To provide recommendations on the use of poly(ADP-ribose) polymerase inhibitors (PARPis) for management of epithelial ovarian, tubal, or primary peritoneal cancer (EOC).
Randomized, controlled, and open-labeled trials published from 2011 through 2020 were identified in a literature search. Guideline recommendations were based on the review of the evidence, US Food and Drug Administration approvals, and consensus when evidence was lacking.
The systematic review identified 17 eligible trials.
The guideline pertains to patients who are PARPi naïve. All patients with newly diagnosed, stage III-IV EOC whose disease is in complete or partial response to first-line, platinum-based chemotherapy with high-grade serous or endometrioid EOC should be offered PARPi maintenance therapy with niraparib. For patients with germline or somatic pathogenic or likely pathogenic variants in
(g/s
1) or
(g/s
2) genes should be treated with olaparib. The addition of olaparib to bevacizumab may be offered to patients wiBRCA1/2, or whose tumor demonstrates genomic instability. PARPis are not recommended for use in combination with chemotherapy, other targeted agents, or immune-oncology agents in the recurrent setting outside the context of a clinical trial. Recommendations for managing specific adverse events are presented. Data to support reuse of PARPis in any setting are needed.Additional information is available at www.asco.org/gynecologic-cancer-guidelines.
To assess the role of NOD-like receptor C5 (NLRC5; a major NLRC family protein that regulates immunity, inflammation and tissue fibrosis), in cerebral ischemia-reperfusion injury, characterized by inflammation and oxidative damage.
Blood NLRC5 levels were assessed in neonates with cerebral ischemia and in healthy controls. A stable PC12 cell line was established that overexpressed or knocked down NLRC5. Inflammatory responses, apoptosis rate and oxidative damage in PC12 cells under oxygen-glucose deprivation/reperfusion (OGD/R) conditions were evaluated using enzyme-linked immunosorbent assay (ELISA), terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) and reactive oxygen species (ROS) assay.
Blood NLRC5 levels were suppressed in neonates with cerebral ischemia. ELISAs showed that NLRC5 suppressed levels of tumour necrosis factor-α, interleukin (IL)-6, IL-1β, ROS and superoxide dismutase in OGD/R-treated PC12 cells. Furthermore, NLRC5 overexpression was associated with reduced apoptosis rate in PC12 cells treated by OGD/R. read more Overexpression of NLRC5 also inhibited levels of toll-like receptor (TLR)4, myeloid differentiation primary response protein MyD88 (MyD88) and phosphorylated nuclear factor kappa B-transcription factor p65 (NF-κB p-p65) in PC12 cells, and decreased nuclear levels of NF-κB p-p65.
NLRC5 alleviated inflammatory responses, oxidative damage and apoptosis in PC12 cells under OGD/R conditions by suppressing activation of the TLR4/MyD88/NF-κB pathway.
NLRC5 alleviated inflammatory responses, oxidative damage and apoptosis in PC12 cells under OGD/R conditions by suppressing activation of the TLR4/MyD88/NF-κB pathway.
Field identification and treatment of ST-segment elevation myocardial infarction (STEMI) by paramedics is an important component of care for these patients. There is a paucity of studies in the setting of paramedic-identified STEMI. This study investigated mortality and factors associated with mortality in a large state-wide prehospital STEMI sample.
Included were adult STEMI patients identified and treated with reperfusion therapy by paramedics in the field between January 2016 and December 2018 in Queensland, Australia. 30-day and one-year all-cause mortality was compared between two prehospital reperfusion pathways prehospital fibrinolysis versus direct referral to a hospital for primary percutaneous coronary intervention (direct percutaneous coronary intervention [PCI] referral). For prehospital fibrinolysis patients, factors associated with failed fibrinolysis were investigated. For direct PCI referral patients, factors associated with mortality were examined.
The 30-day mortality was 2.2% for pr8% for direct PCI referral group (p = 0.661). One-year mortality for the two groups was 2.7% and 3.2%, respectively (p = 0.732). Failed prehospital fibrinolysis was observed in 20.1% of patients receiving this therapy, with male gender and history of heart failure being predictors. For direct PCI referral group, low left ventricular ejection fraction (LVEF) on admission and cardiogenic shock prior to PCI were predictors of both 30-day and one-year mortality. Aboriginal and Torres Strait Islander status, and impaired kidney function on admission, were associated with one-year but not 30-day mortality. Being overweight was associated with lower 30-day mortality. Conclusions Mortality in STEMI patients identified and treated by paramedics was low, and the prehospital fibrinolysis treatment pathway was effective with a mortality rate comparable to that of patients undergoing primary PCI. Key words prehospital; Queensland; cardiac reperfusion; STEMI.
Local treatment of liver and/or lung metastases from colorectal cancer (CRC) is increasingly used in daily practice and comprises resection, radiofrequency ablation (RFA) and stereotactic radiotherapy (SBRT). The need for prognostic markers for patients undergoing such treatment is currently unmet. We investigated post-treatment circulating tumor-specific DNA (ctDNA) analysis and address a possible prognostic value in a pilot study.
From July 2015 to September 2017, patients undergoing standard of care local treatment of liver and/or lung metastases were included in a prospective translational study. Blood samples were drawn 2 weeks after local treatment and during follow-up. CtDNA was detected by ddPCR and a mass spectrometry-based platform MassARRAY
.
Post treatment blood samples were available for 35 patients including five with detectable ctDNA (KRAS mutation,
= 2; NRAS mutation,
= 2; BRAF mutation,
= 1) by ddPCR. 17 out of 35 patients (49%) developed recurrence within a median of 273 days (95%CI 95-NA) among patients positive for ctDNA, while the median time to recurrence was not reached for the group of patients negative for ctDNA (
= .read more
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