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BMC Gastroenterology Jun 2023In metastatic pancreatic ductal adenocarcinoma (mPDAC), first line treatment options usually include combination regimens of folinic acid, 5-fluorouracil (5-FU),... (Meta-Analysis)
Meta-Analysis
BACKGROUND
In metastatic pancreatic ductal adenocarcinoma (mPDAC), first line treatment options usually include combination regimens of folinic acid, 5-fluorouracil (5-FU), irinotecan, and oxaliplatin (FOLFIRINOX or mFOLFIRINOX) or gemcitabine based regimens such as in combination with albumin-bound paclitaxel (GEM + nab-PTX). After progression, multiple regimens including NALIRI + 5-FU and folinic acid, FOLFIRINOX, 5-FU-based oxaliplatin doublets (OFF, FOLFOX, or XELOX), or 5-FU-based monotherapy (FL, capecitabine, or S-1) are considered appropriate by major guidelines. This network meta-analysis (NMA) aimed to compare the efficacy of different treatment strategies tested as second-line regimens for patients with mPDAC after first-line gemcitabine-based systemic treatment.
METHODS
Randomized phase II and III clinical trials (RCTs) were included if they were published or presented in English. Trials of interest compared two active systemic treatments as second-line regimens until disease progression or unacceptable toxicity. We performed a Bayesian NMA with published hazard ratios (HRs) and 95%confidence intervals (CIs) to evaluate the comparative effectiveness of different second-line therapies for mPDAC. The main outcomes of interest were overall survival (OS) and progression free survival (PFS), secondary endpoints were grade 3-4 toxicities. We calculated the relative ranking of agents for each outcome as their surface under the cumulative ranking (SUCRA). A higher SUCRA score meant a higher ranking for efficacy outcomes.
RESULTS
A NMA of 9 treatments was performed for OS (n = 2521 patients enrolled). Compared with 5-FU + folinic acid both irinotecan or NALIRI + fluoropyrimidines had a trend to better OS (HR = 0.76, 95%CI 0.21-2.75 and HR = 0.74, 95%CI 0.31-1.85). Fluoropyrimidines + folinic acid + oxaliplatin were no better than the combination without oxaliplatin. The analysis of treatment ranking showed that the combination of NALIRI + 5-FU + folinic acid was most likely to yield the highest OS results (SUCRA = 0.7). Furthermore, the NMA results indicated that with the highest SUCRA score (SUCRA = 0.91), NALIRI + 5-FU + folinic acid may be the optimal choice for improved PFS amongst all regimens studied.
CONCLUSIONS
According to the NMA results, NALIRI + 5-FU, and folinic acid may represent the best second-line treatment for improved survival outcomes in mPDAC. Further evidence from prospective trials is needed to determine the best treatment option for this group of patients.
Topics: Humans; Pancreatic Neoplasms; Irinotecan; Antineoplastic Combined Chemotherapy Protocols; Oxaliplatin; Leucovorin; Network Meta-Analysis; Bayes Theorem; Prospective Studies; Fluorouracil; Clinical Trials, Phase II as Topic; Randomized Controlled Trials as Topic
PubMed: 37337148
DOI: 10.1186/s12876-023-02853-w -
International Immunopharmacology Mar 2021Pemphigus encompasses a rare heterogeneous group of autoimmune blistering diseases characterized by cutaneous and/or mucosal blistering. Multiple factors, such as some...
Pemphigus encompasses a rare heterogeneous group of autoimmune blistering diseases characterized by cutaneous and/or mucosal blistering. Multiple factors, such as some specific types of drugs, have been found to be involved in the induction of pemphigus. Here, we have designed a systematic review by searching PubMed/Medline and Embase databases to find the drugs, involved in pemphigus induction and exacerbation (updated on 19 August 2019). From 1856 initially found articles, 134 studies (198 patients; 170 patients in the drug-induced patients and 28 in exacerbation group) have been included. Regarding drug-induced cases, the mean age was 57.19 ± 16.9-year-old (ranged 8-105), and patients had developed pemphigus within a mean of 154.27 days. Pemphigus vulgaris (38.9%), pemphigus foliaceus (33.5%), and paraneoplastic pemphigus (3.6%) were the most common subtypes. Furthermore, penicillamine (33.1%), captopril (7.7%), and bucillamine (6.5%) were the most reported drugs related to pemphigus induction; penicillamine was associated with the most persistent disease. Regardless of disease subtype, cutaneous, mucocutaneous, and mucosal involvements were reported in 68.6%, 30.1%, and 1.3% of patients, respectively. In total, the IgG deposition in the pathological studies, being positive for autoreactive antibodies in the serum against desmoglein 3 (Dsg3), and desmoglein 1 (Dsg1), were reported in 93%, 34.9%, and 72.7% of reported patients, respectively. Regarding the management of such patients, in 75% of healed cases, treatment (mainly transient systemic and topical corticosteroids and/or azathioprine) was needed besides stopping the probable pemphigus-inducing culprit drug, while drug cessation was enough to control the disease in 25%. As the outcomes, the lesions in 129 of 147 (87.8%) patients had been healed, while in 18 (12.2%), no healing was reported; fifteen out of 18 had died. In conclusion, some specific groups of treatments can induce pemphigus, including penicillamine, captopril, and bucillamine; despite the similar clinical and pathological manifestations to classical pemphigus, most of the cases are less severe and have a better prognosis.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Antihypertensive Agents; Antirheumatic Agents; Captopril; Cysteine; Drug-Related Side Effects and Adverse Reactions; Humans; Pemphigus; Penicillamine
PubMed: 33418246
DOI: 10.1016/j.intimp.2020.107299 -
Molecules (Basel, Switzerland) May 2023Advanced carbon nanomaterials have been widely applied in various fields such as microelectronics, energy storage, catalysis, adsorption, biomedical engineering, and... (Review)
Review
Advanced carbon nanomaterials have been widely applied in various fields such as microelectronics, energy storage, catalysis, adsorption, biomedical engineering, and material strengthening. With the increasing demand for porous carbon nanomaterials, many studies have explored obtaining porous carbon nanomaterials from biomass, which is highly abundant. Pomelo peel, a type of biomass rich in cellulose and lignin, has been widely upgraded into porous carbon nanomaterials with large yield and significant applications. Here, we systematically review the recent progress in pyrolysis, activation, and applications of synthesizing porous carbon nanomaterials from waste pomelo peels. Moreover, we provide a perspective on the remaining challenges and potential future research directions.
Topics: Carbon; Charcoal; Porosity; Lignin; Nanostructures
PubMed: 37298905
DOI: 10.3390/molecules28114429 -
Frontiers in Pharmacology 2022N-Acetylcysteine (NAC) is used as an antidote in acetaminophen (APAP) overdose to prevent and mitigate drug-induced liver injury (DILI). Our objective was to...
N-Acetylcysteine (NAC) is used as an antidote in acetaminophen (APAP) overdose to prevent and mitigate drug-induced liver injury (DILI). Our objective was to systematically review evidence of the use of NAC as a therapeutic option for APAP overdose and APAP-related DILI in order to define the optimal treatment schedule and timing to start treatment. Bibliographic databases (PubMed, Web of Science, Embase, and MEDLINE) were searched for retrospective and prospective cohort studies, case series, and clinical trials. The prespecified primary outcomes were DILI-related mortality, hepatotoxicity, and adverse events (AEs). In total, 34 studies of NAC usage in APAP-related DILI cases with 19,580 patients were identified, of which 2,376 patients developed hepatotoxicities. The mortality rate across different studies ranged from 0 to 52%. Large variability of NAC regimens was found, i.e., intravenous (I.V.) (100-150 mg/kg) and oral (70-140 mg/kg), and length of treatment varied-12, 24, or 48 h for I.V. regimen and 72 h for oral administration. The timing of initiation of NAC treatment showed different results in terms of occurrence of hepatotoxicity and mortality; if started within 8 h and no more than 24 h from APAP overdose, either intravenously or orally, NAC administration was efficacious in terms of mortality. The most frequent AEs reported were anaphylactic reactions, followed by cutaneous AEs for the IV route and intestinal AEs for the oral one. NAC improves hepatotoxicity and reduces mortality. Timing of treatment, ranging from 8 to 24 h from APAP overdose, regardless of the regimen or route of administration, is important to prevent or minimize liver damage, particularly in children and in elderly and obese patients.
PubMed: 36034775
DOI: 10.3389/fphar.2022.828565 -
Annals of Surgical Oncology Jul 2024Treatment of unresectable colorectal liver metastases (UCRLM) includes locoregional and systemic therapy. A comprehensive analysis capturing long-term outcomes of these... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Treatment of unresectable colorectal liver metastases (UCRLM) includes locoregional and systemic therapy. A comprehensive analysis capturing long-term outcomes of these treatment options has not been performed.
OBJECTIVE
A systematic review and meta-analysis was performed to calculate pooled outcomes of hepatic artery infusion with systemic chemotherapy (HAI-S), transarterial chemoembolization with systemic chemotherapy (TACE-S), transarterial radioembolization with systemic chemotherapy (TARE-S), doublet (FOLFOX, FOLFIRI), and triplet chemotherapy (FOLFOXIRI).
METHODS
Outcomes included overall survival (OS), progression-free survival (PFS), rate of conversion to resection (CTR), and response rate (RR).
RESULTS
A total of 32, 7, 9, and 14 publications were included in the HAI-S, TACE-S, and TARE-S chemotherapy arms. The 6/12/24/36-month OS estimates for HAI-S, TACE-S, TARE-S, FOLFOX, FOLFIRI, and FOLFOXIRI were 97%/80%/54%/35%, 100%/83%/40%/14%, 82%/61%/34%/21%, 96%/83%/53%/36%, and 96%/93%/72%/55%. Similarly, the 6/12/24/36-month PFS estimates were 74%/44%/19%/14%, 66%/20%/9%/3%, 57%/23%/10%/3%, 69%/30%/12%/7%, and 88%/55%/18%/11%. The corresponding CTR and RR rates were 31, 20%, unmeasurable (TARE-S), 35, 53; and 49, 45, 45, 50, 80%, respectively. The majority of chemotherapy studies included first-line therapy and liver-only metastases, whereas most HAI-S studies were pretreated. On subgroup analysis in first-line setting with liver-only metastases, the HAI-S arm had comparable outcomes to FOLFOXIRI and outperformed doublet chemotherapy regimens. Although triplet chemotherapy appeared to outperform other arms, high toxicity and inclusion of potentially resectable patients must be considered while interpreting results.
CONCLUSIONS
HAI-S and multiagent chemotherapy are effective therapies for UCRLM. To make definitive conclusions, a randomized trial with comparable patient characteristics and line of therapy will be required. The upcoming EA2222 PUMP trial may help to address this question.
Topics: Humans; Liver Neoplasms; Colorectal Neoplasms; Hepatic Artery; Antineoplastic Combined Chemotherapy Protocols; Chemoembolization, Therapeutic; Infusions, Intra-Arterial; Survival Rate; Prognosis; Fluorouracil; Leucovorin
PubMed: 38502296
DOI: 10.1245/s10434-024-15187-y -
World Journal of Urology Nov 2023To perform a systematic review of case reports and case series to investigate risk factors, treatment modalities, and the outcome of penile calciphylaxis.
PURPOSE
To perform a systematic review of case reports and case series to investigate risk factors, treatment modalities, and the outcome of penile calciphylaxis.
METHOD
We performed a systematic search of the MEDLINE and Scopus databases to identify case reports or case series of penile calciphylaxis. The patient characteristics, laboratory investigations, diagnostic modalities, treatment modalities, and outcomes were extracted. We compared clinical characteristics and treatment between patients who survived or demised and between patients with clinical improvement and those without to identify the poor prognostic risk factors.
RESULTS
Ninety-four articles were included from 86 case reports and 8 case series with 121 patients. Most of the patients were on hemodialysis (78.9%). The median time since starting dialysis was 48 months (24-96 months). Sodium thiosulfate was used to treat penile calciphylaxis in 23.6%. For surgical management, partial or total penectomy was performed in 45.5% of the patients. There was no association between sodium thiosulfate use, partial or total penectomy, and improvement in clinical outcomes. The mortality rate in patients with penile calciphylaxis was 47.8% and the median time to death was 3 months (0.75-9 months). The presence of extragenital involvement was significantly related to mortality (p = 0.03).
CONCLUSION
A calcified penile artery results in penile calciphylaxis, a rare vascular phenomenon associated with high morbidity and mortality. Management of penile calciphylaxis includes the medical management of risk factors, surgical debridement, or penectomy. Therefore, early prevention and diagnosis as well as immediate appropriate treatment are needed.
Topics: Humans; Male; Calciphylaxis; Kidney Failure, Chronic; Penis; Risk Factors; Thiosulfates; Case Reports as Topic
PubMed: 37782324
DOI: 10.1007/s00345-023-04611-9 -
Thrombosis Research Dec 2020Direct thrombin inhibitor, dabigatran and factor Xa inhibitors, apixaban, edoxaban, and rivaroxaban (DOACs/NOACs), are currently the first-choice drugs in some... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Direct thrombin inhibitor, dabigatran and factor Xa inhibitors, apixaban, edoxaban, and rivaroxaban (DOACs/NOACs), are currently the first-choice drugs in some indications. Life-threatening bleeding occurring during DOACs treatment may benefit from the use of reversal agents, however there are some concerns regarding potential rebound thrombotic events. In this systematic review we aimed to estimate the incidence of thrombotic events in patients treated with idarucizumab or andexanet alfa.
METHODS
This systematic review included all prospective and retrospective studies, enrolling patients that received specific antidotes (idarucizumab, andexanet alfa and cirapantag) for anticoagulation reversal, published until October 2019 in CENTRAL, MEDLINE and PsycINFO. Studies in healthy individuals and those with less than 10 patients were excluded. The primary outcome was the incidence of thrombotic events and the secondary outcome was all-cause mortality. Studies screening and data extraction was performed in duplicate by reviewers. A random-effects meta-analysis was performed using the Freeman-Tukey transformation of the data. The results are expressed in percentages, with 95%-confidence intervals (CI), limited between 0 and 100% due to the data transformation.
RESULTS
Overall 16 studies with 1774 patients were included (13 studies enrolling 1384 patients that received idarucizumab; 3 studies enrolling 390 patients that received andexanet alfa; cirapantag studies were not found). The pooled incidence rate of thrombotic events in the patients treated with specific antidote was 5.5% (95% CI 2.0-10.1%) until 30-90 days. The incidence of all-cause mortality was 13.3% (95% CI 9.6-17.5%).
CONCLUSIONS
In patients requiring idarucizumab or andexanet alfa to reach haemostasis, our data shows that there were 5.5% thrombotic events. The causality of harm associated to antidotes remains to be established due to the design of studies without a control group.
Topics: Administration, Oral; Antibodies, Monoclonal, Humanized; Anticoagulants; Antidotes; Factor Xa; Factor Xa Inhibitors; Humans; Incidence; Prospective Studies; Recombinant Proteins; Retrospective Studies
PubMed: 32949961
DOI: 10.1016/j.thromres.2020.09.003 -
Journal of Hazardous Materials Feb 2022Biochar, a carbonaceous material with engineering potential, has gained attention as an efficient catalyst in persulfate-based advanced oxidation processes (PS-AOPs).... (Review)
Review
Biochar, a carbonaceous material with engineering potential, has gained attention as an efficient catalyst in persulfate-based advanced oxidation processes (PS-AOPs). Although biomass feedstocks are known as a critical factor for the performance of biochar, the relationship between the catalytic efficiency/mechanism and the types of biomass feedstocks is still unclear. Thus, according to recent advances in experimental and theoretical researches, this paper provides a systematic review of the properties of biochar, and the relationship between catalytic performance in PS-AOPs and biomass feedstocks, where the differences in physicochemical properties (surface properties, pore structure, etc.) and activation path of different sourced biochars, are introduced. In addition, how the tailoring of biochar (such as heteroatomic doping and co-pyrolysis of biomass) affects its activation efficiency and mechanism in PS-AOPs is summarized. Finally, the suitable application scenarios or systems of different sourced biochars, appropriate methods to improve the catalytic performance of different types of biochar and the prospects and challenges for the development of biochar in PS-AOPs are proposed.
Topics: Biomass; Catalysis; Charcoal; Pyrolysis
PubMed: 34799169
DOI: 10.1016/j.jhazmat.2021.127663 -
International Journal of Environmental... Oct 2022Occupational exposure may involve a variety of toxic compounds. A mutagenicity analysis using the Ames test can provide valuable information regarding the toxicity of... (Review)
Review
Occupational exposure may involve a variety of toxic compounds. A mutagenicity analysis using the Ames test can provide valuable information regarding the toxicity of absorbed xenobiotics. Through a search of relevant databases, this systematic review gathers and critically discusses the published papers (excluding other types of publications) from 2001-2021 that have assessed urinary mutagenicity (Ames test with ) in an occupational exposure context. Due to the heterogeneity of the study methods, a meta-analysis could not be conducted. The characterized occupations were firefighters, traffic policemen, bus drivers, mail carriers, coke oven and charcoal workers, chemical laboratory staff, farmers, pharmacy workers, and professionals from several other industrial sectors. The genetically modified bacterial strains (histidine dependent) TA98, TA100, YG1041, YG1021, YG1024 and YG1042 have been used for the health risk assessment of individual (e.g., polycyclic aromatic hydrocarbons) and mixtures of compounds (e.g., diesel engine exhaust, fire smoke, industrial fumes/dyes) in different contexts. Although comparison of the data between studies is challenging, urinary mutagenicity can be very informative of possible associations between work-related exposure and the respective mutagenic potential. Careful interpretation of results and their direct use for occupational health risk assessment are crucial and yet complex; the use of several strains is highly recommended since individual and/or synergistic effects of complex exposure to xenobiotics can be overlooked. Future studies should improve the methods used to reach a standardized protocol for specific occupational environments to strengthen the applicability of the urinary mutagenicity assay and reduce inter- and intra-individual variability and exposure source confounders.
Topics: Humans; Mutagens; Mutagenicity Tests; Coke; Charcoal; Histidine; Vehicle Emissions; Polycyclic Aromatic Hydrocarbons; Smoke; Coloring Agents
PubMed: 36293654
DOI: 10.3390/ijerph192013074 -
European Review For Medical and... Sep 2022Multi-agent regimens such as Folfirinox and gemcitabine plus nab-paclitaxel have shown significant improvements compared with single-agent gemcitabine as neoadjuvant... (Meta-Analysis)
Meta-Analysis
Efficacy and safety of neoadjuvant Folfirinox and Gemcitabine plus Nab-Paclitaxel for borderline resectable and locally advanced pancreatic cancer: a systematic review and meta-analysis.
OBJECTIVE
Multi-agent regimens such as Folfirinox and gemcitabine plus nab-paclitaxel have shown significant improvements compared with single-agent gemcitabine as neoadjuvant chemotherapy for patients with borderline resectable or locally advanced pancreatic cancer. However, the efficacy and safety of Folfirinox and GNP as NAC for BRPC and LAPC is still controversial.
MATERIALS AND METHODS
The eligible studies including prospective, retrospective, and randomized controlled trial related to Folfirinox and GNP as NAC for patients with BRPC or LAPC up to March 2022 were searched and assessed. Pooled analysis for chemotherapy response rate, resection rate, R0 resection rate, progress free survival, overall survival, and grade 3/4 events of toxicity were performed in the study.
RESULTS
Eight studies were included in this meta-analysis. Compared with GNP, Folfirinox had higher resection rate (HR=0.82; 95% CI 0.59-1.14) and R0 resection rate (HR=0.77; 95% CI 0.60-0.97), better PFS (HR=0.78; 95% CI 0.55-1.12) and OS (HR=0.68; 95% CI 0.46-0.99), and without increasing severe toxicity rate (HR=0.95; 95% CI 0.71-1.28). There are no differences in rate of stable disease (HR=1.06; 95% CI 0.92-1.22) and partial/complete regression (HR=0.85; 95% CI 0.59-1.23) between two groups.
CONCLUSIONS
Higher resection and R0 resection rate and better PFS and OS results were obtained in Folfirinox group compared with GNP group for patients with BRPC and LAPC. There was no increased severe toxicity rate for Folfirinox compared with GNP.
Topics: Albumins; Antineoplastic Combined Chemotherapy Protocols; Deoxycytidine; Fluorouracil; Humans; Irinotecan; Leucovorin; Neoadjuvant Therapy; Oxaliplatin; Paclitaxel; Pancreatic Neoplasms; Prospective Studies; Retrospective Studies; Gemcitabine
PubMed: 36111933
DOI: 10.26355/eurrev_202209_29656