Prevalence of nonfounder BRCA1/2 mutations in Ashkenazi Jewish patients presenting for genetic testing at a hereditary breast and ovarian cancer center.

BACKGROUND: Genetic assessment in Ashkenazi Jewish (AJ) patients often is limited to BRCA1/2 founder mutation testing. With access to time-efficient and cost-efficient multigene panel testing, some advocate expanding genetic testing in this population. However, to the best of the authors' knowledge, rates of nonfounder BRCA1/2 mutations and mutations in cancer-associated genes other than BRCA1/2 among AJ are not known. In the current study, the authors sought to assess the prevalence of mutations other than BRCA1/2 founder mutations among AJ patients undergoing genetic assessment. METHODS: The authors reviewed the medical records for all AJ patients who underwent genetic assessment at a single institution between June 2013 and December 2016. Mutations were categorized as 1) BRCA1/2 AJ founder mutations (BRCA1 185delAG, BRCA1 5382insC, or BRCA2 6174delT); 2) nonfounder BRCA1/2 mutations; or 3) mutations in non-BRCA1/2 cancer-associated genes. RESULTS: A total of 732 AJ patients underwent genetic assessment. Of these, 371 patients (51%) had a personal history of breast or ovarian cancer, 540 patients (73.8%) had a family history of breast cancer, and 132 patients (18%) had a family history of ovarian cancer. In the study population, 101 patients (13.8%) were found to have a pathogenic mutation, 78 patients (10.7%) had a BRCA1/2 founder mutation, 3 patients (0.4%) had a nonfounder BRCA1/2 mutation, and 20 patients (2.7%) had a mutation in a non-BRCA1/2 cancer-associated gene. Non-BRCA1/2 cancer-associated genes harboring mutations included RAD51D, TP53, mutS homolog 6 (MSH6), checkpoint kinase 2 (CHEK2), adenomatous polyposis coli (APC), and Fanconi anemia group C protein (FANCC). CONCLUSIONS: Among AJ patients found to have a pathogenic mutation on genetic assessment, approximately 22.8% had a mutation that would be missed with BRCA1/2 AJ founder mutation testing. Comprehensive multigene panel sequencing can provide clinically relevant genetic information for AJ patients and should be considered for genetic assessment in this population.

Fertility preservation with random-start controlled ovarian stimulation and embryo cryopreservation for early pregnancy-associated breast cancer.

We report a case of fertility preservation using random-start controlled ovarian stimulation (COS), intracytoplasmic sperm injection (ICSI) and embryo cryopreservation in a patient with early pregnancy-associated breast cancer. A 34-year-old nulliparous woman at 5 weeks of gestation was diagnosed with estrogen receptor (ER) positive, progesterone receptor (PR) positive and human epidermal growth factor receptor-2 (HER-2) negative infiltrating intraductal carcinoma. Urgent neoadjuvant chemotherapy was deemed necessary and the patient decided to terminate the pregnancy. Random-start COS was initiated 5 days after pregnancy termination using a letrozole-based protocol. The beta human chorionic gonadotropin level on the day of COS start was 119.8 mIU/mL. Twenty-nine oocytes were retrieved after 11 days of COS. Seventeen oocytes underwent successful fertilization and 10 blastocysts were cryopreserved. The patient subsequently initiated neoadjuvant chemotherapy with her oncologist. The current case highlights the feasibility of random-start COS and embryo cryopreservation for fertility preservation immediately after the termination of an early pregnancy in a patient with pregnancy-associated breast cancer.

Choices and Outcomes of the Oldest Old Admitted During the First Wave of COVID-19 in New York City.

Objectives: Morbidity and mortality are higher in older adults with COVID-19, but their decisions about aggressive care, severity of disease, and outcomes during the first surge in New York City are not well characterized. We sought to determine if the oldest patients chose intubation and comfort care at different rates compared to younger geriatric patients. We also studied outcomes among patients admitted with severe disease and those who chose aggressive versus comfort care. Methods: This retrospective analysis used electronic health record data from patients 65 years and older at two medical centers in New York City admitted between 3/5/2020 and 5/15/2020. The primary outcome was comfort care orders, and secondary outcomes included death, palliative care consultation, goals of care discussion, code status, and ventilator weaning. Results: Of the 854 patients, 214 were in the oldest old (OO, age > = 85) group, 269 middle old (MO, age 75-84), and 371 young old (YO, age 65-74). Among those with serious disease, the OO were more likely to choose comfort care (45% vs. 21% MO and 6.8% YO), less likely to be intubated (17% vs. 37% MO and 44% YO), more likely to have a palliative care consult, more likely to be DNR/DNI on admission (60% vs. 17% MO and 9.3%% YO), and more likely to die during admission (65% vs. 42% MO and 21% YO) (all p-values < 0.001). Of all 216 intubated patients, 78% of the OO died, versus 66% of the MO and 36% of the YO (p = <0.001). Conclusions: Adults 85 and above admitted with COVID-19 were more likely to forego intubation and die with comfort-based care. Irrespective of intubation choice, patients 85 and older had a markedly poorer prognosis than other cohorts over 65.

Sex-Related Differences in Clinical Presentation and Risk Factors for Mortality in Patients Hospitalized With Coronavirus Disease 2019 in New York City.

We evaluated sex-related differences in symptoms and risk factors for mortality in 4798 patients hospitalized with coronavirus disease 2019 in New York City. When adjusted for age and comorbidities, being male was an independent predictor of death with mortality significantly higher than females, even with low severe acute respiratory syndrome coronavirus 2 viral load at admission.

Incorrect Electrocardiogram Lead Placement in ST-Segment-Elevation Myocardial Infarction.

This case report describes a patient in their 70s with acute onset waxing and waning chest pressure, which radiated to both arms and was accompanied by shortness of breath.