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Advances in Experimental Medicine and... 2024Ventricular septal defects (VSDs) are recognized as one of the commonest congenital heart diseases (CHD), accounting for up to 40% of all cardiac malformations, and...
Ventricular septal defects (VSDs) are recognized as one of the commonest congenital heart diseases (CHD), accounting for up to 40% of all cardiac malformations, and occur as isolated CHDs as well as together with other cardiac and extracardiac congenital malformations in individual patients and families. The genetic etiology of VSD is complex and extraordinarily heterogeneous. Chromosomal abnormalities such as aneuploidy and structural variations as well as rare point mutations in various genes have been reported to be associated with this cardiac defect. This includes both well-defined syndromes with known genetic cause (e.g., DiGeorge syndrome and Holt-Oram syndrome) and so far undefined syndromic forms characterized by unspecific symptoms. Mutations in genes encoding cardiac transcription factors (e.g., NKX2-5 and GATA4) and signaling molecules (e.g., CFC1) have been most frequently found in VSD cases. Moreover, new high-resolution methods such as comparative genomic hybridization enabled the discovery of a high number of different copy number variations, leading to gain or loss of chromosomal regions often containing multiple genes, in patients with VSD. In this chapter, we will describe the broad genetic heterogeneity observed in VSD patients considering recent advances in this field.
Topics: Humans; Chromosome Aberrations; DNA Copy Number Variations; Genetic Predisposition to Disease; Heart Septal Defects, Ventricular; Mutation; Transcription Factors
PubMed: 38884729
DOI: 10.1007/978-3-031-44087-8_27 -
Archives of Disease in Childhood. Fetal... Jun 2024The Gaps in the Congenital Diaphragmatic Hernia (CDH) Journey Priority Setting Partnership (PSP) was developed in collaboration with CDH Australia, James Lind Alliance...
OBJECTIVES
The Gaps in the Congenital Diaphragmatic Hernia (CDH) Journey Priority Setting Partnership (PSP) was developed in collaboration with CDH Australia, James Lind Alliance (JLA) and the Murdoch Children's Research Institute to identify research priorities for people with CDH, their families and healthcare workers in Australasia.
DESIGN
Research PSP in accordance with the JLA standardised methodology.
SETTING
Australian community and institutions caring for patients with CDH and their families.
PATIENTS
CDH survivors, families of children born with CDH (including bereaved) and healthcare professionals including critical care physicians and nurses (neonatal and paediatric), obstetric, surgical, allied health professionals (physiotherapists, speech pathologists and speech therapists) and general practitioners.
MAIN OUTCOME MEASURE
Top 10 research priorities for CDH.
RESULTS
377 questions, from a community-based online survey, were categorised and collated into 50 research questions. Through a further prioritisation process, 21 questions were then discussed at a prioritisation workshop where they were ranked by 21 participants (CDH survivors, parents of children born with CDH (bereaved and not) and 11 multidisciplinary healthcare professionals) into their top 10 research priorities.
CONCLUSION
Stakeholders' involvement identified the top 10 CDH-related research questions, spanning from antenatal care to long-term functional outcomes, that should be prioritised for future research to maximise meaningful outcomes for people with CDH and their families.
PubMed: 38880507
DOI: 10.1136/archdischild-2024-327108 -
Scientific Reports Jun 2024Congenital diaphragmatic hernia (CDH) is a birth defect characterized by incomplete closure of the diaphragm, herniation of abdominal organs into the chest, and...
Congenital diaphragmatic hernia (CDH) is a birth defect characterized by incomplete closure of the diaphragm, herniation of abdominal organs into the chest, and compression of the lungs and the heart. Besides complications related to pulmonary hypoplasia, 1 in 4 survivors develop neurodevelopmental impairment, whose etiology remains unclear. Using a fetal rat model of CDH, we demonstrated that the compression exerted by herniated organs on the mediastinal structures results in decreased brain perfusion on ultrafast ultrasound, cerebral hypoxia with compensatory angiogenesis, mature neuron and oligodendrocyte loss, and activated microglia. In CDH fetuses, apoptosis was prominent in the subventricular and subgranular zones, areas that are key for neurogenesis. We validated these findings in the autopsy samples of four human fetuses with CDH compared to age- and sex-matched controls. This study reveals the molecular mechanisms and cellular changes that occur in the brain of fetuses with CDH and creates opportunities for therapeutic targets.
Topics: Animals; Hernias, Diaphragmatic, Congenital; Neurons; Oligodendroglia; Rats; Humans; Brain; Female; Stem Cells; Fetus; Disease Models, Animal; Pregnancy; Male
PubMed: 38871804
DOI: 10.1038/s41598-024-64412-x -
Journal of Minimally Invasive Gynecology Jun 2024To assess the feasibility, effectiveness and safety of the robotic surgical approach in the treatment of severe diaphragmatic endometriosis (DE).
STUDY OBJECTIVE
To assess the feasibility, effectiveness and safety of the robotic surgical approach in the treatment of severe diaphragmatic endometriosis (DE).
DESIGN
Retrospective single-center study using data prospectively recorded in the Franco-European Multidisciplinary Institute of Endometriosis (IFEMendo) database and National observatory for endometriosis (NoEndo) database.
SETTING
Tertiary referral center. Endometriosis care center.
PATIENTS
Sixty consecutive patients undergoing robotic excision of severe DE from January 2020 to July 2023.
INTERVENTIONS
Robotic excision of severe DE.
MEASUREMENT
Categorical and continuous variables were evaluated and compared using descriptive statistics. A p-value of <0.05 was considered statistically significant.
MAIN RESULTS
Full thickness diaphragmatic resection was performed in 76.7% of patients (46/60), partial diaphragmatic muscle resection in 10% (6/60) of cases. Peritoneal stripping technique was performed in 60% (36/60) of patients, divided as follows: as the only technique in case of extensive superficial diaphragmatic involvement in 13.3% of cases (8/60); in addition to full-thickness or partial diaphragmatic resection in case of concomitant multiple foci in 46.7% of patients (28/60). Median operative time was 79.6 minutes with no statistically significative difference related to the surgeon performing surgery (p>0.05). Intraoperative and postoperative complications occurred in 1.7% (1/60) and 6.6% (4/60) of cases, respectively. Diaphragmatic hernia (Clavien-Dindo 3b) was the most common postoperative complication and required surgical repair in all cases. Median hospital stay was 24 hours. The rate of patients with complete recovery from DE symptoms has gradually increased during follow-up, reaching 89% after 12 months from surgery.
CONCLUSION
In this case series, robotic treatment of severe diaphragmatic endometriosis in expert hands was feasible, effective and safe.
SUMMATION
A robotic stepwise approach allows safe and radical excision of a severe form of diaphragmatic endometriosis.
PubMed: 38866098
DOI: 10.1016/j.jmig.2024.06.002 -
International Journal of Surgery Case... Jul 2024Sternutation is, by definition, a situation that increases abdominal pressure. However, it has not been clearly linked to protrusion of abdominal content through...
INTRODUCTION AND IMPORTANCE
Sternutation is, by definition, a situation that increases abdominal pressure. However, it has not been clearly linked to protrusion of abdominal content through weaknesses in the abdominal boundaries.
CASE PRESENTATION
Here we present a case report in which the only trigger factor found for an abdominal content protrusion was a sternutation episode. The patient arrived in our institution with the diagnosis of a transdiaphragmatic intercostal hernia, proven in CT-scan. He was, then, submitted to emergent surgery, where through thoracotomy and subcostal laparotomy, hernia content was reduced. The patient had a favorable evolution.
CLINICAL DISCUSSION
TDIH is a rare entity, for which there are still no consensus regarding its management. This makes clinical practice more challenging, leaving to the surgeon the therapeutic decision tailored to each patient.
CONCLUSION
This entity should be further studied, and consensus reached regarding its management.
PubMed: 38865944
DOI: 10.1016/j.ijscr.2024.109824 -
Prenatal Diagnosis Jun 2024To evaluate the diagnostic yield of exome sequencing (ES) in fetuses and neonates with prenatally detected congenital diaphragmatic hernia (CDH) and normal copy number...
OBJECTIVE
To evaluate the diagnostic yield of exome sequencing (ES) in fetuses and neonates with prenatally detected congenital diaphragmatic hernia (CDH) and normal copy number variant (CNV) analysis.
METHODS
We conducted a retrospective cohort study of prenatally diagnosed CDH cases seen between 2019 and 2022. All cases who underwent prenatal or postnatal genetic testing were reviewed. The results from the ES analysis that identified pathogenic or likely pathogenic single nucleotide variants are described.
RESULTS
In total, 133 fetuses with CDH were seen, of whom 98 (74%) had an isolated CDH and 35 (26%) had a complex CDH (associated structural anomalies) on prenatal examination. ES was performed in 68 cases, and eight pathogenic or likely pathogenic variants were found, accounting for a 12% diagnostic yield (10% [5/50] in isolated cases and 17% [3/18] in complex CDH).
CONCLUSIONS
In 12% of fetuses and neonates with CDH and normal CNV analysis results, pathogenic or likely pathogenic variants were identified with ES. These data indicate that there is a substantial diagnostic yield when offering ES in prenatally detected CDH, both in complex and isolated cases.
PubMed: 38862387
DOI: 10.1002/pd.6622 -
International Journal of Surgery Case... Jul 2024Right-side diaphragmatic hernia is a very rare cause of bowel obstruction and strangulation in adults, which is usually a congenital disorder.
INTRODUCTION
Right-side diaphragmatic hernia is a very rare cause of bowel obstruction and strangulation in adults, which is usually a congenital disorder.
CASE PRESENTATION
A- 55-year-old male presented to the emergency department of our hospital complaining of abdominal pain, nausea, vomiting, abdominal distension, fever, and constipation for 4 days. On physical examination, the patient was fibril, toxic, tachycardic, and hypotensive. The patient had a distended abdomen with exaggerated bowel sounds, abdominal tenderness, guarding, and rigidity mostly in the right upper quadrant. There were some degrees of tempanicity on percussion. The digital rectal examination was normal with no evidence of impacted stool.
DISCUSSION
Patients with a diaphragmatic hernia frequently present with manifestations of internal herniation, incarceration, obstruction, ischemia from strangulation, or perforation. The patient may present with respiratory symptoms such as dyspnea, absence of breath sounds in the thorax, or abdominal symptoms such as abdominal pain and bowel dilatation.
CONCLUSION
Diaphragmatic hernia, which is a rare case, should be included in the differential diagnosis of small bowel obstruction to preclude complications.
PubMed: 38852557
DOI: 10.1016/j.ijscr.2024.109831 -
Journal of Medical Genetics Jun 2024Tonne-Kalscheuer syndrome (TOKAS) is a recessive X-linked multiple congenital anomaly disorder caused by variations. Of the 41 patients reported, only 7 antenatal cases...
INTRODUCTION
Tonne-Kalscheuer syndrome (TOKAS) is a recessive X-linked multiple congenital anomaly disorder caused by variations. Of the 41 patients reported, only 7 antenatal cases were described.
METHOD
After the antenatal diagnosis of TOKAS by exome analysis in a family followed for over 35 years because of multiple congenital anomalies in five male fetuses, a call for collaboration was made, resulting in a cohort of 11 previously unpublished cases.
RESULTS
We present a TOKAS antenatal cohort, describing 11 new cases in 6 French families. We report a high frequency of diaphragmatic hernia (9 of 11), differences in sex development (10 of 11) and various visceral malformations. We report some recurrent dysmorphic features, but also pontocerebellar hypoplasia, pre-auricular skin tags and olfactory bulb abnormalities previously unreported in the literature. Although no clear genotype-phenotype correlation has yet emerged, we show that a recurrent p.(Arg611Cys) variant accounts for 66% of fetal TOKAS cases. We also report two new likely pathogenic variants in , outside of the two previously known mutational hotspots.
CONCLUSION
Overall, we present the first fetal cohort of TOKAS, describe the clinical features that made it a recognisable syndrome at fetopathological examination, and extend the phenotypical spectrum and the known genotype of this rare disorder.
PubMed: 38849204
DOI: 10.1136/jmg-2024-109854 -
Cureus May 2024Congenital diaphragmatic hernias (CDH) occur as a result of genetic and environmental factors that occur during the early stages of fetal development. Overall, CDH are...
Congenital diaphragmatic hernias (CDH) occur as a result of genetic and environmental factors that occur during the early stages of fetal development. Overall, CDH are considered to be quite rare and are often discovered when patients are neonates. The patient in this case underwent a routine colonoscopy for high-risk polyps but then developed the sudden onset of cramping abdominal pain and PO (per os) intolerance. She was found to have a right-sided diaphragmatic hernia which ultimately required operative intervention. Retrospectively, a close review of prior imaging revealed a potential diaphragm defect. Post-colonoscopy diaphragmatic hernias are very rare and right-sided ones are rarer, making this case report an important addition to the literature.
PubMed: 38846239
DOI: 10.7759/cureus.59761 -
Langenbeck's Archives of Surgery Jun 2024The objective of this study is to compare the operative time, intraoperative complications, length of stay, readmission rates, overall complications, mortality, and cost... (Meta-Analysis)
Meta-Analysis Comparative Study
PURPOSE
The objective of this study is to compare the operative time, intraoperative complications, length of stay, readmission rates, overall complications, mortality, and cost associated with Robotic Surgery (RS) and Laparascopic Surgery (LS) in anti-reflux and hiatal hernia surgery.
METHODS
A comprehensive literature search was conducted using MEDLINE (via PubMed), Web of Science and Scopus databases. Studies comparing short-term outcomes and cost between RS and LS in patients with anti-reflux and hiatal hernia were included. Data on operative time, complications, length of stay, readmission rates, overall complications, mortality, and cost were extracted. Quality assessment of the included studies was performed using the MINORS scale.
RESULTS
Fourteen retrospective observational studies involving a total of 555,368 participants were included in the meta-analysis. The results showed no statistically significant difference in operative time, intraoperative complications, length of stay, readmission rates, overall complications, and mortality between RS and LS. However, LS was associated with lower costs compared to RS.
CONCLUSION
This systematic review and meta-analysis demonstrates that RS has non-inferior short-term outcomes in anti-reflux and hiatal hernia surgery, compared to LS. LS is more cost-effective, but RS offers potential benefits such as improved visualization and enhanced surgical techniques. Further research, including randomized controlled trials and long-term outcome studies, is needed to validate and refine these findings.
Topics: Humans; Hernia, Hiatal; Robotic Surgical Procedures; Laparoscopy; Gastroesophageal Reflux; Operative Time; Herniorrhaphy; Treatment Outcome; Length of Stay; Fundoplication; Patient Readmission; Postoperative Complications
PubMed: 38842610
DOI: 10.1007/s00423-024-03368-y