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The Oncologist Jun 2024There is little evidence on the safety, efficacy, and survival benefit of restarting immune checkpoint inhibitors (ICI) in patients with cancer after discontinuation due...
BACKGROUNDS
There is little evidence on the safety, efficacy, and survival benefit of restarting immune checkpoint inhibitors (ICI) in patients with cancer after discontinuation due to immune-related adverse events (irAEs) or progressive disease (PD). Here, we performed a meta-analysis to elucidate the possible benefits of ICI rechallenge in patients with cancer.
METHODS
Systematic searches were conducted using PubMed, Embase, and Cochrane Library databases. The objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and incidence of irAEs were the outcomes of interest.
RESULTS
Thirty-six studies involving 2026 patients were analyzed. ICI rechallenge was associated with a lower incidence of all-grade (OR, 0.05; 95%CI, 0.02-0.13, P < .05) and high-grade irAEs (OR, 0.37; 95%CI, 0.21-0.64, P < .05) when compared with initial ICI treatment. Though no significant difference was observed between rechallenge and initial treatment regarding ORR (OR, 0.69; 95%CI, 0.39-1.20, P = .29) and DCR (OR, 0.85; 95%CI, 0.51-1.40, P = 0.52), patients receiving rechallenge had improved PFS (HR, 0.56; 95%CI, 0.43-0.73, P < .05) and OS (HR, 0.55; 95%CI, 0.43-0.72, P < .05) than those who discontinued ICI therapy permanently. Subgroup analysis revealed that for patients who stopped initial ICI treatment because of irAEs, rechallenge showed similar safety and efficacy with initial treatment, while for patients who discontinued ICI treatment due to PD, rechallenge caused a significant increase in the incidence of high-grade irAEs (OR, 4.97; 95%CI, 1.98-12.5, P < .05) and a decrease in ORR (OR, 0.48; 95%CI, 0.24-0.95, P < .05).
CONCLUSION
ICI rechallenge is generally an active and feasible strategy that is associated with relative safety, similar efficacy, and improved survival outcomes. Rechallenge should be considered individually with circumspection, and randomized controlled trials are required to confirm these findings.
PubMed: 38940446
DOI: 10.1093/oncolo/oyae134 -
Frontiers in Oncology 2024To assess the efficacy and safety of nimotuzumab in combination with radiotherapy or chemoradiotherapy for locally advanced head and neck squamous cell carcinoma.
Nimotuzumab combined with radiotherapy+/- chemotherapy for definitive treatment of locally advanced squamous cell carcinoma of head and neck: a metanalysis of randomized controlled trials.
OBJECTIVES
To assess the efficacy and safety of nimotuzumab in combination with radiotherapy or chemoradiotherapy for locally advanced head and neck squamous cell carcinoma.
METHODS
Systematic searches were performed on PubMed, Web of Science, Embase, Cochrane Library, China National Knowledge Infrastructure, China Biomedical Medicine, Wanfang, VIP databases. Seven eligible randomized controlled trials (n = 1012) were selected through rigorous inclusion and exclusion criteria.
RESULTS
A total of 1012 cases were included. including 508 (50.2%) in the nimotuzumab combination treatment group; There were 504 cases (49.8%) in the control group. The results of meta-analysis showed that the overall survival (Hazard Ratio [HR]=0.75, 95% Confidence Interval [CI]: 0.62-0.90, P<0.05), progression-free survival (HR=0.69, 95% CI: 0.54-0.87, P<0.05), complete response rate (Risk Ratio [RR]=1.52, 95% CI: 1.24-1.86, P<0.05), and objective response rate (RR=1.32, 95% CI: 1.17-1.48, P<0.05) were significantly improved in the nimotuzumab combination treatment group compared with the control group. In terms of the incidence of adverse effects, only the incidence of rash was the nimotuzumab combination group higher than in the treatment alone group, and there was no significant difference between the remaining adverse reactions (neutropenia, anemia, nausea/vomiting, mucositis, dermatitis, dysphagia).
CONCLUSION
Nimotuzumab combined with radiotherapy or chemoradiotherapy is more effective than radiotherapy alone or chemoradiotherapy in locally advanced squamous cell carcinoma of the head and neck, and the safety profile is controllable. Therefore, the addition of nimotuzumab to treatment is expected to be an effective treatment option for this disease. However, more prospective randomized controlled trials are needed to fully explore the effectiveness of this treatment in patients with locally advanced head and neck squamous cell carcinoma.
SYSTEMATIC REVIEW REGISTRATION
identifier PROSPERO (CRD: 42022383313).
PubMed: 38939342
DOI: 10.3389/fonc.2024.1380428 -
Cureus May 2024Non-small cell lung carcinoma (NSCLC) is a prevalent and aggressive form of lung cancer, with a poor prognosis for metastatic disease. Immunotherapy, particularly immune... (Review)
Review
Non-small cell lung carcinoma (NSCLC) is a prevalent and aggressive form of lung cancer, with a poor prognosis for metastatic disease. Immunotherapy, particularly immune checkpoint inhibitors (ICIs), has revolutionized the management of NSCLC, but response rates are highly variable. Identifying reliable predictive biomarkers is crucial to optimize patient selection and treatment outcomes. This systematic review aimed to evaluate the current state of artificial intelligence (AI) and machine learning (ML) applications in predicting the response to immunotherapy in NSCLC. A comprehensive literature search identified 19 studies that met the inclusion criteria. The studies employed diverse AI/ML techniques, including deep learning, artificial neural networks, support vector machines, and gradient boosting methods, applied to various data modalities such as medical imaging, genomic data, clinical variables, and immunohistochemical markers. Several studies demonstrated the ability of AI/ML models to accurately predict immunotherapy response, progression-free survival, and overall survival in NSCLC patients. However, challenges remain in data availability, quality, and interpretability of these models. Efforts have been made to develop interpretable AI/ML techniques, but further research is needed to improve transparency and explainability. Additionally, translating AI/ML models from research settings to clinical practice poses challenges related to regulatory approval, data privacy, and integration into existing healthcare systems. Nonetheless, the successful implementation of AI/ML models could enable personalized treatment strategies, improve treatment outcomes, and reduce unnecessary toxicities and healthcare costs associated with ineffective treatments.
PubMed: 38939246
DOI: 10.7759/cureus.61220 -
Alzheimer's Research & Therapy Jun 2024Non-invasive brain stimulation (NIBS) combined with cognitive training (CT) may have shown some prospects on improving cognitive function in patients with Alzheimer's... (Meta-Analysis)
Meta-Analysis Review
The cognitive effect of non-invasive brain stimulation combined with cognitive training in Alzheimer's disease and mild cognitive impairment: a systematic review and meta-analysis.
BACKGROUND
Non-invasive brain stimulation (NIBS) combined with cognitive training (CT) may have shown some prospects on improving cognitive function in patients with Alzheimer's disease (AD) and mild cognitive impairment (MCI). However, data from clinical trials or meta-analysis involving NIBS combined with CT have shown controversial results. The aim of this systematic review and meta-analysis was to evaluate short-term and long-term effects of NIBS combined with CT on improving global cognition and other specific cognitive domains in patients with AD and MCI.
METHODS
This systematic review and meta-analysis was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Five electronic databases including PubMed, Web of Science, EBSCO, Cochrane Library and Embase were searched up from inception to 20 November 2023. The PEDro scale and the Cochrane's risk of bias assessment were used to evaluate risk of bias and methodological quality of included studies. All statistical analyses were conducted with Review Manager 5.3.
RESULTS
We included 15 studies with 685 patients. The PEDro scale was used to assess methodological quality with a mean score of 7.9. The results of meta-analysis showed that NIBS combined with CT was effective on improving global cognition in AD and MCI (SMD = 0.52, 95% CI (0.18, 0.87), p = 0.003), especially for patients accepting repetitive transcranial magnetic stimulation (rTMS) combined with CT (SMD = 0.46, 95% CI (0.14, 0.78), p = 0.005). AD could achieve global cognition improvement from NIBS combined with CT group (SMD = 0.77, 95% CI (0.19, 1.35), p = 0.01). Transcranial direct current stimulation (tDCS) combined with CT could improve language function in AD and MCI (SMD = 0.29, 95% CI (0.03, 0.55), p = 0.03). At evaluation follow-up, rTMS combined with CT exhibited larger therapeutic responses to AD and MCI in global cognition (SMD = 0.55, 95% CI (0.09, 1.02), p = 0.02). AD could achieve global cognition (SMD = 0.40, 95% CI (0.03, 0.77), p = 0.03) and attention/working memory (SMD = 0.72, 95% CI (0.23, 1.20), p = 0.004) improvement after evaluation follow-up from NIBS combined with CT group.
CONCLUSIONS
Overall, NIBS combined with CT, particularly rTMS combined with CT, has both short-term and follow-up effects on improving global cognition, mainly in patients with AD. tDCS combined with CT has advantages on improving language function in AD and MCI. Future more studies need evaluate cognitive effects of NIBS combined with CT on other specific cognitive domain in patients with cognitive deterioration.
Topics: Humans; Cognitive Dysfunction; Alzheimer Disease; Transcranial Magnetic Stimulation; Transcranial Direct Current Stimulation; Cognitive Behavioral Therapy; Cognition; Combined Modality Therapy; Cognitive Training
PubMed: 38937842
DOI: 10.1186/s13195-024-01505-9 -
Medical Mycology Jun 2024In response to the growing global threat of fungal infections, in 2020 the World Health Organisation (WHO) established an Expert Group to identify priority fungi and...
In response to the growing global threat of fungal infections, in 2020 the World Health Organisation (WHO) established an Expert Group to identify priority fungi and develop the first WHO fungal priority pathogen list (FPPL). The aim of this systematic review was to evaluate the features and global impact of invasive infections caused by Pichia kudriavzevii (formerly known as Candida krusei). PubMed and Web of Science were used to identify studies published between 1 January 2011 and 18 February 2021 reporting on the criteria of mortality, morbidity (defined as hospitalisation and length of stay), drug resistance, preventability, yearly incidence, and distribution/emergence. Overall, 33 studies were evaluated. Mortality rates of up to 67% in adults were reported. Despite the intrinsic resistance of P. kudriavzevii to fluconazole with decreased susceptibility to amphotericin B, resistance (or non-wild-type rate) to other azoles and echinocandins was low, ranging between 0 and 5%. Risk factors for developing P. kudriavzevii infections included low birth weight, prior use of antibiotics/antifungals, and an underlying diagnosis of gastrointestinal disease or cancer. The incidence of infections caused by P. kudriavzevii is generally low (∼5% of all Candida-like blood isolates) and stable over the 10-year timeframe, although additional surveillance data are needed. Strategies targeting the identified risk factors for developing P. kudriavzevii infections should be developed and tested for effectiveness and feasibility of implementation. Studies presenting data on epidemiology and susceptibility of P. kudriavzevii were scarce, especially in low- and middle-income countries (LMICs). Thus, global surveillance systems are required to monitor the incidence, susceptibility, and morbidity of P. kudriavzevii invasive infections to inform diagnosis and treatment. Timely species-level identification and susceptibility testing should be conducted to reduce the high mortality and limit the spread of P. kudriavzevii in healthcare facilities.
Topics: Humans; Drug Resistance, Fungal; Antifungal Agents; World Health Organization; Pichia; Incidence; Risk Factors; Candidiasis
PubMed: 38935911
DOI: 10.1093/mmy/myad132 -
Medical Mycology Jun 2024The World Health Organization, in response to the growing burden of fungal disease, established a process to develop a fungal pathogen priority list. This systematic...
The World Health Organization, in response to the growing burden of fungal disease, established a process to develop a fungal pathogen priority list. This systematic review aimed to evaluate the epidemiology and impact of infections caused by Talaromyces marneffei, Coccidioides species, and Paracoccidioides species. PubMed and Web of Sciences databases were searched to identify studies published between 1 January 2011 and 23 February 2021 reporting on mortality, complications and sequelae, antifungal susceptibility, preventability, annual incidence, and trends. Overall, 25, 17, and 6 articles were included for T. marneffei, Coccidioides spp. and Paracoccidioides spp., respectively. Mortality rates were high in those with invasive talaromycosis and paracoccidioidomycosis (up to 21% and 22.7%, respectively). Hospitalization was frequent in those with coccidioidomycosis (up to 84%), and while the duration was short (mean/median 3-7 days), readmission was common (38%). Reduced susceptibility to fluconazole and echinocandins was observed for T. marneffei and Coccidioides spp., whereas >88% of T. marneffei isolates had minimum inhibitory concentration values ≤0.015 μg/ml for itraconazole, posaconazole, and voriconazole. Risk factors for mortality in those with talaromycosis included low CD4 counts (odds ratio 2.90 when CD4 count <200 cells/μl compared with 24.26 when CD4 count <50 cells/μl). Outbreaks of coccidioidomycosis and paracoccidioidomycosis were associated with construction work (relative risk 4.4-210.6 and 5.7-times increase, respectively). In the United States of America, cases of coccidioidomycosis increased between 2014 and 2017 (from 8232 to 14 364/year). National and global surveillance as well as more detailed studies to better define sequelae, risk factors, outcomes, global distribution, and trends are required.
Topics: Talaromyces; Humans; Paracoccidioides; Antifungal Agents; Coccidioides; World Health Organization; Mycoses; Paracoccidioidomycosis; Coccidioidomycosis; Microbial Sensitivity Tests
PubMed: 38935909
DOI: 10.1093/mmy/myad133 -
Medical Mycology Jun 2024In response to the growing global burden of fungal infections with uncertain impact, the World Health Organization (WHO) established an Expert Group to identify priority...
In response to the growing global burden of fungal infections with uncertain impact, the World Health Organization (WHO) established an Expert Group to identify priority fungal pathogens and establish the WHO Fungal Priority Pathogens List for future research. This systematic review aimed to evaluate the features and global impact of invasive candidiasis caused by Candida tropicalis. PubMed and Web of Science were searched for studies reporting on criteria of mortality, morbidity (defined as hospitalization and disability), drug resistance, preventability, yearly incidence, diagnostics, treatability, and distribution/emergence from 2011 to 2021. Thirty studies, encompassing 436 patients from 25 countries were included in the analysis. All-cause mortality due to invasive C. tropicalis infections was 55%-60%. Resistance rates to fluconazole, itraconazole, voriconazole and posaconazole up to 40%-80% were observed but C. tropicalis isolates showed low resistance rates to the echinocandins (0%-1%), amphotericin B (0%), and flucytosine (0%-4%). Leukaemia (odds ratio (OR) = 4.77) and chronic lung disease (OR = 2.62) were identified as risk factors for invasive infections. Incidence rates highlight the geographic variability and provide valuable context for understanding the global burden of C. tropicalis infections. C. tropicalis candidiasis is associated with high mortality rates and high rates of resistance to triazoles. To address this emerging threat, concerted efforts are needed to develop novel antifungal agents and therapeutic approaches tailored to C. tropicalis infections. Global surveillance studies could better inform the annual incidence rates, distribution and trends and allow informed evaluation of the global impact of C. tropicalis infections.
Topics: Candida tropicalis; Humans; Antifungal Agents; World Health Organization; Drug Resistance, Fungal; Candidiasis, Invasive; Incidence; Global Health; Risk Factors
PubMed: 38935905
DOI: 10.1093/mmy/myae040 -
Medical Mycology Jun 2024The World Health Organization, in response to the growing burden of fungal disease, established a process to develop a fungal priority pathogens list. This systematic...
The World Health Organization, in response to the growing burden of fungal disease, established a process to develop a fungal priority pathogens list. This systematic review aimed to evaluate the epidemiology and impact of eumycetoma. PubMed and Web of Science were searched to identify studies published between 1 January 2011 and 19 February 2021. Studies reporting on mortality, inpatient care, complications and sequelae, antifungal susceptibility, risk factors, preventability, annual incidence, global distribution, and emergence during the study time frames were selected. Overall, 14 studies were eligible for inclusion. Morbidity was frequent with moderate to severe impairment of quality of life in 60.3%, amputation in up to 38.5%, and recurrent or long-term disease in 31.8%-73.5% of patients. Potential risk factors included male gender (56.6%-79.6%), younger age (11-30 years; 64%), and farming occupation (62.1%-69.7%). Mycetoma was predominantly reported in Sudan, particularly in central Sudan (37%-76.6% of cases). An annual incidence of 0.1/100 000 persons and 0.32/100 000 persons/decade was reported in the Philippines and Uganda, respectively. In Uganda, a decline in incidence from 3.37 to 0.32/100 000 persons between two consecutive 10-year periods (2000-2009 and 2010-2019) was detected. A community-based, multi-pronged prevention programme was associated with a reduction in amputation rates from 62.8% to 11.9%. With the pre-specified criteria, no studies of antifungal drug susceptibility, mortality, and hospital lengths of stay were identified. Future research should include larger cohort studies, greater drug susceptibility testing, and global surveillance to develop evidence-based treatment guidelines and to determine more accurately the incidence and trends over time.
Topics: Humans; Mycetoma; Incidence; Antifungal Agents; World Health Organization; Risk Factors; Male; Female; Quality of Life
PubMed: 38935904
DOI: 10.1093/mmy/myae044 -
Medical Mycology Jun 2024The World Health Organization, in response to the growing burden of fungal disease, established a process to develop a fungal priority pathogens list (FPPL). This...
The World Health Organization, in response to the growing burden of fungal disease, established a process to develop a fungal priority pathogens list (FPPL). This systematic review aimed to evaluate the epidemiology and impact of invasive fungal disease due to Mucorales. PubMed and Web of Science were searched to identify studies published between January 1, 2011 and February 23, 2021. Studies reporting on mortality, inpatient care, complications and sequelae, antifungal susceptibility, risk factors, preventability, annual incidence, global distribution, and emergence during the study time frames were selected. Overall, 24 studies were included. Mortality rates of up to 80% were reported. Antifungal susceptibility varied across agents and species, with the minimum inhibitory concentrations lowest for amphotericin B and posaconazole. Diabetes mellitus was a common risk factor, detected in 65%-85% of patients with mucormycosis, particularly in those with rhino-orbital disease (86.9%). Break-through infection was detected in 13.6%-100% on azole or echinocandin antifungal prophylaxis. The reported prevalence rates were variable, with some studies reporting stable rates in the USA of 0.094-0.117/10 000 discharges between 2011 and 2014, whereas others reported an increase in Iran from 16.8% to 24% between 2011 and 2015. Carefully designed global surveillance studies, linking laboratory and clinical data, are required to develop clinical breakpoints to guide antifungal therapy and determine accurate estimates of complications and sequelae, annual incidence, trends, and global distribution. These data will provide robust estimates of disease burden to refine interventions and better inform future FPPL.
Topics: Humans; Mucorales; Antifungal Agents; Mucormycosis; World Health Organization; Risk Factors; Invasive Fungal Infections; Microbial Sensitivity Tests; Prevalence; Drug Resistance, Fungal; Incidence; Global Health
PubMed: 38935901
DOI: 10.1093/mmy/myad130 -
American Journal of Clinical Oncology Jun 2024Hemophagocytic lymphohistiocytosis (HLH) is a severe immunologic disorder that can be fatal if left untreated. The condition is characterized by excessive immune system...
BACKGROUND
Hemophagocytic lymphohistiocytosis (HLH) is a severe immunologic disorder that can be fatal if left untreated. The condition is characterized by excessive immune system activation and is often triggered by infections such as Epstein-Barr virus (EBV). Rituximab, an anti-CD20 monoclonal antibody, has been suggested as a treatment, particularly for EBV-associated HLH.
METHODS
A systematic review was conducted using PRISMA guidelines, with a literature search spanning PubMed, Scopus, Web of Science, and the Cochrane Library. The inclusion criteria focused on studies that assessed rituximab's efficacy in treating HLH. Quality assessment was performed using the Joanna Briggs Institute Critical Appraisal Checklist for Case Reports.
RESULTS
Of 783 identified records, 24 studies were included in the final analysis. Rituximab was typically administered at 375 mg/m2, with varying doses and treatment frequency. Clinical response, often seen within 1 month, was assessed by improvements in clinical symptoms and laboratory findings. Survival rates posttreatment displayed a wide range, with instances of complete remission and disease-free periods, as well as reports of relapse and mortality.
CONCLUSION
Rituximab demonstrates the potential for significant clinical benefit in treating HLH, particularly when associated with EBV, showing promise in reducing disease activity and contributing to remission. These findings encourage further research and clinical trials to refine the therapeutic protocols and better understand the long-term effects of rituximab in HLH management.
PubMed: 38934172
DOI: 10.1097/COC.0000000000001119