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Frontiers in Immunology 2024Immunotherapy treatments aim to modulate the host's immune response to either mitigate it in inflammatory/autoimmune disease or enhance it against infection or cancer....
Immunotherapy treatments aim to modulate the host's immune response to either mitigate it in inflammatory/autoimmune disease or enhance it against infection or cancer. Among different immunotherapies reaching clinical application during the last years, chimeric antigen receptor (CAR) immunotherapy has emerged as an effective treatment for cancer where different CAR T cells have already been approved. Yet their use against infectious diseases is an area still relatively poorly explored, albeit with tremendous potential for research and clinical application. Infectious diseases represent a global health challenge, with the escalating threat of antimicrobial resistance underscoring the need for alternative therapeutic approaches. This review aims to systematically evaluate the current applications of CAR immunotherapy in infectious diseases and discuss its potential for future applications. Notably, CAR cell therapies, initially developed for cancer treatment, are gaining recognition as potential remedies for infectious diseases. The review sheds light on significant progress in CAR T cell therapy directed at viral and opportunistic fungal infections.
Topics: Humans; Receptors, Chimeric Antigen; Immunotherapy; Immunotherapy, Adoptive; Neoplasms; Communicable Diseases
PubMed: 38352878
DOI: 10.3389/fimmu.2024.1289303 -
Seminars in Oncology Nursing Oct 2023This systematic review aims to describe an overview of the overall care, patient and parent education, staff training, and management of complications from a nursing... (Review)
Review
OBJECTIVES
This systematic review aims to describe an overview of the overall care, patient and parent education, staff training, and management of complications from a nursing perspective of pediatric patients undergoing chimeric antigen receptor T (CAR-T) cell infusion in order to provide an updated summary of the approach to the management of these patients. CAR-T cellular therapy represents an innovation within pediatric hematology and oncology used to treat relapse and refractory leukemias, solid tumors, and lymphomas when standard therapy has not worked. However, this type of therapy could lead to the onset of some clinical complications that must be managed appropriately and promptly. Although their use is constantly increasing, the knowledge and resources in the literature are still limited.
DATA SOURCES
The review was conducted from January 2022 to July 2022 in PubMed, CINAHL, Scopus, and Cochrane and produced 502 articles. Based on the selection criteria and after removing duplicate articles, 26 articles were included in the study.
CONCLUSION
From these analyzed articles, it was possible to have an overview regarding the management, patient and parent education, staff training, and management of complications from a nursing perspective of pediatric patients undergoing CAR-T cell infusion.
IMPLICATIONS FOR NURSING PRACTICE
The management of hematology-oncology patients undergoing CAR-T cell therapy from a nursing perspective is not simple. We hope this review can be used as a tool to guide nursing staff. In this regard, we have developed a summary table with the actions to be taken in the case of assisting a pediatric patient being treated with CAR-T.
Topics: Humans; Child; Receptors, Chimeric Antigen; Immunotherapy, Adoptive; Neoplasms; Leukemia; Cell- and Tissue-Based Therapy
PubMed: 37544775
DOI: 10.1016/j.soncn.2023.151478 -
British Journal of Haematology Dec 2023
Meta-Analysis
Topics: Humans; Receptors, Chimeric Antigen; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma; Receptors, Antigen, T-Cell; Burkitt Lymphoma; Immunotherapy, Adoptive; Antigens, CD19
PubMed: 37814795
DOI: 10.1111/bjh.19149 -
Clinical Reviews in Allergy & Immunology Apr 2024An acute aseptic meningitis has been occasionally observed on intravenous polyclonal human immunoglobulin therapy. Since case reports cannot be employed to draw... (Meta-Analysis)
Meta-Analysis Review
An acute aseptic meningitis has been occasionally observed on intravenous polyclonal human immunoglobulin therapy. Since case reports cannot be employed to draw inferences about the relationships between immunoglobulin therapy and meningitis, we conducted a systematic review and meta-analysis of the literature. Eligible were cases, case series, and pharmacovigilance studies. We found 71 individually documented cases (36 individuals ≤ 18 years of age) of meningitis. Ninety percent of cases presented ≤ 3 days after initiating immunoglobulin therapy and recovered within ≤ 7 days (with a shorter disease duration in children: ≤ 3 days in 29 (94%) cases). In 22 (31%) instances, the authors noted a link between the onset of meningitis and a rapid intravenous infusion of immunoglobulins. Cerebrospinal fluid analysis revealed a predominantly neutrophilic (N = 46, 66%) pleocytosis. Recurrences after re-exposure were observed in eight (N = 11%) patients. Eight case series addressed the prevalence of meningitis in 4089 patients treated with immunoglobulins. A pooled prevalence of 0.6% was noted. Finally, pharmacovigilance data revealed that meningitis temporally associated with intravenous immunoglobulin therapy occurred with at least five different products. In conclusion, intravenous immunoglobulin may cause an acute aseptic meningitis. The clinical features remit rapidly after discontinuing the medication.
Topics: Humans; Meningitis, Aseptic; Immunoglobulins, Intravenous; Acute Disease; Child; Adolescent; Pharmacovigilance; Child, Preschool; Immunization, Passive
PubMed: 38739354
DOI: 10.1007/s12016-024-08989-1 -
Zeitschrift Fur Evidenz, Fortbildung... Mar 2024Up-to-date systematic reviews (SRs) are essential for making evidence-based decisions. During the 2019 coronavirus (COVID-19) pandemic, there was a particular need for...
INTRODUCTION
Up-to-date systematic reviews (SRs) are essential for making evidence-based decisions. During the 2019 coronavirus (COVID-19) pandemic, there was a particular need for up-to-date evidence, making the living systematic review (LSR) approach an appropriate review type. However, this approach poses certain challenges.
OBJECTIVE AND OUTLINE
We aim to provide practice insights and report challenges that we faced while conducting two Cochrane LSRs on COVID-19 treatments with (i) convalescent plasma and (ii) systemic corticosteroids. We address our objective with an experience report and share challenges of the following components based on Iannizzi et al. (2022): study design, publication types, intervention/comparator, outcomes, search strategy, review updates and transparent reporting of differences between review updates.
RESULTS
Regarding the study design, the plasma LSR included different study designs because RCT data were not available at the beginning of the pandemic, whereas for the corticosteroids LSR, which started several months later, RCT data were already available. The challenges in both LSRs included the publication types (preprints were included with caution) and the intervention/comparator, for instance the unavailability of standard of care for either LSR, or SARS-CoV-2 variants occurrence. Further challenges in both LSRs occurred in the components "outcome sets" (which had to be adjusted) and "literature search". The decision criteria for updating were based on important studies and available resources in both LSRs and policy relevance in the plasma LSR. Transparent reporting of the differences between the various update versions were discussed for both LSRs.
DISCUSSION AND CONCLUSION
In summary, there are similarities and differences regarding challenges of review components for both LSRs. It is important to keep in mind that the two LSR examples presented here were conducted in the wake of the COVID-19 pandemic. Therefore, many of the challenges are attributable to the pandemic and are not specific to LSRs, such as constant adjustments of the outcome sets or changes in the database search. Nevertheless, we believe that some of these aspects are helpful for LSR authors and are applicable to other LSRs outside the pandemic context, particularly in areas where new evidence is rapidly emerging.
Topics: Humans; COVID-19; SARS-CoV-2; Pandemics; COVID-19 Serotherapy; Germany; Adrenal Cortex Hormones
PubMed: 38220533
DOI: 10.1016/j.zefq.2023.11.004 -
Systematic Reviews Sep 2023Adoptive cell therapy (ACT) is a rapidly evolving field. Patient-reported outcomes (PROs) allow patients to report the impact of treatment on their quality of life...
INTRODUCTION
Adoptive cell therapy (ACT) is a rapidly evolving field. Patient-reported outcomes (PROs) allow patients to report the impact of treatment on their quality of life during and after treatment. The systematic review aims to characterise the breadth of PROs utilised in ACT cancer care and provide guidance for the use of PROs in this patient population in the future.
METHODS
A systematic search was conducted (MEDLINE, PsycINFO, Embase and CINAHL) in August 2021 by two reviewers. Search terms covered the following: "adoptive cell therapy", "patient-reported outcomes" and "cancer". Studies were included if they used a PRO measure to report the impact of ACT. The methodological quality of PROs was assessed. Forward and backward reference searching was conducted of any relevant papers. A quality grading scale was applied based on Cochrane and Revenson criteria for classification of high-quality studies. Key data from the studies and the included PROs was extracted by two researchers and tabulated.
RESULTS
One-hundred nine papers were identified; 11 papers were included. The majority of studies were single-arm trials or observational studies. Twenty-two different PROs were identified; none was ACT specific. The PROMIS-29 and EQ-5D were most commonly used. Few studies collected PRO data in the first 1-2 weeks. Four studies followed patients up for over a year, and a further four studies followed patients for approximately 3 months.
DISCUSSION
None of the PROs identified have been designed specifically for ACT. Appropriateness of existing instruments should be considered. It should be considered whether it is appropriate to collect data more frequently in the acute stage and then less frequently during follow-up. It should be considered if one tool is suitable at all time points or if the tool should be adapted depending on time since treatment. More research is needed to identify the exact timings of PRO assessments, and qualitative work with patients is needed to determine the most important issues for them throughout the treatment and follow-up.
Topics: Humans; Quality of Life; Immunotherapy, Adoptive; Neoplasms; Patient Reported Outcome Measures
PubMed: 37777816
DOI: 10.1186/s13643-023-02337-8 -
BMC Health Services Research Jul 2023Individual participant data meta-analyses (IPD-MAs), which involve harmonising and analysing participant-level data from related studies, provide several advantages over...
BACKGROUND
Individual participant data meta-analyses (IPD-MAs), which involve harmonising and analysing participant-level data from related studies, provide several advantages over aggregate data meta-analyses, which pool study-level findings. IPD-MAs are especially important for building and evaluating diagnostic and prognostic models, making them an important tool for informing the research and public health responses to COVID-19.
METHODS
We conducted a rapid systematic review of protocols and publications from planned, ongoing, or completed COVID-19-related IPD-MAs to identify areas of overlap and maximise data request and harmonisation efforts. We searched four databases using a combination of text and MeSH terms. Two independent reviewers determined eligibility at the title-abstract and full-text stages. Data were extracted by one reviewer into a pretested data extraction form and subsequently reviewed by a second reviewer. Data were analysed using a narrative synthesis approach. A formal risk of bias assessment was not conducted.
RESULTS
We identified 31 COVID-19-related IPD-MAs, including five living IPD-MAs and ten IPD-MAs that limited their inference to published data (e.g., case reports). We found overlap in study designs, populations, exposures, and outcomes of interest. For example, 26 IPD-MAs included RCTs; 17 IPD-MAs were limited to hospitalised patients. Sixteen IPD-MAs focused on evaluating medical treatments, including six IPD-MAs for antivirals, four on antibodies, and two that evaluated convalescent plasma.
CONCLUSIONS
Collaboration across related IPD-MAs can leverage limited resources and expertise by expediting the creation of cross-study participant-level data datasets, which can, in turn, fast-track evidence synthesis for the improved diagnosis and treatment of COVID-19.
TRIAL REGISTRATION
10.17605/OSF.IO/93GF2.
Topics: Humans; COVID-19; Pandemics; COVID-19 Serotherapy; Prognosis; Publications
PubMed: 37415216
DOI: 10.1186/s12913-023-09726-8 -
The Lancet. Microbe May 2024Surrogates of antiviral efficacy are needed for COVID-19. We aimed to investigate the relationship between the virological effect of treatment and clinical efficacy as... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Surrogates of antiviral efficacy are needed for COVID-19. We aimed to investigate the relationship between the virological effect of treatment and clinical efficacy as measured by progression to severe disease in outpatients treated for mild-to-moderate COVID-19.
METHODS
In this systematic review and meta-analysis, we searched PubMed, Scopus, and medRxiv from database inception to Aug 16, 2023, for randomised placebo-controlled trials that tested virus-directed treatments (ie, any monoclonal antibodies, convalescent plasma, or antivirals) in non-hospitalised individuals with COVID-19. We only included studies that reported both clinical outcomes (ie, rate of disease progression to hospitalisation or death) and virological outcomes (ie, viral load within the first 7 days of treatment). We extracted summary data from eligible reports, with discrepancies resolved through discussion. We used an established meta-regression model with random effects to assess the association between clinical efficacy and virological treatment effect, and calculated I to quantify residual study heterogeneity.
FINDINGS
We identified 1718 unique studies, of which 22 (with a total of 16 684 participants) met the inclusion criteria, and were in primarily unvaccinated individuals. Risk of bias was assessed as low in 19 of 22 studies for clinical outcomes, whereas for virological outcomes, a high risk of bias was assessed in 11 studies, some risk in ten studies, and a low risk in one study. The unadjusted relative risk of disease progression for each extra log copies per mL reduction in viral load in treated compared with placebo groups was 0·12 (95% CI 0·04-0·34; p<0·0001) on day 3, 0·20 (0·08-0·50; p=0·0006) on day 5, and 0·53 (0·30-0·94; p=0·030) on day 7. The residual heterogeneity in our meta-regression was estimated as low (I=0% [0-53] on day 3, 0% [0-71] on day 5, and 0% [0-43] on day 7).
INTERPRETATION
Despite the aggregation of studies with differing designs, and evidence of risk of bias in some virological outcomes, this review provides evidence that treatment-induced acceleration of viral clearance within the first 5 days after treatment is a potential surrogate of clinical efficacy to prevent hospitalisation with COVID-19. This work supports the use of viral clearance as an early phase clinical trial endpoint of therapeutic efficacy.
FUNDING
Australian Government Department of Health, Medical Research Future Fund, and Australian National Health and Medical Research Council.
Topics: Humans; COVID-19; Antiviral Agents; Viral Load; SARS-CoV-2; Treatment Outcome; COVID-19 Drug Treatment; Outpatients; Immunization, Passive; Randomized Controlled Trials as Topic; COVID-19 Serotherapy; Disease Progression; Hospitalization
PubMed: 38583464
DOI: 10.1016/S2666-5247(23)00398-1 -
Ocular adverse events following CAR-T cell therapy: A pharmacovigilance study and systematic review.European Journal of Haematology Jul 2024The rise of immuno-oncology, including the use of chimeric antigen receptor T-cell (CAR-T) therapy is bringing in a new wave of cancer treatments, particularly in...
The rise of immuno-oncology, including the use of chimeric antigen receptor T-cell (CAR-T) therapy is bringing in a new wave of cancer treatments, particularly in hematologic malignancies. However, data on their adverse events, particularly of the eye, is under-reported. To assess the ocular adverse events associated with the six FDA-approved CAR-T cell therapies, a disproportionality analysis utilizing the FAERS database was conducted from the first quarter of 2017 to the third quarter of 2023, as well as a systematic review of case reports of ocular events following CAR-T cell therapy up to December 20, 2023. A total of 53 ocular adverse events were identified from the FDAs FAERS database. The adverse events most frequently observed were mydriasis and xerophthalmia with tisagenlecleucel (Kymriah). The systematic review resulted in 8 case reports encompassing 19 patients which included a total of 27 events. This study demonstrates the importance of anticipation of potential ocular adverse events by ophthalmologists and oncologists as they can greatly contribute to morbidity in patients with cancer.
Topics: Humans; Eye Diseases; Hematologic Neoplasms; Immunotherapy, Adoptive; Pharmacovigilance
PubMed: 38549191
DOI: 10.1111/ejh.14208 -
The Lancet. Global Health Jun 2024Respiratory syncytial virus (RSV) represents a substantial global health challenge, with a disproportionately high disease burden in low-income and middle-income...
BACKGROUND
Respiratory syncytial virus (RSV) represents a substantial global health challenge, with a disproportionately high disease burden in low-income and middle-income countries. RSV exhibits seasonality in most areas globally, and a comprehensive understanding of within-country variations in RSV seasonality could help to define the timing of RSV immunisation programmes. This study focused on China, and aimed to describe the geographical distribution of RSV seasonality, identify distinct RSV transmission zones, and evaluate the potential suitability of a seasonal RSV prevention strategy.
METHODS
We did a systematic analysis of RSV seasonality in China, with use of data on RSV activity extracted from a systematic review of studies published on Embase, MEDLINE, Web of Science, China National Knowledge Infrastructure, Wanfang Data, Chongqing VIP Information, and SinoMed, from database inception until May 5, 2023. We included studies of any design in China reporting at least 25 RSV cases, which aggregated RSV case number by calendar month or week at the province level, and with data covering at least 12 consecutive months before the year 2020 (prior to the COVID-19 pandemic). Studies that used only serology for RSV testing were excluded. We also included weekly data on RSV activity from open-access online databases of the Taiwan National Infection Disease Statistics System and Hong Kong Centre for Health Protection, applying the same eligiblity requirements. Across all datasets, we excluded data on RSV activity from Jan 1, 2020, onwards. We estimated RSV seasonal epidemic onset and duration using the annual average percentage (AAP) approach, and summarised seasonality at the provincial level. We used Pearson's partial correlation analysis to assess the correlation between RSV season duration and the latitude and longitude of the individual provinces. To define transmission zones, we used two independent approaches, an infant-passive-immunisation-driven approach (the moving interval approach, 6-month interval) and a data-driven approach (k-means), to identify groups of provinces with similar RSV seasonality. The systematic review was registered on PROSPERO, CRD42022376993.
FINDINGS
A total of 157 studies were included along with the two online datasets, reporting data on 194 596 RSV cases over 442 study-years (covering the period from Jan 1, 1993 to Dec 31, 2019), from 52 sites in 23 provinces. Among 21 provinces with sufficient data (≥100 reported cases), the median duration of RSV seasonal epidemics was 4·6 months (IQR 4·1-5·4), with a significant latitudinal gradient (r=-0·69, p<0·0007), in that provinces on or near the Tropic of Cancer had the longest epidemic duration. We found no correlation between longitude and epidemic duration (r=-0·15, p=0·53). 15 (71%) of 21 provinces had RSV epidemics from November to March. 13 (62%) of 21 provinces had clear RSV seasonality (epidemic duration ≤5 months). The moving interval approach categorised the 21 provinces into four RSV transmission zones. The first zone, consisting of five provinces (Fujian, Guangdong, Hong Kong, Taiwan, and Yunnan), was assessed as unsuitable for seasonal RSV immunisation strategies; the other three zones were considered suitable for seasonal RSV immunisation strategies with the optimal start month varying between September (Hebei), October (Anhui, Chongqing, Henan, Hubei, Jiangsu, Shaanxi, Shandong, Shanghai, Sichuan, and Xinjiang), and November (Beijing, Gansu, Guizhou, Hunan, and Zhejiang). The k-means approach identified two RSV transmission zones, primarily differentiated by whether the province was on or near the Tropic of Cancer (Fujian, Guangdong, Hong Kong, Taiwan, Yunan, and Hunan) or not (the remaining 15 provinces).
INTERPRETATION
Although substantial variations in RSV seasonality were observed across provinces of China, our study identified distinct transmission zones with shared RSV circulating patterns. These findings could have important implications for decision making on RSV passive immunisation strategy. Furthermore, the methodological framework in this study for defining RSV seasons and identifying RSV transmission zones is potentially applicable to other countries or regions.
FUNDING
Nanjing Medical University.
TRANSLATION
For the Chinese translation of the abstract see Supplementary Materials section.
Topics: Humans; Respiratory Syncytial Virus Infections; China; Seasons; Respiratory Syncytial Virus, Human
PubMed: 38670132
DOI: 10.1016/S2214-109X(24)00090-1