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This issue of the Journal of Psychology and Theology focuses on the intersection between humility, religion, and spirituality. In this introduction to the special issue, we first define humility, religion, [...]

Competing Interests: Conflicts of interest Drs Hook, Olshan, Billings, and Aleshin are employees of Natera, Inc., with stock/options to own stock in the company. Drs Park, Harris, Lacy, Daniels, Lee, Lambrecht, and Gao and Author Kannan do not have any conflicts of interest to declare.

The number of pregnant women with cancer is on the rise. These patients and their providers encounter complex medical management decisions. Standard-of-care systemic therapy and radiological imaging can impair fetal development and affect viability. Conversely, insufficient monitoring and treatment can lead to cancer progression, compromising the health of the patient. Personalized and tumor-informed circulating tumor DNA (ctDNA) testing (Signatera™, bespoke mPCR NGS assay) is a validated, noninvasive blood test that can accurately assess cancer progression and tumor response to treatment ahead of radiological imaging, across solid tumors. In this case series of four patients, we explore the clinical utility of longitudinal ctDNA testing in the medical management of pregnant patients with solid tumors, to aid in informed decision-making for patients and providers., Competing Interests: S.C. acknowledges an advisory role at Natera, Inc., Pfizer, and Taiho. “N.H., M.K., G.B., A.K.M., J.M., R.J., P.O., P.R.B., and A.A. are employees of Natera, Inc. with stock/options” to own stock in the company. A.P. acknowledges membership of the Bristol Myers Squibb speakers' bureau, role as a consultant for Novartis, participatory role in a Natera Ad Board, and role as a speaker for Natera and Grail., (Copyright © 2022 Stacey A. Cohen et al.)

Introduction: Colorectal cancer (CRC) is a highly prevalent disease, wherein, ~30%-40% of patients with CRC relapse postresection. In some patients with CRC, adjuvant chemotherapy can help delay recurrence or be curative. However, current biomarkers show limited clinical utility in determining if/when chemotherapy should be administered, to provide benefit. Circulating tumour DNA (ctDNA) can measure molecular residual disease (MRD) and relapse with high specificity and sensitivity. This study protocol investigates the clinical utility of ctDNA for optimal use of adjuvant chemotherapy in patients with surgically resected CRC and to detect early disease progression in the surveillance setting., Methods and Analysis: This is a multicentre prospective, observational cohort study. A total of 2000 stage I-IV patients will be enrolled in up to 200 US sites, and patients will be followed for up to 2 years with serial ctDNA analysis, timed with the standard-of-care visits. The primary endpoints are to observe the impact of bespoke ctDNA testing on adjuvant treatment decisions and to measure CRC recurrence rates while asymptomatic and without imaging correlate. The secondary endpoints are MRD clearance rate (MRD+ to MRD-) during or after adjuvant chemotherapy, percentage of patients that undergo surgery for oligometastatic recurrence, survival of MRD-negative patients treated with adjuvant chemotherapy versus no adjuvant chemotherapy (active surveillance), overall survival, examine the number of stage I CRC that have recurrent disease detected postsurgery, and patient-reported outcomes., Ethics and Dissemination: This study has received ethical approval from the Advarra Institutional Review Board (IRB) protocol: Natera-20-041-NCP/3766.01, BESPOKE Study of ctDNA Guided Therapy in Colorectal Cancer (BESPOKE CRC) (Pro00041473) on 10 June 2021. Data protection and privacy regulations will be strictly observed in the capturing, forwarding, processing and storing of patients' data. Publication of any study results will be approved by Natera in accordance with the site-specific contract., Trial Registration Number: NCT04264702., Competing Interests: Competing interests: PMK: consultancy/advisory board: Taiho Oncology, Ipsen, Natera, Foundation Medicine; Research/Trial Support (to institution): BMS, Celgene, AstraZeneca, BTG, Advanced Accelerator Applications, Array Biopharma. AG: Research funding from Array BioPharma, Bayer, Boston Biomedical, Daiichi Sankyo, Eisai, Genentech/Roche, Lilly, Pfizer. SKo: research funding from Amgen, Array BioPharma, Biocartis, EMD Serono, Genentech/Roche, Guardant Health, Lilly, MedImmune, Novartis, Sanofi. All other authors are employees of Natera, Inc. with stock/options to own stock on the company. This study is being sponsored by Natera, Inc., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Genetic counseling and testing for hereditary cancer susceptibility is a rapidly evolving field and partly a result of next-generation sequencing (NGS) allowing analysis of multiple cancer susceptibility genes simultaneously. This qualitative study explored laboratory perspectives on hereditary cancer panels. Semi-structured interviews were conducted with representatives of clinical laboratories offering hereditary cancer panels via NGS. Several themes emerged from the responses pertaining to hereditary cancer panel development, the importance of communication of panel properties with patients, variant reporting policies, and the future of hereditary cancer gene testing. Clinical utility was discussed as primary consideration during panel development. In addition, while participants indicated gene and syndrome overlap prompted panel development in general, laboratories differed in their opinions of whether phenotypic overlap warrants offering pan-cancer panels only versus cancer specific panels. Participants stressed the importance of patients understanding implications of panel testing, including what is tested for and limitations of testing. While all laboratories discussed the limitations of a variant of uncertain significance result, they differed significantly in their reporting methods. This study provides healthcare providers information on the laboratory approach to panel testing, highlighting both commonalities and differences in laboratory approaches, and may allow providers to make more informed decisions when ordering hereditary cancer panels.

The aggressive lipid-lowering goals recommended by the second Adult Treatment Panel (ATP II) have created an increasing demand for treatment with 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors. Fluvastatin is the first completely synthetic agent in this class and offers a considerable price advantage over the other HMG-CoA therapies. In May 1994, the Buffalo Veterans Affairs Medical Center Lipid Clinic adopted a fluvastatin-preferred program in which all patients who were recommended for an HMG-CoA reductase inhibitor would be treated with fluvastatin as a first-line agent. Fluvastatin was started at 20 mg daily and titrated to goal. Patients who were stable with other HMG-CoA reductase inhibitors were converted to fluvastatin as just described. Preliminary analysis shows that, for new patients, 20 mg of fluvastatin daily at bedtime reduced low density lipoprotein cholesterol (LDL-C) by an average of 22% (range, 5-32%). Preliminary results for patients converted from another HMG-CoA reductase inhibitor showed that fluvastatin produced an additional LDL-C reduction of 18% (range, 5-30%). With a daily dose of 20 mg fluvastatin, patients with no heart disease (primary prevention) achieved ATP II goals in 60% of cases. For patients with established heart disease (secondary prevention), the goals of ATP II are lower but, despite this, 30% of patients taking fluvastatin at 20 mg daily achieved these goals. The patients in both groups who failed to achieve ATP II goals were titrated to a 40 mg daily dose, but the results of this titration are not yet available. Pharmacoeconomic outcomes were favorable.(ABSTRACT TRUNCATED AT 250 WORDS)

A gene amplification method that combines the polymerase chain reaction with detection of amplified DNA in a solution hybridization/enzyme immunoassay (PCR-EIA) was developed for HPV-16 DNA. Samples were amplified with primers for the E7-E1 region of HPV-16. Amplified DNA products were identified and quantitated by hybridization in solution with a biotinylated RNA probe. Labeled DNA/RNA hybrids were measured semiquantitatively in an enzyme immunoassay using solid phase anti-biotin antibody and liquid phase B-d-galactosidase labeled monoclonal antibody against DNA-RNA hybrids. Enzyme bound to the solid phase was quantitated with a fluorogenic substrate. The assay was linear over 2 log10 dilutions of SiHa cells and the detection limit was three copies of HPV-16 genome. The sensitivity of PCR-EIA for detection of PCR amplified products compared favorably with slot and Southern blots using a 32P-labeled RNA probe. The assay was used to assess HPV-16 infection of uterine cervix in women attending a clinic for sexually transmitted diseases. Twenty-one of the 81 specimens (25.9%), obtained by cervicovaginal lavage, were positive for HPV-16 by PCR-EIA. The assay provides a convenient means to objectively measure HPV DNA amplified with PCR.

Fifty patients admitted to the hospital for elective noncardiac surgery were carefully assessed for cardiac risk by exercise stress testing. Twenty-five of 38 (66%) patients with adequate testing had abnormal stress test results. Patients with symptoms of angina had a high incidence of abnormal stress test results (15 of 20). In the majority of these patients, the exercise stress test was true-positive, so that on angiography, severe coronary artery disease was present. In patients with no cardiac symptoms, 33% (ten of 30) had abnormal stress test results and seven patients had significant coronary artery disease. Our preliminary data indicate that exercise stress testing is a good noninvasive screening test to detect asymptomatic coronary artery disease. Those patients who have an abnormal stress test or an abnormal ECG or angina should undergo coronary angiography to determine extent of coronary disease.