Individualized Novel Therapies for Patients with Tumor Suppressor Genes BRCA1 and BRCA2 Mutated Epithelial Ovarian Cancer

Ovarian cancer is the leading cause of death in women with gynecological cancer, since a large proportion of patients are diagnosed at later stages of the disease. The incidence of ovarian cancer in the general population is 2%, but patients with germline mutations in the BRCA genes have a risk of developing ovarian cancer of up to 2050% with a cumulative risk of ovarian cancer at 70 years of age of 40% in BRCA1 and 18% in BRCA2 mutation carriers. Although it is a chemosensitive tumor, most of the patients after surgery and chemotherapy based on taxanes and platinum will relapse later in life. Due to the high risk of developing ovarian cancer in patients with BRCA germline mutations, new treatments rely increasingly on histological and molecular characteristics of the primary tumor, achieving greater selectivity and lower toxicity compared with standard cytotoxic agents. Poly (ADP-ribose) polymerase (PARPS) inhibitors are the first biologically active agents for patients with ovarian cancer with alterations in the DNA repair pathway, particularly in the high-grade serous subtype of ovarian cancer

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

OVARIAN CANCER ; CLINICAL AND THERAPEUTIC PERSPECTIVES

vi, 338 hlm ; 17 x 24 c

OVARIAN CANCER ' BASIC SCIENCE PERSPECTIVE

ix, 385 hlm, 17 x 24 c

OVARIAN CANCER ; CLINICAL AND THERAPEUTIC PERSPECTIVE

ix, 327 hlm ; 17 x 24 c

Early markers of renal damage in obstructive sleep apnea syndrome (OSAS) patients with or without diabetes mellitus

Background: Although obstructive sleep apnea syndrome (OSAS) has been associated with chronic kidney disease CKD, there are little data about early screening of renal affection in OSAS patients. Aim of the work: To evaluate renal function in OSAS patients with or without diabetes mellitus (DM) using blood indices [mean platelet volume (MPV) and red cell distribution width (RDW)] and serum neutrophil gelatinase associated lipocalin (NGAL) as early markers of kidney injury. Patients and methods: This case control analytic study was designed to enroll 20 OSAS patients with DM, 20 OSAS patients without DM, and 20 non OSAS diabetic patients as control group. All patients underwent full over-night attended diagnostic polysomnography. Those with AHI ≥5 were considered to have OSAS. Laboratory parameters including complete blood count with MPV and RDW, serum glucose, urea, creatinine, Hemoglobin A1c, urine albumin creatinine ratio UACR and serum NGAL were done to all enrolled participants. Results: Urine albumin creatinine ratio UACR ≥ 3 mg/mmol was found in 11 (55%) of OSAS diabetic group, 6 (30%) of non diabetic OSAS group and in 11 (55%) of D.M group. Both diabetic and non diabetic OSAS patients had significantly higher RDW and NGAL compared to non OSAS diabetic. The diabetic OSAS group had also significantly higher serum urea and creatinine compared to DM group. In OSAS patients, RDW had significant positive correlation with UACR. Meanwhile both RDW and NGAL were determined to have significant positive correlation with desaturation index during sleep, but not correlated to AHI. Conclusion: Renal impairment is common in OSAS patients but more frequent if associated with diabetes mellitus. RDW% can be used as simple screening test for early detection of renal injury in OSAS patients with or without diabetes mellitus