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Ultrasound in Obstetrics & Gynecology :... Dec 2016To quantify the prevalence of chromosomal anomalies in fetuses with persistent left superior vena cava (PLSVC), assess the strength of the association between PLSVC and... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
To quantify the prevalence of chromosomal anomalies in fetuses with persistent left superior vena cava (PLSVC), assess the strength of the association between PLSVC and coarctation of the aorta and ascertain the diagnostic accuracy of antenatal ultrasound in correctly identifying isolated cases of PLSVC.
METHODS
MEDLINE, EMBASE, CINHAL and the Cochrane databases were searched from the year 2000 onwards using combinations of keywords 'left superior vena cava' and 'outcome'. Two authors reviewed all abstracts independently. Quality assessment of the included studies was performed using the Newcastle-Ottawa Scale for cohort studies. The rates of the following outcomes were analyzed: chromosomal abnormalities; associated intracardiac anomalies (ICAs) and extracardiac anomalies (ECAs) diagnosed prenatally; additional ICAs and ECAs detected only at postnatal imaging or clinical evaluation but missed at prenatal imaging; and association of PLSVC and coarctation of the aorta. Meta-analyses of proportions were used to combine data.
RESULTS
In total, 2708 articles were identified and 13 (n = 501) were included in the systematic review. Associated ICAs and ECAs were detected at the prenatal ultrasound examination or at a follow-up assessment in 60.7% (95% CI, 44.2-75.9%) and 37.8% (95% CI, 31.0-44.8%) of cases, respectively. Chromosomal anomalies occurred in 12.5% (95% CI, 9.0-16.4%) of cases in the overall population of fetuses with PLSVC and in 7.0% (95% CI, 2.7-13.0%) of isolated cases. Additional ICAs and ECAs were detected only after birth and missed at ultrasound in 2.4% (95% CI, 0.5-5.8%) and 6.7% (95% CI, 2.2-13.2%) of cases, respectively. Coarctation of the aorta was associated with isolated PLSVC in 21.3% (95% CI, 13.6-30.3%) of cases.
CONCLUSIONS
PLSVC is commonly associated with ICAs, ECAs and chromosomal anomalies. Fetuses with isolated PLSVC should be followed up throughout pregnancy in order to rule out coarctation of the aorta. As most of the data in this review were derived from high-risk pregnancies, the rate of associated abnormalities is likely to be higher than that in the general population of fetuses with PLSVC, for which more data are needed. Revisión sistemática y metaanálisis de la persistencia de la vena cava superior izquierda en la ecografía prenatal: anomalías asociadas, precisión del diagnóstico y resultado postnatal RESUMEN OBJETIVOS: Cuantificar la prevalencia de anomalías cromosómicas en fetos con vena cava superior izquierda persistente (VCSIP), evaluar la solidez de la asociación entre la VCSIP y la coartación aórtica, y determinar la precisión del diagnóstico de la ecografía prenatal como método para identificar correctamente casos aislados de VCSIP. MÉTODOS: Se buscó en las bases de datos de MEDLINE, EMBASE, CINHAL y Cochrane artículos publicados desde el año 2000 en adelante, usando combinaciones de las palabras clave "vena cava superior izquierda" y "resultado". Dos de los autores revisaron de forma independiente todos los resúmenes encontrados. La evaluación de calidad de los estudios incluidos se realizó mediante la escala Newcastle-Ottawa para estudios de cohortes. Se analizaron las tasas de los siguientes resultados: anomalías cromosómicas; anomalías intracardíacas (AIC) y anomalías extracardíacas (AEC) asociadas diagnosticadas prenatalmente; AIC y AEC adicionales detectadas sólo en ecografías postnatales o mediante evaluación clínica, pero no observadas en ecografías prenatales; y la asociación entre la VCSIP y la coartación aórtica. Se utilizó un meta-análisis de proporciones para combinar los datos.
RESULTADOS
En total, se identificaron 2708 artículos y se incluyeron 13 (n = 501) en la revisión sistemática. En la ecografía prenatal o en una revisión de seguimiento se detectaron AIC y AEC asociadas en el 60,7% (IC 95%, 44,2-75,9%) y el 37,8% (IC 95%, 31,0-44,8%) de los casos, respectivamente. Se produjeron anomalías cromosómicas en el 12,5% (IC 95%, 9,0-16,4%) de los casos en la población general de fetos con VCSIP y en el 7,0% (IC 95%, 2,7-13,0%) de casos aislados. Las AIC y AEC adicionales sólo se detectaron después del nacimiento y en el 6,7% (IC 95%, 2,2-13,2%) de los casos, respectivamente. La coartación aórtica se encontró asociada con la VCSIP aislada en un 21,3% (IC 95%, 13,6-30,3%) de los casos.
CONCLUSIONES
La VCSIP está comúnmente asociada a AIC, AEC y anomalías cromosómicas. Los fetos con VCSIP aislada deben ser objeto de seguimiento durante todo el embarazo, con el fin de descartar la coartación aórtica. Como la mayoría de los datos de esta revisión proceden de embarazos de alto riesgo, es probable que la tasa de anomalías asociadas sea más alta que la de la población general de fetos con VCSIP, por lo que se necesitan más datos.
Topics: Aortic Coarctation; Chromosome Aberrations; Cohort Studies; Female; Humans; Pregnancy; Pregnancy Outcome; Sensitivity and Specificity; Ultrasonography, Prenatal; Vascular Malformations; Vena Cava, Superior
PubMed: 26970258
DOI: 10.1002/uog.15914 -
BMC Cancer Sep 2018Our goal was to investigate the prevalence of the epidermal growth factor receptor (EGFR) mutation in Middle East and African countries and to compare its prevalence... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Our goal was to investigate the prevalence of the epidermal growth factor receptor (EGFR) mutation in Middle East and African countries and to compare its prevalence with that shown in other populations.
METHODS
We used PubMed and the Cochrane Library databases to conduct a literature search using the terms "[EGFR] AND [mutation] AND [Non Small Cell Lung Cancer] AND [Middle East OR Africa]." We assessed studies published in English and French from 2004 until 2016.
RESULTS
Ten relevant studies were included in this systematic review. Overall, 1215 patients with non-small cell lung cancer (NSCLC) were included in this analysis. The overall ratio of male to female patients was 2.15. Of total patients included, 41.1% had never smoked and 85.8% had been diagnosed with adenocarcinoma. In 8 of the 10 studies, polymerase chain reaction (PCR) analyses were conducted to identify EGFR mutations. In total, 257 patients had an EGFR mutation, corresponding to a prevalence of 21.2%. The most frequent abnormality detected in all of the studies was in exon 19. In addition, all studies concluded the presence of a correlation between EGFR mutation status and female sex, non-smoking status, and adenocarcinoma subtype.
CONCLUSIONS
The EGFR mutation frequency in Middle East and African patients is higher than that shown in white populations but still lower than the frequency reported in Asian populations.
Topics: Africa; Asian People; Carcinoma, Non-Small-Cell Lung; ErbB Receptors; Female; Humans; Male; Middle East; Mutation; Mutation Rate; White People
PubMed: 30217176
DOI: 10.1186/s12885-018-4774-y -
The Cochrane Database of Systematic... Jan 2017Sickle cell disease is a genetic chronic haemolytic and pro-inflammatory disorder. The clinical manifestations of sickle cell disease result from the presence of... (Review)
Review
BACKGROUND
Sickle cell disease is a genetic chronic haemolytic and pro-inflammatory disorder. The clinical manifestations of sickle cell disease result from the presence of mutations on the beta globin genes that generate an abnormal haemoglobin product (called haemoglobin S) within the red blood cell. Sickle cell disease can lead to many complications such as acute chest syndrome, stroke, acute and chronic bone complications (including painful vaso-occlusive crisis, osteomyelitis, osteonecrosis and osteoporosis). With increased catabolism and deficits in energy and nutrient intake, individuals with sickle cell disease suffer multiple macro- and micro-nutritional deficiencies, including vitamin D deficiency. Since vitamin D maintains calcium homeostasis and is essential for bone mineralisation, its deficiency may worsen musculoskeletal health problems encountered in sickle cell disease. Therefore, there is a need to review the effects and the safety of vitamin D supplementation in sickle cell disease.
OBJECTIVES
To investigate the hypothesis that vitamin D supplementation increases serum 25-hydroxyvitamin D level in children and adults with sickle cell disease.To determine the effects of vitamin D supplementation on general health such as growth status and health-related quality of life; on musculoskeletal health including bone mineral density, pain crises, bone fracture and muscle health; on respiratory health which includes lung function tests, acute chest syndrome, acute exacerbation of asthma and respiratory infections; and the safety of vitamin D supplementation in children and adults with sickle cell disease.
SEARCH METHODS
We searched the Cochrane Haemoglobinopathies Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. We also searched database such as PubMed, clinical trial registries and the reference lists of relevant articles and reviews.Date of last search: 15 December 2016.
SELECTION CRITERIA
Randomised controlled studies and quasi-randomised controlled studies (controlled clinical studies) comparing oral administration of any form of vitamin D supplementation to another type of vitamin D or placebo or no supplementation at any dose and for any duration, in people with sickle cell disease, of all ages, gender, and phenotypes including sickle cell anaemia, haemoglobin sickle cell disease and sickle beta-thalassaemia diseases.
DATA COLLECTION AND ANALYSIS
Two authors independently extracted the data and assessed the risk of bias of the included study. They used the GRADE guidelines to assess the quality of the evidence.
MAIN RESULTS
One double-blind randomised controlled study including 46 people with sickle cell disease (HbSS, HbSC, HbSβ+thal and HbSβ0thal) was eligible for inclusion in this review. Of the 46 enrolled participants, seven withdrew before randomisation leaving 39 participants who were randomised. Only 25 participants completed the full six months of follow up. Participants were randomised to receive oral vitamin D3 (cholecalciferol) (n = 20) or placebo (n = 19) for six weeks and were followed up to six months. Two participants from the treatment group have missing values of baseline serum 25-hydroxyvitamin D, therefore the number of samples analysed was 37 (vitamin D n = 18, placebo n = 19).The included study had a high risk of bias with regards to incomplete outcome data (high dropout rate in the placebo group), but a low risk of bias for other domains such as random sequence generation, allocation concealment, blinding of participants, personnel and outcome assessors, selective outcome reporting; and an unclear risk of other biases.Compared to the placebo group, the vitamin D group had significantly higher serum 25-hydroxyvitamin D (25(OH)D) levels at eight weeks, mean difference 29.79 (95% confidence interval 26.63 to 32.95); at 16 weeks, mean difference 12.67 (95% confidence interval 10.43 to 14.90); and at 24 weeks, mean difference 15.52 (95% confidence interval 13.50 to 17.54). We determined the quality of the evidence for this outcome to be moderate. There was no significant difference of adverse events (tingling of lips or hands) between the vitamin D and placebo groups, risk ratio 3.16 (95% confidence interval 0.14 to 72.84), but the quality of the evidence was low. Regarding the frequency of pain, the vitamin D group had significantly fewer pain days compared to the placebo group, mean difference -10.00 (95% confidence interval -16.47 to -3.53), but again the quality of the evidence was low. Furthermore, the review included physical functioning PedsQL scores which was reported as absolute change from baseline. The vitamin D group had a lower (worse) health-related quality of life score than the placebo group but this was not significant at eight weeks, mean difference -2.02 (95% confidence interval -6.34 to 2.30). However, the difference was significant at both 16 weeks, mean difference -12.56 (95% confidence interval -16.44 to -8.69) and 24 weeks, mean difference -12.59 (95% confidence interval -17.43 to -7.76). We determined the quality of evidence for this outcome to be low.
AUTHORS' CONCLUSIONS
We included only one low-quality clinical study which had a high risk of bias with regards to incomplete outcome data. Therefore, we consider that the evidence is not of sufficient quality to guide clinical practice. Until further evidence becomes available, clinicians should consider the relevant existing guidelines for vitamin D supplementation (e.g. the Endocrine Society Clinical Practice Guidelines) and dietary reference intakes for calcium and vitamin D (e.g. from the USA Institute of Medicine). Evidence of vitamin D supplementation in sickle cell disease from high quality studies is needed. Well-designed, randomised, placebo-controlled studies of parallel design, are required to determine the effects and the safety of vitamin D supplementation in children and adults with sickle cell disease.
Topics: Anemia, Sickle Cell; Cholecalciferol; Humans; Pain; Quality of Life; Randomized Controlled Trials as Topic; Time Factors; Vitamin D; Vitamin D Deficiency
PubMed: 28105733
DOI: 10.1002/14651858.CD010858.pub2 -
Frontiers in Medicine 2021Keratoconus (KC) is an etiologically heterogeneous corneal ectatic disorder. To systematically display the pathogenesis of keratoconus (KC), this study reviewed all the...
Keratoconus (KC) is an etiologically heterogeneous corneal ectatic disorder. To systematically display the pathogenesis of keratoconus (KC), this study reviewed all the reported genes involved in KC, and performed an enrichment analysis of genes identified at the genome, transcription, and protein levels respectively. Combined analysis of multi-level results revealed their shared genes, gene ontology (GO), and pathway terms, to explore the possible pathogenesis of KC. After an initial search, 80 candidate genes, 2,933 transcriptional differential genes, and 947 differential proteins were collected. The candidate genes were significantly enriched in extracellular matrix (ECM) related terms, Wnt signaling pathway and cytokine activities. The enriched GO/pathway terms of transcription and protein levels highlight the importance of ECM, cell adhesion, and inflammatory once again. Combined analysis of multi-levels identified 13 genes, 43 GOs, and 12 pathways. The pathogenic relationships among these overlapping factors maybe as follows. The gene mutations/variants caused insufficient protein dosage or abnormal function, together with environmental stimulation, leading to the related functions and pathways changes in the corneal cells. These included response to the glucocorticoid and reactive oxygen species; regulation of various signaling (P13K-AKT, MAPK and NF-kappaB), apoptosis and aging; upregulation of cytokines and collagen-related enzymes; and downregulation of collagen and other ECM-related proteins. These undoubtedly lead to a reduction of extracellular components and induction of cell apoptosis, resulting in the loosening and thinning of corneal tissue structure. This study, in addition to providing information about the genes involved, also provides an integrated insight into the gene-based etiology and pathogenesis of KC.
PubMed: 35141241
DOI: 10.3389/fmed.2021.770138 -
Ultrasound in Obstetrics & Gynecology :... Apr 2016Use of recent antenatal screening guidelines for cardiac abnormalities has increased fetal diagnoses of right aortic arch (RAA). We aimed to establish the outcome of... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
Use of recent antenatal screening guidelines for cardiac abnormalities has increased fetal diagnoses of right aortic arch (RAA). We aimed to establish the outcome of fetal RAA without intracardiac abnormalities (ICA) to guide postnatal management.
METHODS
In the retrospective cohort part of our study, outcome measures were rates of chromosomal abnormalities, 22q11.2 deletion, fetal extracardiac abnormalities (ECA), postnatal ICA and ECA, and symptoms of and surgery for vascular ring. A systematic review and meta-analysis was also performed; results are reported as proportions. Kaplan-Meier analysis of vascular ring cases with surgery as endpoint was performed.
RESULTS
Our cohort included 86 cases; 41 had a vascular ring. Rates of chromosomal abnormalities, 22q11.2 deletion and fetal ECA were 14.1%, 6.4% and 17.4%, respectively. Sixteen studies including our cohort (312 fetuses) were included in the systematic review. Overall rates of chromosomal abnormalities and 22q11.2 deletion were 9.0% (95% CI, 6.0-12.5%) and 6.1% (95% CI, 3.6-9.3%), whilst the respective rates for cases with no ECA were 4.6% (95% CI, 2.3-7.8%) and 5.1% (95% CI, 2.4-8.6%). ECA were seen in 14.6% (95% CI, 10.6-19.0%) prenatally and in 4.0% (95% CI, 1.5-7.6%) after birth. Postnatal ICA were identified in 5.0% (95% CI, 2.7-7.9%). Rate of symptoms of vascular rings (follow-up ≥ 24 months postpartum) was 25.2% (95% CI, 16.6-35.0%), and 17.1% (95% CI, 9.9-25.7%) had surgery. Two-year freedom from surgery was 83.0% (95% CI, 74.3-90.1%).
CONCLUSIONS
Fetal RAA without ICA is more frequently associated with ECA than with chromosomal abnormalities. Most cases, however, are isolated. Vascular-ring symptoms occur in about 25% of cases. Postnatal surveillance is required mainly in the first 2 years after delivery.
Topics: Abnormalities, Multiple; Aorta, Thoracic; Aortic Arch Syndromes; Chromosome Aberrations; Cohort Studies; DiGeorge Syndrome; Female; Fetal Diseases; Fetal Heart; Heart Defects, Congenital; Humans; Kaplan-Meier Estimate; Pregnancy; Prenatal Diagnosis; Retrospective Studies; Ultrasonography, Prenatal
PubMed: 26643657
DOI: 10.1002/uog.15805 -
Pathology Oncology Research : POR Jul 2020We aimed to classify undifferentiated/dedifferentiated carcinoma (UDC/DDC) according to the four TCGA molecular subgroups of endometrial cancer:... (Meta-Analysis)
Meta-Analysis
We aimed to classify undifferentiated/dedifferentiated carcinoma (UDC/DDC) according to the four TCGA molecular subgroups of endometrial cancer: microsatellite-instable/hypermutated (MSI), POLE-mutant/ultramutated (POLE), copy-number-low/p53-wild-type (p53wt), and copy-number-high/p53-abnormal (p53abn), through a systematic review and meta-analysis. Electronic databases were searched from January 2013 to July 2019 for studies assessing the TCGA classification in endometrial UDC/DDC series. Pooled prevalence of each TCGA subgroup on the total UDC/DDCs was calculated. Three studies with 73 patients were included. Pooled prevalence of the TCGA subgroups were: 12.4% for the POLE subgroup, 44% for the MSI subgroup, 18.6% for the p53abn subgroup, 25% for the p53wt group. All TCGA groups are represented in UDC/DDC, with a predominance of the MSI group, indicating a biological heterogeneity. Hypermutated/ultramutated cancers constitute the majority of UDC/DDC, suggesting a crucial difference with other high-risk histologies of endometrial carcinoma.
Topics: Endometrial Neoplasms; Female; Gene Dosage; Humans; Mutation; Transcriptome
PubMed: 31811476
DOI: 10.1007/s12253-019-00784-0 -
Health Technology Assessment... 2012Sickle cell disease (SCD) is a recessive genetic blood disorder, caused by a mutation in the β-globin gene. For children with SCD, the risk of stroke is estimated to be... (Review)
Review
BACKGROUND
Sickle cell disease (SCD) is a recessive genetic blood disorder, caused by a mutation in the β-globin gene. For children with SCD, the risk of stroke is estimated to be up to 250 times higher than in the general childhood population. Transcranial Doppler (TCD) ultrasonography is a non-invasive technique which measures local blood velocity in the proximal portions of large intracranial arteries. Screening with TCD ultrasonography identifies individuals with high cerebral blood velocity; these children are at the highest risk of stroke. A number of primary stroke prevention strategies are currently used in clinical practice in the UK including blood transfusion, treatment with hydroxycarbamide and bone marrow transplantation (BMT). No reviews have yet assessed the clinical effectiveness and cost effectiveness of primary stroke prevention strategies in children with SCD identified to be at high risk of stroke using TCD ultrasonography.
OBJECTIVE
To assess the clinical effectiveness and cost-effectiveness of primary stroke prevention treatments for children with SCD who are identified (using TCD ultrasonography) to be at high risk of stroke.
DATA SOURCES
Electronic databases were searched from inception up to May 2011, including the Cochrane Database of Systematic Reviews (CDSR), the Cochrane Central Register of Controlled Trials (CENTRAL), the Database of Abstracts of Reviews of Effects (DARE), EMBASE, the Health Technology Assessment (HTA) database, ISI Web of Science Proceedings, ISI Web of Science Citation Index, the NHS Economic Evaluation Database (NHS EED) and MEDLINE.
REVIEW METHODS
The assessment was conducted according to accepted procedures for conducting and reporting systematic reviews and economic evaluations. A de novo Markov model was developed to determine the cost-effectiveness of TCD ultrasonography and blood transfusion, where clinically appropriate, in patients with SCD.
RESULTS
Two randomised controlled trials met the inclusion criteria involving a study population of 209 participants. One compared blood transfusion with standard care for children who are identified as being at high risk of stroke using TCD ultrasonography. In this trial, one patient in the transfusion group had a stroke (1/63) compared with 11 children in the standard care group (11/67). The other trial assessed the impact of halting chronic transfusion in patients with SCD. Sixteen patients in the transfusion-halted group had an event (16/41) (two patients experienced stroke and 14 reverted to abnormal TCD velocity); there were no events in the continued-transfusion group (0/38). No meta-analyses of these trials were undertaken. No relevant economic evaluations were identified for inclusion in the review. The de novo modelling suggests that blood transfusions plus TCD scans (compared with just TCD scans) for patients with SCD at high risk of stroke, aged ≥ 2 years, may be good value for money. The intervention has an incremental cost-effectiveness ratio of £24,075 per quality-adjusted life-year gained, and helps avoid 68 strokes over the lifetime of a population of 1000 patients. The intervention costs an additional £13,751 per patient and generates 0.6 extra years of life in full health per patient. The data available for the economic analysis are limited. Sensitivity analyses and validation against existing data and expert opinion provide some reassurance that the conclusion of the model is reliable but further research is required to validate these findings.
LIMITATIONS
The main limitations relate to the availability of published clinical data; no completed randomised controlled trials were identified which evaluated the efficacy of either BMT or hydroxycarbamide for primary stroke prevention. Both the clinical and cost data available for use in the economic analysis are limited. Sensitivity analyses and validation against existing data and expert opinion provide some reassurance that the conclusions of the model are reliable, but further research is required to validate these findings.
CONCLUSIONS
The use of TCD ultrasonography to identify children at high risk of stroke, and treating these children with prophylactic blood transfusions, appears to be both clinically effective and cost-effective compared with TCD ultrasonography only. However, given the limitations in the data available, further research is required to verify this conclusion. Several research recommendations can be proposed from this review. Clinically, more research is needed to assess the effects and optimal duration of long-term blood transfusion and the potential role of hydroxycarbamide in primary stroke prevention. From an economics perspective, further research is required to generate more robust data on which to base estimates of cost-effectiveness or against which model outputs can be calibrated. More data are required to explain how utility weights vary with age, transfusions and strokes. Research is also needed around the cost of paediatric stroke in the UK.
STUDY REGISTRATION
PROSPERO CRD42011001496.
FUNDING
The National Institute for Health Research Health Technology Assessment programme.
Topics: Anemia, Sickle Cell; Antisickling Agents; Blood Transfusion; Bone Marrow Transplantation; Cerebrovascular Circulation; Child; Cost-Benefit Analysis; Humans; Hydroxyurea; Markov Chains; Primary Prevention; Quality-Adjusted Life Years; Randomized Controlled Trials as Topic; Stroke; Ultrasonography, Doppler, Transcranial
PubMed: 23140544
DOI: 10.3310/hta16430 -
Molecular Vision 2011Congenital corneal opacification (CCO) encompasses a broad spectrum of disorders that have different etiologies, including genetic and environmental. Terminology used in... (Review)
Review
Congenital corneal opacification (CCO) encompasses a broad spectrum of disorders that have different etiologies, including genetic and environmental. Terminology used in clinical phenotyping is commonly not specific enough to describe separate entities, for example both the terms Peters anomaly and sclerocornea have been ascribed to a clinical picture of total CCO, without investigating the presence or absence of iridocorneal adhesions. This is not only confusing but also unhelpful in determining valid genotype-phenotype correlations, and thereby revealing clues for pathogenesis. We undertook a systematic review of the literature focusing on CCO as part of anterior segment developmental anomalies (ASDA), and analyzed its association specifically with chromosomal abnormalities. Genes previously identified as being associated with CCO are also summarized. All reports were critically appraised to classify phenotypes according to described features, rather than the given diagnosis. Some interesting associations were found, and are discussed.
Topics: Chromosome Aberrations; Chromosomes, Human; Cornea; Corneal Opacity; Databases, Bibliographic; Diagnosis, Differential; Eye Proteins; Female; Genetic Association Studies; Genetic Linkage; Genetic Loci; Humans; Male; Mutation
PubMed: 21738392
DOI: No ID Found -
Blood Cancer Journal Jan 2024Extra copies of chromosome 1q21 (+1q: gain = 3 copies, amp >= 4 copies) are associated with worse outcomes in multiple myeloma (MM). This systematic review assesses...
Extra copies of chromosome 1q21 (+1q: gain = 3 copies, amp >= 4 copies) are associated with worse outcomes in multiple myeloma (MM). This systematic review assesses the current reporting trends of +1q, the efficacy of existing regimens on +1q, and its prognostic implications in MM randomized controlled trials (RCTs). Pubmed, Embase and Cochrane Registry of RCTs were searched from January 2012 to December 2022. Only MM RCTs were included. A total of 124 RCTs were included, of which 29 (23%) studies reported on +1q. Among them, 10% defined thresholds for +1q, 14% reported survival data separately for gain and amp, and 79% considered +1q a high-risk cytogenetic abnormality. Amongst RCTs that met the primary endpoint showing improvement in progression free survival (PFS), lenalidomide maintenance (Myeloma XI), selinexor (BOSTON), and isatuximab (IKEMA and ICARIA) were shown to improve PFS for patients with evidence of +1q. Some additional RCT's such as Myeloma XI+ (carfilzomib), ELOQUENT-3 (elotuzumab), and HOVON-65/GMMG-HD4 (bortezomib) met their endpoint showing improvement in PFS and also showed improvement in PFS in the +1q cohort, although the confidence interval crossed 1. All six studies that reported HR for +1q patients vs. without (across both arms) showed worse OS and PFS for +1q. There is considerable heterogeneity in the reporting of +1q. All interventions that have shown to be successful in RCTs and have clearly reported on the +1q subgroup have shown concordant direction of results and benefit of the applied intervention. A more standardized approach to reporting this abnormality is needed.
Topics: Humans; Antineoplastic Combined Chemotherapy Protocols; Bortezomib; Chromosome Aberrations; Chromosomes, Human, Pair 1; Lenalidomide; Multiple Myeloma; Prognosis; Randomized Controlled Trials as Topic
PubMed: 38272897
DOI: 10.1038/s41408-024-00985-0 -
Cancers Jun 2022Despite the major advances in screening and therapeutic approaches, gynaecological malignancies still present as a leading cause of death among women of reproductive... (Review)
Review
Despite the major advances in screening and therapeutic approaches, gynaecological malignancies still present as a leading cause of death among women of reproductive age. Cervical cancer, although largely preventable through vaccination and regular screening, remains the fourth most common and most lethal cancer type in women, while the available treatment schemes still pose a fertility threat. Ovarian cancer is associated with high morbidity rates, primarily due to lack of symptoms and high relapse rates following treatment, whereas endometrial cancer, although usually curable by surgery, it still represents a therapeutic problem. On the other hand, benign abnormalities, such as fibroids, endometriosis, placental, and embryo implantation disorders, although not life-threatening, significantly affect women's life and fertility and have high socio-economic impacts. In the last decade, targeted gene therapy approaches toward both malignant and benign gynaecological abnormalities have led to promising results, setting the ground for successful clinical trials. The above therapeutic strategies employ both viral and non-viral systems for mutation compensation, suicide gene therapy, oncolytic virotherapy, antiangiogenesis and immunopotentiation. This review discusses all the major advances in gene therapy of gynaecological disorders and highlights the novel and potentially therapeutic perspectives associated with such an approach.
PubMed: 35805007
DOI: 10.3390/cancers14133238