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Equitable access to contraception and contraceptive education has the potential to mitigate health disparities related to unintended pregnancy. Pregnancy and the postpartum window frequently offer reduced insurance barriers to healthcare, increased interaction with healthcare systems and family planning providers, and an opportune time for many individuals to receive contraception; however, there are additional considerations in method type for postpartum individuals, and contraceptive counseling must be thoughtfully conducted to avoid coercion and promote shared decision-making. This commentary reviews method-specific considerations and suggests priorities for achieving equity in postpartum contraceptive access.

Tissue fusion transcript panel gene coverage (55 genes)

Purpose:The clinical utility of plasma cell-free DNA (cfDNA) has not been assessed prospectively in patients with glioblastoma (GBM). We aimed to determine the prognostic impact of plasma cfDNA in GBM, as well as its role as a surrogate of tumor burden and substrate for next-generation sequencing (NGS).Experimental Design:We conducted a prospective cohort study of 42 patients with newly diagnosed GBM. Plasma cfDNA was quantified at baseline prior to initial tumor resection and longitudinally during chemoradiotherapy. Plasma cfDNA was assessed for its association with progression-free survival (PFS) and overall survival (OS), correlated with radiographic tumor burden, and subjected to a targeted NGS panel.Results:Prior to initial surgery, GBM patients had higher plasma cfDNA concentration than age-matched healthy controls (mean 13.4 vs. 6.7 ng/mL, P < 0.001). Plasma cfDNA concentration was correlated with radiographic tumor burden on patients' first post-radiation magnetic resonance imaging scan (ρ = 0.77, P = 0.003) and tended to rise prior to or concurrently with radiographic tumor progression. Preoperative plasma cfDNA concentration above the mean (>13.4 ng/mL) was associated with inferior PFS (median 4.9 vs. 9.5 months, P = 0.038). Detection of ≥1 somatic mutation in plasma cfDNA occurred in 55% of patients and was associated with nonstatistically significant decreases in PFS (median 6.0 vs. 8.7 months, P = 0.093) and OS (median 5.5 vs. 9.2 months, P = 0.053).Conclusions:Plasma cfDNA may be an effective prognostic tool and surrogate of tumor burden in newly diagnosed GBM. Detection of somatic alterations in plasma is feasible when samples are obtained prior to initial surgical resection.

Circulating tumor DNA next-generation sequencing gene coverage (74 genes)

Figure S1. Sample cohort of this study, which included 204 subjects in total. Workflow shows patient cohorts involved in each classification. * indicated 8 patients repeated in the discovery set and the training set. ** indicated 32 locally advanced patients that were not used in the occult metastases detection as training set did not have locally advanced PDAC patients.

Figure S5. Distribution of time to metastasis (TTM) for clinical M0 PDAC patients within our training and test sets. Cross indicates no metastasis observed yet

Figure S2. miRNA sequencing to discover miRNA biomarkers to discern PDAC from non-cancer. (A) Raw miRNA sequencing data from 6 healthy controls, 6 non-cancer disease controls, 5 M0 PDAC patients, and 12 M1 PDAC patients. (B) 8 potential miRNA candidates were selected using least absolute shrinkage and selection operator (LASSO) for cancer versus non-cancer, achieving AUC=1 within discovery cohort. (C) We selected 5 out of 8 miRNA candidates based on their abundance as detected by qPCR (Cq < 40) and show the average fold changes of these 5 miRNAs between patient groups. (D) We validated these miRNAs by calculating the correlation coefficient between their qPCR data and the miRNA sequencing data. The overall R2 = 0.6

Figure S3. Multi-analyte panel generation procedure of PDAC/NC diagnosis and occult metastases detection

Tissue next-generation sequencing gene coverage (152 genes)

Plasma cell-free DNA (cfDNA) concentration (ng/mL) is correlated with (A), total radiographic tumor burden (contrast-enhancing tumor + T2/FLAIR non-enhancing tumor) and (B), contrast-enhancing tumor burden at the first post-radiation MRI scan in patients with newly diagnosed glioblastoma

Complete list of variants detected in 20 subjects who had both tissue and plasma next generation sequencing

The importance of family planning and preconception care are reviewed in detail in this chapter. Counseling and assessment about childbearing and contraception are covered as well as care for women wishing to conceive. The reader is presented information regarding the recommended frequency and specimen collection technique for cervical Pap smears in HIV-infected women, the role of human papillomavirus (HPV) testing, and indications for specialist referral for colposcopy. The chapter concludes with an overview of the clinical management of HIV-positive pregnant women, including recommendations for use of antiretroviral agents and drug disposition.

Purpose: To determine whether a multianalyte liquid biopsy can improve the detection and staging of pancreatic ductal adenocarcinoma (PDAC). Experimental Design: We analyzed plasma from 204 subjects (71 healthy, 44 non-PDAC pancreatic disease, and 89 PDAC) for the following biomarkers: tumor-associated extracellular vesicle miRNA and mRNA isolated on a nanomagnetic platform that we developed and measured by next-generation sequencing or qPCR, circulating cell-free DNA (ccfDNA) concentration measured by qPCR, ccfDNA KRAS G12D/V/R mutations detected by droplet digital PCR, and CA19-9 measured by electrochemiluminescence immunoassay. We applied machine learning to training sets and subsequently evaluated model performance in independent, user-blinded test sets. Results: To identify patients with PDAC versus those without, we generated a classification model using a training set of 47 subjects (20 PDAC and 27 noncancer). When applied to a blinded test set (N = 136), the model achieved an AUC of 0.95 and accuracy of 92%, superior to the best individual biomarker, CA19-9 (89%). We next used a cohort of 20 patients with PDAC to train our model for disease staging and applied it to a blinded test set of 25 patients clinically staged by imaging as metastasis-free, including 9 subsequently determined to have had occult metastasis. Our workflow achieved significantly higher accuracy for disease staging (84%) than imaging alone (accuracy = 64%; P < 0.05). Conclusions: Algorithmically combining blood-based biomarkers may improve PDAC diagnostic accuracy and preoperative identification of nonmetastatic patients best suited for surgery, although larger validation studies are necessary.

Purpose: The role of plasma-based tumor mutation burden (pTMB) in predicting response to pembrolizumab-based first-line standard-of-care therapy for metastatic non–small cell lung cancer (mNSCLC) has not been explored. Experimental Design: A 500-gene next-generation sequencing panel was used to assess pTMB. Sixty-six patients with newly diagnosed mNSCLC starting first-line pembrolizumab-based therapy, either alone or in combination with chemotherapy, were enrolled (Clinicaltrial.gov identifier: NCT03047616). Response was assessed using RECIST 1.1. Associations were made for patient characteristics, 6-month durable clinical benefit (DCB), progression-free survival (PFS), and overall survival (OS). Results: Of 66 patients, 52 (78.8%) were pTMB-evaluable. Median pTMB was 16.8 mutations per megabase (mut/Mb; range, 1.9–52.5) and was significantly higher for patients achieving DCB compared with no durable benefit (21.3 mut/Mb vs. 12.4 mut/Mb, P = 0.003). For patients with pTMB ≥ 16 mut/Mb, median PFS was 14.1 versus 4.7 months for patients with pTMB < 16 mut/Mb [HR, 0.30 (0.16–0.60); P < 0.001]. Median OS for patients with pTMB ≥ 16 was not reached versus 8.8 months for patients with pTMB < 16 mut/Mb [HR, 0.48 (0.22–1.03); P = 0.061]. Mutations in ERBB2 exon 20, STK11, KEAP1, or PTEN were more common in patients with no DCB. A combination of pTMB ≥ 16 and absence of negative predictor mutations was associated with PFS [HR, 0.24 (0.11–0.49); P < 0.001] and OS [HR, 0.31 (0.13–0.74); P = 0.009]. Conclusions: pTMB ≥ 16 mut/Mb is associated with improved PFS after first-line standard-of-care pembrolizumab-based therapy in mNSCLC. STK11/KEAP1/PTEN and ERBB2 mutations may help identify pTMB-high patients unlikely to respond. These results should be validated in larger prospective studies.

Purpose: The clinical utility of plasma cell-free DNA (cfDNA) has not been assessed prospectively in patients with glioblastoma (GBM). We aimed to determine the prognostic impact of plasma cfDNA in GBM, as well as its role as a surrogate of tumor burden and substrate for next-generation sequencing (NGS). Experimental Design: We conducted a prospective cohort study of 42 patients with newly diagnosed GBM. Plasma cfDNA was quantified at baseline prior to initial tumor resection and longitudinally during chemoradiotherapy. Plasma cfDNA was assessed for its association with progression-free survival (PFS) and overall survival (OS), correlated with radiographic tumor burden, and subjected to a targeted NGS panel. Results: Prior to initial surgery, GBM patients had higher plasma cfDNA concentration than age-matched healthy controls (mean 13.4 vs. 6.7 ng/mL, P < 0.001). Plasma cfDNA concentration was correlated with radiographic tumor burden on patients' first post-radiation magnetic resonance imaging scan (ρ = 0.77, P = 0.003) and tended to rise prior to or concurrently with radiographic tumor progression. Preoperative plasma cfDNA concentration above the mean (>13.4 ng/mL) was associated with inferior PFS (median 4.9 vs. 9.5 months, P = 0.038). Detection of ≥1 somatic mutation in plasma cfDNA occurred in 55% of patients and was associated with nonstatistically significant decreases in PFS (median 6.0 vs. 8.7 months, P = 0.093) and OS (median 5.5 vs. 9.2 months, P = 0.053). Conclusions: Plasma cfDNA may be an effective prognostic tool and surrogate of tumor burden in newly diagnosed GBM. Detection of somatic alterations in plasma is feasible when samples are obtained prior to initial surgical resection.

We report a case of arthrogryposis-renal dysfunction-cholestasis (ARC) syndrome in a girl with a novel VPS33B mutation. To our knowledge, this is the first reported case of ARC syndrome in the United States.

The Severity of Alopecia Tool serves as a tool for alopecia research and a clinical guideline for following progression of disease. The original Severity of Alopecia Tool score does not take into account pediatric age groups. As new clinical trials for alopecia areata include more children, a more accurate tool should be available for this population. By collecting images from patients 2-21 years of age and aligning the hair-bearing regions of the scalp, we created an adaptation of the Severity of Alopecia Tool for scoring hair loss percentage of the top, parietal, and occipital scalp in individuals 2-5, 6-11, and 12-21 years of age.

Alopecia areata (AA) is a clinically heterogeneous disease that is characterized by nonscarring hair loss, nail changes, and increased risk of other autoimmune disease. During clinical visits, children with AA often report bullying. We report survey results that highlight the prevalence of bullying and surrounding emotional impact of AA in pediatric patients. We found that bullying was common overall and additional psychological impact, including impairment of social and home life, was even more common. Children of all ages experienced bullying. Boys reported increased physical bullying. Interestingly, those with more severe disease and longer duration of disease experienced less bullying than those with less severe disease.