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Allergy Jun 2022There is substantial interest in immunotherapy and biologicals in IgE-mediated food allergy. (Meta-Analysis)
Meta-Analysis
BACKGROUND
There is substantial interest in immunotherapy and biologicals in IgE-mediated food allergy.
METHODS
We searched six databases for randomized controlled trials about immunotherapy alone or with biologicals (to April 2021) or biological monotherapy (to September 2021) in food allergy confirmed by oral food challenge. We pooled the data using random-effects meta-analysis.
RESULTS
We included 36 trials about immunotherapy with 2126 mainly child participants. Oral immunotherapy increased tolerance whilst on therapy for peanut (RR 9.9, 95% CI 4.5.-21.4, high certainty); cow's milk (RR 5.7, 1.9-16.7, moderate certainty) and hen's egg allergy (RR 8.9, 4.4-18, moderate certainty). The number needed to treat to increase tolerance to a single dose of 300 mg or 1000 mg peanut protein was 2. Oral immunotherapy did not increase adverse reactions (RR 1.1, 1.0-1.2, low certainty) or severe reactions in peanut allergy (RR 1,6, 0.7-3.5, low certainty), but may increase (mild) adverse reactions in cow's milk (RR 3.9, 2.1-7.5, low certainty) and hen's egg allergy (RR 7.0, 2.4-19.8, moderate certainty). Epicutaneous immunotherapy increased tolerance whilst on therapy for peanut (RR 2.6, 1.8-3.8, moderate certainty). Results were unclear for other allergies and administration routes. There were too few trials of biologicals alone (3) or with immunotherapy (1) to draw conclusions.
CONCLUSIONS
Oral immunotherapy improves tolerance whilst on therapy and is probably safe in peanut, cow's milk and hen's egg allergy. More research is needed about quality of life, cost and biologicals.
Topics: Allergens; Animals; Cattle; Chickens; Desensitization, Immunologic; Egg Hypersensitivity; Female; Food Hypersensitivity; Humans; Immunoglobulin E; Quality of Life
PubMed: 35001400
DOI: 10.1111/all.15211 -
Frontiers in Immunology 2022Recombinant Adeno-associated virus (rAAV) is one of the main delivery vectors for gene therapy. To assess immunogenicity, toxicity, and features of AAV gene therapy in... (Meta-Analysis)
Meta-Analysis
Recombinant Adeno-associated virus (rAAV) is one of the main delivery vectors for gene therapy. To assess immunogenicity, toxicity, and features of AAV gene therapy in clinical settings, a meta-analysis of 255 clinical trials was performed. A total of 7,289 patients are planned to be dosed. AAV2 was the most dominantly used serotype (29.8%, n=72), and 8.3% (n=20) of trials used engineered capsids. 38.7% (n=91) of trials employed neutralizing antibody assays for patient enrollment, while 15.3% (n=36) used ELISA-based total antibody assays. However, there was high variability in the eligibility criteria with cut-off tiers ranging from 1:1 to 1:1,600. To address potential immunogenicity, 46.3% (n=118) of trials applied immunosuppressants (prophylactic or reactive), while 32.7% (n=18) of CNS and 37.5% (n=24) of ocular-directed trials employed immunosuppressants, possibly due to the immune-privileged status of CNS and retina. There were a total of 11 patient deaths across 8 trials, and 18 out of 30 clinical holds were due to toxicity findings in clinical studies. 30.6% (n=78) of trials had treatment-emergent serious adverse events (TESAEs), with hepatotoxicity and thrombotic microangiopathy (systemic delivery) and neurotoxicity (CNS delivery) being the most prominent. Additionally, the durability of gene therapy may be impacted by two distinct decline mechanisms: 1) rapid decline presumably due to immune responses; or 2) gradual decline due to vector dilution. The durability varied significantly depending on disease indication, dose, serotypes, and patient individuals. Most CNS (90.0%) and muscle trials (73.3%) achieved durable transgene expression, while only 43.6% of ocular trials had sustained clinical outcomes. The rAAV production system can affect rAAV quality and thus immunogenicity and toxicity. Out of 186 trials that have disclosed production system information, 63.0% (n=126) of trials used the transient transfection of the HEK293/HEK293T system, while 18.0% (n=36) applied the baculovirus/Sf9 (rBac/Sf9) system. There were no significant differences in TESAEs and durability between AAV generated by rBac/Sf9 and HEK293/HEK293T systems. In summary, rAAV immunogenicity and toxicity poses significant challenges for clinical development of rAAV gene therapies, and it warrants collaborative efforts to standardize monitoring/measurement methods, design novel strategies to overcome immune responses, and openly share relevant information.
Topics: Humans; Dependovirus; HEK293 Cells; Genetic Vectors; Genetic Therapy; Immunosuppressive Agents
PubMed: 36389770
DOI: 10.3389/fimmu.2022.1001263 -
Multiple Sclerosis (Houndmills,... Jul 2023With the new highly active drugs available for people with multiple sclerosis (pwMS), vaccination becomes an essential part of the risk management strategy. (Review)
Review
BACKGROUND
With the new highly active drugs available for people with multiple sclerosis (pwMS), vaccination becomes an essential part of the risk management strategy.
OBJECTIVE
To develop a European evidence-based consensus for the vaccination strategy of pwMS who are candidates for disease-modifying therapies (DMTs).
METHODS
This work was conducted by a multidisciplinary working group using formal consensus methodology. Clinical questions (defined as population, interventions, and outcomes) considered all authorized DMTs and vaccines. A systematic literature search was conducted and quality of evidence was defined according to the Oxford Centre for Evidence-Based Medicine Levels of Evidence. The recommendations were formulated based on the quality of evidence and the risk-benefit balance.
RESULTS
Seven questions, encompassing vaccine safety, vaccine effectiveness, global vaccination strategy and vaccination in sub-populations (pediatric, pregnant women, elderly and international travelers) were considered. A narrative description of the evidence considering published studies, guidelines, and position statements is presented. A total of 53 recommendations were agreed by the working group after three rounds of consensus.
CONCLUSION
This first European consensus on vaccination in pwMS proposes the best vaccination strategy according to current evidence and expert knowledge, with the goal of homogenizing the immunization practices in pwMS.
Topics: Aged; Child; Female; Humans; Pregnancy; Consensus; Evidence-Based Medicine; Immunization; Multiple Sclerosis; Vaccination
PubMed: 37293841
DOI: 10.1177/13524585231168043 -
Archives of Medical Research Jan 2021Human Mesenchymal Stem Cells (hMSCs) are multipotent stem cells capable of renewing themselves and differentiation in vitro into different kinds of tissues. In vivo...
INTRODUCTION
Human Mesenchymal Stem Cells (hMSCs) are multipotent stem cells capable of renewing themselves and differentiation in vitro into different kinds of tissues. In vivo hMSCs are sources of trophic factors modulating the immune system and inducing intrinsic stem cells to repair damaged tissues. Currently, there are multiple clinical trials (CT) using hMSCs for therapeutic purposes in a large number of clinical settings.
MATERIAL AND METHODS
The search strategy on clinicaltrials.gov has focused on the key term "Mesenchymal Stem Cells", and the inclusion and exclusion criteria were separated into two stages. Stage 1, CT on phases 1-4: location, the field of application, phase, and status. For stage 2, CT that have published outcome results: field of application, treatment, intervention model, source, preparation methods, and results.
RESULTS
By July 2020, there were a total of 1,138 registered CT. Most studies belong to either phase 2 (61.0%) or phase 1 (30.8%); most of them focused in the fields of traumatology, neurology, cardiology, and immunology. Only 18 clinical trials had published results: the most common source of isolation was bone marrow; the treatment varied from 1-200 M hMSCs; all of them have similar preparation methods; all of them have positive results with no serious adverse effects.
CONCLUSIONS
There appears to be a broad potential for the clinical use of hMSCs with no reported serious adverse events. There are many trials in progress, their future results will help to explore the therapeutic potential of these promising cellular sources of medicinal signals.
Topics: Cell Differentiation; Clinical Trials as Topic; Humans; Medicine; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Regenerative Medicine
PubMed: 32977984
DOI: 10.1016/j.arcmed.2020.08.006 -
Critical Care (London, England) Jul 2023Definitions for massive transfusion (MT) vary widely between studies, contributing to challenges in interpretation of research findings and practice evaluation. In this... (Review)
Review
BACKGROUND
Definitions for massive transfusion (MT) vary widely between studies, contributing to challenges in interpretation of research findings and practice evaluation. In this first systematic review, we aimed to identify all MT definitions used in randomised controlled trials (RCTs) to date to inform the development of consensus definitions for MT.
METHODS
We systematically searched the following databases for RCTs from inception until 11 August 2022: MEDLINE, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, Cumulative Index to Nursing and Allied Health Literature, and Transfusion Evidence Library. Ongoing trials were sought from CENTRAL, ClinicalTrials.gov, and World Health Organisation International Clinical Trials Registry Platform. To be eligible for inclusion, studies had to fulfil all the following three criteria: (1) be an RCT; (2) include an adult patient population with major bleeding who had received, or were anticipated to receive, an MT in any clinical setting; and (3) specify a definition for MT as an inclusion criterion or outcome measure.
RESULTS
Of the 8,458 distinct references identified, 30 trials were included for analysis (19 published, 11 ongoing). Trauma was the most common clinical setting in published trials, while for ongoing trials, it was obstetrics. A total of 15 different definitions of MT were identified across published and ongoing trials, varying greatly in cut-offs for volume transfused and time period. Almost all definitions specified the number of red blood cells (RBCs) within a set time period, with none including plasma, platelets or other haemostatic agents that are part of contemporary transfusion resuscitation. For completed trials, the most commonly used definition was transfusion of ≥ 10 RBC units in 24 h (9/19, all in trauma), while for ongoing trials it was 3-5 RBC units (n = 7), with the timing for transfusion being poorly defined, or in some trials not provided at all (n = 5).
CONCLUSIONS
Transfusion of ≥ 10 RBC units within 24 h was the most commonly used definition in published RCTs, while lower RBC volumes are being used in ongoing RCTs. Any consensus definitions should reflect the need to incorporate different blood components/products for MT and agree on whether a 'one-size-fits-all' approach should be used across different clinical settings.
Topics: Adult; Humans; Hemorrhage; Hemostatics; Blood Transfusion; Blood Platelets; Erythrocyte Transfusion
PubMed: 37407998
DOI: 10.1186/s13054-023-04537-z -
Cancer Research and Treatment Jul 2023We intend to evaluate the efficacy of salvage treatments for relapsed or refractory diffuse large B-cell lymphoma (R/R DLBCL) through meta-analysis. (Meta-Analysis)
Meta-Analysis
Efficacy of Salvage Treatments in Relapsed or Refractory Diffuse Large B-Cell Lymphoma Including Chimeric Antigen Receptor T-Cell Therapy: A Systematic Review and Meta-Analysis.
PURPOSE
We intend to evaluate the efficacy of salvage treatments for relapsed or refractory diffuse large B-cell lymphoma (R/R DLBCL) through meta-analysis.
MATERIALS AND METHODS
R/R DLBCL trials were divided into two groups based on eligibility for autologous stem-cell transplantation (ASCT), and meta-analysis of each group was performed. Random effects models were used to estimate the 1-year progression-free survival (PFS) rate, and chimeric antigen receptor (CAR) T-cell therapy was used as reference treatment.
RESULTS
Twenty-six ASCT-eligible cohorts from 17 studies comprising 2,924 patients and 59 ASCT-ineligible cohorts from 53 studies comprising 3,617 patients were included in the pooled analysis. In the ASCT-eligible group, the pooled 1-year PFS rate was 0.40 (95% confidence interval [CI], 0.15 to 0.65) for the CAR T-cell group and 0.34 (95% CI, 0.30 to 0.37) for the group with chemotherapy followed by ASCT intention. The two treatments were not significantly different in meta-regression analysis. In the ASCT-ineligible group, the pooled 1-year PFS was 0.40 (95% CI, 0.35 to 0.46) for CAR T-cell, and the highest primary outcome was 0.47 (95% CI, 0.37 to 0.57) for the tafasitamab group. CAR T-cell therapy showed significantly better outcomes than chemotherapy and therapies based on ibrutinib, lenalidomide, and selinexor. However, loncastuximab, polatuzumab plus bendamustine and rituximab, and the tafasitamab group showed no different efficacy than CAR T-cell therapy after adjusting for median number of previous lines of treatment.
CONCLUSION
Although several regimens were crudely grouped for classification, CAR T-cell therapy did not outperform chemotherapy followed by ASCT in the second-line setting or several recently developed agents in the ASCT-ineligible setting.
Topics: Humans; Receptors, Chimeric Antigen; Immunotherapy, Adoptive; Combined Modality Therapy; Antineoplastic Combined Chemotherapy Protocols; Salvage Therapy; Neoplasm Recurrence, Local; Hematopoietic Stem Cell Transplantation; Lymphoma, Large B-Cell, Diffuse
PubMed: 36915243
DOI: 10.4143/crt.2022.1658 -
Journal of Periodontology Mar 2020Orthodontic treatment can greatly impact the periodontium, especially in dentitions with a thin periodontal phenotype. Orthodontic tooth movement can result into...
BACKGROUND
Orthodontic treatment can greatly impact the periodontium, especially in dentitions with a thin periodontal phenotype. Orthodontic tooth movement can result into iatrogenic sequelae to these vulnerable anatomic conditions, such as development and exacerbation of bony dehiscence or fenestration defects, which can manifest loss of periodontal support and gingival recession (GR). This systematic review aimed to investigate whether periodontal phenotype modification therapy (PhMT) involving hard tissue augmentation (PhMT-b) or soft tissue augmentation (PhMT-s) has clinical benefits for patients undergoing orthodontic treatment.
METHODS
An electronic search was performed in two major databases for journals published in English language from January 1975 to January 2019 and a hand search of printed journals was also performed to identify human clinical trials reporting clinical and radiographic outcomes of patients receiving orthodontic treatment with or without hard and soft tissue augmentation procedures. Data were extracted and organized into tables for qualitative assessment.
RESULTS
Eight studies were identified evaluating the outcomes of PhMT in patients undergoing orthodontic therapy. Six studies evaluated patients receiving PhMT-b via corticotomy-assisted orthodontic therapy (CAOT) and simultaneous bone augmentation while the other two received PhMT-s before tooth movement. No studies investigated PhMT-b alone without CAOT and most studies focused on the mandibular anterior decompensation movements. There was high heterogeneity in the study design and inconsistency of the reported outcomes; therefore, a meta-analysis was not performed. Evidence at this moment supports CAOT with hard tissue augmentation accelerated tooth movement. However, only two studies provided direct comparison to support that CAOT with PhMT-b reduced the overall treatment time compared with conventional orthodontic treatment. No periodontal complications or evidence of severe root resorption were reported for both groups. Four studies provided radiographic assessment of the PhMT-b and demonstrated increased radiographic density or thicker facial bone after the treatment. Two studies reported an expanded tooth movement. One study reported an increase in keratinized tissue width post-CAOT plus PhMT-b, while another study with a 10-year follow-up showed a lower degree of relapse using the mandibular irregularity index when compared with conventional tooth movement alone. Two studies examined the effect of PhMT-s before orthodontic treatment. Unfortunately, no conclusions can be drawn because of the limited number of studies with contradicting outcomes.
CONCLUSIONS
Within the limited studies included in this systematic review, PhMT-b via particulate bone grafting together with CAOT may provide clinical benefits such as modifying periodontal phenotype, maintaining or enhancing facial bone thickness, accelerating tooth movement, expanding the scope of safe tooth movement for patients undergoing orthodontic tooth movement. The benefits of PhMT-s alone for orthodontic treatment remain undetermined due to limited studies available. However, PhMT-b appears promising and with many potential benefits for patients undergoing orthodontic tooth movement. There is a need for a higher quality of randomized controlled trials or case control studies with longer follow-up to investigate the effects of different grafting materials and surgical sites other than mandibular anterior region.
Topics: Bone Transplantation; Gingival Recession; Humans; Phenotype; Root Resorption; Tooth Movement Techniques; United States
PubMed: 31670836
DOI: 10.1002/JPER.19-0037 -
The Cochrane Database of Systematic... Oct 2016There is considerable uncertainty regarding the optimal haemoglobin threshold for the use of red blood cell (RBC) transfusions in anaemic patients. Blood is a scarce... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
There is considerable uncertainty regarding the optimal haemoglobin threshold for the use of red blood cell (RBC) transfusions in anaemic patients. Blood is a scarce resource, and in some countries, transfusions are less safe than others because of a lack of testing for viral pathogens. Therefore, reducing the number and volume of transfusions would benefit patients.
OBJECTIVES
The aim of this review was to compare 30-day mortality and other clinical outcomes in participants randomized to restrictive versus liberal red blood cell (RBC) transfusion thresholds (triggers) for all conditions. The restrictive transfusion threshold uses a lower haemoglobin level to trigger transfusion (most commonly 7 g/dL or 8 g/dL), and the liberal transfusion threshold uses a higher haemoglobin level to trigger transfusion (most commonly 9 g/dL to 10 g/dL).
SEARCH METHODS
We identified trials by searching CENTRAL (2016, Issue 4), MEDLINE (1946 to May 2016), Embase (1974 to May 2016), the Transfusion Evidence Library (1950 to May 2016), the Web of Science Conference Proceedings Citation Index (1990 to May 2016), and ongoing trial registries (27 May 2016). We also checked reference lists of other published reviews and relevant papers to identify any additional trials.
SELECTION CRITERIA
We included randomized trials where intervention groups were assigned on the basis of a clear transfusion 'trigger', described as a haemoglobin (Hb) or haematocrit (Hct) level below which a red blood cell (RBC) transfusion was to be administered.
DATA COLLECTION AND ANALYSIS
We pooled risk ratios of clinical outcomes across trials using a random-effects model. Two people extracted the data and assessed the risk of bias. We conducted predefined analyses by clinical subgroups. We defined participants randomly allocated to the lower transfusion threshold as 'restrictive transfusion' and to the higher transfusion threshold as 'liberal transfusion'.
MAIN RESULTS
A total of 31 trials, involving 12,587 participants, across a range of clinical specialities (e.g. surgery, critical care) met the eligibility criteria. The trial interventions were split fairly equally with regard to the haemoglobin concentration used to define the restrictive transfusion group. About half of them used a 7 g/dL threshold, and the other half used a restrictive transfusion threshold of 8 g/dL to 9 g/dL. The trials were generally at low risk of bias .Some items of methodological quality were unclear, including definitions and blinding for secondary outcomes.Restrictive transfusion strategies reduced the risk of receiving a RBC transfusion by 43% across a broad range of clinical specialties (risk ratio (RR) 0.57, 95% confidence interval (CI) 0.49 to 0.65; 12,587 participants, 31 trials; high-quality evidence), with a large amount of heterogeneity between trials (I² = 97%). Overall, restrictive transfusion strategies did not increase or decrease the risk of 30-day mortality compared with liberal transfusion strategies (RR 0.97, 95% CI 0.81 to 1.16, I² = 37%; N = 10,537; 23 trials; moderate-quality evidence) or any of the other outcomes assessed (i.e. cardiac events (low-quality evidence), myocardial infarction, stroke, thromboembolism (high-quality evidence)). Liberal transfusion did not affect the risk of infection (pneumonia, wound, or bacteraemia).
AUTHORS' CONCLUSIONS
Transfusing at a restrictive haemoglobin concentration of between 7 g/dL to 8 g/dL decreased the proportion of participants exposed to RBC transfusion by 43% across a broad range of clinical specialities. There was no evidence that a restrictive transfusion strategy impacts 30-day mortality or morbidity (i.e. mortality at other points, cardiac events, myocardial infarction, stroke, pneumonia, thromboembolism, infection) compared with a liberal transfusion strategy. There were insufficient data to inform the safety of transfusion policies in certain clinical subgroups, including acute coronary syndrome, myocardial infarction, neurological injury/traumatic brain injury, acute neurological disorders, stroke, thrombocytopenia, cancer, haematological malignancies, and bone marrow failure. The findings provide good evidence that transfusions with allogeneic RBCs can be avoided in most patients with haemoglobin thresholds above 7 g/dL to 8 g/dL.
Topics: Anemia; Erythrocyte Transfusion; Hematocrit; Hemoglobin A; Humans; Practice Guidelines as Topic; Randomized Controlled Trials as Topic; Reference Values; Transplantation, Autologous; Transplantation, Homologous
PubMed: 27731885
DOI: 10.1002/14651858.CD002042.pub4 -
The Cochrane Database of Systematic... Aug 2016Severe bleeding and coagulopathy are serious clinical conditions that are associated with high mortality. Thromboelastography (TEG) and thromboelastometry (ROTEM) are... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Severe bleeding and coagulopathy are serious clinical conditions that are associated with high mortality. Thromboelastography (TEG) and thromboelastometry (ROTEM) are increasingly used to guide transfusion strategy but their roles remain disputed. This review was first published in 2011 and updated in January 2016.
OBJECTIVES
We assessed the benefits and harms of thromboelastography (TEG)-guided or thromboelastometry (ROTEM)-guided transfusion in adults and children with bleeding. We looked at various outcomes, such as overall mortality and bleeding events, conducted subgroup and sensitivity analyses, examined the role of bias, and applied trial sequential analyses (TSAs) to examine the amount of evidence gathered so far.
SEARCH METHODS
In this updated review we identified randomized controlled trials (RCTs) from the following electronic databases: Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 1); MEDLINE; Embase; Science Citation Index Expanded; International Web of Science; CINAHL; LILACS; and the Chinese Biomedical Literature Database (up to 5 January 2016). We contacted trial authors, authors of previous reviews, and manufacturers in the field. The original search was run in October 2010.
SELECTION CRITERIA
We included all RCTs, irrespective of blinding or language, that compared transfusion guided by TEG or ROTEM to transfusion guided by clinical judgement, guided by standard laboratory tests, or a combination. We also included interventional algorithms including both TEG or ROTEM in combination with standard laboratory tests or other devices. The primary analysis included trials on TEG or ROTEM versus any comparator.
DATA COLLECTION AND ANALYSIS
Two review authors independently abstracted data; we resolved any disagreements by discussion. We presented pooled estimates of the intervention effects on dichotomous outcomes as risk ratio (RR) with 95% confidence intervals (CIs). Due to skewed data, meta-analysis was not provided for continuous outcome data. Our primary outcome measure was all-cause mortality. We performed subgroup and sensitivity analyses to assess the effect based on the presence of coagulopathy of a TEG- or ROTEM-guided algorithm, and in adults and children on various clinical and physiological outcomes. We assessed the risk of bias through assessment of trial methodological components and the risk of random error through TSA.
MAIN RESULTS
We included eight new studies (617 participants) in this updated review. In total we included 17 studies (1493 participants). A total of 15 trials provided data for the meta-analyses. We judged only two trials as low risk of bias. The majority of studies included participants undergoing cardiac surgery.We found six ongoing trials but were unable to retrieve any data from them. Compared with transfusion guided by any method, TEG or ROTEM seemed to reduce overall mortality (7.4% versus 3.9%; risk ratio (RR) 0.52, 95% CI 0.28 to 0.95; I(2) = 0%, 8 studies, 717 participants, low quality of evidence) but only eight trials provided data on mortality, and two were zero event trials. Our analyses demonstrated a statistically significant effect of TEG or ROTEM compared to any comparison on the proportion of participants transfused with pooled red blood cells (PRBCs) (RR 0.86, 95% CI 0.79 to 0.94; I(2) = 0%, 10 studies, 832 participants, low quality of evidence), fresh frozen plasma (FFP) (RR 0.57, 95% CI 0.33 to 0.96; I(2) = 86%, 8 studies, 761 participants, low quality of evidence), platelets (RR 0.73, 95% CI 0.60 to 0.88; I(2) = 0%, 10 studies, 832 participants, low quality of evidence), and overall haemostatic transfusion with FFP or platelets (low quality of evidence). Meta-analyses also showed fewer participants with dialysis-dependent renal failure.We found no difference in the proportion needing surgical reinterventions (RR 0.75, 95% CI 0.50 to 1.10; I(2) = 0%, 9 studies, 887 participants, low quality of evidence) and excessive bleeding events or massive transfusion (RR 0.38, 95% CI 0.38 to 1.77; I(2) = 34%, 2 studies, 280 participants, low quality of evidence). The planned subgroup analyses failed to show any significant differences.We graded the quality of evidence as low based on the high risk of bias in the studies, large heterogeneity, low number of events, imprecision, and indirectness. TSA indicates that only 54% of required information size has been reached so far in regards to mortality, while there may be evidence of benefit for transfusion outcomes. Overall, evaluated outcomes were consistent with a benefit in favour of a TEG- or ROTEM-guided transfusion in bleeding patients.
AUTHORS' CONCLUSIONS
There is growing evidence that application of TEG- or ROTEM-guided transfusion strategies may reduce the need for blood products, and improve morbidity in patients with bleeding. However, these results are primarily based on trials of elective cardiac surgery involving cardiopulmonary bypass, and the level of evidence remains low. Further evaluation of TEG- or ROTEM-guided transfusion in acute settings and other patient categories in low risk of bias studies is needed.
Topics: Adult; Blood Coagulation Disorders; Cardiac Surgical Procedures; Child; Erythrocyte Transfusion; Hemorrhage; Humans; Liver Transplantation; Outcome Assessment, Health Care; Plasma; Randomized Controlled Trials as Topic; Thrombelastography
PubMed: 27552162
DOI: 10.1002/14651858.CD007871.pub3 -
Gynecologic Oncology Jun 2022Adoptive cell therapy (ACT) has shown promise in hematologic and solid tumors. While data supports immunogenicity of gynecologic cancers, the benefit of ACT is not yet... (Meta-Analysis)
Meta-Analysis Review
Adoptive cell therapy (ACT) has shown promise in hematologic and solid tumors. While data supports immunogenicity of gynecologic cancers, the benefit of ACT is not yet clear. To address this question, we performed a comprehensive systematic review and meta-analysis. Eligible studies included those reporting oncologic response or toxicity data in at least one patient with any gynecologic cancer treated with ACT. Chi-square test and multivariable logistic regression were performed to identify predictors of response. We retrieved 281 articles, and 28 studies met our inclusion criteria. These comprised of 401 patients including 238 patients with gynecologic cancers (61.8% ovarian, 34.0% cervical, 2.9% endometrial, and 1.2% other). In patients with gynecologic cancers, response rates to ACT were 8.1% complete response, 18.2% partial response, and 31.4% stable disease, for an objective response rate (ORR) of 26.3%, disease control rate (DCR) of 57.6%, and median response duration of 5.5 months. Patients in studies reporting ≤1 median line of prior therapy had a higher ORR (52.9% vs. 22.6% for >1, p < 0.001), although DCR in the >1 group was still 53.2%. ORRs by ACT type were tumor infiltrating lymphocytes (TIL) 41.4%, natural killer cells 26.7%, peripheral autologous T-cells 18.4%, T-cell receptor-modified T-cells 15.4%, and chimeric antigen receptor T-cells 9.5% (p = 0.001). ORR was significantly improved with inclusion of lymphodepletion (34.8% vs. 15.4% without, p = 0.001). On multivariable analysis controlling for cancer type and lymphodepletion, TIL therapy was predictive of objective response (odds ratio 2.6, p = 0.011). The rate of grade 3 or 4 toxicity was 46.0%. All grade adverse events included fever, hypotension, dyspnea, confusion, hematologic changes, nausea/vomiting, fatigue, and diarrhea. In conclusion, ACT is a promising treatment modality in gynecologic cancer. We observed a particular benefit of TIL therapy and suggest inclusion of lymphodepletion in future trials.
Topics: Cell- and Tissue-Based Therapy; Female; Genital Neoplasms, Female; Humans; Immunotherapy, Adoptive; Lymphocytes, Tumor-Infiltrating; Receptors, Antigen, T-Cell
PubMed: 35400527
DOI: 10.1016/j.ygyno.2022.03.013