MYC Inhibition Potentiates CD8+ T Cells Against Multiple Myeloma and Overcomes Immunomodulatory Drug Resistance.

PURPOSE: Immunomodulatory drugs (IMiDs), such as lenalidomide and pomalidomide, are cornerstone therapies in Multiple Myeloma (MM), yet patients inevitably become refractory. IMiDs exert cytotoxicity through inducing Cereblon-dependent proteasomal degradation of IKZF1 and IKZF3, resulting in downregulation of the oncogenic transcription factors IRF4 and MYC. To date, clinical IMiD resistance independent of CRBN or IKZF1/3 has not been well-explored. Here, we investigated the roles of IRF4 and MYC in this context. EXPERIMENTAL DESIGN: Using bone marrow aspirates from patients with IMiD naïve or refractory MM, we examined IKZF1/3 protein levels and IRF4/MYC gene expression following ex vivo pomalidomide treatment via flow cytometry and qPCR. We also assessed ex vivo sensitivity to the MYC inhibitor, MYCi975, using flow cytometry. RESULTS: We discovered that while pomalidomide frequently led to IKZF1/3 degradation in MM cells, MYC gene expression was unaffected by pomalidomide in most IMiD refractory samples. We subsequently demonstrated that MYCi975 exerted strong anti-MM effects in both IMiD naïve and refractory samples. Unexpectedly, we identified CD8+ T cells from patients with MM as crucial effectors of MYCi975-induced cytotoxicity in primary MM samples, and we discovered MYCi975 enhanced the cytotoxic functions of memory CD8+ T cells. We lastly observed synergy between MYCi975 and pomalidomide in IMiD refractory samples, suggesting restoring MYC downregulation can re-sensitize refractory MM to IMiDs. CONCLUSION: Our study supports the concept that MYC represents an Achille's heel in MM across disease states and that MYCi975 may be a promising therapeutic for patients with MM, particularly in combination with IMiDs.

Social media's impact on patient provider choice.

OBJECTIVE: This study aimed to investigate if social media (SM) impacts a patient's provider choice in the field of reproductive endocrinology and infertility (REI). METHODS: This was a survey-based study completed in July 2022. A survey link was distributed using Amazon Mechanical Turk, which directed participants to a Qualtrics-based survey. Participants were 18-50 years old. The primary outcome was to identify the preferred method for finding a REI provider based on time spent on SM (< 1 h, 1-3 h, 3 + h). RESULTS: A total of 336 responses were analyzed. Fifty-four percent of respondents used SM < 1 h, 33.33% used 1-3 h, and 12.80% used 3 + h. The majority (69.05%) of respondents stated that they would seek out a REI provider/clinic if they had difficulty conceiving. Most respondents identified asking their primary care physician (44.64%) as the primary means for finding an REI provider/clinic and did not prefer to use SM. Although Facebook (< 1 h: 30.94%, 1-3 h: 31.25%, 3 + h: 27.91%) was the most utilized SM platform among respondents, YouTube was the preferred SM platform if respondents were to follow a REI clinic with a preference for posts focusing on education (< 1 h: 55.68%, 1-3 h: 43.12%, 3 + h: 58.14%) or stress management (< 1 h: 17.61%, 1-3 h: 29.36%, 3 + h: 20.94%). CONCLUSION: Most respondents utilize traditional methods when choosing their REI provider or clinic and would not utilize SM. However, SM, primarily through YouTube, may be helpful for educating infertility patients and providing support and stress relief while they undergo treatment.

CD46-ADC Reduces the Engraftment of Multiple Myeloma Patient-Derived Xenografts.

An antibody-drug conjugate (ADC) targeting CD46 conjugated to monomethyl auristatin has a potent anti-myeloma effect in cell lines in vitro and in vivo, and patient samples treated ex vivo. Here, we tested if CD46-ADC may have the potential to target MM-initiating cells (MM-ICs). CD46 expression was measured on primary MM cells with a stem-like phenotype. A patient-derived xenograft (PDX) model was implemented utilizing implanted fetal bone fragments to provide a humanized microenvironment. Engraftment was monitored via serum human light chain ELISA, and at sacrifice via bone marrow and bone fragment flow cytometry. We then tested MM regeneration in PDX by treating mice with CD46-ADC or the nonbinding control-ADC. MM progenitor cells from patients that exhibit high aldehyde dehydrogenase activity also have a high expression of CD46. In PDX, newly diagnosed MM patient samples engrafted significantly more compared to relapsed/refractory samples. In mice transplanted with newly diagnosed samples, CD46-ADC treatment showed significantly decreased engraftment compared to control-ADC treatment. Our data further support the targeting of CD46 in MM. To our knowledge, this is the first study to show preclinical drug efficacy in a PDX model of MM. This is an important area for future study, as patient samples but not cell lines accurately represent intratumoral heterogeneity.

The effects of male anxiety and depression on IVF outcomes.

STUDY QUESTION: What are the effects of male anxiety and depression on IVF outcomes? SUMMARY ANSWER: Men with anxiety had lower final total motile sperm counts (fTMSC) during IVF compared to men without anxiety; however, there were no differences in live birth rates (LBRs). WHAT IS KNOWN ALREADY: Studies have shown that male anxiety causes low sperm motility, worse sperm morphology, and increased DNA fragmentation, which are known to be influential factors on fertilization rates and embryo quality during IVF. However, data are lacking on whether there is a direct association between male anxiety and/or depression and IVF outcomes. STUDY DESIGN, SIZE, DURATION: This was a survey-based, retrospective cohort study completed at a single, large hospital-affiliated fertility center with 222 respondents who underwent IVF with or without ICSI. The study was conducted between 6 September 2018 and 27 December 2022. PARTICIPANTS/MATERIALS, SETTING, METHODS: Male partners of couples who underwent IVF or IVF/ICSI completed a Hospital Anxiety and Depression Scale (HADS) questionnaire. They were separated into two groups for both anxiety (HADS-A ≥ 8 or HADS-A < 8) and depression (HADS-D ≥ 8 or HADS-D < 8). Men with an elevated HADS-A or HADS-D score ≥8 were considered to have anxiety or depression, respectively. The primary outcome was LBR. Secondary outcomes included semen parameters at the time of IVF, cycle outcomes, pregnancy outcomes, and prevalence of erectile dysfunction and low libido. MAIN RESULTS AND THE ROLE OF CHANCE: There were a total of 222 respondents, of whom 22.5% had a HADS-A ≥ 8 and 6.5% had a HADS-D ≥ 8. The average age of respondents was 37.38 ± 4.90 years old. Antidepressant use was higher in the respondents with a HADS-A or HADS-D ≥ 8 (P < 0.05). Smoking use was similar between groups for both HADS-A and HADS-D (P > 0.05). When adjusted for male BMI, antidepressant use and smoking, men with a HADS-A or HADS-D ≥ 8 had similar rates of erectile dysfunction (adjusted relative risk (aRR) = 1.12 (95% CI 0.60, 2.06)) and low libido (aRR = 1.70 (95% CI 0.91, 3.15)) compared to those with a HADS-A or HADS-D ≤ 8. Men with a HADS-A ≥ 8 were more likely to have a lower fTMSC on the day of oocyte retrieval (11.8 ≥ 8 vs 20.1 < 8, adjusted ß = -0.66 (95% CI -1.22, -0.10)). However, the LBR per embryo transfer (ET) was similar between the HADS-A groups (43.2% ≥8 vs 45.1% <8, adjusted relative risk = 0.90 (95% CI 0.65, 1.06)). Although depression was uncommon in the entire cohort, the HADS-D groups were clinically similar for fTMSC (18.7 ≥ 8 vs 16.0 < 8) and LBR per ET (46.7% ≥8 vs 45.4% <8). LIMITATIONS, REASONS FOR CAUTION: Limitations of our study are the survey-based design, the lack of sperm morphology assessment at the time of IVF, our inability to fully assess the HADS-D ≥ 8 cohort due to the small sample size and the large Caucasian demographic. WIDER IMPLICATIONS OF THE FINDINGS: Couples undergoing IVF have an increased likelihood of suffering from anxiety and/or depression. There is currently a debate on whether or not men should be treated with antidepressants while attempting to conceive due to potential detrimental effects on sperm quality. Our study shows that, regardless of antidepressant use, couples with men who did or did not report anxiety and/or depression have similar LBRs when undergoing IVF. Therefore, it is important to assess both partners for mental health and to not withhold treatment due to a concern about a potential impact of antidepressants or anxiety/depression on sperm quality. STUDY FUNDING/COMPETING INTEREST(S): There was no funding to report for this study. Z.W. is a contributing author for UptoDate. S.S.S. is on the advisory board for Ferring Pharmaceuticals. E.G. was a medical consultant for Hall-Matson Esq, Teladoc, and CRICO and is a contributing author for UptoDate. The remaining authors have nothing to report. TRIAL REGISTRATION NUMBER: N/A.

Near-infrared and hysteroscopy-guided robotic excision of uterine isthmocele with laser fiber: a novel high-precision technique.

OBJECTIVE: To describe a novel high-precision technique for robotic excision of uterine isthmocele, employing a carbon dioxide laser fiber, under hysteroscopic guidance, and near-infrared guidance. DESIGN: Video article. PATIENT(S): A 36-year-old multipara with 3 prior cesarean sections presented to our infertility clinic with secondary infertility. The patient had been trying to conceive for 6 months without success. The patient underwent a hystero-salpingo contrast sonography that identified a large cesarean scar defect with a 1.4-mm residual myometrial thickness (RMT). The patient was counseled on surgical management with robotic approach because of RMT <3 mm precluding her from hysteroscopic resection and the potential risk for a cesarean scar ectopic or abnormal placentation if she were to become pregnant in the future. She elected to undergo excision and repair and informed consent was obtained from the patient. INTERVENTION(S): The robot was docked for traditional gynecologic robotic surgery. The uterus was injected with 5 units of vasopressin. We used a carbon dioxide laser fiber (Lumenis FIberLase) at a power of 5 watts as the sole energy source for dissection. The bladder was dissected off the uterus to identify the general area of the isthmocele. At that point, diagnostic hysteroscopy was performed using a 30-degree 5-mm hysteroscope (Karl Storz) to identify and enter the isthmocele. Near-infrared vision (da Vinci Firefly, Intuitive USA) was activated to precisely outline the extent of the isthmocele, which was not visible with simple transillumination from the hysteroscope. We proceeded with laser excision in infrared/gray scale using the laser at a power of 20 watts removing the entire area that was highlighted by the Firefly. After full excision of the isthmocele, the hysteroscope was removed and was eventually replaced by a uterine manipulator (ConMed VCare DX). The hysterotomy was closed with a 2-layer closure: 4 mattress sutures of 2-0 Vicryl (Ethicon) followed by a running 2-0 PDS Stratafix (Ethicon). The peritoneal layer was closed over these 2 layers with 2-0 PDS Stratafix (Ethicon) in a running fashion. The uterine manipulator was removed and a 14 French Malecot catheter (Bard) was placed in the uterine cavity to allow the healing to proceed with minimal risk of cervical stenosis. The bladder was backfilled to ensure integrity of the bladder wall. Interceed adhesion barrier (Gynecare) was then placed over the area of the repair and the procedure was concluded. The patient included in this video gave consent for publication of the video and posting of the video online including social media, the journal website, scientific literature websites (such as PubMed, ScienceDirect, Scopus, etc.), and other applicable sites. MAIN OUTCOME MEASURE(S): Completion of excision and repair of cesarean scar defect without surgical complications. RESULT(S): Robotic excision and repair of a sizable uterine isthmocele with carbon dioxide laser fiber and da Vinci Firefly was completed successfully without any surgical complications. Diagnostic hysteroscopy was used to positively identify the isthmocele and provide transillumination. However, the thickness of the cervical myometrium only allows the hysteroscopic light to shine through the thinnest portion of myometrium at the apex of the isthmocele, whereas the near-infrared vision allowed by the da Vinci Firefly technology was used to precisely identify the borders of the defect. The carbon dioxide laser was used to completely remove the defect while avoiding damage to delicate reproductive tissue and over-excision. No complications were identified during the postoperative visit. Magnetic resonance imaging 3 months after the surgery revealed an RMT of 10 mm at the location of excision compared with the initial RMT of 1.4 mm. CONCLUSION(S): Currently, there is no gold-standard technique for surgical management of isthmocele. This is the first description of the combined use of hysteroscopy, near-infrared vision, and laser fiber for the robotic excision of isthmocele. This specific setup proves to be a useful technical improvement. The use of near-infrared vision combined with precise hysteroscopic targeting allows much clearer definition of he isthmocele borders, and the flexible laser fiber allows millimetric xcision in the absence of appreciable lateral thermal spread. Further investigation is warranted to identify a gold-standard surgical technique for patients with cesarean scar defect.

CD38 antibody re-treatment in daratumumab-refractory multiple myeloma after time on other therapies.

Monoclonal antibodies targeting CD38 are important for treatment of both newly diagnosed and relapsed multiple myeloma (MM). Daratumumab and isatuximab are anti-CD38 antibodies with the US Food and Drugs Administration approval in multiple different combinations. Despite good initial efficacy, patients inevitably develop drug resistance. Whether patients can be effectively re-treated with these antibodies in subsequent lines of therapy is unclear. Thus far, studies have mostly been limited to clinical retrospectives with short washout periods. To answer whether patients regain sensitivity after longer washouts, we used ex vivo sensitivity testing to isolate the anti-CD38 antibody-specific cytotoxicity in samples obtained from patients who had been exposed to and then off daratumumab for up to 53 months. MM cells from patients who had been off daratumumab for >1 year showed greater sensitivity than those with <1 year, although they still were less sensitive than those who were daratumumab naïve. CD38 expression on MM cells gradually recovered, although, again, not to the level of anti-CD38 antibody-naïve patients. Interestingly, low MM CD38 explained only 45% of cases identified to have daratumumab resistance. With clinical follow-up, we found ex vivo sensitivity predicted subsequent clinical response but CD38 overexpression did not. Patients clinically re-treated with anti-CD38 antibodies had <6 months of clinical benefit, but 1 patient who was daratumumab exposed but not refractory achieved complete response lasting 13 months. We conclude that transient efficacy can be achieved by waiting 1 year before CD38 antibody rechallenge, but this approach may be best used as a bridge to, or after, chimeric antigen receptor T-cell therapy.

Ultra-low-dose and very-low-dose Lupron downregulation protocols for poor responders based on POSEIDON group 3 and 4 classifications.

PURPOSE: The objective of this study was to assess if very-low-dose Lupron (VLDL) and ultra-low-dose Lupron (ULDL) protocols can have comparable cycle outcomes when compared to other "poor responder" stimulation protocols based on POSEIDON classification groups 3 (PG3) and 4 (PG4). METHODS: A retrospective cohort study at a single, large academic center was performed. Women in PG3 (age < 35, AMH < 1.2 ng/mL) or PG4 (age ≥ 35, AMH < 1.2 ng/mL) undergoing in vitro fertilization using an ULDL (Lupron 0.1 to 0.05 mg daily), VLDL (Lupron 0.2 to 0.1 mg daily), microflare (Lupron 0.05 mg twice a day), estradiol priming/antagonist, antagonist, or minimal stimulation protocols from 2012 to 2021 were included. The primary outcome was the number of mature oocytes (MII) obtained. The secondary outcome was live birth rate (LBR). RESULTS: The cohort included 3601 cycles. The mean age was 38.1 ± 3.8 years. In the PG3 group, ULDL and VLDL protocols produced a comparable number of MIIs (5.8 ± 4.3 and 5.9 ± 5.4, respectively) and live births (33.3% and 33.3%, respectively) when compared to other protocols. In the PG4 group, ULDL and VLDL protocols resulted in a higher percentage of MIIs when compared to microflare or minimal stimulation (Microflare/ULDL: adjusted relative risk (aRR) 0.78 (95% CI 0.65, 0.95); min stim/ULDL: aRR 0.47 (95% CI 0.38, 0.58); microflare/VLDL: aRR 0.77 (95% CI 0.63, 0.95); min stim/VLDL: aRR 0.47 (95% CI 0.38, 0.95)). There were no significant differences in LBR. CONCLUSION: Dilute Lupron downregulation protocols have comparable outcomes to other poor responder protocols and are reasonable to use.

What to do with one good quality blastocyst and where do we place the emphasis?

The use of preimplantation genetic testing for aneuploidy (PGT-A) in poor responders undergoing assisted reproductive technology has been a topic of debate with controversial results. It is critical to note the denominators used in data presented. Herein, we comment on the results found in the study by Kahraman et al. on the utility of PGT-A in poor responders with a single, good-quality blastocyst.

Geographic disparities in peripartum cardiomyopathy outcomes.

BACKGROUND: Cardiomyopathy causes more than a third of late postpartum pregnancy-related deaths in the United States, and racial disparities in outcomes among pregnant individuals with cardiomyopathy exist. Underlying community factors may contribute to disparities in peripartum cardiomyopathy outcomes. OBJECTIVE: This study aimed to identify the geographic distribution of and disparities in peripartum cardiomyopathy outcomes, hypothesizing that patients living in communities with higher social vulnerability may have worse outcomes. STUDY DESIGN: This was a retrospective cohort study of patients with peripartum cardiomyopathy per the National Heart, Lung, and Blood Institute definition from January 2000 to November 2017 at a single center, excluding those with a post office box address as a post office box address may not reflect the census tract in which a patient resides. Severe peripartum cardiomyopathy (vs less severe peripartum cardiomyopathy) was defined as ejection fraction <30%, death, intensive care unit admission, left ventricular assist device or implantable cardioverter defibrillator placement, or transplant. The US census tract for the patient's address was linked to the Centers for Disease Control and Prevention Social Vulnerability Index, a 0 to 1 scale of a community's vulnerability to external stresses on health, with higher values indicating greater vulnerability. The Social Vulnerability Index includes social factors divided into socioeconomic, household composition, minority status, and housing type and transportation themes. The Social Vulnerability Index and Social Vulnerability Index components were compared among patients by peripartum cardiomyopathy severity. RESULTS: Of 95 patients in the original cohort, 5 were excluded because of the use of a post office box address. Of the remaining 90 patients, 56 met severe peripartum cardiomyopathy criteria. At baseline, individuals with and without severe peripartum cardiomyopathy had similar ages, marital status, payor type, tobacco use, gestational age at delivery, and mode of delivery; however, individuals with severe peripartum cardiomyopathy were more likely to be Black (vs White) (59% vs 29%; P<.007) and less likely to recover ejection fraction (EF) to ≥55% by 12 months (36% vs 62%; P=.02) than individuals with less severe peripartum cardiomyopathy. Patients with severe peripartum cardiomyopathy were more likely to live in areas with a higher Social Vulnerability Index (0.51 vs 0.31; P=.002) and with more residents who were unemployed, impoverished, without a high school diploma, in single-parent households, of minority status, without a vehicle, and in institutionalized group quarters than patients with less severe peripartum cardiomyopathy. The median income was lower in communities of individuals with severe peripartum cardiomyopathy than in communities of individuals with less severe peripartum cardiomyopathy. CONCLUSION: Patients with severe peripartum cardiomyopathy outcomes were more likely to live in communities with greater social vulnerability than patients with less severe peripartum cardiomyopathy outcomes. To reduce disparities and maternal mortality rates, resources may need to be directed to socially vulnerable communities.

Aquaporins: New players in breast cancer progression and treatment response.

Aquaporins (AQPs) are a family of small transmembrane proteins that selectively transport water and other small molecules and ions following an osmotic gradient across cell plasma membranes. This enables them to regulate numerous functions including water homeostasis, fat metabolism, proliferation, migration, and adhesion. Previous structural and functional studies highlight a strong biological relationship between AQP protein expression, localization, and key biological functions in normal and cancer tissues, where aberrant AQP expression correlates with tumorigenesis and metastasis. In this review, we discuss the roles of AQP1, AQP3, AQP4, AQP5, and AQP7 in breast cancer progression and metastasis, including the role of AQPs in the tumor microenvironment, to highlight potential contributions of stromal-derived to epithelial-derived AQPs to breast cancer. Emerging evidence identifies AQPs as predictors of response to cancer therapy and as targets for increasing their sensitivity to treatment. However, these studies have not evaluated the requirements for protein structure on AQP function within the context of breast cancer. We also examine how AQPs contribute to a patient's response to cancer treatment, existing AQP inhibitors and how AQPs could serve as novel predictive biomarkers of therapy response in breast cancer. Future studies also should evaluate AQP redundancy and compensation as mechanisms used to overcome aberrant AQP function. This review highlights the need for additional research into how AQPs contribute molecularly to therapeutic resistance and by altering the tumor microenvironment.

Optofluidic Particle Manipulation: Optical Trapping in a Thin-Membrane Microchannel.

We demonstrate an optofluidic device which utilizes the optical scattering and gradient forces for particle trapping in microchannels featuring 300 nm thick membranes. On-chip waveguides are used to direct light into microfluidic trapping channels. Radiation pressure is used to push particles into a protrusion cavity, isolating the particles from liquid flow. Two different designs are presented: the first exclusively uses the optical scattering force for particle manipulation, and the second uses both scattering and gradient forces. Trapping performance is modeled for both cases. The first design, referred to as the orthogonal force design, is shown to have a 80% capture efficiency under typical operating conditions. The second design, referred to as the gradient force design, is shown to have 98% efficiency under the same conditions.

Assessment of lesbian, gay, bisexual, transgender, and questioning experiences within a large southeast training program.

The USA has become increasingly diverse resulting in greater strides to improve workforce diversity and inclusivity. The objective of this study is to compare the experiences of trainees in Graduate Medical Education who identify as Lesbian, Gay, Bisexual, Transgender or Questioning (LGBTQ) to the experiences of non-LGBTQ trainees within the medical workplace. We conducted a cross-sectional, exploratory survey from 1 December 2020 to 14 January 2021 at a single, large teaching institution. We collected data anonymously and stored it in a REDCap database. We excluded surveys in which trainees did not respond to sexual orientation. We used contingency tables and Fisher's exact test to identify outcomes associated with sexual orientation and gender identity particularly with regard to professionalism, well-being, and satisfaction with training. We distributed the survey to 840 trainees. 730 trainees were included (23 (3.2%) LGBTQ and 707 (96%) Straight). LGBTQ trainees were more likely to experience offensive remarks based on race/ethnicity (p = 0.03) and sexual orientation (p = 0.01). Secondary analysis based on race found that Blacks and Other were more likely to report differences based on professionalism and satisfaction with their training program. There was no difference seen among LGBTQ trainees based on race. We found trainees who identified as LGBTQ were more likely to experience discrimination/microaggressions. Also, racial and ethnic groups that are underrepresented in medicine were more likely to encounter discrimination and dissatisfaction with their training. More efforts are needed in academics to promote safe and supportive LGBTQ and minority training experiences.

Optofluidic Particle Manipulation Platform with Nanomembrane.

We demonstrate a method for fabricating and utilizing an optofluidic particle manipulator on a silicon chip that features a 300 nm thick silicon dioxide membrane as part of a microfluidic channel. The fabrication method is based on etching silicon channels and converting the walls to silicon dioxide through thermal oxidation. Channels are encapsulated by a sacrificial polymer which fills the length of the fluid channel by way of spontaneous capillary action. The sacrificial material is then used as a mold for the formation of a nanoscale, solid-state, silicon dioxide membrane. The hollow channel is primarily used for fluid and particle transport but is capable of transmitting light over short distances and utilizes radiation pressure for particle trapping applications. The optofluidic platform features solid-core ridge waveguides which can direct light on and off of the silicon chip and intersect liquid channels. Optical loss values are characterized for liquid and solid-core structures and at interfaces. Estimates are provided for the optical power needed to trap particles of various sizes.

Oocyte cryopreservation review: outcomes of medical oocyte cryopreservation and planned oocyte cryopreservation.

BACKGROUND: The utilization of oocyte cryopreservation (OC) has become popularized with increasing numbers of reproductive-aged patients desiring to maintain fertility for future family building. OC was initially used for fertility preservation in postmenarchal patients prior to gonadotoxic therapies; however, it is now available to patients to circumvent age-related infertility and other diagnoses associated with early loss of ovarian reserve. The primary aim of this paper is to provide a narrative review of the most recent and robust data on the utilization and outcomes of OC in both patient populations. OC results in similar oocyte yield in patients facing gonadotoxic therapies and patients undergoing planned OC. Available data are insufficient to predict the live birth rates or the number of oocytes needed to result in live birth. However, oocyte yield and live birth rates are best among patients < 37.5 years old or with anti-mullerian hormone levels > 1.995 ng/dL, at the time of oocyte retrieval. There is a high 'no use' rate (58.9%) in patients using planned OC with 62.5% returning to use frozen oocytes with a spouse. The utilization rate in medical OC patients is < 10%. There is currently no data on the effects of BMI, smoking, or ethnicity on planned OC outcomes. CONCLUSION: It is too early to draw any final conclusions on outcomes of OC in medical OC and planned OC; however, preliminary data supports that utilization of OC in both groups result in preservation of fertility and subsequent live births in patients who return to use their cryopreserved eggs. Higher oocyte yield, with fewer ovarian stimulation cycles, and higher live birth rates are seen in patients who seek OC at younger ages, reinforcing the importance of age on fertility preservation. More studies are needed in medical OC and planned OC to help guide counseling and decision-making in patients seeking these services.

Racial disparities in peripartum cardiomyopathy: eighteen years of observations.

BACKGROUND: Black women have greater than a three-fold risk of pregnancy-associated death compared to White women; cardiomyopathy is a leading cause of maternal mortality. OBJECTIVES: This study examined racial disparities in health outcomes among women with peripartum cardiomyopathy. STUDY DESIGN: Retrospective cohort of women with peripartum cardiomyopathy per the National Heart, Lung, and Blood Institute definition from January 2000 to November 2017 from a single referral center. Selected health outcomes among Black and White women were compared; primary outcome was ejection fraction at diagnosis. Secondary outcomes included cardiovascular outcomes, markers of maternal morbidity, resource utilization, and subsequent pregnancy outcomes. RESULTS: Ninety-five women met inclusion criteria: 48% Black, 52% White. Nearly all peripartum cardiomyopathy diagnoses were postpartum (95.4% Black, 93% White, p=.11). Ejection fraction at diagnosis was not different between Black and White women (26.8 ± 12.5 vs. 28.7 ± 9.9, p=.41). Though non-significant, fewer Black women had myocardial recovery to EF ≥55% (35 vs. 53%, p=.07); however, 11 (24%) of Black women vs. 1 (2%) White woman had an ejection fraction ≤35% at 6-12 months postpartum (p<.01). More Black women underwent implantable cardioverter defibrillator placement: n = 15 (33%) vs. n = 7 (14%), p=.03. Eight women (8.4%) died in the study period, not different by race (p=.48). Black women had higher rates of healthcare utilization. In the subsequent pregnancy, Black women had a lower initial ejection fraction (40 vs. 55%, p=.007) and were less likely to recover postpartum (37.5 vs. 55%, p=.02). CONCLUSIONS: Black and White women have similar mean ejection fraction at diagnosis of peripartum cardiomyopathy, but Black women have more severe left ventricular systolic dysfunction leading to worse outcomes, increased resource use, and lower ejection fraction entering the subsequent pregnancy.

The Effects of Antepartum Depressive Symptoms on Postcesarean Opioid Consumption.

OBJECTIVE: The study aimed to test the hypothesis that higher Edinburgh Postnatal Depression Scale (EPDS) scores are associated with increased pain scores and opioid use during postpartum hospitalization following cesarean section. STUDY DESIGN: We conducted a retrospective cohort of English or Spanish-speaking women ≥18 years who had prenatal care for a singleton gestation and delivered by cesarean at ≥36 weeks within a tertiary center during 2017. Exclusions included women with fetal anomalies, intrauterine fetal demise, sickle cell disease, previously diagnosed pain disorders (e.g., chronic pain or fibromyalgia), substance use disorder (based on documented prescription or use of methadone or buprenorphine), or reoperation during hospital stay. Women without an EPDS recorded antenatally were also excluded. Major depressive symptoms (MDS) were defined as a documented antenatal EPDS ≥12. Women with and without MDS were compared, and multivariable linear regression models were generated to evaluate associations between MDS status and both pain scores and opioid use. RESULTS: Of the 891 women meeting other inclusion criteria, 676 (76%) had documented antenatal EPDS scores, and 104 (15.4%) of those had MDS. Women with MDS were more likely to be use tobacco and have general anesthesia for cesarean delivery, but groups were otherwise similar. Women with MDS reported higher daily and average pain scores postpartum (2.4 vs. 1.7 average; p < 0.001). Women with MDS used more morphine milligram equivalents (MME) each day during their postpartum hospitalization, leading to a higher total MME use (121 mg [60.5-214.5] vs. 75 mg [28.5-133.5], p < 0.001). CONCLUSION: We found an association between antepartum depressive symptoms and acute pain after cesarean delivery leading to increased opioid use. Given the current focus on opioid stewardship, further research into this association, exploration of tailored pain control, and determining whether treatment of antepartum MDS reduces postpartum pain, and therefore opioid use, will be of the utmost priority. KEY POINTS: · Women with MDS report higher pain scores postcesarean.. · Women with MDS use more opioids postcesarean.. · Future studies are needed for the treatment of MDS..

Do cognitive training applications improve executive function in children with adverse childhood experiences? A pilot study.

Executive function (EF) is comprised of inhibitory control, working memory and cognitive flexibility, core components which more complex skills and abilities develop from, including problem solving, reasoning and planning. Adverse childhood experiences (ACE) negatively impact the development of these skills and in turn life outcomes. This pilot-study explores the use of computerized cognitive training applications (CCTA) (software-based training programs) in school, to improve these skills in children aged 6-11 with ACE. A pre-post-test, between-subject experimental design using an experimental and a placebo-control group was used. The control group were matched to the experimental group by prior academic attainment level and age. A one-way multivariate analysis of covariance (MANCOVA) assessed changes in EF across two time-points between the experimental and the control group. Both groups of participants were selected based on an ACE parent-report questionnaire score of 4+ (n = 32). EF was measured using the Behavior Rating Inventory of Executive Function (BRIEF), assessing far-transfer of training to behavioral measures of EF. Results show CCTA had a significant positive impact on executive function, particularly on working memory. This small-scale pilot study presents exciting directions for future research into the role of CCTA in order to confirm conclusions drawn.