A new Light on Lung Disease in Congenital Diaphragmatic Hernia

Congenital diaphragmatic hernia (CDH) is a rare congenital anomaly of the diaphragm with an incidence of approximately 1 per 2500 births. Typically, the abdominal organs will herniate into the chest cavity, with resulting maldevelopment of the alveoli and pulmonary vessels. The defect is usually – reportedly in 84% of the cases – located on the left side of the diaphragm. Right-sided CDH and bilateral CDH, which occur in 14% and 2% of cases, are associated with a worse prognosis. CDH can present as an isolated defect or in combination with other congenital anomalies, such as congenital heart disease or chromosomal anomalies. The condition may be life threatening and key determinants of mortality are the severity of pulmonary hypoplasia and the presence of therapy resistant pulmonary hypertension. Smaller number and generations of airways, thickened alveolar septa, and abnormal architecture of the respiratory acinus characterize pulmonary hypoplasia. Pulmonary hypertension may result from medial hyperplasia and adventitial thickening associated with under- and maldevelopment of the pulmonary vessels. Although survival rates have improved over the years, mortality rates in live-born patients still range from 10-35%, depending on case selection. Moreover, surviving neonates carry a substantial risk of developing secondary morbidity, such as cardiopulmonary, gastro-intestinal and neurological problems

BRCA1/2 testing rates in epithelial ovarian cancer:A focus on the untested patients

Background: Since 2015, Dutch guidelines have recommended BRCA1/2 pathogenic variant testing for all patients with epithelial ovarian cancer. Recently, recommendations shifted from germline testing to the tumor-first approach, in which tumor tissue is tested first, and subsequent germline testing is performed only in those with BRCA1/2 tumor pathogenic variants or a positive family history. Data on testing rates and on characteristics of patients missing out on testing remain scarce.Objective: To evaluate BRCA1/2 testing rates in patients with epithelial ovarian cancer and compare testing rates of germline testing (performed from 2015 until mid-2018) versus tumor-first testing (implemented mid-2018).Methods: A consecutive series of 250 patients diagnosed with epithelial ovarian cancer between 2016 and 2019 was included from the OncoLifeS data-biobank of the University Medical Center Groningen, the Netherlands. Testing rates were analyzed for the overall study population and for germline testing (period I) and tumor-first testing (period II) separately. Characteristics of tested and untested patients were compared and predictors for receiving testing were assessed with multivariable logistic regression.Results: Median age was 67.0 years (IQR 59.0-73.0) and 173 (69.2%) patients were diagnosed with high-grade serous carcinoma. Overall, 201 (80.4%) patients were tested. In period I, 137/171 (80.1%) patients were tested and in period II this was 64/79 (81.0%). Patients with non-high-grade serous carcinoma were significantly less likely to receive BRCA1/2 testing than patients with high-grade serous carcinoma (OR=0.23, 95% CI 0.11 to 0.46, p&lt;0.001).Conclusions: The results show that BRCA1/2 testing rates are suboptimal and suggest that clinicians may not be choosing to test patients with epithelial ovarian cancer with non-high-grade serous ovarian carcinoma, although guidelines recommend BRCA1/2 testing in all patients with epithelial ovarian cancer. Suboptimal testing rates limit optimization of care for patients with epithelial ovarian cancer and counseling of potentially affected relatives.</p

BRCA1/2 testing rates in epithelial ovarian cancer:A focus on the untested patients

Background: Since 2015, Dutch guidelines have recommended BRCA1/2 pathogenic variant testing for all patients with epithelial ovarian cancer. Recently, recommendations shifted from germline testing to the tumor-first approach, in which tumor tissue is tested first, and subsequent germline testing is performed only in those with BRCA1/2 tumor pathogenic variants or a positive family history. Data on testing rates and on characteristics of patients missing out on testing remain scarce.Objective: To evaluate BRCA1/2 testing rates in patients with epithelial ovarian cancer and compare testing rates of germline testing (performed from 2015 until mid-2018) versus tumor-first testing (implemented mid-2018).Methods: A consecutive series of 250 patients diagnosed with epithelial ovarian cancer between 2016 and 2019 was included from the OncoLifeS data-biobank of the University Medical Center Groningen, the Netherlands. Testing rates were analyzed for the overall study population and for germline testing (period I) and tumor-first testing (period II) separately. Characteristics of tested and untested patients were compared and predictors for receiving testing were assessed with multivariable logistic regression.Results: Median age was 67.0 years (IQR 59.0-73.0) and 173 (69.2%) patients were diagnosed with high-grade serous carcinoma. Overall, 201 (80.4%) patients were tested. In period I, 137/171 (80.1%) patients were tested and in period II this was 64/79 (81.0%). Patients with non-high-grade serous carcinoma were significantly less likely to receive BRCA1/2 testing than patients with high-grade serous carcinoma (OR=0.23, 95% CI 0.11 to 0.46, p&lt;0.001).Conclusions: The results show that BRCA1/2 testing rates are suboptimal and suggest that clinicians may not be choosing to test patients with epithelial ovarian cancer with non-high-grade serous ovarian carcinoma, although guidelines recommend BRCA1/2 testing in all patients with epithelial ovarian cancer. Suboptimal testing rates limit optimization of care for patients with epithelial ovarian cancer and counseling of potentially affected relatives.</p

Risk Factors for Chronic Lung Disease and Mortality in Newborns with Congenital Diaphragmatic Hernia

Background: Congenital diaphragmatic hernia (CDH) is associated with a mortality rate of 10-35% in live-born infants. Moreover, CDH survivors have a substantial risk of developing long-term pulmonary sequelae, such as bronchopulmonary dysplasia (BPD). Objectives: This study aims to evaluate risk factors associated with BPD and mortality in neonates with CDH, with particular focus on the initial ventilation mode. Methods: Eligible for inclusion were live-born infants with CDH born from 2001 through 2006 at the centers participating in the CDH Study Group. BPD (defined as oxygen dependency at day 30) and/or mortality by day 30 served as the primary endpoint. Results: A total of 2,078 neonates were included in the analysis. At day 30, 56% of the patients had either died or met the criteria for BPD. In infants who survived until day 30, the prevalence of BPD was 41%. The overall mortality rate was 31%. High-frequency oscillatory ventilation as initial ventilation mode, a right-sided defect, a prenatal diagnosis, a lower Apgar score at 5 min, a cardiac anomaly, a chromosomal anomaly and a lower gestational age were all associated with BPD and/or mortality by day 30. Conclusions: Despite improvements in neonatal care, the rates of BPD and early mortality in newborns with CDH are still considerable. Several important risk factors for a worse outcome are reported in this nonrandomized prospe