-
European Urology Nov 2022International variations in the rates of kidney cancer (KC) are considerable. An understanding of the risk factors for KC development is necessary to generate... (Review)
Review
CONTEXT
International variations in the rates of kidney cancer (KC) are considerable. An understanding of the risk factors for KC development is necessary to generate opportunities to reduce its incidence through prevention and surveillance.
OBJECTIVE
To retrieve and summarize global incidence and mortality rates of KC and risk factors associated with its development, and to describe known familial syndromes and genetic alterations that represent biologic risk factors.
EVIDENCE ACQUISITION
A systematic review was conducted via Medline (PubMed) and Scopus to include meta-analyses, reviews, and original studies regarding renal cell carcinoma, epidemiology, and risk factors.
EVIDENCE SYNTHESIS
Our narrative review provides a detailed analysis of KC incidence and mortality, with significant variations across time, geography, and sex. In particular, while KC incidence has continued to increase, mortality models have leveled off. Among the many risk factors, hypertension, obesity, and smoking are the most well established. The emergence of new genetic data coupled with observational data allows for integrated management and surveillance strategies for KC care.
CONCLUSIONS
KC incidence and mortality rates vary significantly by geography, sex, and age. Associations of the development of KC with modifiable and fixed risk factors such as obesity, hypertension, smoking, and chronic kidney disease (CKD)/end-stage kidney disease (ESKD) are well described. Recent advances in the genetic characterization of these cancers have led to a better understanding of the germline and somatic mutations that predispose patients to KC development, with potential for identification of therapeutic targets that may improve outcomes for these at-risk patients.
PATIENT SUMMARY
We reviewed evidence on the occurrence of kidney cancer (KC) around the world. Currently, the main avoidable causes are smoking, obesity, and high blood pressure. Although other risk factors also contribute, prevention and treatment of these three factors provide the best opportunities to reduce the risk of developing KC at present.
Topics: Biological Products; Carcinoma, Renal Cell; Humans; Hypertension; Kidney Neoplasms; Obesity
PubMed: 36100483
DOI: 10.1016/j.eururo.2022.08.019 -
British Journal of Haematology Mar 2023The prognosis of multiple myeloma (MM) has dramatically improved with the development of new drugs, and it has become important to determine the appropriate combinations... (Meta-Analysis)
Meta-Analysis Review
The prognosis of multiple myeloma (MM) has dramatically improved with the development of new drugs, and it has become important to determine the appropriate combinations of these novel agents. This study was a systematic review and network meta-analysis (NMA) of randomized trials in patients with relapsed and/or refractory (RR) MM. The PubMed, Cochrane, and Embase databases were searched for randomized trials from 1 January 2002 to 28 February 2022 of patients treated for MM. The primary end-point was progression-free survival (PFS), evaluated as a hazard ratio (HR) with a 95% confidence interval (95% CI) compared to dexamethasone (DEX). The p-score was used to rank treatments. Of a total of 1136 abstracts screened, 37 studies were selected, including 34 treatment options for RRMM. Daratumumab, lenalidomide and DEX was found to be the best treatment for RRMM, with the best HR compared to DEX (HR, 0.13; 95% CI, 0.08-0.20; p-score 0.9796). There was no evidence of significant heterogeneity (I , 41.3%; p = 0.146). The current NMA confirmed the excellent efficacy of three-drug regimens including anti-CD38 antibodies to treat RRMM and provides background data to evaluate the efficacy of chimeric antigen receptor T-cell treatments and bispecific T-cell engager therapies.
Topics: Humans; Multiple Myeloma; Network Meta-Analysis; Antineoplastic Combined Chemotherapy Protocols; Lenalidomide; Progression-Free Survival; Dexamethasone
PubMed: 36661264
DOI: 10.1111/bjh.18654 -
Clinical Gastroenterology and... Apr 2022Advances in genomic technologies have led to increasing reports of monogenic inflammatory bowel disease (IBD). Here, we systematically review the literature to determine... (Review)
Review
BACKGROUND & AIMS
Advances in genomic technologies have led to increasing reports of monogenic inflammatory bowel disease (IBD). Here, we systematically review the literature to determine the clinical features, genetic profile, and previously used treatment strategies in monogenic IBD.
METHODS
A systematic review of MEDLINE articles published between January 2000 and December 2020 was conducted. A total of 750 individual monogenic IBD cases were identified from 303 eligible articles.
RESULTS
The most frequently reported monogenic IBD genes were IL10RA/B, XIAP, CYBB, LRBA, and TTC7A. In total, 63.4% of patients developed IBD before 6 years of age, 17.4% developed IBD between ages 10 and 17.9 years, and 10.9% developed IBD after age 18. There was a substantial difference between these age groups and the underlying monogenic disorders. Only 31.7% had any history of extraintestinal comorbidity (EIC) before IBD onset, but 76.0% developed at least 1 EIC during their clinical course. The most common EICs were atypical infection (44.7%), dermatologic abnormality (38.4%), and autoimmunity (21.9%). Bowel surgery, biologic therapy, and hematopoietic stem cell transplantation were performed in 27.1%, 32.9%, and 23.1% of patients, respectively.
CONCLUSIONS
Monogenic IBD cases, although rare, have varied extraintestinal comorbidities and limited treatment options including surgery and transplant. Early identification and improved understanding of the characteristics of the genes and underlying disease processes in monogenic IBD is important for effective management.
Topics: Adaptor Proteins, Signal Transducing; Adolescent; Age of Onset; Colitis; Humans; Inflammatory Bowel Diseases; Proteins
PubMed: 33746097
DOI: 10.1016/j.cgh.2021.03.021 -
Journal of Hepatology Dec 2022HBV reactivation (HBVr) can be prevented by nucleos(t)ide analogues (NAs). We conducted a systematic review and meta-analysis on the risk of HBVr associated with new... (Meta-Analysis)
Meta-Analysis Review
HBV reactivation (HBVr) can be prevented by nucleos(t)ide analogues (NAs). We conducted a systematic review and meta-analysis on the risk of HBVr associated with new classes of immunosuppressive and immunomodulatory therapies and developed guidance on NA prophylaxis. An expert panel reviewed the data and categorised the risk of HBVr associated with each class of drugs into low (<1%), intermediate (1-10%), and high (>10%). Our search uncovered 59 studies, including 3,424 HBsAg+ and 5,799 HBsAg-/anti-HBc+ patients, which met our eligibility criteria. Based on medium-high quality evidence, immune checkpoint inhibitors, tyrosine kinase inhibitors, cytokine inhibitors, chimeric antigen receptor T-cell immunotherapies, and corticosteroids were associated with high HBVr risk in HBsAg+ patients; cytokine inhibitors, chimeric antigen receptor T-cell immunotherapies, and corticosteroids with intermediate risk in HBsAg-/anti-HBc+ patients; and anti-tumour necrosis factor agents and immune checkpoint inhibitors with low risk in HBsAg-/anti-HBc+ patients. Provisional recommendations are provided for drugs with low quality evidence. NA prophylaxis is recommended when using drugs associated with a high HBVr risk, while monitoring with on-demand NAs is recommended for low-risk drugs - either approach may be appropriate for intermediate-risk drugs. Consensus on definitions and methods of reporting HBVr, along with inclusion of HBsAg+, and HBsAg-/anti-HBc+ patients in clinical trials, will be key to gathering reliable data on the risk of HBVr associated with immunosuppressive or immunomodulatory therapies.
Topics: Humans; Hepatitis B virus; Hepatitis B Surface Antigens; Hepatitis B; Immunosuppressive Agents; Virus Activation; Expert Testimony; Immune Checkpoint Inhibitors; Receptors, Chimeric Antigen; Antiviral Agents; Hepatitis B Antibodies; Adjuvants, Immunologic; Cytokines
PubMed: 35850281
DOI: 10.1016/j.jhep.2022.07.003 -
The Journal of Allergy and Clinical... 2019There is no recent systematic review on the risk of cross-reactivity to cephalosporins and carbapenems in penicillin-allergic patients despite many new studies on the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
There is no recent systematic review on the risk of cross-reactivity to cephalosporins and carbapenems in penicillin-allergic patients despite many new studies on the subject. All past reviews have several limitations such as not including any patient with a T-cell-mediated penicillin allergy.
OBJECTIVES
To determine the risk of cross-reactivity to cephalosporins and carbapenems in patients with a proven IgE- or T-cell-mediated penicillin allergy. To measure the association between R1 side chain similarity on cephalosporins and penicillins and the risk of cross-reactivity.
METHODS
MEDLINE and EMBASE were searched from January 1980 to March 2019. Studies had to include at least 10 penicillin-allergic subjects whose allergy had been confirmed by a positive skin test (ST) or drug provocation test (DPT) result. Cross-reactivity had to be assessed to at least 1 cephalosporin or carbapenem through ST or DPT. Both random-effects and fixed-effect models were used to combine data. A bioinformatic model was used to quantify the similarity between R1 side chains.
RESULTS
Twenty-one observational studies on cephalosporin cross-reactivity involving 1269 penicillin-allergic patients showed that the risk of cross-reactivity varied with the degree of similarity between R1 side chains: 16.45% (95% CI, 11.07-23.75) for aminocephalosporins, which share an identical side chain with a penicillin (similarity score = 1), 5.60% (95% CI, 3.46-8.95) for a few cephalosporins with an intermediate similarity score (range, 0.563-0.714), and 2.11% (95% CI, 0.98-4.46) for all those with low similarity scores (below 0.4), irrespective of cephalosporin generation. The higher risk associated with aminocephalosporins was observed whether penicillin allergy was IgE- or T-cell-mediated. Eleven observational studies on carbapenem cross-reactivity involving 1127 penicillin-allergic patients showed that the risk of cross-reactivity to any carbapenem was 0.87% (95% CI, 0.32-2.32).
CONCLUSIONS
Although it remains possible that these meta-analyses overestimated the risk of cross-reactivity, clinicians should consider the increased risk of cross-reactivity associated with aminocephalosporins, and to a lesser extent with intermediate-similarity-score cephalosporins, compared with the very low risk associated with low-similarity-score cephalosporins and all carbapenems when using beta-lactams in patients with a suspected or proven penicillin allergy.
Topics: Carbapenems; Cephalosporins; Cross Reactions; Drug Hypersensitivity; Humans; Penicillins
PubMed: 31170539
DOI: 10.1016/j.jaip.2019.05.038 -
Biochimica Et Biophysica Acta.... Jan 2023DNA methylation profiles are in dynamic equilibrium via the initiation of methylation, maintenance of methylation and demethylation, which control gene expression and... (Review)
Review
DNA methylation profiles are in dynamic equilibrium via the initiation of methylation, maintenance of methylation and demethylation, which control gene expression and chromosome stability. Changes in DNA methylation patterns play important roles in carcinogenesis and primarily manifests as hypomethylation of the entire genome and the hypermethylation of individual loci. These changes may be reflected in blood-based DNA, which provides a non-invasive means for cancer monitoring. Previous blood-based DNA detection objects primarily included circulating tumor DNA/cell-free DNA (ctDNA/cfDNA), circulating tumor cells (CTCs) and exosomes. Researchers gradually found that methylation changes in peripheral blood mononuclear cells (PBMCs) also reflected the presence of tumors. Blood-based DNA methylation is widely used in early diagnosis, prognosis prediction, dynamic monitoring after treatment and other fields of clinical research on cancer. The reversible methylation of genes also makes them important therapeutic targets. The present paper summarizes the changes in DNA methylation in cancer based on existing research and focuses on the characteristics of the detection objects of blood-based DNA, including ctDNA/cfDNA, CTCs, exosomes and PBMCs, and their application in clinical research.
Topics: Humans; DNA Methylation; Leukocytes, Mononuclear; Biomarkers, Tumor; Circulating Tumor DNA; Neoplasms; Cell-Free Nucleic Acids
PubMed: 36270476
DOI: 10.1016/j.bbadis.2022.166583 -
Blood Advances Oct 2023Bispecific antibodies, a novel immunotherapy with promising efficacy against multiple myeloma, form immune synapses between T-cell surface marker CD3 and malignant cell... (Meta-Analysis)
Meta-Analysis
Bispecific antibodies, a novel immunotherapy with promising efficacy against multiple myeloma, form immune synapses between T-cell surface marker CD3 and malignant cell markers, including B-cell maturation antigen (BCMA), FcRH5, and G protein-coupled receptor GPRC5D. These bispecific antibodies so effectively deplete plasma cells (and to some extent T-cells) that patients are at increased risk of developing infections. A systematic review and meta-analysis of infections in published studies of patients with myeloma treated with bispecific antibodies was conducted to better characterize the infection risks. A literature search used MEDLINE, EMBASE, and Cochrane to identify relevant studies between inception and February 10, 2023, including major conference presentations. Phase 1b-3 clinical trials and observational studies were included. Sixteen clinical trials comprising 1666 patients were included. Median follow-up was 7.6 months and 38% of the cohort had penta-drug refractory disease. Pooled prevalence of all-grade infections was 56%, whereas the prevalence of grade ≥3 infections was 24%. Patients who were treated with BCMA-targeted bispecifics had significantly higher rates of grade ≥3 infections than non-BCMA bispecifics (25% vs 20%). Similarly, patients treated with bispecifics in combination with other agents had significantly higher rate of all-grade infection than those receiving monotherapy (71% vs 52%). In observational studies (n = 293), excluded from the primary analysis to ensure no overlap with patients in clinical trials, several infections classically associated with T-cell depletion were identified. This systematic review identifies BCMA-targeted bispecifics and bispecific combination therapy as having higher infection risk, requiring vigilant infection screening and prophylaxis strategies.
Topics: Humans; Multiple Myeloma; Antibodies, Bispecific; B-Cell Maturation Antigen; Immunotherapy; T-Lymphocytes; CD3 Complex
PubMed: 37467036
DOI: 10.1182/bloodadvances.2023010539 -
Nutrients Dec 2022Lycopene is a nutraceutical with health-promoting and anti-cancer activities, but due to a lack of evidence, there are no recommendations regarding its use and dosage.... (Review)
Review
Lycopene is a nutraceutical with health-promoting and anti-cancer activities, but due to a lack of evidence, there are no recommendations regarding its use and dosage. This review aimed to evaluate the benefits of lycopene supplementation in cancer prevention and treatment based on the results of in vivo studies. We identified 72 human and animal studies that were then analysed for endpoints such as cancer incidence, improvement in treatment outcomes, and the mechanisms of lycopene action. We concluded that the results of most of the reviewed in vivo studies confirmed the anti-cancer activities of lycopene. Most of the studies concerned prostate cancer, reflecting the number of in vitro studies. The reported mechanisms of lycopene action in vivo included regulation of oxidative and inflammatory processes, induction of apoptosis, and inhibition of cell division, angiogenesis, and metastasis formation. The predominance of particular mechanisms seemed to depend on tumour organ localisation and the local storage capacity of lycopene. Finally, there is a need to look for predictive factors to identify a population that may benefit from lycopene supplementation. The potential candidates appear to be race, single nucleotide polymorphisms in carotene-cleaving enzymes, some genetic abbreviations, and insulin-like growth factor-dependent and inflammatory diseases.
Topics: Male; Animals; Humans; Lycopene; Carotenoids; Prostatic Neoplasms; Apoptosis; Dietary Supplements
PubMed: 36501182
DOI: 10.3390/nu14235152 -
Cells Aug 2021Folic acid has been identified to be integral in rapid tissue growth and cell division during fetal development. Different studies indicate folic acid's importance in...
Folic acid has been identified to be integral in rapid tissue growth and cell division during fetal development. Different studies indicate folic acid's importance in improving childhood behavioral outcomes and underline its role as a modifiable risk factor for autism spectrum disorders. The aim of this systematic review is to both elucidate the potential role of folic acid in autism spectrum disorders and to investigate the mechanisms involved. Studies have pointed out a potential beneficial effect of prenatal folic acid maternal supplementation (600 µg) on the risk of autism spectrum disorder onset, but opposite results have been reported as well. Folic acid and/or folinic acid supplementation in autism spectrum disorder diagnosed children has led to improvements, both in some neurologic and behavioral symptoms and in the concentration of one-carbon metabolites. Several authors report an increased frequency of serum auto-antibodies against folate receptor alpha (FRAA) in autism spectrum disorder children. Furthermore, methylene tetrahydrofolate reductase (MTHFR) polymorphisms showed a significant influence on ASD risk. More clinical trials, with a clear study design, with larger sample sizes and longer observation periods are necessary to be carried out to better evaluate the potential protective role of folic acid in autism spectrum disorder risk.
Topics: Autism Spectrum Disorder; Autoantibodies; Dietary Supplements; Folate Receptor 1; Folic Acid; Humans; Methylenetetrahydrofolate Reductase (NADPH2); Polymorphism, Single Nucleotide; Risk Factors
PubMed: 34440744
DOI: 10.3390/cells10081976 -
Transplantation and Cellular Therapy Jun 2022Chimeric antigen receptor (CAR) T cell therapy is a novel therapy for patients with relapsed or refractory hematologic malignancies. Most CAR T cell therapy recipients... (Review)
Review
Clinical Presentation, Risk Factors, and Outcomes of Immune Effector Cell-Associated Neurotoxicity Syndrome Following Chimeric Antigen Receptor T Cell Therapy: A Systematic Review.
Chimeric antigen receptor (CAR) T cell therapy is a novel therapy for patients with relapsed or refractory hematologic malignancies. Most CAR T cell therapy recipients will experience clinical features of the immune effector cell-associated neurotoxicity syndrome (ICANS), a potentially life-threatening condition. Here we describe the clinical, biological, and radiological findings associated with ICANS in adults with hematologic malignancies treated with CAR T cell therapy, as well as the acute and long-term outcomes of ICANS. A literature search of Ovid Medline, Embase, PubMed, Scopus, Web of Science Core Collection, Cochrane Library, and Google Scholar was conducted from each database's inception through February 1, 2022, using search terms reflecting CAR T cell therapy and ICANS. We included studies that enrolled adults (age ≥18 years) who received CAR T cell therapy as management for hematologic malignancies and reported the clinical presentation, predictors, and/or acute or long-term outcomes of ICANS. Two reviewers independently extracted data following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) reporting guidelines. Quality was assessed using the Joanna Briggs Institute critical appraisal tool for cohort studies. Of the 2928 studies screened, 23 observational studies (10 prospective, 11 retrospective, 1 mixed design, and 1 cross-sectional) with a total of 1666 participants met our eligibility criteria and were included in our review. The most common hematologic malignancies were diffuse large B cell lymphoma, acute lymphocytic leukemia, non-Hodgkin lymphoma, and chronic lymphocytic leukemia. ICANS onset was most often associated with the presence and severity of cytokine release syndrome, as well as with C-reactive protein and ferritin levels. Aphasia was the most common ICANS-related symptom reported, although the neurologic manifestations of ICANS were highly variable. Neuroimaging studies (magnetic resonance imaging or computed tomography) were often normal in cases of ICANS; however, electroencephalography often showed generalized background slowing, abnormal rhythmic, and periodic discharge patterns. The pooled mean (± SD) onset of ICANS was 6.4 ± 3.2 days, with a pooled mean duration of 8.3 ± 10.5 days. Two of the 23 studies (9%) reported 5 ICANS-related deaths among 233 participants. A subset of patients experienced persistent neurocognitive complaints at ≥1-year after CAR T cell therapy. The clinical presentation, onset, severity, long-term sequelae, and grading system of ICANS are variable. Future studies should consider using a consensus grading/reporting scale that would permit cross-trial comparisons of the safety profile of various CAR T cell products and enable the development of interventions to mitigate or manage these neurotoxicities. © 2022 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. This systematic review was conducted according to a published protocol (PROSPERO CRD42020207864) and followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) and Synthesis without Meta-Analysis (SWiM) in systematic review reporting guidelines (Supplementary Table S1) [15,16].
Topics: Adult; Cell- and Tissue-Based Therapy; Cross-Sectional Studies; Hematologic Neoplasms; Humans; Immunotherapy, Adoptive; Neurotoxicity Syndromes; Prospective Studies; Receptors, Chimeric Antigen; Retrospective Studies; Risk Factors
PubMed: 35288347
DOI: 10.1016/j.jtct.2022.03.006