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British Journal of Cancer Jun 2023Costello syndrome (CS) is a cancer-predisposition disorder caused by germline pathogenic variants in HRAS. We conducted a systematic review using case reports and case... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Costello syndrome (CS) is a cancer-predisposition disorder caused by germline pathogenic variants in HRAS. We conducted a systematic review using case reports and case series to characterise cancer risk in CS.
METHODS
We conducted a systematic review to identify CS cases to create a retrospective cohort. We tested genotype-phenotype correlations and calculated cumulative incidence and hazard rates (HR) for cancer and cancer-free death, standardised incidence rates (SIR) and survival after cancer.
RESULTS
This study includes 234 publications reporting 621 patients from 35 countries. Over nine percent had cancer, including rhabdomyosarcoma, bladder, and neuroblastoma. The rate of cancer and death associated with p.Gly12Ser were lower when compared to all other variants (P < 0.05). Higher mortality for p.Gly12Cys, p.Gly12Asp, p.Gly12Val and p.Gly60Val and higher malignancy rate for p.Gly12Ala were confirmed (P < 0.05). Cumulative incidence by age 20 was 13% (cancer) and 11% (cancer-free death). HR (death) was 3-4% until age 3. Statistically significant SIRs were found for rhabdomyosarcoma (SIR = 1240), bladder (SIR = 1971), and neuroblastoma (SIR = 60). Survival after cancer appeared reduced.
CONCLUSIONS
This is the largest investigation of cancer in CS to date. The high incidence and SIR values found to highlight the need for rigorous surveillance and evidence-based guidelines for this high-risk population.
Topics: Humans; Costello Syndrome; Retrospective Studies; Genotype; Rhabdomyosarcoma; Neuroblastoma
PubMed: 36966234
DOI: 10.1038/s41416-023-02229-7 -
The Journal of Clinical Endocrinology... Jan 2022Anti-Mullerian hormone (AMH) was originally described in the context of sexual differentiation in the male fetus but has gained prominence now as a marker of ovarian...
CONTEXT
Anti-Mullerian hormone (AMH) was originally described in the context of sexual differentiation in the male fetus but has gained prominence now as a marker of ovarian reserve and fertility in females. In this mini-review, we offer an updated synopsis on AMH and its clinical utility in pediatric patients.
DESIGN AND RESULTS
A systematic search was undertaken for studies related to the physiology of AMH, normative data, and clinical role in pediatrics. In males, AMH, secreted by Sertoli cells, is found at high levels prenatally and throughout childhood and declines with progression through puberty to overlap with levels in females. Thus, serum AMH has clinical utility as a marker of testicular tissue in males with differences in sexual development and cryptorchidism and in the evaluation of persistent Mullerian duct syndrome. In females, serum AMH has been used as a predictive marker of ovarian reserve and fertility, but prepubertal and adolescent AMH assessments need to be interpreted cautiously. AMH is also a marker of tumor burden, progression, and recurrence in germ cell tumors of the ovary.
CONCLUSIONS
AMH has widespread clinical diagnostic utility in pediatrics but interpretation is often challenging and should be undertaken in the context of not only age and sex but also developmental and pubertal stage of the child. Nonstandardized assays necessitate the need for assay-specific normative data. The recognition of the role of AMH beyond gonadal development and maturation may usher in novel diagnostic and therapeutic applications that would further expand its utility in pediatric care.
Topics: Anti-Mullerian Hormone; Child; Child Development; Cryptorchidism; Disorder of Sex Development, 46,XY; Female; Gonads; Humans; Male; Ovarian Reserve; Sexual Maturation
PubMed: 34537849
DOI: 10.1210/clinem/dgab687 -
Orphanet Journal of Rare Diseases Jul 2022Primary ciliary dyskinesia (PCD) represents a highly heterogenous disorder with extensive clinical and genetic patterns among populations of different geographic... (Review)
Review
BACKGROUND
Primary ciliary dyskinesia (PCD) represents a highly heterogenous disorder with extensive clinical and genetic patterns among populations of different geographic location and ethnic origin. However, data about Chinese patients are limited. We aimed to summarize the clinical and genetic spectrum of Chinese PCD patients based on all available literatures.
METHODS
We searched Embase, Pubmed, Web of Science and Chinese databases including CNKI, SinoMed and Wanfang from 1981 to 2021, to identify articles reporting patients with PCD in China, which had included information about transmission electron microscopy and/or genetic testing.
RESULTS
A total of 244 Chinese PCD patients in 52 articles were included. Of these patients, the mean age was 13.1 years, and 55 patients (22.5%) were diagnosed with PCD after 18 years old. Compared with patients diagnosed with PCD in childhood or infancy, patients diagnosed with PCD in adulthood had a higher prevalence of chronic wet cough, sinusitis, Pseudomonas aeruginosa (PA) isolation and radiological bronchiectasis as well as worse lung function. 25 PCD-related genes were identified in 142 patients, and DNAH5, DNAH11, CCDC39 and CCDC40 were the most frequently detected mutations. More than half of genetic variants were loss-of-function mutations, and the majority of these variants were seen only once. Correlations between PCD phenotype, genotype and ciliary ultrastructure were also evidenced.
CONCLUSIONS
Diagnostic delay and under-recognition of PCD remain a big issue in China, which contributes to progressive lung disease and PA infection indicating worse outcome. Specialist equipment and expertise are urgently required to facilitate the early diagnosis and treatment of PCD.
TRIAL REGISTRY
PROSPERO; No.: CRD42021257804; URL: www.crd.york.ac.uk/prospero/.
Topics: Cilia; Ciliary Motility Disorders; Delayed Diagnosis; Genotype; Humans; Kartagener Syndrome; Mutation; Phenotype
PubMed: 35854386
DOI: 10.1186/s13023-022-02427-1 -
Foot (Edinburgh, Scotland) Dec 2021The standard of care in the treatment of symptomatic tarsal coalitions is open surgery. However, certain limitations exist with open surgery, which include limited... (Review)
Review
INTRODUCTION
The standard of care in the treatment of symptomatic tarsal coalitions is open surgery. However, certain limitations exist with open surgery, which include limited visualization leading to an incomplete resection and possible recurrence of the tarsal coalition. Arthroscopic tarsal coalition resection (TCR) is an alternative that is gaining traction, primarily as the safety profile of posterior ankle and subtalar arthroscopy is more well understood. This study provides a systematic review of the outcomes of arthroscopic TCR.
METHODS
PubMed and Embase were searched independently by 2 reviewers for relevant articles based on predetermined criteria. The subject heading "tarsal coalition" and its related key terms were used.
RESULTS
A total of 416 studies were revealed by the initial search, out of which only 6 met our predetermined inclusion criteria. A total of 42 patients (average age: 17.6 years) were treated with arthroscopic TCR. Thirty-three (78.6%) and 9 (21.4%) patients had talocalcaneal and calcaneonavicular coalitions, respectively. The follow-up period ranged from 6 to 60 months (mean: 26 months), and no recurrence of the tarsal coalition was detected (0.0%). Complications occurred in two (4.8%) patients only, with one developing complex regional pain syndrome (CRPS), and another patient developing hyperesthesia on the medial aspect of the calcaneus.
CONCLUSION
Arthroscopic TCR is a feasible and effective surgery for both CNC and TCC with minimal complications and no disease recurrence at an average of 26 months follow-up. Future high-level of evidence studies are needed to compare the outcomes of open versus arthroscopic TCR.
Topics: Adolescent; Arthroscopy; Calcaneus; Humans; Synostosis; Tarsal Bones; Tarsal Coalition
PubMed: 34597922
DOI: 10.1016/j.foot.2021.101864 -
Oral Surgery, Oral Medicine, Oral... Dec 2023We examined the range, nature, and extent of research conducted regarding the oral and dental implications of hereditary hemorrhagic telangiectasia (HHT) to identify... (Review)
Review
OBJECTIVE
We examined the range, nature, and extent of research conducted regarding the oral and dental implications of hereditary hemorrhagic telangiectasia (HHT) to identify gaps in the research and knowledge of the field.
STUDY DESIGN
We performed a scoping review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews and 2017 Guidance for the Conduct of Joanna Briggs Institute Scoping Reviews. We searched the MEDLINE and Web of Science databases for all full-text articles published in English from December 1946 to October 2022.
RESULTS
We identified 103 articles describing oral and dental considerations of patients with HHT, primarily case reports. Most reported oral telangiectasias of the tongue, lips, and palate. Many reported management of bleeding and the use or recommendation of prophylactic antibiotics before dental procedures.
CONCLUSIONS
Oral telangiectasias are commonly found in patients with hereditary hemorrhagic telangiectasia, and dental professionals may be the first to diagnose it in their patients. Early detection and diagnosis are important to prevent potentially fatal outcomes, and prophylactic antibiotics before procedures may be warranted.
Topics: Humans; Telangiectasia, Hereditary Hemorrhagic; Telangiectasis; Hemorrhage; Anti-Bacterial Agents
PubMed: 37752017
DOI: 10.1016/j.oooo.2023.08.001 -
European Journal of Vascular and... Dec 2022Since the first description of the median arcuate ligament syndrome (MALS), the existence for the syndrome and the efficacy of treatment for it have been questioned. (Review)
Review
OBJECTIVE
Since the first description of the median arcuate ligament syndrome (MALS), the existence for the syndrome and the efficacy of treatment for it have been questioned.
METHODS
A systematic review conforming to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement was conducted, with a broader view on treatment for MALS including any kind of coeliac artery release, coeliac plexus resection, and coeliac plexus blockage, irrespective of age. Online databases were used to identify papers published between 1963 and July 2021. The inclusion criteria were abdominal symptoms, proof of MALS on imaging, and articles reporting at least three patients. Primary outcomes were symptom relief and quality of life (QoL).
RESULTS
Thirty-eight studies describing 880 adult patients and six studies describing 195 paediatric patients were included. The majority of the adult studies reported symptom relief of more than 70% from three to 228 months after treatment. Two adult studies showed an improved QoL after treatment. Half of the paediatric studies reported symptom relief of more than 70% from six to 62 months after laparoscopic coeliac artery release, and four studies reported an improved QoL. Thirty-five (92%) adult studies and five (83%) paediatric studies scored a high or unclear risk of bias for the majority of the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) items. The meaning of coeliac plexus resection or blockage could not be substantiated.
CONCLUSION
This systematic review suggests a sustainable symptom relief of more than 70% after treatment for MALS in the majority of adult and paediatric studies; however, owing to the heterogeneity of the inclusion criteria and outcome parameters, the risk of bias was high and a formal meta-analysis could not be performed. To improve care for patients with MALS the next steps would be to deal with reporting standards, outcome definitions, and consensus descriptions of the intervention(s), after which an appropriate randomised controlled trial should be performed.
Topics: Adult; Humans; Child; Median Arcuate Ligament Syndrome; Quality of Life; Constriction, Pathologic; Celiac Artery; Decompression, Surgical
PubMed: 36075541
DOI: 10.1016/j.ejvs.2022.08.033 -
Hernia : the Journal of Hernias and... Feb 2022Bochdalek hernia is a congenital diaphragmatic hernia. The incidence in adults is estimated around 0.17%. Right-sided hernias are much more seldom than left-sided ones... (Review)
Review
PURPOSE
Bochdalek hernia is a congenital diaphragmatic hernia. The incidence in adults is estimated around 0.17%. Right-sided hernias are much more seldom than left-sided ones because of faster closure of the right pleuroperitoneal canal and the protective effect of the liver. Due to its rarity, there have been no large prospective or retrospective studies following great need for evidence-based diagnostics and treatment strategies. In this systematic review, we evaluated the current evidence of diagnostics, treatment, and follow-up of adult right-sided Bochdalek hernias.
METHODS
According to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines a systematic literature review was conducted in PubMed and Cochrane library from 2004 to January 2021. The literature search included all studies with non-traumatic right-sided Bochdalek hernias. Literature on left- or both-sided, pregnancy-associated, pediatric, and other types of hernias were explicitly excluded. Quality assessment of the included studies was performed.
RESULTS
Database search identified 401 records. After eligibility screening 41 studies describing 44 cases of right-sided non-traumatic Bochdalek hernias in adulthood were included for final analysis. Based upon the systematic literature review, the current diagnostic, therapeutic, and follow-up management pathway for this rare surgical emergency is presented.
CONCLUSION
This systematic review underlined that most studies investigating management of adult non-traumatic right-sided Bochdalek hernias are of moderate to low methodological quality. Hernias tend to occur more frequently in middle-aged and older women presenting with abdominal pain and dyspnea. A rapid and accurate diagnosis following surgical repair and regular follow-up is mandatory. High-quality studies focusing on the management of this rare entity are urgently needed.
Topics: Abdomen; Adult; Aged; Child; Female; Hernias, Diaphragmatic, Congenital; Herniorrhaphy; Humans; Middle Aged; Pregnancy; Prospective Studies; Retrospective Studies
PubMed: 34216313
DOI: 10.1007/s10029-021-02445-1 -
Journal of the Peripheral Nervous... Sep 2023Several widely used medications, with a relevant efficacy profile, are toxic to the peripheral nervous system and an even larger number of agents are suspected to be... (Review)
Review
BACKGROUND AND AIMS
Several widely used medications, with a relevant efficacy profile, are toxic to the peripheral nervous system and an even larger number of agents are suspected to be neurotoxic. There are concerns about the use of these drugs in patients with Charcot-Marie-Tooth disease (CMT), a hereditary motor and sensory neuropathy. This review provides evidence-based updated recommendations on this clinically relevant topic.
METHODS
A systematic review of the available studies/reports written in English was performed from July to September 2022 including in the search string all reported putative neurotoxic drugs.
RESULTS
The results of our systematic review provide evidence-based support for the statement that use of vincristine, and possibly paclitaxel, can occasionally induce an atypical, and more severe, course of drug-related peripheral neurotoxicity in CMT patients. It is therefore reasonable to recommend caution in the use of these compounds in CMT patients. However, no convincing evidence for a similar recommendation could be found for all other drugs.
INTERPRETATION
It is important that patients with CMT are not denied effective treatments that may prolong life expectancy for cancer or improve their health status if affected by non-oncological diseases. Accurate monitoring of peripheral nerve function in CMT patients treated with any neurotoxic agent remains mandatory to detect the earliest signs of neuropathy worsening and atypical clinical courses. Neurologists monitoring CMT patients as part of their normal care package or for natural history studies should keep detailed records of exposures to neurotoxic medications and support reporting of accelerated neuropathy progression if observed.
Topics: Humans; Charcot-Marie-Tooth Disease; Hereditary Sensory and Motor Neuropathy; Neoplasms; Neurotoxicity Syndromes
PubMed: 37249082
DOI: 10.1111/jns.12566 -
European Journal of Obstetrics &... Jul 2021We aimed to review and analyze studies focusing on the efficacy of metronidazole in reducing the risk of preterm birth and the safety of metronidazole taking into... (Review)
Review
OBJECTIVE
We aimed to review and analyze studies focusing on the efficacy of metronidazole in reducing the risk of preterm birth and the safety of metronidazole taking into account the different doses, duration of treatment and routes of administration.
STUDY DESIGNS
Embase, Cochrane Library and PubMed were searched up to 29 July 2019 to identify studies assessing metronidazole exposure during pregnancy. Additional studies were identified from reference lists of retrieved papers. Measured outcomes were preterm births (<37 weeks of gestation) and associated delivery outcomes such as spontaneous abortions (≤ 20 weeks of gestation), stillbirths (≥20 weeks of gestation) and low birth weight (<2500 g) irrespective of the period of exposure and major malformations after first-trimester exposure. Overall effect estimates for RCTs and observational studies were calculated using the random-effects model and pooled using Risk Ratios (RR) and Odds Ratios (OR) respectively. ROB-2 and ROBINS-I tool were used to assess Risk of Bias for RCTs and observational studies, respectively.
RESULTS
Twenty-four studies (17 observational studies and 7 RCTs) were selected. Pooled RR was 1.10 (95 % CI 0.78-1.55; n = 7; I = 72 %) for preterm birth. Subgroup analysis found RR 1.67; 95 % CI 1.07-2.62; n = 3; I² = 32 %) for treatment duration of ≤3 days among women with a previous preterm delivery. Pooled OR for spontaneous abortion was 1.72 (95 % CI 1.40-2.12; n = 5; I = 72 %) and 1.15 (95 % CI 0.98-1.34; n = 12; I = 25 %) for major malformations. After exclusion of studies with critical risk of bias, pooled OR were 1.7 (1.42-2.04; n = 3; I = 19 %) and 1.13 (0.93-1.36; n = 9; I = 28 %) respectively. Among several specific malformations analyzed, only congenital hydrocephaly was significantly increased at 4.06 (95 % CI 1.75-9.42; n = 2; I² = 0%).
CONCLUSIONS
Data do not confirm the efficacy of metronidazole in reducing the risk of preterm birth and associated delivery outcomes. Further research is required to confirm the effect of high dose and short duration of metronidazole treatment on preterm birth among the high-risk group. Regarding the increased odds of spontaneous abortion, RCTs are required to assess the role of the underlying infection. The need for further studies to confirm the risk of congenital hydrocephaly is paramount.
PubMed: 34136799
DOI: 10.1016/j.eurox.2021.100128 -
Scientific Reports Sep 2023Outcomes of conventional mechanical ventilation (CMV) and high-frequency oscillatory ventilation (HFOV) in patients with congenital diaphragmatic hernia (CDH) were... (Meta-Analysis)
Meta-Analysis
Outcomes of conventional mechanical ventilation (CMV) and high-frequency oscillatory ventilation (HFOV) in patients with congenital diaphragmatic hernia (CDH) were compared through a systematic review and meta-analysis. Outcome measures included mortality and incidence of chronic lung disease (CLD). Odds ratio (OR) and 95% confidence interval (95%CI) were evaluated. Subgroup analyses were performed according to the strategy for applying HFOV in CDH patients. Group A: CMV was initially applied in all CDH patients, and HFOV was applied in unstable patients. Group B: chronologically analyzed. (CMV and HFOV era) Group C: CMV or HFOV was used as the initial MV. Of the 2199 abstracts screened, 15 full-text articles were analyzed. Regarding mortality, 16.7% (365/2180) and 32.8% (456/1389) patients died in CMV and HFOV, respectively (OR, 2.53; 95%CI 2.12-3.01). Subgroup analyses showed significantly worse, better, and equivalent mortality for HFOV than that for CMV in group A, B, and C, respectively. CLD occurred in 32.4% (399/1230) and 49.3% (369/749) patients in CMV and HFOV, respectively (OR, 2.37; 95%CI 1.93-2.90). The evidence from the literature is poor. Mortality and the incidence of CLD appear worse after HFOV in children with CDH. Cautious interpretation is needed due to the heterogeneity of each study.
Topics: Child; Humans; Respiration, Artificial; Hernias, Diaphragmatic, Congenital; High-Frequency Ventilation; Death; Cytomegalovirus Infections
PubMed: 37752154
DOI: 10.1038/s41598-023-42344-2