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A major barrier to the impact of genomic diagnosis in patients with congenital malformations is the lack of understanding regarding how sequence variants contribute to disease pathogenesis and whether this information could be used to generate patient-specific therapies. Congenital diaphragmatic hernia (CDH) is among the most common and severe of all structural malformations; however, its underlying mechanisms are unclear. We identified loss-of-function sequence variants in the epigenomic regulator gene SIN3A in two patients with complex CDH. Tissue-specific deletion of Sin3a in mice resulted in defects in diaphragm development, lung hypoplasia, and pulmonary hypertension, the cardinal features of CDH and major causes of CDH-associated mortality. Loss of SIN3A in the lung mesenchyme resulted in reduced cellular differentiation, impaired cell proliferation, and increased DNA damage. Treatment of embryonic Sin3a mutant mice with anacardic acid, an inhibitor of histone acetyltransferase, reduced DNA damage, increased cell proliferation and differentiation, improved lung and pulmonary vascular development, and reduced pulmonary hypertension. These findings demonstrate that restoring the balance of histone acetylation can improve lung development in the Sin3a mouse model of CDH.

Aim: The aim of the present study was to assess the diaphragmatic and lung USG to predict the outcome of weaning process. Methods: The proposed study has been conducted on critically ill post-surgical patients on mechanical ventilation aged between 18-65 years, in intensive care unit of Department of Anaesthesiology and CCM, Nehru hospital, B.R.D. Medical College, Gorakhpur, Uttar Pradesh from December 2020 to November 2021. 110 patients were included in the study. Results: There was significant difference observed in failure rate of extubation among different age groups as age increases the rate of failure also increases significantly (p<0.0001). There was no significant difference observed in success rate of extubation across gender (success rate: male vs female: 88.2% vs 86.8%, p=0.839). Failure rate of extubation was significantly higher in those patients who had any comorbidities as compared to those who had no comorbidities. Mean LUS Score on CPAP was significantly lower in success group as compared to failure group. Mean LUS Score after extubation was significantly lower in success group as compared to failure group. Mean DTF on CPAP was significantly higher in success group as compared to failure group. Mean DTF on T piece was significantly higher in success group as compared to failure group. Mean DTF after Extubation was significantly higher in success group as compared to failure group. Likewise, Mean E on CPAP was significantly higher in success group as compared to failure group. Mean E on T piece was significantly higher in success group as compared to failure group. Mean E after extubation was significantly higher in success group as compared to failure group. Conclusion: The weaning outcome can be predicted by LUS score, diaphragmatic thickness fraction (DTF), diaphragmatic excursion (E) in mechanically ventilated patients. A value of LUS score on T-piece ≤10 predicts the successful weaning final outcome. A value of DTF on T-piece ≥31% predicts the successful weaning final outcome. Similarly, a value of E on Tpiece ≥18mm also predicts a successful weaning outcome. Increased rate of weaning failure observed in older age group, patients with co-morbidities and high SOFA score. Also prolonged duration of mechanical ventilation caused failure in weaning. [ABSTRACT FROM AUTHOR]

Congenital diaphragmatic hernia (CDH) is a relatively common and genetically heterogeneous structural birth defect associated with high mortality and morbidity. We describe eight unrelated families with an X-linked condition characterized by diaphragm defects, variable anterior body-wall anomalies, and/or facial dysmorphism. Using linkage analysis and exome or genome sequencing, we found that missense variants in plastin 3 (PLS3), a gene encoding an actin bundling protein, co-segregate with disease in all families. Loss-of-function variants in PLS3 have been previously associated with X-linked osteoporosis (MIM: 300910), so we used in silico protein modeling and a mouse model to address these seemingly disparate clinical phenotypes. The missense variants in individuals with CDH are located within the actin-binding domains of the protein but are not predicted to affect protein structure, whereas the variants in individuals with osteoporosis are predicted to result in loss of function. A mouse knockin model of a variant identified in one of the CDH-affected families, c.1497G>C (p.Trp499Cys), shows partial perinatal lethality and recapitulates the key findings of the human phenotype, including diaphragm and abdominal-wall defects. Both the mouse model and one adult human male with a CDH-associated PLS3 variant were observed to have increased rather than decreased bone mineral density. Together, these clinical and functional data in humans and mice reveal that specific missense variants affecting the actin-binding domains of PLS3 might have a gain-of-function effect and cause a Mendelian congenital disorder.

Introduction: Congenital diaphragmatic hernia, in which viscera herniate into the thoracic cavity, is one of the common causes of onset of respiratory distress in neonates and children. Developmentally they may have a sac in rare cases. Aim: To analyse the clinical profile and the outcome of congenital diaphragmatic hernia with a sac in neonates and children in a paediatric referral centre. Material and methods: All surgically repaired patients with a congenital diaphragmatic hernia with sac, admitted and treated over a period of sixteen years from January 2005 to December 2021 in a tertiary care referral neonatal and paediatric centre, were included in this study. Forty-three children including neonates were analysed by their clinical characteristics, risk factors and mode of surgical interventions. Congenital diaphragmatic eventration and diaphragmatic hernial defects were excluded from this study. Results: Forty-three study subjects were grouped into two groups for clinical and statistical analysis, based on their pre-operative and intra-operative findings as well their final diagnosis. Cases of left-sided congenial diaphragmatic hernia with sac (LCDHS) were included in group I (n = 30) and cases of right-sided congenital diaphragmatic hernia with sac (RCDHS) were included in group II (n = 13). Each group was further subclassified into A, B, C according to the age of presentation and side of the lesion in order to determine the prognosis in each subgroup. Level of evidence IV. Conclusions: Mere awareness and clinical suspicion of such a rare embryological defect -- a congenital diaphragmatic hernia with sac -- from the attending clinicians can improve the prognosis of affected babies, avoiding morbid consequences if referred early to a tertiary care paediatric and neonatal centre. [ABSTRACT FROM AUTHOR]

Objectives: Congenital diaphragmatic hernia (CDH) is defined as organ protrusion from the abdominal to the thoracic cavity. The Hadlock formula is the most commonly used tool for calculating estimated fetal weight (EFW). The anatomical nature of CDH usually leads to underestimation of the abdominal circumference, resulting in underestimation of fetal weight. Accurate weight estimation is essential before birth for counselling, preparation before surgery and ECMO. The research is made to compare the accuracy of Hadlock's formula and Faschingbauer's formula for fetal weight estimation in CDH fetuses population. Methods: In our study, we investigated differences between EFW and actual birthweight in 42 fetuses with CDH as compared to 80 healthy matched controls. EFW was calculated using the Hadlock formula and a recently introduced formula described by Faschingbauer et al., which was tailored for fetuses with CDH. Additionally, both of the formulas were adjusted for the interval between the ultrasound and delivery for both of the groups. Results: The majority of hernias were left-sided (92.8% vs. 7.2%). EFW adjusted for the interval between the ultrasound and delivery had the highest correlation with the actual birthweight in both, study group and controls. We compared the results for both tools and found the Hadlock formula to predict birthweight in CDH children with a 7.8 ± 5.5% error as compared to 7.9 ± 6.5% error for the Faschingbauer's formula. Conclusions: The Hadlock formula adjusted for the interval between the ultrasound and delivery is a more precise method of calculating EFW in fetuses with CDH. Routine biometry scan using Hadlock's formula remains reliable for predicting birthweight. [ABSTRACT FROM AUTHOR]

Right-sided congenital diaphragmatic hernia (RCDH) is a rare and often fatal congenital anomaly, primarily attributed to lung hypoplasia, which is associated with small branch pulmonary artery (PA). This study investigated whether postnatal PA measurements obtained through echocardiography are associated with mortality or the extracorporeal membrane oxygenation (ECMO) requirement in neonates with RCDH. A retrospective study was conducted on neonates with RCDH born between 2008 and 2022. Echocardiography was performed on the day of birth. The diameter of the main PA (MPA) was measured at the maximal dimension, and the diameters of the left PA (LPA) and right PA (RPA) were measured at the bifurcation. The primary outcome was mortality or ECMO requirement. Parameters, including the LPA:MPA ratio, RPA:MPA ratio, Nakata index, McGoon ratio, and ejection fraction (EF), were analyzed and compared with the observed-to-expected lung-to-head ratio (o/e LHR), initial blood gas, and defect size as predictive values. Among 39 neonates with RCDH, 25 (64.1 %) survived without ECMO. The non-survivor or ECMO group exhibited lower o/e LHR, reduced EF, smaller LPA and RPA diameters, and larger MPA diameter than survivors. Lower LPA:MPA ratio, Nakata index, McGoon ratio, and higher initial PaCO 2 were associated with adverse outcomes. Notably, the LPA:MPA ratio showed the highest predictive capability (area under the curve, 0.983; p < 0.001). The LPA:MPA ratio is a promising postnatal predictor of mortality or ECMO requirement in neonates with RCDH. Additionally, Nakata index, McGoon ratio, and initial PaCO 2 are significantly correlated with outcomes. This is a level III. Prognostic study. • What is currently known about this topic? Currently, there are no conclusive prognostic factors for right-sided congenital diaphragmatic hernia (RCDH), particularly those assessed postnatally. • What new information is contained in this article? This article provides novel insights into the postnatal prognostication of neonates with RCDH using the pulmonary artery (PA) diameter. This introduces, the left PA: main PA ratio, as a robust predictor of poor outcome. [ABSTRACT FROM AUTHOR]

BACKGROUND: Diaphragmatic hernia (DH) presenting acutely can be a potentially life-threatening condition. Its management continues to be debatable. METHODS: A bibliographic search using major databases was performed using the terms emergency surgery diaphragmatic hernia, traumatic diaphragmatic rupture and congenital diaphragmatic hernia. GRADE methodology was used to evaluate the evidence and give recommendations. RESULTS: CT scan of the chest and abdomen is the diagnostic gold standard to evaluate complicated DH. Appropriate preoperative assessment and prompt surgical intervention are important for a clinical success. Complicated DH repair is best performed via the use of biological and bioabsorbable meshes which have proven to reduce recurrence. The laparoscopic approach is the preferred technique in hemodynamically stable patients without significant comorbidities because it facilitates early diagnosis of small diaphragmatic injuries from traumatic wounds in the thoraco-abdominal area and reduces postoperative complications. Open surgery should be reserved for situations when skills and equipment for laparoscopy are not available, where exploratory laparotomy is needed, or if the patient is hemodynamically unstable. Damage Control Surgery is an option in the management of critical and unstable patients. CONCLUSIONS: Complicated diaphragmatic hernia is a rare life-threatening condition. CT scan of the chest and abdomen is the gold standard for diagnosing the diaphragmatic hernia. Laparoscopic repair is the best treatment option for stable patients with complicated diaphragmatic hernias. Open repair is considered necessary in majority of unstable patients in whom Damage Control Surgery can be life-saving.

Acquired diaphragmatic hernia is typically caused by blunt trauma to the abdomen. It can be challenging to diagnose in acute cases due to a wide range of symptoms. Delayed presentation of traumatic diaphragmatic hernia is uncommon and can lead to respiratory issues or bowel complications like incarceration, perforation, or strangulation. Computed tomography is the preferred diagnostic tool. For acute case, laparotomy is indicated traditionally; however, the choice of surgery is dependent upon the surgeon's expertise and availability of resources. [ABSTRACT FROM AUTHOR]

IntroductionCongenital diaphragmatic hernia (CDH) repair is an area of active research. Large defects requiring patches have a hernia recurrence rate of up to 50%. We designed a biodegradable polyurethane (PU)-based elastic patch that matches the mechanical properties of native diaphragm muscle. We compared the PU patch to a non-biodegradable Gore-Tex™ (polytetrafluoroethylene) patch.MethodsThe biodegradable polyurethane was synthesized from polycaprolactone, hexadiisocyanate and putrescine, and then processed into fibrous PU patches by electrospinning. Rats underwent 4 mm diaphragmatic hernia (DH) creation via laparotomy followed by immediate repair with Gore-Tex™ (n = 6) or PU (n = 6) patches. Six rats underwent sham laparotomy without DH creation/repair. Diaphragm function was evaluated by fluoroscopy at 1 and 4 weeks. At 4 weeks, animals underwent gross inspection for recurrence and histologic evaluation for inflammatory reaction to the patch materials.ResultsThere were no hernia recurrences in either cohort. Gore-Tex™ had limited diaphragm rise compared to sham at 4 weeks (1.3 mm vs 2.9 mm, p = 0.003), but no difference was found between PU and sham (1.7 mm vs 2.9 mm, p = 0.09). There were no differences between PU and Gore-Tex™ at any time point. Both patches formed an inflammatory capsule, with similar thicknesses between cohorts on the abdominal (Gore-Tex™ 0.07 mm vs. PU 0.13 mm, p = 0.39) and thoracic (Gore-Tex™ 0.3 mm vs. PU 0.6 mm, p = 0.09) sides.ConclusionThe biodegradable PU patch allowed for similar diaphragmatic excursion compared to control animals. There were similar inflammatory responses to both patches. Further work is needed to evaluate long-term functional outcomes and further optimize the properties of the novel PU patch in vitro and in vivo.Level of evidenceLevel II, Prospective Comparative Study.

Traumatic diaphragmatic hernia is a sign of severe thoracoabdominal trauma that is often difficult to detect because of nonspecific presenting symptoms, delayed presentation, and distracting injuries. Diagnosis depends on imaging and a high degree of suspicion in patients who present with respiratory or gastrointestinal symptoms after trauma, and prompt surgical repair is required. This case reviews a patient who presented to the emergency department with burning epigastric pain radiating to the left chest and hematemesis ~1 month after sustaining a blunt abdominal injury. Imaging studies revealed a substantial portion of the gastric body in the left hemithorax. Robot-assisted reduction of the stomach was performed followed by repair with tension-free primary closure without mesh reinforcement and gastropexy. The patient was monitored for return of bowel function and discharged upon recovery. This case report highlights the diagnostic challenges of traumatic diaphragmatic hernia and the benefit of robot-assisted repair. [ABSTRACT FROM AUTHOR]

ObjectiveTo explore the relationship between Oxygenation Index (OI) and Oxygen Saturation Index (OSI) among infants with Congenital Diaphragmatic Hernia (CDH), both within the first 24 h after birth and in extended observations in those who survived until their surgical intervention.MethodsSeven- years retrospective review of CDH cases at a single Level III neonatal intensive care unit. The correlations of various combinations of OI-OSI pairs were assessed using the Spearman's rho Correlation Coefficient. Additionally, during the initial 24 h, the correlations between admission (first), best (lowest), highest, and mean OI and OSI values were determined. The predictive ability of the first 24 h oxygen and oxygen saturation indices for mortality and other adverse outcomes were assessed using the Area Under the Curve (AUC) analysis.ResultsThirty-seven infants with CDH were included in the analysis. A strong correlation was observed between all pairs of OI/OSI (2,289) (Spearman's rho = 0.843), matched pairs of Postductal OI/OSI (1,232 pairs) (Spearman's rho = 0.835) and the unmatched pairs of Postductal OI and Preductal OSI (1,057 pairs) (Spearman's rho = 0.852). Using the regression equations for all pairs, matched and unmatched OI/OSI pairs, we deduced that for clinically pertinent OI thresholds of 10, 15, 20 and 40, the corresponding OSI values were 5, 8, 11, and 23, respectively. Furthermore, in the first 24 h, strong correlations were evident between OI/OSI: at admission (Spearman's rho = 0.783), best OI/OSI (Spearman's rho = 0.848), and highest OI/OSI (Spearman's rho = 0.921). The most robust correlation was observed between the mean OI/OSI with a Spearman's rho of 0.928. First (AUC = 0.849), best (AUC = 0.927), highest (AUC = 0.942) and mean day 1 OI (AUC = 0.946) were all predictive of mortality. Similarly, first (AUC = 1.00), best (AUC = 0.989), highest (AUC = 1.00) and the mean OSI in day 1 (AUC = 0.978) were all predictive of mortality. All of the OIs and OSIs in day 1 except for the admission OSI (AUC = 0.683) were predictive of pulmonary hypertension. Additionally, all of OI and OSI indices in the first 24-hour except for the best day 1 OI (AUC = 0.674) were predictive of the need for rescue HFOV.ConclusionThere were a strong correlation between the OI and OSI in infants with CDH. Oxygenation indices and OSI in the first 24 h were predictive of mortality and other adverse outcomes in infants with CDH.

Congenital diaphragmatic hernia (CDH) can occur in isolation or in conjunction with other birth defects (CDH+). A molecular etiology can only be identified in a subset of CDH cases. This is due, in part, to an incomplete understanding of the genes that contribute to diaphragm development. Here, we used clinical and molecular data from 36 individuals with CDH+ who are cataloged in the DECIPHER database to identify genes that may play a role in diaphragm development and to discover new phenotypic expansions. Among this group, we identified individuals who carried putatively deleterious sequence or copy number variants affecting CREBBP, SMARCA4, UBA2, and USP9X. The role of these genes in diaphragm development was supported by their expression in the developing mouse diaphragm, their similarity to known CDH genes using data from a previously published and validated machine learning algorithm, and/or the presence of CDH in other individuals with their associated genetic disorders. Our results demonstrate how data from DECIPHER, and other public databases, can be used to identify new phenotypic expansions and suggest that CREBBP, SMARCA4, UBA2, and USP9X play a role in diaphragm development.

Objective: To analyze the effectiveness of diaphragmatic ultrasound to predict the outcome of extubation in the adult patient in the ICU. Methodology: It is a bibliographic review, and therefore, the information search was carried out in the Wiley, PubMed, Science Direct, and Scopus databases, according to the inclusion criteria. Results: In its main findings it is evident that diaphragmatic ultrasound is a predictive tool for extubation in adult patients, with the variables of diaphragmatic excursion, thickening fraction and/or diaphragmatic thickness. Conclusion: This study contains practical implications that can be taken into account in the control and management of critically ill patients in order to achieve successful extubation goals through ultrasonographic measurements of the diaphragm muscle. [ABSTRACT FROM AUTHOR]

Anxiety and stress plague populations worldwide. Voluntary regulated breathing practices offer a tool to address this epidemic. We examined peer-reviewed published literature to understand effective approaches to and implementation of these practices. PubMed and ScienceDirect were searched to identify clinical trials evaluating isolated breathing-based interventions with psychometric stress/anxiety outcomes. Two independent reviewers conducted all screening and data extraction. Of 2904 unique articles, 731 abstracts, and 181 full texts screened, 58 met the inclusion criteria. Fifty-four of the studies' 72 interventions were effective. Components of effective and ineffective interventions were evaluated to develop a conceptual framework of factors associated with stress/anxiety reduction effectiveness. Effective breath practices avoided fast-only breath paces and sessions <5 min, while including human-guided training, multiple sessions, and long-term practice. Population, other breath paces, session duration ≥5 min, and group versus individual or at-home practices were not associated with effectiveness. Analysis of interventions that did not fit this framework revealed that extensive standing, interruptions, involuntary diaphragmatic obstruction, and inadequate training for highly technical practices may render otherwise promising interventions ineffective. Following this evidence-based framework can help maximize the stress/anxiety reduction benefits of breathing practices. Future research is warranted to further refine this easily accessible intervention for stress/anxiety relief. [ABSTRACT FROM AUTHOR]

Abstract Background To predict whether the left pulmonary artery (LPA) to the main pulmonary artery (MPA) ratio measured by echocardiography in left congenital diaphragmatic hernia (CDH) was related to death or need for extracorporeal membrane oxygenation (ECMO). Methods This retrospective study analyzed neonates with left CDH born between 2018 and 2022 in a single tertiary medical institution. Echocardiography was performed immediately after birth. The diameter of the LPA was measured at the bifurcation, and the diameter of the MPA was measured at the maximal dimension during the systolic phase. The Nakata index, McGoon ratio, and ejection fraction (EF) were analyzed and compared with the LPA: MPA ratio as predictive values. Results Seventy-two neonates with left CDH were included, 19 (26.4%) died or needed ECMO, and 53 (73.6%) survived without ECMO. The lower observed/expected lung-to-head ratio, lower EF, lower LPA: MPA ratio, lower RPA: MPA ratio, lower Nakata index, and lower McGoon ratio were associated with death or need for ECMO. By multivariate analysis, lower LPA: MPA ratio, RPA: MPA ratio, and Nakata index were independent postnatal risk factors for death or need for ECMO. Among the measurements, the LPA: MPA ratio had the highest area under the curve (0.957) with a sensitivity of 84.2% and specificity of 96.3% at a cut-off value of 31.2%. Conclusion In patients with left CDH, the LPA: MPA ratio measured by echocardiography could be used as an independent postnatal predictor of death or need for ECMO.

Congenital diaphragmatic hernia (CDH) is a severe congenital anomaly that is often accompanied by other anomalies. Although the role of genetics in the pathogenesis of CDH has been established, only a small number of disease-associated genes have been identified. To further investigate the genetics of CDH, we analyzed de novo coding variants in 827 proband-parent trios and confirmed an overall significant enrichment of damaging de novo variants, especially in constrained genes. We identified LONP1 (lon peptidase 1, mitochondrial) and ALYREF (Aly/REF export factor) as candidate CDH-associated genes on the basis of de novo variants at a false discovery rate below 0.05. We also performed ultra-rare variant association analyses in 748 affected individuals and 11,220 ancestry-matched population control individuals and identified LONP1 as a risk gene contributing to CDH through both de novo and ultra-rare inherited largely heterozygous variants clustered in the core of the domains and segregating with CDH in affected familial individuals. Approximately 3% of our CDH cohort who are heterozygous with ultra-rare predicted damaging variants in LONP1 have a range of clinical phenotypes, including other anomalies in some individuals and higher mortality and requirement for extracorporeal membrane oxygenation. Mice with lung epithelium-specific deletion of Lonp1 die immediately after birth, most likely because of the observed severe reduction of lung growth, a known contributor to the high mortality in humans. Our findings of both de novo and inherited rare variants in the same gene may have implications in the design and analysis for other genetic studies of congenital anomalies.

Abstract Background Mechanical ventilation causes diaphragmatic atrophy and reduces diaphragmatic efficiency. Patients with diaphragmatic dysfunction have longer mechanical ventilation durations and intensive care unit stay. There is currently a scarcity of data on the effect of different modes of mechanical ventilation on diaphragmatic function and ultrasound-guided assessment of diaphragmatic efficiency. Results Sixty mechanically ventilated patients were randomly divided into four equal groups (15 each): patients were ventilated using either assist control pressure-controlled mode (group A), synchronized intermittent mandatory ventilation pressure-controlled mode (group S), bi-level-positive airway pressure mode (group B) or pressure support ventilation mode (group P). The primary outcome was to assess the diaphragmatic excursion, while the secondary outcomes were to assess the diaphragmatic thickness fraction and the duration of the ICU stay. Patients in the P group had the highest diaphragmatic excursion indicating better diaphragmatic function. Conclusions When compared to other pressure-targeted ventilation modes, the pressure support ventilation mode may have the least risk of diaphragmatic dysfunction as preserves diaphragmatic structure and strength. Trial registration The clinical trial was retrospectively registered at http://www.pactr.org PACTR202112653971335.

Gastric volvulus (GV) is a rare but lethal condition, mostly presenting secondary to eventration of the diaphragm, with a common underlying pathology: laxity or absence of intraperitoneal ligaments. Here, we present a similar case in a 2-year-old child associated with a wandering spleen (WS), complicated by a splenic volvulus (SV) and eventration of the small and large intestines up till the splenic flexure. Understanding the importance of timely detection and invasive intervention is integral in such cases and more research is needed to understand the pathophysiology, clinical management, and long-term effects of this unusual mix.

Background: To predict whether the left pulmonary artery (LPA) to the main pulmonary artery (MPA) ratio measured by echocardiography in left congenital diaphragmatic hernia (CDH) was related to death or need for extracorporeal membrane oxygenation (ECMO). Methods: This retrospective study analyzed neonates with left CDH born between 2018 and 2022 in a single tertiary medical institution. Echocardiography was performed immediately after birth. The diameter of the LPA was measured at the bifurcation, and the diameter of the MPA was measured at the maximal dimension during the systolic phase. The Nakata index, McGoon ratio, and ejection fraction (EF) were analyzed and compared with the LPA: MPA ratio as predictive values. Results: Seventy-two neonates with left CDH were included, 19 (26.4%) died or needed ECMO, and 53 (73.6%) survived without ECMO. The lower observed/expected lung-to-head ratio, lower EF, lower LPA: MPA ratio, lower RPA: MPA ratio, lower Nakata index, and lower McGoon ratio were associated with death or need for ECMO. By multivariate analysis, lower LPA: MPA ratio, RPA: MPA ratio, and Nakata index were independent postnatal risk factors for death or need for ECMO. Among the measurements, the LPA: MPA ratio had the highest area under the curve (0.957) with a sensitivity of 84.2% and specificity of 96.3% at a cut-off value of 31.2%. Conclusion: In patients with left CDH, the LPA: MPA ratio measured by echocardiography could be used as an independent postnatal predictor of death or need for ECMO. [ABSTRACT FROM AUTHOR]

ObjectivesCongenital diaphragmatic hernia (CDH) can cause a significant mass effect in the fetal thorax, displacing the heart into the opposite hemithorax. In left-sided CDH (L-CDH), this is associated with smaller left-sided cardiac structures and reduced left-ventricular cardiac output (LVCO). The effect of these physiologic changes on cerebral blood flow is not well understood. We sought to describe the middle cerebral artery (MCA) pulsatility index (PI), a measure of cerebrovascular impedance, in fetuses with L-CDH and those with right-sided CDH (R-CDH) compared with unaffected fetuses, and the relationship between MCA-PI and LVCO. We hypothesized that MCA-PI would be lower in fetuses with L-CDH and similar in those with R-CDH compared to controls, and that MCA-PI would be correlated with LVCO.MethodsWe identified all fetuses with CDH evaluated at The University of California San Francisco, San Francisco, CA, USA from 2011 to 2018. Fetal echocardiograms and ultrasound scans were reviewed. Umbilical artery and MCA Doppler examinations were assessed to calculate pulsatility indices. Ventricular outputs were calculated using Doppler-derived stroke volume and fetal heart rate. Lung-to-head ratio (LHR), estimated fetal weight, biparietal diameter (BPD) and head circumference (HC) were obtained from fetal sonograms. Measurements in fetuses with CDH, according to the side of the defect, were compared with those in unaffected, gestational age-matched controls. A subset of CDH survivors had available data on neurodevelopmental outcome, as assessed using the Bayley Scales of Infant Development, 3rd edition.ResultsA total of 64 fetuses with CDH (L-CDH, n = 53; R-CDH, n = 11) comprised the study groups, with 27 unaffected fetuses serving as controls. Mean gestational age at evaluation was similar between the three groups. Compared to controls, fetuses with L-CDH had significantly lower LVCO expressed as a percentage of combined cardiac output (CCO) (32%; 95% CI, 29-35% vs 38%; 95% CI, 33-42%; P = 0.04) and lower MCA-PI Z-score (-1.3; 95% CI, -1.7 to -1.0 vs 0.08; 95% CI, -0.5 to 0.6; P

The aim of this study was to analyze the exhaled volatile organic compounds (VOCs) profile, airway microbiome, lung function and exercise performance in congenital diaphragmatic hernia (CDH) patients compared to healthy age and sex-matched controls. A total of nine patients (median age 9 years, range 6-13 years) treated for CDH were included. Exhaled VOCs were measured by GC-MS. Airway microbiome was determined from deep induced sputum by 16S rRNA gene sequencing. Patients underwent conventional spirometry and exhausting bicycle spiroergometry. The exhaled VOC profile showed significantly higher levels of cyclohexane and significantly lower levels of acetone and 2-methylbutane in CDH patients. Microbiome analysis revealed no significant differences for alpha-diversity, beta-diversity and LefSe analysis. CDH patients had significantly lower relative abundances of Pasteurellales and Pasteurellaceae. CDH patients exhibited a significantly reduced Tiffeneau Index. Spiroergometry showed no significant differences. This is the first study to report the VOCs profile and airway microbiome in patients with CDH. Elevations of cyclohexane observed in the CDH group have also been reported in cases of lung cancer and pneumonia. CDH patients had no signs of impaired physical performance capacity, fueling controversial reports in the literature.

Objective To explore the clinical outcomes and prognostic factors associated with infants of congenital diaphragmatic hernia (CDH) under multidisciplinary treatments. Methods The relevant clinical data were collected from 103 cases of prenatally diagnosed CDH treated from January 2016 to Augnst 2022. Based upon whether or not fulfilling the criteria for using extracorporeal membrane oxygenation ( ECMO) within 24h post-birth, they were assigned into two groups of ECMO-indicated ( n = 39) and non-ECMO-indicated ( n = 64). Clinical outcomes, echocardiographic findings and independent risk factors were examined for mortality in ECMO-indicated group. Results The overall discharge mortality rate was 29. 1 % ( 95% CI: 20. 6% - 38. 9% ). And mortality rate in ECMO-indicated group was higher than that in non-indicated group [ 53. 9% ( 95% CI :37. 2%-69. 9%) vs. 14. 1 % ( 95% C/: 6. 6%- 25%)]. The median duration of invasive ventilator use in survivors was 336. 5 ( 160. 5, 578. 5) hours with a median hospital stay of 37. 5 ( 22. 8, 51. 3) days. In contrast, 177. O( 121. 0 - 311. 0) hours and 25 ( 19,34) days in non-indicated group respectively. Proportion of right-sided diaphragmatic hernia, occurrence of hepatic hernia and extent of diaphragmatic defect were higher in ECMO-indicated group ( P < 0. 05). Early pulmonary hypertension of ECMO-indicated group was more severe (P <0.01) with higher incidences of right heart enlargement (69. 7% vs. 27. 3%, P <0.01) and left ventricular dysfunction ( 18. 2% vs. 0, P < 0. 0l). Multivariate regression analysis revealed that for ECMO-indicated group, a diagnostic gestational age of 25 weeks, PaCO2 and oxygenation index ( OI) are independent morality risk factors ( P < 0. 05). Conclusion Despite non-using ECMO, our center achieved a mortality rate comparable to that of international high-volume treatment centers for high-risk CDH patients through strengthening an integrated management model before, during and after childbirth. ECMO-indicated CDH patients have more severe pulmonary arterial hypertension and a higher incidence of heart dysfunction. In addition, gestational age at diagnosis < 25 weeks, PCO2 and OI were independent risk factors for mortality in this cohort of patients. [ABSTRACT FROM AUTHOR]

Background: Mechanical ventilation causes diaphragmatic atrophy and reduces diaphragmatic efficiency. Patients with diaphragmatic dysfunction have longer mechanical ventilation durations and intensive care unit stay. There is currently a scarcity of data on the effect of different modes of mechanical ventilation on diaphragmatic function and ultrasound-guided assessment of diaphragmatic efficiency. Results: Sixty mechanically ventilated patients were randomly divided into four equal groups (15 each): patients were ventilated using either assist control pressure-controlled mode (group A), synchronized intermittent mandatory ventilation pressure-controlled mode (group S), bi-level-positive airway pressure mode (group B) or pressure support ventilation mode (group P). The primary outcome was to assess the diaphragmatic excursion, while the secondary outcomes were to assess the diaphragmatic thickness fraction and the duration of the ICU stay. Patients in the P group had the highest diaphragmatic excursion indicating better diaphragmatic function. Conclusions: When compared to other pressure-targeted ventilation modes, the pressure support ventilation mode may have the least risk of diaphragmatic dysfunction as preserves diaphragmatic structure and strength. Trial registration: The clinical trial was retrospectively registered at http://www.pactr.org PACTR202112653971335. [ABSTRACT FROM AUTHOR]

Objective Our systematic review aims to compare recurrence rates and complications of biological versus synthetic patches for the repair of congenital diaphragmatic herniae. Methods Studies from January 1, 1980 to April 25, 2020, with patients under the age of 16 years and with a minimum 6-month follow-up, were included from MEDLINE, Embase, and Cochrane databases. Funnel plots for recurrence rates were constructed for biological and synthetic patches. Subgroup analysis was performed for recurrence rate at the 1-year time-point and data were gathered on individual adverse events from relevant studies. Results A total of 47 studies with 986 patients (226 biological, 760 synthetic) were included. Funnel plot analysis determined overall recurrence rates of 16.7% for synthetic and 30.3% for biological patches. Subgroup analysis of 493 and 146 patients with synthetic and biological patches, respectively, showed recurrence rates of 9.9 and 26%, respectively. The most commonly used patch types—PTFE (polytetrafluoroethylene) and SIS (small intestinal submucosa)—had 11.5 and 33.3% recurrence, respectively. Adhesive bowel obstruction rates ranged from 4 to 29% in studies that systematically reported it for synthetic, and 7 to 35% for biological patches. Gastroesophageal reflux rates ranged from 25 to 48% in studies that systematically reported it for synthetic, and 21 to 42% for biological patches. Pectus deformity rates were reported as high as 80% for synthetic patches. Conclusion Biological patches appear to have higher recurrence rates than synthetic patches, while skeletal deformities are associated more commonly with synthetic patches. Results of biological patches are mainly using SIS and this may overestimate complications of current superior biological patches. [ABSTRACT FROM AUTHOR]

BACKGROUND: In refractory respiratory failure, extracorporeal membrane oxygenation (ECMO) is a rescue therapy to prevent ventilator-induced lung injury. Optimal ventilator parameters during ECMO remain unknown. Our objective was to describe the association between mortality and ventilator parameters during ECMO for neonatal and pediatric respiratory failure. METHODS: We performed a secondary analysis of the Bleeding and Thrombosis on ECMO dataset. Ventilator parameters included breathing frequency, tidal volume, peak inspiratory pressure, PEEP, dynamic driving pressure, pressure support, mean airway pressure, and FIO2. Parameters were evaluated before cannulation, on the calendar day of ECMO initiation (ECMO day 1), and the day before ECMO separation. RESULTS: Of 237 included subjects analyzed, 64% were neonates, of whom 36% had a congenital diaphragmatic hernia. Of all the subjects, 67% were supported on venoarterial ECMO. Overall in-hospital mortality was 35% (n = 83). The median (interquartile range) PEEP on ECMO day 1 was 8 (5.0-10.0) cm H2O for neonates and 10 (8.0-10.0) cm H2O for pediatric subjects. By multivariable analysis, higher PEEP on ECMO day 1 in neonates was associated with lower odds of in-hospital mortality (odds ratio 0.77, 95% CI 0.62-0.92; P = .01), with a further amplified effect in neonates with congenital diaphragmatic hernia (odds ratio 0.59, 95% CI 0.41-0.86; P = .005). No ventilator type or parameter was associated with mortality in pediatric subjects. CONCLUSIONS: Avoiding low PEEP on ECMO day 1 for neonates on ECMO may be beneficial, particularly those with a congenital diaphragmatic hernia. No additional ventilator parameters were associated with mortality in either neonatal or pediatric subjects. PEEP is a modifiable parameter that may improve neonatal survival during ECMO and requires further investigation. [ABSTRACT FROM AUTHOR]

Although the mortality of infants with congenital diaphragmatic hernia (CDH) has been improving since the late 1990s, this observation has not been paralleled among the CDH cohort receiving extracorporeal membrane oxygenation (ECMO). We sought to elucidate why the mortality rate in the CDH-ECMO population has remained at approximately 50% despite consistent progress in the field by examining the baseline risk profile/characteristics of neonates with CDH before ECMO (pre-ECMO). Neonates with a diagnosis of CDH were identified in the Extracorporeal Life Support Organization (ELSO) Registry from 1992 to 2015. Individual pre-ECMO risk score (RS) for mortality was categorized to pre-ECMO risk-stratified cohorts. Temporal trends based on individual-level mortality by risk cohorts were assessed by logistic regression. We identified 6,696 neonates with CDH. The mortality rates during this time period were approximately 50%. The average baseline pre-ECMO RS increased during this period: mean increase of 0.35 (95% confidence interval [CI]: 0.324-0.380). In the low-risk cohort, the likelihood of mortality increased over time: each 5 year change was associated with a 7.3% increased likelihood of mortality (odds ratio [OR]: 1.0726; 95% CI: 1.0060-1.1437). For the moderate-risk cohort, the likelihood of mortality decreased by 7.05% (OR: 0.9295; 95% CI: 0.8822-0.9793). There was no change in the odds of mortality for the high-risk cohort (OR: 0.9650; 95% CI: 0.8915-1.0446). Although the overall mortality rate remained approximately constant over time, the individual likelihood of death has declined over time in the moderate-risk cohort, increased in the low-risk cohort, and remained unchanged in the high-risk cohort.

Abstract Background Most studies examining survival of neonates with congenital diaphragmatic hernia (CDH) are in high-income countries. We aimed to describe the management, survival to hospital discharge rate, and factors associated with survival of neonates with unilateral CDH in a middle-income country. Methods We retrospectively reviewed the medical notes of neonates with unilateral CDH admitted to a pediatric intensive care unit (PICU) in a tertiary referral center over a 15-year period, from 2003–2017. We described the newborns’ respiratory care pathways and then compared baseline demographic, hemodynamic, and respiratory indicators between survivors and non-survivors. The primary outcome measure was survival to hospital discharge. Results Altogether, 120 neonates were included with 43.3% (52/120) diagnosed antenatally. Stabilization occurred in 38.3% (46/120) with conventional ventilation, 13.3% (16/120) with high-frequency intermittent positive-pressure ventilation, and 22.5% (27/120) with high frequency oscillatory ventilation. Surgical repair was possible in 75.0% (90/120). The overall 30-day survival was 70.8% (85/120) and survival to hospital discharge was 66.7% (80/120). Survival to hospital discharge tended to improve over time (p > 0.05), from 56.0% to 69.5% before and after, respectively, a service reorganization. For those neonates who could be stabilized and operated on, 90.9% (80/88) survived to hospital discharge. The commonest post-operative complication was infection, occurring in 43.3%. The median survivor length of stay was 32.5 (interquartile range 18.8–58.0) days. Multiple logistic regression modelling showed vaginal delivery (odds ratio [OR] = 4.8; 95% confidence interval [CI] [1.1–21.67]; p = 0.041), Apgar score $$\ge$$ ≥ 7 at 5 min (OR = 6.7; 95% CI [1.2–36.3]; p = 0.028), and fraction of inspired oxygen (FiO2)

Many complications are known to occur in association with a diaphragmatic hernia. Acute pancreatitis occurring in this situation is very rare. In this paper, we report a case and describe the radiographic features of this complication. We report an unusual case of acute pancreatitis complicating a neglected post-traumatic diaphragmatic hernia in a 30-year-old male. This patient had a history of an abdominal trauma 5 years ago, and arrived at the emergency room with epigastria and left chest pain and vomiting. Serum lipase was elevated. Acute pancreatitis could be considered as an exceptional complication of diaphragmatic hernia. It is a serious diagnostic and therapeutic challenge. The fundamental roles of CT are to determine the diaphragmatic defect, the abdominal content involving, the Balthazar scoring of pancreatitis, and the presence of local complications. Even if a conservative approach is preferred when facing a diagnosis of pancreatitis, timing of surgery should be carefully considered.

Anxiety and stress plague populations worldwide. Voluntary regulated breathing practices offer a tool to address this epidemic. We examined peer-reviewed published literature to understand effective approaches to and implementation of these practices. PubMed and ScienceDirect were searched to identify clinical trials evaluating isolated breathing-based interventions with psychometric stress/anxiety outcomes. Two independent reviewers conducted all screening and data extraction. Of 2904 unique articles, 731 abstracts, and 181 full texts screened, 58 met the inclusion criteria. Fifty-four of the studies’ 72 interventions were effective. Components of effective and ineffective interventions were evaluated to develop a conceptual framework of factors associated with stress/anxiety reduction effectiveness. Effective breath practices avoided fast-only breath paces and sessions

PURPOSE: Muscle atrophy and diaphragm dysfunction are common with prolonged mechanical ventilation (PMV). Electrical stimulation on peripheral muscles has been shown to be beneficial in the improvement of muscle function. This study examined the effects of transcutaneous electrical diaphragmatic stimulation (TEDS) on respiratory muscle strength and weaning outcomes in patients with PMV. METHODS: Participants on ventilation for ≥21 days were randomly assigned to TEDS (n = 29) and control (n = 30) groups. The TEDS group received muscle electrical stimulation for 30 min/session/day throughout the intervention. Pulmonary function parameters (tidal volume, respiratory rate, and rapid shallow breathing index), and respiratory muscle strength (Pimax, Pemax) were assessed. The hospitalization outcome, including weaning rate and length of stay, was followed up until discharge. RESULTS: After TEDS, there was a significant increase in Pemax (10 [8–20] vs. 20 [10–22] cmH2O, P = 0.034) in the intervention group. At the end of the study, the improvement of minute volume in the TEDS group (0.64 (−0.67) was significantly higher than the control group (−0.64 (−2.5–0.78) (P = 0.008). In the control group, there was no significant difference between pre- and post-measurement of weaning parameters. There was a significant difference between groups in the weaning rate, with a higher rate in the TEDS group (90%) when compared with that in the control group (66.7%) (P =0.021). CONCLUSION: TEDS was significantly associated with increased respiratory muscle strength in patients with PMV. TEDS may be useful to facilitate weaning in this population.

Background: A diaphragmatic hernia is a defect or hole in the diaphragm through which abdominal contents can enter the chest cavity. Diaphragmatic hernias may be congenital (Morgagni hernia, Bochdalek hernia), a hiatal hernia, or acquired (iatrogenic and traumatic). Bochdalek's hernia typically occurs on the left side and rarely occurs in adults. Less than 100 cases of left Bochdalek's hernia in adults have been described in the literature. Most of them are asymptomatic. Case report: We report a complicated left Bochdalek hernia in a 43-year-old adult male who is a smoker. He came to the pulmonary clinic with symptoms and signs of pneumonia of the left lower lobe with persistent dyspeptic symptoms. Chest radiography revealed evidence of a left diaphragmatic hernia, which was confirmed by computed tomography of the chest and abdomen, and subsequently treated by left diaphragmatic repair via limited left thoracotomy. Conclusion: We report a rare case of a left Bochdalek hernia in an adult who underwent an appropriate left thoracotomy. Bochdalek hernias in adults are rare and usually asymptomatic, but when they become symptomatic, surgical intervention is required to avoid complications. BH should be considered in the differential diagnosis when radiographs suggest pneumothorax and should be treated early to avoid complications.

PurposePrevious studies comparing extracorporeal membrane oxygenation (ECMO) modality for congenital diaphragmatic hernia (CDH) have not accounted for confounding by indication. We therefore hypothesized that using a propensity score (PS) approach to account for selection bias may identify outcome differences based on ECMO modality for infants with CDH.MethodsWe utilized ELSO Registry data (2000-2016). Patients with CDH were divided to either venoarterial (VA) or venovenous (VV) ECMO. Patients were matched by PS to control for nonrandom treatment assignment. Subgroup analyses were conducted based on timing of CDH repair relative to ECMO. Primary analysis was the "intent-to-treat" cohort based on the initial ECMO mode. Mortality was the primary outcome, and severe neurologic injury (SNI) was a secondary outcome.ResultsPS matching (3:1) identified 3304 infants (VA = 2470, VV = 834). In the main group, mortality was not different between VA and VV ECMO (OR = 1.01, 95% CI: 0.86-1.18) and there was no difference in SNI between VA and VV (OR = 0.80; 95% CI: 0.63-1.01). For the pre-ECMO CDH repair subgroup, 175 VA cases were matched to 70 VV. In these neonates, mortality was higher for VV compared to VA (OR = 2.10, 95% CI: 1.19-3.69), without any difference in SNI (OR = 1.48; 95% CI: 0.59-3.71). For the subgroup that did not have pre-ECMO CDH repair, 2030 VA cases were matched to 683 VV cases. In this subgroup, VV was associated with 27% lower risk of SNI relative to VA (OR = 0.73, 95% CI: 0.56-0.95) without any difference in mortality (OR = 0.94, 95% CI: 0.79-1.11).ConclusionThis study revalidates that ECMO mode does not significantly affect mortality or SNI in infants with CDH. In the subset of infants who require pre-ECMO CDH repair, VA favors survival, whereas, in the subgroup of infants that did not have pre-ECMO CDH repair, VV favors lower rates of SNI. We conclude that neither mode appears consistently superior across all situations, and clinical judgment should remain a multifactorial decision.Level of evidenceLevel III.

The purpose of our study was to develop and validate extracorporeal membrane oxygenation (ECMO)-specific mortality risk models for congenital diaphragmatic hernia (CDH). We utilized the data from the Extracorporeal Life Support Organization Registry (2000-2015). Prediction models were developed using multivariable logistic regression. We identified 4,374 neonates with CDH with an overall mortality of 52%. Predictive discrimination (C statistic) for pre-ECMO mortality model was C = 0.65 (95% confidence interval, 0.62-0.68). Within the highest risk group, based on the pre-ECMO risk score, mortality was 87% and 75% in the training and validation data sets, respectively. The pre-ECMO risk score included pre-ECMO ventilator settings, pH, prior diaphragmatic hernia repair, critical congenital heart disease, perinatal infection, and demographics. For the on-ECMO model, mortality prediction improved substantially: C = 0.73 (95% confidence interval, 0.71-0.76) with the addition of on-ECMO-associated complications. Within the highest risk group, defined by the on-ECMO risk score, mortality was 90% and 86% in the training and validation data sets, respectively. Mortality among neonates with CDH needing ECMO can be reliably predicted with validated clinical variables identified in this study. ECMO-specific mortality prediction tools can allow risk stratification to be used in research and quality improvement efforts, as well as with caution for individual case management.

ObjectiveTo examine the external validity of a well-known congenital diaphragmatic hernia (CDH) clinical prediction model using a population-based cohort.Study designNewborns with CDH born in California between 2007 and 2012 were extracted from the Vital Statistics and Patient Discharge Data Linked Files. The total CDH risk score was calculated according to the Congenital Diaphragmatic Hernia Study Group (CDHSG) model using 5 independent predictors: birth weight, 5-minute Apgar, pulmonary hypertension, major cardiac defects, and chromosomal anomalies. CDHSG model performance on our cohort was validated for discrimination and calibration.ResultsA total of 705 newborns with CDH were extracted from 3 213 822 live births. Newborns with CDH were delivered in 150 different hospitals, whereas only 28 hospitals performed CDH repairs (1-85 repairs per hospital). The observed mortality for low-, intermediate-, and high-risk groups were 7.7%, 34.3%, and 54.7%, and predicted mortality for these groups were 4.0%, 23.2%, and 58.5%. The CDHSG model performed well within our cohort with a c-statistic of 0.741 and good calibration.ConclusionsWe successfully validated the CDHSG prediction model using an external population-based cohort of newborns with CDH in California. This cohort may be used to investigate hospital volume-outcome relationships and guide policy development.

Congenital diaphragmatic hernia (CDH) results from incomplete formation of the diaphragm leading to herniation of abdominal organs into the thoracic cavity. CDH is associated with pulmonary hypoplasia, congenital heart disease, and pulmonary hypertension. Genetically, it is associated with aneuploidies, chromosomal copy-number variants, and single gene mutations. CDH is the most expensive noncardiac congenital defect. Management frequently requires implementation of extracorporeal membrane oxygenation (ECMO), which increases management expenditures 2.4-3.5-fold. The cost of management of CDH has been estimated to exceed $250 million per year. Despite in-hospital survival of 80%-90%, current management is imperfect, as a great proportion of surviving children have long-term functional deficits. We report the case of a premature infant prenatally diagnosed with CDH and congenital heart disease, who had a protracted and complicated course in the intensive care unit with multiple surgical interventions, including postcardiac surgery ECMO, gastrostomy tube placement with Nissen fundoplication, tracheostomy for respiratory failure, recurrent infections, and developmental delay. Rapid whole-genome sequencing (rWGS) identified a de novo, likely pathogenic, c.3096_ 3100delCAAAG (p.Lys1033Argfs*32) variant in ARID1B, providing a diagnosis of Coffin-Siris syndrome. Her parents elected palliative care and she died later that day.

PURPOSE:With the exception of neonatal respiratory failure, most centers are now using centrifugal over roller-type pumps for the delivery of extracorporeal membrane oxygenation (ECMO). Evidence supporting the use of centrifugal pumps specifically in infants with congenital diaphragmatic hernia (CDH) remains lacking. We hypothesized that the use of centrifugal pumps in infants with CDH would not affect mortality or rates of severe neurologic injury (SNI). METHODS:Infants with CDH were identified within the ELSO registry (2000-2016). Patients were then divided into those undergoing ECMO with rollertype pumps or centrifugal pumps. Patients were matched based on propensity score (PS) for the ECMO pump type based on pre-ECMO covariates. This was done for all infants and separately for each ECMO mode, venovenous (VV) and venoarterial (VA) ECMO. RESULTS:We identified 4,367 infants who were treated with either roller or centrifugal pumps from 2000-2016. There was no difference in mortality or SNI between the two pump types in any of the groups (all infants, VA-ECMO infants, VV-ECMO infants). However, there was at least a six-fold increase in the odds of hemolysis for centrifugal pumps in all groups: all infants (odds ratio [OR] 6.99, p

A critical event in the adaptation to extrauterine life is relaxation of the pulmonary vasculature at birth, allowing for a rapid increase in pulmonary blood flow that is essential for efficient gas exchange. Failure of this transition leads to pulmonary hypertension (PH), a major cause of newborn mortality associated with preterm birth, infection, hypoxia, and malformations including congenital diaphragmatic hernia (CDH). While individual vasoconstrictor and dilator genes have been identified, the coordination of their expression is not well understood. Here, we found that lung mesenchyme-specific deletion of CDH-implicated genes encoding pre-B cell leukemia transcription factors (Pbx) led to lethal PH in mice shortly after birth. Loss of Pbx genes resulted in the misexpression of both vasoconstrictors and vasodilators in multiple pathways that converge to increase phosphorylation of myosin in vascular smooth muscle (VSM) cells, causing persistent constriction. While targeting endothelin and angiotensin, which are upstream regulators that promote VSM contraction, was not effective, treatment with the Rho-kinase inhibitor Y-27632 reduced vessel constriction and PH in Pbx-mutant mice. These results demonstrate a lung-intrinsic, herniation-independent cause of PH in CDH. More broadly, our findings indicate that neonatal PH can result from perturbation of multiple pathways and suggest that targeting the downstream common effectors may be a more effective treatment for neonatal PH.

Background/purposeRestrictions for ECMO in neonates include birth weight less than 2kg (BW

Fetal surgery corrects severe congenital anomalies in utero to prevent their severe consequences on fetal development. The significant risk of open fetal operations to the pregnant mother has driven innovation toward minimally invasive procedures that decrease the risks inherent to hysterotomy. In this article, we discuss the basic principles of minimally invasive fetal surgery, the general history of its development, specific conditions and procedures used to treat them, and the future of the field.

Traumatic diaphragmatic hernia is defined as the passage of abdominal contents into the thoracic cavity through a defect in the diaphragm caused by trauma. The diagnosis of traumatic diaphragmatic hernia is difficult, it can often go unnoticed, due to the seriousness of the accompanying injuries. The keys to diagnosis are a high degree of suspicion and knowledge of the various signs on computed tomography. Once the diaphragmatic rupture is diagnosed, it is surgically repaired in order to avoid complications. The case of an 88-year-old male patient with a history of having suffered closed thoracoabdominal trauma 35 years earlier, who presented with a clinical picture of intestinal obstruction is presented. This case is published because, in addition to being a rare entity, knowledge of this disease is important, in order to assess it within the diagnostic possibilities, in those patients who suffer from symptoms related to its complications [ABSTRACT FROM AUTHOR]

Background: In stroke patients with tracheotomy, reduced lung function heightens pulmonary infection risk. Body position can affect lung function; however, its impact in stroke patients with tracheostomy remains unclear., Objective: To investigate the influence of five body positions on pulmonary function in stroke patients with tracheotomy., Methods: Pulmonary function was assessed in five body positions (supine, supine 30°, supine 60°, sitting, and prone) in 47 stroke patients who underwent tracheotomy. Diaphragmatic excursion during quiet breathing (DE Q ), diaphragmatic thickening fraction during quiet breathing (DTF Q ), and diaphragmatic excursion during coughing (DE C ) were measured using ultrasound. Peak cough flow (PCF) was measured using an electronic peak flow meter., Results: Different positions had a significant impact on DE Q , DE C , and PCF in stroke patients with tracheotomy, although not on DTF Q . DE Q showed no significant differences between supine 60°, sitting, and prone positions. Both DE C and PCF reached their maximum values in the sitting position. In the sub-group analysis, DE Q in females did not show significant differences across different positions. Both males and females exhibited significantly higher PCF in the sitting compared to supine position. The lung function of obese patients was significantly better in the sitting than in the supine and supine 30° position. Regardless of the patient's level of consciousness and whether the brainstem was injured, lung function in the sitting position was significantly higher than in the supine position., Conclusions: Body posture influences lung function in stroke patients with tracheotomy. Patients should adopt a sitting position to enhance pulmonary function.

Background: Most studies examining survival of neonates with congenital diaphragmatic hernia (CDH) are in high-income countries. We aimed to describe the management, survival to hospital discharge rate, and factors associated with survival of neonates with unilateral CDH in a middle-income country.Methods: We retrospectively reviewed the medical notes of neonates with unilateral CDH admitted to a pediatric intensive care unit (PICU) in a tertiary referral center over a 15-year period, from 2003-2017. We described the newborns' respiratory care pathways and then compared baseline demographic, hemodynamic, and respiratory indicators between survivors and non-survivors. The primary outcome measure was survival to hospital discharge.Results: Altogether, 120 neonates were included with 43.3% (52/120) diagnosed antenatally. Stabilization occurred in 38.3% (46/120) with conventional ventilation, 13.3% (16/120) with high-frequency intermittent positive-pressure ventilation, and 22.5% (27/120) with high frequency oscillatory ventilation. Surgical repair was possible in 75.0% (90/120). The overall 30-day survival was 70.8% (85/120) and survival to hospital discharge was 66.7% (80/120). Survival to hospital discharge tended to improve over time (p > 0.05), from 56.0% to 69.5% before and after, respectively, a service reorganization. For those neonates who could be stabilized and operated on, 90.9% (80/88) survived to hospital discharge. The commonest post-operative complication was infection, occurring in 43.3%. The median survivor length of stay was 32.5 (interquartile range 18.8-58.0) days. Multiple logistic regression modelling showed vaginal delivery (odds ratio [OR] = 4.8; 95% confidence interval [CI] [1.1-21.67]; p = 0.041), Apgar score [Formula: see text] 7 at 5 min (OR = 6.7; 95% CI [1.2-36.3]; p = 0.028), and fraction of inspired oxygen (FiO2) < 50% at 24 h (OR = 89.6; 95% CI [10.6-758.6]; p < 0.001) were significantly associated with improved survival to hospital discharge.Conclusions: We report a survival to hospital discharge rate of 66.7%. Survival tended to improve over time, reflecting a greater critical volume of cases and multi-disciplinary care with early involvement of the respiratory team resulting in improved transitioning from PICU. Vaginal delivery, Apgar score [Formula: see text] 7 at 5 min, and FiO2 < 50% at 24 h increased the likelihood of survival to hospital discharge. [ABSTRACT FROM AUTHOR]

Bochdalek hernia is a very rare congenital diaphragmatic hernia among adults. Due to the scarcity of the condition, it is frequently misdiagnosed, particularly in non-traumatic patients in . the Emergency Department. Incorrect diagnosis has resulted in ineffective interventions, some of which have resulted in death. We report such a case presented to our department. [ABSTRACT FROM AUTHOR]

BackgroundThere is no published data regarding the relationship between hospital volume and outcomes in patients undergoing laparoscopic diaphragmatic hernia repair. We hypothesize that hospitals performing high case volume have improved outcomes compared to low-volume hospitals.Materials and methodsWe reviewed the National Inpatient Sample (NIS) database between 2008 and 2012 for adults with the diagnosis of diaphragmatic hernia who underwent elective laparoscopic repair of diaphragmatic Hernia and/or Nissen fundoplication. Pediatric, emergent, and open cases were excluded. Main outcome measures included logistic regression analysis of factors predictive of in-hospital mortality and outcomes according to annual hospital case volume.ResultsA total of 31,228 laparoscopic diaphragmatic hernia operations were analyzed. The overall in-hospital mortality was 0.14%. Risk factors for higher in-hospital mortality included renal failure (AOR: 6.26; 95% CI: 2.48-15.78; p 60 years (AOR: 5.06; 95% CI: 2.38-10.76; p

Background: Mechanical ventilation (MV) causes diaphragmatic atrophy and reduces diaphragmatic efficiency. Patients with diaphragmatic dysfunction (DD) have longer MV durations and intensive care unit (ICU) stay. There is currently a scarcity of data on the effect of different modes of MV on diaphragmatic function and ultrasound-guided assessment of diaphragmatic efficiency. Methodology: Sixty mechanically ventilated patients were randomly divided into four equal groups (15 each), patients were ventilated using either Assist Control Pressure Controlled mode (ACPC group)(Group A), Synchronized Intermittent Mandatory Ventilation Pressure Controlled mode (SIMV)(Group S), Bi-level Positive Airway Pressure mode (BiPAP)(Group B), or Pressure Support Ventilation mode (PSV)(Group P). The primary outcomes were diaphragmatic motion & structure in terms of Diaphragmatic Excursion (DE) & Diaphragmatic Thickness Fraction (DTF) respectively. The duration of the ICU stay was the secondary outcome. Results: The PSV group had the highest DE indicating better diaphragmatic function. In addition, MV for longer durations led to diaphragmatic thinning and decreased DTF resulting in DD. Conclusion: Among the various modes of ventilation employed in the study, PSV was found to be the mode with the lowest risk ofDD. Trial Registry: PACTR202112653971335. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to identify prognostic factors based on treatment outcomes for congenital diaphragmatic hernia (CDH) at a single-center and to identify factors that may improve these outcomes. Methods: Thirty-five neonates diagnosed with CDH between January 2011 and December 2021 were retrospectively analyzed. Pre- and postnatal factors were correlated and analyzed with postnatal clinical outcomes to determine the prognostic factors. Highest oxygenation index (OI) within 24 hours of birth was also calculated. Treatment strategy and outcome analysis of published literatures were also performed. Results: Overall survival rate of this cohort was 60%. Four patients were unable to undergo anesthesia and/or surgery. Three patients who commenced extracorporeal membrane oxygenation (ECMO) post-surgery were non-survivors. Compared to the survivor group, the non-survivor group had a significantly higher occurrence of pneumothorax on the first day, need for high-frequency ventilator and inhaled nitric oxide use, and high OI within the first 24 hours. The non-survivor group showed an early trend towards the surgery timing and a greater number of patch closures. Area under the receiver operating characteristic curve was 0.878 with a sensitivity of 76.2% and specificity of 92.9% at an OI cut off value of 7.75. Conclusion: OI within 24 hours is a valuable predictor of survival. It is expected that the application of ECMO based on OI monitoring may help improve the opportunity for surgical repair, as well as the prognosis of CDH patients. [ABSTRACT FROM AUTHOR]

Objective To summarize the clinical features of neonatal congenital diaphragmatic hernia ( CDH) treated at a single center over the last 6 years and explore the related factors of poor prognosis. Methods From April 2014 to July 2020, clinical data were retrospectively reviewed for 73 CDH children. According to the prognosis, they were divided into two groups of good prognosis ( 54 survivors) and poor prognosis ( 19 deaths) . The clinical data of children in two groups were collected, including gender, whether or not gestational week of birth < 37 weeks, birth weight < 2. 5 kg, gestational age of diagnosis ::::; 25 weeks, surgical approach, operative duration < 24h after birth, operative duration < 180 min, liver position, hernia position, gestational week of birth and operative duration. Multivariate Logistic regression was employed for examining the related factors of poor prognosis. Results There were 46 boys and 27 girls. The involved side was left ( n = 58) and right ( n = 15). Sixty-three cases were detected through a prenatal diagnosis and 10 cases confirmed by chest radiography for postnatal respiratory distress. Fifty-four children ( 54/ 73, 73. 9%) survived and 19 ( 19/ 73, 26. 1 % ) died. Fifty-four children were discharged from hospital after recovery and their parents were instructed to exercise lung function. During an average follow-up period of 2. 78 years, outpatient or telephone follow-ups were performed. The survival rates of 90 d, 112/ 5-year after discharge were 100%. Multivariate Logistic regression indicated that low birth weight, operation within 24h after birth, open operation and diagnosis of gestational age ~25 weeks were the related factors for poor prognosis ( P < 0. 05). Conclusion Low birth weight, diagnosis of gestational age 25 weeks and operation timing <24 h may be risk factors for poor prognosis of CDH. Thoracoscopic repair may be preferred if a surgeon is experienced. [ABSTRACT FROM AUTHOR]

Background: Mechanical ventilation (MV) is required for most cases introduced the intensive care unit (ICU) as a portion of their process of care. However, either MV or the chronic illness can result in diaphragm dysfunction, an incident that may contribute to the incapability of MV separation to be done. Prolonged use of the ventilator significantly increases health-care expenses and subject morbidity and mortality. However, muscle disease symptoms and manifestations are frequently difficult to evaluate in a bedridden state ICU case due to complicating variables. A typical evaluation of diaphragm function lacks, non-invasive, time preservative, easy-to-perform bedside equipment or needs subject involvement. Lately, the utilization of ultrasound (US) has elevated a lot of interest as a simple, non-invasive approach for the assessment of diaphragmatic contractile activity. Objective: This narrative review aimed to briefly describe the common methods of diaphragmatic function assessment using ultrasound techniques. Methods: These databases were searched for articles published in English in 4 databases [PubMed - Egyptian Knowledge Bank - Google scholar-Science direct] and Boolean operators (AND, OR, NOT) had been used such as [Diaphragmatic AND Ultrasound OR Diaphragm function] and in peer-reviewed articles between 1985 and 2021. Conclusion: Diaphragmatic ultrasonography has been widely investigated and is still being explored as a predictor of effective mechanical ventilation weaning. Due to the substantial heterogeneity in research design and population, it remains difficult to draw general generalizations from individual studies. Even worse, terminology such as a failed breathing trial or unsuccessful extubation has not been defined across research, making comparisons of outcome measures unfeasible. [ABSTRACT FROM AUTHOR]

Aim: Although intestinal obstruction following living donor liver transplantation (LDLT) is relatively common, diaphragmatic hernia (DH) as the attributing cause is rarely reported. The study aimed to find out the incidence, clinical presentation, and management of DH after liver transplant in pediatric patients. Materials and Methods: A retrospective review of all cases of pediatric liver transplants was performed. Case sheets, operation records, and investigations including radiology were studied. Results: Out of 79 cases of pediatric liver transplants, two cases of posttransplant DH were identified. The first case is a 2-year-old male child who was transplanted for progressive familial intrahepatic cholestasis, and the second one is a 4-year-old boy who underwent LDLT for hepatitis A-induced acute liver failure. The first child presented abdominal symptoms and the second one with pulmonary symptoms. The DHs were diagnosed at 132 and 70 days, respectively, posttransplant by chest radiographs and computed tomography scan. The defects were located at the posteromedial aspect of the diaphragm in both the cases and were closed by primary closure with mesh reinforcement. Both the children are doing well with no recurrence. Conclusion: High index of clinical suspicion is mandated in pediatric patients after liver transplant and once the diagnosis is confirmed, urgent surgical exploration is mandatory.