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Clinical Lymphoma, Myeloma & Leukemia Apr 2024Chimeric Antigen Receptor T-cell (CAR T-cell) therapy is an effective treatment for relapsed/refractory (R/R) large B cell lymphoma (LBCL). However, patients with... (Meta-Analysis)
Meta-Analysis Review
Chimeric Antigen Receptor T-cell (CAR T-cell) therapy is an effective treatment for relapsed/refractory (R/R) large B cell lymphoma (LBCL). However, patients with central nervous system (CNS) lymphoma were excluded in most of the CAR T-cell therapy trials. This meta-analysis assesses the efficacy with CAR T-cell therapy in LBCL patients with CNS involvement. Two reviewers independently searched PubMed and Cochrane Library to identify all published literature associated with United States Food and Drug Administration approved CAR T-cell therapies for LBCL. Patients with CNS LBCL were included. Meta-analysis of proportion was performed to evaluate the overall response (ORR), complete response (CR) for efficacy, and cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome for safety assessment. Nineteen studies were qualified for inclusion with 141 CNS LBCL patients. The ORR and CR rates were 61% and 55% respectively. The median overall survival (OS) was 8.8 months, and the median progression free survival (PFS) was 4.4 months. Severe immune effector cell-associated neurotoxicity syndrome (grade≥3) were reported in 25% (32/130) patients and severe cytokine release syndrome (grade≥3) were found in 10% (13/124) of the patients. The safety and efficacy of CAR T-cell therapy in CNS LBCL patients appears comparable to patients without CNS involvement.
Topics: Humans; Immunotherapy, Adoptive; Receptors, Chimeric Antigen; Cytokine Release Syndrome; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Neurotoxicity Syndromes; Central Nervous System; Cell- and Tissue-Based Therapy; Antigens, CD19
PubMed: 38267353
DOI: 10.1016/j.clml.2023.12.012 -
Frontiers in Medicine 2023Acute carbon monoxide poisoning (COP) is one of the leading causes of intoxication among patients presenting to the emergency department (ED). COP symptoms are not...
INTRODUCTION
Acute carbon monoxide poisoning (COP) is one of the leading causes of intoxication among patients presenting to the emergency department (ED). COP symptoms are not always specific and may vary from mild to critical. In the last few years, COHb pulse oximeters have been developed and applied to the setting of suspected COP. The aim of this systematic review is to assess the diagnostic accuracy of CO pulse oximetry (SpCO) with carboxyhemoglobin (COHb) levels measured by blood gas analysis, used as a reference standard, in patients with suspected COP.
METHODS
We developed our search strategy according to the PICOS framework, population, index/intervention, comparison, outcome, and study, considering the diagnostic accuracy of SpCO compared to COHb levels measured by blood gas analysis, used as a reference standard, in patients with suspected COP enrolled in cross-sectional studies in English. The search was performed on MEDLINE/PubMed and EMBASE in February 2022. Quality assessment was performed using the QUADAS-2 methodology. A COHb cutoff of 10% was chosen to test the sensitivity and specificity of the index test. A bivariate model was used to perform the meta-analysis. The protocol was registered on PROSPERO (CRD42022359144).
RESULTS
A total of six studies (1734 patients) were included. The pooled sensitivity of the test was 0.65 (95% CI 0.44-0.81), and the pooled specificity was 0.93 (95% CI 0.83-0.98). The pooled LR+ was 9.4 (95% CI 4.4 to 20.1), and the pooled LR- was 0.38 (95% CI 0.24 to 0.62).
CONCLUSION
Our results show that SpCO cannot be used as a screening tool for COP in the ED due to its low sensitivity. Because of its high LR+, it would be interesting to evaluate, if SpCO could have a role in the prehospital setting as a tool to quickly identify COP patients and prioritize their transport to specialized hospitals on larger samples with a prospective design.
PubMed: 38223786
DOI: 10.3389/fmed.2023.1250845 -
The Science of the Total Environment Mar 2024Elevations in antibiotic resistance genes (ARGs) are due not only to the antibiotic burden, but also to numerous environmental pressures (e.g., pesticides, metal ions,... (Review)
Review
Elevations in antibiotic resistance genes (ARGs) are due not only to the antibiotic burden, but also to numerous environmental pressures (e.g., pesticides, metal ions, or psychotropic pharmaceuticals), which have led to an international public health emergency. Metal-based nanoparticles (MNPs) poison bacteria while propelling nanoresistance at ambient or sub-lethal concentrations, acting as a wide spectrum germicidal agent. Awareness of MNPs driven antibiotic resistance has created a surge of investigation into the molecule mechanisms of evolving and spreading environmental antibiotic resistome. Co-occurrence of MNPs resistance and antibiotic resistance emerge in environmental pathogens and benign microbes may entail a crucial outcome for human health. In this review we expound on the systematic mechanism of ARGs proliferation under the stress of MNPs, including reactive oxygen species (ROS) induced mutation, horizontal gene transfer (HGT) relevant genes regulation, nano-property, quorum sensing, and biofilm formation and highlighting on the momentous contribution of nanoparticle released ion. As antibiotic resistance pattern alteration is closely knit with the mediate activation of nanoparticle in water, soil, manure, or sludge habitats, we have proposed a virulence and evolution based antibiotic resistance risk assessment strategy for MNP contaminated areas and discussed practicable approaches that call for risk management in critical environmental compartments.
Topics: Humans; Drug Resistance, Microbial; Bacteria; Genes, Bacterial; Anti-Bacterial Agents; Metal Nanoparticles
PubMed: 38220012
DOI: 10.1016/j.scitotenv.2024.170080 -
Journal of Ethnopharmacology May 2024Traditional plant-based medicines (TMs) have been widely used to prevent chronic oxaliplatin-induced peripheral neurotoxicity (OIPN). However, the prevention and safety... (Meta-Analysis)
Meta-Analysis
Efficacy and safety of traditional plant-based medicines for preventing chronic oxaliplatin-induced peripheral neurotoxicity in patients with colorectal cancer: A systematic review and meta-analysis with core herb contribution.
ETHNOPHARMACOLOGICAL RELEVANCE
Traditional plant-based medicines (TMs) have been widely used to prevent chronic oxaliplatin-induced peripheral neurotoxicity (OIPN). However, the prevention and safety of TMs for chronic OIPN remain ambiguous. Furthermore, diverse TM prescriptions and complicated components limit in-depth research on the mechanisms of TMs.
AIM OF THIS STUDY
To determine core TMs and potential pharmacological pathways on the basis of a thorough investigation into the preventive benefits and safety of oral TMs for chronic OIPN in colorectal cancer (CRC).
METHODS
A search of the PubMed, Cochrane, Embase, CNKI, VIP, and Wanfang databases for RCTs reporting on TMs for chronic OIPN was conducted through December 1, 2022. Subgroup analysis, sensitivity analysis and meta-regression were applied to assess the impacts of influencing variables. The assessment of Risk of Bias was relied on Cochrane Risk of Bias tool. The funnel plot, Egger's test, and the Trim and Fill method were applied to identify potential publication bias. Trial sequential analyses (TSA) were carried out by the TSA tool to increase the robustness. The assessment of the quality of evidence was according to the GRADE system. System pharmacology analysis was employed to screen core herbal combinations to elucidate possible mechanisms for preventing chronic OIPN in CRC.
RESULTS
The pooled effect estimate with robustness increased by TSA analysis demonstrated that oral TMs appeared to significantly decrease the incidence of chronic OIPN (RR = 0.66, 95% CI (0.56, 0.78); P<0.00001), leukocytopenia (RR = 0.65, 95% CI (0.54,0.79); P<0.00001), and nausea and vomiting (RR = 0.72, 95% CI (0.61,0.84); P<0.0001) as well as improve the Objective Response Rate (ORR) (RR = 1.31, 95% CI (1.09,1.56); P = 0.003). The incidence of severe chronic OIPN was revealed a significant reduction, particularly when chemotherapy was administered for periods of time shorter than six months (RR = 0.33, 95% CI (0.15,0.71); P = 0.005; actuation duration<3 months; RR = 0.33, 95% CI (0.17,0.62); P = 0.0007; actuation duration≥3 months, <6 months). The considerable heterogeneity among studies may be attributable to the severity of dysfunction categorized by grade and accumulated dosage. Using core TMs consisting of Astragalus membranaceus (Fisch.) Bunge, Atractylodes Macrocephala Koidz., Poria cocos (Schw.) Wolf, and Codonopsis pilosula (Franch.) Nannf. To regulate nuclear factor-kappa B against inflammation caused by activation of microglia might be an approach to preventing chronic OIPN.
CONCLUSIONS
TMs appear to be effective and safe in the prevention of chronic OIPN, especially severe chronic OIPN. Additionally, core TMs consisting of Astragalus membranaceus (Fisch.) Bunge, Atractylodes Macrocephala Koidz., Poria cocos (Schw.) Wolf, and Codonopsis pilosula (Franch.) Nannf were presumably responsible for reducing the incidence of chronic OIPN, and the mechanism may be related to relieving inflammation. However, quality-assured trials with long-term follow-up for exploring inflammatory factors and preliminary research on core TMs and pharmacological pathways are needed.
Topics: Animals; Humans; Oxaliplatin; Wolves; Neurotoxicity Syndromes; Colorectal Neoplasms; Inflammation
PubMed: 38211824
DOI: 10.1016/j.jep.2024.117735 -
RMD Open Jan 2024Immune-suppressing drugs can cause liver, kidney or blood toxicity. Prognostic factors for these adverse-events are poorly understood.
Prognostic factors for liver, blood and kidney adverse events from glucocorticoid sparing immune-suppressing drugs in immune-mediated inflammatory diseases: a prognostic systematic review.
BACKGROUND
Immune-suppressing drugs can cause liver, kidney or blood toxicity. Prognostic factors for these adverse-events are poorly understood.
PURPOSE
To ascertain prognostic factors associated with liver, blood or kidney adverse-events in people receiving immune-suppressing drugs.
DATA SOURCES
MEDLINE, Web of Science, EMBASE and the Cochrane library (01 January 1995 to 05 January 2023), and supplementary sources.
DATA EXTRACTION AND SYNTHESIS
Data were extracted by one reviewer using a modified CHARMS-PF checklist and validated by another. Two independent reviewers assessed risk of bias using Quality in Prognostic factor Studies tool and assessed the quality of evidence using a Grading of Recommendations Assessment, Development and Evaluation-informed framework.
RESULTS
Fifty-six studies from 58 papers were included. High-quality evidence of the following associations was identified: elevated liver enzymes (6 studies) and folate non-supplementation (3 studies) are prognostic factors for hepatotoxicity in those treated with methotrexate; that mercaptopurine (vs azathioprine) (3 studies) was a prognostic factor for hepatotoxicity in those treated with thiopurines; that mercaptopurine (vs azathioprine) (3 studies) and poor-metaboliser status (4 studies) were prognostic factors for cytopenia in those treated with thiopurines; and that baseline elevated liver enzymes (3 studies) are a prognostic factor for hepatotoxicity in those treated with anti-tumour necrosis factors. Moderate and low quality evidence for several other demographic, lifestyle, comorbidities, baseline bloods/serologic or treatment-related prognostic factors were also identified.
LIMITATIONS
Studies published before 1995, those with less than 200 participants and not published in English were excluded. Heterogeneity between studies included different cut-offs for prognostic factors, use of different outcome definitions and different adjustment factors.
CONCLUSIONS
Prognostic factors for target-organ damage were identified which may be further investigated for their potential role in targeted (risk-stratified) monitoring.
PROSPERO REGISTRATION NUMBER
CRD42020208049.
Topics: Humans; Azathioprine; Chemical and Drug Induced Liver Injury; Glucocorticoids; Kidney; Mercaptopurine; Prognosis
PubMed: 38199851
DOI: 10.1136/rmdopen-2023-003588 -
Clinical and Experimental Pediatrics Jan 2024Unexplained acute kidney injury (AKI) in children owing to diethylene glycol (DEG) contamination during drug production has gained attention in recent years. This...
Unexplained acute kidney injury (AKI) in children owing to diethylene glycol (DEG) contamination during drug production has gained attention in recent years. This qualitative study investigated the effects of DEG exposure on the incidence of unknown AKI in children. A systematic review following the PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analysis) guidelines was proposed to search for studies using predefined search terms in the PubMed, EBSCO, and Web of Science databases without publication date restrictions. The inclusion criteria are observational study, case study, case report, and case series design; and having provided accurate data for DEG poisoning and AKI diagnosis in children. All authors performed the study screening, data extraction, and data synthesis processes. Consensus was reached by mutual agreement. The data synthesis was conducted according to the DEG and unexplained AKI in children by examining the statistical data using Microsoft Excel 2017 and storing the data using the cloud service of Universitas Islam Indonesia. Of the 115 included studies, 21 met the inclusion criteria, including 2 case-control studies, 1 cross-sectional study, 4 case studies, and 14 case reports. DEG-contaminated paracetamol caused unexplained AKI in children. Other drugs including cough expectorants, antihistamines, and sedatives were administered. Chemicals other than DEG, such as propylene glycol and ethylene glycol, also induce AKI owing to overprescription and unintentional exposure. A recent epidemic of unexplained AKI showed contaminated paracetamol as the poisoning agent regardless of formula.
PubMed: 38186259
DOI: 10.3345/cep.2023.01039 -
ASAIO Journal (American Society For... May 2024Extracorporeal membrane oxygenation (ECMO) has had increasing prevalence and indications in the last decade. Calcium channel blocker overdose (CCBOD) can lead to...
Extracorporeal membrane oxygenation (ECMO) has had increasing prevalence and indications in the last decade. Calcium channel blocker overdose (CCBOD) can lead to significant cardiopulmonary dysfunction and has also increased in recent years. CCBOD results in cardiac depression, vasoplegia, and hyperglycemia. Expert consensus recommends treatment with calcium, high-dose insulin, inotropes, and vasopressors. Our systematic review evaluated when to initiate ECMO in the CCBOD population and the mortality rate associated with use. Electronic literature review identified all relevant studies for CCBOD and ECMO. PRISMA guidelines for systematic review were followed. Three independent authors reviewed abstracts and full texts, and only CCB ingestion without polypharmacy was included. Two authors independently collected data, which included demographics, current medical treatments, ECMO type, and survival. From 314 abstracts, 25 papers were included with a median publication year of 2019. Twenty-six patients were included with an average age of 32.7 years and 42%/58% male/female. Average time on ECMO 4.3 days. VA and VV ECMO use were 92.3% and 7.7%, respectively, and 84.6% of patients survived to hospital discharge. Before ECMO, most patients received 4-5 medical treatments (53.8%). Our systematic review demonstrates ECMO is a newly used, yet valuable therapy for CCBOD when medical treatment fails. Survival to discharge after ECMO for CCBOD is substantially higher than standard VV or VA ECMO. Medical management is still the mainstay therapy for CCBOD, but we show that a persistently unstable patient may benefit from prompt evaluation at an ECMO center for treatment.
Topics: Extracorporeal Membrane Oxygenation; Humans; Calcium Channel Blockers; Drug Overdose; Female; Male; Adult
PubMed: 38165982
DOI: 10.1097/MAT.0000000000002129 -
Environmental Science and Pollution... Jan 2024This study presents a systematic review of the scientific and technological production related to the use of systems based on UV, HO, and Cl for the elimination of... (Review)
Review
Systematic analysis of the scientific-technological production on the use of the UV, HO, and/or Cl systems in the elimination of bacteria and associated antibiotic resistance genes.
This study presents a systematic review of the scientific and technological production related to the use of systems based on UV, HO, and Cl for the elimination of antibiotic-resistant bacteria (ARB) and genes associated with antibiotic resistance (ARGs). Using the Pro Know-C (Knowledge Development Process-Constructivist) methodology, a portfolio was created and analyzed that includes 19 articles and 18 patents published between 2011 and 2022. The results show a greater scientific-technological production in UV irradiation systems (8 articles and 5 patents) and the binary combination UV/HO (9 articles and 4 patents). It was emphasized that UV irradiation alone focuses mainly on the removal of ARB, while the addition of HO or Cl, either individually or in binary combinations with UV, enhances the removal of ARB and ARG. The need for further research on the UV/HO/Cl system is emphasized, as gaps in the scientific-technological production of this system (0 articles and 2 patents), especially in its electrochemically assisted implementation, have been identified. Despite the gaps identified, there are promising prospects for the use of combined electrochemically assisted UV/HO/Cl disinfection systems. This is demonstrated by the effective removal of a wide range of contaminants, including ARB, fungi, and viruses, as well as microorganisms resistant to conventional disinfectants, while reducing the formation of toxic by-products.
Topics: Hydrogen Peroxide; Angiotensin Receptor Antagonists; Water Purification; Chlorine; Angiotensin-Converting Enzyme Inhibitors; Drug Resistance, Microbial; Bacteria; Disinfection; Ultraviolet Rays
PubMed: 38165540
DOI: 10.1007/s11356-023-31435-2 -
The Western Journal of Emergency... Nov 2023Acetaminophen poisoning is commonly treated by emergency physicians. First-line therapy is N-acetylcysteine (NAC), traditionally administered intravenously via a US Food...
INTRODUCTION
Acetaminophen poisoning is commonly treated by emergency physicians. First-line therapy is N-acetylcysteine (NAC), traditionally administered intravenously via a US Food and Drug Administration (FDA)-approved three-bag protocol in which each bag has a unique concentration and infusion duration. Recently, simplified, off-label two-bag NAC infusion protocols have become more common. The purpose of this review is to summarize the effectiveness and safety of two-bag NAC.
METHODS
We undertook a comprehensive search of PubMed, EMBASE, and MEDLINE from inception to December 13, 2022, for articles describing human acetaminophen poisonings treated with two-bag NAC, defined as any regimen involving two discrete infusions in two separate bags. Outcomes included effectiveness (measured by incidence of liver injury); incidence of non-allergic anaphylactoid reactions (NAAR); gastrointestinal, cutaneous, and systemic reactions; treatments for NAARs; incidence of NAC-related medication errors; and delays or interruptions in NAC administration.
RESULTS
Twelve articles met final inclusion, 10 of which compared two-bag NAC to the three-bag regimen. Nine articles evaluated the two-bag/20-hour regimen, a simplified version of the FDA-approved three-bag regimen in which the traditional first and second bags are combined into a single four-hour infusion. Nine articles assessed comparative effectiveness of two-bag NAC in terms of liver injury, most commonly assessed for by incidence of hepatotoxicity (aspartate aminotransferase or alanine aminotransferase >1,000 international units per liter). No difference in liver injury was observed between two-bag and three-bag regimens. Of nine articles comparing incidence of NAARs, eight demonstrated statistically fewer NAARs with two-bag regimens, and one showed no difference. In seven articles evaluating treatment for NAARs (antihistamines, corticosteroids, epinephrine), all showed that patients received fewer medications for NAARs with two-bag NAC. Three articles evaluated NAC-related medication errors; two demonstrated no difference, while one study evaluating only children showed fewer errors with two-bag NAC. Two studies evaluated delays and/or interruptions in NAC infusions; both favored two-bag NAC.
CONCLUSION
For patients with acetaminophen poisoning, two-bag NAC regimens appear to have similar outcomes to the traditional three-bag regimen in terms of liver injury. Two-bag NAC regimens are associated with fewer adverse events and fewer treatments for those events than the three-bag regimen and fewer interruptions in antidotal therapy.
Topics: Child; Humans; Acetaminophen; Acetylcysteine; Analgesics, Non-Narcotic; Antidotes; Drug Overdose; Drug-Related Side Effects and Adverse Reactions; Infusions, Intravenous
PubMed: 38165196
DOI: 10.5811/westjem.59099 -
Journal of Global Health Dec 2023There are significant disparities in the burden of disease due to poisoning between children in low- and high-income countries (HICs). However, there is limited data on...
Epidemiology, risk factors, and strategies to prevent and manage poisonings due to pharmaceuticals in children in low income and low-middle income countries: A systematic review.
BACKGROUND
There are significant disparities in the burden of disease due to poisoning between children in low- and high-income countries (HICs). However, there is limited data on the impact of increasing pharmaceutical access in low income countries (LICs) and low-middle income countries (LMICs) on the epidemiology of and risk factors associated with poisoning in children in these settings. Furthermore, while strategies in HICs have effectively reduced the burden of disease due to poisonings in children, there is limited information regarding the efficacy of these interventions in LICs/LMICs.
METHODS
We conducted a systematic review in eight databases for literature published between January 2000 to April 2022 to evaluate the epidemiology and risk factors associated with poisonings due to pharmaceuticals and effective strategies to prevent and manage them in children in LICs/LMICs. From 16 061 retrieved articles, 41 were included in the final analysis.
RESULTS
Pharmaceuticals were a common cause of poisoning in children in LICs/LMICs, occurring in between 12.4% and 72.36% of cases. Major risk factors were unsafe medication storage and inadequate caregiver knowledge. Delayed access to care and younger age were associated with increased mortality. Prevention strategies that included education demonstrated improvements in knowledge; however, their impact on incidence and mortality was unclear. Management strategies detailed individual patient care interventions, most commonly gastric lavage and activated charcoal. Meanwhile, delayed presentation, limited provider knowledge, and inadequate laboratory resources to support therapeutic monitoring hindered optimal management.
CONCLUSIONS
The combination of educational interventions for prevention, along with regulatory processes to maximise medication storage and formulation safety, could be effective in reducing the burden of poisoning in LICs/LMICs. The development of national or regional protocols for the management of common medication poisonings, augmented by the development of poison control centers and expansion of laboratory access in facilities may help reduce the morbidity and mortality associated with pharmaceutical poisonings in children in LICs/LMICs. Further evidence regarding contextual factors, risk and benefit profiles, the pattern of poisoning, and the impact of preventive and treatment interventions specific to LICs/LMICs is needed to better refine recommendations in these settings.
REGISTRATION
PROSPERO: CRD42022315686.
Topics: Child; Humans; Developing Countries; Poverty; Income; Risk Factors; Pharmaceutical Preparations
PubMed: 38154015
DOI: 10.7189/jogh.13.04173