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Gynecologic Oncology Mar 2023Investigating for mismatch repair protein deficiency (MMRd), microsatellite instability (MSI), and Lynch syndrome (LS) is widely accepted in endometrial cancer, but... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Investigating for mismatch repair protein deficiency (MMRd), microsatellite instability (MSI), and Lynch syndrome (LS) is widely accepted in endometrial cancer, but knowledge is limited on its value in epithelial ovarian cancer (EOC). The primary objective was to evaluate the prevalence of mismatch repair protein deficiency (MMRd), microsatellite instability (MSI)-high, and Lynch syndrome (LS) in epithelial ovarian cancer (EOC), as well as the diagnostic accuracy of LS screening tests. The secondary objective was to determine the prevalence of MMRd, MSI-high, and LS in synchronous ovarian endometrial cancer and in histological subtypes.
METHODS
We systematically searched the MEDLINE, Epub Ahead of Print, MEDLINE In-Process and Other Non-Indexed Citations, Cochrane Central Register of Controlled Trials, and Embase databases. We included studies analysing MMR, MSI, and/or LS by sequencing.
RESULTS
A total of 55 studies were included. The prevalence of MMRd, MSI-high, and LS in EOC was 6% (95% confidence interval (CI) 5-8%), 13% (95% CI 12-15%), and 2% (95% CI 1-3%) respectively. Hypermethylation was present in 76% of patients with MLH1 deficiency (95% CI 64-84%). The MMRd prevalence was highest in endometrioid (12%) followed by non-serous non-mucinous (9%) and lowest in serous (1%) histological subtypes. MSI-high prevalence was highest in endometrioid (12%) and non-serous non-mucinous (12%) and lowest in serous (9%) histological subtypes. Synchronous and endometrioid EOC had the highest prevalence of LS pathogenic variants at 7% and 3% respectively, with serous having lowest prevalence (1%). Synchronous ovarian and endometrial cancers had highest rates of MMRd (28%) and MSI-high (28%). Sensitivity was highest for IHC (91.1%) and IHC with MSI (92.8%), while specificity was highest for IHC with methylation (92.3%).
CONCLUSION
MMRd and germline LS testing should be considered for non-serous non-mucinous EOC, particularly for endometrioid.
PRECIS
The rates of mismatch repair deficiency, microsatellite instability high, and mismatch repair germline mutations are highest in endometrioid subtype and non-serous non-mucinous ovarian cancer. The rates are lowest in serous histologic subtype.
Topics: Humans; Female; Colorectal Neoplasms, Hereditary Nonpolyposis; Carcinoma, Ovarian Epithelial; Microsatellite Instability; Ovarian Neoplasms; Carcinoma, Endometrioid; Endometrial Neoplasms; Protein Deficiency; DNA Mismatch Repair; MutL Protein Homolog 1
PubMed: 36682091
DOI: 10.1016/j.ygyno.2022.12.008 -
The Cochrane Database of Systematic... Nov 2016Among pediatric patients, newborns are at highest risk of developing thromboembolism. Neonatal thromboembolic (TE) events may consist of both venous and arterial... (Review)
Review
BACKGROUND
Among pediatric patients, newborns are at highest risk of developing thromboembolism. Neonatal thromboembolic (TE) events may consist of both venous and arterial thromboses and often iatrogenic complications (eg, central catheterization). Treatment guidelines for pediatric patients with TE events most often are extrapolated from the literature regarding adults. Options for the management of neonatal TE events include expectant management; nitroglycerin ointment; thrombolytic therapy or anticoagulant therapy, or a combination of the two; and surgery. Since the 1990s, low molecular weight heparin (LMWH) has become the neonatal anticoagulant of choice. Reasons for its appeal include predictable dose response, no need for venous access, and limited monitoring requirements. The overall major complication rate is around 5%. Whether preterm infants are at increased risk is unclear. No data are available on the frequency of osteoporosis, heparin-induced thrombocytopenia (HIT), or other hypersensitivity reactions in children and neonates exposed to LMWH.
OBJECTIVES
To assess whether heparin treatment (both unfractionated heparin [UFH] and LMWH) reduces mortality and morbidity rates in preterm and term newborn infants with diagnosed thrombosis. The intervention is compared with placebo or no treatment. Also, to assess the safety of heparin therapy (both UFH and LMWH) for potential harms.Subgroup analyses were planned to examine gestational age, birth weight, mode of thrombus diagnosis, presence of a central line, positive family history for genetic disorders (thrombophilia, deficiency of protein S and protein C, methylenetetrahydrofolate reductase [MTHFR] mutation), route of heparin administration, type of heparin used, and location of thrombus (see "Subgroup analysis and investigation of heterogeneity").
SEARCH METHODS
We used the standard search strategy of the Cochrane Neonatal Review Group to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 4), MEDLINE via PubMed (1966 to May 9, 2016), Embase (1980 to May 9, 2016), and the Cumulative Index to Nursing and Allied Health Literature (CINAHL; 1982 to May 9, 2016). We searched clinical trials databases, conference proceedings, and the reference lists of retrieved articles for randomized controlled trials and quasi-randomized trials.
SELECTION CRITERIA
Randomized, quasi-randomized, and cluster-randomized controlled trials comparing heparin versus placebo or no treatment in preterm and term neonates with a diagnosis of thrombosis.
DATA COLLECTION AND ANALYSIS
We used the standard methods of the Cochrane Neonatal Review Group. Two review authors independently assessed studies identified by the search strategy for inclusion.
MAIN RESULTS
Our search strategy yielded 1160 references. Two review authors independently assessed all references for inclusion. We found no completed studies and no ongoing trials for inclusion.
AUTHORS' CONCLUSIONS
We found no studies that met our inclusion criteria and no evidence from randomized controlled trials to recommend or refute the use of heparin for treatment of neonates with thrombosis.
Topics: Anticoagulants; Heparin; Heparin, Low-Molecular-Weight; Humans; Infant, Newborn; Thrombosis
PubMed: 27820879
DOI: 10.1002/14651858.CD012185.pub2 -
European Review For Medical and... Jan 2017Thyroid disorders, especially Hashimoto's thyroiditis (HT), are observed significantly more often in patients with polycystic ovary syndrome (PCOS) than in the general... (Review)
Review
OBJECTIVE
Thyroid disorders, especially Hashimoto's thyroiditis (HT), are observed significantly more often in patients with polycystic ovary syndrome (PCOS) than in the general population - approximately 27% and 8%, respectively. This is extremely important in young women, because both disorders are connected with fertility problems. As HT and PCOS occur together, fertility problems may become a serious clinical issue in these patients.
MATERIALS AND METHODS
A systematic literature review in PubMed of PCOS- and HT-related articles in English, published until December 2015 was conducted.
RESULTS
The reasons for joint prevalence still remain unclear. Genetic and autoimmune backgrounds are recognized to be possible common etiological factors. Three genetic polymorphisms have been described to play a role in PCOS as well as in HT. They are polymorphism of the gene for fibrillin 3 (FBN3) regulating the activity of transforming growth factor-b (TGF-b) and regulatory T cell levels, gonadotropin-releasing hormone receptor (GnRHR) polymorphism and CYP1B1 polymorphism standing for estradiol hydroxylation. High estrogen-to-progesterone ratios owing to anovulatory cycles, as well as high estrogen levels during prenatal life, disrupt development of the thymus and its function in maintaining immune tolerance, and are suspected to enhance autoimmune response in PCOS. Vitamin D deficiency could be also involved in the pathogenesis of HT and PCOS.
CONCLUSIONS
The above-mentioned common etiological factors associated with fertility problems in HT and PCOS require further research.
Topics: Cytochrome P-450 CYP1B1; Female; Fibrillins; Hashimoto Disease; Humans; Polycystic Ovary Syndrome; Receptors, LHRH; Transforming Growth Factor beta
PubMed: 28165551
DOI: No ID Found -
Human Reproduction (Oxford, England) Apr 2021Is there an association between hereditary thrombophilia in pregnant women and risk of recurrent pregnancy loss (RPL)? (Meta-Analysis)
Meta-Analysis
STUDY QUESTION
Is there an association between hereditary thrombophilia in pregnant women and risk of recurrent pregnancy loss (RPL)?
SUMMARY ANSWER
Pregnant women with hereditary thrombophilia have an increased risk of RPL, especially for pregnant women with the G1691A mutation of the factor V Leiden (FVL) gene, the G20210A mutation of the prothrombin gene (PGM), and deficiency of protein S (PS).
WHAT IS KNOWN ALREADY
Prior studies have suggested that pregnant women with hereditary thrombophilia have a higher risk of RPL, however, the results are inconsistent; furthermore, a complete overview is missing. This lack of information is an obstacle to the risk assessment of RPL in pregnant women with hereditary thrombophilia. A comprehensive meta-analysis on the relation between hereditary thrombophilia and the risk of RPL is needed.
STUDY DESIGN, SIZE, DURATION
A systematic review and meta-analysis was performed using observational studies published in English before 1 April 2020 to evaluate the relation between hereditary thrombophilia and risk of RPL.
PARTICIPANTS/MATERIALS, SETTING, METHODS
Relevant studies were identified from PubMed, Web of Science, and EMBASE searches and complemented with perusal of bibliographies of retrieved articles. The exposure of interest was hereditary thrombophilia, including FVL mutation, PGM, deficiency of antithrombin (AT), deficiency of protein C (PC), and deficiency of PS. The overall risk estimates were pooled using random effects models. Subgroup and sensitivity analyses were carried out to explore possible sources of heterogeneity and assess the robustness of the results.
MAIN RESULTS AND THE ROLE OF CHANCE
A total of 89 studies involving 30 254 individuals were included. Results showed that women with FVL mutation (odds ratio (OR): 2.44, 95% CI: 1.96-3.03), PGM (OR: 2.08, 95% CI: 1.61-2.68), or deficiency of PS (OR: 3.45, 95% CI: 1.15-10.35) had higher risks of developing RPL. Compared with the reference group, there was no observed relation between a deficiency in AT or PC and RPL (all P > 0.05). Heterogeneity in the risk estimates of RPL was partially explained by geographic region, definitions of RPL, types of RPL, and controlled confounders. Sensitivity analyses validated the robustness of the findings.
LIMITATIONS, REASONS FOR CAUTION
Only 39 of the included studies controlled for one or more confounders, and the heterogeneity across all included studies was high. Based on the data available, we cannot determine whether this association is confounded by other potential risk factors of RPL.
WIDER IMPLICATIONS OF THE FINDINGS
This systematic review and meta-analysis show a possible association between hereditary thrombophilia and an increased risk of RPL, suggesting that testing for hereditary thrombophilia should be considered in individuals with RPL.
STUDY FUNDING/COMPETING INTEREST(S)
The study was funded by the Hunan Provincial Key Research and Development Program (Grant number: 2018SK2062) and National Natural Science Foundation Program (Grant number: 81973137). There are no conflicts of interest.
REGISTRATION NUMBER
N/A.
Topics: Abortion, Habitual; Female; Humans; Mutation; Odds Ratio; Pregnancy; Risk Factors; Thrombophilia
PubMed: 33575779
DOI: 10.1093/humrep/deab010 -
Children (Basel, Switzerland) Mar 2023Vitamin B6-dependent epilepsies include treatable diseases responding to pyridoxine or pyridoxal-5Iphosphate (ALDH7A1 deficiency, PNPO deficiency, PLP binding protein... (Review)
Review
BACKGROUND
Vitamin B6-dependent epilepsies include treatable diseases responding to pyridoxine or pyridoxal-5Iphosphate (ALDH7A1 deficiency, PNPO deficiency, PLP binding protein deficiency, hyperprolinemia type II and hypophosphatasia and glycosylphosphatidylinositol anchor synthesis defects).
PATIENTS AND METHODS
We conducted a systematic review of published pediatric cases with a confirmed molecular genetic diagnosis of vitamin B6-dependent epilepsy according to PRISMA guidelines. Data on demographic features, seizure semiology, EEG patterns, neuroimaging, treatment, and developmental outcomes were collected.
RESULTS
497 published patients fulfilled the inclusion criteria. Seizure onset manifested at 59.8 ± 291.6 days (67.8% of cases in the first month of life). Clonic, tonic-clonic, and myoclonic seizures accounted for two-thirds of the cases, while epileptic spasms were observed in 7.6%. Burst-suppression/suppression-burst represented the most frequently reported specific EEG pattern (14.4%), mainly in PLPB, ALDH7A1, and PNPO deficiency. Pyridoxine was administered to 312 patients (18.5% intravenously, 76.9% orally, 4.6% not specified), and 180 also received antiseizure medications. Pyridoxine dosage ranged between 1 and 55 mg/kg/die. Complete seizure freedom was achieved in 160 patients, while a significant seizure reduction occurred in 38. PLP, lysine-restricted diet, and arginine supplementation were used in a small proportion of patients with variable efficacy. Global developmental delay was established in 30.5% of a few patients in whom neurocognitive tests were performed.
CONCLUSIONS
Despite the wide variability, the most frequent hallmarks of the epilepsy phenotype in patients with vitamin B6-dependent seizures include generalized or focal motor seizure semiology and a burst suppression/suppression burst pattern in EEG.
PubMed: 36980111
DOI: 10.3390/children10030553 -
Clinical and Experimental Immunology Jul 2021Cytotoxic T lymphocyte antigen 4 (CTLA-4) haploinsufficiency (CHAI) and lipopolysaccharide-responsive beige-like anchor (LRBA) deficiency (LATAIE) are newly identified... (Review)
Review
Cytotoxic T lymphocyte antigen 4 (CTLA-4) haploinsufficiency (CHAI) and lipopolysaccharide-responsive beige-like anchor (LRBA) deficiency (LATAIE) are newly identified inborn errors of immunity with shared molecular pathomechanisms and clinical manifestations. In this review, we aimed to provide differential comparisons regarding demographic, clinical, immunological and molecular characteristics between these two similar conditions. A literature search was conducted in PubMed, Web of Science and Scopus databases and included studies were systematically evaluated. Overall, 434 (222 CHAI and 212 LATAIE) patients were found in 101 eligible studies. The CHAI patients were mainly reported from North America and western Europe, while LATAIE patients were predominantly from Asian countries. In CHAI, positive familial history (P < 0·001) and in LATAIE, consanguineous parents (P < 0·001) were more common. In CHAI patients the rates of granulomas (P < 0·001), malignancies (P = 0·001), atopy (P = 0·001), cutaneous disorders (P < 0·001) and neurological (P = 0·002) disorders were higher, while LATAIE patients were more commonly complicated with life-threatening infections (P = 0·002), pneumonia (P = 0·006), ear, nose and throat disorders (P < 0·001), organomegaly (P = 0·023), autoimmune enteropathy (P = 0·038) and growth failure (P < 0·001). Normal lymphocyte subsets and immunoglobulins except low serum levels of CD9 B cells (14·0 versus 38·4%, P < 0·001), natural killer (NK) cells (21 versus 41·1%, P < 0·001), immunoglobulin (Ig)G (46·9 versus 41·1%, P = 0·291) and IgA (54·5 versus 44·7%, P = 0·076) were found in the majority of CHAI and LATAIE patients, respectively. The most frequent biological immunosuppressive agents prescribed for CHAI and LATAIE patients were rituximab and abatacept, respectively. Further investigations into the best conditioning and treatment regimens pre- and post-transplantation are required to improve the survival rate of transplanted CHAI and LATAIE patients.
Topics: Adaptor Proteins, Signal Transducing; CTLA-4 Antigen; Haploinsufficiency; Humans; Immunoglobulins; Immunosuppressive Agents; Lymphocytes
PubMed: 33788257
DOI: 10.1111/cei.13600 -
Andrology Sep 2023Although selective estrogen receptor modulators have been proposed as a treatment for men with central functional hypogonadism, only a few data have been produced in men... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Although selective estrogen receptor modulators have been proposed as a treatment for men with central functional hypogonadism, only a few data have been produced in men with obesity-related functional androgen deficiency.
OBJECTIVE
To determine whether and to what extent selective estrogen receptor modulators are an effective and safe therapy in men with obesity-related functional androgen deficiency.
MATERIALS AND METHODS
A thorough search of PubMed, Web of Science, Scopus, and Cochrane Library databases was performed to identify studies comparing testosterone levels before and after treatment. Mean differences with 95% coefficient intervals were combined using random effects models. Funnel plot, Egger's test, and trim-and-fill analysis were used to assess publication bias.
RESULTS
Seven studies met the inclusion criteria providing information on 292 men with obesity-related functional androgen deficiency treated with clomiphene citrate (12.5-50 mg daily) or enclomiphene citrate (12.5-25 mg daily) for 1.5-4 months. The pooled estimates indicated a significant increase in testosterone levels both with clomiphene (mean difference: 11.56 nmol/L; 95% coefficient interval: 9.68, 13.43; I = 69%, p = 0.01) and enclomiphene citrate (mean difference: 7.50 nmol/L; 95% coefficient interval: 6.52, 8.48; I = 4%, p = 0.37). After the exclusion of one study on severely obese men, who exhibited the highest response rate to clomiphene citrate, the heterogeneity disappeared (mean difference: 10.27 nmol/L; 95% coefficient interval: 9.39, 11.16; I = 0%, p = 0.66). No publication bias was revealed by Egger's test and trim-and-fill analysis. No treatment-related unexpected findings regarding safety profile were registered.
DISCUSSION AND CONCLUSION
Treatment with clomiphene citrate and enclomiphene citrate may be an effective and safe alternative to testosterone replacement therapy in men with obesity-related functional androgen deficiency. Further long-term studies are warranted to define clinical reflections of the selective estrogen receptor modulators-induced increase in testosterone levels and to better clarify the safety profile.
Topics: Humans; Male; Androgens; Clomiphene; Enclomiphene; Eunuchism; Hypogonadism; Obesity; Receptors, Estrogen; Selective Estrogen Receptor Modulators; Testosterone
PubMed: 36604313
DOI: 10.1111/andr.13373 -
Experimental Gerontology Aug 2020Nutrition is critical to the health of the elderly, since most of them have a deficiency in key nutrient. The use of whey protein may be a food strategy to increase... (Review)
Review
UNLABELLED
Nutrition is critical to the health of the elderly, since most of them have a deficiency in key nutrient. The use of whey protein may be a food strategy to increase protein intake. The objective of this work was to evaluate the ingestion of whey protein for the elderly and the association with physical performance and clinical outcomes. A systematic review was conducted in order to find papers that shed some light in the correlation between whey protein and the elderly.
INCLUSION CRITERIA
population: elderly; intervention: use of whey protein when compared to control group; outcome: related to health, nutrition, or quality of life.
DATABASE
PubMed, with papers published in the last 5 years.
SEARCH STRATEGY
(elder OR senior OR elderly OR aging OR aged OR old OR older) AND (whey OR "whey protein"). 35 papers were selected of which 22 had a physical performance outcome and 13 had clinical outcomes. Studies indicate that whey protein supplements promote protein synthesis in the elderly, improving muscle performance and aerobic capacity, protecting against sarcopenia and reducing the risk for falls. In the papers studied, the age group considered to be elderly was ≥65 years in 27 papers and ≥60 years in the other 8 papers. Whey protein also appears to contribute to improved health, recovery from disease, prevention of cardiovascular and metabolic risks, and hepatic steatosis complications. Data suggest that whey protein supplements may be promising for the health improvement of the elderly.
Topics: Aged; Diet; Dietary Supplements; Eating; Humans; Physical Functional Performance; Quality of Life; Whey Proteins
PubMed: 32289487
DOI: 10.1016/j.exger.2020.110936 -
Open Heart Oct 2020We conducted a systematic review and meta-analysis of studies that compared levels of molecular biomarkers in women with peripartum cardiomyopathy (PPCM) to those in... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
We conducted a systematic review and meta-analysis of studies that compared levels of molecular biomarkers in women with peripartum cardiomyopathy (PPCM) to those in healthy pregnant and postpartum women to: (1) assess the evidence for prolactin (PRL) metabolism in PPCM, (2) ascertain the evidence for biomarkers of iron deficiency in PPCM, (3) identify other biomarkers associated with PPCM.
METHODS
We searched Medline, Embase, Cumulated Index to Nursing and Allied Health Literature (CINAHL) and the Global Health Library from inception without language restriction for studies that compared biomarkers levels in PPCM cases to healthy controls. Pooled standardised mean difference (SMD) was generated using a random effects model for the difference in levels of biomarkers.
RESULTS
Two studies assessed the association of PRL with PPCM, and reported that PPCM cases have higher levels of total PRL. No studies investigated iron metabolism in PPCM. Other biomarkers associated with PPCM included serum levels of natriuretic peptides (SMD=3.77, 95% CI 0.71 to 6.82), albumin (SMD=-0.67, 95% CI -1.01 to -0.32), C-reactive protein (SMD=1.67, 95% CI 0.22 to 3.12), selenium (SMD=-0.73, 95% CI -1.58 to 0.12), cardiac troponins (SMD=1.06, 95% CI 0.33 to 1.80), creatinine (SMD=0.51, 95% CI 0.33 to 0.69), white bloodcells (SMD=0.44, 95 % CI 0.07 to 0.82), haemoglobin (SMD=-0.45, 95% CI -0.64 to-0.26).
CONCLUSIONS
More robust molecular studies are needed to explore the association between prolactin and PPCM in human subjects and to determine the extent to which iron deficiency (with or without anaemia) contributes to the risk of PPCM.
Topics: Anemia, Iron-Deficiency; Biomarkers; Cardiomyopathies; Female; Heart Disease Risk Factors; Humans; Iron; Iron Deficiencies; Peripartum Period; Pregnancy; Pregnancy Complications, Cardiovascular; Prognosis; Prolactin; Risk Assessment
PubMed: 33060142
DOI: 10.1136/openhrt-2020-001430 -
European Geriatric Medicine Apr 2020Since there is only limited evidence available for geriatric rehabilitation patients, this systematic review and meta-analysis aims to characterize the nutritional... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
Since there is only limited evidence available for geriatric rehabilitation patients, this systematic review and meta-analysis aims to characterize the nutritional status in this population and its relationship with functionality.
METHODS
Eight databases were searched for full-text articles reporting baseline nutritional intake and status of adults ≥ 60 years in rehabilitation settings. Pooled estimates were calculated for prevalence of malnutrition and risk of malnutrition based on the Mini Nutritional Assessment (MNA) and for mean body mass index (BMI). Associations between nutritional status (MNA, MNA short form and BMI) and functional status (Barthel Index and Functional Independence Measure) and prevalence of sarcopenia were reviewed.
RESULTS
62 out of 1717 references were eligible for inclusion. Pooled prevalence [95% confidence interval (CI)] of malnutrition and risk of malnutrition were 13 (5-20) % and 47 (40-54) %. Pooled estimate (95% CI) for BMI was 23.8 (23.2-24.5) kg/m. Existing data suggest a risk for low protein and energy intake and vitamin D deficiency. Functional status differed widely. Seven out of ten studies reported significant associations between reduced nutritional status and reduced functionality, whilst two out of seven studies reported significant associations between higher BMI and functionality. Prevalence of sarcopenia was high with 40-76% in this population.
CONCLUSIONS
Although geriatric rehabilitation populations and settings were heterogeneous, a relevant percentage of geriatric rehabilitation patients were affected by a reduced nutritional status. Nutritional status was associated with decreased functionality. This emphasizes the need for screening for malnutrition and targeted nutritional intervention.
Topics: Aged; Geriatric Assessment; Humans; Malnutrition; Nutrition Assessment; Nutritional Status; Sarcopenia
PubMed: 32297199
DOI: 10.1007/s41999-020-00294-2