olaparib (myChoice CDx)

A Successful Multimodal Treatment for High-Grade Serous Ovarian Cancer with BRCA2 Heterozygous Deletion with Multiple Recurrences: A Case Report.

Chu Hsiao-Han HH, Liu Feng-Yuan FY, Wang Chun-Chieh CC, Lin Mei-Chun MC et al.

Management of recurrent high-grade serous ovarian cancer (HGSOC) remains a challenge. This case presents a successful multimodal treatment plan in a BRCA-mutated patient with repeated recurrences. A 60-year-old woman diagnosed with FIGO stage III HGSOC received initial debulking surgery followed by chemotherapy at another hospital in December 2017. The patient presented to our institution in March 2019 for further management because of a suboptimal response to 2nd-line chemotherapy. A disseminated disease extent was identified. She progressed (new bone metastasis) during the 3rd- to 5th-line platinum-based chemotherapy, but achieved complete remission after changing to pembrolizumab and weekly paclitaxel. She had a 3rd relapse at the anterior mediastinum (proven by thoracoscopic resection in April 2020, and the tumor was found to harbor a BRCA2 heterozygous deletion), which was controlled by adjuvant radiotherapy combined with nivolumab and nab-paclitaxel, followed by maintenance therapy nivolumab plus olaparib, and eventually olaparib monotherapy. A 4th recurrence at the perigastric lymph nodes was found through periodic positron emission tomography surveillance with normal CA-125 in September 2021. Resection of metastasis and hyperthermic intraperitoneal chemotherapy (HIPEC) were performed, and maintenance therapy was again with olaparib. She has maintained remission since then. A durable remission is possible by multimodality management, including the strategic use of chemo-immunotherapy, localized resection plus HIPEC/adjuvant radiotherapy, and poly (ADP-ribose) polymerase (PARP) inhibitor maintenance, in BRCAm-HGSOC with multiple recurrences.

Practicalities of Obesity Management for the Cardiologist: A "Quick Start" Companion to the CKM Guidelines.

Pagidipati Neha J NJ

Understanding the diagnostic tests and challenges in host genetic selection against Johne's disease in New Zealand dairy cattle.

Km Venkatesh V, Dukkipati Vsr V, Gupta S K SK, Lopez-Villalobos N N et al.

Johne's disease (JD) is a common endemic gastrointestinal disease of ruminants caused by Mycobacterium avium subspecies paratuberculosis (MAP). With no effective treatment or vaccine preventing infection, control is currently based on the identification of infected animals and prevention of the spread of infection. The aim of this review is to critically assess the diagnostic tests currently used to detect MAP infection in NZ dairy cattle and to evaluate the current understanding of the host's genetics in preventing the disease. Multiple diagnostic tests for MAP infection, such as ELISA and faecal quantitative PCR, are currently available in NZ, but none are close to a gold-standard test. The lack of new tests in NZ has resulted in the development of multiple testing strategies such as parallel and serial testing with combinations of tests to improve specificity and sensitivity, pooling samples to reduce costs, whole herd testing to optimise culling before drying off, or selection of cows to produce replacements. However, these strategies need further testing to confirm their cost-benefit, especially in relation to varying infection pressures at the individual cow and herd levels. There is limited understanding of how the host's genetic variation contributes to the range of responses - the JD phenotype - seen in animals in contact with MAP. Canonically, this is described in terms of susceptibility, resistance and resilience. However, within field studies, it is very difficult to identify animals with these characteristics. For example, the combination of repeated and combined diagnostic testing, together with longitudinal production data required to identify resilient animals, can be very expensive. This review shows that more NZ-based research is required around strategies that optimise the use and value of what are inevitably imperfect diagnostic tests. Such work should be undertaken alongside a focus on identifying the genetic differences behind the JD phenotypes.

Author Correction: From cell atlases to mechanisms: bridging scRNA-seq discovery with in vivo genetics.

Zhou Bin B