-
Hematology (Amsterdam, Netherlands) Dec 2024To explore the efficacy and safety of venetoclax-based combination therapy for older patients with newly diagnosed acute myeloid leukemia (AML). (Meta-Analysis)
Meta-Analysis Review
PURPOSE
To explore the efficacy and safety of venetoclax-based combination therapy for older patients with newly diagnosed acute myeloid leukemia (AML).
METHODS
We performed a systematic review and meta-analysis of clinical trials comparing venetoclax plus hypomethylating agents (HMAs) or low-dose cytarabine (LDAC) with mono-HMAs or LDAC. The random or fixed effects model was applied to the studies based on heterogeneity. Dichotomous data were summarized using the risk ratio (RR) and 95% confidence interval (CI). Continuous variable data were reported as weighted mean differences (WMDs).
RESULTS
Nine studies, including a total of 1232 patients, were included in this meta-analysis. Thec complete remission (CR)/complete remission with incomplete hematological recovery (CRi) rate of the venetoclax (Ven) + azacytidine (Aza) group was significantly greater than that of the Aza monotherapy group (RR: 2.42; 95% CI: 1.85-3.15; < 0.001). Similarly, the CR/CRi rate of the Ven + LDAC group was also significantly greater than that of the LDAC monotherapy group (RR: 2.57; 95% CI: 1.58-4.17; = 0.00). The same results were observed for OS among these groups. However, the incidence of febrile neutropenia was greater in the Ven + Aza group than in the Ven + Decitabine (Dec) or monotherapy Aza group (RR: 0.69; 95% CI: 0.53-0.90; = 0.006 and RR: 2.19; 95% CI: 1.58-3.03; < 0.001, respectively). In addition, the Ven + LDAC group had significantly greater rates of constipation, diarrhea, nausea, and vomiting than the LDAC monotherapy group, with RRs and CIs of 0.61 (95% CI 0.44-0.83, = 0.002), 1.81 (95% CI 1.22-2.67, = 0.003), 1.39 (95% CI 1.06-1.82, = 0.016), and 1.80 (95% CI 1.19-2.72, = 0.005), respectively.
CONCLUSION
Venetoclax combined with azacitidine, decitabine, or LDAC significantly improved the CR/CRi and OS of patients with previously untreated AML. However, venetoclax plus azacitidine or LDAC was more likely to lead to increased febrile neutropenia and gastrointestinal toxicity.
Topics: Humans; Bridged Bicyclo Compounds, Heterocyclic; Sulfonamides; Leukemia, Myeloid, Acute; Antineoplastic Combined Chemotherapy Protocols; Azacitidine; Treatment Outcome; Aged; Cytarabine
PubMed: 38703055
DOI: 10.1080/16078454.2024.2343604 -
Virology Journal May 2024Multiple studies have provided evidence of suboptimal or poor immune responses to SARS-CoV-2 vaccines in recipients of hematopoietic stem cell transplantation (HSCT) and... (Meta-Analysis)
Meta-Analysis Review
Immunologic responses to the third and fourth doses of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines in cell therapy recipients: a systematic review and meta-analysis.
BACKGROUND
Multiple studies have provided evidence of suboptimal or poor immune responses to SARS-CoV-2 vaccines in recipients of hematopoietic stem cell transplantation (HSCT) and chimeric antigen receptor-T (CAR-T) cell therapy compared to healthy individuals. Given the dynamic nature of SARS-CoV2, characterized by the emergence of many viral variations throughout the general population, there is ongoing discussion regarding the optimal quantity and frequency of additional doses required to sustain protection against SARS-CoV2 especially in this susceptible population. This systematic review and meta-analysis investigated the immune responses of HSCT and CAR-T cell therapy recipients to additional doses of the SARS-CoV-2 vaccines.
METHODS
Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, the study involved a comprehensive search across PubMed, Scopus, Web of Science Core Collection, Embase, and Cochrane Biorxiv and medRxiv, focusing on the serological responses to the third and fourth vaccine doses in HSCT and CAR-T cell patients.
RESULTS
This study included 32 papers, with 31 qualifying for the meta-analysis. Results showed that after the third dose, the seroconversion rate in HSCT and CAR-T cell therapy recipients who didn't respond to the second dose was 46.10 and 17.26%, respectively. Following the fourth dose, HSCT patients had a seroconversion rate of 27.23%. Moreover, post-third-dose seropositivity rates were 87.14% for HSCT and 32.96% for CAR-T cell therapy recipients. Additionally, the seropositive response to the fourth dose in the HSCT group was 90.04%.
CONCLUSION
While a significant portion of HSCT recipients developed antibodies after additional vaccinations, only a minority of CAR-T cell therapy patients showed a similar response. This suggests that alternative vaccination strategies are needed to protect these vulnerable groups effectively. Moreover, few studies have reported cellular responses to additional SARS-CoV-2 vaccinations in these patients. Further studies evaluating cellular responses are required to determine a more precise assessment of immunogenicity strength against SARS-CoV-2 after additional doses.
Topics: Humans; COVID-19 Vaccines; COVID-19; SARS-CoV-2; Hematopoietic Stem Cell Transplantation; Antibodies, Viral; Vaccination; Immunotherapy, Adoptive; Cell- and Tissue-Based Therapy
PubMed: 38702752
DOI: 10.1186/s12985-024-02375-1 -
Journal of Epidemiology and Global... May 2024Soil-transmitted helminthic (STH) infections are the leading cause of stunting among children. To lessen the burden, the World Health Organization (WHO) recommended a...
BACKGROUND
Soil-transmitted helminthic (STH) infections are the leading cause of stunting among children. To lessen the burden, the World Health Organization (WHO) recommended a periodic deworming program through the use of single-dose therapy in the endemic regions. Therefore, the purpose of this study was to synthesize evidence about the efficacy of anthelminthic drugs against STH infections among preschool and school-age children.
METHODS
The Preferred Reposting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria were followed in this study. Relevant electronic databases, including PubMed, Scopus, Embase, DOAJ, Science Direct, the WHO Clinical Trials.gov library, Google Scholar, and AJOL databases, were searched for relevant publications. Randomized controlled trials (RCTs) and non-randomized interventional studies focused on the efficacy of albendazole and mebendazole against STHs in children were included in the study. Review Manager was used to analyze the data. A random effects model was used to obtain the pooled estimated efficacy. To evaluate heterogeneity, the I test and Cochrane Q (χ) were employed. The risk of publication bias was investigated using Egger's test and the funnel plot. The protocol of this review was registered at the PROSPERO international prospective register of systematic reviews (CRD42023401196).
RESULTS
Of the 69 publications selected for the systematic review, 66 with complete data were included in the meta-analysis. Single doses of albendazole and mebendazole have shown satisfactory efficacy [egg reduction rate (ERR)] against Ascaris lumbricoides [95.54% (95% CI: 88.75-102.34%) and 98.69% (95% CI: 97.68-99.65%), respectively. The effectiveness of these two drugs against Trichuris trichiura and hookworms was comparatively low (< 80% ERR), except for albendazole, which showed high ERRs [93.44% (95%CI: 92.39-94.49%)] against hookworms. The cure rate (CR) of albendazole against T. trichiura, A. lumbricoides, and hookworms were 50.8%, 91.3%, and 78.32%, respectively. Likewise, mebendazole showed CRs of 48.15%, 92.8%, and 49.32% against T. trichiura, A. lumbricoides, and hookworms, respectively. Subgroups such as studies conducted after 2000, diagnostic type (McMaster), and longer follow-up weeks significantly reduced the efficacy of the two drugs against T. trichura. While the combination of albendazole or mebendazole with other drugs and RCT showed significantly improved efficacy against T. trichura. The count of eggs per gram of stool (EPG) was identified as one of the variables that negatively and significantly influenced the efficacy of albendazole or mebendazole against A. lumbricoides.
CONCLUSION
Despite the wide range of ERRs and CR reported in the different articles included in this review, the pooled estimated efficacy of albendazole and mebendazole against STHs falls in the satisfactory category of WHO recommendations. Further evaluation of the combination of anthelminthic drugs as a preventive chemotherapy option and routine drug efficacy testing are necessary to prevent the emergence and widespread use of drug-resistant STHs.
PubMed: 38696109
DOI: 10.1007/s44197-024-00231-7 -
Neurosurgical Focus May 2024In the treatment of skull base chordoma (SBC) surgery is considered the mainstay approach, and gross-total resection has an established relationship with... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
In the treatment of skull base chordoma (SBC) surgery is considered the mainstay approach, and gross-total resection has an established relationship with progression-free survival (PFS) and overall survival (OS). However, the tumor's location often interferes with attempts at complete resection. In this case, surgery for maximal resection followed by high-dose radiotherapy has been demonstrated to be the standard treatment. In this context, various modalities are available, yet no consensus exists on the most effective. This systematic review and meta-analysis aimed to evaluate the efficacy and safety of different radiotherapy modalities for SBC.
METHODS
Following PRISMA guidelines, the authors systematically searched for the treatment of SBC with radiation modalities in the PubMed, Cochrane, Web of Science, and EMBASE databases. Outcomes assessed for each modality were as follows: OS, PFS, local control (LC), and complications. The random-effects model was adopted. A single-proportion analysis with 95% CI was used to measure the effects in single-arm analysis. For the comparative analysis, the OR with 95% CI was used to compare outcome treatment effects. Heterogeneity was assessed using I2 statistics, and statistical significance was defined as p < 0.05.
RESULTS
A total of 32 studies comprising 3663 patients, with 2322 patients who were treated with radiotherapeutic modalities, were included. Regarding 5-year OS findings in each modality study, the findings were as follows: in photon fractionated radiotherapy, an estimated rate of 77% (69%-84%, 568 patients); in conventional fractionated radiotherapy, 76% (65%-87%, 517 cases); in proton-based + carbon ion-based radiotherapy, 85% (82%-88%, 622 cases); and in a comparative analysis of proton-based and carbon ion-based therapy, there was an OR of 1.2 (95% CI 0.59-2.43, 306 cases). Regarding the 5-year PFS estimate, the rates were as follows: 35% (26%-45%, 95 cases) for photon fractionated therapy; 35% (25%-45%, 85 cases) for stereotactic radiotherapy; 77% (50%-100%, 180 cases) for proton-based and carbon ion-based radiotherapy; and 74% (45%-100%, 102 cases) for proton-based radiotherapy. Regarding LC in periods of 3 and 5 years after proton- and carbon ion-based therapy, the overall estimated rates were 84% (78%-90%, 326 cases) and 75% (65%-85%, 448 cases), respectively. For proton-based radiotherapy and carbon ion-based therapy, the 5-year LC rates were 76% (67%-86%, 259 cases) and 75% (59%-91%, 189 cases), respectively.
CONCLUSIONS
The analysis highlights the finding that particle-based modalities like proton beam radiotherapy and carbon ion radiotherapy are the most effective radiation therapies available for the treatment of SBC. Furthermore, it reinforces the idea that surgery followed by radiotherapy constitutes the standard treatment.
Topics: Humans; Skull Base Neoplasms; Chordoma; Treatment Outcome; Radiosurgery
PubMed: 38691862
DOI: 10.3171/2024.2.FOCUS2413 -
Nutrition Journal Apr 2024Whole grains have recently been promoted as beneficial to diabetes prevention. However, the evidence for the glycemic benefits of whole grains seems to conflict between... (Meta-Analysis)
Meta-Analysis
PURPOSE
Whole grains have recently been promoted as beneficial to diabetes prevention. However, the evidence for the glycemic benefits of whole grains seems to conflict between the cohort studies and randomized control trials (RCTs). To fill the research gap, we conducted a meta-analysis to determine the effects of whole grains on diabetes prevention and to inform recommendations.
METHODS
We searched PubMed, Clarivate Web of Science, and Cochrane Library until March 2024. We used the risk ratio (RR) of type 2 diabetes to represent the clinical outcomes for cohort studies, while the biomarkers, including fasting blood glucose and insulin, HbA, and HOMA-IR, were utilized to show outcomes for RCTs. Dose-response relationships between whole grain intakes and outcomes were tested with random effects meta-regression models and restricted cubic splines models. This study is registered with PROSPERO, CRD42021281639.
RESULTS
Ten prospective cohort studies and 37 RCTs were included. Cohort studies suggested a 50 g/day whole grain intake reduced the risk of type 2 diabetes (RR = 0.761, 95% CI: 0.700 to 0.828, I = 72.39%, P < 0.001) and indicated a monotonic inverse relationship between whole grains and type 2 diabetes rate. In RCTs, whole grains significantly reduced fasting blood glucose (Mean difference (MD) = -0.103 mmol/L, 95% CI: -0.178 to -0.028; I = 72.99%, P < 0.01) and had modest effects on HbA (MD = -0.662 mmol/mol (-0.06%), 95% CI: -1.335 to 0.010; I = 64.55%, P = 0.05) and HOMA-IR (MD = -0.164, 95% CI: -0.342 to 0.013; I = 33.38%, P = 0.07). The intake of whole grains and FBG, HbA, and HOMA-IR were significantly dose-dependent. The restricted spline curves remained flat up to 150 g/day and decreased afterward. Subgroup analysis showed that interventions with multiple whole-grain types were more effective than those with a single type.
CONCLUSION
Our study findings suggest that a daily intake of more than 150 g of whole grain ingredients is recommended as a population approach for diabetes prevention.
Topics: Humans; Whole Grains; Randomized Controlled Trials as Topic; Diabetes Mellitus, Type 2; Glycemic Control; Blood Glucose; Prospective Studies; Diet; Glycated Hemoglobin; Insulin
PubMed: 38664726
DOI: 10.1186/s12937-024-00952-2 -
Frontiers in Medicine 2024COVID-19 vaccines are generally safe and effective; however, they are associated with various vaccine-induced cutaneous side effects. Several reported cases of primary...
INTRODUCTION
COVID-19 vaccines are generally safe and effective; however, they are associated with various vaccine-induced cutaneous side effects. Several reported cases of primary cutaneous lymphomas (CLs) following the COVID-19 vaccination have raised concerns about a possible association. This systematic review aims to investigate and elucidate the potential link between CLs and SARS-CoV-2 vaccines.
METHODS
We performed a systematic literature search on PubMed, EBSCO and Scopus from January 01, 2019, to March 01, 2023, and analyzed studies based on determined eligibility criteria. The systematic review was performed based on the PRISMA protocol.
RESULTS
A total of 12 articles (encompassing 24 patients) were included in this analysis. The majority of CLs were indolent cutaneous T-cell lymphomas (CTCLs) (66,7%; 16/24), with Lymphomatoid papulosis (LyP) being the most common type (33,3%; 8/24). Most patients (79,2%; 19/24) developed lesions after receiving the COVID-19 mRNA-based vaccines, and predominantly after the first immunization dose (54,2%; 13/24). The presented CLs cases exhibited a tendency to exacerbate following subsequent COVID-19 vaccinations. Nevertheless, CLs were characterized by a favorable course, leading to remission in most cases.
CONCLUSION
The available literature suggests an association between the occurrence and exacerbation of CLs with immune stimulation following COVID-19 vaccination. We hypothesize that post-vaccine CLs result from an interplay between cytokines and disrupted signaling pathways triggered by vaccine components, concurrently playing a pivotal role in the pathomechanism of CLs. However, establishing a definitive causal relationship between these events is currently challenging, primarily due to the relatively low rate of reported post-vaccine CLs. Nonetheless, these cases should not be disregarded, and patients with a history of lymphoproliferative disorders require post-COVID-19 vaccination monitoring to control the disease's course.Systematic review registrationwww.researchregistry.com, identifier [1723].
PubMed: 38660418
DOI: 10.3389/fmed.2024.1325478 -
Journal of Crohn's & Colitis Apr 2024Subcutaneous (SC) infliximab may provide multiple benefits over intravenous (IV) formulations. However, studies for efficacy and safety in inflammatory bowel disease...
BACKGROUND
Subcutaneous (SC) infliximab may provide multiple benefits over intravenous (IV) formulations. However, studies for efficacy and safety in inflammatory bowel disease (IBD) have been constrained by small sizes that limit the interpretation of outcomes, especially for subgroups potentially at high-risk of disease relapse.
METHODS
We conducted a systematic review and random-effects meta-analysis up to January 2023 to evaluate the change in clinical remission after transitioning from IV to SC infliximab in patients with IBD in clinical remission. The primary outcome was measured using the relative risk for meta-analysis.
RESULTS
15 studies of patients established ≥3 months on IV infliximab were identified, consisting of 1371 patients and 840 patient-years of follow-up. There was no loss of clinical remission in the IBD cohort overall, Crohn's disease (CD), and perianal CD p=0.55 & p=0.11 at 9-12 months, and p=0.50 at 6 months respectively). Neither prior IV dose (≤10mg/kg 6-weekly) (p=0.48) nor IBD disease subtype was associated with an increased clinical relapse rate at 6 months (p=0.48 and p=0.45 (UC vs CD), respectively).
CONCLUSION
Changing patients established on IV infliximab to an SC formulation is associated with a high ongoing clinical remission and low adverse event rate. Furthermore, there are no signals for adverse outcomes among different IBD disease subtypes, nor in those on escalated IV infliximab dosing schedules up to 10mg/kg 6-weekly. This data should provide patients and clinicians alike with confidence in SC infliximab use in IBD.
PubMed: 38656784
DOI: 10.1093/ecco-jcc/jjae059 -
Frontiers in Oncology 2024FLASH-radiotherapy delivers a radiation beam a thousand times faster compared to conventional radiotherapy, reducing radiation damage in healthy tissues with an...
FLASH-radiotherapy delivers a radiation beam a thousand times faster compared to conventional radiotherapy, reducing radiation damage in healthy tissues with an equivalent tumor response. Although not completely understood, this radiobiological phenomenon has been proved in several animal models with a spectrum of all kinds of particles currently used in contemporary radiotherapy, especially electrons. However, all the research teams have performed FLASH preclinical studies using industrial linear accelerator or LINAC commonly employed in conventional radiotherapy and modified for the delivery of ultra-high-dose-rate (UHDRs). Unfortunately, the delivering and measuring of UHDR beams have been proved not to be completely reliable with such devices. Concerns arise regarding the accuracy of beam monitoring and dosimetry systems. Additionally, this LINAC totally lacks an integrated and dedicated Treatment Planning System (TPS) able to evaluate the internal dose distribution in the case of in vivo experiments. Finally, these devices cannot modify dose-time parameters of the beam relevant to the flash effect, such as average dose rate; dose per pulse; and instantaneous dose rate. This aspect also precludes the exploration of the quantitative relationship with biological phenomena. The dependence on these parameters need to be further investigated. A promising advancement is represented by a new generation of electron LINAC that has successfully overcome some of these technological challenges. In this review, we aim to provide a comprehensive summary of the existing literature on in vivo experiments using electron FLASH radiotherapy and explore the promising clinical perspectives associated with this technology.
PubMed: 38655137
DOI: 10.3389/fonc.2024.1373453 -
Frontiers in Cardiovascular Medicine 2024Anticoagulation is crucial for patients hospitalized with coronavirus disease 2019 (COVID-19) due to the high risk of venous thromboembolism (VTE). However, the optimal...
OBJECTIVE
Anticoagulation is crucial for patients hospitalized with coronavirus disease 2019 (COVID-19) due to the high risk of venous thromboembolism (VTE). However, the optimal anticoagulation regimen needs further exploration. Therefore, we evaluated the efficacy and safety of diverse anticoagulation dosage dosages for COVID-19.
METHODS
An updated meta-analysis was performed to assess the effect of thromboprophylaxis (standard, intermediate, and therapeutic dose) on the incidence of VTE, mortality and major bleeding among COVID-19 patients. Literature was searched via PubMed, EMBASE, Web of Science, and China National Knowledge Infrastructure (CNKI) database. The odds ratio (OR) and 95% confidence interval (CI) were calculated for effect estimates.
RESULTS
Nineteen studies involving 25,289 participants without VTE history were included. The mean age of patients was 59.3 years old. About 50.96% were admitted to the intensive care unit. In the pooled analysis, both therapeutic-dose and intermediate-dose anticoagulation did not have a significant advantage in reducing VTE risk over standard dosage (OR = 1.09, 95% CI: 0.58-2.02, and OR = 0.89, 95% CI: 0.70-1.12, respectively). Similarly, all-cause mortality was not further decreased in either therapeutic-dose group (OR = 1.12, 95% CI: 0.75-1.67) or intermediate-dose group (OR = 1.34, 95% CI: 0.83-2.17). While the major bleeding risk was significantly elevated in the therapeutic-dose group (OR = 2.59, 95%CI: 1.87-3.57) as compared with the standard-dose regimen. Compared with intermediate dosage, therapeutic anticoagulation did not reduce consequent VTE risk (OR = 0.85, 95% CI: 0.52-1.38) and all-cause mortality (OR = 0.84, 95% CI: 0.60-1.17), but significantly increased major bleeding rate (OR = 2.42, 95% CI: 1.58-3.70). In subgroup analysis of patients older than 65 years, therapeutic anticoagulation significantly lowered the incidence of VTE in comparation comparison with standard thromboprophylaxis, however, at the cost of elevated risk of major bleeding.
CONCLUSION
Our results indicated that for most hospitalized patients with COVID-19, standard-dose prophylactic anticoagulation might be the optimal choice. For elderly patients at low risk of bleeding, therapeutic-dose anticoagulation could further reduce VTE risk and should be considered especially when there were other strong risk factors of VTE during hospital stay.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/PROSPERO, identifier, CRD42023388429.
PubMed: 38646150
DOI: 10.3389/fcvm.2024.1381408 -
Central European Journal of Urology 2024The aim of this review was to assess the outcomes of partial nephrectomy using indocyanine green (ICG) regarding ischemia time, positive surgical margins (PSM),... (Review)
Review
INTRODUCTION
The aim of this review was to assess the outcomes of partial nephrectomy using indocyanine green (ICG) regarding ischemia time, positive surgical margins (PSM), estimated blood loss (EBL) and estimated GFR reduction while also suggesting the optimal dosage scheme.
MATERIAL AND METHODS
A systematic review was performed using Medline (PubMed), ClinicalTrials.gov, and Cochrane Library (CENTRAL) databases, in concordance with the PRISMA statement. Studies in English regarding the use of indocyanine green in partial nephrectomy were reviewed. Reviews and meta-analyses, editorials, perspectives, and letters to the editors were excluded.
RESULTS
Individual ICG dose was 5 mg in most of the studies. The mean warm ischemia time (WIT) on each study ranged from 11.6 minutes to 27.2 minutes. The reported eGFR reduction ranged from 0% to 15.47%. Lowest mean EBL rate was 48.2 ml and the highest was 347 ml. Positive surgical margin rates were between 0.3% to 11%.
CONCLUSIONS
Indocyanine green seems to be a useful tool in partial nephrectomy as it can assist surgeons in identifying tumor and its related vasculature. Thereby, warm ischemia time can be reduced and, in some cases, selective ischemia can be implemented leading to better renal functional preservation.
PubMed: 38645804
DOI: 10.5173/ceju.2023.155