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Cell Transplantation 2024Posttransplant lymphoproliferative disorder (PTLD) is a rare lymphoid and/or plasmocytic proliferation that occurs after allogeneic hematopoietic stem cell...
Posttransplant lymphoproliferative disorder (PTLD) is a rare lymphoid and/or plasmocytic proliferation that occurs after allogeneic hematopoietic stem cell transplantation (allo-HSCT). We aimed to identify the pathologic features and clinical outcomes of T-cell PTLD, an extremely rare subtype of PTLD, after allo-HSCT. In this study, six allo-HSCT recipients with T-cell PTLD from five transplant centers in China were enrolled. All the T-cell PTLD were donor-derived, and three patients were with monomorphic and three with polymorphic types, respectively. All patients received cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP)-based chemotherapy. Five patients achieved complete response (CR), and one experienced progressive disease (PD). The median time from HSCT to onset was 4 (range: 0.6-72) months, analyzed in combination with the other 16 patients with T-cell PTLD identified from previous reports. About 56.3% of the T-cell samples (9/16) were positive for in situ hybridization with an Epstein-Barr virus (EBV)-encoded small nuclear early region (EBER ISH). CHOP-based chemotherapy might be the optimal strategy for patients who showed no response to empiric therapy with a CR rate of 87.5%. In conclusion, our study observed that T-cell PTLD has distinct clinical manifestations and morphological features, which characterized by less relation to EBV, later occurrence, and poorer prognosis when compared with B-cell PTLD.
Topics: Humans; Hematopoietic Stem Cell Transplantation; Lymphoproliferative Disorders; Male; Female; Adult; T-Lymphocytes; Transplantation, Homologous; Adolescent; Child; Middle Aged; Young Adult; Cyclophosphamide
PubMed: 38856035
DOI: 10.1177/09636897241259722 -
Journal of Pharmaceutical Analysis May 2024The presence of -nitroso compounds, particularly -nitrosamines, in pharmaceutical products has raised global safety concerns due to their significant genotoxic and... (Review)
Review
The presence of -nitroso compounds, particularly -nitrosamines, in pharmaceutical products has raised global safety concerns due to their significant genotoxic and mutagenic effects. This systematic review investigates their toxicity in active pharmaceutical ingredients (APIs), drug products, and pharmaceutical excipients, along with novel analytical strategies for detection, root cause analysis, reformulation strategies, and regulatory guidelines for nitrosamines. This review emphasizes the molecular toxicity of -nitroso compounds, focusing on genotoxic, mutagenic, carcinogenic, and other physiological effects. Additionally, it addresses the ongoing nitrosamine crisis, the development of nitrosamine-free products, and the importance of sensitive detection methods and precise risk evaluation. This comprehensive overview will aid molecular biologists, analytical scientists, formulation scientists in research and development sector, and researchers involved in management of nitrosamine-induced toxicity and promoting safer pharmaceutical products.
PubMed: 38799236
DOI: 10.1016/j.jpha.2023.12.009 -
La Medicina Del Lavoro Apr 2024Several antiblastic drugs (ADs) are classified as carcinogenic, mutagenic, and/or toxic for reproduction. Despite established guidelines and safe handling technologies,...
Several antiblastic drugs (ADs) are classified as carcinogenic, mutagenic, and/or toxic for reproduction. Despite established guidelines and safe handling technologies, ADs contamination of the work environments could occur in healthcare settings, leading to potential exposure of healthcare staff. This systematic review aims to investigate the main techniques and practices for assessing ADs occupational exposure in healthcare settings. The reviewed studies unveil that workplace contamination by ADs appears to be a still-topical problem in healthcare settings. These issues are linked to difficulties in guaranteeing: (i) the adherence to standardized protocols when dealing with ADs, (ii) the effective use of personal protective equipment by operators involved in the administration or management of ADs, (iii) a comprehensive training of the healthcare personnel, and (iv) a thorough health surveillance of exposed workers. A "multi-parametric" approach emerges as a desirable strategy for exposure assessment. In parallel, exposure assessment should coincide with the introduction of novel technologies aimed at minimizing exposure (i.e., risk management). Assessment must consider various departments and health operators susceptible to ADs contamination, with a focus extended beyond worst-case scenarios, also considering activities like surface cleaning and logistical tasks related to ADs management. A comprehensive approach in ADs risk assessment enables the evaluation of distinct substance behaviors and subsequent exposure routes, affording a more holistic understanding of potential risks.
Topics: Humans; Occupational Exposure; Risk Assessment; Health Personnel; Drug Compounding; Personal Protective Equipment; Health Facilities
PubMed: 38686575
DOI: 10.23749/mdl.v115i2.15609 -
Toxics Apr 2024Biomonitoring of human populations exposed to chemical substances that can act as potential mutagens or carcinogens, may enable the detection of damage and early disease... (Review)
Review
Biomonitoring of human populations exposed to chemical substances that can act as potential mutagens or carcinogens, may enable the detection of damage and early disease prevention. In recent years, the comet assay has become an important tool for assessing DNA damage, both in environmental and occupational exposure contexts. To evidence the role of the comet assay in human biomonitoring, we have analysed original research studies of environmental or occupational exposure that used the comet assay in their assessments, following the PRISMA-ScR method (preferred reporting items for systematic reviews and meta-analyses extension for scoping reviews). Groups of chemicals were designated according to a broad classification, and the results obtained from over 300 original studies (n = 123 on air pollutants, n = 14 on anaesthetics, n = 18 on antineoplastic drugs, n = 57 on heavy metals, n = 59 on pesticides, and n = 49 on solvents) showed overall higher values of DNA strand breaks in the exposed subjects in comparison with the unexposed. In summary, our systematic scoping review strengthens the relevance of the use of the comet assay in assessing DNA damage in human biomonitoring studies.
PubMed: 38668493
DOI: 10.3390/toxics12040270 -
The Science of the Total Environment Jun 2024Mycotoxins are secondary metabolites produced by fungi and identified as contaminants in animal feed. They have potentially harmful effects, including carcinogenicity,... (Meta-Analysis)
Meta-Analysis
Mycotoxins are secondary metabolites produced by fungi and identified as contaminants in animal feed. They have potentially harmful effects, including carcinogenicity, mutagenicity, and repro-toxicity in animals and humans. As a result of climate change, there is the potential for a change in the prevalence and concentration of mycotoxins in animal feed components. This necessitates an assessment of the present and emerging threats to the food supply chain from mycotoxins. This systematic review and meta-analysis study synthesised studies on mycotoxin contamination and prevalence in cattle feed components. The studies were collected from scientific databases Web of Knowledge, Scopus, and Embase between 2011 and 2022. The meta-analysis synthesised 97 studies on the prevalence and the concentration of aflatoxins, ochratoxin A, deoxynivalenol, zearalenone, fumonisin and T-2/HT-2 toxins in feed components. Aflatoxin was highly prevalent (59 %), with a concentration of 2.58-3.92 μg kg in feed components. Ochratoxin A had a global prevalence of 31 % with a concentration of 5.56-12.41 μg kg. Deoxynivalenol had a global concentration of 233.17-327.73 μg kg and a prevalence of 74 %. Zearalenone had a prevalence of 70 % and a concentration of 42.47-66.19 μg kg. The concentration and prevalence of fumonisins was 232.19-393.07 μg kg and 65 %, respectively. The prevalence and concentration of T-2/HT-2 toxins were 45 % and 23.54-35.12 μg kg, respectively. The synthesised concentration of the mycotoxins in the overall feed components was lower than the regulated and guidance values set by the European Union. However, in a few cases, the 95th percentile exceeded these concentration values due to high levels of uncertainty attributed to lower sample size, and thus, need to be considered while conducting risk assessments. The study highlights climates and regions likely to be conducive to the emergence of mycotoxin risk, especially considering the potential influences of climate change.
Topics: Animal Feed; Mycotoxins; Animals; Food Contamination; Cattle; Aflatoxins
PubMed: 38608906
DOI: 10.1016/j.scitotenv.2024.172323 -
BMC Cancer Apr 2024Triple-negative breast cancer (TNBC) is a life-threatening subtype of breast cancer with limited treatment options. Therefore, this network meta-analysis (NMA) aimed to... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Triple-negative breast cancer (TNBC) is a life-threatening subtype of breast cancer with limited treatment options. Therefore, this network meta-analysis (NMA) aimed to evaluate and compare the effect of various neoadjuvant chemotherapy (NCT) options on the long-term survival of patients with TNBC.
METHODS
PubMed, Embase, Medline, Cochrane Library, Web of Science, and major international conference databases were systematically searched for randomized controlled trials (RCTs) on the efficacy of various NCT options in patients with TNBC. Searches were performed from January 2000 to June 2023. Study heterogeneity was assessed using the I statistic. Hazard ratios (HRs) and 95% confidence intervals (CIs) were used to evaluate disease-free survival (DFS) and overall survival (OS). Odds ratios (ORs) and 95% CIs were used to evaluate the pathologic complete response (pCR). The primary outcome was DFS.
RESULTS
We conducted an NMA of 21 RCTs involving 8873 patients with TNBC. Our study defined the combination of anthracyclines and taxanes as the preferred treatment option. On this basis, the addition of any of the following new drugs is considered a new treatment option: bevacizumab (B), platinum (P), poly-ADP-ribose polymerase inhibitors (PARPi), and immune checkpoint inhibitor (ICI). Based on the surface under the cumulative ranking curve (SUCRA) values, the top three SUCRA area values of DFS were taxanes, anthracycline, and cyclophosphamide (TAC; 89.23%); CT (84.53%); and B (81.06%). The top three SUCRA area values of OS were CT (83.70%), TAC (62.02%), and B-containing regimens (60.06%). The top three SUCRA area values of pCR were B + P-containing regimens (82.7%), ICI + P-containing regimens (80.2%), and ICI-containing regimens (61.8%).
CONCLUSIONS
This NMA showed that standard chemotherapy is a good choice with respect to long-term survival. Moreover, B associated with P-containing regimens is likely to be the optimal treatment option for neoadjuvant TNBC in terms of pCR.
Topics: Humans; Triple Negative Breast Neoplasms; Neoadjuvant Therapy; Network Meta-Analysis; Taxoids; Cyclophosphamide; Antibiotics, Antineoplastic; Anthracyclines; Antineoplastic Combined Chemotherapy Protocols
PubMed: 38594636
DOI: 10.1186/s12885-024-12222-9 -
BMC Endocrine Disorders Jan 2024To evaluate the efficacy and safety of combined glucocorticoids (GCs) and cyclophosphamide (CYC) treatment in Graves' ophthalmopathy (GO). (Meta-Analysis)
Meta-Analysis
PURPOSE
To evaluate the efficacy and safety of combined glucocorticoids (GCs) and cyclophosphamide (CYC) treatment in Graves' ophthalmopathy (GO).
METHODS
We searched PubMed, Embase, Cochrane Library, and four Chinese databases (Chinese National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database (VIP), WanFang, and SinoMed) for any published randomized controlled trials (RCTs) produced from inception to December 1, 2023. Articles obtained using appropriate keywords were selected independently by two reviewers according to the established inclusion and exclusion criteria.
FINDINGS
We retrieved 1120 records which were eventually reduced to 13 RCTs which were then included in this evaluation. Pooled results indicated that the experimental group (CYC/GCs) showed a higher response rate than control group (GCs or negative control) (RR 1.27; 95% confidence interval 1.19 to 1.37). The subgroup analysis showed that the difference in response rates among treatment protocols (CYC/P, CYC/MPS, CYC/DEX) was not statistically significant (p = 0.23).
IMPLICATIONS
The combination of GCs and CYC could be recommended as a therapeutic option for GO, especially in patients who experience recurrence after a withdrawal GCs, have a poor response to GCs, or cannot obtain monoclonal antibody agents for various reasons.
Topics: Humans; Glucocorticoids; Graves Ophthalmopathy; Cyclophosphamide; China
PubMed: 38273269
DOI: 10.1186/s12902-024-01545-0 -
Scientific Reports Jan 2024We aimed to summarize the cancer risk among patients with indication of group I pharmaceuticals as stated in monographs presented by the International Agency for... (Meta-Analysis)
Meta-Analysis
We aimed to summarize the cancer risk among patients with indication of group I pharmaceuticals as stated in monographs presented by the International Agency for Research on Cancer working groups. Following the PRISMA guidelines, a comprehensive literature search was conducted using the PubMed database. Pharmaceuticals with few studies on cancer risk were identified in systematic reviews; those with two or more studies were subjected to meta-analysis. For the meta-analysis, a random-effects model was used to calculate the summary relative risks (SRRs) and 95% confidence intervals (95% CIs). Heterogeneity across studies was presented using the Higgins I square value from Cochran's Q test. Among the 12 group I pharmaceuticals selected, three involved a single study [etoposide, thiotepa, and mustargen + oncovin + procarbazine + prednisone (MOPP)], seven had two or more studies [busulfan, cyclosporine, azathioprine, cyclophosphamide, methoxsalen + ultraviolet (UV) radiation therapy, melphalan, and chlorambucil], and two did not have any studies [etoposide + bleomycin + cisplatin and treosulfan]. Cyclosporine and azathioprine reported increased skin cancer risk (SRR = 1.32, 95% CI 1.07-1.62; SRR = 1.56, 95% CI 1.25-1.93) compared to non-use. Cyclophosphamide increased bladder and hematologic cancer risk (SRR = 2.87, 95% CI 1.32-6.23; SRR = 2.43, 95% CI 1.65-3.58). Busulfan increased hematologic cancer risk (SRR = 6.71, 95% CI 2.49-18.08); melphalan was associated with hematologic cancer (SRR = 4.43, 95% CI 1.30-15.15). In the systematic review, methoxsalen + UV and MOPP were associated with an increased risk of skin and lung cancer, respectively. Our results can enhance persistent surveillance of group I pharmaceutical use, establish novel clinical strategies for patients with indications, and provide evidence for re-categorizing current group I pharmaceuticals into other groups.
Topics: Humans; Etoposide; Methoxsalen; Azathioprine; Melphalan; Busulfan; Neoplasms; Hematologic Neoplasms; Cyclophosphamide; Cyclosporins; Pharmaceutical Preparations
PubMed: 38172159
DOI: 10.1038/s41598-023-50602-6 -
Supportive Care in Cancer : Official... Dec 2023This systematic review updates the MASCC/ESMO recommendations for high-emetic-risk chemotherapy (HEC) published in 2016-2017. HEC still includes cisplatin, carmustine,...
PURPOSE
This systematic review updates the MASCC/ESMO recommendations for high-emetic-risk chemotherapy (HEC) published in 2016-2017. HEC still includes cisplatin, carmustine, dacarbazine, mechlorethamine, streptozocin, and cyclophosphamide in doses of > 1500 mg/m and the combination of cyclophosphamide and an anthracycline (AC) in women with breast cancer.
METHODS
A systematic review report following the PRISMA guidelines of the literature from January 1, 2015, until February 1, 2023, was performed. PubMed (Ovid), Scopus (Google), and the Cochrane Database of Systematic Reviews were searched. The literature search was limited to randomized controlled trials, systematic reviews, and meta-analyses.
RESULTS
Forty-six new references were determined to be relevant. The main topics identified were (1) steroid-sparing regimens, (2) olanzapine-containing regimens, and (3) other issues such as comparisons of antiemetics of the same drug class, intravenous NK receptor antagonists, and potentially new antiemetics. Five updated recommendations are presented.
CONCLUSION
There is no need to prescribe steroids (dexamethasone) beyond day 1 after AC HEC, whereas a 4-day regimen is recommended in non-AC HEC. Olanzapine is now recommended as a fixed part of a four-drug prophylactic antiemetic regimen in both non-AC and AC HEC. No major differences between 5-HT receptor antagonists or between NK receptor antagonists were identified. No new antiemetic agents qualified for inclusion in the updated recommendations.
Topics: Female; Humans; Emetics; Antiemetics; Consensus; Olanzapine; Nausea; Vomiting; Antineoplastic Agents; Cyclophosphamide; Anthracyclines
PubMed: 38127246
DOI: 10.1007/s00520-023-08221-4 -
Renal Failure 2023This study was to assess the safety and effectiveness of immunosuppressive agents, specifically Voclosporin, when used in conjunction with mycophenolate mofetil (MMF)... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
This study was to assess the safety and effectiveness of immunosuppressive agents, specifically Voclosporin, when used in conjunction with mycophenolate mofetil (MMF) induction therapy for the management of lupus nephritis (LN).
METHODS
A systematic review and network meta-analysis (NMA) was conducted on randomized controlled trials investigating the efficacy of immunosuppressant-induced therapy for LN. The random effects model was used in the analysis. I was used to evaluate the heterogeneity of the model. Odds ratios (OR) and 95% credible intervals (CrI) were computed to assess and compare the relative effectiveness and safety of various treatment protocols.
RESULTS
The study included a total of 16 randomized controlled trials (RCTs) involving 2444 patients with LN. The analysis results indicated that there was no significant difference in terms of partial remission (PR) between the drugs. However, when considering complete remission (CR), the combination of Voclosporin with MMF showed the highest remission rate, followed by Tacrolimus (TAC). Unfortunately, Voclosporin in combination with MMF had the highest risk of infection and serious infection, indicating a lower safety profile.
CONCLUSIONS
Voclosporin in combination with MMF demonstrated the highest efficacy as an induction therapy for LN. However, it should be noted that the risk of infection and serious infection was found to be high with this regimen. On the other hand, TAC not only showed efficacy but also had a lower risk of infection and serious infection, making it a favorable option in terms of safety. This study did' not include results on other adverse events.
Topics: Humans; Lupus Nephritis; Cyclophosphamide; Induction Chemotherapy; Network Meta-Analysis; Treatment Outcome; Immunosuppressive Agents; Tacrolimus; Mycophenolic Acid; Remission Induction; Randomized Controlled Trials as Topic
PubMed: 38087473
DOI: 10.1080/0886022X.2023.2290365