Potential Targeted Therapies in Ovarian Cancer.

BACKGROUND: We aimed to identify somatic pathogenic and likely pathogenic mutations using next-generation sequencing (NGS). The mutational findings were held against clinically well-described data to identify potential targeted therapies in Danish patients diagnosed with high-grade serous ovarian cancer (HGSC). METHODS: We characterized the mutational profile of 128 HGSC patients. Clinical data were obtained from the Danish Gynecological Database and tissue samples were collected through the Danish CancerBiobank. DNA was analyzed using NGS. RESULTS: 47 (37%) patients were platinum-sensitive, 32 (25%) partially platinum-sensitive, 35 (27%) platinum-resistant, and three (2%) platinum-refractory, while 11 (9%) patients did not receive chemotherapy. Overall, 27 (21%) had known druggable targets. Twelve (26%) platinum-sensitive patients had druggable targets for PARP inhibitors: one for tyrosine kinase inhibitors and one for immunotherapy treatment. Eight (25%) partially platinum-sensitive patients had druggable targets: seven were eligible for PARP inhibitors and one was potentially eligible for alpesilib and hormone therapy. Seven (20%) platinum-resistant patients had druggable targets: six (86%) were potentially eligible for PARP inhibitors, one for immunotherapy, and one for erdafitinib. CONCLUSIONS: PARP inhibitors are the most frequent potential targeted therapy in HGSC. However, other targeted therapies remain relevant for investigation according to our mutational findings.

Organoids and epithelial ovarian cancer - a future tool for personalized treatment decisions? (Review).

Epithelial ovarian cancer (EOC) is the 5th leading cause of cancer-associated death in females worldwide. Although 80% of cases respond well to initial treatment, >70% develop recurrent disease and become chemoresistant within the first two years. Therefore, there is a great need for predictive biomarkers to guide treatment. In the era of precision medicine, organoids are studied as a functional method to predict treatment response to oncological treatment. The overall purpose of the present systematic review was to uncover the current status of patient-derived organoids and their ability to perform drug screenings for EOC. A systematic search for studies investigating ovarian cancer and organoids was performed using PubMed and the Cochrane Library. A total of 10 studies fulfilled the inclusion criteria. The growth rates of organoids were described in six studies and varied between 29 and 90%. Only four studies included data on clinical outcomes and indicated a positive correlation between clinical response and drug screening results. Inter- and intratumoral heterogeneity was examined in seven studies. They all suggested that the organoids recapture the tumor heterogeneity. Only one study performed drug screenings on organoids obtained from different tumor sites and metastasis from the same patient with EOC and revealed a different response to at least one drug for all patients. In conclusion, organoids may provide a platform for predicting the clinical response to chemotherapy and gene-targeting therapy. However, the results are only exploratory and the number of published drug screening studies is minimal. Further research is required to prove that organoids are able to support the choice of oncological treatment in patients with EOC.

[Folate deficiency as a differential diagnosis to severe pre-eclampsia].

In this case report, a 26-year-old pregnant woman presented with headache, visual disturbances, mega-loblastic anaemia, thrombocytopenia and proteinuria in her third trimester. These symptoms were initially misinterpreted as HELLP-syndrome, but due to normal blood pressure and liver function the patient was diagnosed with severe folate deficiency despite her daily supplements of folate to avoid neural tube defects and deficiency. The reason was onset of coeliac disease during pregnancy. Careful examination may help discriminate HELLP-syndrome from folate deficiency and thus avoid preterm delivery.

[Failed epidural analgesia during birth].

Epidural analgesia is regarded as the most effective pain relief option, and it is used in 25% of all child births in Denmark. Despite the large number of epidural blocks, there is no consensus on, how failed epidural analgesia (FEA) should be defined. There are several different definitions and probably therefore a wide incidence (8.5-23%). In this review, we attempt to provide an overview of the many definitions of FEA and to identify the risk factors. In addition, we suggest recommendations on how to reduce the number of FEA in the future.

Long-Term Lung Function and Exercise Capacity in Postinfectious chILD.

Background: Severe postinfectious diffuse pulmonary disease may clinically mimic other entities of children's interstitial lung disease and is clinically challenging comprising various disease severities despite treatment. Long-term lung function trend and physical capacity in children with postinfectious diffuse pulmonary disease are rarely reported. We investigated trends in pulmonary function by long-term follow-up and assessed physical capacity in such patients. Methods: We performed a descriptive, single-center follow-up study in children with biopsy-verified postinfectious diffuse pulmonary disease. Patients with completed primary treatment course were eligible for follow-up, including pulmonary function and exercise (VO2peak) testing. Results: Thirty patients with postinfectious diffuse pulmonary disease were identified and included. Median (range) age at diagnose was 27.5 (2-172) months after a mean lag time of 23 months. H. influenzae and rhinovirus were the most frequent pathogens. Fifteen patients were available for follow-up after mean (range) 7.6 (2-15) years of treatment completion. Lung clearance index (LCI2.5), forced expiratory volume in 1 second (FEV1), and bronchodilator responsiveness were abnormal in 80%, 53%, and 44%, respectively. Diffusion capacity for monoxide was abnormal in 7% and total lung capacity in 33%. Only 8% demonstrated low VO2peak, while 40% reported difficulties during physical exertion. Longitudinal data on spirometry (n = 14) remained unchanged from end of treatment throughout follow-up. A significant association was found between zLCI2.5 and zFEV1 (multiple linear regression; r 2 = 0.61; P = 0.0003). Conclusion: Postinfectious diffuse pulmonary disease in children carries a varying degree of chronic pulmonary impairment with onset of symptoms in the first months of life and a typical considerable lag time before diagnosis. Follow-up several years after the initial injury demonstrated moderate-to-severe peripheral airway impairment although no further lung function decline was found years after completion of treatment. Despite acceptable VO2peak, a considerable proportion struggled during heavy exercise.

Pulmonary function and fitness years after treatment for hypersensitivity pneumonitis during childhood.

BACKGROUND: Hypersensitivity pneumonitis (HP) is an immune-mediated diffuse lung disease. Significant improvement in lung function and diffusing capacity after treatment was previously demonstrated, while long-term data focusing specifically on peripheral airway impairment and peak oxygen uptake (fitness) are lacking. Hence, the aim of this study was to conduct a comprehensive study to determine the stability of pulmonary function and fitness in patients previously diagnosed with HP. METHODS: We performed a cross-sectional follow-up study with inclusion of longitudinal data if available in patients previously diagnosed with biopsy and high-resolution computed tomography-verified HP during childhood. We performed multiple breath wash-out (LCI2.5 ), spirometry (FEV1 ), bronchiodilator responsiveness test, diffusing capacity (DLCO and DLCO /VA ), body-plethysmography (TLC), and peak oxygen uptake (VO2peak ). St. George Respiratory Questionnaire was used as a measure of respiratory quality of life. RESULTS: Twenty two patients were assessed. LCI2.5 was abnormal in 47.4% compared to abnormal FEV1 in only 9.1% and without significant bronchiodilator responsiveness. DLCO and TLC were abnormal in 40.9 and 13.6%, respectively, while DLCO /VA was within normal range. Only 11.1% demonstrated abnormal VO2peak . All longitudinally assessed outcomes remained unchanged between end of treatment and time of follow up. CONCLUSIONS: A large proportion of patients previously diagnosed with HP had abnormal LCI2.5 in contrast to normal spirometry. Spirometric outcomes, TLC, and diffusing capacity were persistently slightly reduced, but stable, and VO2peak was excellent at time of follow-up. Long-term prognosis in children with HP appears favorable although persistent peripheral airway involvement of unknown clinical significance was demonstrated in almost half of the patients. Pediatr Pulmonol. 2016;51:830-837. © 2015 Wiley Periodicals, Inc.