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Biochemistry Research International 2021This study aimed to describe the clinical symptoms, laboratory findings, treatment, and outcomes of coronavirus disease 2019-related multisystem inflammatory syndrome in... (Review)
Review
BACKGROUND
This study aimed to describe the clinical symptoms, laboratory findings, treatment, and outcomes of coronavirus disease 2019-related multisystem inflammatory syndrome in children to provide a reference for clinical practice.
METHODS
We employed a literature search of databases such as PubMed, Web of Science, EMBASE, and Johns Hopkins University for articles on COVID-19-related multisystem inflammatory syndrome in children published between April 1, 2020, and January 15, 2021. High-quality articles were selected for analysis on the basis of their quality standard scores. Using R3.6.3 software, meta-analyses of random- or fixed-effects models were used to determine the prevalence of comorbidities. Subgroup analysis was also performed to determine heterogeneity.
RESULTS
A total of 57 articles (2,290 pediatric patients) were included in the study. . :ncidences of fever, gastrointestinal symptoms, respiratory symptoms, and musculoskeletal symptoms (myalgias or arthralgias) were 99.91% (95% CI: 99.67-100%), 82.72% (95% CI: 78.19-86.81%), 53.02% (45.28-60.68%), and 14.16% (95% CI: 8.4-21.12%), respectively. The incidences of rash, conjunctival injection, lymphadenopathy, dry cracked lips, neurologic symptoms (headache, altered mental status, or confusion), swollen hands and feet, typical Kawasaki disease, and atypical Kawasaki disease were 59.34% (95% CI: 54.73-63.87%), 55.23% (95% CI: 50.22-60.19%), 27.07% (95% CI: 19.87-34.93%), 46.37% (95% CI: 39.97-52.83%), 28.87% (95% CI: 22.76-35.40%), 28.75% (95% CI: 21.46-36.64%), 17.32% (95% CI: 15.44-19.29%), and 36.19% (95% CI: 21.90-51.86%), respectively. The incidences of coronary artery dilation, aneurysm, pericardial effusion, myocarditis, myocardial dysfunction, high troponin, and -terminal pro-B-type natriuretic peptide were 17.83%, 6.85%, 20.97%, 35.97%, 56.32%, 76.34%, and 86.65%, respectively. The incidences of reduced lymphocytes, thrombocytopenia, hypoalbuminemia, elevated C-reactive protein, ferritin, LDH, interleukin-6, PCT, and FIB were 61.51%, 26.42%, 77.92%, 98.5%, 86.79%, 80.59%, 89.30%, 85.10%, and 87.01%, respectively. . The incidences of PICU hospitalization or with shock were 72.79% and 55.68%, respectively. The mortality rate was 1.00%. . PICU hospitalization and shock rates of multisystem inflammatory syndrome in children associated with COVID-19 were high, and its cumulative multiorgans and inflammatory indicators are increased, but if treated in time, the mortality rate was low.
PubMed: 34336288
DOI: 10.1155/2021/5596727 -
International Journal of Molecular... Sep 2023Intracranial aneurysms (IAs) are abnormal dilations of the cerebral vessels, which pose a persistent threat of cerebral hemorrhage. Inflammation is known to contribute... (Review)
Review
Intracranial aneurysms (IAs) are abnormal dilations of the cerebral vessels, which pose a persistent threat of cerebral hemorrhage. Inflammation is known to contribute to IA development. The nuclear factor "kappa-light-chain-enhancer" of activated B-cells (NF-κB) is the major driver of inflammation. It increases the expression of inflammatory markers and matrix metalloproteinases (MMPs), which contribute heavily to the pathogenesis of IAs. NF-κB activation has been linked to IA rupture and resulting subarachnoid hemorrhage. Moreover, NF-κB activation can result in endothelial dysfunction, smooth muscle cell phenotypic switching, and infiltration of inflammatory cells in the arterial wall, which subsequently leads to the initiation and progression of IAs and consequently results in rupture. After a systematic search, abstract screening, and full-text screening, 30 research articles were included in the review. In this systematic review, we summarized the scientific literature reporting findings on NF-κB's role in the pathogenesis of IAs. In conclusion, the activation of the NF-κB pathway was associated with IA formation, progression, and rupture.
Topics: Humans; NF-kappa B; Intracranial Aneurysm; Signal Transduction; Arteries; Inflammation
PubMed: 37762520
DOI: 10.3390/ijms241814218 -
BMJ Open Feb 2024The use of minimally invasive endoluminal treatment for urethral strictures has been a subject for debate for several decades. The aim of this study was to review and... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
The use of minimally invasive endoluminal treatment for urethral strictures has been a subject for debate for several decades. The aim of this study was to review and discuss the safety, efficacy and factors influencing the clinical application of balloon dilation for the treatment of male urethral strictures.
DESIGN
Systematic review and meta-analysis.
DATA SOURCES
Embase, Medline, Web of Science, Cochrane Library and Scopus were searched for publications published before 17 July 2022.
STUDY SELECTION
Two independent researchers screened and assessed the results, and all clinical studies on balloon dilation for the treatment of urethral strictures in men were included.
DATA EXTRACTION AND SYNTHESIS
The success rate, rate of adverse events, International Prostate Symptom Scores, maximum uroflow (Qmax) and postvoid residual urine volume were the main outcomes. Stata V.14.0 was used for statistical analysis.
RESULTS
Fifteen studies with 715 patients were ultimately included in this systematic review. The pooled results of eight studies showed that the reported success rate of simple balloon dilation for male urethral strictures was 67.07% (95% confidence interval [CI]: 55.92% to 77.36%). The maximum urinary flow rate at 3 months (risk ratio [RR]= 2.6510, 95% CI: 1.0681 to 4.2338, p<0.01) and the maximum urinary flow rate at 1 year (RR= 1.6637, 95% CI: 1.1837 to 2.1437, p<0.05) were significantly different after dilation. There is insufficient evidence to suggest that balloon dilation is superior to optical internal urethrotomy or direct visual internal urethrotomy (DVIU) (RR= 1.4754, 95% CI: 0.7306 to 2.9793, p=0.278).
CONCLUSION
Balloon dilation may be an intermediate step before urethroplasty and is a promising alternative therapy to simple dilation and DVIU. The balloon is a promising drug delivery tool, and paclitaxel drug-coated balloon dilation is effective in reducing retreatment rates in patients with recurrent anterior urethral strictures. The aetiology, location, length, previous treatment of urethral stricture may be associated with the efficacy of balloon dilation.
PROSPERO REGISTRATION NUMBER
CRD42022334403.
Topics: Humans; Male; Urethral Stricture; Dilatation; Urethra; Catheterization; Retreatment
PubMed: 38320837
DOI: 10.1136/bmjopen-2023-071923 -
American Journal of Cardiovascular... Jan 2024Pulmonary arterial hypertension (PAH) is a progressive, cureless disease, characterized by increased pulmonary vascular resistance and remodeling, with subsequent... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Pulmonary arterial hypertension (PAH) is a progressive, cureless disease, characterized by increased pulmonary vascular resistance and remodeling, with subsequent ventricular dilatation and failure. New therapeutic targets are being investigated for their potential roles in improving PAH patients' symptoms and reversing pulmonary vascular pathology.
METHOD
We aimed to address the available knowledge from the published randomized controlled trials (RCTs) regarding the role of Rho-kinase (ROCK) inhibitors, bone morphogenetic protein 2 (BMP2) inhibitors, estrogen inhibitors, and AMP-activated protein kinase (AMPK) activators on the PAH evaluation parameters. This systematic review (SR) was registered in the International Prospective Register of Systematic Reviews (PROSPERO) database (CDR42022340658) and followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.
RESULTS
Overall, 5092 records were screened from different database and registries; 8 RCTs that met our inclusion criteria were included. The marked difference in the study designs and the variability of the selected outcome measurement tools among the studies made performing a meta-analysis impossible. However, the main findings of this SR relate to the powerful potential of the AMPK activator and the imminent antidiabetic drug metformin, and the BMP2 inhibitor sotatercept as promising PAH-modifying therapies. There is a need for long-term studies to evaluate the effect of the ROCK inhibitor fasudil and the estrogen aromatase inhibitor anastrozole in PAH patients. The role of tacrolimus in PAH is questionable. The discrepancy in the hemodynamic and clinical parameters necessitates defining cut values to predict improvement. The differences in the PAH etiologies render the judgment of the therapeutic potential of the tested drugs challenging.
CONCLUSION
Metformin and sotatercept appear as promising therapeutic drugs for PAH.
CLINICAL TRIALS REGISTRATION
This work was registered in PROSPERO (CDR42022340658).
Topics: Humans; Pulmonary Arterial Hypertension; Hypertension, Pulmonary; AMP-Activated Protein Kinases; Familial Primary Pulmonary Hypertension; Estrogens; Metformin
PubMed: 37945977
DOI: 10.1007/s40256-023-00613-5 -
Arab Journal of Urology Mar 2021: To systematically review the use of drug-eluting stents (DES) and drug-coated balloons (DCB) in urology. (Review)
Review
OBJECTIVE
: To systematically review the use of drug-eluting stents (DES) and drug-coated balloons (DCB) in urology.
MATERIALS AND METHODS
The systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. PubMed, Scopus, Web of science and Cochrane Library online databases were searched in February 2019. Experimental and clinical studies, which included the placement of a DES or dilatation with DCB for investigating their potential use in the urinary tract for the management of ureteric or urethral pathologies, were included. The primary endpoint was to evaluate the current use of DES and DCB in urology.
RESULTS
A total of 29 articles were included in the systematic review. A total of 10 studies tested DES or DCB containing anti-proliferative agents (paclitaxel, zotarolimus, sirolimus, halofugione). Antibiotic agent-containing DES were tested in nine studies (triclosan, quinolones, teicoplanin, nitrofurantoin, silver sulfadiazine). A total of eight studies investigated the release of anti-inflammatory agents by DES (ketorolac, indomethacin, EW-7197). Another group studied heparin-eluting stents.
CONCLUSION
Despite the inconclusive outcomes of the three randomised controlled trials, drug-coated/eluting devices constitute a promising field in urology for the prevention of complications associated with conventional stents including pain and encrustation. Pre-clinical and studies have shown their ability to mitigate inflammation, inhibit re-stenosis and improve pain as indicated by declined use of anti-inflammatory drugs.: DES: drug-eluting stents; DCB: drug-coated balloons; DCS: drug-coated stents; HF: halofungione; MCP-1: monocyte chemoattractant protein 1; PRISMA, Preferred Reporting Items for Systematic Reviews and Meta-Analyses; PTCA: percutaneous transluminal coronary angioplasty; RANTES: regulated on activation, normal T-cell expressed and secreted; RCT: randomised controlled trial; USSQ, Ureteric Stent Symptoms Questionaire.
PubMed: 34104496
DOI: 10.1080/2090598X.2021.1885948 -
PLoS Medicine Aug 2023The optimal approach to prevent preterm birth (PTB) in twins has not been fully established yet. Recent evidence suggests that placement of cervical cerclage in twin... (Meta-Analysis)
Meta-Analysis
Cervical cerclage for prevention of preterm birth and adverse perinatal outcome in twin pregnancies with short cervical length or cervical dilatation: A systematic review and meta-analysis.
BACKGROUND
The optimal approach to prevent preterm birth (PTB) in twins has not been fully established yet. Recent evidence suggests that placement of cervical cerclage in twin pregnancies with short cervical length at ultrasound or cervical dilatation at physical examination might be associated with a reduced risk of PTB. However, such evidence is based mainly on small studies thus questioning the robustness of these findings. The aim of this systematic review was to determine the role of cervical cerclage in preventing PTB and adverse maternal or perinatal outcomes in twin pregnancies.
METHODS AND FINDINGS
Key databases searched and date of last search: MEDLINE, Embase, and CINAHL were searched electronically on 20 April 2023. Eligibility criteria: Inclusion criteria were observational studies assessing the risk of PTB among twin pregnancies undergoing cerclage versus no cerclage and randomized trials in which twin pregnancies were allocated to cerclage for the prevention of PTB or to a control group (e.g., placebo or treatment as usual). The primary outcome was PTB <34 weeks of gestation. The secondary outcomes were PTB <37, 32, 28, 24 weeks of gestation, gestational age at birth, the interval between diagnosis and birth, preterm prelabor rupture of the membranes (pPROM), chorioamnionitis, perinatal loss, and perinatal morbidity. Subgroup analyses according to the indication for cerclage (short cervical length or cervical dilatation) were also performed. Risk of bias assessment: The risk of bias of the included randomized controlled trials (RCTs) was assessed using the Revised Cochrane risk-of-bias tool for randomized trials, while that of the observational studies using the Newcastle-Ottawa scale (NOS). Statistical analysis: Summary risk ratios (RRs) of the likelihood of detecting each categorical outcome in exposed versus unexposed women, and (b) summary mean differences (MDs) between exposed and unexposed women (for each continuous outcome), with their 95% confidence intervals (CIs) were computed using head-to-head meta-analyses. Synthesis of the results: Eighteen studies (1,465 twin pregnancies) were included. Placement of cervical cerclage in women with a twin pregnancy with a short cervix at ultrasound or cervical dilatation at physical examination was associated with a reduced risk of PTB <34 weeks of gestation (RR: 0.73, 95% CI [0.59, 0.91], p = 0.005 corresponding to a 16% difference in the absolute risk, AR), <32 (RR: 0.69, 95% CI [0.57, 0.84], p < 0.001; AR: 16.92%), <28 (RR: 0.54, 95% [CI 0.43, 0.67], 0.001; AR: 18.29%), and <24 (RR: 0.48, 95% CI [0.23, 0.97], p = 0.04; AR: 15.57%) weeks of gestation and a prolonged gestational age at birth (MD: 2.32 weeks, 95% [CI 0.99, 3.66], p < 0.001). Cerclage in twin pregnancy with short cervical length or cervical dilatation was also associated with a reduced risk of perinatal loss (RR: 0.38, 95% CI [0.25, 0.60], p < 0.001; AR: 19.62%) and composite adverse outcome (RR: 0.69, 95% CI [0.53, 0.90], p = 0.007; AR: 11.75%). Cervical cerclage was associated with a reduced risk of PTB <34 weeks both in women with cervical length <15 mm (RR: 0.74, 95% CI [0.58, 0.95], p = 0.02; AR: 29.17%) and in those with cervical dilatation (RR: 0.68, 95% CI [0.57, 0.80], p < 0.001; AR: 35.02%). The association between cerclage and prevention of PTB and adverse perinatal outcomes was exclusively due to the inclusion of observational studies. The quality of retrieved evidence at GRADE assessment was low.
CONCLUSIONS
Emergency cerclage for cervical dilation or short cervical length <15 mm may be potentially associated with a reduction in PTB and improved perinatal outcomes. However, these findings are mainly based upon observational studies and require confirmation in large and adequately powered RCTs.
Topics: Female; Humans; Infant, Newborn; Pregnancy; Cerclage, Cervical; Cervix Uteri; Labor Stage, First; Pregnancy, Twin; Premature Birth
PubMed: 37535682
DOI: 10.1371/journal.pmed.1004266 -
World Journal of Radiology Feb 2023Paraduodenal pancreatitis (PP) represents a diagnostic challenge, especially in non-referral centers, given its potential imaging overlap with pancreatic cancer. There...
BACKGROUND
Paraduodenal pancreatitis (PP) represents a diagnostic challenge, especially in non-referral centers, given its potential imaging overlap with pancreatic cancer. There are two main histological variants of PP, the cystic and the solid, with slightly different imaging appearances. Moreover, imaging findings in PP may change over time because of disease progression and/or as an effect of its risk factors exposition, namely alcohol intake and smoking.
AIM
To describe multimodality imaging findings in patients affected by PP to help clinicians in the differential diagnosis with pancreatic cancer.
METHODS
The systematic review was conducted according to the Preferred Reporting Items for Systematic reviews and Meta-analyses 2009 guidelines. A Literature search was performed on PubMed, Embase and Cochrane Library using (groove pancreatitis [Title/Abstract]) OR (PP [Title/Abstract]) as key words. A total of 593 articles were considered for inclusion. After eliminating duplicates, and title and abstract screening, 53 full-text articles were assessed for eligibility. Eligibility criteria were: Original studies including 8 or more patients, fully written in English, describing imaging findings in PP, with pathological confirmation or clinical-radiological follow-up as the gold standard. Finally, 14 studies were included in our systematic review.
RESULTS
Computed tomography (CT) findings were described in 292 patients, magnetic resonance imaging (MRI) findings in 231 and endoscopic ultrasound (EUS) findings in 115. Duodenal wall thickening was observed in 88.8% of the cases: Detection rate was 96.5% at EUS, 91.0% at MRI and 84.1% at CT. Second duodenal portion increased enhancement was recognizable in 76.3% of the cases: Detection rate was 84.4% at MRI and 72.1% at CT. Cysts within the duodenal wall were detected in 82.6% of the cases: Detection rate was 94.4% at EUS, 81.9% at MRI and 75.7% at CT. A solid mass in the groove region was described in 40.9% of the cases; in 78.3% of the cases, it showed patchy enhancement in the portal venous phase, and in 100% appeared iso/hyperintense during delayed phase imaging. Only 3.6% of the lesions showed restricted diffusion. The prevalence of radiological signs of chronic obstructive pancreatitis, namely main pancreatic duct dilatation, pancreatic calcifications, and pancreatic cysts, was extremely variable in the different articles.
CONCLUSION
PP has peculiar imaging findings. MRI is the best radiological imaging modality for diagnosing PP, but EUS is more accurate than MRI in depicting duodenal wall alterations.
PubMed: 36874260
DOI: 10.4329/wjr.v15.i2.42 -
The Cochrane Database of Systematic... Aug 2020Traumatic eye complaints account for 3% of all hospital emergency department visits. The most common traumatic injury to the eye is blunt trauma, which accounts for 30%... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Traumatic eye complaints account for 3% of all hospital emergency department visits. The most common traumatic injury to the eye is blunt trauma, which accounts for 30% of these visits. Blunt trauma frequently leads to traumatic iridocyclitis, thus causing anterior uveitis. Iridocyclitis frequently causes tearing, photophobia, eye pain, and vision loss. These symptoms are a result of the inflammatory processes and ciliary spasms to iris muscles and sphincter. The inflammatory process is usually managed with topical corticosteroids, while the ciliary spasm is blunted by dilating the pupils with topical mydriatic agents, an adjuvant therapy. However, the effectiveness of mydriatic agents has not been quantified in terms of reduction of ocular pain and visual acuity loss.
OBJECTIVES
To evaluate the effectiveness and safety of topical mydriatics as adjunctive therapy to topical corticosteroids for traumatic iridocyclitis.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) which contains the Cochrane Eyes and Vision Trials Register (2019, issue 6); Ovid MEDLINE; Embase.com; Cumulative Index to Nursing and Allied Health Literature (CINAHL) Plus; PubMed; ClinicalTrials.gov and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP). We did not use any date or language restrictions in the electronic search for trials. We last searched the electronic databases on 12 June 2019.
SELECTION CRITERIA
We planned to include randomized controlled trials (RCTs) that compared topical mydriatic agents in conjunction with topical corticosteroid therapy versus topical corticosteroids alone, in participants with traumatic iridocyclitis.
DATA COLLECTION AND ANALYSIS
Two review authors (JH, MK) independently screened titles and abstracts, then full-text reports, against eligibility criteria. We planned to have two authors independently extract data from included studies. We resolved differences in opinion by discussion.
MAIN RESULTS
There were no eligible RCTs that compared the interventions of interest in people with traumatic iridocyclitis.
AUTHORS' CONCLUSIONS
We did not find any evidence from RCTs about the efficacy of topical mydriatic agents as an adjunctive therapy with topical corticosteroids for treating traumatic iridocyclitis. In the absence of these types of studies, we cannot draw any firm conclusions. Controlled trials that compare the combined use of topical mydriatic agents and corticosteroid drops against standard corticosteroid drops alone, in people with traumatic iridocyclitis are required. These may provide evidence about the efficacy and risk of topical mydriatic drops as adjuvant therapy for traumatic iridocyclitis.
PubMed: 35659470
DOI: 10.1002/14651858.CD013260.pub2 -
Journal of Cardiothoracic Surgery Jul 2023Valve-sparing aortic root replacement (VSARR) is a safe and effective surgical procedure to treat aortic root aneurysm. This meta-analysis aimed to investigate how this... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Valve-sparing aortic root replacement (VSARR) is a safe and effective surgical procedure to treat aortic root aneurysm. This meta-analysis aimed to investigate how this procedure might differ in patients with bicuspid aortic valve (BAV) and tricuspid aortic valve (TAV).
DESIGN
Meta-analysis with meta-regression and systematic review.
SETTING
Systematic search in the following databases: PubMed, Cochrane Central Register of Controlled Trials, and Embase.
INTERVENTIONS
All observational studies of VSARR in patients with BAV or TAV were included in our study. Studies were included without any restrictions on language or publication date. A trial sequential analysis and a post-hoc meta-regression was performed on the main outcomes.
RESULT
Eleven articles met the inclusion criteria. A total of 1138 patients in BAV group, and 2125 patients in TAV group. No significant differences in gender and age were observed between BAV and TAV patients. BAV and TAV patients showed no differences in in-hospital mortality rate [0.00% vs. 1.93%; RR (95% CI) 0.33 (0.09, 1.26), I = 0%, P = 0.11] and the rate of in-hospital reoperation [5.64% vs. 5.99%; RR (95% CI) 1.01(0.59, 1.73), I = 33%, P = 0.98]. The overall long-term mortality rate of BAV patients was better than that of TAV patients [1.63% vs. 8.15%; RR (95% CI) 0.34 (0.13, 0.86), I = 0%, P = 0.02]. During the follow-up observation period, patients in TAV group showed small but no statistic advantage in 3-year, 5-year, and over 10-year incidences of reintervention. Regarding the secondary endpoints, the two groups showed similar aortic cross-clamping time and total cardiopulmonary bypass time.
CONCLUSION
The VSARR techniques yielded similar clinical outcomes in both BAV and TAV patients. Although patients with BAV might have a higher incidence of reinterventions after initial VSARR, it is still a safe and effective approach to treat aortic root dilation with or without aortic valve insufficiency. TAV patients showed small but no statistic advantage in long-term (over 10 years) reintervention rate, which means, patients with BAV may face a higher risk of reintervention in the clinic.
Topics: Humans; Aortic Valve; Bicuspid Aortic Valve Disease; Heart Valve Diseases; Aorta; Tricuspid Valve; Transcatheter Aortic Valve Replacement; Aortic Valve Stenosis; Retrospective Studies; Treatment Outcome; Observational Studies as Topic
PubMed: 37400892
DOI: 10.1186/s13019-023-02329-8 -
Journal of Clinical Medicine Nov 2021Although gastroschisis is often diagnosed by prenatal ultrasound, there is still a gap in the literature about which prenatal ultrasound markers can predict complex... (Review)
Review
Although gastroschisis is often diagnosed by prenatal ultrasound, there is still a gap in the literature about which prenatal ultrasound markers can predict complex gastroschisis. This systematic review and meta-analysis aimed to investigate the ultrasound markers that characterize complex gastroschisis. A systematic review of the literature was conducted according to the guidelines of PRISMA. The protocol was registered (PROSPERO ID CRD42020211685). Meta-analysis was displayed graphically on Forest plots, which estimate prevalence rates and risk ratios, with 95% confidence intervals, using STATA version 15.0. The combined prevalence of intestinal complications in fetuses with complex gastroschisis was 27.0%, with a higher prevalence of atresia (about 48%), followed by necrosis (about 25%). The prevalence of deaths in newborns with complex gastroschisis was 15.0%. The predictive ultrasound markers for complex gastroschisis were intraabdominal bowel dilatation (IABD) (RR 3.01, 95% CI 2.22 to 4.07; I = 15.7%), extra-abdominal bowel dilatation (EABD) (RR 1.55, 95% CI 1.01 to 2.39; I = 77.1%), and polyhydramnios (RR 3.81, 95% CI 2.09 to 6.95; I = 0.0%). This review identified that IABD, EABD, and polyhydramnios were considered predictive ultrasound markers for complex gastroschisis. However, evidence regarding gestational age at the time of diagnosis is needed.
PubMed: 34830497
DOI: 10.3390/jcm10225215