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Chinese Clinical Oncology Jun 2023Mutations in the BRCA1/2 (BRCA) genes are associated with response to poly(ADP-ribose) polymerase (PARP) inhibitors (PARPi). In addition, there are different homologous... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Mutations in the BRCA1/2 (BRCA) genes are associated with response to poly(ADP-ribose) polymerase (PARP) inhibitors (PARPi). In addition, there are different homologous recombination deficiency (HRD) biomarkers available in clinical practice [e.g., genome-wide loss-of-heterozygosity (gLOH) and myChoice® score] that identify patients who can benefit from PARPi. Inconsistencies in biomarkers used in PARPi clinical trials make it challenging to identify clinically relevant predictive biomarkers. This study aims to compare clinically available HRD biomarkers in terms of benefits from PARPi.
METHODS
We performed database search for phase II or III randomized clinical trials comparing PARPi versus chemotherapy, and meta-analysis using generic inverse variance and a Random Effects model. Patients were classified according to their HRD status: (I) BRCAm (patients with BRCA mutation of germline or somatic origin); (II) non-BRCA HRD [patients BRCA wild-type (wt) with another HRD biomarker-gLOH or myChoice®]; and (III) homologous recombination proficiency (HRP) (BRCAwt and without HRD biomarkers). From those that were BRCAwt, we compared myChoice®+ with gLOH-high.
RESULTS
Five studies (3,225 patients) analyzing PARPi in first line setting were included. Patients with BRCAmut had progression-free survival (PFS) with hazard ratio (HR) 0.33 [95% confidence interval (CI): 0.30-0.43]; patients with non-BRCA HRD had a PFS HR 0.49 (95% CI: 0.37-0.65), and patients with HRP had a PFS HR 0.78 (95% CI: 0.58-1.03). Eight studies (5,529 patients) with PARPi including first line and recurrence settings were included. BRCAmut had PFS HR 0.37 (95% CI: 0.30-0.48), BRCAwt & HRD 0.45 (95% CI: 0.37-0.55) and HRP 0.70 (95% CI: 0.57-0.85). Patients with BRCAwt & myChoice® ≥42 had PFS HR 0.43 (95% CI: 0.34-0.56), similar to patients with BRCAwt & gLOH-high with PFS HR 0.42 (95% CI: 0.28-0.62).
CONCLUSIONS
Patients with HRD derived significantly more benefit from PARPi when compared to patients with HRP. The benefit of PARPi in patients with HRP tumors was limited. Careful cost-effectiveness analysis, and alternative therapies or clinical trial enrollment should strongly be considered for patients with HRP tumors. Among patients with BRCAwt, a similar benefit was found in patients with gLOH-high and those myChoice®+. The clinical development of further HRD biomarkers (e.g., Sig3) may help identify more patients who benefit from PARPi.
Topics: Humans; Female; BRCA1 Protein; BRCA2 Protein; Poly(ADP-ribose) Polymerase Inhibitors; Ovarian Neoplasms; Homologous Recombination; Biomarkers
PubMed: 37211773
DOI: 10.21037/cco-22-114 -
BMC Pregnancy and Childbirth Nov 2022Vitamin D deficiency, a common problem among pregnant women, is linked with maternal inflammation, oxidative stress and consequent adverse pregnancy outcomes. The aim of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Vitamin D deficiency, a common problem among pregnant women, is linked with maternal inflammation, oxidative stress and consequent adverse pregnancy outcomes. The aim of this systematic review was to evaluate the effect of vitamin D supplementation on oxidative stress and inflammatory biomarkers in pregnant women according to the PRISMA guidance.
METHODS
Four databases including PubMed/MEDLINE, Scopus, Web of Science and Cochrane were used for searching papers published until 25 July 2022. Clinical trials that assessed 25-Hydroxyvitamin D (25(OH)D), inflammatory markers (including high sensitivity C-reactive protein (hs-CRP) and certain cytokines) and oxidative stress markers (including malondialdehyde (MDA), total antioxidant capacity (TAC) and glutathione (GSH)) in pregnant women, were included in this review. The primary search of three databases displayed 21571 records. After removing duplicates and irrelevant articles, 17 eligible RCTs included for more evaluation. Random effect model and Der Simonian-Laird method were used to pool the data of studies. Risk of bias assessed according to version 2 of the Cochrane risk-of-bias tool for randomized trials.
RESULTS
According to the meta-analysis result, vitamin D supplementation caused a significant increase in the maternal circulating concentrations of 25(OH)D (SMD 2.07; 95%, CI 1.51, 2.63; p < 0.001), TAC (SMD 2.13, 95% CI 1.04 to 3.23, p < 0.001) and GSH (SMD 4.37, 95% CI 2.9 to 5.74, p < 0.001) as well as a significant decrease in the levels of MDA (SMD -0.46, 95% CI -0.87 to -0.05, p = 0.02). However, it had no significant impact on hs-CRP concentrations (SMD 0.24; 95% CI, -0.55, 1.03; p = 0.50).
CONCLUSION
In the present study, vitamin D supplementation led to increased levels of 25(OH)D, TAC and GSH and also decreased concentration of MDA. Nevertheless, because of low certainty of evidence, these findings have to be declared conservatively.
TRIAL REGISTRATION
Registration code in PROSPERO website: CRD42020202600.
Topics: Female; Pregnancy; Humans; C-Reactive Protein; Dietary Supplements; Pregnant Women; Oxidative Stress; Biomarkers; Vitamin D; Antioxidants
PubMed: 36335311
DOI: 10.1186/s12884-022-05132-w -
Asian Pacific Journal of Cancer... 2015Several studies have investigated predictive and prognostic biomarkers for patients treated with anti-epidermal growth factor receptor (EGFR) agents in lung cancer.... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Several studies have investigated predictive and prognostic biomarkers for patients treated with anti-epidermal growth factor receptor (EGFR) agents in lung cancer. However, the conclusion is controversial.
MATERIALS AND METHODS
A meta-analysis was conducted to evaluate the associations of mutant K-ras, PIK3CA and PTEN deficiency with the efficacy of anti-EGFR agents in lung cancer. The primary endpoint was objective response rate (ORR). The secondary endpoints were overall survival (OS) and progression-free survival (PFS).
RESULTS
A total of 61 studies were included in the final meta-analysis. The result showed that K-ras mutation was a good predictor for ORR (RR=0.42, 95%CI, 0.33-0.55, p=0.000) and an effective prognostic marker for OS (HR=1.37, 95%CI, 1.15-1.65, p=0.001) and PFS (HR=1.33, 95%CI, 1.05-1.69, p=0.019). However, PTEN deficiency or PIK3CA mutation did not show any significance predictive value for ORR (PTEN, RR=0.82, 95%CI, 0.56-1.19, p=0.286; PIK3CA, RR=1.08, 95%CI, 0.17-6.66, P=0.938). And PTEN deficiency or expression of PIK3CA did not show significance prognostic value for OS (PTEN, HR=0.88, 95%CI, 0.31-2.46,P=0.805; PIK3CA, HR=0.79, 95%CI: 0.23-2.68, P=0.706).
CONCLUSIONS
Our meta-analysis showed that K-ras mutation may be an effective predictor in lung cancer patients treated with anti-EGFR agents. Whereas, the predictive and prognostic value of PTEN deficiency and PIK3CA mutation need to be further investigated.
Topics: Antineoplastic Agents; Biomarkers, Tumor; ErbB Receptors; Humans; Lung Neoplasms; Molecular Targeted Therapy; Prognosis
PubMed: 26107237
DOI: 10.7314/apjcp.2015.16.11.4759 -
Cureus Apr 2020Cerebral venous sinus thrombosis (CVST) is a rare condition characterized by elevated intracranial pressure due to impaired cerebral venous drainage, potentially... (Review)
Review
Cerebral venous sinus thrombosis (CVST) is a rare condition characterized by elevated intracranial pressure due to impaired cerebral venous drainage, potentially leading to life-threatening consequences. We searched the PubMed electronic database for 'cerebral venous sinus thrombosis' and 'prothrombotic' cases reported in adults (19+ years) and conducted a systematic review for the published literature in the English language pooled with a case from our institution. Data were analyzed regarding patient demographics, risk factors, clinical features, treatment modalities, and outcomes when available. Thirty cases of CVST were identified (29 case reports, of whom two were described in a case series, and the one case from our institution). The patients' mean age was 39 years (range: 19 - 65). The male: female ratio was 1.14:1. The majority (73.3%) had at least one preexisting risk factor, with prescription drug use being the most common risk factor (33.3%) shared among all patients. Most patients (83.3%) presented with at least two symptoms. The most common presenting symptoms were headache (70%), gastrointestinal disturbance (50%), and seizures (40%). Focal deficits (36.7%), vision disturbances (30%), and altered consciousness (20%) were the remaining presenting complaints. Twelve cases (40%) commented on papilledema, with 10 (83.3%) having papilledema present. Anticoagulation abnormalities were examined in 26 cases (86.7%), out of which four cases (15.4%) had isolated protein S (PS) deficiency, three cases (11.5%) had isolated antithrombin III (ATIII) deficiency, and one case (3.8%) had isolated protein C (PC) deficiency. The most common initial imaging modality (22 cases, 73.3%), and most commonly used overall (23 cases, 76.7%), was computed tomography (CT). Magnetic resonance imaging (MRI) was the second most common imaging modality for initial use (five cases, 16.7%), diagnosis or confirmation of CVST (eight cases, 26.7%), and overall (21 cases, 70%). Heparin treatment was involved in the treatment of 18 cases (60%), and warfarin treatment was used in 10 cases (33.3%). Heparin-warfarin combination treatment was utilized in eight cases (26.7%). Most patients survived (28 cases, 93.3%), while the two remaining patients died secondary to brain death from the CVST (6.7%). The findings from this study highlight the clinical characteristics of CVST. Therefore, this study aims to increase awareness of this rare entity. Physicians should maintain a high index of suspicion in order to diagnose patients presenting in the proper clinical context, given this case shares various forms of presentations with other common clinical conditions but requires long-term anticoagulation.
PubMed: 32411555
DOI: 10.7759/cureus.7654 -
Frontiers in Neuroscience 2023Spinal cord injury (SCI) is a severe neurological injury for which no effective treatment exists. Granulocyte colony-stimulating factor (G-CSF) is used to treat... (Review)
Review
BACKGROUND
Spinal cord injury (SCI) is a severe neurological injury for which no effective treatment exists. Granulocyte colony-stimulating factor (G-CSF) is used to treat autologous bone marrow transplantation, chemotherapy-induced granulocytopenia, Acquired Immune Deficiency Syndrome (AIDS), etc. Recent research has revealed the potential application of G-CSF on neuroprotective effectiveness. In central nervous system diseases, G-CSF can be used to alleviate neuronal injury.
OBJECTIVE
To investigate the effects of G-CSF on Basso, Beattie, and Bresnahan (BBB) scale score, inclined plane test, electrophysiologic exam, quantitative analysis of TUNEL-positive cells, and quantitative analysis of glial fibrillary acidic protein (GFAP) immunostaining images in animal models of SCI.
METHODS
We searched PubMed, Web of Science, and Embase databases for all articles on G-CSF intervention with animal models of SCI reported before November 2022. A total of 20 studies met the inclusion criteria.
RESULTS
Results revealed that G-CSF intervention could improve the BBB scale score in both groups at 3, 7, 14, 28, and 35 days [at 35 days, weighted mean differences (WMD) = 2.4, 95% CI: 1.92-2.87, < 0.00001, I = 69%]; inclined plane test score; electrophysiologic exam; quantitative analysis of TUNEL-positive cell numbers; quantitative analysis of GFAP immunostaining images in animal models of SCI. Subgroup analysis revealed that treatment with normal saline, phosphate-buffered saline, and no treatment resulted in significantly different neurological function effectiveness compared to the G-CSF therapy. SD rats and Wistar rats with SCI resulted in significant neurological function effectiveness. C57BL/6 mice showed no difference in the final effect. The T9-T10 or T10 segment injury model and the T8-T9 or T9 segment injury model resulted in significant neurological function effectiveness. The BBB score data showed no clear funnel plot asymmetry. We found no bias in the analysis result (Egger's test, = 0.42). In our network meta-analysis, the SUCRA ranking showed that 15 mg/kg-20 mg/kg was an optimal dose for long-term efficacy.
CONCLUSION
Our meta-analysis suggests that G-CSF therapy may enhance the recovery of motor activity and have a specific neuroprotective effect in SCI animal models.: PROSPERO, identifier: CRD42023388315.
PubMed: 37449274
DOI: 10.3389/fnins.2023.1168764 -
PeerJ 2022FGF10, as an FGFR2b-specific ligand, plays a crucial role during cell proliferation, multi-organ development, and tissue injury repair. The developmental importance of...
FGF10, as an FGFR2b-specific ligand, plays a crucial role during cell proliferation, multi-organ development, and tissue injury repair. The developmental importance of has been emphasized by the identification of abnormalities in human congenital disorders affecting different organs and systems. Single-nucleotide variants in or -involving copy-number variant deletions have been reported in families with lacrimo-auriculo-dento-digital syndrome, aplasia of the lacrimal and salivary glands, or lethal lung developmental disorders. Abnormalities involving have also been implicated in cleft lip and palate, myopia, or congenital heart disease. However, the exact developmental role of and large phenotypic heterogeneity associated with disruption remain incompletely understood. Here, we review human and animal studies and summarize the data on mechanism of action, expression, multi-organ function, as well as its variants and their usefulness for clinicians and researchers.
Topics: Animals; Humans; Cleft Lip; Cleft Palate; Lacrimal Apparatus Diseases; Lacrimal Apparatus; Syndactyly; Lung Diseases; Fibroblast Growth Factor 10
PubMed: 36124135
DOI: 10.7717/peerj.14003 -
International Journal of Molecular... Dec 2021Medulloblastoma is a common fatal pediatric brain tumor. More treatment options are required to prolong survival and decrease disability. mTOR proteins play an essential... (Review)
Review
Medulloblastoma is a common fatal pediatric brain tumor. More treatment options are required to prolong survival and decrease disability. mTOR proteins play an essential role in the disease pathogenesis, and are an essential target for therapy. Three generations of mTOR inhibitors have been developed and are clinically used for immunosuppression and chemotherapy for multiple cancers. Only a few mTOR inhibitors have been investigated for the treatment of medulloblastoma and other pediatric tumors. The first-generation mTOR, sirolimus, temsirolimus, and everolimus, went through phase I clinical trials. The second-generation mTOR, AZD8055 and sapanisertib, suppressed medulloblastoma cell growth; however, limited studies have investigated possible resistance pathways. No clinical trials have been found to treat medulloblastoma using third-generation mTOR inhibitors. This systematic review highlights the mechanisms of resistance of mTOR inhibitors in medulloblastoma and includes IDO1, T cells, Mnk2, and eIF4E, as they prolong malignant cell survival. The findings promote the importance of combination therapy in medulloblastoma due to its highly resistant nature.
Topics: Antineoplastic Agents; Child; Drug Resistance, Neoplasm; Humans; Medulloblastoma; Protein Kinase Inhibitors; TOR Serine-Threonine Kinases
PubMed: 35008889
DOI: 10.3390/ijms23010464 -
Italian Journal of Pediatrics Jan 2023Nutrition practices for preterm infants include phases of parenteral nutrition, gradually interrupted parenteral nutrition (transition phase), and full enteral... (Review)
Review
Nutrition practices for preterm infants include phases of parenteral nutrition, gradually interrupted parenteral nutrition (transition phase), and full enteral nutrition. However, nutrition management during the transition phase is frequently overlooked. This review examined the relationship between nutrient intake during the transition phase and preterm infant growth. PubMed, Embase, Web of Science, Cochrane, Chinese National Knowledge Infrastructure Database, Wanfang Database, and Chinese Science and Technique Journals Database were searched for studies examining the relationship between nutrient intake during the transition phase and postnatal growth of preterm infants from each database's earliest inception through February 28, 2022. The quality of the studies was assessed using the Newcastle-Ottawa scale. A total of three studies conducted in the USA, Italy and China met the inclusion criteria. The growth indicators were extrauterine growth restriction (weight < 10th percentile for post-menstrual age) or inadequate weight growth velocity (growth velocity < 15 g/kg/d) at discharge or the end of the transition phase. The transition phase was divided into two periods in two studies: the early period (parenteral energy intake > 50% of total energy intake) and the late period (enteral energy intake > 50% of the total energy intake). The cumulative protein intake in the transition phase was generally lower in preterm infants with extrauterine growth restriction or inadequate weight growth velocity, especially in the early transition phase. The deficiency of energy and protein intake during the transition phase cannot be explicitly determined due to differences in growth indicators and definitions of the transition phase. However, enteral protein intake should be closely monitored in the early transition phase to ensure a better growth rate for preterm infants. To elucidate potential associations, further well-designed research will be required.
Topics: Infant; Infant, Newborn; Humans; Infant, Premature; Nutritional Status; Enteral Nutrition; Energy Intake; Eating; Infant, Very Low Birth Weight
PubMed: 36670430
DOI: 10.1186/s13052-022-01406-3 -
The Journal of Nutrition Jul 2021Many nutrients have powerful immunomodulatory actions with the potential to alter susceptibility to coronavirus disease 2019 (COVID-19) infection, progression to...
BACKGROUND
Many nutrients have powerful immunomodulatory actions with the potential to alter susceptibility to coronavirus disease 2019 (COVID-19) infection, progression to symptoms, likelihood of severe disease, and survival.
OBJECTIVE
The aim was to review the latest evidence on how malnutrition across all its forms (under- and overnutrition and micronutrient status) may influence both susceptibility to, and progression of, COVID-19.
METHODS
We synthesized information on 13 nutrition-related components and their potential interactions with COVID-19: overweight, obesity, and diabetes; protein-energy malnutrition; anemia; vitamins A, C, D, and E; PUFAs; iron; selenium; zinc; antioxidants; and nutritional support. For each section we provide: 1) a landscape review of pertinent material; 2) a systematic search of the literature in PubMed and EMBASE databases, including a wide range of preprint servers; and 3) a screen of 6 clinical trial registries. All original research was considered, without restriction to study design, and included if it covered: 1) severe acute respiratory syndrome coronavirus (CoV) 2 (SARS-CoV-2), Middle East respiratory syndrome CoV (MERS-CoV), or SARS-CoV viruses and 2) disease susceptibility or 3) disease progression, and 4) the nutritional component of interest. Searches took place between 16 May and 11 August 2020.
RESULTS
Across the 13 searches, 2732 articles from PubMed and EMBASE, 4164 articles from the preprint servers, and 433 trials were returned. In the final narrative synthesis, we include 22 published articles, 38 preprint articles, and 79 trials.
CONCLUSIONS
Currently there is limited evidence that high-dose supplements of micronutrients will either prevent severe disease or speed up recovery. However, results of clinical trials are eagerly awaited. Given the known impacts of all forms of malnutrition on the immune system, public health strategies to reduce micronutrient deficiencies and undernutrition remain of critical importance. Furthermore, there is strong evidence that prevention of obesity and type 2 diabetes will reduce the risk of serious COVID-19 outcomes. This review is registered at PROSPERO as CRD42020186194.
Topics: Anemia; Antioxidants; COVID-19; Comorbidity; Diabetes Mellitus; Dietary Supplements; Disease Progression; Fatty Acids, Omega-3; Fatty Acids, Omega-6; Humans; Iron; Nutritional Status; Nutritional Support; Obesity; Protein-Energy Malnutrition; SARS-CoV-2; Selenium; Severity of Illness Index; Vitamins; Zinc
PubMed: 33982105
DOI: 10.1093/jn/nxab059 -
Advances in Nutrition (Bethesda, Md.) May 2018Hypothyroidism due to iodine deficiency can impair physical development, most visibly in the marked stunting of myxedematous cretinism caused by severe in utero iodine...
Hypothyroidism due to iodine deficiency can impair physical development, most visibly in the marked stunting of myxedematous cretinism caused by severe in utero iodine deficiency. Whether iodine repletion improves growth in noncretinous children is uncertain. Therefore, the aim of our systematic review was to assess the effects of iodine fortification or supplementation on prenatal and postnatal growth outcomes in noncretinous children. Following Cochrane methods and PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) reporting guidelines, we searched 10 databases including 2 Chinese databases (latest search February 2017). We included randomized and nonrandomized controlled trials (RCTs; non-RCTs), controlled before-after (CBA) studies, and interrupted time-series studies in pregnant women and children (≤18 y), which compared the effects of iodine (any form, dose, regimen) to placebo, noniodized salt, or no intervention on prenatal and postnatal growth outcomes. We calculated mean differences with 95% CIs, performed random-effects meta-analyses, and assessed the quality of evidence with the use of GRADE (Grading of Recommendations Assessment, Development and Evaluation). We included 18 studies (13 RCTs, 4 non-RCTs, 1 CBA) (n = 5729). Iodine supplementation of severely iodine-deficient pregnant women increased mean birthweight [mean difference (MD): 200 g; 95% CI: 183, 217 g; n = 635; 2 non-RCTs] compared to controls, but the quality of this evidence was assessed as very low. Iodine repletion across the other groups showed no effects on primary growth outcomes (quality of evidence mostly low and very low). Meta-analyses showed a positive effect in moderate-to-mildly iodine-deficient schoolchildren on insulin-like growth factor-1 (MD: 38.48 ng/mL; 95% CI: 6.19, 70.76 ng/mL; n = 498; 2 RCTs, low-quality evidence) and insulin-like growth factor binding protein-3 (MD: 0.46 μg/mL; 95% CI: 0.25, 0.66 μg/mL; n = 498; 2 RCTs, low-quality evidence). In conclusion, we identified few well-designed trials examining the effects of iodine repletion on growth. We are uncertain whether prenatal iodine repletion increases infant growth. Postnatal iodine repletion may improve growth factors but has no clear effects on somatic growth. Our systematic review was registered with PROSPERO as CRD42014012940.
Topics: Birth Weight; Deficiency Diseases; Dietary Supplements; Female; Fetal Growth Retardation; Food, Fortified; Growth Disorders; Humans; Iodine; Maternal Nutritional Physiological Phenomena; Pregnancy; Pregnancy Complications; Sodium Chloride, Dietary; Somatomedins
PubMed: 29767700
DOI: 10.1093/advances/nmy009