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Pulmonary hypertension (PH) in interstitial lung disease (ILD) is relatively common, affecting up to 50% of patients with idiopathic pulmonary fibrosis (IPF). It occurs more frequently in advanced fibrotic ILD, although it may also complicate milder disease and carries significant clinical implications in terms of morbidity and mortality. Key pathological processes driving ILD-PH include hypoxic pulmonary vasoconstriction and pulmonary vascular remodelling. While current understanding of the complex cell signalling pathways and molecular mechanisms underlying ILD-PH remains incomplete, there is evidence for an interplay between the disease pathogenesis of fibrotic ILD and PH, with interest in the role of the pulmonary endothelium in driving pulmonary fibrogenesis more recently. This review examines key clinical trials in ILD-PH therapeutics, including recent research showing promise for the treatment of both ILD-PH and the underlying pulmonary fibrotic process, further supporting the hypothesis of interrelated pathogenesis. Other important management considerations are discussed, including the value of accurate phenotyping in ILD-PH and the success of the "pulmonary vascular" phenotype. This article highlights the close and interconnected nature of fibrotic ILD and PH disease pathogenesis, a perspective likely to improve our understanding and therapeutic approach to this complex condition in the future. [ABSTRACT FROM AUTHOR]

For women achieving clinical remission after the completion of initial treatment for epithelial ovarian cancer, 80% with advanced-stage disease will develop recurrence. However, the standard treatment of women with recurrent platinum-sensitive diseases remains poorly defined. Secondary (SCS), tertiary (TCS) or quaternary (QCS) cytoreduction surgery for recurrence has been suggested to be associated with increased overall survival (OS). We searched five databases for studies reporting death rate, OS, cytoreduction rates, post-operative morbidity/mortality and diagnostic models predicting complete cytoreduction in a platinum-sensitive disease recurrence setting. Death rates calculated from raw data were pooled based on a random-effects model. Meta-regression/linear regression was performed to explore the role of complete or optimal cytoreduction as a moderator. Pooled death rates were 45%, 51%, 66% for SCS, TCS and QCS, respectively. Median OS for optimal cytoreduction ranged from 16–91, 24–99 and 39–135 months for SCS, TCS and QCS, respectively. Every 10% increase in complete cytoreduction rates at SCS corresponds to a 7% increase in median OS. Complete cytoreduction rates ranged from 9–100%, 35–90% and 33–100% for SCS, TCS and QCS, respectively. Major post-operative thirty-day morbidity was reported to range from 0–47%, 13–33% and 15–29% for SCS, TCS and QCS, respectively. Thirty-day post-operative mortality was 0–6%, 0–3% and 0–2% for SCS, TCS and QCS, respectively. There were two externally validated diagnostic models predicting complete cytoreduction at SCS, but none for TCS and QCS. In conclusion, our data confirm that maximal effort higher order cytoreductive surgery resulting in complete cytoreduction can improve survival. [ABSTRACT FROM AUTHOR]

Tubo-ovarian cancer is the most lethal gynaecological cancer. More than 75% of patients are diagnosed at an advanced stage, which is associated with poorer overall survival. Symptoms at presentation are vague and non-specific, contributing to late diagnosis. Multimodal risk models have improved the diagnostic accuracy of adnexal mass assessment based on patient risk factors, coupled with findings on imaging and serum-based biomarker tests. Newly developed ultrasonographic assessment algorithms have standardised documentation and enable stratification of care between local hospitals and cancer centres. So far, no screening test has proven to reduce ovarian cancer mortality in the general population. This review is an update on the evidence behind ovarian cancer diagnostic strategies. [ABSTRACT FROM AUTHOR]

Simple Summary: Multigene testing in ovarian cancer has received increased support due to its' applicability for cancer treatment and the impact it has on cancer prevention in families. This study shows that multi-gene germline and somatic testing uptake after counselling by a member of the multidisciplinary cancer clinical team in women with ovarian cancer, was high (97%). A total of 15.5% of women were identified to have germline BRCA1/BRCA2 pathogenic variants and 7.8% had somatic BRCA1/BRCA2 pathogenic variants. A total of 2.3% patients had RAD51C/RAD51D/BRIP1 pathogenic variants. We found that 11% of germline pathogenic variants were large-genomic-rearrangements and were missed by somatic testing. Our findings support prospective parallel somatic-&-germline panel testing to maximize variant identification. We present findings of a cancer multidisciplinary-team (MDT) coordinated mainstreaming pathway of unselected 5-panel germline BRCA1/BRCA2/RAD51C/RAD51D/BRIP1 and parallel somatic BRCA1/BRCA2 testing in all women with epithelial-OC and highlight the discordance between germline and somatic testing strategies across two cancer centres. Patients were counselled and consented by a cancer MDT member. The uptake of parallel multi-gene germline and somatic testing was 97.7%. Counselling by clinical-nurse-specialist more frequently needed >1 consultation (53.6% (30/56)) compared to a medical (15.0% (21/137)) or surgical oncologist (15.3% (17/110)) (p < 0.001). The median age was 54 (IQR = 51–62) years in germline pathogenic-variant (PV) versus 61 (IQR = 51–71) in BRCA wild-type (p = 0.001). There was no significant difference in distribution of PVs by ethnicity, stage, surgery timing or resection status. A total of 15.5% germline and 7.8% somatic BRCA1/BRCA2 PVs were identified. A total of 2.3% patients had RAD51C/RAD51D/BRIP1 PVs. A total of 11% germline PVs were large-genomic-rearrangements and missed by somatic testing. A total of 20% germline PVs are missed by somatic first BRCA-testing approach and 55.6% germline PVs missed by family history ascertainment. The somatic testing failure rate is higher (23%) for patients undergoing diagnostic biopsies. Our findings favour a prospective parallel somatic and germline panel testing approach as a clinically efficient strategy to maximise variant identification. UK Genomics test-directory criteria should be expanded to include a panel of OC genes. [ABSTRACT FROM AUTHOR]