-mediated afflictions in broilers. Nonetheless, the relationship between OS-related indicators and exposure to LPS remains a topic of debate. The aim of this investigation was to precisely and holistically evaluate the effect of LPS exposure on OS-associated markers. We conducted a systematic search of four electronic databases-PubMed, Web of Science, Scopus, and Cochrane for relevant studies, and a total of 31 studies were included. The overall results showed that the LPS treatment significantly increased the levels of oxygen radicals and their products, such as malondialdehydes (MDA), reactive oxygen species (ROS), and 8-hydroxy-2-deoxyguanosine (8-OHdG), while significantly reduced the levels of antioxidants, such as total antioxidative capacity (T-AOC), total superoxide dismutase (T-SOD), catalase (CAT), glutathione peroxidase (GSH-Px), and glutathione (GSH), in the chickens. Intriguingly, though the observed trends in alterations were not strictly correlated with LPS concentrations, the enzyme activity levels were indeed influenced by the concentration of LPS. This observation highlights the complex relationship between LPS exposure and the body's antioxidant response. Despite some limitations, all the included studies were deemed credible. Subgroup evaluations revealed that the jejunum and duodenum has demonstrated stronger antioxidant capability compared to other tissues. Overall, our study presents compelling evidence that exposure to LPS induces significant OS in chickens. And we also found that the extent of OS was related to LPS doses, target tissues, and dietary ingredients.
Topics: Animals; Antioxidants; Chickens; Lipopolysaccharides; Oxidative Stress; Glutathione; Reactive Oxygen Species; 8-Hydroxy-2'-Deoxyguanosine; Biomarkers; Dietary Supplements
PubMed: 37866038
DOI: 10.1016/j.ecoenv.2023.115606 -
Clinical Infectious Diseases : An... Feb 2024The HIV Prevention Trials Network (HPTN) 083/084 trials showed up to 88% increased efficacy of long-acting cabotegravir (CAB-LA) versus continuous oral tenofovir...
BACKGROUND
The HIV Prevention Trials Network (HPTN) 083/084 trials showed up to 88% increased efficacy of long-acting cabotegravir (CAB-LA) versus continuous oral tenofovir disoproxil fumarate/emtricitabine (TDF/FTC). However, CAB-LA's high price limits the number of people who can be treated within fixed prevention budgets. Global human immunodeficiency virus (HIV) prevention budgets are highly limited, with TDF/FTC widely available as a low-cost generic. In randomized clinical trials, event-driven TDF/FTC has shown similar preventive efficacy to continuous TDF/FTC.
METHODS
A systematic review of global HIV incidence studies was conducted. Weighted incidence was calculated in each at-risk population. HIV infection rates were evaluated for 5 prevention strategies, with additional HIV testing, education, and service access costs assumed for each ($18 per person per year). Assumed efficacies were 90% (continuous CAB-LA), 60% (continuous TDF/FTC), and 60% (event-driven TDF/FTC). Using weighted incidence and an assumed 100 000 target population, annual HIV infection rates by population were calculated for each prevention strategy.
RESULTS
Ninety-eight studies in 5 230 189 individuals were included. Incidence per 100 person-years ranged from 0.03 (blood donors) to 3.82 (people who inject drugs). Using the number needed to treat to benefit for each strategy, a mean incidence of 2.6 per 100 person-years in at-risk populations, and a 100 000 target population, current-price continuous CAB-LA cost $949 487 per HIV infection successfully prevented, followed by target-price CAB-LA ($11 453), continuous TDF/FTC ($4231), and event-driven TDF/FTC ($1923).
CONCLUSIONS
High prices of CAB-LA limit numbers treatable within fixed budgets. Low-cost event-driven TDF/FTC consistently prevents the most HIV infections within fixed budgets.
Topics: Humans; HIV Infections; Incidence; Adenine; Organophosphonates; Deoxycytidine; Tenofovir; Emtricitabine; Anti-HIV Agents; HIV-1; Costs and Cost Analysis; Pre-Exposure Prophylaxis; Pyridones; Diketopiperazines
PubMed: 37665213
DOI: 10.1093/cid/ciad537 -
JAMA Aug 2023A 2019 review for the US Preventive Services Task Force (USPSTF) found oral preexposure prophylaxis (PrEP) associated with decreased HIV infection risk vs placebo or no...
IMPORTANCE
A 2019 review for the US Preventive Services Task Force (USPSTF) found oral preexposure prophylaxis (PrEP) associated with decreased HIV infection risk vs placebo or no PrEP in adults at increased HIV acquisition risk. Newer PrEP regimens are available.
OBJECTIVE
To update the 2019 review on PrEP, to inform the USPSTF.
DATA SOURCES
Ovid MEDLINE, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, and Embase (January 2018 to May 16, 2022); surveillance through March 24, 2023.
STUDY SELECTION
Randomized clinical trials of PrEP vs placebo or no PrEP or newer vs older PrEP regimens and diagnostic accuracy studies of instruments for predicting incident HIV infection.
DATA EXTRACTION AND SYNTHESIS
Dual review of titles and abstracts, full-text articles, study quality, and data abstraction. Data were pooled using the DerSimonian and Laird random-effects model.
MAIN OUTCOMES AND MEASURES
HIV acquisition, mortality, and harms; and diagnostic test accuracy.
RESULTS
Thirty-two studies were included in the review (20 randomized clinical trials [N = 36 543] and 12 studies of diagnostic accuracy [N = 5 544 500]). Eleven trials in the 2019 review found oral PrEP associated with decreased HIV infection risk vs placebo or no PrEP (n = 18 172; relative risk [RR], 0.46 [95% CI, 0.33-0.66]). Higher adherence was associated with greater efficacy. One new trial (n = 5335) found oral tenofovir alafenamide/emtricitabine (TAF/FTC) to be noninferior to tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) in men who have sex with men (RR, 0.47 [95% CI, 0.19-1.14]). Two new trials found long-acting injectable cabotegravir associated with decreased risk of HIV infection vs oral TDF/FTC (RR, 0.33 [95% CI, 0.18-0.62] in cisgender men who have sex with men and transgender women [n = 4490] and RR, 0.11 [95% CI, 0.04-0.31] in cisgender women [n = 3178]). Discrimination of instruments for predicting incident HIV infection was moderate in men who have sex with men (5 studies; n = 25 488) and moderate to high in general populations of persons without HIV (2 studies; n = 5 477 291).
CONCLUSIONS AND RELEVANCE
In adults at increased HIV acquisition risk, oral PrEP was associated with decreased risk of acquiring HIV infection compared with placebo or no PrEP. Oral TAF/FTC was noninferior to oral TDF/FTC, and injectable cabotegravir reduced the risk of HIV infection compared with oral TDF/FTC in the populations studied.
Topics: Adult; Female; Humans; Male; Administration, Oral; Anti-HIV Agents; Emtricitabine; HIV Infections; Homosexuality, Male; Injections; Practice Guidelines as Topic; Pre-Exposure Prophylaxis; Randomized Controlled Trials as Topic; Risk; Sexual and Gender Minorities; Tenofovir
PubMed: 37606667
DOI: 10.1001/jama.2023.9865 -
Current Oncology (Toronto, Ont.) Jul 2023Pancreatic cancer is the seventh leading cause of cancer deaths worldwide, accounting for 4.7% of all cancer deaths, and is expected to climb significantly over the next... (Review)
Review
Pancreatic cancer is the seventh leading cause of cancer deaths worldwide, accounting for 4.7% of all cancer deaths, and is expected to climb significantly over the next decade. The purpose of this systematic review and guidance document was to synthesize the evidence surrounding the role of adjuvant treatment (chemotherapy and chemoradiation therapy [CRT], and stereotactic body radiation therapy [SBRT]) in resected pancreatic ductal adenocarcinoma (PDAC). Systematic literature searches of MEDLINE, EMBASE, and 11 guideline databases were conducted. Both direct and indirect comparisons indicate adjuvant chemotherapy offers a survival advantage over surgery alone. The optimal regimens recommended are mFOLFIRINOX with alternative options of gemcitabine plus capecitabine, gemcitabine alone, or S-1 (which is not available in North America). Trials comparing a CRT strategy to modern chemotherapy regimens are lacking. However, current evidence demonstrates that the addition of CRT to chemotherapy does not result in a survival advantage over chemotherapy alone and is therefore not recommended. Trials evaluating SBRT in PDAC are also lacking. SBRT should only be used within a clinical trial or multi-institutional registry.
Topics: Humans; Deoxycytidine; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Pancreatic Ductal; Pancreatic Neoplasms; Chemotherapy, Adjuvant
PubMed: 37504342
DOI: 10.3390/curroncol30070482 -
Safety and Efficacy of Long-Acting Injectable Agents for HIV-1: Systematic Review and Meta-Analysis.JMIR Public Health and Surveillance Jul 2023HIV-1 infection continues to affect global health. Although antiretrovirals can reduce the viral load or prevent HIV-1 infection, current drugs require daily oral use... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
HIV-1 infection continues to affect global health. Although antiretrovirals can reduce the viral load or prevent HIV-1 infection, current drugs require daily oral use with a high adherence level. Long-acting antiretrovirals (LA-ARVs) significantly improve medication adherence and are essential for HIV-1 prophylaxis and therapy.
OBJECTIVE
This study aimed to investigate the safety and efficacy of long-acting cabotegravir (CAB-LA) and long-acting rilpivirine (RPV-LA) in the prevention and treatment of HIV-1 infection.
METHODS
PubMed, Embase, and the Cochrane Library were searched for studies from database inception to November 12, 2022. We included studies that reported efficacy and safety data on LA-ARV intervention in people living with HIV and excluded reviews, animal studies, and articles with missing or duplicate data. Virological suppression was defined as plasma viral load <50 copies/mL 6 months after antiviral therapy initiation. We extracted outcomes for analysis and expressed dichotomous data as risk ratios (RRs) and continuous data as mean differences. Depending on the heterogeneity assessment, a fixed- or random-effects model was used for data synthesis. We performed subgroup analyses of the partial safety and efficacy outcomes of CAB-LA+RPV-LA. The protocol was registered with the Open Science Framework.
RESULTS
We included 12 trials comprising 10,957 individuals, of which 7 were prevention trials and 5 were treatment trials. CAB-LA and RPV-LA demonstrated safety profiles comparable with those of the placebo in terms of adverse event-related withdrawal. Moreover, the efficacy data showed that CAB-LA had a better effect on HIV-1 prevention than tenofovir disoproxil fumarate-emtricitabine (17/5161, 0.33% vs 75/5129, 1.46%; RR 0.21, 95% CI 0.07-0.61; I=70%). Although CAB-LA+RPV-LA had more drug-related adverse events (556/681, 81.6% vs 37/598, 6.2%; RR 12.50, 95% CI 3.98-39.23; I=85%), a mild or moderate injection site reaction was the most common reaction, and its frequency decreased over time. The efficacy of CAB-LA+RPV-LA was comparable with that of daily oral drugs at 48 and 96 weeks (1302/1424, 91.43% vs 915/993, 92.2%; RR 0.99, 95% CI 0.97-1.02; I=0%), and a high level of virological suppression of 80.9% (186/230) was maintained even after 5 years of LA-ARV use. Similar efficacy outcomes were observed in both treatment-naive and treatment-experienced patients (849/911, 93.2% vs 615/654, 94%; RR 0.99, 95% CI 0.96-1.02; I=0%). According to the questionnaires, more than 85% of people living with HIV favored LA-ARVs.
CONCLUSIONS
LA-ARVs showed favorable safety profiles for both the prevention and treatment of HIV-1 infection and were well tolerated. CAB-LA has more satisfactory efficacy than tenofovir disoproxil fumarate-emtricitabine, significantly reducing the rate of HIV-1 infection. CAB-LA+RPV-LA maintains virological suppression for a long time and may be a viable switching strategy with enhanced public health benefits by reducing transmission. However, further trials are required to confirm the efficacy of these drugs.
Topics: Humans; Anti-HIV Agents; Emtricitabine; HIV Infections; HIV-1; Tenofovir
PubMed: 37498645
DOI: 10.2196/46767 -
Clinical & Translational Oncology :... Feb 2024The purpose of this meta-analysis is to evaluate the efficacy and safety of TAS-102 in treating metastatic colorectal cancer (mCRC) using the most recent data available. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
The purpose of this meta-analysis is to evaluate the efficacy and safety of TAS-102 in treating metastatic colorectal cancer (mCRC) using the most recent data available.
METHODS
The literature on the efficacy and safety of TAS-102 versus placebo and/or best supportive care (BSC) in mCRC was obtained through a systematic search of PubMed, Embase, and Web of Science databases through January 2023. Identify the included literature and extract pertinent data, such as the overall survival (OS), progression-free survival (PFS), time to treatment failure (TTF), disease control rate (DCR), incidence of adverse events (AEs) and serious adverse events (SAEs).
RESULTS
There were eight eligible articles that included 2903 patients (1964 TAS-102 versus 939 Placebo and/or BSC). In this meta-analysis, TAS-102 treatment resulted in longer OS, PFS, TTF, and higher DCR in patients with mCRC versus placebo and/or BSC. TAS-102 improved OS and PFS in subgroup analyses of mCRC patients with KRAS wild-type and KRAS mutant-type. In addition, TAS-102 did not increase the incidence of serious adverse events.
CONCLUSION
TAS-102 can enhance the prognosis of mCRC patients whose standard therapy has failed, regardless of KRAS mutation status, and its safety is acceptable.
Topics: Humans; Trifluridine; Uracil; Colorectal Neoplasms; Proto-Oncogene Proteins p21(ras); Colonic Neoplasms; Rectal Neoplasms; Drug Combinations; Antineoplastic Combined Chemotherapy Protocols; Pyrrolidines; Thymine
PubMed: 37414979
DOI: 10.1007/s12094-023-03268-5 -
JAMA Dermatology Aug 2023Chemotherapy-induced pseudocellulitis is an ill-defined term for a poorly understood phenomenon. Encompassing a myriad of cellulitis-mimicking oncologic adverse...
IMPORTANCE
Chemotherapy-induced pseudocellulitis is an ill-defined term for a poorly understood phenomenon. Encompassing a myriad of cellulitis-mimicking oncologic adverse cutaneous drug reactions (ACDRs), pseudocellulitis may be difficult to diagnosis, and the lack of treatment guidance may mean unnecessary antibiotic exposure and interruptions to oncologic care.
OBJECTIVES
To use case reports to characterize the various cellulitis-mimicking reactions caused by chemotherapeutic medications, to understand how these reactions affect patient care (ie, antibiotic exposure and interruptions to oncologic treatment), and to make recommendations for improved diagnosis and care of patients with chemotherapy-induced pseudocellulitis.
EVIDENCE REVIEW
A systematic review of case reports of patients with pseudocellulitis was performed. Reports were identified through database searches using PubMed and Embase, with subsequent reference searches. Included publications described at least 1 case of chemotherapy-induced ACDR and used the term pseudocellulitis or showed evidence of cellulitis mimicry. Cases of radiation recall dermatitis were excluded. Data were extracted from a total of 32 publications representing 81 patients diagnosed with pseudocellulitis.
FINDINGS
Of the 81 cases (median [range] age, 67 [36-80] years; 44 [54%] male patients), most were associated with gemcitabine use; pemetrexed use was reported less frequently. Only 39 were considered to be true chemotherapy-induced pseudocellulitis. These cases resembled infectious cellulitis and did not meet diagnostic criteria for any known diagnoses; therefore, these were described solely as pseudocellulitis. Of this group, 26 patients (67%) had been administered antibiotics before the correct diagnosis was made, and 14 patients (36%) experienced interruptions to their oncologic treatment plans.
CONCLUSIONS AND RELEVANCE
This systematic review found a variety of chemotherapy-induced ACDRs that mimic infectious cellulitis, including a group of reactions termed pseudocellulitis that do not meet criteria for other diagnoses. A more universally accepted definition and clinical research on chemotherapy-induced pseudocellulitis would allow for more accurate diagnosis, effective treatment, antibiotic stewardship, and continuation of oncologic treatment.
Topics: Humans; Male; Aged; Female; Deoxycytidine; Cellulitis; Antimetabolites, Antineoplastic; Gemcitabine; Drug-Related Side Effects and Adverse Reactions; Anti-Bacterial Agents
PubMed: 37379014
DOI: 10.1001/jamadermatol.2023.1735 -
Current Oncology (Toronto, Ont.) May 2023Colorectal cancer is the most prevalent gastrointestinal neoplasm. When metastatic, the disease has limited systemic treatment options. Novel targeted therapies have... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Colorectal cancer is the most prevalent gastrointestinal neoplasm. When metastatic, the disease has limited systemic treatment options. Novel targeted therapies have expanded these options for subsets with specific molecular alterations, such as microsatellite instability (MSI)-high cancers, but additional treatments and combinations are in urgent need to improve outcomes and improve survival of this incurable disease. The fluoropyrimidine-derivative trifluridine, in combination with tipiracil, has been introduced as a third-line treatment, and more recently, it was studied in combination with bevacizumab. This meta-analysis reports on studies with this combination in clinical practice outside clinical trials.
METHODS
A literature search in the Medline/PubMed and Embase databases was executed for finding series of trifluridine/tipiracil with bevacizumab in metastatic colorectal cancer. Criteria for inclusion in the meta-analysis were English or French language of the report, inclusion of twenty or more patients with metastatic colorectal cancer treated with trifluridine/tipiracil in combination with bevacizumab outside of a trial and containing information regarding response rates, progression-free survival (PFS), and overall survival (OS). Information on the demographics of the patients and on adverse effects of treatment was also collected.
RESULTS
Eight series with a total of 437 patients were eligible for the meta-analysis. The performed meta-analysis discovered a summary response rate (RR) of 2.71% (95% confidence interval (CI): 1.11-4.32%) and a disease control rate (DCR) of 59.63% (95% CI: 52.06-67.21%). Summary PFS was 4.56 months (95% CI: 3.57-5.55 months), and summary OS was 11.17 months (95% CI: 10.15-12.19 months). Common adverse effects identified mirrored the adverse-effect profile of the two components of the combination.
CONCLUSION
The current systematic review and meta-analysis reports the efficacy of trifluridine/tipiracil with bevacizumab in advanced lines of therapy for metastatic colorectal cancer in the setting of clinical practice outside clinical trials. Discovery of predictive biomarkers of response to trifluridine/tipiracil with bevacizumab will promote the tailoring of this treatment to individual patients to maximize clinical benefit.
Topics: Humans; Bevacizumab; Uracil; Colorectal Neoplasms; Trifluridine; Antineoplastic Combined Chemotherapy Protocols; Colonic Neoplasms; Rectal Neoplasms
PubMed: 37366880
DOI: 10.3390/curroncol30060397