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Adverse effects in hematologic malignancies treated with chimeric antigen receptor (CAR) T cell therapy: a systematic review and Meta-analysis.
Luo, W, Li, C, Zhang, Y, Du, M, Kou, H, Lu, C, Mei, H, Hu, Y
BMC cancer. 2022;(1):98
Abstract
BACKGROUND Recently, chimeric antigen receptor-modified (CAR) T cell therapy for hematological malignancies has shown clinical efficacy. Hundreds of clinical trials have been registered and lots of studies have shown hematologic toxic effects were very common. The main purpose of this review is to systematically analyze hematologic toxicity in hematologic malignancies treated with CAR-T cell therapy. METHODS We searched databases including PubMed, Web of Science, Embase and Cochrane up to January 2021. For safety analysis of overall hematologic toxicity, the rate of neutrophil, thrombocytopenia and anemia were calculated. Subgroup analysis was performed for age, pathological type, target antigen, co-stimulatory molecule, history of hematopoietic stem cell transplantation (HSCT) and prior therapy lines. The incidence rate of aspartate transferase (AST) increased, alanine transaminase (ALT) increased, serum creatine increased, APTT prolonged and fibrinogen decreased were also calculated. RESULTS Overall, 52 studies involving 2004 patients were included in this meta-analysis. The incidence of any grade neutropenia, thrombocytopenia and anemia was 80% (95% CI: 68-89%), 61% (95% CI: 49-73%), and 68% (95%CI: 54-80%) respectively. The incidences of grade ≥ 3 neutropenia, thrombocytopenia and anemia were 60% (95% CI: 49-70%), 33% (95% CI: 27-40%), and 32% (95%CI: 25-40%) respectively. According to subgroup analysis and the corresponding Z test, hematological toxicity was more frequent in younger patients, in patients with ≥4 median lines of prior therapy and in anti-CD19 cases. The subgroup analysis of CD19 CAR-T cell constructs showed that 41BB resulted in less hematological toxicity than CD28. CONCLUSION CAR-T cell therapy has dramatical efficacy in hematological malignancies, but the relevant adverse effects remain its obstacle. The most common ≥3 grade side effect is hematological toxicity, and some cases die from infections or severe hemorrhage in early period. In long-term follow-up, hematological toxicity is less life-threatening generally and most suffered patients recover to adequate levels after 3 months. To prevent life-threatening infections or bleeding events, clinicians should pay attention to intervention of hematological toxicity in the early process of CAR-T cell therapy.
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Clinical efficacy and safety of Tanreqing injection combined with antibiotics versus antibiotics alone in the treatment of pulmonary infection patients after chemotherapy with lung cancer: A systematic review and meta-analysis.
Tong, Y, Wen, J, Yang, T, Li, H, Wei, S, Jing, M, Wang, M, Zou, W, Zhao, Y
Phytotherapy research : PTR. 2021;(1):122-137
Abstract
This study aimed to evaluate the efficacy and safety of Tanreqing injection (TRQi) in the treatment of pulmonary infection after chemotherapy in patients with lung cancer. Cochrane Library, PubMed, Web of Science, EMbase, CNKI, VMIS, Wan-Fang, and CBM databases were comprehensively searched from established to March 2020. randomized controlled trials (RCTs) of TRQi were selected. The evaluation manual of Cochrane RCT was used to evaluate the methodological quality of all included studies, Stata 13.0 and Review Manager 5.3 software was used for meta-analysis. This study is registered with PROSPERO (CRD42020175533). Eighteen RCTs with a total of 1,438 patients were met the inclusion criteria. Meta-analysis showed that compared with antibiotics alone, TRQi plus antibiotics could significantly improve the clinical efficacy, defervescence time, lung rale disappearance time, cough disappearance time, and average hospitalization time, reduce white blood cell, C-reactive protein, and procalcitonin levels, and adverse reactions. However, due to the small sample size and low quality of the study, more rigorous and more RCTs are needed for further verification. In conclusion, this study provides useful evidence for the efficacy and safety of TRQi combined with antibiotics in the treatment of pulmonary infection after chemotherapy with lung cancer.
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Effect of Neutropenic Diet on Infection Rates in Cancer Patients With Neutropenia: A Meta-analysis of Randomized Controlled Trials.
Ball, S, Brown, TJ, Das, A, Khera, R, Khanna, S, Gupta, A
American journal of clinical oncology. 2019;(3):270-274
Abstract
INTRODUCTION Neutropenic diets are commonly prescribed to cancer patients with neutropenia with the intention of reducing rates of infection. These diets are restrictive and are associated with lower patient satisfaction and possibly malnutrition. Further, it is unclear if these restrictive diets are effective in reducing infection. We performed a meta-analysis on the rates of infection reported in trials comparing the neutropenic diet to unrestricted diets in cancer patients with neutropenia. METHODS AND MATERIALS A comprehensive database search for all published randomized controlled trials comparing infection rates in cancer patients receiving a neutropenic diet versus an unrestricted diet was performed for all publications in English language from database's inception until September 12, 2017. The search strategy, study selection, and subsequent analysis adhered to PRISMA guidelines. Random effects modeling was used to obtain pooled relative risks. The primary outcome measure was the rate of infection. RESULTS Five randomized controlled trials with a total of 388 patients were included in the final analysis. Patients mostly had acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), or sarcoma. Infection was noted in 53.7% patients in the neutropenic diet group, as compared with 50% in the unrestricted diet group. No significant difference in infection rate was observed between the neutropenic diet versus unrestricted diet groups, pooled risk ratio (RR) 1.13 (95% CI, 0.98-1.30; P=0.10). CONCLUSIONS This meta-analysis of randomized controlled trials suggests that the use of neutropenic diet was not associated with decreased risk of infection in neutropenic cancer patients. The continued use of neutropenic diets should be questioned.
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Safety of Intravenous Iron in Dialysis: A Systematic Review and Meta-Analysis.
Hougen, I, Collister, D, Bourrier, M, Ferguson, T, Hochheim, L, Komenda, P, Rigatto, C, Tangri, N
Clinical journal of the American Society of Nephrology : CJASN. 2018;(3):457-467
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Abstract
BACKGROUND AND OBJECTIVES The safety of intravenous iron dosing in dialysis is uncertain. Higher-dose intravenous iron may be associated with a higher risk of infections, cardiovascular events, hospitalizations, and mortality. This systematic review aimed to determine the safety of higher-dose versus lower-dose intravenous iron, oral iron, or no iron supplementation in adult patients treated with dialysis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS We searched Medline, EMBASE, Cochrane library, and CINAHL from inception to January 6, 2017 for randomized, controlled trials and observational studies comparing higher-dose intravenous iron with lower-dose intravenous iron, oral iron, or no iron in patients treated with dialysis that had all-cause mortality, infection, cardiovascular events, or hospitalizations as outcomes. RESULTS Of the 2231 eligible studies, seven randomized, controlled trials and 15 observational studies met inclusion criteria. The randomized, controlled trials showed no association between higher-dose intravenous iron (>400 mg/mo for most studies) and mortality (six studies; n=970; pooled relative risk, 0.93; 95% confidence interval, 0.47 to 1.84; follow-up ranging from 35 days to 26 months) or infection (four studies; n=743; relative risk, 1.02; 95% confidence interval, 0.74 to 1.41). The observational studies showed no association between higher-dose intravenous iron (>200 mg/mo for most studies) and mortality (eight studies; n=241,408; hazard ratio, 1.09; 95% confidence interval, 0.98 to 1.21; follow-up ranging from 3 to 24 months), infection (eight studies; n=135,532; pooled hazard ratio, 1.13; 95% confidence interval, 0.99 to 1.28), cardiovascular events (seven studies; n=135,675; hazard ratio, 1.18; 95% confidence interval, 0.90 to 1.56), or hospitalizations (five studies; n=134,324; hazard ratio, 1.08; 95% confidence interval, 0.97 to 1.19). CONCLUSIONS Higher-dose intravenous iron does not seem to be associated with higher risk of mortality, infection, cardiovascular events, or hospitalizations in adult patients on dialysis. Strength of this finding is limited by small numbers of participants and events in the randomized, controlled trials and statistical heterogeneity in observational studies.
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Perioperative immunonutrition for gastrointestinal cancer: a systematic review of randomized controlled trials.
Zhang, Y, Gu, Y, Guo, T, Li, Y, Cai, H
Surgical oncology. 2012;(2):e87-95
Abstract
BACKGROUND To improve the clinical outcome, immunonutrition (IN) was usually used in the patients undergoing elective gastrointestinal caner surgery. However, its effectiveness remains uncertain. METHODS Randomized controlled trials (RCTs) published between 1995 and 2011 were identified and extracted by two reviewers independently from electronic databases, including PubMed, EMBASE, and Cochrane Library. The quality of included trials was assessed according to the handbook for Cochrane reviewer (V5.0.1). Statistical analysis was carried out with RevMan software. RESULTS Nineteen RCTs involving a total of 2331 patients were included in our meta-analysis. The results showed perioperative IN significantly reduced length of hospital stay (WMD, -2.62; 95% CI, -3.26 to -1.97; P < 0.01) and morbidity of postoperative infectious complication (RR, 0.44; 95% CI, 0.32 to 0.60; P < 0.01) compared with standard diet. Moreover, perioperative IN also significantly decreased morbidity of postoperative non-infectious complication in comparison with standard diet (RR, 0.72; 95% CI, 0.54 to 0.97; P = 0.03). CONCLUSION Perioperative IN is effective and safe to reduce postoperative infection, non-infection complication and length of hospital stay.
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Iron supplementation in early childhood: health benefits and risks.
Iannotti, LL, Tielsch, JM, Black, MM, Black, RE
The American journal of clinical nutrition. 2006;(6):1261-76
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The prevalence of iron deficiency among infants and young children living in developing countries is high. Because of its chemical properties--namely, its oxidative potential--iron functions in several biological systems that are crucial to human health. Iron, which is not easily eliminated from the body, can also cause harm through oxidative stress, interference with the absorption or metabolism of other nutrients, and suppression of critical enzymatic activities. We reviewed 26 randomized controlled trials of preventive, oral iron supplementation in young children (aged 0-59 mo) living in developing countries to ascertain the associated health benefits and risks. The outcomes investigated were anemia, development, growth, morbidity, and mortality. Initial hemoglobin concentrations and iron status were considered as effect modifiers, although few studies included such subgroup analyses. Among iron-deficient or anemic children, hemoglobin concentrations were improved with iron supplementation. Reductions in cognitive and motor development deficits were observed in iron-deficient or anemic children, particularly with longer-duration, lower-dose regimens. With iron supplementation, weight gains were adversely affected in iron-replete children; the effects on height were inconclusive. Most studies found no effect on morbidity, although few had sample sizes or study designs that were adequate for drawing conclusions. In a malaria-endemic population of Zanzibar, significant increases in serious adverse events were associated with iron supplementation, whereas, in Nepal, no effects on mortality in young children were found. More research is needed in populations affected by HIV and tuberculosis. Iron supplementation in preventive programs may need to be targeted through identification of iron-deficient children.
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A systematic review of multivitamin and multimineral supplementation for infection.
Stephen, AI, Avenell, A
Journal of human nutrition and dietetics : the official journal of the British Dietetic Association. 2006;(3):179-90
Abstract
BACKGROUND Infections are major causes of morbidity and mortality worldwide. Micronutrients have important functions in the body's immune system. This systematic review examined the evidence from randomized controlled trials (RCTs) on whether multivitamin and multimineral supplementation is effective in reducing infection. METHODS Electronic databases searched: Cochrane Controlled Trials Register, EMBASE, MEDLINE, BIOSIS, CAB abstracts. Hand searching of nutrition journals and reference lists was carried out. RCTs and quasi-randomized trials of supplementation of adults with at least two vitamins or minerals or a combination were selected. Study results were combined in meta-analysis plots where appropriate. RESULTS Twenty studies were included in the review. Small numbers were available for each meta-analysis. Results are presented here without the Chandra group studies. No significant difference was found in the number of episodes of infection in older people (>or = 65 years) between those supplemented and those not supplemented; (WMD) 0.06 [95% confidence interval (CI) -0.04, 0.16], P = 0.25. In other adults groups, there were significantly less episodes of infection in those supplemented; (WMD) -1.20 (95% CI -2.08, -0.32), P = 0.008. There was no significant difference between those older people supplemented and those not supplemented in the number with at least one infection; relative risk (RR) 0.98 (95% CI 0.86, 1.11), P = 0.77. Similarly, there was no significant difference in the numbers in other adult groups who had at least one episode of infection between those supplemented and those taking placebo; (RR) 0.81 (95% CI 0.65, 1.00), P = 0.06. Subgroup analyses suggested that supplemented people aged 65 years or over may benefit more if they are undernourished and supplemented for over 6 months, WMD -0.67 infections (95% CI -1.24, -0.10), P = 0.02. CONCLUSION Further large trials are needed, particularly in undernourished older people. Trials of supplementation periods of over 6 months are recommended.
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Postsurgical infections are reduced with specialized nutrition support.
Waitzberg, DL, Saito, H, Plank, LD, Jamieson, GG, Jagannath, P, Hwang, TL, Mijares, JM, Bihari, D
World journal of surgery. 2006;(8):1592-604
Abstract
OBJECTIVE The objective was to examine the relationship between pre-, peri-, and postoperative specialized nutritional support with immune-modulating nutrients and postoperative morbidity in patients undergoing elective surgery. METHODS Studies were identified by searching MEDLINE, review article bibliographies, and abstracts and proceedings of scientific meetings. All randomized clinical trials in which patients were supplemented by the IMPACT formula before and/or after elective surgery and the clinical outcomes reported were included in the meta-analysis. Seventeen studies (n=2,305), 14 published (n=2,102), and 3 unpublished (n=203), fulfilled the inclusion criteria. Ten studies (n=1,392) examined the efficacy of pre- or perioperative IMPACT supplementation in patients undergoing elective surgery, whereas 7 (n=913) assessed postoperative efficacy. Fourteen of the studies (n=2,083) involved gastrointestinal (GI) surgical patients. Postoperative complications, mortality, and length of stay in hospital (LOS) were major outcomes of interest. RESULTS IMPACT supplementation, in general, was associated with significant (39%-61%) reductions in postoperative infectious complications and a significant decrease in LOS in hospital by an average of 2 days. The greatest improvement in postoperative outcomes was observed in patients receiving specialized nutrition support as part of their preoperative treatment. In GI surgical patients, anastomotic leaks were 46% less prevalent when IMPACT supplementation was part of the preoperative treatment. CONCLUSION This study identifies a dosage (0.5-1 l/day) and duration (supplementation for 5-7 days before surgery) of IMPACT that contributes to improved outcomes of morbidity in elective surgery patients, particularly those undergoing GI surgical procedures. The cost effectiveness of such practice is supported by recent health economic analysis. Findings suggest preoperative IMPACT use for the prophylaxis of postoperative complications in elective surgical patients.