Integrating reproductive health care into substance use disorder services.

People who use drugs face layered stigma and barriers to accessing reproductive health care services. At the same time, they have unique needs for compassionate, trauma-informed, low-barrier reproductive health care. We review the literature on collocated reproductive health care and substance use treatment services in this population and advocate for expansion of reproductive health care services at sites providing care for substance use disorder. Through this review article, we outline the evidence for and best practices in collocating reproductive health care within substance use disorder services.

Intubation and intensive care after laminaria anaphylaxis in second-trimester abortion.

Laminaria are cervical dilators inserted for several days preceding second-trimester abortions and other uterine procedures. Our patient was intubated after a life-threatening anaphylactic reaction to laminaria prior to her surgical abortion. Abortions with laminaria dilators are frequently performed outpatient across the United States. Due to stigma, increasing restrictions, and forced closure of family planning clinics, these procedures are often obtained covertly and remotely. Patients may present obtunded, in shock, without records or proxy, and with no external evidence of the allergen's location or continued presence. Emergency and critical care physicians may consider this etiology in obtunded women with anaphylaxis who are responding poorly to standard care.

A Validation Study of Maternal Early Warning Systems: A Retrospective Cohort Study.

OBJECTIVE: We compare validation characteristics of four early warning systems for maternal morbidity. STUDY DESIGN: We used a retrospective cohort of severe maternal morbidity cases between January 2016 and December 2016 compared with a cohort of controls. We determined if the modified early obstetric warning score (MEOWS), maternal early recognition criteria (MERC), modified early warning system (MEWS), or maternal early warning trigger (MEWT) would have alerted. We developed criteria to determine which of these alerts was considered clinically "relevant." RESULTS: We reviewed 79 morbidity cases and 123 controls. MEOWS and MERC were more sensitive than MEWS or MEWT (67.1 and 67.1% vs. 19% and 40.5%, p < 0.001); however, MEWT and MEWS were more specific (88.6% MEWT and 93.5% MEWS vs. 51.2% MEOWS and 60.2% MERC, p < 0.001). In the control population, 70% of MEWT alerts still appeared "relevant" to the clinical scenario in contrast to the MEOWS (32%) or MERC systems (31%). CONCLUSION: There are limited comparative data regarding how early warning systems perform in an American population for maternal morbidity. None of the systems performs with high sensitivity and specificity. High-volume, high-acuity units may decide that the lower sensitivity of the MEWT is relatively acceptable when considering the high false trigger rate of the other more sensitive systems. In addition, triggers in the MEWT system were more likely to be clinically relevant even in cases that did not have severe morbidity.

Wnt signaling directs a metabolic program of glycolysis and angiogenesis in colon cancer.

Much of the mechanism by which Wnt signaling drives proliferation during oncogenesis is attributed to its regulation of the cell cycle. Here, we show how Wnt/ß-catenin signaling directs another hallmark of tumorigenesis, namely Warburg metabolism. Using biochemical assays and fluorescence lifetime imaging microscopy (FLIM) to probe metabolism in vitro and in living tumors, we observe that interference with Wnt signaling in colon cancer cells reduces glycolytic metabolism and results in small, poorly perfused tumors. We identify pyruvate dehydrogenase kinase 1 (PDK1) as an important direct target within a larger gene program for metabolism. PDK1 inhibits pyruvate flux to mitochondrial respiration and a rescue of its expression in Wnt-inhibited cancer cells rescues glycolysis as well as vessel growth in the tumor microenvironment. Thus, we identify an important mechanism by which Wnt-driven Warburg metabolism directs the use of glucose for cancer cell proliferation and links it to vessel delivery of oxygen and nutrients.

The TCF C-clamp DNA binding domain expands the Wnt transcriptome via alternative target recognition.

LEF/TCFs direct the final step in Wnt/ß-catenin signalling by recruiting ß-catenin to genes for activation of transcription. Ancient, non-vertebrate TCFs contain two DNA binding domains, a High Mobility Group box for recognition of the Wnt Response Element (WRE; 5'-CTTTGWWS-3') and the C-clamp domain for recognition of the GC-rich Helper motif (5'-RCCGCC-3'). Two vertebrate TCFs (TCF-1/TCF7 and TCF-4/TCF7L2) use the C-clamp as an alternatively spliced domain to regulate cell-cycle progression, but how the C-clamp influences TCF binding and activity genome-wide is not known. Here, we used a doxycycline inducible system with ChIP-seq to assess how the C-clamp influences human TCF1 binding genome-wide. Metabolic pulse-labeling of nascent RNA with 4'Thiouridine was used with RNA-seq to connect binding to the Wnt transcriptome. We find that the C-clamp enables targeting to a greater number of gene loci for stronger occupancy and transcription regulation. The C-clamp uses Helper sites concurrently with WREs for gene targeting, but it also targets TCF1 to sites that do not have readily identifiable canonical WREs. The coupled ChIP-seq/4'Thiouridine-seq analysis identified new Wnt target genes, including additional regulators of cell proliferation. Thus, C-clamp containing isoforms of TCFs are potent transcriptional regulators with an expanded transcriptome directed by C-clamp-Helper site interactions.

Vaginal Bleeding Before 20 Weeks Gestation.

Conditions that often present with vaginal bleeding before 20 weeks are common and can cause morbidity and mortality. Clinically stable patients can choose their management options. Clinically unstable patients require urgent procedural management: uterine aspiration, dilation and evacuation, or surgical removal of an ectopic pregnancy. Septic abortion requires prompt procedural management, intravenous antibiotics, and intravenous fluids. Available data on prognosis with expectant management of pre-viable rupture of membranes in the United States are poor for mothers and fetuses.

Persistently elevated hCG in a patient with no clear evidence of pregnancy.

BACKGROUND: We describe a case of a female patient with a complex medical history, including squamous cell carcinoma of the tongue, and persistent elevation in serum hCG and no confirmed intrauterine or extrauterine pregnancy. METHODS: The clinical chemistry laboratory was called upon to help clarify the situation and reach a diagnosis. RESULTS: Multiple potential sources of elevated hCG were considered and excluded. CONCLUSIONS: This case shows a rare example of paraneoplastic hCG expression and highlights the role of the clinical chemistry laboratory in resolving diagnostic dilemmas and interpreting laboratory results in patients with multiple medical comorbidities.

Contraceptive Need, Intimate Partner Violence, and Reproductive Coercion Among Women Attending a Syringe Exchange Program.

OBJECTIVE: Women who use drugs are at high risk of unintended pregnancy. This study describes contraceptive need, explores relationships between contraceptive use, intimate partner violence (IPV) and reproductive coercion, and unintended pregnancy, and assesses the acceptability of receiving contraceptive care at a syringe exchange program (SEP). METHODS: Between August and October, 2017, written surveys were administered to 96 reproductive-aged women attending an SEP in Santa Ana, California. Data were analyzed using descriptive, bivariate, and multivariate statistics. RESULTS: Most women used methamphetamines (79%) and/or heroin (74%). The majority (62%) did not use contraception during last sex with a man. Half (50%) reported a history of unintended pregnancy. Many (62%) experienced IPV or reproductive coercion in the previous 3 months. Experiencing IPV or reproductive coercion was not associated with contraceptive use or unintended pregnancy. The majority (56%) were interested in receiving contraceptive care from the SEP; history of unintended pregnancy (adjusted odds ratio [aOR] 3.5, 95% confidence interval [CI] 1.3-10.0) and depression (aOR 4.55, 95% CI 1.24-16.69) were associated with interest in contraceptive services. CONCLUSIONS: Our findings suggest that referrals for contraceptive care and direct provision of contraceptive methods at SEPs may be an acceptable approach to addressing the unmet family planning needs of women who use substances. Innovative approaches like these have the potential to impact the high prevalence of unintended pregnancy among this population; however, high prevalence of IPV and reproductive coercion must also be acknowledged by providers when providing counseling for contraceptive services.

Students as effective harm reductionists and needle exchange organizers.

BACKGROUND: Needle exchange programs are safe, highly effective programs for promoting health among people who inject drugs. However, they remain poorly funded, and often illegal, in many places worldwide due to fear and stigma surrounding drug use. Continued advocacy, education, and implementation of new needle exchanges are thus essential to improve public health and reduce structural inequality. COMMENTARY: We argue that students, and especially professional and graduate students, have the potential to play an important role in advancing harm reduction. Students benefit from the respect given to the professions they are training to enter, which gives them leverage to navigate the political hurdles often faced by needle exchange organizers, especially in areas that presently lack services. In addition, due to their relative simplicity, needle exchanges do not require much of the licensing, clinical knowledge, and infrastructure associated with more traditional student programs, such as student-run free medical clinics. Students are capable of learning harm reduction cultural approaches and techniques if they remain humble, open-minded, and seek the help of the harm reduction community. Consequently, students can generate tremendous benefits to their community without performing beyond their appropriate clinical limitations. Students benefit from organizing needle exchanges by gaining applied experience in advocacy, organization-building, and political finesse. Working in a needle exchange significantly helps erode stigma against multiple marginalized populations. Students in health-related professions additionally learn clinically-relevant knowledge that is often lacking from their formal training, such as an understanding of structural violence and inequality, root causes of substance use, client-centered approaches to health services, and interacting with clients as peers, rather than through the standard hierarchical medical interaction. CONCLUSION: We therefore encourage students to learn about and consider organizing needle exchanges during their training. Our experience is that students can be successful in developing sustainable programs which benefit their clients, the broader harm reduction movement, and themselves alike.

Lactate/pyruvate transporter MCT-1 is a direct Wnt target that confers sensitivity to 3-bromopyruvate in colon cancer.

BACKGROUND: There is increasing evidence that oncogenic Wnt signaling directs metabolic reprogramming of cancer cells to favor aerobic glycolysis or Warburg metabolism. In colon cancer, this reprogramming is due to direct regulation of pyruvate dehydrogenase kinase 1 (PDK1) gene transcription. Additional metabolism genes are sensitive to Wnt signaling and exhibit correlative expression with PDK1. Whether these genes are also regulated at the transcriptional level, and therefore a part of a core metabolic gene program targeted by oncogenic WNT signaling, is not known. RESULTS: Here, we identify monocarboxylate transporter 1 (MCT-1; encoded by SLC16A1) as a direct target gene supporting Wnt-driven Warburg metabolism. We identify and validate Wnt response elements (WREs) in the proximal SLC16A1 promoter and show that they mediate sensitivity to Wnt inhibition via dominant-negative LEF-1 (dnLEF-1) expression and the small molecule Wnt inhibitor XAV939. We also show that WREs function in an independent and additive manner with c-Myc, the only other known oncogenic regulator of SLC16A1 transcription. MCT-1 can export lactate, the byproduct of Warburg metabolism, and it is the essential transporter of pyruvate as well as a glycolysis-targeting cancer drug, 3-bromopyruvate (3-BP). Using sulforhodamine B (SRB) assays to follow cell proliferation, we tested a panel of colon cancer cell lines for sensitivity to 3-BP. We observe that all cell lines are highly sensitive and that reduction of Wnt signaling by XAV939 treatment does not synergize with 3-BP, but instead is protective and promotes rapid recovery. CONCLUSIONS: We conclude that MCT-1 is part of a core Wnt signaling gene program for glycolysis in colon cancer and that modulation of this program could play an important role in shaping sensitivity to drugs that target cancer metabolism.