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Laboratory Investigation; a Journal of... Jul 2023The Klotho protein, known as an antiaging protein, is expressed mainly in the kidney, and kidney disorders may contribute to the disrupted expression of renal Klotho.... (Review)
Review
The Klotho protein, known as an antiaging protein, is expressed mainly in the kidney, and kidney disorders may contribute to the disrupted expression of renal Klotho. The purpose of this systematic review was to determine if there are biological and nutraceutical therapies that increase the expression of Klotho and can help prevent complications associated with chronic kidney disease. A systematic literature review was carried out through the consultation of PubMed, Scopus, and Web of Science. Records between the years 2012 and 2022 in Spanish and English were selected. Cross-sectional or prevalence and analytical studies were included that evaluated the effects of Klotho therapy. A total of 22 studies were identified after the critical reading of these selected studies: 3 investigated the association between Klotho and growth factors, 2 evaluated the relationship between the concentration of Klotho and the type of fibrosis, 3 focused on the relationship between vascular calcifications and vitamin D, 2 assessed the relationship between Klotho and bicarbonate, 2 investigated the relationship between proteinuria and Klotho, 1 demonstrated the applicability of synthetic antibodies as a support for Klotho deficiency, 1 investigated Klotho hypermethylation as a renal biomarker, 2 investigated the relationship between proteinuria and Klotho, 4 linked Klotho as an early marker of chronic kidney disease, and 1 investigated Klotho levels in patients with autosomal dominant polycystic kidney disease. In conclusion, no study has addressed the comparison of these therapies in the context of their use with nutraceutical agents that raise the expression of Klotho.
Topics: Humans; Cross-Sectional Studies; Glucuronidase; Kidney; Proteinuria; Renal Insufficiency, Chronic; Klotho Proteins
PubMed: 37207706
DOI: 10.1016/j.labinv.2023.100178 -
Heliyon Jul 2023Axenfeld-Rieger Syndrome (ARS) is comprised of a group of autosomal dominant disorders that are each characterized by anterior segment abnormalities of the eye.... (Review)
Review
Axenfeld-Rieger Syndrome (ARS) is comprised of a group of autosomal dominant disorders that are each characterized by anterior segment abnormalities of the eye. Mutations in the transcription factors or are the most well-studied genetic manifestations of this syndrome. Due to the rarity this syndrome, ARS-associated neurological manifestations have not been well characterized. The purpose of this systematic review is to characterize and describe ARS neurologic manifestations that affect the cerebral vasculature and their early and late sequelae. PRISMA guidelines were followed; studies meeting inclusion criteria were analyzed for study design, evidence level, number of patients, patient age, whether the patients were related, genotype, ocular findings, and nervous system findings, specifically neurostructural and neurovascular manifestations. 63 studies met inclusion criteria, 60 (95%) were case studies or case series. The gene was most commonly found, followed by , then . The most commonly described structural neurological findings were white matter abnormalities in 26 (41.3%) of studies, followed by Dandy-Walker Complex 12 (19%), and agenesis of the corpus callosum 11 (17%). Neurovascular findings were examined in 6 (9%) of studies, identifying stroke, cerebral small vessel disease (CSVD), tortuosity/dolichoectasia of arteries, among others, with no mention of moyamoya. This is the first systematic review investigating the genetic, neurological, and neurovascular associations with ARS. Structural neurological manifestations were common, yet often benign, perhaps limiting the utility of MRI screening. Neurovascular abnormalities, specifically stroke and CSVD, were identified in this population. Stroke risk was present in the presence and absence of cardiac comorbidities. These findings suggest a relationship between ARS and neurovascular findings; however, larger scale studies are necessary inform therapeutic decisions.
PubMed: 37539177
DOI: 10.1016/j.heliyon.2023.e18225 -
Dentistry Journal Dec 2023The aim of this systematic review was to describe the clinical and genetic features of syndromes showing oligodontia as a sign. The review was performed according to the... (Review)
Review
The aim of this systematic review was to describe the clinical and genetic features of syndromes showing oligodontia as a sign. The review was performed according to the PRISMA 2020 checklist guidelines, and the search was conducted using PubMed, Scopus, Lilacs, Web of science, Livivo, and EMBASE and supplemented by a gray literature search on Google Scholar and ProQuest, applying key terms relevant to the research questions. The systematic review identified 47 types of syndromes in 83 studies, and the most common was hypohidrotic ectodermal dysplasia, which was reported in 24 patients in 22 studies. Other common syndromes that reported oligodontia included Axenfeld-Rieger syndrome, Witkop's syndrome, Ellis-van Creveld syndrome, blepharocheilodontic syndrome, and oculofaciocardiodental syndrome. The X-linked mode of inheritance was the most reported (n = 13 studies), followed by the autosomal dominant (n = 13 studies). The review describes the main syndromes that may have oligodontia as a clinical sign and reinforces the need for orodental-facial examining for adequate diagnosis and treatment of the affected patients. Molecular analysis in order to better understand the occurrence of oligodontia is imperative.
PubMed: 38132417
DOI: 10.3390/dj11120279 -
Cerebellum (London, England) Nov 2023Next-generation sequencing (NGS), comprising targeted panels (TP), exome sequencing (ES), and genome sequencing (GS) became robust clinical tools for diagnosing... (Review)
Review
Next-generation sequencing (NGS), comprising targeted panels (TP), exome sequencing (ES), and genome sequencing (GS) became robust clinical tools for diagnosing hereditary ataxia (HA). Determining their diagnostic yield (DY) is crucial for optimal clinical decision-making. We conducted a comprehensive systematic literature review on the DY of NGS tests for HA. We searched PubMed and Embase databases for relevant studies between 2016 and 2022 and manually examined reference lists of relevant reviews. Eligible studies described the DY of NGS tests in patients with ataxia as a significant feature. Data from 33 eligible studies showed a median DY of 43% (IQR = 9.5-100%). The median DY for TP and ES was 46% and 41.9%, respectively. Higher DY was associated with specific phenotype selection, such as episodic ataxia at 68.35% and early and late onset of ataxia at 46.4% and 54.4%. Parental consanguinity had a DY of 52.4% (p = 0.009), and the presumed autosomal recessive (AR) inheritance pattern showed 62.5%. There was a difference between the median DY of studies that performed targeted sequencing (tandem repeat expansion, TRE) screening and those that did not (p = 0.047). A weak inverse correlation was found between DY and the extent of previous genetic investigation (rho = - 0.323; p = 0.065). The most common genes were CACNA1A and SACS. DY was higher for presumed AR inheritance pattern, positive family history, and parental consanguinity. ES appears more advantageous due to the inclusion of rare genes that might be excluded in TP.
PubMed: 37950147
DOI: 10.1007/s12311-023-01629-y -
The Cochrane Database of Systematic... Sep 2021Cystic fibrosis is an autosomal recessive multisystem disorder with an approximate prevalence of 1 in 3500 live births. Allergic bronchopulmonary aspergillosis is a lung... (Review)
Review
BACKGROUND
Cystic fibrosis is an autosomal recessive multisystem disorder with an approximate prevalence of 1 in 3500 live births. Allergic bronchopulmonary aspergillosis is a lung disease caused by aspergillus-induced hypersensitivity with a prevalence of 2% to 15% in people with cystic fibrosis. The mainstay of treatment includes corticosteroids and itraconazole. The treatment with corticosteroids for prolonged periods of time, or repeatedly for exacerbations of allergic bronchopulmonary aspergillosis, may lead to many adverse effects. The monoclonal anti-IgE antibody, omalizumab, has improved asthma control in severely allergic asthmatics. The drug is given as a subcutaneous injection every two to four weeks. Since allergic bronchopulmonary aspergillosis is also a condition resulting from hypersensitivity to specific allergens, as in asthma, it may be a candidate for therapy using anti-IgE antibodies. Therefore, anti-IgE therapy, using agents like omalizumab, may be a potential therapy for allergic bronchopulmonary aspergillosis in people with cystic fibrosis. This is an updated version of the review.
OBJECTIVES
To evaluate the efficacy and adverse effects of anti-IgE therapy for allergic bronchopulmonary aspergillosis in people with cystic fibrosis.
SEARCH METHODS
We searched the Cochrane Cystic Fibrosis Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. We also searched the reference lists of relevant articles and reviews. Last search: 09 September 2021. We searched two ongoing trial registries (Clinicaltrials.gov and the WHO trials platform). Date of latest search: 16 August 2021.
SELECTION CRITERIA
Randomized and quasi-randomized controlled trials comparing anti-IgE therapy to placebo or other therapies for allergic bronchopulmonary aspergillosis in people with cystic fibrosis.
DATA COLLECTION AND ANALYSIS
Two review authors independently extracted data and assessed the risk of bias in the included study. They planned to perform data analysis using Review Manager.
MAIN RESULTS
Only one study enrolling 14 participants was eligible for inclusion in the review. The double-blind study compared a daily dose of 600 mg omalizumab or placebo along with twice daily itraconazole and oral corticosteroids, with a maximum daily dose of 400 mg. Treatment lasted six months but the study was terminated prematurely and complete data were not available. We contacted the study investigator and were told that the study was terminated due to the inability to recruit participants into the study despite all reasonable attempts. One or more serious side effects were encountered in six out of nine (66.67%) and one out of five (20%) participants in omalizumab group and placebo group respectively.
AUTHORS' CONCLUSIONS
There is lack of evidence for the efficacy and safety of anti-IgE (omalizumab) therapy in people with cystic fibrosis and allergic bronchopulmonary aspergillosis. There is a need for large prospective randomized controlled studies of anti-IgE therapy in people with cystic fibrosis and allergic bronchopulmonary aspergillosis with both clinical and laboratory outcome measures such as steroid requirement, allergic bronchopulmonary aspergillosis exacerbations and lung function.
Topics: Antibodies, Anti-Idiotypic; Antifungal Agents; Aspergillosis, Allergic Bronchopulmonary; Cystic Fibrosis; Humans; Prospective Studies; Randomized Controlled Trials as Topic
PubMed: 34550603
DOI: 10.1002/14651858.CD010288.pub5 -
The Cochrane Database of Systematic... Dec 2023Cystic fibrosis (CF) is a life-shortening, autosomal recessive disease that leads to abnormal electrolyte concentration in exocrine secretions. Secretion stasis in... (Review)
Review
BACKGROUND
Cystic fibrosis (CF) is a life-shortening, autosomal recessive disease that leads to abnormal electrolyte concentration in exocrine secretions. Secretion stasis in paranasal sinuses determines chronic rhinosinusitis (CRS) and nasal polyposis. Endoscopic sinus surgery is used to open the sinuses and allow medical treatment to work properly.
OBJECTIVES
To determine the effects of sinus surgery alone or in combination with medical treatment (non-surgical) compared to medical treatment (non-surgical) alone on both nasal and pulmonary function in people with CF diagnosed with CRS with nasal polyposis. Further, to evaluate the impact of sinus surgery (with or without medical treatment) on hospitalization rates, use of antibiotics and pulmonary exacerbation rates.
SEARCH METHODS
We searched the Cochrane Cystic Fibrosis Trials Register, compiled from electronic database searches and hand searching of journals and conference abstract books. Date of last search: 4 July 2022. We also searched other databases (Pubmed, Embase, World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP), Virtual Health Library and ClinicalTrials.gov). Date of last search: 18 September 2022.
SELECTION CRITERIA
Randomized controlled trials (RCTs) comparing groups who underwent endoscopic sinus surgery and groups with medical treatment alone.
DATA COLLECTION AND ANALYSIS
The review authors independently selected studies, extracted data, assessed the risk of bias and evaluated the certainty of the evidence using GRADE. They contacted the authors of the included study for additional information.
MAIN RESULTS
We identified 66 publications relating to 50 studies from electronic searches. Only one study fulfilled the inclusion criteria, and only limited information was available. In this study, 28 participants aged 19 to 28 years were randomized in equal numbers to either nasal irrigation alone or nasal irrigation with surgery (endoscopic polypectomy with extended sinusotomy). The certainty of the evidence was very low according to the GRADE approach. We are uncertain whether, compared to medical treatment alone, the addition of surgical intervention improves nasal symptoms, or reduces bacterial colonization, the use of antibiotics and pulmonary exacerbations. We are also uncertain whether the addition of surgery to medical treatment leads to changes in pulmonary function. There was one episode of bleeding during surgery that was corrected during the procedure with no further consequences. The study did not report on survival.
AUTHORS' CONCLUSIONS
Very low-certainty evidence means we are not certain if endoscopic sinus surgery to treat chronic rhinosinusitis with nasal polyposis in cystic fibrosis is effective. Future research should be multicentric to increase the number of participants and increase statistical power. Adequate randomization and allocation concealment are important to guarantee that the groups are similar. Blinding, however, may not be possible in an ethical trial; even without blinding, results can achieve high-level evidence if the outcomes used are objective parameters. Future research should follow participants of all ages for at least 12 months to evaluate the evolution of nasal polyposis, its recurrence and how symptoms may return. We also consider mortality an important outcome to be assessed. Future clinical research should consider the effects of cystic fibrosis transmembrane conductance regulators, a new group of drugs that may affect the development of nasal polyps.
Topics: Humans; Cystic Fibrosis; Nasal Polyps; Anti-Bacterial Agents; Sinusitis; Chronic Disease; Randomized Controlled Trials as Topic
PubMed: 38063253
DOI: 10.1002/14651858.CD014084.pub2 -
The Cochrane Database of Systematic... Oct 2022Premature ovarian insufficiency (POI) is a clinical syndrome resulting from loss of ovarian function before the age of 40. It is a state of hypergonadotropic... (Review)
Review
BACKGROUND
Premature ovarian insufficiency (POI) is a clinical syndrome resulting from loss of ovarian function before the age of 40. It is a state of hypergonadotropic hypogonadism, characterised by amenorrhoea or oligomenorrhoea, with low ovarian sex hormones (oestrogen deficiency) and elevated pituitary gonadotrophins. POI with primary amenorrhoea may occur as a result of chromosomal and genetic abnormalities, such as Turner syndrome, Fragile X, or autosomal gene defects; secondary amenorrhoea may be iatrogenic after the surgical removal of the ovaries, radiotherapy, or chemotherapy. Other causes include autoimmune diseases, viral infections, and environmental factors; in most cases, POI is idiopathic. Appropriate replacement of sex hormones in women with POI may facilitate the achievement of near normal uterine development. However, the optimal effective hormone therapy (HT) regimen to maximise the reproductive potential for women with POI remains unclear.
OBJECTIVES
To investigate the effectiveness and safety of different hormonal regimens on uterine and endometrial development in women with POI.
SEARCH METHODS
We searched the Cochrane Gynaecology and Fertility (CGF) Group trials register, CENTRAL, MEDLINE, Embase, PsycINFO, CINAHL, and two trials registers in September 2021. We also checked references of included studies, and contacted study authors to identify additional studies.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) investigating the effect of various hormonal preparations on the uterine development of women diagnosed with POI.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures recommended by Cochrane. The primary review outcome was uterine volume; secondary outcomes were endometrial thickness, endometrial histology, uterine perfusion, reproductive outcomes, and any reported adverse events.
MAIN RESULTS
We included three studies (52 participants analysed in total) investigating the role of various hormonal preparations in three different contexts, which deemed meta-analysis unfeasible. We found very low-certainty evidence; the main limitation was very serious imprecision due to small sample size. Conjugated oral oestrogens versus transdermal 17ß-oestradiol We are uncertain of the effect of conjugated oral oestrogens compared to transdermal 17ß-oestradiol (mean difference (MD) -18.2 (mL), 95% confidence interval (CI) -23.18 to -13.22; 1 RCT, N = 12; very low-certainty evidence) on uterine volume, measured after 12 months of treatment. The study reported no other relevant outcomes (including adverse events). Low versus high 17ß-oestradiol dose We are uncertain of the effect of a lower dose of 17ß-oestradiol compared to a higher dose of 17ß-oestradiol on uterine volume after three or five years of treatment, or adverse events (1 RCT, N = 20; very low-certainty evidence). The study reported no other relevant outcomes. Oral versus vaginal administration of oestradiol and dydrogesterone We are uncertain of the effect of an oral or vaginal administration route on uterine volume and endometrial thickness after 14 or 21 days of administration (1 RCT, N = 20; very low-certainty evidence). The study reported no other relevant outcomes (including adverse events).
AUTHORS' CONCLUSIONS
No clear conclusions can be drawn in this systematic review, due to the very low-certainty of the evidence. There is a need for pragmatic, well designed, randomised controlled trials, with adequate power to detect differences between various HT regimens on uterine growth, endometrial development, and pregnancy outcomes following the transfer of donated gametes or embryos in women diagnosed with POI.
Topics: Amenorrhea; Dydrogesterone; Endometrium; Estradiol; Estrogens; Female; Humans; Menopause, Premature; Pregnancy
PubMed: 36200708
DOI: 10.1002/14651858.CD008209.pub2 -
The Laryngoscope Jul 2022To describe cochlear implantation (CI) outcomes, with speech perception, auditory, language, and parent-reported auditory and speech behaviors, in children with an... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE(S)
To describe cochlear implantation (CI) outcomes, with speech perception, auditory, language, and parent-reported auditory and speech behaviors, in children with an enlarged vestibular aqueduct (EVA) and incomplete partition type 2 (IP-II) and compare to control children without inner ear malformations (IEMs) and to determine cerebrospinal fluid gusher rates and effect on outcomes.
STUDY DESIGN
Systematic review and meta-analysis.
METHODS
MEDLINE, Embase, Cochrane, and CINAHL databases were searched from inception to February 2020. Studies reporting relevant outcomes in children with EVA or EVA + IP-II and controls without IEMs undergoing CI were included. Mean differences in speech perception, auditory, and language scores between cases and controls were meta-analyzed. Gusher rates were determined by proportion meta-analyses.
RESULTS
Of 214 identified articles, 42 met inclusion criteria, evaluating 775 cases and 2,191 controls. Of -cases, 578 (74.6%) had EVA and 197 (25.4%) had EVA + IP-II. Cases showed a significant improvement in speech perception, auditory and language performance, comparable to controls. Parent-reported auditory and speech production behaviors outcomes were positive among cases and comparable to controls. Pooled gusher proportions in EVA and EVA + IP-II cases were 27.7% (95% CI: 17.6-39.1) and 48.6% (95% CI: 28.6-69.0), respectively, with a proportion difference of 20.9% (95% CI: 11.0-30.1). Gusher occurrence did not impact speech perception or language outcomes.
CONCLUSION
Outcomes in children with EVA or EVA + IP-II undergoing CI are favorable and largely comparable to outcomes in children with hearing loss undergoing CI without IEMs. Intraoperative gusher is more prevalent among children with EVA + IP-II as compared to iEVA. Gusher does not influence speech perception and language development outcomes.
LEVEL OF EVIDENCE
NA Laryngoscope, 132:1459-1472, 2022.
Topics: Child; Cochlear Implantation; Cochlear Implants; Hearing Loss, Sensorineural; Humans; Retrospective Studies; Vestibular Aqueduct
PubMed: 34233033
DOI: 10.1002/lary.29742 -
World Neurosurgery Feb 2022Hemangioblastomas (HBs) are well-vascularized, benign central nervous system tumors and the third most common primary spinal cord tumor after astrocytoma/ependymoma,... (Review)
Review
BACKGROUND
Hemangioblastomas (HBs) are well-vascularized, benign central nervous system tumors and the third most common primary spinal cord tumor after astrocytoma/ependymoma, occurring sporadically or as a part of autosomal dominant von Hippel-Lindau disease, in which tumors are often multiple and prone to relapse. Spinal HBs are commonly located in the cervical cord and associated with a syrinx formation. Owing to location and growth trends, they may cause significant neurological deficit, impairing quality of life. We conducted a systematic review to understand better clinical insights into spinal HB in adults and compare spinal HB versus posterior cranial fossa HB.
METHODS
Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines for conducting systematic reviews, we reviewed the English-language literature on adult spinal HB in the MEDLINE/PubMed database over the last 40 years.
RESULTS
We reviewed 237 articles on adult spinal HB and analyzed national and continental distribution, clinical symptoms, tumor location and presence of syringomyelia, treatment strategies and postoperative complications, histology and immunochemistry, and treatment outcomes. We compared individual characteristics in sporadic and von Hippel-Lindau disease spinal HBs. Finally, we compared features of posterior cranial fossa and spinal HBs.
CONCLUSIONS
Spinal cord HBs most commonly have a dorsal intramedullary location. Total surgical tumor resection is the first treatment option; preoperative embolization may be performed to reduce intraoperative bleeding and surgical time. HBs located in the spine have decreased mortality and rate of infection, but increased rates of cardiopulmonary complications compared with HBs in the posterior cranial fossa.
Topics: Adult; Hemangioblastoma; Humans; Neoplasm Recurrence, Local; Quality of Life; Spinal Cord Neoplasms; Syringomyelia; von Hippel-Lindau Disease
PubMed: 34687932
DOI: 10.1016/j.wneu.2021.10.105 -
Developmental Medicine and Child... Sep 2023To explore altered structural and functional connectivity and network organization in cerebral palsy (CP), by clinical CP subtype (unilateral spastic, bilateral spastic,... (Review)
Review
AIM
To explore altered structural and functional connectivity and network organization in cerebral palsy (CP), by clinical CP subtype (unilateral spastic, bilateral spastic, dyskinetic, and ataxic CP).
METHOD
PubMed and Embase databases were systematically searched. Extracted data included clinical characteristics, analyses, outcome measures, and results.
RESULTS
Sixty-five studies were included, of which 50 investigated structural connectivity, and 20 investigated functional connectivity using functional magnetic resonance imaging (14 studies) or electroencephalography (six studies). Five of the 50 studies of structural connectivity and one of 14 of functional connectivity investigated whole-brain network organization. Most studies included patients with unilateral spastic CP; none included ataxic CP.
INTERPRETATION
Differences in structural and functional connectivity were observed between investigated clinical CP subtypes and typically developing individuals on a wide variety of measures, including efferent, afferent, interhemispheric, and intrahemispheric connections. Directions for future research include extending knowledge in underrepresented CP subtypes and methodologies, evaluating the prognostic potential of specific connectivity and network measures in neonates, and understanding therapeutic effects on brain connectivity.
Topics: Infant, Newborn; Humans; Cerebral Palsy; Muscle Spasticity; Brain; Magnetic Resonance Imaging
PubMed: 36750309
DOI: 10.1111/dmcn.15516